bluuebunny/crossref_metadata_2025 huggingface dataset:
Inclusion, reporting and analysis of demographic variables in chronobiology and sleep research
Authors: Tir Selma , White Rhiannon , Spitschan Manuel
Published: March 2023

Many aspects of sleep and circadian physiology appear to be sensitive to participant-level characteristics. While recent research robustly highlights the importance of considering participant-level demographic information, it is not clear to what extent this information is available within the large body of existing literature. This article investigates study sample characteristics within the published sleep and chronobiology research over the past 40 years. 6,777 articles were identified and a random sample of 20% was included. The reporting of sample size, age, sex, gender, ethnicity, level of education, socio-economic status, and profession of the study population was scored, and any reported aggregate summary statistics for these variables were recorded. We found that while >90% of studies reported age or sex, all other variables were reported in <25% of cases. Reporting quality was highly variable, indicating an opportunity to standardize reporting guidelines for participant-level characteristics to facilitate meta analyses.

In this article, we address the question of how representative, diverse and inclusive are published articles in sleep and chronobiology research. We analyzed a sample of >1300 articles published in sleep and chronobiology journals between 1979 and 2019 for its inclusion, reporting and analysis of study population characteristics, including age, sex, gender, race/ethnicity, level of education, socio-economic status, and profession. We found that while >90% of studies reported age or sex, all other variables were reported in <25% of cases, with the frequency of reporting changing over time. We identify opportunities for improving the reporting of demographic variables.

Research Agenda

Future research needs to: 1. Establish schemas for reporting demographic variables in a harmonized way across geographical and cultural contexts; 2. Identify gaps in the sleep and chronobiology literature with respect to understudied populations; 3. Understand the extent to which research practices allow for the inclusion of diverse populations in all stages of the research cycle, and how this can exacerbate health inequities.

Practice Points

Published studies on circadian and sleep physiology should be carefully examined.

Reporting of demographic variables should be done deliberately and systematically.

Inclusion and diversity of different populations across the field needs to be ensured.
Basal forebrain activity predicts functional degeneration in the entorhinal cortex and decreases with Alzheimer’s Disease progression
Authors: Mieling Marthe , Göttlich Martin , Yousuf Mushfa , Bunzeck Nico ,   the Alzheimer’s Disease Neuroimaging Initative
Published: March 2023

BACKGROUND AND OBJECTIVES

Recent models of Alzheimer’s Disease (AD) suggest the nucleus basalis of Meynert (NbM) as the origin of structural degeneration followed by the entorhinal cortex (EC). However, the functional properties of NbM and EC regarding amyloid-β and hyperphosphorylated tau remain unclear.

METHODS

We analyzed resting-state (rs)fMRI data with CSF assays from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, n=71) at baseline and two years later.

RESULTS

At baseline, local activity, as quantified by fractional amplitude of low-frequency fluctuations (fALFF), differentiated between normal and abnormal CSF groups in the NbM but not EC. Further, NbM activity linearly decreased as a function of CSF ratio, resembling the disease status. Finally, NbM activity predicted the annual percentage signal change in EC, but not the reverse, independent from CSF ratio.

DISCUSSION

Our findings give novel insights into the pathogenesis of AD by showing that local activity in NbM is affected by proteinopathology and predicts functional degeneration within the EC.
Conversion of methionine biosynthesis inE. colifrom trans- to direct-sulfurylation enhances extracellular methionine levels
Authors: Gruzdev Nadya , Hacham Yael , Haviv Hadar , Stern Inbar , Gabay Matan , Bloch Itai , Amir Rachel , Gal Maayan , Yadid Itamar
Published: March 2023

Methionine is an essential amino acid in mammals and a critical metabolite in all organisms. As such, various applications, including food, feed, and pharmaceuticals, necessitate the addition of L-methionine. Although amino acids and other metabolites are commonly produced through bacterial fermentation, high-yield biosynthesis of L-methionine remains a significant challenge due to the strict cellular regulation of the biosynthesis pathway. As a result, methionine is produced primarily synthetically, resulting in a racemic mixture of D,L-methionine. This study aimed to enhance methionine bio-production yields inE. coliby replacing its highly regulated trans-sulfurylation pathway with the more common direct-sulfurylation pathway used by other bacteria. To this end, we generated an auxotrophE. colistrain (MG1655) by simultaneously deletingmetAandmetBgenes and complementing them withmetXandmetYfrom different bacteria. Complementation of the genetically modifiedE. coliwithmetX/metYfromCyclobacterium marinumorDeinococcus geothermalis, together with the deletion of the global repressormetJand overexpression of the transporter YjeH, resulted in a substantial increase of up to 126 and 160-fold methionine relative to the wild-type strain, respectively, and accumulation of up to 700 mg/L using minimal MOPS medium and 2 ml culture. Our findings provide a method to study methionine biosynthesis and a chassis for enhancing L-methionine production by fermentation.

