bluuebunny/crossref_metadata_2025 huggingface dataset:
Thymectomy in myasthenia gravis
Authors: Rath Jakob , Moser Bernhard , Zimprich Fritz
Published: August 2023

Purpose of review

Thymectomy has long been used in the treatment of patients with myasthenia gravis and antibodies against the acetylcholine receptor. However, its effectiveness has only been proven a few years ago in a randomized controlled trial in patients under the age of 65. Here, we review the current literature focusing on patient subgroups, potential biomarkers for outcome prediction and the choice of surgical approach.

Recent findings

Long-term follow-up studies after thymectomy confirmed that the benefits regarding clinical outcome parameters and a reduced need for immunosuppressive treatment persist. Nevertheless, a substantial proportion of patients in real-world cohorts do not reach complete stable remission after thymectomy indicating that the underlying autoimmune process is sustained in the periphery. Our understanding of the responsible mechanisms has improved with recent studies. Presently, outcome data after thymectomy in several patient subgroups, such as those aged over 50 years, those with juvenile onset or those with purely ocular symptoms are limited and have been the focus of recent research activities. Similarly, biomarkers guiding an appropriate patient selection for thymectomy are under investigation. A number of cohort studies demonstrated that minimal invasive surgical techniques such as extended robotic thymectomy lead to similar positive outcomes as a transsternal approach with potentially fewer short-term adverse effects.

Thymectomy is an effective treatment option in adult patients with early onset acetylcholine-receptor positive myasthenia gravis but uncertainty remains with regard to certain patient subgroups.
Advanced brain imaging for the diagnosis of Alzheimer disease
Authors: Wang Yi-Ting Tina , Rosa-Neto Pedro , Gauthier Serge
Published: August 2023

Purpose of review

The purpose is to review the latest advances of brain imaging for the diagnosis of Alzheimer disease (AD).

Recent findings

Brain imaging techniques provide valuable and complementary information to support the diagnosis of Alzheimer disease in clinical and research settings. The recent FDA accelerated approvals of aducanumab, lecanemab and donanemab made amyloid-PET critical in helping determine the optimal window for anti-amyloid therapeutic interventions. Tau-PET, on the other hand, is considered of key importance for the tracking of disease progression and for monitoring therapeutic interventions in clinical trials. PET imaging for microglial activation, astrocyte reactivity and synaptic degeneration are still new techniques only used in the research field, and more studies are needed to validate their use in the clinical diagnosis of AD. Finally, artificial intelligence has opened new prospective in the early detection of AD using MRI modalities.

Brain imaging techniques using PET improve our understanding of the different AD-related pathologies and their relationship with each other along the course of disease. With more robust validation, machine learning and deep learning algorithms could be integrated with neuroimaging modalities to serve as valuable tools for clinicians to make early diagnosis and prognosis of AD.
A patient with neuropathy and ataxia: what do I have to consider?
Authors: Roberts Leslie J. , Szmulewicz David J.
Published: August 2023

Purpose of review

An increasing number of peripheral neuro(no)pathies are identified as involving other components of the neurological system, particularly those that further impair balance. Here we aim to outline an evidence-based approach to the diagnosis of patients who present with a somatosensory disorder which also involves at least one other area of neurological impairment such as the vestibular, auditory, or cerebellar systems.

Recent findings

Detailed objective investigation of patients who present with sensory impairment, particularly where the degree of imbalance is greater than would be expected, aids the accurate diagnosis of genetic, autoimmune, metabolic, and toxic neurological disease.

Diagnosis and management of complex somatosensory disorders benefit from investigation which extends beyond the presenting sensory impairment.
Performance of ChatGPT in Diagnosis of Corneal Eye Diseases
Authors: Delsoz Mohammad , Madadi Yeganeh , Munir Wuqaas M , Tamm Brendan , Mehravaran Shiva , Soleimani Mohammad , Djalilian Ali , Yousefi Siamak
Published: August 2023

Introduction

Assessing the capabilities of ChatGPT-4.0 and ChatGPT-3.5 for diagnosing corneal eye diseases based on case reports and compare with human experts.

Methods

We randomly selected 20 cases of corneal diseases including corneal infections, dystrophies, degenerations, and injuries from a publicly accessible online database from the University of Iowa. We then input the text of each case description into ChatGPT-4.0 and ChatGPT3.5 and asked for a provisional diagnosis. We finally evaluated the responses based on the correct diagnoses then compared with the diagnoses of three cornea specialists (Human experts) and evaluated interobserver agreements.

Results

The provisional diagnosis accuracy based on ChatGPT-4.0 was 85% (17 correct out of 20 cases) while the accuracy of ChatGPT-3.5 was 60% (12 correct cases out of 20). The accuracy of three cornea specialists were 100% (20 cases), 90% (18 cases), and 90% (18 cases), respectively. The interobserver agreement between ChatGPT-4.0 and ChatGPT-3.5 was 65% (13 cases) while the interobserver agreement between ChatGPT-4.0 and three cornea specialists were 85% (17 cases), 80% (16 cases), and 75% (15 cases), respectively. However, the interobserver agreement between ChatGPT-3.5 and each of three cornea specialists was 60% (12 cases).

Conclusions

The accuracy of ChatGPT-4.0 in diagnosing patients with various corneal conditions was markedly improved than ChatGPT-3.5 and promising for potential clinical integration.

