bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐Cell RNA Sequencing Reveals the Tumor Heterogeneity and Immunosuppressive Microenvironment in Urothelial Carcinoma
Authors: Lyu Tianqi , Wu Kerong , Zhou Yincong , Kong Tong , Li Lin , Wang Kaizhe , Fu Pan , Wei Pengyao , Chen Ming , Zheng Jianping
Published: December 2024

Urothelial carcinoma (UC) can arise from either the lower urinary tract or the upper tract; they represent different disease entities and require different clinical treatment strategies. A full understanding of the cellular characteristics in UC may guide the development of novel therapies. Here, we performed single‐cell transcriptome analysis from four patients with UC of the bladder (UCB), five patients with UC of the ureter (UCU), and four patients with UC of the renal pelvis (UCRP) to develop a comprehensive cell atlas of UC. We found the rare epithelial cell subtype EP9 with epithelial‐to‐mesenchymal transition (EMT) and cancer stem cell (CSC) features, and specifically expressed SOX6, which was associated with poor prognosis. We also found that ACKR1+ endothelial cells and inflammatory cancer‐associated fibroblasts (iCAFs) were more enriched in UCU, which may promote pathogenesis. While ESM1+ endothelial cells may more actively participate in UCB and UCRP tumorigenesis by promoting angiogenesis. Additionally, CD8 + effector T cells were more enriched in UCU and UCRP patients, while Tregs were mainly enriched in UCB tumors. C1QC+ macrophages and LAMP3+ dendritic cells were more enriched in UCB, which is closely related to the formation of the heterogeneous immunosuppressive microenvironment. Furthermore, we found strong interactions between iCAFs, EP9, and Endo_ESM1, and different degrees of activation of the FGF‐FGFR3 axis and immune checkpoint pathway were observed in different UC subtypes. Our study elucidated the cellular heterogeneity and the components of the microenvironment in UC arising from the upper and lower urinary tracts and provided novel therapeutic targets.
Hereditary Spastic Paraplegia Linked to Abnormal Splicing From an AIMP1 Missense Variant
Authors: Morais Sara , Leal Loureiro José , Brandão Eva , Sequeiros Jorge , Stevanin Giovanni , Santos Mariana
Published: December 2024

Hereditary spastic paraplegias (HSP) are a diverse group of neurodegenerative diseases characterized by lower limb spasticity and weakness. To date, over 80 genes have been associated with HSP, but many families remain without a molecular diagnosis.

In this study, linkage analysis and whole‐exome sequencing (WES) were performed to identify the causal gene in a HSP family with autosomal recessive inheritance. Multipoint linkage analysis revealed a maximum significant multipoint LOD score of 4.6 on chromosome 4. WES analysis focused on this region led to the identification of a homozygous missense variant in AIMP1 (c.223G>A). Minigene assays showed that the presumed missense variant in AIMP1 caused loss of the exon 3 donor splice site. Ultimately, this led to the use of an alternative splice site within the intron and the insertion of a premature stop codon.

The identification of a novel AIMP1 causal variant contributes to the growing list of HSP genes. Furthermore, it shows that, considering also previous reported cases, disruption of AIMP1 causes a spectrum of disorders ranging from intellectual disability to more complex neurodegenerative diseases.
HPSCAN: Human Perception‐Based Scattered Data Clustering
Authors: Hartwig S. , Onzenoodt C. v. , Engel D. , Hermosilla P. , Ropinski T.
Published: December 2024

Cluster separation is a task typically tackled by widely used clustering techniques, such as k‐means or DBSCAN. However, these algorithms are based on non‐perceptual metrics, and our experiments demonstrate that their output does not reflect human cluster perception. To bridge the gap between human cluster perception and machine‐computed clusters, we propose HPSCAN, a learning strategy that operates directly on scattered data. To learn perceptual cluster separation on such data, we crowdsourced the labeling of bivariate (scatterplot) datasets to 384 human participants. We train our HPSCAN model on these human‐annotated data. Instead of rendering these data as scatterplot images, we used their x and y point coordinates as input to a modified PointNet++ architecture, enabling direct inference on point clouds. In this work, we provide details on how we collected our dataset, report statistics of the resulting annotations, and investigate the perceptual agreement of cluster separation for real‐world data. We also report the training and evaluation protocol for HPSCAN and introduce a novel metric, that measures the accuracy between a clustering technique and a group of human annotators. We explore predicting point‐wise human agreement to detect ambiguities. Finally, we compare our approach to 10 established clustering techniques and demonstrate that HPSCAN is capable of generalizing to unseen and out‐of‐scope data.
Safety and Phosphate‐Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers
Authors: Pergola Pablo E. , Joy Melanie S. , Garsd Armando , Hasal Steve J. , Khare Atul , Reddy Guru , Gupta Pramod , Finn William F.
Published: December 2024