Highlights

Replacement ofE. coli metAandmetBwithmetXandmetYrecovered its growth

The engineeredE. colihas a 160-fold increase in extracellular methionine levels

Selection of differentmetXandmetYleads to varying growth rates and enhanced methionine levels
Sensory neuron LKB1 mediates ovarian and reproductive function
Authors: Lenert Melissa E , Burton Michael D
Published: March 2023

Treatments for reproductive disorders in women primarily consist of hormone replacement therapy, which can have negative health impacts. Bidirectional communication between sensory neurons and innervated organs is an emerging area of interest in tissue physiology with potential relevance for reproductive disorders. Indeed, the metabolic activity of sensory neurons can have profound effects on reproductive phenotypes. To investigate this phenomenon, we utilized a murine model with conditional deletion in sensory neurons of liver kinase B1 (LKB1), a serine/threonine kinase that regulates cellular metabolism. Female mice with this LKB1 deletion (Nav1.8cre;LKB1fl/fl) had significantly more pups per litter compared to wild-type females. Interestingly, the LKB1 genotype of male breeders had no effect on fertility outcomes, thus indicating a female-specific role of sensory neuron metabolism in fertility. LKB1 deletion in sensory neurons resulted in reduced ovarian innervation from dorsal root ganglia neurons and increased follicular turnover compared to littermate controls. In summary, LKB1 expression in peripheral sensory neurons plays an important role in modulating fertility of female mice via ovarian sensory innervation.
Ground-truth validation of uni- and multivariate lesion inference approaches
Authors: Zavaglia Melissa , Malherbe Caroline , Schlaadt Sebastian , Nachev Parashkev , Hilgetag Claus C
Published: March 2023

Lesion analysis aims to reveal causal contributions of brain regions to brain functions. Various strategies have been used for such lesion inferences. These approaches can be broadly categorized as univariate or multivariate methods. Here we analysed data from 581 patients with acute ischemic injury, parcellated into 41 Brodmann areas, and systematically investigated the inferences made by two univariate and two multivariate lesion analysis methods via ground-truth simulations, in which we defined a priori contributions of brain areas to assumed brain function. Particularly, we analysed single-region models, with only single areas presumed to contribute functionally, and multiple-region models, with two contributing regions that interacted in a synergistic, redundant or mutually inhibitory mode. The functional contributions could vary in proportion to the lesion damage or in a binary way. The analyses showed a considerably better performance of the tested multivariate than univariate methods in terms of accuracy and mis-inference error. Specifically, the univariate approaches of Lesion Symptom Mapping (LSM) as well as Lesion Symptom Correlation (LSC) mis-inferred substantial contributions from several areas even in the single-region models, and also after accounting for lesion size. By contrast, the multivariate approaches of Multi- Area Pattern Prediction (MAPP), which is based on machine learning, and Multi-perturbation Shapley value Analysis (MSA), based on coalitional game theory, delivered consistently higher accuracy and specificity. Our findings suggest that the tested multivariate approaches produce largely reliable lesion inferences, without requiring lesion size consideration, while the application of the univariate methods may yield substantial mis-localizations that limit the reliability of functional attributions.
Visual integration of omics data to improve 3D models of fungal chromosomes
Authors: Poinsignon Thibault , Gallopin Mélina , Grognet Pierre , Malagnac Fabienne , Lelandais Gaëlle , Poulain Pierre
Published: March 2023

The functions of eukaryotic chromosomes and their spatial architecture in the nucleus are reciprocally dependent. Hi-C experiments are routinely used to study chromosome 3D organization by probing chromatin interactions. Standard representation of the data has relied on contact maps that show the frequency of interactions between parts of the genome. In parallel, it has become easier to build 3D models of the entire genome based on the same Hi-C data, and thus benefit from the methodology and visualization tools developed for structural biology. 3D modeling of entire genomes leverages the understanding of their spatial organization. However, this opportunity for original and insightful modeling is under exploited. In this paper, we show how seeing the spatial organization of chromosomes can bring new perspectives to Hi-C data analysis. We assembled state-of-the-art tools into a workflow that goes from Hi-C raw data to fully annotated 3D models and we re-analysed public Hi-C datasets available for three fungal species. Besides the well-described properties of the spatial organization of their chromosomes (Rabl conformation, hypercoiling and chromosome territories), our 3D models highlightedi)inSaccharomyces cerevisiae, the backbones of the cohesin anchor regions, which were aligned all along the chromosomes,ii)inSchizosaccharomyces pombe, the oscillations of the coiling of chromosome arms throughout the cell cycle andiii)inNeurospora crassa, the massive relocalization of histone marks in mutants of heterochromatin regulators. 3D modeling of the chromosomes brings new opportunities for visual integration. This holistic perspective supports intuition and lays the foundation for building new concepts.
Parallel loss of type VI secretion systems in two multi-drug resistantEscherichia colilineages
Authors: Cummins Elizabeth A. , Moran Robert A. , Snaith Ann E. , Hall Rebecca J. , Connor Chris H. , Dunn Steven J. , McNally Alan
Published: March 2023

