bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique tau‐ and synuclein‐dependent metabolic reprogramming in neurons distinct from normal aging
Authors: Yadav Shweta , Graham Aidan , Al Hammood Farazdaq , Garbark Chris , Vasudevan Deepika , Pandey Udai , Asara John M. , Rajasundaram Dhivyaa , Parkhitko Andrey A.
Published: August 2024

Neuronal cells are highly specialized cells and have a specific metabolic profile to support their function. It has been demonstrated that the metabolic profiles of different cells/tissues undergo significant reprogramming with advancing age, which has often been considered a contributing factor towards aging‐related diseases including Alzheimer's (AD) and Parkinson's (PD) diseases. However, it is unclear if the metabolic changes associated with normal aging predispose neurons to disease conditions or a distinct set of metabolic alterations happen in neurons in AD or PD which might contribute to disease pathologies. To decipher the changes in neuronal metabolism with age, in AD, or in PD, we performed high‐throughput steady‐state metabolite profiling on heads in wildtype Drosophila and in Drosophila models relevant to AD and PD. Intriguingly, we found that the spectrum of affected metabolic pathways is dramatically different between normal aging, Tau, or Synuclein overexpressing neurons. Genetic targeting of the purine and glutamate metabolism pathways, which were dysregulated in both old age and disease conditions partially rescued the neurodegenerative phenotype associated with the overexpression of wildtype and mutant tau. Our findings support a “two‐hit model” to explain the pathological manifestations associated with AD where both aging‐ and Tau/Synuclein‐ driven metabolic reprogramming events cooperate with each other, and targeting both could be a potent therapeutic strategy.
Aging human abdominal subcutaneous white adipose tissue at single cell resolution
Authors: Whytock K. L. , Divoux A. , Sun Y. , Pino M. F. , Yu G. , Jin C. A. , Robino J. J. , Plekhanov A. , Varlamov O. , Smith S. R. , Walsh M. J. , Sparks L. M.
Published: August 2024

White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell‐specific transcriptional aberrations that occur in WAT with aging. We leveraged full‐length snRNA‐Seq and histology to characterize the cellular landscape of human abdominal subcutaneous WAT in a prospective cohort of 10 younger (≤30 years) and 10 older individuals (≥65 years) balanced for sex and body mass index (BMI). The older group had greater cholesterol, very‐low‐density lipoprotein, triglycerides, thyroid stimulating hormone, and aspartate transaminase compared to the younger group (p < 0.05). We highlight that aging WAT is associated with adipocyte hypertrophy, increased proportions of lipid‐associated macrophages and mast cells, an upregulation of immune responses linked to fibrosis in pre‐adipocyte, adipocyte, and vascular populations, and highlight CXCL14 as a biomarker of these processes. We show that older WAT has elevated levels of senescence marker p16 in adipocytes and identify the adipocyte subpopulation driving this senescence profile. We confirm that these transcriptional and phenotypical changes occur without overt fibrosis and in older individuals that have comparable WAT insulin sensitivity to the younger individuals.
Does image sentiment of major public emergency affect the stock market performance? New insight from deep learning techniques
Authors: Liu Yun , Huang Dengshi , Zhou Jianan , Wang Sirui
Published: August 2024

Leveraging deep learning to analyse COVID‐19 image sentiment, this study reveals its significant impact on stock market dynamics. It highlights how vivid imagery prompts marked emotional responses, altering market performance and how news sentiment can modulate this effect. Further, it underscores the pivotal role of forum‐based investor sentiment, particularly affecting small‐minus‐big stocks during downturns and trading week commencements. This research not only advances behavioural finance understanding but also informs management and regulatory strategies.
Diagnostic value of structural, functional and effective connectivity in bipolar disorder
Authors: Gencheva Teodora M. , Valkov Bozhidar V. , Kandilarova Sevdalina S. , Maes Michael H. J. , Stoyanov Drozdstoy S.
Published: August 2024

Introduction

The aim of this systematic review is to assess the functional magnetic resonance imaging (fMRI) studies of bipolar disorder (BD) patients that characterize differences in terms of structural, functional, and effective connectivity between the patients with BD, patients with other psychiatric disorders and healthy controls as possible biomarkers for diagnosing the disorder using neuroimaging.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA), guidelines a systematic search for recent (since 2015) original studies on connectivity in bipolar disorder was conducted in PUBMED and SCOPUS.

Results

A total of 60 studies were included in this systematic review: 20 of the structural connectivity, 33 of the functional connectivity, and only 7 of the studies focused on effective connectivity complied with the inclusion and exclusion criteria.