Despite the widespread use of currently available serum phosphate management options, elevated serum phosphate is common in patients with end‐stage kidney disease on dialysis. Characteristics of currently available phosphate binders that lead to poor patient experiences such as large drug volume size of required daily medication (e.g., many large tablets) and adverse gastrointestinal effects may decrease compliance to labeled dosing instructions, thus decreasing their efficacy. Oxylanthanum carbonate is a new molecule yielding the same phosphate‐binding capacity as lanthanum carbonate, but in a much smaller drug volume and tablet size. It is formulated as small tablets that can be easily swallowed. In a double‐blind dose‐escalation phase 1 study, healthy volunteers (n = 32) were randomly divided into four treatment arms and randomly assigned to receive oxylanthanum carbonate tablets or a placebo over a period of 4 days to evaluate safety, urinary and fecal excretion of phosphorus, and pharmacokinetics. Each treatment arm evaluated a different dose of oxylanthanum carbonate: 500, 1000, 1500, or 2000 mg three times a day (TID). The study drug was well‐tolerated. Oxylanthanum carbonate effectively decreased dietary phosphorus absorption, demonstrated by decreased urinary phosphorus excretion and increased fecal phosphorus excretion. Systemic absorption of oxylanthanum carbonate was minimal, with lanthanum serum concentration values below the level of quantification (0.500 ng/mL) in all subjects receiving 500 mg TID and did not exceed 0.7 ng/mL at other doses. Future studies should evaluate and confirm the ability of oxylanthanum carbonate to reduce pill burden and improve dose administration, patient tolerability, adherence, and treatment outcomes.

Trial Registration: ClinicalTrials.gov identifier: NCT01560884
The impact of novel probiotics isolated from the human gut on the gut microbiota and health
Authors: Caesar Robert
Published: December 2024

The gut microbiota plays a pivotal role in influencing the metabolism and immune responses of the body. A balanced microbial composition promotes metabolic health through various mechanisms, including the production of beneficial metabolites, which help regulate inflammation and support immune functions. In contrast, imbalance in the gut microbiota, known as dysbiosis, can disrupt metabolic processes and increase the risk of developing diseases, such as obesity, type 2 diabetes, and inflammatory disorders. The composition of the gut microbiota is dynamic and can be influenced by environmental factors such as diet, medication, and the consumption of live bacteria. Since the early 1900s, bacteria isolated from food and have been used as probiotics. However, the human gut also offers an enormous reservoir of bacterial strains, and recent advances in microbiota research have led to the discovery of strains with probiotic potentials. These strains, derived from a broad spectrum of microbial taxa, differ in their ecological properties and how they interact with their hosts. For most probiotics bacterial structural components and metabolites, such as short‐chain fatty acids, contribute to the maintenance of metabolic and immunological homeostasis by regulating inflammation and reinforcing gut barrier integrity. Metabolites produced by probiotic strains can also be used for bacterial cross‐feeding to promote a balanced microbiota. Despite the challenges related to safety, stability, and strain‐specific properties, several newly identified strains offer great potential for personalized probiotic interventions, allowing for targeted health strategies.
Anti‐diabetic effects of GLP‐1 receptor agonists on obese and overweight patients across diabetes status, administration routes, treatment duration and baseline characteristics: A systematic review
Authors: Wong Hon Jen , Lin Norman H. Y. , Teo Yao Hao , Yeo Brian S. Y. , Toh Keith Zhi Xian , Teo Yao Neng , Chan Mark Y. , Yeo Leonard L. L. , Poh Kian Keong , Kong William K. F. , Eng Pei Chia , Tan Benjamin Y. Q. , Dalakoti Mayank , Sia Ching‐Hui
Published: December 2024

Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are increasingly used for anti‐obesity indications. However, little is known of the comparative effect of GLP‐1 RAs and their glycemic impact across the different routes of administration, diabetic statuses and durations of prescription. PubMed, EMBASE and CENTRAL were searched from inception to 13 February 2024. Only randomised controlled trials were included in this systematic review and meta‐analysis. Adults aged above 18 years old, who were in the overweight/obesity range, with or without type 2 diabetes mellitus (T2DM) were included. Baseline characteristics and changes in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were obtained. GLP1‐RAs demonstrated an overall reduction in HbA1c of −0.72% (95% confidence interval [CI] −0.79 to −0.65, p < 0.01) and in FPG of −1.00 mmol/L (95% CI −1.16 to −0.84, p < 0.01). HbA1c reduction in pre‐DM patients was −0.44% (95% CI −0.54 to −0.18, p < 0.01). Patients who were followed up for more than a year experienced a smaller reduction of HbA1c. Meta‐regression showed that the GLP‐1 RAs are more efficacious at higher HbA1c and lower body mass index. Overall, GLP‐1 RAs consistently led to a significant reduction in HbA1c at −0.72% and FPG at −1.00 mmol/L. These effects may be equally efficacious in pre‐DM patients with obesity and those at lower BMI. With pre‐DM and obesity being risk factors for metabolic syndrome, these findings may provide newer perspectives in expanding indications for GLP‐1 RA initiation.
Temporal changes in taxon abundances are positively correlated but poorly predicted at the global scale
Authors: Lertzman‐Lepofsky Gavia , Dolezal Aleksandra J. , Waters Mia Tayler , Fuster‐Calvo Alexandre , Black Emily N. , Flaman Stephanie , Straus Sam , Langendorf Ryan E. , Eckert Isaac , Fan Sophia , Branch Haley A. , Chardon Nathalie Isabelle , Collins Courtney G.
Published: December 2024