The repeated emergence of multi-drug resistant (MDR)Escherichia coliclones is a threat to public health globally. In recent work, drug resistantE. coliwere shown to be capable of displacing commensalE. coliin the human gut. Given the rapid colonisation observed in travel studies, it is possible that the presence of a type VI secretion system (T6SS) may be responsible for the rapid competitive advantage of drug resistantE. coliclones. We employed large scale genomic approaches to investigate this hypothesis. First, we searched for T6SS genes across a curated dataset of over 20,000 genomes representing the full phylogenetic diversity ofE. coli. This revealed large, non-phylogenetic variation in the presence of T6SS genes. No association was found between T6SS gene carriage and MDR lineages. However, multiple clades containing MDR clones have lost essential structural T6SS genes. We characterised the T6SS loci of ST410 and ST131 and identified specific recombination and insertion events responsible for the parallel loss of essential T6SS genes in two MDR clones.

Data Summary

The genome sequence data generated in this study is publicly available from NCBI under BioProject PRJNA943186, alongside a complete assembly in GenBank under accessionsCP120633-CP120634. All other sequence data used in this paper has been taken from ENA with the appropriate accession numbers listed within the methods section. TheE. coligenome data sets used in this work are from a previous publication, the details of which can be found in the corresponding supplementary data files 10.6084/m9.figshare.21360108 [1].

Impact Statement

Escherichia coliis a globally significant pathogen that causes the majority of urinary tract infections. Treatment of these infections is exacerbated by increasing levels of drug resistance. Pandemic multi-drug resistant (MDR) clones, such as ST131-C2/H30Rx, contribute significantly to global disease burden. MDRE. coliclones are able to colonise the human gut and displace the resident commensalE. coli. It is important to understand how this process occurs to better understand why these pathogens are so successful. Type VI secretion systems may be one of the antagonistic systems employed byE. coliin this process. Our findings provide the first detailed characterisation of the T6SS loci in ST410 and ST131 and shed light on events in the evolutionary pathways of the prominent MDR pathogens ST410-B4/H42RxC and ST131-C2/H30Rx.
Prediction of G4 formation in live cells with epigenetic data: a deep learning approach
Authors: Korsakova Anna , Phan Anh Tuân
Published: March 2023

G-quadruplexes (G4s) are secondary structures abundant in DNA that may play regulatory roles in cells. Despite the ubiquity of the putative G-quadruplex sequences (PQS) in the human genome, only a small fraction forms secondary structures in cells. Folded G4, histone methylation and chromatin accessibility are all parts of the complexcisregulatory landscape. We propose an approach for G4 formation prediction in cells that incorporates epigenetic and chromatin accessibility data. The novel approach termedepiG4NNefficiently predicts cell-specific G4 formation in live cells based on a local epigenomic snapshot. Our architecture confirms the close relationship between H3K4me3 histone methylation, chromatin accessibility and G4 structure formation. Trained on A549 cell data,epiG4NNwas then able to predict G4x formation in HEK293T and K562 cell lines. We observe the dependency of model performance with different epigenetic features on the underlying experimental condition of G4 detection. We expect that this approach will contribute to the systematic understanding of correlations between structural and epigenomic feature landscape.
BRWD3 promotes KDM5 degradation to maintain H3K4 methylation levels
Authors: Han Dongsheng , Schaffner Samantha H. , Davies Jonathan P. , Benton Mary Lauren , Plate Lars , Nordman Jared T.
Published: March 2023

Histone modifications are critical for regulating chromatin structure and gene expression. Dysregulation of histone modifications likely contributes to disease states and cancer. Depletion of the chromatin-binding protein BRWD3, a known substrate-specificity factor of the Cul4-DDB1 E3 ubiquitin ligase complex, results in increased in H3K4me1 levels. The underlying mechanism linking BRWD3 and H3K4 methylation, however, has yet to be defined. Here, we show that depleting BRWD3 not only causes an increase in H3K4me1 levels, but also causes a decrease in H3K4me3 levels, indicating that BRWD3 influences H3K4 methylation more broadly. Using immunoprecipitation coupled to quantitative mass spectrometry, we identified an interaction between BRWD3 and the H3K4-specific demethylase 5 (KDM5/Lid), an enzyme that removes tri- and di- methyl marks from H3K4. Moreover, analysis of ChIP-seq data revealed that BRWD3 and KDM5 are significantly co- localized throughout the genome and that sites of H3K4me3 are highly enriched at BRWD3 binding sites. We show that BRWD3 promotes K48-linked polyubiquitination and degradation of KDM5 and that KDM5 degradation is dependent on both BRWD3 and Cul4. Critically, depleting KDM5 fully restores altered H3K4me3 levels and partially restores H3K4me1 levels upon BRWD3 depletion. Together, our results demonstrate that BRWD3 regulates KDM5 activity to balance H3K4 methylation levels.
The G protein-coupled receptor TBXA2R activates ERMs to control cell motility and invasion of triple-negative breast cancer cells.
Authors: Leguay Kevin , Naffati Omaima , He Yu Yan , Rogue Mireille , Tesniere Chloe , Gombos Melania , Kuasne Hellen , Gaboury Louis , Le Gouill Christian , Meloche Sylvain , Bouvier Michel , Carreno Sebastien
Published: March 2023

