bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal relationship between gut microbiota and idiopathic pulmonary fibrosis: A two-sample Mendelian randomization
Authors: Fan Shiqin , Xue Baorui , Ma Jing
Published: July 2024

To explore the causal relationship between gut microbiota (GM) and Idiopathic pulmonary fibrosis (IPF), we performed a two-sample Mendelian randomization (MR). GM was used as an exposure factor, and instrumental variables were determined from the GWAS of 18,340 participants. GWAS of IPF (including 1028 IPF patients and 196,986 controls) from the FinnGen was used as the outcome factor. The primary analysis method is the inverse variance weighted (IVW) method, and sensitivity analysis was used to validate the reliability. Family Bacteroidaceae (OR = 1.917 95% CI = 1.083–3.393, P = .026), order Gastranaerophilales (OR = 1.441 95% CI = 1.019–2.036, P = .039), genus Senegalimassilia (OR = 2.28 95% CI = 1.174–4.427, P = .015), phylum Cyanobacteria (OR = 1.631 95% CI = 1.035–2.571, P = .035) were positively correlated with IPF. FamilyXIII(OR = 0.452 95% CI = 0.249–0.82, P = .009), order Selenomonadale (OR = 0.563 95% CI = 0.337–0.941, P = .029), genus Veillonella (OR = 0.546 95% CI = 0.304–0.982, P = .043) (OR = 0.717 95% CI = 0.527–0.976, P = .034), genus Ruminococcusgnavus (OR = 0.717 95% CI = 0.527–0.976, P = .034), genus Oscillibacter (OR = 0.571 95% CI = 0.405–0.806, P = .001) was negatively correlated with IPF. Sensitivity analysis showed no evidence of pleiotropy or heterogeneity (P > .05). The results of MR demonstrated a causal relationship between GM and IPF. Further studies are needed to investigate the intrinsic mechanisms of the GM in the pathogenesis of IPF.
Cardio-cerebrovascular adverse outcomes in patients with influenza with and without preexisting cardiovascular disease: Oral antiviral agents impact
Authors: Park Kyung-Teak , Choi Minjea , Kim Jun Hyung , Kang Ki-Woon
Published: July 2024

This study aimed to compare the 2-year cardio-cerebrovascular adverse outcomes of patients with influenza with and without preexisting cardiovascular disease (preCVD) treated with oral antiviral agents in the outpatient clinic. Oral antiviral agents are routinely prescribed to treat influenza infection with a positive rapid-antigen test in the outpatient clinic; however, influenza-associated cardio-cerebrovascular outcomes have not yet been characterized in patients with preCVD treated with oral antiviral agents. Data between 2006 and 2016 were extracted from the National Health Database of South Korea. A total of 865,522 patients with influenza treated with oral antiviral agents were selected in South Korea and classified as preexisting ischemic heart disease (IHD), heart failure (HF), or atrial fibrillation (AF), and 2-year cardio-cerebrovascular outcomes were analyzed using a Cox proportional hazard regression model. Among the participants, 96,433 had preCVD (11.1%; mean age, 46 years) including IHD (86.4%), HF (23.1%), and AF (12.5%). The incidence of new-onset IHD, AF, HF, and death was similar between patients with influenza with and without preCVD. The incidences of IHD and stroke were 0.489 and 0.047 per 100-person year in the preCVD group, respectively. The incidence of cardiovascular mortality was 0.489 per 100-person year in the preCVD group, and the hazard ratio for cardiovascular mortality in the preCVD group was not significantly different from that in patients without preCVD. Based on the national health data, 2-year cardio-cerebrovascular adverse outcomes were not significantly different between patients with and without preCVD treated with oral antiviral agents.
Culture-based bacterial evaluation of the appendix lumen and antibiotic susceptibility of acute appendicitis in Japan: A single-center retrospective analysis
Authors: Kitahara Hiroe , Park Yonfan , Seharada Kai , Yoshimura Masaki , Horiuchi Akira , Karasawa Yukihiko
Published: July 2024

The question of whether to perform an appendectomy or conservative treatment for acute appendicitis can differ depending on the facility or surgeon, but antibiotic treatment is administered regardless of whether an appendectomy or conservative treatment is selected. We investigated the contemporary bacteriology for acute appendicitis and evaluated the antibiotic sensitivity of the bacteria that are currently associated with appendicitis. We retrospectively analyzed the bacterial culture results and antibiotic susceptibility of 141 patients who underwent appendicitis surgery, including the identification and antimicrobial susceptibility of the cultured bacteria within the excised appendices. Bacterial cultures were positive in 131 cases (92.9%). The most commonly isolated bacteria were Escherichia coli (90 isolates, 66.7%), followed by Enterococcus species (n = 19, 14.5%), Pseudomonas aeruginosa (n = 18, 13.7%), Streptococcus species (n = 15, 11.5%), and Klebsiella species (n = 8, 6.1%). Eight strains (8.8%) of E coli were extended-spectrum β-lactamase producers, and ten strains (11.1%) were fluoroquinolone-resistant. Tazobactam/piperacillin and meropenem inhibited the growth of 100% of the major identified bacteria. The patients with appendicoliths had a significantly higher bacterial culture rate. Enterococcus species were frequently isolated from the patients with complicated appendicitis. For the antibiotic treatment of appendicitis, it is essential to understand the patient’s microbiological profile and antibiotic susceptibilities. Research from Asian countries such as Japan can enhance our knowledge of regional antibiotic resistance patterns and inform effective treatment strategies.
Total management of hemangiopericytoma/solitary fibrous tumor of the buttock: A case report
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Ito Tomohiko , Kakinoki Ryosuke , Goto Koji
Published: July 2024

Background:

Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient’s demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review.