Discussion

Despite the great heterogeneity in the findings, there are several trends that emerge. In structural connectivity studies, the main abnormalities in bipolar disorder patients were in the frontal gyrus, anterior, as well as posterior cingulate cortex and differences in emotion and reward‐related networks. Cerebellum (vermis) to cerebrum functional connectivity was found to be the most common finding in BD. Moreover, prefrontal cortex and amygdala connectivity as part of the rich‐club hubs were often reported to be disrupted. The most common findings based on effective connectivity were alterations in salience network, default mode network and executive control network.

Although more studies with larger sample sizes are needed to ascertain altered brain connectivity as diagnostic biomarker, there is a perspective that the method could be used as a single marker of diagnosis in the future, and the process of adoption could be accelerated by using approaches such as semiunsupervised machine learning.
Antibiofilm effect of different concentrations of silver nanoparticles combined with calcium hydroxide against Enterococcus faecalis biofilm: An ex vivo study
Authors: Basudan Sumaya , Alqahtani Alanoud , Alrwais Fatemah , Almeaither Reem , Auda Sayed , Balto Hanan A.
Published: August 2024

This study aimed to evaluate the antibiofilm activity of different concentrations of silver nanoparticles (AgNPs) in combination with calcium hydroxide [Ca(OH)2] against Enterococcus faecalis biofilm. On an E. faecalis biofilm on dentin discs, the following medicaments were applied for 7 days (n = 13/group): 0.005% AgNPs+Ca(OH)2, 0.01% AgNPs+Ca(OH)2, 0.02% AgNPs + Ca(OH)2, Ca(OH)2 and saline/control. Specimens were stained with LIVE/DEAD® BacLight™ dye and analysed with confocal laser scanning microscopy. Proportion of dead bacteria was calculated and analysed. There was a significant reduction in E. faecalis biofilm in all medicament groups (43.5%, 49.1%, 69.1%, 48.7%) respectively, compared with control group (2.54%) (p < 0.001). The 0.02% AgNPs + Ca(OH)2 group demonstrated the most significantly superior antibiofilm effect, with no significant difference between remaining groups. In conclusion, combining 0.02% AgNPs enhanced the antibiofilm effect of Ca(OH)2 on E. faecalis biofilm compared with lower AgNPs concentrations.
The risk of psychiatric disorders in finasteride users with benign prostatic hyperplasia and androgenetic alopecia: A population‐based case–control study
Authors: Lyakhovitsky Anna , Amichai Boaz , Galili Eran , Cohen Arnon , Kridin Khalaf , Segal Zvi , Netzer Doron
Published: August 2024

Background

There is a long‐standing debate if finasteride, a medication used to treat benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA), can cause psychiatric side effects.

Objective

The goal of this large‐scale population‐based study was to determine whether finasteride therapy for BPH and AGA is associated with the emergence of mental health conditions.

Methods

This observational case–control study compared the data from patients with BPH who received finasteride 5 mg daily and patients with AGA who received finasteride 1 mg daily with age‐ and gender‐matched controls. The incidence of psychological health outcomes such as depression, anxiety, neuroses, bipolar disorder, schizophrenia, psychoses and alcohol abuse within 2 years of the initiation of finasteride therapy has been evaluated and compared between the finasteride groups and controls.

Results

The BPH group included 307 men with a mean age of 61.5 (±17.4) years and 1218 controls. Mental health outcomes recorded in 2.3% of the patients, with no significant increase in rate when compared to controls. The AGA group consisted of 23,227 men with a mean age of 31.4 (±10.3) years and 39,444 controls. One percent of AGA patients developed psychiatric disorders. In comparison to controls, patients with AGA had higher rates of anxiety and depression (0.6% vs. 0.4%, p = 0.04, and 0.5% vs. 0.4%, p = 0.007, respectively). In multivariate regression models, finasteride was found as one of the risk factors for anxiety (OR 1.449, p = 0.002) and depression (OR 1.439, p = 0.003) when stratified to age, sector, socioeconomic status and comorbidities.

Conclusions

According to our research, finasteride users had a very low rate of adverse mental health effects, with no increase in psychological sequelae in BPH patients and a slight increase in anxiety and depression in AGA patients.
Long non‐coding RNA TPT1‐AS1 inhibits ferroptosis in ovarian cancer by regulating GPX4 via CREB1 regulation
Authors: Cao Lei , Wang Yan , Liu Juanni , Bai Xiaoying , Chi Xiaohong
Published: August 2024

Background

Long non‐coding RNAs (lncRNAs) play crucial roles in cellular processes, with dysregulation implicated in various diseases, including cancers. The lncRNA TPT1‐AS1 (TPT1 Antisense RNA 1) promotes tumor progression in several cancers, including ovarian cancer (OC), but its influence on ferroptosis and interaction with other proteins remains underexplored.