Cell migration and invasion are critical processes for cancer cell metastasis, relying on the ability of cells to adapt their morphology. Proteins of the ezrin, radixin, and moesin (ERM) family are key regulators of cell morphogenesis and essential determinants of cancer cell metastasis. However, the mechanisms by which ERMs are activated in metastatic cells remain poorly understood. Here, we identify the thromboxane A2 receptor (TBXA2R), a G protein-coupled receptor overexpressed in multiple cancers, as a critical activator of ERMs, enhancing the motility and invasion of triple-negative breast cancer (TNBC) cells. We found that TBXA2R activates ERMs by engaging the Gαq/11 and Gα12/13 subfamilies, the small GTPase RhoA, and its Ser/Thr kinase effectors SLK and LOK. Furthermore, we demonstrate that TBXA2R promotes TNBC cell motility and invasion in vitro and metastatic colonization in vivo, dependent on ERM function. These findings reveal a novel signaling axis by which a member of the largest class of receptors activates key metastatic determinants, thereby controlling various aspects of metastasis. This discovery opens new avenues for developing targeted therapies against cancer metastasis.
Mathematical modeling suggests cytotoxic T lymphocytes control growth of B16 tumor cells in collagin-fibrin gels by cytolytic and non-lytic mechanisms
Authors: Majumder Barun , Budhu Sadna , Ganusov Vitaly V.
Published: March 2023

Cytotoxic T lymphocytes (CTLs) are important in controlling some viral infections, and therapies involving transfer of large numbers of cancer-specific CTLs have been successfully used to treat several types of cancers in humans. While molecular mechanisms of how CTLs kill their targets are relatively well understood we still lack solid quantitative understanding of the kinetics and efficiency at which CTLs kill their targets in different conditions. Collagen-fibrin gel-based assays provide a tissue-like environment for the migration of CTLs, making them an attractive system to study the cytotoxicity in vitro. Budhuet al.[1] systematically varied the number of peptide (SIINFEKL)- pulsed B16 melanoma cells and SIINFEKL-specific CTLs (OT-1) and measured remaining targets at different times after target and CTL co-inoculation into collagen-fibrin gels. The authors proposed that their data were consistent with a simple model in which tumors grow exponentially and are killed by CTLs at a per capita rate proportional to the CTL density in the gel. By fitting several alternative mathematical models to these data we found that this simple “exponential-growth-mass-action-killing” model does not precisely fit the data. However, determining the best fit model proved difficult because the best performing model was dependent on the specific dataset chosen for the analysis. When considering all data that include biologically realistic CTL concentrations (E≤ 107cell/ml) the model in which tumors grow exponentially and CTLs suppress tumor’s growth non-lytically and kill tumors according to the mass-action law (SiGMA model) fitted the data with best quality. Results of power analysis suggested that longer experiments (∼ 3 − 4 days) with 4 measurements of B16 tumor cell concentrations for a range of CTL concentrations would best allow to discriminate between alternative models. Taken together, our results suggest that interactions between tumors and CTLs in collagen-fibrin gels are more complex than a simple exponential-growth- mass-action killing model and provide support for the hypothesis that CTLs impact on tumors may go beyond direct cytotoxicity.
The immune response to a fungus in pancreatic cancer samples
Authors: Brayer KJ , Hanson JA , Cingam S , Martinez C , Ness SA , Rabinowitz I
Published: March 2023

Pancreatic ductal adenocarcinoma (PDAC) is a poor prognosis cancer with an .aggressive growth profile that is often diagnosed at late stage and that has few curative or therapeutic options. PDAC growth has been linked to alterations in the pancreas microbiome, which could include the presence of the fungusMalassezia. We used RNA-sequencing to compare 14 paired tumor and normal (tumor adjacent) pancreatic cancer samples and foundMalasseziaRNA in both the PDAC and normal tissues. Although the presence ofMalasseziawas not correlated with tumor growth, a set of immune- and inflammatory-related genes were up-regulated in the PDAC compared to the normal samples, suggesting that they are involved in tumor progression. Gene set enrichment analysis suggests that activation of the complement cascade pathway and inflammation could be involved in pro PDAC growth.
Bayesian Multi-Study Non-Negative Matrix Factorization for Mutational Signatures
Authors: Grabski Isabella N. , Trippa Lorenzo , Parmigiani Giovanni
Published: March 2023