Key summary points

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The aim of this work was to evaluate the performance of ChatGPT-4 and ChatGPT-3.5 for providing the provisional diagnosis of different corneal eye diseases based on case descriptions and compared them with three cornea specialists.

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The accuracy of ChatGPT-4.0 in diagnosing patients with various corneal conditions was significantly better than ChatGPT-3.5 based on the specific cases.

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The interobserver agreement between ChatGPT-4.0 and ChatGPT-3.5 was 65% while the interobserver agreement between ChatGPT-4.0 and three cornea specialists were 85%, 80%, and 75%, respectively.
Retrieval induced forgetting in a non-monotonic hippocampal model
Authors: Midler Benjamin , McClelland James
Published: August 2023

Retrieval induced forgetting (RIF) occurs when the retrieval of one item negatively impacts the recall probability of related items stored in memory (Anderson et al., 1994). Recently, Ritvo et al. (2023) demonstrated RIF emerges in a neural network model equipped with non-monotonic plasticity. Their finding supports the non-monotonic plasticity hypothesis (NMPH; Ritvo et al., 2019): the theory that connection changes in the brain follow a “U” shaped function of post-synaptic stimulation. Here, we apply a unique implementation of non-monotonic plasticity to a neural network model of an idealized hippocampus (HPC) and evaluate it with an adaptation of a classic RIF task. The model evidences the behavioral and representational characteristics of RIF, replicating Ritvo et al. (2023). As a monotonic baseline model failed these tests, we provide evidence of non-monotonic plasticity’s sufficiency for RIF. In addition to demonstrating the NMPH is robust to multiple implementations and evaluative paradigms, we conduct additional analysis to provide a mechanistic explanation for how non-monotonic plasticity brings about RIF. Lastly, we evaluate the model with an expansion of RIF: reverse RIF. The model fails this final test, raising questions for future research on the necessary parameters of non-monotonic plasticity and whether it must pair with complementary processes in the brain.
Structural Determinants of Tendon Function During Development and Their Sensitivity to Mechanical Stimulation
Authors: Peterson Benjamin E. , Canonicco Castro Maria L. , McCarthy Helen , Buckley Niamh , Dunne Nicholas , Rolfe Rebecca , Murphy Paula , Szczesny Spencer E.
Published: August 2023

The load-bearing capabilities of tendon are acquired during neonatal stages of development, characterized by an abrupt increase in multiscale mechanical properties. While prior work has identified numerous changes within the collagenous structure during these developmental periods, the primary structural elements that give rise to this abrupt mechanical functionality, and their mechanobiological sensitivity, remains unclear. To address this gap in knowledge, we leveraged a combination of ultrastructural imaging, biochemical/thermodynamic assays, multiscale mechanical testing, and shear lag modeling to probe the dynamic structure-function relationships and establish their sensitivity to mechanical stimulation during tenogenesis. Mechanical testing and modeling suggested that the rapid increase in multiscale mechanics can be explained by a increasing fibril length and intrafibrillar crosslinking. To test this, we inhibited collagen crosslinking during development and observed a drastic reduction in multiscale mechanical capabilities that was explained by a reduction in both fibril modulus and length. Using muscle paralysis to investigate mechanosensitivity, we observed a significantly impaired multiscale mechanical response despite small changes in fibril diameter and fibril area fraction. While there was no change in crosslinking density, there was a decrease in thermal stability with flaccid paralysis, and our shear-lag model suggested that flaccid paralysis produces a reduction in fibril length and intrafibrillar crosslinking. Together, these data suggest that both intrafibrillar crosslink formation and fibril elongation are critical to the formation of load-bearing capabilities in tenogenesis and are sensitive to musculoskeletal activity. These findings provide critical insights into the biological mechanisms that give rise to load-bearing soft tissue.
Evaluation of the appropriateness of pesticide administration-concentrations to honey beeApis melliferacolony in long-term field experiments and modest proposal
Authors: Yamada Toshiro
Published: August 2023

For investigating the effects of pesticides on bee colonies in actual apiaries, field experiments in an open environment are effective. It is natural to assume that the total food or pesticide intake taken by a honey bee colony includes their intakes from nature in addition to each administered in the field experiment. Therefore, in field experiments, setting the administration-concentration of pesticides for honey bee colonies is one of the most difficult tasks.

The validity of pesticide concentrations administered to bee colonies was evaluated by various intakes of pesticides and foods obtained from five long-term field experiments conducted in Midwest Japan with distinct changes of four seasons and Maui, U.S.A. without cold winter.

The author found a relationship, logPBD=logCP–2.4, between pesticide concentration (CP) and the average daily intake of pesticide ingested by one bee (PBD), and found that their ratioPBD/CPwas about 1/250, which was significantly lower than theLD50value.

This fact supports that the concentration of pesticide administration in long-term field experiments conducted so far was not too high, but rather reasonable.

In addition, the average daily intakes of sugar syrup and pollen paste ingested by one bee was found to be 3.1 mg/bee/day and 0.8 mg/bee/day, respectively, and notwithstanding their wide variation, be roughly constant regardless of the concentration of pesticides.