Methods

In this study, we employed a multi‐faceted approach to investigate the functional significance of TPT1‐AS1 in OC. We assessed TPT1‐AS1 expression in OC specimens and cell lines using RT‐qPCR, in situ hybridization (ISH), and fluorescence in situ hybridization (FISH) assays. Functional assays included evaluating the impact of TPT1‐AS1 knockdown on OC cell proliferation, migration, invasiveness, and cell cycle progression. Further, we explored and validated the interaction of TPT1‐AS1 with other proteins using bioinformatics. Finally, we investigated TPT1‐AS1 involvement in erastin‐induced ferroptosis using Iron Assay, Malondialdehyde (MDA) assay, and reactive oxygen species (ROS) detection.

Results

Our findings revealed that TPT1‐AS1 overexpression in OC correlated with an unfavorable prognosis. TPT1‐AS1 knockdown suppressed cell proliferation, migration, and invasiveness. Additionally, TPT1‐AS1 inhibited erastin‐induced ferroptosis, and in vivo experiments confirmed its oncogenic impact on tumor development. Mechanistically, TPT1‐AS1 was found to regulate Glutathione Peroxidase 4 (GPX4) transcription via CREB1 (cAMP response element‐binding protein 1) and interact with RNA‐binding protein (RBP) KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) to regulate CREB1.

Conclusion

TPT1‐AS1 promotes OC progression by inhibiting ferroptosis and upregulating CREB1, forming a regulatory axis with KHDRBS3. These findings highlight the regulatory network involving lncRNAs, RBPs, and transcription factors in cancer progression.
Bayesian analysis of multivariate mixed longitudinal ordinal and continuous data
Authors: Zhang Xiao
Published: August 2024

Multivariate longitudinal ordinal and continuous data exist in many scientific fields. However, it is a rigorous task to jointly analyse them due to the complicated correlated structures of those mixed data and the lack of a multivariate distribution. The multivariate probit model, assuming there is a multivariate normal latent variable for each multivariate ordinal data, becomes a natural modeling choice for longitudinal ordinal data especially for jointly analysing with longitudinal continuous data. However, the identifiable multivariate probit model requires the variances of the latent normal variables to be fixed at 1, thus the joint covariance matrix of the latent variables and the continuous multivariate normal variables is restricted at some of the diagonal elements. This constrains to develop both the classical and Bayesian methods to analyse mixed ordinal and continuous data. In this investigation, we proposed three Markov chain Monte Carlo (MCMC) methods: Metropolis–Hastings within Gibbs algorithm based on the identifiable model, and a Gibbs sampling algorithm and parameter‐expanded data augmentation based on the constructed non‐identifiable model. Through simulation studies and a real data application, we illustrated the performance of these three methods and provided an observation of using non‐identifiable model to develop MCMC sampling methods.
Limiting access to assisted reproductive technologies for males of advanced age—Pros and cons from a Nordic perspective
Authors: Hanevik Hans Ivar , Bergh Christina , Laivuori Hannele , Spangmose Anne Lærke , Magnusson Åsa , Pinborg Anja , Piltonen Terhi
Published: August 2024

It is not controversial to state that parental age is increasing in several countries. But how to deal with this increase might be. Some Nordic countries have set an upper age limit for females seeking assisted reproduction in their national legislation, but none have done so for males. There are also recommendations in place that restrict access to publicly funded assisted reproduction for both females and males of advanced age in some Nordic countries. As recent data now show somatic and psychiatric health risks related to advanced paternal age, we ask if the time has come for countries to set an upper age limit for males seeking assisted reproduction like there already is for females, and summarize some of the risks and rewards involved in treating couples with advanced age in fertility clinics.
Agile 3+ and Agile 4 scores predict chronic kidney disease development in metabolic dysfunction‐associated steatotic liver disease
Authors: Jung Chan‐Young , Lee Jung Il , Ahn Sang Hoon , Kim Seung Up , Kim Beom Seok
Published: August 2024

Background and Aims

Despite the development of transient elastography (TE)‐based Agile scores for diagnosing fibrotic burden in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD), their applicability in predicting kidney outcomes remains unclear. We aimed to investigate the association between liver fibrotic burden, as assessed by Agile scores, and the risk of incident chronic kidney disease (CKD) in patients with MASLD.

Methods

A total of 3240 participants with MASLD but without pre‐existing CKD who underwent TE between July 2006 and October 2018 were selected. The primary outcome was incident CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria (≥1+ on dipstick) on two consecutive measurements. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits.

Results

During a median follow‐up of 3.6 years, 187 participants (5.8%) developed incident CKD. When stratified into three groups according to Agile 3+ scores, multivariable Cox models revealed that risk of incident CKD was 2.77‐fold (95% confidence interval [CI], 1.89–4.07; p < 0.001) higher in the high‐risk group (Agile 3+ >0.68), compared to the low‐risk group (Agile 3+ <0.45). During a median follow‐up of 3.4 years, the high‐risk group had a 2.41‐fold higher risk (95% CI, 1.86–3.12; p < 0.001) of experiencing the secondary outcome, compared to the low‐risk group. Similar findings were observed for Agile 4 scores. Prediction testing revealed that Agile scores were better predictors of kidney outcomes, compared to liver stiffness measured by TE.