Abstract

Mutational signatures shed insight into the range of mutational processes giving rise to tumors and allow a better understanding of cancer origin. They are typically identified from high-throughput sequencing data of cancer genomes using non-negative matrix factorization (NMF), and many such techniques have been developed towards this aim. However, it is often of particular interest to compare mutational signatures across multiple conditions, e.g. to understand which signatures are present across different treatments, or to identify signatures that are shared or specific across cancer types. Existing techniques within the NMF context only allow decomposition within a single dataset, so that integrating results across multiple conditions requires running separate analyses on each dataset, followed by subjective and manual comparisons of the identified signatures. To address this issue, we propose a Bayesian multi-study NMF method that jointly decomposes multiple studies or conditions to identify signatures that are common, specific, or partially shared by any subset. We propose two models: a “discovery-only” model that estimates de novo signatures in a completely unsupervised manner, and a “recovery-discovery” model that builds informative priors from previously known signatures to both update the estimates of these signatures and identify any novel signatures. We then further extend these models to estimate the effects of sample-level covariates on the exposures to each signature, enforcing sparsity through a non-local spike-and-slab prior. We demonstrate our approach on a range of simulations, and apply our method to colorectal cancer samples to show its utility.
Competence for transcellular infection in the root cortex involves a post-replicative, cell-cycle exit decision inMedicago truncatula
Authors: Batzenschlager Morgane , Lace Beatrice , Zhang Ning , Su Chao , Egli Sabrina , Krohn Pascal , Salfeld Jule , Ditengou Franck Anicet , Laux Thomas , Ott Thomas
Published: March 2023

During root nodule symbiosis (RNS), cell-division activity is re-initiated and sustained in the root cortex to create a hospitable cellular niche. Such temporary and spatially confined site is required to render host cells compatible with the intracellular progression of rhizobia. Although it has been suggested that early infection events might involve a pre-mitotic cell-cycle arrest, this process has not been dissected with cellular resolution. Here, we show that a dual-colour Medicago histone reporter robustly identifies cells with different mitotic or endoreduplication activities in the root cortex. By imaging deep root tissues, we found that a confined trajectory of cortical cells that are transcellularly passed by infection threads are in a stage of the cell-cycle that is distinct from directly adjacent cells. Distinctive features of infected cells include nuclear widening and large-scale chromatin rearrangements consistent with a cell-cycle exit prior to differentiation. Using a combination of fluorescent reporters demarcating cell-cycle phase progression, we confirmed that a reduced proliferation potential and modulating the G2/M transition, a process possibly controlled by the NF-YA1 transcription factor, mark the success of rhizobial delivery to nodule cells.
Design and implementation of suspended drop crystallization
Authors: Gillman Cody , Nicolas William J. , Martynowycz Michael W. , Gonen Tamir
Published: March 2023

We have developed a novel crystal growth method known as suspended drop crystallization. Unlike traditional methods, this technique involves mixing protein and precipitant directly on an electron microscopy grid without any additional support layers. The grid is then suspended within a crystallization chamber which we designed, allowing for vapor diffusion to occur from both sides of the drop. A UV transparent window above and below the grid enables the monitoring of crystal growth via light, UV, or fluorescence microscopy. Once crystals have formed, the grid can be removed and utilized for x-ray crystallography or microcrystal electron diffraction (MicroED) directly without having to manipulate the crystals. To demonstrate the efficacy of this method, we grew crystals of the enzyme proteinase K and determined its structure by MicroED following FIB/SEM milling to render the sample thin enough for cryoEM. Suspended drop crystallization overcomes many of the challenges associated with sample preparation, providing an alternative workflow for crystals embedded in viscous media, sensitive to mechanical stress, and/or suffering from preferred orientation on EM grids.
KGETCDA: an efficient representation learning framework based on knowledge graph encoder from transformer for predicting circRNA-disease associations
Authors: Wu Jinyang , Ning Zhiwei , Ding Yidong , Wang Ying , Peng Qinke , Fu Laiyi
Published: March 2023

Recent studies have demonstrated the significant role that circRNA plays in the progression of human diseases. Identifying circRNA-disease associations (CDA) in an efficient manner can offer crucial insights into disease diagnosis. While traditional biological experiments can be time-consuming and labor-intensive, computational methods have emerged as a viable alternative in recent years. However, these methods are often limited by data sparsity and their inability to explore high-order information. In this paper, we introduce a novel method named Knowledge Graph Encoder from Transformer for predicting CDA (KGETCDA). Specifically, KGETCDA first integrates more than 10 databases to construct a large heterogeneous non-coding RNA dataset, which contains multiple relationships between circRNA, miRNA, lncRNA and disease. Then, a biological knowledge graph is created based on this dataset and Transformer-based knowledge representation learning and attentive propagation layers are applied to obtain high-quality embeddings with accurately captured high-order interaction information. Finally, multilayer perceptron is utilized to predict the matching scores of CDA based on their embeddings. Our empirical results demonstrate that KGETCDA significantly outperforms other state-of-the-art models. To enhance user experience, we have developed an interactive web-based platform named HNRBase that allows users to visualize, download data and make predictions using KGETCDA with ease.
Molecular Evidence of Internal Carbon-Driven Partial Denitrification Annamox (PdNA) in a mainstream Pilot A-B System Coupled with Side-stream EBPR treating municipal wastewater
Authors: Kang Da , Han IL , Lee Jangho , McCullough Kester , Li Guangyu , Wang Dongqi , Klaus Stephanie , Zheng Ping , Srinivasan Varun , Bott Charles , Gu April Z.
Published: March 2023