I believe that this paper will help provide new guidelines for setting pesticide dosing concentrations, which have not been clear so far, in field experiments on the administration of pesticides to bee colonies.
Contributions of individual satellite cells to muscle regeneration assessed using a confetti mouse model
Authors: Heemskerk Hans , Jagannathan N. Suhas , Nasir N. Jannah M. , Nguyen Binh P. , Sacadevan Keshmarathy , Matsudaira Paul T. , So Peter T.C. , Tucker-Kellogg Lisa
Published: August 2023

Insufficient regeneration is implicated in muscle pathologies, but much remains unknown about the regenerative output of individual muscle stem cells, called satellite cells (SCs). Prior work showed that individual SCs contribute to regeneration of more than one muscle fiber (“fiber-crossing”) after full-muscle damage. We investigated whether fiber-crossing also occurred in peripheral regions of a localized muscle injury. To assess fiber-crossing with a minimum number of mice, we used lineage tracing with confetti fluorescence, and developed a novel stochastic modeling method to interpret the ambiguity of multi-color fluorescent lineage tags. Microscopy of the regenerated muscle showed that adjacent fibers often expressed the same-colored tags. Computational analysis concluded that the observed color patches would be extremely unlikely to occur by chance unless SCs contributed myonuclei to multiple adjacent fibers (26-33% of SCs contributing to at most 1-2 additional fibers). Interestingly, these results were similar across the different regions studied, suggesting that severe destruction is not required for fiber-crossing. Our method to assess fiber-crossing may be useful for future study of gene and cell therapies that use fiber-crossing to aid muscle regeneration.
The highly rugged yet navigable regulatory landscape of the bacterial transcription factor TetR
Authors: Westmann Cauã Antunes , Goldbach Leander , Wagner Andreas
Published: August 2023

Transcription factor binding sites (TFBSs) are important sources of evolutionary innovations. Understanding how evolution navigates the sequence space of such sites can be achieved by mapping TFBS adaptive landscapes. In such a landscape, an individual location corresponds to a TFBS bound by a transcription factor. The elevation at that location corresponds to the strength of transcriptional regulation conveyed by the sequence. We developed anin vivomassively parallel reporter assay to map the landscape of bacterial TFBSs. We applied this assay to the TetR repressor, for which few TFBSs are known. We quantify the strength of transcriptional repression for 17,765 TFBSs and show that the resulting landscape is highly rugged, with 2,092 peaks. Only a few peaks convey stronger repression than the wild type. Non-additive (epistatic) interactions between mutations are frequent. Despite these hallmarks of ruggedness, most high peaks are evolutionarily accessible. They have large basins of attraction and are reached by around 20% of populations evolving on the landscape. Which high peak is reached during evolution is unpredictable and contingent on the mutational path taken. This first in-depth analysis of a prokaryotic gene regulator reveals a landscape that is navigable but much more rugged than the landscapes of eukaryotic regulators.

Significance

Understanding how evolution explores the vast space of genotypic possibilities is a fundamental question in evolutionary biology. The mapping of genotypes to quantitative traits (such as phenotypes and fitness) allows us to delineate adaptive landscapes and their topological properties, shedding light on how evolution can navigate such vast spaces. In this study, we focused on mapping a transcription factor binding site (TFBS) landscape to gene expression levels, as changes in gene expression patterns play a crucial role in biological innovation. We developed a massively parallel reporter assay and mapped the first comprehensive in vivo gene regulatory landscape for a bacterial transcriptional regulator, TetR. Surprisingly, this landscape is way more rugged than those observed in eukaryotic regulators. Despite its ruggedness, the landscape remains highly navigable through adaptive evolution. Our study presents the first high-resolution landscape for a bacterial TFBS, offering valuable insights into the evolution of TFBS in vivo. Moreover, it holds promise as a framework for discovering new genetic components for synthetic biological systems.
The genetic basis of apple shape and size unraveled by digital phenotyping
Authors: Keller Beat , Jung Michaela , Bühlmann-Schütz Simone , Hodel Marius , Studer Bruno , Broggini Giovanni AL , Patocchi Andrea
Published: August 2023

Great diversity of shape, size, and skin color is observed among the fruits of different apple genotypes. These traits are critical for consumers and therefore interesting targets for breeding new apple varieties. However, they are difficult to phenotype and their genetic basis, especially for fruit shape and ground color, is largely unknown. We used the fruit FruitPhenoBox to digitally phenotype 506 genotypes of the apple reference population (apple REFPOP) genotyped for 303,148 single nucleotide polymorphism (SNP) markers. From the apple images, 573 highly heritable features describing fruit shape and size as well as 17 highly heritable features for fruit skin color were extracted to explore genotype-phenotype relationships. Out of these features, nine and four principal components (PCs) as well as 16 and eight uncorrelated features were chosen to carry out genome-wide association studies for fruit shape, size, and fruit skin color, respectively. In total, 69 SNPs scattered over all 17 apple chromosomes were significantly associated with round, conical, cylindrical, or symmetric fruit shapes and fruit size. Novel associations with major effect on round or conical fruit shapes and fruit size were identified on chromosomes 1 and 2. Additionally, 16 SNPs associated with PCs and uncorrelated features related to red over color as well as green and yellow ground color were found on eight chromosomes. The identified associations can be used to advance marker-assisted selection in apple fruit breeding to systematically select for desired fruit appearance.
iSanXoT: a Standalone Application for the Integrative Analysis of Mass Spectrometry-Based Quantitative Proteomics Data
Authors: Rodríguez Jose Manuel , Jorge Inmaculada , Barrero-Rodríguez Rafael , Magni Ricardo , Núñez Estefanía , Laguillo Andrea , Devesa Cristina A. , López Juan A. , Camafeita Emilio , Vázquez Jesús
Published: August 2023