Linking changes in taxon abundance to biotic and abiotic drivers over space and time is critical for understanding biodiversity responses to global change. Furthermore, deciphering temporal trends in relationships among taxa, including correlated abundance changes (e.g. synchrony), can facilitate predictions of future shifts. However, what drives these correlated changes over large scales are complex and understudied, impeding our ability to predict shifts in ecological communities. We used two global datasets containing abundance time‐series (BioTIME) and biotic interactions (GloBI) to quantify correlations among yearly changes in the abundance of pairs of geographically proximal taxa (genus pairs). We used a hierarchical linear model and cross‐validation to test the overall magnitude, direction and predictive accuracy of correlated abundance changes among genera at the global scale. We then tested how correlated abundance changes are influenced by latitude, biotic interactions, disturbance and time‐series length while accounting for differences among studies and taxonomic categories. We found that abundance changes between genus pairs are, on average, positively correlated over time, suggesting synchrony at the global scale. Furthermore, we found that abundance changes are more positively correlated with longer time‐series, with known biotic interactions and in disturbed habitats. However, the magnitude of these ecological drivers alone are relatively weak, with model predictive accuracy increasing approximately two‐fold with the inclusion of study identity and taxonomic category. This suggests that while patterns in abundance correlations are shaped by ecological drivers at the global scale, these drivers have limited utility in forecasting changes in abundances among unknown taxa or in the context of future global change. Our study indicates that including taxonomy and known ecological drivers can improve predictions of biodiversity loss over large spatial and temporal scales, but also that idiosyncrasies of different studies continue to weaken our ability to make global predictions.
Selection for increased sexual bimaturism in the common housefly, Musca domestica
Authors: Petrucci Giovanni , Francuski Ljubinka , Jansen Walter L. , Beukeboom Leo W.
Published: December 2024

The growing demand for insect mass production requires methodologies that allow for easy separation of males and females as the two sexes can have very different economic values. The common housefly, Musca domestica (L.) (Diptera: Muscidae), is one of the candidate species for industrial production. In this species, males typically develop faster and are smaller than females. Exploiting housefly sexual bimaturism (sexual difference in developmental time) could allow the maintenance of colonies with a higher proportion of females, which is favourable in terms of egg yield. Here, we report an artificial selection experiment of breeding early‐emerging males with late‐emerging females for six generations, with the aim to increase the time interval between emergence of males and females. The level of sexual bimaturism was not increased after six generations of selection. The life‐history traits fecundity, egg‐to‐adult survival and hatchability were not affected by the selection procedure. Wing size measurement revealed that early‐ and late‐emerging males did not differ in size, suggesting that developmental time and body size are decoupled in this sex. Still, large females consistently emerged later than small females, suggesting an intricate sex‐specific genetic architecture for size and developmental time in the housefly. Our results are relevant in the context of mass production, providing new insight into the manipulation and maintenance of female‐biased sex ratios in production colonies of the common housefly.
Effects of Age and Atomoxetine on Olfactory Perception and Learning and Underlying Plasticity Mechanisms in Rats
Authors: Abu‐Labdeh Ruhuf , Omoluabi Tamunotonye , Yuan Qi
Published: December 2024

The locus coeruleus (LC) plays a vital role in cognitive function through norepinephrine release. Impaired LC neuronal health and function is linked to cognitive decline during ageing and Alzheimer's disease. This study investigates age‐related alterations in olfactory detection and discrimination learning, along with its reversal, in Long–Evans rats, and examines the effects of atomoxetine (ATM), a norepinephrine uptake inhibitor, on these processes. Adult (6–9 months) and aged (22–24 months) Long–Evans rats underwent odour detection threshold experiments with saline and two doses of ATM (0.3 and 1 mg/kg). Reward‐based odour discrimination learning included simple, difficult and reversal learning tasks. LC neuron density, dopamine beta‐hydroxylase and norepinephrine transporter expression in the piriform cortex (PC) and orbitofrontal cortex were measured. Reversal learning and olfactory threat extinction were used to measure behavioural flexibility. Immunohistochemistry and western blotting were used to analyse phosphorylated cAMP response element binding protein (pCREB) and cFos expression and ex vivo electrophysiology assessed long‐term depression (LTD) in the PC. Whereas adult and aged cohorts showed similar odour detection and discrimination learning, fewer aged rats acquired reversal learning successfully. ATM improved reward‐based odour discrimination in adults but hindered learning reversal. A delayed CREB phosphorylation in the posterior PC associated with atomoxetine administration possibly underlies learning enhancement. ATM resulted in less freezing behaviour in a threat conditioning and extinction paradigm at moderate, but not at higher doses. ATM administration ex vivo prevented PC LTD. These findings highlight the intricate effects of atomoxetine, influenced by target structures, and suggest potential interactions with other neurotransmitters. Our results contribute to understanding the impact of ageing and norepinephrine enhancers on cognitive processes.
Reforming the EU budget, a prerequisite for future enlargements?
Authors: Vitrey Anne , Mornon Afonso Aurélien
Published: December 2024

This article contributes to the ongoing debate on EU budget reform. It proposes a revision of Articles 311 and 312 TFEU in advance of any future enlargements. The reform proposed by the authors is based on four pillars. First, the EU needs to reduce the pressure from and reliance on national budgets by the allocation of new own resources coupled with hybrid and off‐budget instruments. Second, there is a need to adapt the Multiannual Financial Framework to rebalance traditional priorities like the Common Agricultural Policy and Cohesion with emerging political priorities such as sustainability, digitalisation or defense. Third, the European Parliament's role in budgetary decision‐making process needs to be strengthened by modifying the Multi Financial Framework calendar to align it with the Parliament's legislative term and by enshrining the mid‐term review in the treaties. Finally, the use of budgetary conditionality should be extended to ensure sound financial management.
Manual versus reciprocating endodontic debridement of equine cheek teeth: Micro‐computed tomography findings
Authors: Korsós Szabolcs A. , Kibleur Pierre , Josipovic Iván , Boone Matthieu , Vlaminck Lieven
Published: December 2024

Background

In orthograde endodontic treatments, different methods are available to debride the pulp canals of endodontically compromised equine cheek teeth, but their efficacy is unknown.