Achieving mainstream short-cut nitrogen removal via nitrite has been a carbon and energy-efficient goal which wastewater engineers are dedicated to explore. This study applied a novel pilot-scale A-B-S2EBPR system process integrated with sidestream enhanced biological phosphorus removal) to achieve the nitrite accumulation and downstream anammox for treating municipal wastewater. Nitrite accumulated to 5.5 ± 0.3 mg N/L in the intermittently aerated tanks of B-stage with the nitrite accumulation ratio (NAR) of 79.1 ± 6.5%. The final effluent concentration and removal efficiency of total inorganic nitrogen (TIN) were 4.6 ± 1.8 mg N/L and 84.9 ± 5.6%, respectively. Batch nitrification/denitrification activity tests and functional gene abundance of ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) suggested that the nitrite accumulation was mostly caused by partial denitrification without NOB- selection. The unique features of S2EBPR (longer anaerobic HRT/SRT, lower ORPs, high and more complex VFAs etc.) seemed to impact the nitrogen microbial communities: the conventional AOB kept at a very low level of 0.13 ± 0.13% during the operation period, and the dominant candidate internal carbon-accumulating heterotrophic genera ofAcinetobacter(17.8 ± 15.5)% andComamonadaceae(6.7 ± 3.4%) were highly enriched. Furthermore, the single-cell Raman spectroscopy-based intracellular polymer analysis revealed the dominate microorganisms that could utilize polyhydroxyalkanoates (PHA) as the potential internal carbon source to drive partial denitrification. This study provides insights and a new direction for implementing the mainstream PdNA short-cut nitrogen removal via incorporating S2EBPR into sustainable A-B process.
Maternal Infection with Group B Streptococcus Correlates Inversely with Preeclampsia in Pregnant African American Women
Authors: Kwon Keun Soo , Cheng Tzu Hsuan , Zhou Jordan , Cai Huchong , Lee Sharon , Velickovic Ivan , Dalloul Mudar , Wlody David , Zhang Ming
Published: March 2023

Objective

Preeclampsia is more prevalent in African American women than other races. GBS colonization rate in African American women is the highest among different races. We hypothesized there is an association between GBS colonization and preeclampsia among pregnant African American women.

Study Design

We evaluated the relationship between GBS colonization and preeclampsia in 11,766 patients’ records (93% were African Americans patients) between 2010 and 2017.

Results

The preeclampsia rate of GBS colonized patients (2.6%) was 59% less than that of GBS-negative patients (6.3%). This inverse correlation was independently significant after adjusting for other potential risk factors for preeclampsia: chronic hypertension, gestational diabetes mellitus and diabetes mellitus and other covariates. Further analysis among the patients without these risk factors also confirmed that the preeclampsia rate of GBS colonized patients (2.6%) was 55% less than that of GBS negative patients (5.7%). Similarly, patients with HSV+ or HIV+ had lower incidence of preeclampsia than those with HSV- or HIV-.

Conclusions

The unexpected finding of an inverse relationship between GBS colonization and preeclampsia suggests that the maternal immune response to GBS infection may be beneficial in reducing preeclampsia among African American patients.
The meaning and role of the functional-organic distinction: a study of clinicians in psychiatry and neurology services
Authors: Chesterfield Alice , Harvey Jordan , Hendrie Callum , Wilkinson Sam , San Juan Norha Vera , Bell Vaughan
Published: March 2023

Aims

The functional-organic distinction attempts to differentiate disorders with diagnosable biological causes from those without and is a central axis on which diagnoses, medical specialities, and services are organised. Previous studies report poor agreement between clinicians regarding the meanings of the terms and some of the conditions to which they apply, while noting the value-laden implications of relevant diagnoses. Consequently, we aimed to understand how clinicians working in psychiatry and neurology services navigate the functional-organic distinction in their work.

Method

Twenty clinicians (10 physicians, 10 psychologists) working in psychiatry and neurology services participated in semi-structured interviews that were analysed applying a constructivist grounded theory approach.

Results

The distinction was described as often incongruent with how clinicians conceptualise patients’ problems. Organic factors were considered to be objective, unambiguously identifiable, and clearly causative, whereas functional causes were invisible and to be hypothesised through thinking and conversation. Contextual factors – including cultural assumptions, service demands, patient needs, and colleagues’ views – were key in how the distinction was deployed in practice. The distinction was considered theoretically unsatisfactory, eventually to be superseded, but clinical decision-making required it to be used strategically. This included helping communicate medical problems, navigating services, hiding meaning by making psychological explanations more palatable, tackling stigma, giving hope, and giving access to illness identity. Clinicians cited moral issues at individual and societal levels as integral to the conceptual basis and deployment of the functional-organic distinction and described actively navigating these as part of their work.