Numerous bioinformatics tools currently exist to perform quantitative analysis of proteomics experiments. The majority of these tools apply diverse statistical models to assign a quantitative protein value from the mass-spectrometry information. Here we present iSanXoT, a standalone application that allows integrative analysis of quantitative proteomics data. iSanXoT processes relative abundances between MS signals and integrates them sequentially to upper levels using our previously published Generic Integration Algorithm (GIA). iSanXoT offers unique capabilities that complement conventional quantitative softwares, including statistical weighting and independent modeling of error distributions in each integration, aggregation of technical or biological replicates, quantification of posttranslational modifications or analysis of coordinated protein behavior. iSanXoT is a standalone, user-friendly application which accepts output from widespread proteomics pipelines and enables free construction of quantification workflows and fully customizable reports than can be reused across different projects or shared among users. Diverse integrative workflows constructed using GIA for the analysis of high-throughput quantitative proteomics experiments have been successfully applied in numerous publications. iSanXoT has been tested with the main operating systems. Download links for the corresponding distributions are available athttps://github.com/CNIC-Proteomics/iSanXoT/releases.
In silico spatial transcriptomic editing at single-cell resolution
Authors: Wu Jiqing , Koelzer Viktor H.
Published: August 2023

Motivation

Generative artificial intelligence (AI) has enabled fundamental breakthroughs in visual content creation by text-guided editing. However, the utility of such generative models remains largely understudied for processing increasingly complex bioimage data.

Results

We propose to algorithmically edit gene expression data to drive cell-level morphological transitions using Generative Adversarial Networks (GAN) and GAN Inversion models. Leveraging cutting-edge spatial transcriptomic datasets with subcellular in-situ resolution and matched high-content imaging data, we propose an in-silico approach to quantify, model and imitate pathological processes in real-life clinical tissue samples.

Availability and implementation

The code and video demo is accessible viahttps://github.com/CTPLab/In-silico-editing
Beyond Lux: Methods for Species and Photoreceptor-Specific Quantification of Ambient Light for Mammals
Authors: McDowell Richard J , Didikoglu Altug , Woelders Tom , Gatt Mazie J , Hut Roelof A , Brown Timothy M , Lucas Robert J
Published: August 2023

Background

Light is a key environmental regulator of physiology and behaviour. Mistimed or insufficient light disrupts circadian rhythms and is associated with impaired health and well-being across mammals. Appropriate lighting is therefore crucial for indoor housed mammals. The most commonly used measurement for lighting is lux. However, this employs a spectral weighting function based on human perceived brightness and is not suitable for ‘non-visual’ effects of light or use across species. In humans, a photoreceptor-specific (α-opic) metrology system has been proposed as a more appropriate way of measuring light.

Results

Here we establish technology to allow this α-opic measurement approach to be readily extended to any mammalian species, accounting for differences in photoreceptor types, photopigment spectral sensitivities, and eye anatomy. Since measuring photopigment spectral sensitivity can be hard to derive for novel animals and photoreceptors, we developed a high-throughput, easy-to-use, method to derive spectral sensitivities for recombinantly expressed melanopsins and use it to establish the spectral sensitivity of melanopsin from 12 non-human mammals. We further address the need for simple measurement strategies for species-specific α-opic measures by developing an accessible online toolbox for calculating these units and validating an open hardware, low-cost, multichannel light sensor for ‘point and click’ measurement. We finally demonstrate that species-specific α-opic measurements are superior to photopic lux as predictors of physiological responses to light in mice and allow ecologically relevant comparisons of photosensitivity between species.

Conclusion

Our study demonstrates that measuring light more accurately using species-specific α-opic units is superior to the existing unit of photopic lux and holds the promise of improvements to the health and welfare of animals, scientific research reproducibility, agricultural productivity, and energy usage.
Mutational order and epistasis determine the consequences of FBXW7 mutations during colorectal cancer evolution
Authors: Chan Dedrick Kok Hong , Mandal Amit , Zhou Yi , Collins Scott David , Owen Richard , Bundred James , Fuchs Hannah , James Sabrina , Vendrell Iolanda , Flannery Sarah , Fawkner-Corbett David , Househam Jacob , Graham Trevor A , Fischer Roman , Simmons Alison , Lu Xin , Buczacki Simon James Alexander
Published: August 2023

Somatic driver mutations, in genes such as FBXW7, have been discovered in phenotypically normal colonic tissue, however their role in cancer initiation remains elusive. Using normal and gene-edited patient-derived human colon organoids as models of early tumour evolution we observed that FBXW7-/- mutations exerted an epistatic effect on subsequent transcription depending on the mutational background of the cell. Specifically, the timing of acquiring an FBXW7-/- mutation respective to an APC mutation, led to profound phenotypic and transcriptomic differences. When FBXW7 was mutated before APC, a near-normal cell state was maintained alongside repression of the APC transcriptional response. However, when APC was mutated before FBXW7, cells acquired classical cancer-stem cell features. Single-cell RNA sequencing revealed that mutation of FBXW7 in normal tissue subtly switched cells from adult to a foetal/regenerative stem cell state. Further analysis using transposase-accessible chromatin sequencing identified this cellular plasticity was driven by changes in chromatin accessibility of transcriptional start site regions associated with TEAD, SNAI1 and AP-1 motifs, which in turn activate the foetal-like state. Taken together, we demonstrate a critical role of FBXW7 mutations in preventing colorectal cancer initiation and provide exemplar evidence for the importance of epistasis and mutational order in cancer biology.
Examining dynamics of three-dimensional genome organization with multi-task matrix factorization
Authors: Lee Da-Inn , Roy Sushmita
Published: August 2023