Objectives

To explore and compare the efficacy and anatomical changes caused by manual versus reciprocating filing techniques in equine cheek teeth, to explore the presence of instrumentation mishaps described in human dentistry and to explore anatomical complexities of the pulp cavity that often remain uninstrumented using microcomputed tomography (μCT).

Study design

Ex‐vivo randomised experiments.

Methods

Twenty‐two extracted healthy equine cheek teeth were randomised into two groups: debridement with nickel‐titanium (Ni‐Ti) manual H‐files and debridement with Ni‐Ti reciprocating K‐files. All canals of all teeth were instrumented by a single clinician and μCT scans made before and after instrumentation were digitally analysed to compare the change in pulp volume, loss of dental material, percentages of instrumented pulp canal wall at three levels, instrumentation times and instrumentation mishaps between both techniques. The data were analysed using either an Independent samples T‐test or Mann–Whitney U‐test with p < 0.05 denoting a statistically significant difference.

Results

The use of reciprocating files resulted in a statistically significant advantage at apical levels when it comes to the percentage of instrumented root canal surface (p < 0.01; reciprocating mean 12% ± 6; manual mean 3% ± 3). No other significant differences were found between the methods. Instrumentation mishaps were detected in this study and were equally distributed between the two groups. Frequently uninstrumented regions consisted of intercanal communications, root canal branches, narrow corners of pulp canals and branches of pulp horns.

Main limitations

Convenience sample, use of healthy cheek teeth, ex vivo debridement.

Conclusions

The debridement efficacy in equine cheek teeth is generally poor with a slight apical advantage using reciprocating instruments. Instrumentation mishaps should be kept in mind when performing endodontic procedures in the equine patient.
Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction‐associated steatohepatitis
Authors: Vermeulen Isabeau , Li Mengying , van Mourik Hester , Yadati Tulasi , Eijkel Gert , Balluff Benjamin , Godschalk Roger , Temmerman Lieve , Biessen Erik A. L. , Kulkarni Aditya , Theys Jan , Houben Tom , Cillero‐Pastor Berta , Shiri‐Sverdlov Ronit
Published: December 2024

The prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) progressing to metabolic dysfunction‐associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly. Our previous proteomics research has shown that inhibition of extracellular CTSD results in more anti‐inflammatory effects and fewer potential side effects compared to intracellular CTSD inhibition. However, the correlation between reduced side effects and alterations in the hepatic lipid composition remains unknown. This study aims to investigate the correlation between intra‐ and extracellular CTSD inhibition and potential alterations in the hepatic lipid composition in MASH. Low‐density lipoprotein receptor knockout (Ldlr−/−) mice were fed a high‐fat diet for 10 weeks and received subcutaneous injections every 2 days of vehicle, intracellular CTSD inhibitor (GA‐12), or extracellular CTSD inhibitor (CTD‐002). Matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) was used to visualize and compare the lipid composition in liver tissues. Hepatic phosphatidylcholine remodeling was observed with both inhibitors, suggesting their therapeutic potential in treating MASH. Treatment with an intracellular CTSD inhibitor resulted in elevated levels of cardiolipin, reactive oxygen species, phosphatidylinositol, phosphatidylethanolamine, and lipids that are linked to mitochondrial dysfunction and inflammation, and induced more oxidative stress. The observed modifications in lipid composition demonstrate the clinical advantages of extracellular CTSD inhibition as a potentially beneficial therapeutic approach for MASH.
Population‐Level Habitat Breadth Varies With Richness in Reef Fishes
Authors: Granot Itai , Kulbicki Michel , Vigliola Laurent , Belmaker Jonathan
Published: December 2024

Aim

It has been hypothesised that niche breadth decreases with richness due to interactions, such as competition, forcing species to specialise. This hypothesis has been tested at the community‐level using species‐level niche breadth estimates. However, evidence for changes in niche‐breath among populations of the same species are scant. Our aim was to examine the niche breadth to richness relationship within species, which is crucial for understanding the role of interactions, as opposed to large‐scale climate, in altering realised niche breadth.

Location

The Pacific Ocean.

Time Period

1988–2015.

Major Taxa Studied

Fishes.

Methods

We focus on reef fishes along a large‐scale richness gradient not accompanied by marked environmental changes. Fishes were surveyed in four distinct habitats, which allow to estimate habitat‐breadth for each population. We calculated habitat‐breadth across multiple populations of 154 species, and tested how habitat‐breadth varied with richness. We further tested the effect of traits and trait‐distinctiveness on the richness‐sensitivity of habitat‐breadth.