Conclusions

There is a considerable distance between the status of the functional-organic distinction as a sound theoretical concept generalisable across conditions and its role as a gatekeeping tool within the structures of healthcare. Ambiguity and contradictions were considered as both obstacles and benefits when deployed in practice and strategic considerations were important in deciding which to lean on.
Metabolic regulation of misfolded protein import into mitochondria
Authors: Wang Yuhao , Ruan Linhao , Zhu Jin , Zhang Xi , Chang Alexander Chih-Chieh , Tomaszewski Alexis , Li Rong
Published: March 2023

Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the ‘mitochondria as guardian in cytosol’ (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in yeast uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases.
Mycobacterium ulceransnot detected by PCR on human skin in Buruli ulcer endemic areas of south eastern Australia
Authors: Velink Anita , Porter Jessica L. , Stinear Timothy P , Johnson Paul D. R.
Published: March 2023

Introduction

Mycobacterium ulcerans(MU) causes Buruli ulcer (BU), a geographically restricted infection that can result in skin loss, contracture, and permanent scarring. Lesion-location maps compiled from more than 640 cases in south eastern Australia suggest biting insects are likely involved in transmission, but it is unclear whether MU is brought by insects to their target or if MU is already on the skin and inoculation is an opportunistic event that need not be insect dependent.

Methods

We validated a PCR swab detection assay and defined its dynamic range using laboratory culturedM. ulceransand fresh pigskin. We invited volunteers in Buruli-endemic and non-endemic areas to sample their skin surfaces with self-collected skin swabs tested by IS2404 quantitative PCR.

Results

Pigskin validation experiments established a limit-of-detection of 0.06 CFU/cm2at a qPCR cycle threshold (Ct) of 35. Fifty-seven volunteers returned their self-collected kits of 4 swabs (bilateral ankles, calves, wrists, forearms), 10 from control areas and 47 from endemic areas. Collection was timed to coincide with the known peak-transmission period of Buruli. All swabs from human volunteers tested negative (Ct ≥35).

Conclusions

M. ulceranswas not detected on the skin of humans from highly BU endemic areas.

Author Summary

Buruli ulcer (BU) incidence is increasing in temperate south eastern Australia. We have yet to develop public health programs to assist people avoid BU partly because the precise mode of transmission is contentious. Recent research has shown that environmental contamination withM. ulcerans(the cause of BU) is widespread in endemic areas as a result of faecal shedding from infected possums that live close to humans, although direct human-possum contact is rare. We investigated the possibility that the skin of humans in endemic areas could become transiently contaminated withM. ulceranswhile outdoors. If this were the case then BU prevention programs could be developed around skin protection and regular washing/showering. To study this possibility, we developed a sensitive skin swab PCR-assay that we tested using a pigskin laboratory model so we could be confident in our results. We asked volunteers to collect their own skin swabs after spending at least 4 hours outside during the known period of peak Buruli transmission. Fifty seven volunteers returned swab sets for testing. Our results were negative. We did not find evidence that humans in our endemic zone haveM. ulceranscontamination on their skin.
Improving magnetic resonance spectroscopy in the brainstem periaqueductal grey using spectral registration
Authors: Sirucek Laura , Zoelch Niklaus , Schweinhardt Petra
Published: March 2023

Purpose

Functional understanding of the periaqueductal grey (PAG), a clinically relevant brainstem region, can be advanced using proton magnetic resonance spectroscopy (1H-MRS). However, the PAG’s small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve1H-MRS quality in the PAG using spectral registration for frequency and phase error correction, (2) investigate whether spectral registration is particularly useful in cases of greater head motion and (3) examine metabolite quantification using literature-based or individual-based water relaxation times.

Methods

Spectra were acquired in 33 healthy volunteers (50.1 years, SD=17.19, 18 females) on a 3T Philipps MR system using a point-resolved spectroscopy sequence optimized with very selective saturation pulses (OVERPRESS) and voxel-based flip angle calibration (effective volume of interest size: 8.8×10.2×12.2 mm3). Spectra were fitted using LCModel and signal-to-noise ratios (SNR), N-acetylaspartate peak linewidths and Cramér-Rao lower bounds (CRLBs) were measured after spectral registration and after minimal frequency alignment.

Results

Spectral registration improved SNR by 5 % (p=0.026, median value post-correction: 18.0) and spectral linewidth by 23 % (p<0.001, 4.3 Hz), and reduced the metabolites’ CRLBs by 1-15 % (p’s<0.026). Correlational analyses revealed smaller SNR improvements with greater head motion (p=0.010) recorded using a markerless motion tracking system. Higher metabolite concentrations were detected using individual-based compared to literature-based water relaxation times (p’s<0.001).

Conclusion

This study demonstrates high-quality1H-MRS acquisition in the PAG using spectral registration. This shows promise for future1H-MRS studies in the PAG and possibly also other clinically relevant brain regions with similar methodological challenges.
Selection of processed and packaged potato-based snacks among university students: a cross-sectional study regarding food environment and dietary behavior
Authors: Sattar Saima , Khalid Nauman
Published: March 2023

Purpose

Potato-based snacks (PBS) are widely popular among people of all age groups despite known negative health aspects. University students, due to their busy routines and less familiarity with diets are more prone to selecting unhealthy meals and snacks. The study aims to explore the outlook of university students regarding their consumption of processed and packaged PBS in their daily lives and compares gender’s PBS choices with dietary habits and food environment.