Methods:

A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up.

Results:

Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome.

Conclusion:

Long-term monitoring for potential complications remains necessary.
Mowat-Wilson syndrome: Case report
Authors: Wójcik-Niklewska Bogumiła , Filipek Erita
Published: July 2024

Background:

Mowat-Wilson syndrome (MWS) is a rare genetic condition resulting in multiple congenital anomalies, including facial dysmorphism, structural anomalies of the internal organs, functional disorders, and, although less commonly, ocular abnormalities. To present a child with MWS and eye abnormalities.

Methods:

A 3-year-old boy was born at 37 weeks of pregnancy with dysmorphic features, neurodevelopmental disorders, genetically confirmed MWS, nystagmus, strabismus, and suspicion of congenital glaucoma. Ophthalmic examination was carried out under general anesthesia; eyeball ultrasound and electrophysiological examination (flash visual evoked potentials) were also performed.

Results:

The examinations revealed nystagmus, a normal response of pupils to light in both eyes, and normal intraocular pressure, that is, 17 and 18 mm Hg in the right and left eye, respectively. Corneal thickness was 606 µm in the right eye and 588 µm in the left eye. Gonioscopy revealed displacement of Schwalbe line anterior to the limbus of the cornea (posterior embryotoxon). Fundus examination revealed a pink optic disk with a cup-to-disc ratio of 0.5, macular pigment regrouping, and normal blood vessels. Flash visual evoked potentials: P2 latency was normal. P2 amplitude from the left hemisphere was reduced to 50%, and P2 amplitude over the right hemisphere was normal.

Conclusion:

Children with genetically determined congenital anomalies need regular ophthalmic checkups to accurately assess the eye and determine the prospects of vision function development.
A BLAST from the past: revisiting blastp’s E-value
Authors: Lu Yang Young , Noble William Stafford , Keich Uri
Published: July 2024

The Basic Local Alignment Search Tool, BLAST, is an indispensable tool for genomic research. BLAST established itself as the canonical tool for sequence similarity search in large part thanks to its meaningful statistical analysis. Specifically, BLAST reports the E-value of each reported alignment, which is defined as the expected number of optimal local alignments that will score at least as high as the observed alignment score, assuming that the query and the database sequences are randomly generated.

Here we critically evaluate the E-values provided by the standard protein BLAST (blastp), showing that they can be at times significantly conservative while at others too liberal. We offer an alternative approach based on generating a small sample from the null distribution of random optimal alignments, and testing whether the observed alignment score is consistent with it. In contrast with blastp, our significance analysis seems valid, in the sense that it did not deliver inflated significance estimates in any of our extensive experiments. Moreover, although our method is slightly conservative, it is often significantly less so than the blastp E-value. Indeed, in cases where blastp’s analysis is valid (i.e., not too liberal), our approach seems to deliver a greater number of correct alignments. One advantage of our approach is that it works with any reasonable choice of substitution matrix and gap penalties, avoiding blastp’s limited options of matrices and penalties. In addition, we can formulate the problem using a canonical family-wise error rate control setup, thereby dispensing with E-values, which can at times be difficult to interpret.
Molecular consequences of acute versus chronic CDK12 loss in prostate carcinoma nominates distinct therapeutic strategies
Authors: Frank Sander , Persse Thomas , Coleman Ilsa , Bankhead Armand , Li Dapei , DeSarkar Navonil , Wilson Divin , Rudoy Dmytro , Vashisth Manasvita , Galipeau Patty , Yang Michael , Hanratty Brian , Dumpit Ruth , Morrissey Colm , Corey Eva , Bruce Montgomery R. , Haffner Michael C. , Pritchard Colin , Vasioukhin Valera , Ha Gavin , Nelson Peter S.
Published: July 2024