Three-dimensional (3D) genome organization, which determines how the DNA is packaged inside the nucleus, has emerged as a key component of the gene regulation machinery. High-throughput chromosome conformation datasets, such as Hi-C, have become available across multiple conditions and timepoints, offering a unique opportunity to examine changes in 3D genome organization and link them to phenotypic changes in normal and diseases processes. However, systematic detection of higher-order structural changes across multiple Hi-C datasets remains a major challenge. Existing computational methods either do not model higher-order structural units or cannot model dynamics across more than two conditions of interest. We address these limitations with Tree-Guided Integrated Factorization (TGIF), a generalizable multi-task Non-negative Matrix Factorization (NMF) approach that can be applied to time series or hierarchically related biological conditions. TGIF can identify large-scale changes at compartment or subcompartment levels, as well as local changes at boundaries of topologically associated domains (TADs). Compared to existing methods, TGIF boundaries are more enriched in CTCF and reproducible across biological replicates, normalization methods, depths, and resolutions. Application to three multi-sample mammalian datasets shows TGIF can detect differential regions at compartment, subcompartment, and boundary levels that are associated with significant changes in regulatory signals and gene expression enriched in tissue-specific processes. Finally, we leverage TGIF boundaries to prioritize sequence variants for multiple phenotypes from the NHGRI GWAS catalog. Taken together, TGIF is a flexible tool to examine 3D genome organization dynamics across disease and developmental processes.
NRF2 Regulates Contractile Vascular Smooth Muscle Cells Phenotypic Switching In Abdominal Aortic Aneurysm
Authors: Xiao Xiaoyong , Huang Xiaoran , Song Feier , Chen Guona , Zhang Yuelin , Liu Xincheng , Zhou Xueke , Hong Yimei , He Haiwei , Meng Jinxiu , Huang Xiaojia , Zhong Lintao , Li Xin
Published: August 2023

OBJECTIVE

Evidence from previous studies has demonstrated that NRF2 can protect cardiovascular progression,which prompted us to study if NRF2 is involved in AAA development.

APPROACH AND RESULTS

The difference and function of NRF2 in AAA were verified on human aortic tissues combined with scRNA-seq samples.We then used angiotensin II (Ang II) infusion mouse model with VSMCs-specific knockout to study the role of NRF2 in AAA formation.Primary cultured VSMCs were used to study how NRF2 regulates contractile VSMCs phenotype.Patient specimens were obtained to investigate the relevance of NRF2 expression to human AAA disease. NRF2 was induced in abdominal aortic VSMCs in both mouse and human AAA tissues. VSMCs-specific NRF2 knockout increased experimental AAA formation. Mechanistically, NRF2 regulates the contractile VSMCs phenotypic through miRNA145, leading to increased classic contractile protein level to prevent the development of AAA.

CONCLUSIONS

NRF2 is a negative regulator of AAA development, and thus may represent a potentially new therapeutic target to inhibit AAA growth and rupture.
ANOTHER PERSPECTIVE ON THE RELATIONSHIP BETWEEN BREASTFEEDING, NEWBORN CARE AND MATERNAL PERINATAL DEPRESSION IN A RURAL AFRICAN SETTING
Authors: Ogah Adenike Oluwakemi , Ogah James Aaron Ogbole Oluwasegun
Published: August 2023

Background

Maternal postpartum depression (PPD) is still one of the major health challenges across the globe with detrimental consequences on newborn bonding, growth and feeding. However, the bidirectional pathways between breastfeeding and PPD have not been sufficiently characterized. This study investigated the risk factors of poor maternal mental health and its relationship with breastfeeding initiation, in a remote community in East Africa.

Subject and methods

This was a cross-sectional secondary analysis of the baseline data collected for a 2019 prospective cohort study on infant growth in a rural community in East Africa. Healthy, 529 mother-singleton infant pairs were recruited consecutively from Gitwe district hospital. Maternal peri-partum depression score was obtained using the Edinburgh post-partum depression scale. The cut-off point on the depression scale, used in this study was 6.5.