Conclusions

In patients with MASLD, but without CKD, advanced liver fibrosis measured by Agile scores was significantly associated with a higher risk of incident CKD.
Prognostic stratification in DLBCL patients with aberrant MYC gene
Authors: Li Jian‐Rong , Shaw Vikram R. , Parthasarathy Abi , Li Yong , Amos Christopher I. , Cheng Chao
Published: August 2024

Diffuse large B‐cell lymphoma (DLBCL) is a heterogeneous disease characterized by a subset of patients who exhibit treatment resistance and poor prognoses. Genomic assays have been widely employed to identify high‐risk individuals characterized by rearrangements in the MYC, BCL2 and BCL6 genes. These patients typically undergo more aggressive therapeutic treatments; however, there remains a significant variation in their treatment outcomes. This study introduces an MYC signature score (MYCSS) derived from gene expression profiles, specifically designed to evaluate MYC overactivation in DLBCL patients. MYCSS was validated across several independent cohorts to assess its ability to stratify patients based on MYC‐related genetic and molecular aberrations, enhancing the accuracy of prognostic evaluations compared to conventional MYC biomarkers. Our results indicate that MYCSS significantly refines prognostic accuracy beyond that of conventional MYC biomarkers focused on genetic aberrations. More importantly, we found that nearly 50% of patients identified as high risk by traditional MYC metrics actually share similar survival prospects with those having no MYC aberrations. These patients may benefit from standard GCB‐based therapies rather than more aggressive treatments. MYCSS provides a robust signature that identifies high‐risk patients, aiding in the precision treatment of DLBCL, and minimizing the potential for overtreatment.
Remembering history: Autobiographical memory for the COVID‐19 pandemic lockdowns, psychological adjustment, and their relation over time
Authors: Hjuler Tirill Fjellhaugen , Lee Daniel , Ghetti Simona
Published: August 2024

This longitudinal study examined age‐ and gender‐related differences in autobiographical memory about the COVID‐19 pandemic lockdowns and whether the content of these memories predicted psychological adjustment over time. A sample of 247 students (Mage = 11.94, range 8–16 years, 51.4% female, 85.4% White) was recruited from public and private schools in Denmark and assessed three times from June 2020 to June 2021. The findings showed that memories weakened over time in detail and emotional valence. Additionally, psychological well‐being decreased over time, with adolescent females faring the worst. Critically, memories including higher levels of negative affect and factual information about COVID‐19 and the lockdown predicted worse psychological well‐being over time, underscoring aspects of autobiographical memory that might help attenuate the negative consequences of the lockdown.
‘Children should be raised like this’: A history of the neurodiversity movement in Italy and its implications for children's well‐being
Authors: Scavarda Alice , Cascio M. Ariel
Published: August 2024

Childhood Studies scholars have increasingly engaged with the concept of neurodiversity, particularly with respect to neurodivergent children's mental well‐being. The purpose of this paper is to discuss the history of the neurodiversity movement in Italy, and the consequences on children's mental health, drawing on eight in‐depth interviews with movement leaders, researchers and members of parent associations. We argue that Italian education and health services serve as promising sites within which a neurodiversity approach can foster neurodivergent children's self‐esteem and give them powerful tools to fight against oppressive practices.
Allergic contact dermatitis in adults with and without atopic dermatitis: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC)
Authors: Chicharro P. , Munera‐Campos M. , Zaragoza‐Ninet V. , Giménez‐Arnau A. , González‐Pérez R. , Miquel‐Miquel F. J. , Córdoba‐Guijarro S. , Sanz‐Sánchez T. , Ruiz‐González I. , Silvestre‐Salvador J. F. , Serra‐Baldrich E. , Borrego L. , Pastor‐Nieto M. A. , Ortiz de Frutos F. J. , Mercader‐García P. , Heras‐Mendaza F. , Fernández‐Redondo V. , Rodríguez‐Serna M. , Hervella‐García M. , Carrascosa J. M. , Gallego‐Descalzo M. A. , García‐Doval I. , Sánchez‐Pérez J.
Published: August 2024

Background

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined.

Objectives

To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups.

Methods

We analysed two groups (AD and non‐AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them.

Results

A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non‐AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age‐adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61–0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non‐AD individuals.

Conclusions

We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non‐AD population, except for a negative relationship between AD and sensitisation to nickel sulphate.
Assessing contact dermatitis risk among Manitoba workers in the Manitoba Occupational Disease Surveillance System
Authors: Rydz E. , Walld R. , Quinn E. K. , Koehoorn M. W. , McLeod C. B. , Demers P. A. , Peters C. E. , Kraut A.
Published: August 2024

Introduction

This exploratory study aimed to assess contact dermatitis (CD) risk among workers using the Manitoba Occupational Disease Surveillance System (MODSS).