Genomic loss of the transcriptional kinaseCDK12occurs in ∼6% of metastatic castration-resistant prostate cancers (mCRPC) and correlates with poor patient outcomes. Prior studies demonstrate that acute CDK12 loss confers a homologous recombination (HR) deficiency (HRd) phenotype via premature intronic polyadenylation (IPA) of key HR pathway genes, includingATM.However, mCRPC patients have not demonstrated benefit from therapies that exploit HRd such as inhibitors of polyADP ribose polymerase (PARP). Based on this discordance, we sought to test the hypothesis that an HRd phenotype is primarily a consequence of acuteCDK12loss and the effect is greatly diminished in prostate cancers adapted toCDK12loss. Analyses of whole genome sequences (WGS) and RNA sequences (RNAseq) of human mCRPCs determined that tumors with biallelicCDK12alterations (CDK12BAL) lack genomic scar signatures indicative of HRd, despite carrying bi-allelic loss and the appearance of the hallmark tandem-duplicator phenotype (TDP). Experiments confirmed that acute CDK12 inhibition resulted in aberrant polyadenylation and downregulation of long genes (includingBRCA1andBRCA2) but such effects were modest or absent in tumors adapted to chronicCDK12BAL. One key exception wasATM, which did retain transcript shortening and reduced protein expression in the adaptedCDK12BALmodels. However,CDK12BALcells demonstrated intact HR as measured by RAD51 foci formation following irradiation.CDK12BALcells showed a vulnerability to targeting of CDK13 by sgRNA or CDK12/13 inhibitors andin vivotreatment of prostate cancer xenograft lines showed that tumors withCDK12BALresponded to the CDK12/13 inhibitor SR4835, while CDK12-intact lines did not. Collectively, these studies show that aberrant polyadenylation and long HR gene downregulation is primarily a consequence of acute CDK12 deficiency, which is largely compensated for in cells that have adapted to CDK12 loss. These results provide an explanation for why PARPi monotherapy has thus far failed to consistently benefit patients with CDK12 alterations, though alternate therapies that target CDK13 or transcription are candidates for future research and testing.
Adult caudal fin shape is imprinted in the embryonic fin fold
Authors: Surette Eric , Donahue Joan , Robinson Stephanie , McKenna Deirdre , Martinez Crisvely Soto , Fitzgerald Brendan , Karlstrom Rolf O. , Cumplido Nicolas , McMenamin Sarah K.
Published: July 2024

Appendage shape is formed during development (and re-formed during regeneration) according to spatial and temporal cues that orchestrate local cellular morphogenesis. The caudal fin is the primary appendage used for propulsion in most fish species, and exhibits a range of distinct morphologies adapted for different swimming strategies, however the molecular mechanisms responsible for generating these diverse shapes remain mostly unknown. In zebrafish, caudal fins display a forked shape, with longer supportive bony rays at the periphery and shortest rays at the center. Here, we show that a premature, transient pulse ofsonic hedgehog a (shha)overexpression during late embryonic development results in excess proliferation and growth of the central rays, causing the adult caudal fin to grow into a triangular, truncate shape. Both global and regional ectopicshhaoverexpression are sufficient to alter fin shape, and forked shape may be rescued by subsequent treatment with an antagonist of the canonical Shh pathway. The induced truncate fins show a decreased fin ray number and fail to form the hypural diastema that normally separates the dorsal and ventral fin lobes. While forked fins regenerate their original forked morphology, truncate fins regenerate truncate, suggesting that positional memory of the fin rays can be permanently altered by a transient treatment during embryogenesis. Ray finned fish have evolved a wide spectrum of caudal fin morphologies, ranging from truncate to forked, and the current work offers insights into the developmental mechanisms that may underlie this shape diversity.
The asymmetric expression of HSPA2 in blastomeres governs the first embryonic cell-fate decision
Authors: Gao Jiayin , Wang Jiawei , Liu Shiyu , Song Jinzhu , Zhang Chuanxin , Liu Boyang , Wu Keliang
Published: July 2024

The first cell-fate decision is the process by which cells of an embryo take on distinct lineage identities for the first time, thus representing the beginning of developmental patterning. Here, we demonstrate that the molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, is asymmetrically expressed in the late 2-cell stage of mouse embryos. The knockdown ofHspa2in one of the 2-cell blastomeres prevented its progeny predominantly toward the inner cell mass (ICM) fate. In contrast, the overexpression ofHspa2in one of the two-cell blastomeres did not induce blastomeres to differentiate towards the ICM fate. Furthermore, we demonstrated that HSPA2 interacts with CARM1 and its levels correlate with ICM-associated genes and that it interacts with the CARM1. Collectively, our results identify HSPA2 as a critical early regulator of the first cell-fate decision in mammalian 2-cell embryos.
Gene Function Revealed at the Moment of Stochastic Gene Silencing
Authors: Gupta Shreyan , Cai James J.
Published: July 2024

Gene expression is a dynamic and stochastic process characterized by transcriptional bursting followed by periods of silence. Single-cell RNA sequencing (scRNA-seq) is a powerful tool to measure transcriptional bursting and silencing at the individual cell level. In this study, we introduce the single-cell Stochastic Gene Silencing (scSGS) method, which leverages the natural variability in single-cell gene expression to decipher gene function. For a target genegunder investigation, scSGS classifies cells into transcriptionally active (g+) and silenced (g-) samples. It then compares these cell samples to identify differentially expressed genes, referred to as SGS-responsive genes, which are used to infer the function of the target geneg. Analysis of real data demonstrates that scSGS can reveal regulatory relationships up- and downstream of target genes, circumventing the survivorship bias that often affects gene knockout and perturbation studies. scSGS thus offers an efficient approach for gene function prediction, with significant potential to reduce the use of genetically modified animals in gene function research.
Cross-Tissue Comparison of Epigenetic Aging Clocks in Humans
Authors: Apsley Abner T. , Ye Qiaofeng , Caspi Avshalom , Chiaro Christopher , Etzel Laura , Hastings Waylon J. , Heim Christine C. , Kozlosky John , Noll Jennie G. , Schreier Hannah M. C. , Shenk Chad E. , Sugden Karen , Shalev Idan
Published: July 2024