Results

The burden of maternal perinatal depression was 59.7%. Elderly mothers >35years of age (75.9%; p<0.001), poor antenatal visits of less than 4 (74.4%; p<0.001), vaginal delivery (74.7%; p<0.001; OR 5.26; 95% CI 3.57, 7.69), did not give prelacteal feeds (62.4%; p<0.001; OR 7.14; 95% CI 2.94, 16.7), primary education (69.5%, p<0.001), engaged in semi-skilled or skilled jobs (71.8%, p<0.001), poor socioeconomic class (74.8%, p<0.001), Christians (60.9%; p<0.001; OR 8.33; 95% CI 1.89, 33.3), HIV negative (61.6%; p<0.001; OR 4.57; 95% CI 1.90, 11.02), lack of water (82.0%; p<0.001; OR 27.1; 95% CI 16.39, 44.80) and toilet facilities (81.9%; p<0.001; OR 5.68; 95% CI 3.76, 8.58) in their home yard, not being exposed to potentially harmful social habits such as tobacco, alcohol (63.3%; p<0.001; OR 3.22; 95% CI 1.89, 5.56) significantly characterized mothers with high depression score. Peripartum depression was more common among mothers with small for gestational age babies (p=0.004; OR 3.12; 95%CI 1.44, 6.73) and those who initiated breastfeeding early (p<0.001; OR 9.17; 95%CI 5.21, 16.13).

Conclusion and Recommendations

The burden of maternal peripartum depression was high in this community and is still on the increase. Therefore, PPD and its risk factors require early recognition, intervention and follow up during the antenatal period up till at least 12 months postpartum, in order to prevent lactation failure and decline in exclusive breastfeeding and continued breastfeeding rates and duration. The poor WASH situation and difficult road access to health facilities in the community requires urgent attention.
Functionally annotated electrophysiological neuromarkers of healthy ageing and memory function
Authors: Auer Tibor , Goldthorpe Robin , Peach Robert , Hebron Henry , Violante Ines R.
Published: August 2023

The unprecedented increase in life expectancy presents a unique opportunity and the necessity to explore both healthy and pathological aspects of ageing. Electroencephalography (EEG) has been widely used to identify neuromarkers of cognitive ageing due to its affordability and richness in information. However, despite the growing volume of data and methodological advancements, the abundance of contradictory and non-reproducible findings has hindered clinical translation. To address these challenges, our study introduces a comprehensive workflow expanding on previous EEG studies and investigates various static and dynamic power and connectivity estimates as potential neuromarkers of cognitive ageing in a large dataset. We also assess the robustness of our findings by testing their susceptibility to band specification. Finally, we characterise our findings using functionally annotated brain networks to improve their interpretability and multi-modal integration.

Our analysis demonstrates the effect of methodological choices on findings and that dynamic rather than static neuromarkers are not only more sensitive but also more robust. Consequently, they emerge as strong candidates for cognitive ageing neuromarkers. Moreover, we were able to replicate the most established EEG findings in cognitive ageing, such as alpha oscillation slowing, increased beta power, reduced reactivity across multiple bands, and decreased delta connectivity. Additionally, when considering individual variations in alpha band, we clarified that alpha power is characteristic of memory performance rather than ageing, highlighting its potential as a neuromarker for cognitive ageing. Finally, our approach using functionally annotated source reconstruction allowed us to provide insights into domain-specific electrophysiological mechanisms underlying memory performance and ageing.
Ploidy inference from single-cell data: application to human and mouse cell atlases
Authors: Takeuchi Fumihiko , Kato Norihiro
Published: August 2023

Ploidy is relevant to numerous biological phenomena, including development, metabolism, and tissue regeneration. Single-cell RNA-seq and other omics studies are revolutionizing our understanding of biology, yet they have largely overlooked ploidy. This is likely due to the additional assay step required for ploidy measurement. Here, we developed a statistical method to infer ploidy from single-cell ATAC-seq data. When applied to the data from human and mouse cell atlases, our method enabled systematic detection of polyploidy across a range of cell types. This method allows for the integration of ploidy analysis into single-cell studies.

Article summary

Ploidy plays a crucial role in many biological processes. Though modern studies offer deep insights into biology, they often neglect ploidy because it’s challenging to measure. In this research, we have created a new method to detect ploidy using single-cell data. This technique helps identify polyploid cells across various cell types, bridging a gap in our understanding.
The well-being and work-related stress of senior school leaders in Wales and Northern Ireland during the COVID-19 pandemic: A cross-sectional descriptive study
Authors: Marchant Emily , Dowd Joanna , Bray Lucy , Rowlands Gill , Miles Nia , Crick Tom , James Michaela , Dadaczynski Kevin , Okan Orkan
Published: August 2023

The COVID-19 pandemic caused far-reaching societal changes, including significant educational impacts, affecting over 1.6 billion pupils and 100 million education practitioners globally. Senior school leaders were at the forefront; an occupation already reporting high work-related stress and large numbers leaving the profession preceding COVID-19, leaders were exposed to high demands relating to the numerous challenges they had to manage during a “crisis leadership” period. This cross-sectional descriptive study through the international COVID-HL network aimed to examine the well-being and work-related stress of senior school leaders (n=323) in Wales (n=172) and Northern Ireland (n=151) during COVID-19 (2021-2022). Findings suggest that senior school leaders reported high workloads (54.22±11.30 hours/week), low well-being (65.2% n=202, mean WHO-5 40.85±21.57), depressive symptoms (WHO-5 34.8% n=108) and high work-related stress (PSS-10: 29.91±4.92). High exhaustion (BAT: high/very high 89.0% n=285) and specific psychosomatic complaints (experiencing muscle pain 48.2% n=151) were also reported, and females had statistically higher outcomes in these areas. School leaders were engaging in self-endangering working behaviours; 74.7% (n=239) gave up leisure activities in favour of work and 63.4% (n=202) sacrificed sufficient sleep, which was statistically higher for females. These findings are concerning given that the UK is currently experiencing a “crisis” in educational leadership against a backdrop of pandemic-related pressures. Senior leaders’ high attrition rates further exacerbate this, proving costly to educational systems and placing additional financial and other pressures on educational settings and policy response. This has implications for senior leaders and pupil-level outcomes including health, well-being and educational attainment, requiring urgent tailored and targeted support from the education and health sectors. This is particularly pertinent for Wales and Northern Ireland as devolved nations in the UK, who are both implementing or contemplating major education system level reforms, including new statutory national curricula, requiring significant leadership, engagement and ownership from the education profession.
Sucrose-mediated translational stalling involves a conserved ribosomal pocket
Authors: van der Horst Sjors , Englmeier Robert , Hanson Johannes , Smeekens Sjef , Förster Friedrich
Published: August 2023