Methods

The MODSS linked accepted time‐loss claims from the Workers' Compensation Board of Manitoba (2006–2019), with administrative health data from medical and hospital records (1996–2020). CD risk by occupation and industry (hazard ratio, 95% confidence intervals) was estimated using Cox proportional hazard models, adjusted for age and stratified by sex.

Results

Increased risk of new onset CD was observed among some occupations and industries with known skin irritants and allergens. Some occupations with known increased risks of CD remained elevated when removing the accepted WCB cases was performed, suggesting that all CD cases in these occupations may not show up in WCB statistics. Increased risk was also observed for occupations and industries with unknown exposures related to CD, whereas some groups known to be at risk of CD were not observed to have elevated risks in this cohort.

Discussion

The MODSS successfully identified some occupations and industries known to be at high risk of occupational CD, but not others. Some occupations not typically associated with work‐related CD were also identified, which warrants further investigation.
Predictive Value of Lymphocyte‐to‐Neutrophil Ratio and Platelet‐to‐Neutrophil Ratio on PD‐L1 Expression in Lung Cancer
Authors: Cui Shun‐Shun , Shen Ya , Yang Rui‐Qing
Published: August 2024

Objective

This study aimed to examine the predictive effect of the lymphocyte‐to‐neutrophil ratio (LNR) and the platelet‐to‐neutrophil ratio (PNR) on the expression of programmed death receptor ligand 1 (PD‐L1) in patients diagnosed with lung cancer.

Methods

The clinical records of 86 patients diagnosed with lung cancer between January 2020 and February 2022 at Fu Yang People's Hospital were retrospectively analyzed. The records included information on age, gender, smoking history, hematological indices at the time of admission, staging of the lung malignancy, histopathological subtype, comorbidities, and the expression levels of PD‐L1. Patients were stratified into two distinct cohorts based on their PD‐L1 expression levels: Those with an expression level greater than or equal to 1% were classified into the PD‐L1 positive expression group, while the remainder were categorized as the PD‐L1 negative expression group. Univariate analysis and multivariate logistic regression analysis were used to identify the influencing factors of PD‐L1, and the diagnostic efficacy was calculated using the receiver operating characteristic (ROC) curve.

Results

Upon analysis, the PD‐L1 positive expression group manifested notably lower values as compared to their counterparts in the PD‐L1 negative expression group (LNR: 0.262 ± 0.105 vs. 0.390 ± 0.201; PNR: 41.03 [29.64, 50.11] vs. 49.50 [37.38, 73.83]), and these differences were statistically significant. There was a notable disparity in PD‐L1 expression based on gender, with males exhibiting a statistically significant higher positivity rate compared to females. Furthermore, patients in Stages I–III of the disease demonstrated a markedly elevated PD‐L1 positivity rate compared to those in Stage IV (p < 0.05). Incorporating univariates with statistical differences into multivariate logistic regression analysis suggests that stage and LNR are independent risk factors for PD‐L1 negative expression. ROC curve analyses revealed that the area under the ROC curve (AUC) for LNR as an indicator for PD‐L1 positive expression stood at 0.706, while the AUC for PNR was calculated at 0.687.

Conclusion

PD‐L1 expression is correlated with gender and lung cancer staging, and LNR and PNR have a predictive value for PD‐L1 expression.
It Is Time to Get to Know the Neuroendocrine Cell Hyperplasia of Infancy
Authors: Jin Long , Wei Wen
Published: August 2024

In the two decades that have elapsed since the initial proposal of neuroendocrine cell hyperplasia of infancy (NEHI), several hundred cases have been reported and researched. However, a comprehensive analysis of research progress remains absent from the literature. The present article endeavors to evaluate the current progress of NEHI research and offer a reference for the clinical management of this condition.
An interpretable machine learning methodology to generate interaction effect hypotheses from complex datasets
Authors: Nasir Murtaza , Summerfield Nichalin S. , Simsek Serhat , Oztekin Asil
Published: August 2024

Machine learning (ML) models are increasingly being used in decision‐making, but they can be difficult to understand because most ML models are black boxes, meaning that their inner workings are not transparent. This can make interpreting the results of ML models and understanding the underlying data‐generation process (DGP) challenging. In this article, we propose a novel methodology called Simple Interaction Finding Technique (SIFT) that can help make ML models more interpretable. SIFT is a data‐ and model‐agnostic approach that can be used to identify interaction effects between variables in a dataset. This can help improve our understanding of the DGP and make ML models more transparent and explainable to a wider audience. We test the proposed methodology against various factors (such as ML model complexity, dataset noise, spurious variables, and variable distributions) to assess its effectiveness and weaknesses. We show that the methodology is robust against many potential problems in the underlying dataset as well as ML algorithms.
Do overpaid dividends drive stock price crash risk?
Authors: Ling Xiaoting , Shan Yuan George , Wu Wuqing , Zhang Lu , Zhang Xinyue
Published: August 2024