Results

Habitat‐breadth varied with species traits, with larger species more commonly habitat generalists while schooling and planktivorous species more commonly habitat specialists. Importantly, habitat‐breadth was negatively correlated with richness for 109 out of the 154 species, and, across all species, the relationship was highly significant. We found some support that species with distinct traits displayed less sensitivity of habitat‐breadth to richness, but the relationship was dependent on the type of trait‐distinctiveness index used.

Conclusions

This is the first large‐scale evidence that population‐level habitat‐breadth changes with richness. Results suggest that the realised niche is population‐specific and that niche breadth is reduced in high‐diversity settings where more intense interactions, such as competition, are expected. This implies that populations, specifically in species rich areas, do not use their entire fundamental niche. Therefore, the ability to predict habitat preferences response to global changes based on current habitat associations, without accounting for species interactions, may be limited.
How to Encourage the Public to Help People With Dementia in the Community: A Scoping Review
Authors: Zhi Shengze , Li Runze , Fang Shuyan , Gao Shizheng , Song Dongpo , Wu Yifan , Zhong Qiqing , Jin Changxu , Zhang Yuan , Song Haitao , Sun Jiao
Published: December 2024

Background

In a response to the lack of public awareness of dementia, ‘ageing in place’ and ‘dementia‐friendly community’ policies have been proposed, and a number of relevant studies have been carried out.

Aim

To map the evidence of public help for people with dementia in the community.

Design

A scoping review.

Methods

A comprehensive search of nine databases was conducted to find studies from the inception of the databases to January 2024. We developed our inclusion criteria to identify studies about public help for people with dementia in the community. Data from included studies were charted (purposively designed template) and narrated synthesis in relation to the study's research questions.

Results

Of 34 studies included, we found that difficult situations were encountered by people with dementia after developing cognitive, behavioural and psychological symptoms. We identified three types of helping behaviour, namely, formal planned, informal planned and spontaneous helping behaviour, which were influenced by general demographic characteristics, knowledge, attitudes, responsibilities and understanding. Fourteen studies proposed interventions to promote public help for people with dementia in the community, covering three categories of teaching, practical and web‐based methods.

Conclusions

It is necessary to develop a systematic intervention to promote public helping behaviour according to the characteristics of people with dementia and the modifiable influencing factors of helping behaviour.

Patient or Public Contribution

No patient or public contribution. This is a Scoping Review.
Cathepsin B Modulates Alzheimer's Disease Pathology Through SAPK/JNK Signals Following Administration of Porphyromonas gingivalis‐Derived Outer Membrane Vesicles
Authors: Jiang Muzhou , Ge Ziming , Yin Shoucheng , Liu Yanqing , Gao Hanyu , Lu Lijie , Wang Hongyan , Li Chen , Ni Junjun , Pan Yaping , Lin Li
Published: December 2024

Aim

Porphyromonas gingivalis
, a consensus periodontal pathogen, is thought to be involved in Alzheimer's disease (AD) progression, and
P. gingivalis
‐derived outer membrane vesicles (PgOMVs) are a key toxic factor in inducing AD pathology. This study aimed to clarify the regulatory mechanism underlying the PgOMV‐induced AD‐like phenotype.

Materials and Methods

We intraperitoneally injected PgOMVs into the periphery of wild‐type and CatB knockout mice for 4 or 8 weeks to assess the effect of CatB on PgOMV‐induced AD pathology. Mice were evaluated for cognitive change, tau phosphorylation, microglial activation, neuroinflammation and synapse loss. Microglial and primary neuron culture were prepared to verify the in vivo results.

Results

CatB deficiency significantly alleviated PgOMV‐induced cognitive dysfunction, microglia‐mediated neuroinflammation, tau hyperphosphorylation and synapse loss. Subsequent transcriptomic analysis, immunofluorescence and immunoblotting suggested that CatB modulates microglia‐mediated neuroinflammation through stress‐activated protein kinases (SAPK)/Jun amino‐terminal kinases (JNK) signals after administration of PgOMVs, which in turn regulates neuronal tau phosphorylation and synapse loss in a SAPK/JNK‐dependent manner.

Conclusion

Our study unveils a previously unknown role of CatB in regulating PgOMV‐induced AD pathology.
The First Report of Cod Gill Poxvirus in Gills of Atlantic Cod (Gadus morhua L.) Suffering From Cardiorespiratory Disease
Authors: Gjessing Mona C. , Tengs Torstein , Nilsen Hanne , Mohammad Saima , Weli Simon C.
Published: December 2024

Atlantic cod farming experiences renewed growth in Norway, and increased awareness is essential to address emerging diseases in this species. There are few reports on gill diseases in cod, and to date, no viral gill infections of cod have been documented. In this study, we collected samples from three sequential time points in summer 2023 from farmed cod suffering from cardiorespiratory disease. We document severe heart and gill pathology, and a novel double‐strand DNA virus was discovered in the gills. Through comprehensive genetic characterisation and comparative sequence analysis, this virus was classified as a new species in the genus Poxvirus, designated cod gill poxvirus (CGPV). We demonstrate disease causality with severe gill lesions as shown by histopathology and RNA scope in situ hybridisation, and poxvirus particles were identified in gill epithelial cells by transmission electron microscopy. Further, another gill pathogen not previously described in cod, Candidatus. Branchiomonas cysticola, was identified by pcr and in situ hybridisation. Our findings provide strong evidence for poxvirus in Atlantic cod and underscore the imminent threat posed to Atlantic cod farm industry.
Long‐Term Prognostic Factors for Patients Aged 80 and Older With Superficial Esophageal Squamous Cell Carcinoma Undergoing Endoscopic Submucosal Dissection
Authors: Suzuki Yugo , Kikuchi Daisuke , Ohashi Kenichi , Hoteya Shu
Published: December 2024

Background and Aim

Endoscopic submucosal dissection (ESD) is an acceptable treatment for superficial esophageal squamous cell carcinoma (ESCC) even in elderly patients. However, studies on the prognostic factors in very elderly patients are limited. Therefore, we aimed to explore the prognostic factors affecting overall survival (OS) in patients aged ≥ 80 with superficial ESCC who underwent ESD.