Within eukaryotes, 20-50% of the mRNAs contain short open reading frames (uORFs) located upstream of the main ORF. A significant fraction of these uORFs encode conserved peptides (CPuORFs) that regulate translation in response to specific metabolites. A well-studied example includes uORF2 of the plant growth inhibiting transcription factor bZIP11. Elevated intracellular sucrose levels lead to ribosome stalling at the stop codon of uORF2, thus reducing bZIP11 protein synthesis. Similar examples can be found in bacteria and animals, e.g. on the bacterialTnaCand humanCDH1-NPN*ORFs that both induce stalling at the stop codon when in the presence of tryptophan and the drug-like molecule PF846, respectively.

In this study, we affinity-purifiedin vitrotranslated sucrose-stalled wheat ribosomes translating bZIP11-uORF2 and determined the ribosomes’ structures using cryo-electron microscopy. This revealed density inside a pocket in the ribosomal exit tunnel of the plantTriticum aestivum, that colocalizes with the binding locations of tryptophan and PF846 inE. coliand humans, respectively. We suggest this density corresponds to sucrose. Tryptophan and PF846 mode-of-action was previously proposed to inhibit release factor binding or function. Mutation of the uORF2 stop codon shows that its presence is crucial for sucrose-induced stalling, suggesting that the stalling only manifests during termination and not elongation. Moreover, the structural similarities with tryptophan-induced stalled ribosomes near the peptidyl transferase center indicates that an analogous mechanism of inhibition of release factor function is likely. Our findings suggest a conserved mechanistic framework across different organisms, wherein specific molecules interact with the nascent peptide and ribosome to modulate protein synthesis.
Sequential breakdown of the complexCf-9leaf mould resistance locus in tomato byFulvia fulva
Authors: de la Rosa Silvia , Schol Christiaan R. , Peregrina Ángeles Ramos , Winter David J. , Hilgers Anne M. , Maeda Kazuya , Iida Yuichiro , Tarallo Mariana , Jia Ruifang , Beenen Henriek G. , Rocafort Mercedes , de Wit Pierre J.G.M. , Bowen Joanna K. , Bradshaw Rosie E. , Joosten Matthieu H.A.J. , Bai Yuling , Mesarich Carl H.
Published: August 2023

Leaf mould, caused byFulvia fulva, is a devastating disease of tomato plants. In many commercial tomato cultivars, resistance to this disease is governed by theCf-9locus, which comprises five paralogous genes (Cf-9A–9E) that encode receptor-like proteins. Two of these proteins contribute to resistance: Cf-9C recognizes the previously identifiedF. fulvaeffector Avr9 and provides resistance during all plant growth stages, while Cf-9B recognises the yet-unidentifiedF. fulvaeffector Avr9B and provides mature plant resistance only. In recent years,F. fulvastrains have emerged that have overcome theCf-9locus, withCf-9Ccircumvented throughAvr9deletion. To understand howCf-9Bis circumvented, we set out to identifyAvr9B.

Comparative genomics,in plantatransient expression assays and gene complementation experiments were used to identifyAvr9B, while gene sequencing was used to assessAvr9Ballelic variation across a worldwide strain collection.

A strict correlation betweenAvr9deletion and resistance-breaking mutations inAvr9Bwas observed in strains recently collected fromCf-9cultivars, whereasAvr9deletion but no mutations inAvr9Bwere observed in older strains.

This research showcases howF. fulvahas evolved to sequentially break down the two functional resistance genes of the complexCf-9locus and highlights that this locus now has limited value for controlling leaf mould disease in worldwide commercial tomato production.
Supporting college student self-determination through motivational interviewing
Authors: Blankenship Benjamin Buck , Lee Jon
Published: August 2023

Purpose

This study was intended to investigate a small-scale School-based Motivational Interviewing (SBMI) pilot with first-year college students. This approach honors student autonomy, supports self-determination and has the potential to impact educational outcomes in higher education. Motivational Interviewing (MI) is an evidence based conversational skill set, defined as “a collaborative conversational style for strengthening a person's own motivation and commitment to change” (Miller and Rollnick, 2013, p. 12). Student perceptions of satisfaction with the faculty-student mentoring intervention were sought. Relational aspects of MI (partnership, empathy and alliance) were also explored.

Design/methodology/approach

A mixed-method approach was used for the SBMI study, focused on college students with recent academic setbacks (N = 19).

Findings

The intervention was deployed with high levels of MI technical fidelity and relational quality. Participants reported high satisfaction with the intervention. The relational aspects and participant perceived alliance with their faculty were highly correlated across the intervention, adding to the discussion of the mechanisms of MI that contribute to its effectiveness.