Epigenetic clocks are a common group of tools used to measure biological aging – the progressive deterioration of cells, tissues and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e., buccal or saliva) in both research and commercial settings. However, differentiated cell types across body tissues exhibit unique DNA methylation landscapes and age-related alterations to the DNA methylome. Applying epigenetic clocks derived from blood-based tissues to estimate epigenetic age of oral-based tissues may introduce biases. We tested the within-person comparability of common epigenetic clocks across five tissue types: buccal epithelial, saliva, dry blood spots, buffy coat (i.e., leukocytes), and peripheral blood mononuclear cells. We tested 284 distinct tissue samples from 83 individuals aged 9-70 years. Overall, there were significant within-person differences in epigenetic clock estimates from oral-based versus blood-based tissues, with average differences of almost 30 years observed in some age clocks. In addition, most epigenetic clock estimates of blood-based tissues exhibited low correlation with estimates from oral-based tissues despite controlling for cellular proportions and other technical factors. Our findings indicate that application of blood-derived epigenetic clocks in oral-based tissues may not yield comparable estimates of epigenetic age, highlighting the need for careful consideration of tissue type when estimating epigenetic age.
Pf-HaploAtlas: an interactive web app for spatiotemporal analysis ofP. falciparumgenes
Authors: Lee Chiyun , Ünlü Eyyüb S. , White Nina F.D. , Almagro-Garcia Jacob , Ariani Cristina , Pearson Richard D.
Published: July 2024

Monitoring the genomic evolution ofPlasmodium falciparum- the most widespread and deadliest of the human-infecting malaria species - is critical for making decisions in response to changes in drug resistance, diagnostic test failures, and vaccine effectiveness. The MalariaGEN data resources are the world’s largest whole genome sequencing databases forPlasmodiumparasites. The size and complexity of such data is a barrier to many potential end users in both public health and academic research. A user-friendly method for accessing and interpreting data on the genetic variation ofP. falciparumwould greatly enable efforts in studying and controlling malaria. We developed Pf-HaploAtlas, a web application enabling exploration of genomic variation without requiring advanced technical expertise. The app provides analysis-ready data catalogues and visualisations of amino acid haplotypes for all 5,102 coreP. falciparumgenes. Pf-HaploAtlas facilitates comprehensive spatial and temporal analyses of genes and variants of interest by using data from 16,203 samples, from 33 countries, and spread between the years 1984 and 2018. The scope of Pf-HaploAtlas will expand with each new MalariaGENPlasmodiumdata release. Pf-HaploAtlas is available online for public use athttps://apps.malariagen.net/pf-haploatlas, which allows users to download the underlying amino acid haplotype data, and its source code is freely available on GitHub under the MIT licence athttps://github.com/malariagen/pf-haploatlas.
PAX proteinsin silicoprediction inLissachatina fulica
Authors: Dominova Irina N. , Golovneva Kristina , Korshunova Nadezhda , Zhukov Valery V.
Published: July 2024

Prediction of snail PAX group proteins inLisachatina fulicawas performed. For this this purpose, homologous sequences to already known PAX proteins ofCephalopoda, GastropodaandBivalviamolluscs were predicted. The presence of certain domains (Paired box, Homeodomain and octapeptide) in the structure of the primary predicted sequences ofLisachatina fulicaproteins from the GigaDB was analyzed. Also, to confirm that the sequences found belong to the PAX family proteins, their secondary and 3D structures were predicted, and their DNA-binding capacity was compared to the control Paired box domain using molecular docking. As a result, 8 proteins ofLisachatina fulicacontaining PAX characteristic sequences were identified. Based on the results of domain structure search and phylogenetic analysis, the proteins were categorized into 5 subfamilies of PAX proteins, namely I, III, IV, β, and Pox-Neuro. The result provides a starting point for the search for the functional role of PAX proteins in theLisachatina fulica.
Diversified global vegetable oil production can mitigate climate change and achieve socio-environmental co-benefits
Authors: Zeng Siyan , Chen Fu , Zhang Chengcheng , Fan Shenggen , Gu Baojing , Meijaard Erik , Davis Kyle Frankel , Wanger Thomas Cherico
Published: July 2024