We explore the impact of overpaid dividends on future stock price crash risk. Using a dataset of 2662 firms with 15,416 firm‐year observations of China's A‐share listed firms, our result indicates that overpaid dividends are positively related to the likelihood of future stock price crash risk. The results further suggest that high‐quality corporate governance and financial analyst coverage can moderate the positive effect of overpaid dividends on the crash risk. Moreover, continuous overpaid dividends and state‐owned enterprises with overpaid dividends have a stronger impact on the crash risk, and overpaid dividends are significantly affected by their peer firms.
Changes in Rates of Special Considerations in Higher Education Applications Pre‐ and During the COVID‐19 Pandemic in Victoria, Australia
Authors: Gao Caroline X. , Clarke Emily , Nicholas Jennifer , Teo Shu Mei , Koppe Caleb , Peter Gavin , Lum Alex , Barth Tamara , Farish Steve , Rudd Matthew , Gong Yiting , Gan Daniel Z. Q. , Browne Vivienne , Tjia Teresa , Filia Kate M. , Killackey Eóin
Published: August 2024

Background and Aims

Since the onset of the COVID‐19 pandemic, a significant rise in mental ill health has been observed globally in young people, particularly those in their final years of secondary school. Students' negative experiences coincide with a critical transitional period which can disrupt milestones in social and educational development. This study aimed to use innovative population‐level data to map the impact of the pandemic on students entering higher education.

Methods

Pre‐pandemic (2019/2020) and pandemic (2020/2021) tertiary education application data were obtained from the Victorian Tertiary Admissions Centre. Prevalence of applications for special consideration related to mental ill health were compared between cohorts across various geographical areas and applicant demographic subgroups. Relative risk regression models were used to understand the role of different risk factors.

Results

Rates of mental health‐related special consideration applications increased by 38% among all applications (pre‐pandemic: 7.8%, n = 56 916; pandemic: 10.8%, n = 58 260). Highest increases were observed among students in areas with both extended and close‐quarter lockdown experiences, and areas impacted by 2019/2020 black summer bushfires. The increases were higher among Year 12 students and students with other special consideration needs (e.g., physical condition, learning disability). Slightly higher increases were observed in areas with higher socio‐economic status, which may potentially be related to inequality in mental health service access.

Conclusion

As consequences of mental health difficulties and academic disruption in youth can be long lasting, it is critical to establish a mental health support framework both in and outside of higher education to facilitate young people's recovery from the pandemic.
An analytical solution for vertical infiltration in homogeneous bounded profiles
Authors: Argyrokastritis I. , Kalimeris K. , Mindrinos L.
Published: August 2024

In this study, we derive an analytical solution to address the problem of vertical infiltration within 1D homogeneous bounded profiles. Initially, we consider the Richards equation together with Dirichlet boundary conditions. We assume constant diffusivity and linear dependence between the conductivity and the water content, resulting to a linear partial differential equation of diffusion type. To solve the simplified initial boundary value problem over a finite interval, we apply the unified transform, commonly known as the Fokas method. Through this methodology, we obtain an integral representation of the solution that can be efficiently and directly computed numerically, yielding a convergent scheme. We examine various cases, and we compare our solution with well‐known approximate solutions. This work can be seen as a first step to derive analytical solutions for the far more difficult and complex problem of modelling water flow in heterogeneous layered soils.
Cumulative adversity and survival in the wild
Authors: Ortiz‐Ross Xochitl , Blumstein Daniel T.
Published: August 2024

Protecting populations contending with co‐occurring stressors requires a better understanding of how multiple early‐life stressors affect the fitness of natural systems. However, the complexity of such research has limited its advancement and prevented us from answering new questions. In human studies, cumulative risk models predict adult health risk based on early adversity exposure. We apply a similar framework in wild yellow‐bellied marmots (Marmota flaviventer). We tested cumulative adversity indices (CAIs) across different adversity types and time windows. All CAIs were associated with decreased pup survival and were well supported. Moderate and acute, but not standardized CAIs were associated with decreased lifespan, supporting the cumulative stress hypothesis and the endurance of early adversity. Multivariate models showed that differences in lifespan were driven by weaning date, precipitation, and maternal loss, but they performed poorly compared with CAI models. We highlight the development, utility, and insights of CAI approaches for ecology and conservation.
Disturbances can facilitate prior invasions more than subsequent invasions in microbial communities
Authors: Lear Luke , Hesse Elze , Buckling Angus
Published: August 2024