Methods

This study included 155 patients aged ≥ 80 who underwent ESD for superficial ESCC. Clinicopathological findings and long‐term outcomes were examined. The prognostic nutritional index (PNI) and geriatric nutritional index (GNRI) were used to assess pre‐treatment nutritional status.

Results

Twenty‐nine patients (18.7%) were aged ≥ 85. Thirty‐five (22.6%) and 61 (39.4%) patients had a GNRI < 92 and PNI < 45, respectively. Metastatic relapse was observed in five cases, four (80%) of which resulted in death due to the primary disease. The median OS of all patients was 86 months. Although factors specifically associated with disease‐specific survival were not identified, GNRI, PNI, comorbidity, and physical status were associated with OS. In multivariate analysis, age ≥ 85 years (p = 0.03), GNRI (p < 0.01), and PNI (p < 0.01) remained factors associated with OS. Patients aged ≥ 85 with either GNRI ≥ 92 or PNI ≥ 45 had a median OS of 106 months, whereas those aged ≥ 85 with GNRI < 92 had a median OS of 12 months.

Conclusions

GNRI and PNI are important indicators for assessing the suitability of ESD in elderly patients aged ≥ 80. These indices can help predict OS and guide clinical decision‐making for this patient population.
Impact of dyslipidemia and lipid‐lowering therapy with statins in patients with neuroendocrine tumors
Authors: Faggiano Antongiulio , Russo Flaminia , Zamponi Virginia , Sesti Franz , Puliani Giulia , Modica Roberta , Malandrino Pasqualino , Ferraù Francesco , Rinzivillo Maria , Di Muzio Marco , Di Simone Emanuele , Panattoni Nicolò , Dolce Pasquale , Lauretta Rosa , Di Iasi Gianfranco , Prinzi Antonio , Alessi Ylenia , Feola Tiziana , Mazzilli Rossella , Appetecchia Marialuisa , Giannetta Elisa , Panzuto Francesco , Colao Annamaria
Published: December 2024

Dyslipidemia is a potential unfavorable prognostic factor in neuroendocrine tumors (NETs); conversely, statins proved to have antiproliferative effects in NET cell lines and could be a helpful therapeutic strategy for these patients. The main objective of this observational cohort retrospective study is to explore the associations between dyslipidemia and NET progression and evaluate the potential influence of statins in this context. 393 patients with histologically confirmed gastroenteropancreatic or bronchopulmonary NETs from six Italian centres didicated to NET diagnosis and therapy were included. The cohort included 123 patients with dyslipidemia, 81 of which were taking statins. Clinicopathological data, including patient demographics, tumor characteristics, and treatment details as well as the prevalence, timing of dyslipidemia and hypolipemic therapy were collected. The main outcome measure used is progression‐free survival (PFS). Among the 393 patients, 123 (31.3%) had dyslipidemia. Statins were used by 81 (65.8%) dyslipidemic patients, mostly atorvastatin. Median PFS was 87 months overall, 124 months in non‐dyslipidemic patients, and 72 months in dyslipidemic patients (p = .268). Dyslipidemic patients on statins had a significantly better median PFS (108 months) than those not on statins (26 months; p = .024). Recurrence‐free survival (RFS) was also evaluated, but no significant differences were found. In conclusion, while PFS was lower in dyslipidemic patients compared to non‐dyslipidemic patients, the difference was not statistically significant. Statin therapy was associated with improved PFS among dyslipidemic patients, suggesting a potential antiproliferative effect of statins in NETs. These findings warrant further investigation to substantiate the role of statins in the management of NETs.
Aligned, competing, and blurred: Gender and family attitudes in East Asia
Authors: Han Sang Won , Oh Eunsil
Published: December 2024

Objective

This study explores the complexity of how gender and family attitudes relate to each other in East Asia, paying particular attention to heterogeneity and the impact of cognitive structures.

Background

Recent work on gender and family attitudes across post‐industrial societies has shown a rise in the complexity of attitudinal configurations. However, no systematic analysis has been conducted to explore variations in attitudinal configurations and cognitive structures. This study aims to fill this gap.

Method

Data from the 2012 Gender Module of the International Social Survey Programme were used to conduct a relational class analysis to measure relationships and networks among gender and family attitudes in China, Japan, South Korea, and Taiwan (N = 8,007).