Global vegetable oil production is a crucial ingredient for food and household products but also a major source of greenhouse gas (GHG) emissions and other environmental externalities. A diversified supply may improve the sustainability and resilience of profitable vegetable oil production globally. Here, we provide the first spatial assessment of the environmental and economic effects of the globally dominant vegetable oil crops soybean, oil palm, rapeseed, sunflower, groundnut, and olive globally, based on new data from a meta-analysis, life cycle assessment, and process-based crop growth modelling. We show that the total annual GHG emissions, water use, land use, pesticide use, and farmer income of the six vegetable oil crops are 1.2 Gt CO2eq/year, 876.0 km3/year, 168.3 Mha/year, 953.6 kt/year, and 66.5 billion USD/year, respectively. We also found that diversified vegetable oil production, for instance, through increased fractions of a highly productive oil tree cropCamellia oleiferacan reduce GHG emissions, water use, land use, and pesticide use by 14.0%, 4.9%, 7.3%, 9.3%, respectively and increase farmer income by 82.6%. When considering enabling conditions for technology and policy support in a technology-policy-enabling scenario, these benefits increase 1.3, 2.1, 1.8, 1.7, and 3.2 folds, respectively. Our results provide practical guidance on where and how diversified oil crop production can advance a sustainable food system transformation and help to mitigate climate change.
Epigenetics is all you need: A Transformer to decode chromatin structural compartments from the epigenome
Authors: Dodero-Rojas Esteban , Contessoto Vinícius G. , Fehlis Yao , Mayala Nicolas , Onuchic José N.
Published: July 2024

Chromatin within the nucleus adopts complex three-dimensional structures that are crucial for gene regulation and cellular function. Recent studies have revealed the presence of distinct chromatin subcompartments beyond the traditional A/B compartments (eu- and hetero-chromatin), each exhibiting unique structural and functional properties. Here, we introduce TECSAS (Transformer of Epigenetics to Chromatin Structural AnnotationS), a deep learning model based on the Transformer architecture, designed to predict chromatin subcompartment annotations directly from epigenomic data. TECSAS leverages information from histone modifications, transcription factor binding profiles, and RNA-Seq data to decode the relationship between the biochemical composition of chromatin and its 3D structural behavior. TECSAS achieves high accuracy in predicting subcompartment annotations and reveals the influence of long-range epigenomic context on chromatin organization. Furthermore, we demonstrate the model’s capability to predict the association of loci with nuclear bodies, such as the lamina, nucleoli, and speckles, providing insights into the role of these structures in shaping the 3D genome organization. This study highlights the potential of deep learning models for deciphering the complex interplay between epigenomic features and 3D genome organization, allowing us to better understand genome structure and function.
Low-dose interleukin-2 in patients with bipolar depression: a phase 2 randomised double-blind placebo-controlled trial
Authors: Leboyer Marion , Foiselle Marianne , Tchitchek Nicolas , Tamouza Ryad , Lorenzon Roberta , Richard Jean-Romain , Arrouasse Raphaele , Le Corvoisier Philippe , Le Dudal Katia , Vicaut Eric , Ellul Pierre , Rosenzwajg Michelle , Klatzmann David
Published: July 2024

Immune abnormalities including an insufficiency of regulatory T cells (Treg) and increased blood-based inflammatory markers have been observed in bipolar disorders (BD), particularly during depression. As Tregs are pivotal to control inflammation, Treg stimulation by low-dose IL-2 (IL-2LD) could have a therapeutic impact on bipolar depression. We performed a randomized, double-blind, placebo-controlled (2 active: 1 placebo) proof-of-concept trial of add-on IL-2LDin patients with bipolar depression. Patients received a placebo or IL-2LD(1MIU) once a day for 5 days, and then once a week for 4 weeks starting on week 2. The primary objective was to demonstrate a biological Treg response to IL-2LDassessed by fold increase in Treg percentage of CD4+ cells from baseline to day 5. Secondary objectives included safety assessment and mood improvement throughout the study period. This trial is registered with ClinicalTrials.gov, numberNCT04133233. Fourteen patients with bipolar depression were included, with 4 receiving placebo and 10 IL-2LD. Baseline clinical and biological characteristics were balanced between groups. The primary evaluation criterion was met, with IL-2LDexpanding 1.17 [95% CI 1.01-1.34] vs 1.01 [95% CI 0.90 - 1.12] (p=0.0421) and activating Tregs. Secondary evaluation criteria were also met with significant improvements of depressive symptoms and global functioning from day-15 onwards in the IL-2LDtreated patients. The treatment was well-tolerated, with no serious adverse events related to treatment. This proof-of-concept trial shows that stimulating Tregs in patients with bipolar depression is safe and associated with clinical improvements. This supports a pathophysiological role of inflammation in BD and warrants pursuing the evaluation of IL-2LDas an adjunct treatment of major mood disorders.
Exposomics and Cardiovascular Diseases: A Scoping Review of Machine Learning Approaches
Authors: Argyri Katerina D. , Gallos Ioannis K. , Amditis Angelos , Dionysiou Dimitra D.
Published: July 2024