Design/methodology/approach

A total of 122 students from various universities across Pakistan were included in this study. The data were collected using a structured questionnaire and distributed using the snowball method.

Findings

The university students showed a significant difference in their living habits (p = 0.016), where 25.4% of enrolled male students were hostellers as compared to females (14.8%). Significant differences were noticed in choosing PBS that further depends on the familiarity of the product, (p = 0.030), where 9.0% of female students rated familiarity with the product as being important while 20.5% of males responded familiarity as a critical factor. Studying the usual location/point of purchase for a PBS, a significant difference was observed (p = 0.008%) where more male students (27.9%) choose to buy their PBS from a local convenience store as compared to female students (18.9%). Female students (13.1%) would rather choose to buy their PBS on their weekly grocery runs.

Originality/value

This study concluded that female and male students’ attitudes regarding the consumption of PBS were almost the same regardless of environment and brand repute.

Highlights

Dietary behavioral studies of consumption of PBS

The environment and brand reputation have no impact on the consumption of PBS

Gender differences have no impact on the selection of PBS

Awareness and healthy selection of PBS are critical factors that need to be focused
Increasing the organizational performance of online sellers: the powerful back-end management systems
Authors: Ku Edward C.S. , Chen Chun-Der
Published: March 2023

Purpose

This study examines how customer-linking capabilities, the flexibility of back-end management systems, strategic agility and the perceived absorptive capacity of e-commerce influence the organizational performance of online sellers.

Design/methodology/approach

A performance model based on the adaptive structuration theory was employed to test the hypotheses using structural equation modeling (SEM) on a dataset of 325 samples with acceptable responses.

Findings

The results reveal that the customer-linking capability and flexibility of back-end management systems, strategic agility and assimilation of e-commerce activity significantly influence organizational performance in a virtual environment.

Originality/value

The agility of online sellers is becoming increasingly important, and from the perspective of adaptive structuration theory, back-end management systems have been built to manage buyer orders for online sellers.
Exploration of exhaustion in early-career construction professionals in India
Authors: Rastogi Ashish , Singla Harish Kumar
Published: March 2023

Purpose

The purpose of this study is to examine the effect of job, organizational and personal factors on exhaustion (EXH) in early career construction professionals in India.

Design/methodology/approach

A survey questionnaire was developed and circulated among early career construction professionals in India. The responses on job, organizational and personal demands (role ambiguity, stakeholder management and work-family conflict respectively) and job, organizational and personal resources (job autonomy (JA), perceived organizational support and emotional intelligence respectively) were sought using standard measures. The valid data (N = 187) thus collected, was analysed using structural equation modelling (SEM).

Findings

The study finds that in terms of demands, stakeholder management and work family conflict have a significant positive effect on EXH. In other words, EXH level increases with the increase in these two. With respect to resources, JA has a negative effect on EXH. This implies that as JA increases, the EXH level goes down.

Originality/value

This study is the first to examine factors causing EXH in early career construction professionals in India. This study is significant on two counts. First, it proposes a comprehensive theoretical model based in job demands-resources (JD-R) theory customized for construction sector. Second, the empirical examination is situated in the Indian context, which remains underexplored despite its economic and demographic significance.
Improving creativity among SME employees: exploring the role of organization-based self-esteem and psychological capital
Authors: Sujatha Madihalli , Mukherjee Ujjal , Singh Nishant , Bamel Umesh
Published: March 2023

Purpose

Unlike multinational companies, small and mid-size enterprises (SMEs) have budget constraints and, thereby, cannot invest heavily in improving the creativity of employees. They look for alternative budget-friendly ways to do the same. The authors of the current paper attempt to identify two psychological-based constructs which positively influence creativity among employees. Both these psychological constructs may be improved among the employees using suitable interventions from the human resource (HR) professionals and line managers working in the organization. This study is an attempt to test the influence of organization-based self-esteem (OBSE) and psychological capital (PC) (both malleable) on creative performance behaviour (CPB) among SME employees.

Design/methodology/approach

Validated instruments were used to collect data. Structural equation model (SEM) was used to evaluate the 377 responses collected from the employees working in three SME's in India. All three SMEs work in the area of innovative process design and require a high level of creativity among employees.

Findings

PC fully mediates the relationship between OBSE and the CPBs of employees. Employees experiencing higher levels of OBSE will develop higher self-esteem, and these employees will exhibit more creative behaviours, increasing the likelihood of achieving creative results.

Research limitations/implications

This study provides valuable inputs to the creativity literature as it describes the process of how self-esteem influences the creativity of an employee. HR professionals working in SMEs can work on enhancing the OBSE and PC (both malleable) of employees to improve creativity among employees.

Originality/value

To the best of the researcher's knowledge, this is the first attempt to identify frugal ways to improve creativity, especially in SMEs.