Research limitations/implications

This work is formative, yet at this point is not generalizable given the scope of the study.

Practical implications

Findings are encouraging for further development of this innovative pedagogical approach. Possible future applications of research are provided.

Social implications

Discussed herein, SBMI has the potential to meet the needs of traditionally underrepresented student groups.

Originality/value

The reported study is the initial portion of a larger intervention development project.
Breaking incommensurability boundaries? On the production and publication of interparadigmatic research
Authors: Gendron Yves , Paugam Luc , Stolowy Hervé
Published: August 2023

Purpose

This essay takes issue with the incommensurability thesis, which assumes that meaningful research work across different paradigms cannot occur. Could it be that the thesis understates the case for meaningful relationships to develop across paradigms? Is it possible that researchers can authentically and rewardingly collaborate across paradigms and create joint studies published in established journals?

Design/methodology/approach

Based on the observation that interparadigmatic research exists, the authors investigate two questions. How is interparadigmatic research expressed in the accounting research literature? How can we comprehend the process that underlies the development and publication of interparadigmatic research, focusing on cohabitation involving the positivist and interpretive paradigms of research?

Findings

To deal with the first question, the authors focus on two interparadigmatic articles: Greenwood et al. (2002) and Paugam et al. (2021). The authors find each article showcases a dominant paradigm – whereas the role of the other paradigm is represented as secondary; that is, complementing and enriching the dominant paradigm. To address the second question, the authors rely especially on their involvement as coauthors of three interparadigmatic studies, published between 2019 and 2022 in FT50 journals. The authors’ analysis brings to the fore a range of facilitators that fit their experiences, such as the development of cross-paradigmatic agreement within the authorship to cope with the complexity surrounding the object of study, the crafting of methodological compromises (e.g. regarding the number of documents to analyze) and the strategizing that the authorship enacted in dealing with journal gatekeepers.

Originality/value

From the authors’ experiences, they develop a model, which provides a tentative template to make sense of the process by which interparadigmatic research takes place. The model highlights the role of what the authors call “epistemic mediation” in producing interparadigmatic studies.
Slow soil enzyme recovery following invasive tree removal through gradual changes in bacterial and fungal communities
Authors: Sapsford S. J. , Dickie I. A.
Published: August 2023

Biological invasions of plants have profound effects on ecosystem functioning by directly and indirectly altering soil microbiota, especially when invasive plants co‐invade with their associated microbiomes. Ecosystem functions may recover slowly following invader removal, with implications for restoration.

We investigated the recovery of soil ecosystem function (measured as soil enzymes) following the removal, at different densities and times, of invasive Pinus spp. in New Zealand, and how different enzymatic activities responded to pine legacies.

Enzymatic activities were driven by pine legacies via both abiotic (soil nutrients) and biotic (fungi and bacteria) soil properties, with different enzymes showing distinct patterns. The activity of the enzymes cellobiohydrolase (cellulose degrading), β‐glucosidase (cellulose degrading), N‐acetyl‐glucosaminidase (chitin degrading), laccase (lignin oxidising) and acid phosphatase (organic phosphate hydrolysing) were influenced by time since pine removal and by pine density at removal via effects on biotic communities. In comparison, Mn‐peroxidase (lignin oxidising) was positively correlated with density of pines at removal and was negatively correlated with time since removal and was only influenced by fungal communities.

Synthesis. The recovery of soil enzymatic function following invasive species removal is slow and dependent on pine legacies through the gradual changes in fungal and bacterial communities. The cascading effects of these changes suggest potential implications for the success of future plant establishment and restoration of co‐invaded ecosystems.
Artesunate alleviates psoriasis‐like dermatitis by reducing interleukin‐23 expression in tumor necrosis factor‐alpha‐induced HaCaT cells
Authors: Lin Lixian , Huang Zhongzhou , Jianchi Ma , Guo Zhixuan , Shi Zhenrui , Tang Zengqi , Guo Qing , Xiong Hui
Published: August 2023

Artesunate (ART), an antimalarial drug with a multifunctional immunomodulatory effect, reduces psoriasis disease. ART can alleviate psoriasis‐like dermatitis in mice but has no effect on proinflammatory cytokines in the blood. Thus, we hypothesized that the skin might be the target tissue of ART during the treatment of psoriasis. The interleukin (IL)‐23/IL‐17 axis has a key role in the pathogenesis of psoriasis. However, whether and how ART manipulates the IL‐23 signal during psoriasis is unknown. This study found that IL‐23 is highly expressed in the epidermis of psoriasis lesions and positively correlated with histological neutrophil infiltration and clinical psoriasis area and severity index (PASI) scores. Furthermore, ART inhibits the migration and cell cycle, as well as tumor necrosis factor‐alpha (TNF‐α)‐induced IL‐23 expression in HaCaT cells in a dose‐dependent manner, probably through interference with the nuclear factor kappa B (NF‐κB) signalling pathway. Animal experiments in imiquimod (IMQ)‐induced psoriasis‐like mice model also suggested that ART dose‐dependently reduces IL‐23 in the epidermis and ameliorates neutrophil infiltration. These findings thus provide further molecular evidence supporting ART as a promising drug for psoriasis in clinic.