Cardiovascular disease has been established as the world’s number one killer, causing over 20 million deaths per year. This fact, along with the growing awareness of the impact of exposomic risk factors on cardiovascular diseases, has led the scientific community to leverage machine learning strategies as a complementary approach to traditional statistical epidemiological studies that are challenged by the highly heterogeneous and dynamic nature of exposomics data. The principal objective served by this work is to identify key pertinent literature and provide an overview of the breadth of research in the field of machine learning applications on exposomics data with a focus on cardiovascular diseases. Secondarily, we aimed at identifying common limitations and meaningful directives to be addressed in the future. Overall, this work shows that, despite the fact that machine learning on exposomics data is under-researched compared to its application on other members of the -omics family, it is increasingly adopted to investigate different aspects of cardiovascular diseases.
An Application of Nowcasting Methods: Cases of Norovirus during the Winter 2023/2024 in England
Authors: Mellor Jonathon , Tang Maria L , Finch Emilie , Christie Rachel , Polhill Oliver , Overton Christopher E , Hoban Ann , Douglas Amy , Deeny Sarah R , Ward Thomas
Published: July 2024

Background

Norovirus is a leading cause of acute gastroenteritis, adding to strain on healthcare systems. Diagnostic test reporting of norovirus is often delayed, resulting in incomplete data for real-time surveillance.

Methods

To nowcast the real-time case burden of norovirus a generalised additive model, semi-mechanistic Bayesian joint process and delay model, and Bayesian structural time series model including syndromic surveillance data were developed. These models were evaluated over weekly nowcasts using a probabilistic scoring framework.

Results

Modelling current cases clearly outperforms a simple heuristic approach. Models that harnessed a time delay correction had higher skill, overall, relative to forecasting techniques. However, forecasting approaches were found to be more reliable in the event of temporally changeable reporting patterns. The incorporation of norovirus syndromic surveillance data was not shown to improve model skill in this nowcasting task, which may be indicative poor correlation between the indicator and norovirus incidence.

Interpretation

Analysis of surveillance data enhanced by nowcasting reporting delays improves understanding over simple model assumptions, which is important for real-time decision making. The structure of the modelling approach needs to be informed by the patterns of the reporting delay and can have large impacts on operational performance and insights produced.
Comparing Three Approaches to Modelling the Effects of Temperature and Rainfall on Malaria Incidence in Different Climate Regions
Authors: Madito Gladstone T. , Brooke Basil D. , Silal Sheetal P.
Published: July 2024

Background

Malaria transmission is primarily limited to tropical regions where environmental conditions are conducive for the survival ofPlasmodiumparasites andAnophelesmosquitoes. Adequate rainfall provides breeding sites, while suitable temperatures facilitate vector mosquito life-cycles and parasite development. Evaluating the efficacy of vector control interventions is crucial to determine their effectiveness in reducing malaria transmission. The aim of this study was to explore how these factors affect transmission dynamics at varying levels of vector control efficacy.

Methods

We developed a vector-host compartmental mathematical model to compare three published approaches to incorporating weather influences on malaria transmission. The first approach examines mosquito biting behaviour and mortality rates in larval and adult stages. The second focuses on temperature effects on mosquito life-cycle characteristics throughout the aquatic and adult stages. The third considers how temperature and rainfall influence adult mosquito behaviour, environmental carrying capacity, and survival during the aquatic stages. Model simulations were conducted at different annual vector control coverage levels, to identify variations in transmission patterns and seasonal variability in daily and annual incidence across three climate regions.

Results

The first approach indicates sustained seasonal transmission, with lower cases per 1,000 in tropical regions compared to semi-arid and sub-tropical regions, even with enhanced vector control reducing cases. The second approach predicts sharp, brief annual peaks, with zero transmission during winter in tropical and semi-arid regions, while sub-tropical regions experience ongoing transmission. In contrast, the third approach projects multiple irregular peaks, with transmission ceasing in winter across all regions.

Conclusions

Simulations indicate that climatic events like heatwaves or flooding, can trigger mosquito population surges and malaria outbreaks, even in areas previously free of malaria, despite strong vector control efforts. However, the results demonstrate that sustained and effective vector control, particularly in regions with moderate temperatures, can substantially reduce malaria incidence. Effective malaria control requires incorporating weather predictions into intervention plans, and enhancing current vector control strategies with supplementary measures like larval source management. Accurate timing and targeting of these interventions, based on transmission season projections, are crucial for maintaining robust control as weather conditions evolve and to prepare for future challenges.
The politics of land management after disasters: the case of post-earthquake reconstruction in Türkiye
Authors: Özdoğan Fatma , Lizarralde Gonzalo , Herazo Benjamin
Published: July 2024

Purpose

In this paper, we explore the impact of land management practices on post-disaster housing, to draw lessons from the case of reconstruction in Türkiye.

Design/methodology/approach

We conducted two qualitative case studies of two reconstruction experiences following the 2020 Elazığ and İzmir earthquakes. We analyzed 70 articles, technical reports and press releases and then used a set of policy analysis tools to examine five policy documents in depth. Finally, we wanted to understand how key officers interpreted these policy documents, so we closely analyzed the transcripts of eight semi-structured interviews.