Results

Analysis revealed three cognitive structures: aligned, competing, and blurred. The aligned structure represents a cognitively unified belief system. The competing structure identifies beliefs that are in conflict, with a network of attitudes that is partitioned into family versus work. The last group comprises those who cognitively have blurred boundaries across different domains of gender, work, and family. Notably, competing and blurred cognitive structures are characterized by lower life satisfaction and fertility intentions than those with an aligned structure. Further analysis demonstrated that all three groupings exist in China, Japan, South Korea, and Taiwan but vary in prevalence.

Conclusion

The findings shed new light on the complex interplay of gender and family attitudes in East Asia and provide valuable insights into the heterogeneous cognitive structures of attitudes and the consequences of holding unstructured and dissonant attitudinal structures.
“I Need the Shade”: Experiences and Perceptions of Elementary School Children During Recess in Hot Weather
Authors: Poulos Allison , Albaloul Omar , Min Hyungsik , Kulinna Pamela Hodges
Published: December 2024

Background

Few studies have investigated how heat impacts play from the perspective of children. The purpose of this study was to explore children's experiences of recess play during high temperatures.

Methods

We used the draw‐and‐tell method to retrospectively explore the experiences of recess during hot weather among students (N = 38) between the ages of 5–12 attending four elementary schools in one school district in Arizona (United States). Students were asked to imagine themselves at recess on a hot day, select their preferred playground picture (shaded or unshaded), draw a picture of themselves in the playground, and explain their drawings. Drawings and narrations were analyzed using content analysis and constant comparative methods.

Results

Most students (89%) selected the playground picture with shade. Four themes describing students' experiences were found: (a) discomfort, (b) self‐awareness of heat affecting health and safety, (c) influence of heat on play and physical activity, and (d) adaptive strategies for managing heat during recess.

Conclusions

Students are aware that playing outside in the heat has the potential to negatively impact their health and adapt their play to occur in the shade.

Implications for School Health Policy, Practice, and Equity

Outdoor school play spaces should increase access to shade.
Females in Corporate Business: Do Ownership and Homophily Matter in the Context of Tax Avoidance?
Authors: Baatwah Saeed Rabea , Hussainey Khaled , Bajaher Mohammed
Published: December 2024

This study revisits the evidence on the role of females in corporate outcomes by investigating the impact of female shareholders and their interactions with female directors on tax avoidance. We build our investigation on gender socialization and homophily theories and on data from an emerging market, Oman, for the period 2012–2019. Our fixed‐effects regressions reveal that female shareholders are associated with lower tax avoidance. We also find that female shareholders and directors on the board interact to significantly reduce tax avoidance practices. In an additional analysis, we find that the effect of female shareholders is more pronounced in firms with low‐quality audit committees and nonreligious CEOs. Interestingly, we also observe that female shareholders improve the quality of financial reports, consequently reducing tax avoidance. The main findings were verified using various robustness tests including alternative measures and research designs. The novelty of this study is that it provides innocent evidence on the role of female shareholders and their interaction with other females in firm tax activities.
Revisiting ecological specialization: the case of plant–frugivore interactions
Authors: Carlo Tomás A. , Vitor S. Messeder João , Allbee Samantha A. , Cruz-Mendoza Alberto C. , Velázquez Sebastián G. , Andrzejewski Christi M. , Jenkins Tyson J. , Cordeiro Norbert J.
Published: December 2024

Understanding the extent to which organisms exhibit specialization when interacting with or relying on distinct aspects of their biotic and abiotic environment is a central tenet in ecology and evolution. Despite the relevance of the concept and theoretical advances, specialization has and continues to be ambiguously defined. Here we review the uses of the term ‘specialist' using as a case study the field of frugivory and seed dispersal. Our goal is to identify points of clarity and ambiguity to promote a more consistent and coherent use of specialization in plant–frugivore interactions and similar fields. Frugivory and seed dispersal research presents a good case study because specialist–generalist concepts have guided the theoretical framework of the field since its beginnings. Our analyses show that definitions of ‘specialist frugivores' have changed over time and tend to vary also depending on the studied animal taxa, such as birds, bats, or primates. At least some of the ambiguity arises from defining specialization at different scales such as evolutionary versus ecological timeframes. More critical is the finding that specialization is commonly used on frugivore species without knowledge or measure of the biological dependance of the species on specific types of fruit resources. Specifically, we found that most studies use specialization to describe fruit‐preference patterns that – unlike specialization constrained by evolution – can be variable and context‐dependent. We call for increased awareness to distinguish between contextual cases of preferential resource‐uses, from specialized interactions that limit populations and singularly define species.
Freehand Placement of a Transiliac‐Transsacral Screw for Fixation of Posterior Pelvic Ring Injuries
Authors: Liu Guangping , Chen Zhiguang , Cao Wenhao , Zheng Yubo , Li Jiaqi , He Jie , Li Changda , Chen Hua , Tang Peifu
Published: December 2024

Objective

There are many advantages to stabilize the posterior pelvic ring injuries with a transiliac‐transsacral (TITS) screw percutaneously. To identify the correct entry point and insert a guidewire accurately for a TITS screw, we propose a method of specifying the optimal entry point, and introduce a technique of enabling freehand placement of a guidewire with fluoroscopic guidance.