Invasions are commonly found to benefit from disturbance events. However, the importance of the relative timing of the invasion and disturbance for invader success and impact on community composition remains uncertain. Here, we experimentally test this by invading a five‐species bacterial community on eight separate occasions—four before a disturbance and four after. Invader success and impact on community composition was greatest when the invasion immediately followed the disturbance. However, the subsequent invasions had negligible success or impact. Pre‐disturbance, invader success and impact was greatest when the invader was added just before the disturbance. Importantly, however, the first three pre‐disturbance invasion events had significantly greater success than the last three post‐disturbance invasions. Moreover, these findings were consistent across a range of propagule pressures. Overall, we demonstrate that timing is highly important for both the success and impact on community composition of an invader, with both being lower as time since disturbance progresses.
Blockchain, tokens, smart contracts, and “decentralized autonomous organization”: Expanding and renewing the mechanisms of governance?
Authors: Chambefort Cyril , Chaudey Magali
Published: August 2024

Blockchain, tokens, smart contracts, and decentralized autonomous organization (DAO) are increasingly shaping discussions in media and research. The aim of this contribution is to explore how governance theory can clarify these concepts and how the application of theory to this new problem can also enrich governance theory itself.

We focus on the technical environment (blockchain and tokens) that is at the heart of this new form of organization. By exploiting the intrinsic attributes of blockchain (decentralization, immutability, and transparency), smart contracts and DAOs are coordination mechanisms that expand the possibilities of interagent interactions and horizontal coordination, eliminating information asymmetries and the need for trusted third parties. In addition, by taking advantage of the transparency and immutability inherent in blockchain, smart contracts and DAOs make it possible to find and record agreements securely, automating contractual clauses.

We argue that these technologies have a significant potential to renew the contractual approach to governance and to overcome some of the limitations of traditional theory.
Dynamic optical coherence tomography unveils subclinical, vascular differences across actinic keratosis grades I–III
Authors: Fredman Gabriella , Fuchs Christine Sofie Krohn , Wenande Emily , Philipsen Peter A. , Untracht Gavrielle R. , Andersen Flemming , Bjerring Peter , Wiegell Stine R. , Haedersdal Merete
Published: August 2024

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub‐surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D‐OCT) to characterize microvessels in AK I‐III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I‐III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D‐OCT. On D‐OCT, vessel shapes, −pattern and ‐direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D‐OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty‐seven patients with AK I‐III (n = 207) and PD (n = 87) were included. Qualitative D‐OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 μm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p < 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non‐specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p < 0.001). Vessel direction changed in AK II‐III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I‐II than PD (p ≤ 0.025), whereas diameter remained constant. D‐OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D‐OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades.
E‐cadherin staining in the diagnosis of lobular versus ductal neoplasms of the breast: the emperor has no clothes
Authors: Taha Seyed R , Boulos Fouad
Published: August 2024

Categorizing breast neoplasia as ductal or lobular is a daily exercise that relies on a combination of histologic and immunohistochemical tools. The historically robust link between loss of the E‐cadherin molecule and lobular neoplasia has rendered staining for E‐cadherin by immunohistochemistry a staple of this diagnostic process. Unfortunately, discordances between E‐cadherin expression and histomorphology, and variations in E‐cadherin staining patterns and intensities abound in clinical practice, but are often neglected in favour of a binary interpretation of the E‐cadherin result. In this article, we highlight the complexities of E‐cadherin expression through a review of the E‐cadherin protein and its associated gene (CDH1), the mechanisms leading to aberrant/absent E‐cadherin expression, and the implications of these factors on the reliability of the E‐cadherin immunohistochemical stain in the classification of ductal versus lobular mammary neoplasia.
Subungual melanoma: molecular analysis of 31 cases from early stage to invasive melanoma
Authors: Perrin Christophe , Coutts Michael , Dadone‐Montaudié Bérengère
Published: August 2024

Aims

The distinction between the benign subungual melanocytic lesions and an early lesion of subungual melanoma (SUM) remains a diagnostic challenge. We evaluated the routine diagnostic utility of array Comparative Genomic Hybridization (aCGH) to detect whole‐genome copy number variations (CNV) as well as targeted next‐generation sequencing (NGS) in SUM.

Methods and Results

This retrospective study included 20 cases of in situ SUM and 11 cases of invasive SUM. Analysis by aCGH detected common oncogene amplifications in all but one case of invasive SUM (n = 10) and in all cases of in situ SUM with a melanocyte count (MC) >45/mm (n = 4 true positive) and the average number of CNV was 8.5. Thirteen remaining cases of in situ SUM gave false negative results (n = 13), owing to a lack of sufficient melanocytes to analyse (median MC of 35.35; range: 10.16–39.5). Molecular analysis failed in four cases (three in situ SUM and one invasive SUM) due to insufficient amounts of DNA. Across the whole cohort, the sensitivity of aCGH was 52%, but when adjusting the cutoff to MC >45/mm, the sensitivity was 93%. Targeted NGS was less informative than aCGH analyses in our series of SUM.