Findings

Türkiye’s legal framework comprises five main policies that concentrate power in the central government and are not tailored to post-disaster reconstruction. This framework facilitates the construction of rubber-stamped apartment buildings, which disregard cultural and social contexts and practices. The current reconstruction policy neglects alternative options like cooperative housing, which could better respond to communal needs and expectations. It also often leads to the loss of land rights among affected residents.

Research limitations/implications

We only analyzed decision-making processes in two case studies and based our study on a limited number of interviews. Therefore, it is difficult to generalize our results and apply them to other contexts. Further quantitative and qualitative work is necessary to conceptualize the links between land management and post-disaster housing reconstruction.

Practical implications

Our findings suggest a need for legislative frameworks specifically designed to address land management during post-disaster reconstruction. The concentration of power in central governments is problematic, thus it remains crucial to empower local authorities by reinforcing technical expertise and facilitating administrative autonomy.

Originality/value

This study offers unique insights into how power relations influence land management practices in post-disaster housing reconstruction. Examining the centralization of power and its impact on cultural and social practices identifies common forms of dispossession and points to key areas for policy improvement.
“When I started teaching you wouldn’t notice any of that’: teachers’ perceptions of the issues facing children and adolescents’ mental health and well-being”
Authors: O’Connor Eric , Nohilly Margaret
Published: July 2024

Purpose

The purpose of this paper was to establish how the phenomenon of mental health issues among young people has translated into the reality of Irish schools through the lens of Irish teachers.

Design/methodology/approach

This wholly qualitative study adopted a post-positivist and phenomenological approach to gathering data by way of semi-structured interviews of 16 participants, 8 from primary backgrounds and 8 from post-primary backgrounds. Analysis of the data highlighted what teachers perceive to be ongoing issues with the mental health and well-being of pupils and the challenges that both teachers and pupils must overcome.

Findings

Interviewing the participants unearthed three sub-themes with regard to mental health in Irish schools, namely, the prevalence of psychiatric disorders/symptoms of mental ill-health among Irish children and adolescents, the barriers preventing help-seeking and the role of mental health support services in Irish schools.

Research limitations/implications

One limitation in this study was that a wider variety in sample could have yielded a more in-depth volume of results. Furthermore, the study by semi-structured interview presented challenges, such as the use of other people’s viewpoints to support the perceptions of the participants, which could not be validated.

Practical implications

Among the recommendations made by the participants were that schools engage in policy development to combat mental health and well-being issues, that teachers engage in continuous professional development in the area and that mental health support services are sufficiently staffed and funded.

Social implications

The general public should engage more in activities that promote a healthy dialogue around the topic of mental health to reduce stigma. It is recommended that campaigns to raise awareness are continued and bolstered.

Originality/value

Irish teachers are being confronted by a contemporary discourse that has materialised as a by-product of an evolving society. Cultural development has led to increased focus on mental health and well-being in recent years, with this body of research exploring its emergence into school life from teachers’ perspectives.
Occupational stress as a mediator between organisational intelligence traits and digital government service quality: a triangulation design approach
Authors: Ramakrishnan Subashini , Mutum Dilip S. , Chit Myint Moe , Wong Meng Seng
Published: July 2024

Purpose

This paper aims to examine the mediating role of occupational stress in addressing the missing link between organisational intelligence (OI) traits and digital government service quality and propose relevant strategies in sustaining the digital government service quality whilst enhancing the psychological well-being of the service providers.

Design/methodology/approach

This paper utilises a triangulation design approach to interpret the findings of the study and propose pertinent strategies. Firstly, we examined the mediating role of occupational stress in addressing the link between OI traits, and digital government service quality. Next, we examined the priority factors of OI traits and occupational stress to sustain the quality of digital government services via the Importance-Performance Map Analysis (IPMA). These findings were cross-examined with the code’s percentage generated from participants’ open-ended survey feedback on aspects that requires improvement in sustaining service quality.

Findings

In principle, occupational stress mediates the relationship between OI traits at the third-order component level and digital service quality. Analysis at the lower component level shows that the mediation effect of occupational stress is only significant in the presence of employee-oriented OI traits and “Alignment and Congruence”. Accordingly, the IPMA exhibited the importance of “Job engagement”, “Alignment and Congruence” and “Occupational Stress” in sustaining service quality. Conversely, code’s percentage analysis demonstrated the role of other insignificant traits such as “Leadership” and Appetite for Change and Knowledge Deployment’ in ensuring the sustainability of digital service quality.