Methods

In this retrospective study, 116 patients who underwent pelvic CT scans and pelvic lateral radiographs at our institution from January 2020 to April 2022 were enrolled. The optimal entry point for a TITS screw was formulated in the strict mid‐sagittal CT plane, and then transferred to the pelvic lateral radiograph relying on the sacral cortexes which were easily visible even in the poor fluoroscopy. The relative position of this point to other anatomical markers was checked to confirm its feasibility as an entry point. With the method to locate the entry point, 18 patients suffered the posterior pelvic ring injuries were treated with TITS screws through hammering a reverse Kirschner wire (K‐wire) to insert a guidewire assisted by a canula, followed by the validation of the screw placement accuracy.

Results

The transferred point in radiograph was consistently beneath the sacral alar slope, and located posteroinferior to the iliac cortical density (ICD) and anterosuperior to the sacral nerve root tunnel in all 116 patients. In clinical practice, 18 TITS screws were successfully placed in 18 patients without cortex violation. The average operative time for each screw was 20.11 ± 6.29 min, with an average of 14.11 ± 6.81 fluoroscopic shots per screw. At the 3‐month follow‐up, fracture healing was confirmed in all patients. The average Majeed score was 89.61 ± 6.90 at the final follow‐up.

Conclusions

It's feasible to identify an entry point for a TITS screw based on the sacral cortexes, and hammering a reverse K‐wire assisted by a percutaneous kyphoplasty (PKP) canula is a safe and practical technique for guidewire insertion.
Broken Communities: Structural Violence, Dispossession, and the Reign of Terror in Northwestern Nigeria
Authors: Ejiofor Promise Frank
Published: December 2024

Why do some pastoralists join bandit groups in Nigeria? This conundrum is yet to be explored in the emerging scholarly literature on pastoral banditry in Nigeria's troubled northwest region. Whereas the upsurge in pastoralist‐related banditry has been predominantly explicated with the theoretical frameworks of ungoverned spaces and relative deprivation, the role of structural violence in some pastoralists' decision to become bandits has not received sufficient scholarly attention. Drawing on the analytical framework of structural violence first advanced by the Norwegian sociologist Johan Galtung, I contend that some pastoralists take to the composite crime of banditry as a consequence of the inegalitarian distribution of resources and power. Pastoralists resorting to banditry in the northwest region can therefore be considered as a rebellious response, albeit misguided, to the structural violence of everyday life―precisely, poverty and repression―in the Nigerian state that precludes them from meeting their basic human needs. To reverse the mayhem and to heal the broken communities in the banditry‐affected northern states in Nigeria, I argue that federal and state governments should not solely rely on a killing approach fixated on military warfare―or the surveillance of forests and remote areas―but must address the structural factors that nurture alienation amongst some pastoralists.
Rapid Weight Gain After Pediatric Kidney Transplant and Development of Cardiometabolic Risk Factors Among Children Enrolled in the North American Pediatric Renal Trials and Collaborative Studies Cohort
Authors: Twichell Sarah , Hunt Elizabeth A. K. , Ciurea Rodica , Somers Michael J. G. ,   The NAPRTCS investigators
Published: December 2024

Introduction

Given the risks of cardiovascular disease among pediatric kidney transplant recipients, we evaluated whether there was an association between rapid weight gain (RWG) following kidney transplantation and the development of obesity and hypertension among children enrolled in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry.

Methods

This retrospective analysis of the NAPRTCS transplant cohort assessed for RWG in the first year post‐transplant and evaluated for obesity and hypertension in children with and without RWG up to 5 years post‐transplant. We evaluated three separate eras (1986–1999, 2000–2009, and 2010–2021). We performed chi‐square and logistic regression analyses to assess cardiometabolic risk at three time points (1, 3, and 5 years post‐transplant).

Results

The percent of children with RWG decreased across the three eras (1986–1999 37.3%, 2000–2009 23.0%, and 2010–2021 16.4%). Obesity was significantly more common among children with a history of RWG following transplant, with 48%–67% with RWG having obesity 5 years following transplant compared with 22%–25% without RWG. Hypertension was significantly more common in the RWG group than the non‐RWG group at all but two time points. In logistic regression models, the odds of obesity in the RWG group compared with non‐RWG was 2.55 (2.29–2.83), and the odds of hypertension were 1.00 (0.94–1.08). Steroid minimization protocols were associated with significantly less RWG.

Conclusions

RWG was significantly associated with obesity but not hypertension among pediatric kidney transplant recipients enrolled in NAPRTCS. Interventions targeting RWG following kidney transplant should be evaluated as a potential way to modify obesity rates following transplantation.
Two‐Dimensional Shear Wave Ultrasound Elastography for Monitoring Pediatric Liver Transplantation: A Review of Recent Advances
Authors: Abdulla Mohamed , Abdulla Maryam , Al‐Hashimi Hakima , Isa Hasan M. , Dunne Kevin , Blackwell James
Published: December 2024

Pediatric liver transplantation (PLT) is a life‐saving procedure for children with end‐stage liver disease. However, post‐transplant monitoring, particularly the diagnosis and prognosis of complications such as allograft fibrosis, remains challenging. Traditionally, liver biopsy has been the gold standard for assessing allograft fibrosis, despite its invasive nature and inherent procedural risks. Recently, shear wave ultrasound elastography (SWE) has seen increasing use as a noninvasive method to provide real‐time, quantitative measurements of liver stiffness as a proxy for fibrosis. In this review, the latest developments in the use of SWE as a method to assess allograft fibrosis post‐PLT are presented, including the current technical challenges associated with its clinical implementation.