Conclusion

To distinguish malignant from benign lesions, especially in situ SUM versus atypical lentiginous melanocytic proliferations, aCGH analysis should be performed when the MC is above 45 melanocytes per linear millimetre. This pangenomic method can detect oncogene amplifications, as well as a number of CNV >3, which strongly support the diagnosis of malignancy.
Preoperative risk stratification models after radical cystectomy for bladder cancer: A multi‐center study
Authors: Yamane Hiroshi , Morizane Shuichi , Honda Masashi , Muraoka Kuniyasu , Oono Hirofumi , Isoyama Tadahiro , Ono Koji , Sejima Takehiro , Kadowaki Hiroyuki , Takenaka Atsushi
Published: August 2024

Objective

We investigated preoperative patient factors associated with prognosis in 263 bladder cancer (BC) patients undergoing radical cystectomy (RC). We also developed new risk stratification models for prognosis.

Methods

This retrospective study included patients treated at Tottori University Hospital and affiliated hospitals between January 2010 and December 2019. The relationship between preoperative patient factors and overall recurrence‐free and cancer‐specific survival (CSS) was analyzed. The modified Glasgow prognosis score (mGPS) was calculated using serum albumin and C‐reactive protein (CRP) levels. Statistical analyses included the log‐rank test and Cox proportional hazards regression.

Results

Eastern Cooperative Oncology Group performance status (ECOG‐PS), mGPS, and clinical tumor stage independently predicted CSS in multivariate analysis. A new risk stratification model included ECOG‐PS ≥2, clinical tumor stage ≥3, serum albumin <3.5 g/dL, and serum CRP >0.5 mg/dL. Risk groups were defined as 0 factors (low risk), 1–2 factors (intermediate risk), and 3–4 factors (high risk). High‐risk patients showed significantly poorer 3‐year cancer‐free survival: 86.9% (low risk), 76.7% (intermediate risk), and 50.0% (high risk).

Conclusions

ECOG‐PS, clinical tumor stage, and mGPS are predictive of poor cancer‐free survival post‐RC for BC. Our model offers the potential for prognostic prediction in these patients.
Adapting to change: Undergraduate nursing students' sense of belonging transitioning from online to in‐person learning environments
Authors: Montague Janet , Tsui Joyce , Kamstra‐Cooper Krista , Connell Michelle , Atack Lynda , Haghiri‐Vijeh Roya
Published: August 2024

Aim

To examine undergraduate nursing students' sense of belonging as they transitioned from online to in‐person learning.

Design

A mixed‐method design employing a Sense of Belonging Survey and three open‐ended questions.

Methods

Participants were first‐year undergraduate nursing students who were back to in‐person learning after 3 years of online learning during the pandemic. The survey was administered online in April 2023 using Qualtrics survey software. The survey data were analysed using descriptive statistics, and the open‐ended questions were analysed by deductive thematic analysis.

Results

Seventy‐five (48%) of the 155 potential participants responded to the survey. The mean score on the Sense of Belonging Survey was 74%, a positive finding suggesting that many participants feel that they ‘belong’ in the classroom. Three overarching themes were identified in response to the open‐ended questions: factors supporting students' sense of belonging, factors hindering students' sense of belonging and strategies for faculty, administrators and students to increase a sense of belonging.

Conclusion

Understanding the factors that contribute to or hinder nursing students' sense of belonging during this transition will assist in developing strategies to mitigate challenges, foster a positive learning environment and enhance the overall sense of belonging among nursing students.

Impact

The first year of a nursing programme is crucial for student retention as students require tailored programmes and strategies to support their success. Examining and analysing the transition from online to in‐person classroom settings is crucial to identifying strategies to enhance and support first‐year students' sense of belonging and academic success. Exploring nursing students' experiences of belonging during transitions contributes to a more inclusive and equitable educational experience, fostering an environment where all students can thrive and succeed.

Patient or Public Contribution

Not applicable.
Safety and effectiveness of tofogliflozin in Japanese people with type 2 diabetes: A multicenter prospective observational study in routine clinical practice
Authors: Yamada Yuichiro , Yabe Daisuke , Shide Kenichiro , Suzuki Atsushi , Terauchi Yasuo , Sato Yasunori , Shihara Nobuyuki , Seino Yutaka
Published: August 2024

Aims/Introduction

Sodium–glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large‐scale, non‐commercial, investigator‐initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin.

Materials and Methods

This multicenter, open‐label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor‐naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss.

Results

The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104‐week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%–0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94–3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104.

Conclusions

Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high‐incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.