Originality/value

By integrating the Organisational Model of Stress with Public Service-Dominant Logic, this paper rejuvenates the stressors utilised in a traditional work setup and widens the perspective of individual job performance to organisational level performance, to reflect the context of today’s public service delivery. We triangulated the outcome from mediation analysis, IPMA as well as open-ended feedback analysis and propose prioritisation on the aspects of “Employee-oriented traits”, “Psychological Well-being”, “Alignment and Congruence”, “Leadership” and “Appetite for Change and Knowledge Deployment” aspects for sustaining digital government service quality. Considering the significance of occupational stress in sustaining service quality in both quantitative and qualitative analysis, this paper also takes the approach of proposing a stress intervention program at the individual and organisational levels to manage the psychological well-being of the service providers.
Comparing portable x‐ray fluorescence spectroscopy instrumentation for metallome analysis of herbarium specimens
Authors: Purwadi Imam , Erskine Peter D. , Casey Lachlan W. , van der Ent Antony
Published: July 2024

The use of x‐ray fluorescence (XRF) instruments for metallome analysis of herbarium specimens to discover hyperaccumulator plant species has gained popularity, but a growing concern arises about intercomparability from the use of different instrument makes and models. Therefore, this study aimed to assess the performance and comparability of the results generated by three different XRF instruments and three different quantification methods (empirical calibration based on XRF versus inductively coupled plasma atomic emission spectroscopy [ICP‐AES] regression, in‐built manufacturer algorithms, and an independent GeoPIXE software pipeline based on Fundamental Parameters). Three instruments with distinct specifications were chosen to improve the generalizability of the results, ensuring relevance to a wide range of instruments that may be used in the future for metallome analysis of herbarium specimens. Each instrument was used to scan a representative set of dried hyperaccumulator plant leaf samples, and their accuracy in quantifying elemental concentrations was then compared. The manufacturer algorithms overestimate the elemental concentrations and have the highest errors. The empirical calibrations have the closest mean concentration to the mean concentrations reported by ICP‐AES, but can produce negative values. The independent pipeline performance is marginally better than the empirical calibration, but it takes substantially more time and effort to setup the Fundamental Parameters through reverse engineering the instrument hardware parameters. Using the GeoPIXE independent pipeline to extract the XRF peak intensity to use in the empirical calibration performs better than manufacturer algorithms, while avoiding the complicated setup requirements, and this should be considered for further development.
Hospitality workers and gentrification processes: Elective belonging and reflexive complicity
Authors: Threadgold Steven , Molnar Lena , Sharp Megan , Coffey Julia , Farrugia David
Published: July 2024

This paper contributes new understandings of the dynamics and processes of gentrification that contribute to wider transformations of class relations. We argue that the hospitality sector, specifically the tastes, dispositions and practices of young hospitality workers, are central in how gentrification processes currently function. We extend concepts of elective and selective belonging, and reflexive complicity, to analyse how young hospitality workers understand their own labouring practices as contributing to gentrification in their local areas. We show how their aesthetic and ethical orientations to place, especially their workplaces, make their experience of hospitality work more palatable. At the same time, their tastes are ‘put to work’ in venues that contribute to the vibes and aesthetics aimed at middle class consumption practices, while creating symbolic boundaries for long‐term residents who are being ostracised in the process. In this way, the high cultural capital bar workers possess thus become spatial bouncers for high economic capital property developers, where reflexive complicity is instrumentalised as a process of symbolic violence. We propose that hospitality labour, and the everyday relationalities and working practices of young workers, are crucial for understanding the contemporary processes of gentrification and class formation.
Prevalence and classification of congenital thoracic vertebral body abnormalities in neurologically normal brachycephalic ‘screw‐tail’ dog breeds in referral practice in Australia
Authors: Moses WB , Moses IA , Moses EA , Moses PA
Published: July 2024

Objective

To evaluate the prevalence, type, site and breed predisposition of thoracic congenital vertebral malformations (CVM) in neurologically normal brachycephalic ‘screw‐tail’ dog breeds.

Study Design

Retrospective case series.

Animals

Neurologically normal French Bulldogs (n = 63), British Bulldogs (n = 42), Boston Terriers (n = 4) and Pugs (n = 86) presenting for brachycephalic obstructive airway syndrome treatment.

Methods

Either a plain computer tomography scan of the thorax or lateral and dorso‐ventral digital radiographs of the thoracic vertebral column of each dog were assessed for any vertebral malformations and classed according to the Modified McMaster vertebral abnormality classification scheme proposed by Guiterrez et al.

Results

The prevalence of dogs with one or more abnormal vertebrae was 96.82% in French Bulldogs, 90.47% in British Bulldogs, and 76.74% in Pugs. Pugs had significantly lower instances of CVMs than French Bulldogs. The four Boston Terriers all had vertebral malformations, but the results were not considered to be statistically significant due to their small sample size. In French Bulldogs and British Bulldogs, ventral hypoplasia (Type 3) occurred at greater rates than all other types, followed by ventral and median hypoplasia (Types 7) and symmetrical hypoplasia (Type 8). In Pugs, symmetrical hypoplasia (Type 8) was the most common and then ventral hypoplasia (Type 3). The most affected vertebrae were T6–T9 in Pugs and T5–T10 in French Bulldogs and British Bulldogs.

Conclusions

The majority of neurologically normal brachycephalic ‘screw‐tail’ dogs assessed in this paper possessed one or more congenital thoracic vertebral malformations. Dogs with vertebral malformations were found to be more likely to have more than one affected vertebra. Sex had no effect on the prevalence of CVM.

Clinical Relevance

A substantial number of neurologically normal brachycephalic ‘screw‐tail’ dogs suffer from congenital vertebral malformations. Thus, the need for selective breeding programmes to eliminate this hereditary condition is crucial.