bluuebunny/crossref_metadata_2025_split huggingface dataset:
When shareholder power kicks in: corporate financialization as ratchet behaviour and sticky payouts
Authors: Mertens Bakou 
Published: September 2024

Abstract
The rise of payout ratios has been ascribed by financialization scholars to shareholder value orientation (SVO), a governance practice associated with dire consequences. However, it remains unclear how SVO translates into the behaviour that causes these consequences. Yet, identifying behaviour would not only allow us to causally infer what SVO entails for other firm stakeholders and wider society but also to unearth the institutional configurations that catalyse or inhibit it. Using data on all stock-listed firms in the world from 1985 to 2023 this article shows that SVO operates through ratchet behaviour, where shareholders refuse to yield ground when profits decrease. I first illustrate theoretically how this downward rigidity of shareholder remuneration ratchets up payout ratios and structures aggregate payout ratios along the lines of the frequency of ratchet behaviour. Finally, staggered difference-in-differences show that ratchet events indeed cause firms to exhibit persistently higher payout ratios for a decade.
Trusts—A Portuguese perspective and the Madeira’s special case
Authors: Fernandes Ferreira Rogério , Monteiro Duarte Ornelas , Neves Carlos Alcântara 
Published: September 2024

Abstract
The Portuguese perspective on Trusts is very much informed by the fact that it is a legal instrument with no specific regulation in Portugal since it is not legally possible to incorporate a Portuguese Trust besides the special case of Madeira in which the corresponding foreign regulating law will be chosen by the settlor (with the possibility of amending such choice at any time). These Madeira Trusts are also designed to interfere as little as possible with the Portuguese domestic legislative system, which is not designed to entail such a legal concept. However, the Portuguese domestic tax legislation is fully equipped to tax the income potentially derived from foreign Trusts, with some anti-abuse rules and aggravated tax rates potentially applicable when the Trust is domiciled at a blacklisted jurisdiction for Portuguese purposes. We will be discussing the tax treatment in Portugal of the potential income streams derived from a foreign Trust by a private individual, and at the end of the article, we include some explanatory notes on the case of Madeira’s Hybrid Trusts.
Azacitidine and cytarabine induce sustained lymphopenia with abnormal differentiation of common lymphoid progenitors and prolonged suppression of Dnmt3a and Dnmt3b expression in mice
Authors: Matsushita Junya , Miwa Kyoko , Sato Yuri , Honda Kumi , Aida Tetsuo , Tsuchiya Yoshimi 
Published: September 2024

Abstract
Myelosuppression is a major side effect of chemotherapy. Although decreased blood cells are restored with the recovery of bone marrow cells, insufficient recovery of decreased lymphocytes was observed in mice given azacitidine (AZA), a DNA methyltransferase (DNMT) inhibitor, even following the restoration of bone marrow cells. To understand the mechanisms behind this sustained lymphopenia, we examined AZA’s impact on the hematopoietic progenitor cells and the expression of Dnmts and differentiation-related genes. An antimetabolite of cytidine analog, cytarabine (Ara-C), was used as a reference compound. Decreases in almost all blood parameters and common lymphoid progenitors (CLPs) and the downregulation of Dnmts and differentiation-related genes in Lineage−Sca-1+c-kit+ (LSK) cells were observed in mice administered AZA or Ara-C for 7 d. In the posttreatment observation, all parameters, except for lymphocytes and monocytes, exhibited recovery within 3 wk after the final dosing in both treated groups. However, no recovery from the decreases in lymphocytes, especially B cells, and monocytes occurred even after 5 wk. The number of CLPs was elevated after 3 wk. There was a tendency toward recovery from the decreased expression of Dnmt1 and differentiation-related genes, but the expression levels of Dnmt3a and Dnmt3b did not fully recover even 5 wk after the final dosing. Taken together, the findings revealed that the mechanism of sustained lymphopenia observed in mice treated with AZA or Ara-C is associated, at least in part, with the abnormal differentiation of CLPs into B cells accompanied by the prolonged suppression of Dnmt3a and Dnmt3b expression on LSK cells.
Crash-causing information extraction via text-mining techniques: implementation of the Chinese state-related crash narratives
Authors: Zou Guoqing , Huang Helai , Zhou Hanchu , Li Jipu 
Published: September 2024

Abstract
Crash data is the foundation of traffic safety analysis, which can help experts find the cause of crashes and propose corresponding countermeasures. In China, the accident reporting form only allows reporting of one crash cause for each crash based on the prespecified crash cause code. This designation may lead to inaccuracy in recording crash data, especially for state-related crashes. The crash narratives, which are the responding officer's written account of what occurred before, during and after a crash, contain considerable free-form information associated with the crash occurrence. This study investigated the directly contributory factors behind state-related crashes through the development of natural language processing and deep-learning models based on 1625 state-related crash narratives. According to the directly causative factors described in the crash narratives, state-related crashes were labelled speed related, turning related and other causes. Then the crash narratives were vectorized for model training and frequency analysis. The text-CNN, LSTM, GRU and SVM models were applied to reclass the vectorized crash. The results showed that the text-CNN model showed the best model performance in text classification, and the AUC value of this model reached 0.90 for micro-average curves. The results from this study can engage the usage of crash narratives and help identify the actual causative reasons hidden behind some inaccurate crash value designations.
ZymoSoups: A High-Throughput Forward Genetics Method for Rapid Identification of Virulence Genes in Zymoseptoria tritici
Authors: Ali Haider , McDonald Megan C. , Kettles Graeme J. 
Published: September 2024

Septoria tritici blotch is caused by the fungus Zymoseptoria tritici and poses a major threat to wheat productivity. There are over 20 mapped loci in wheat that confer strong (gene-for-gene) resistance against this pathogen, but the corresponding genes in Z. tritici that confer virulence against distinct R genes remain largely unknown. In this study, we developed a rapid forward genetics methodology to identify genes that enable Z. tritici to gain virulence on previously resistant wheat varieties. We used the known gene-for-gene interaction between Stb6 and AvrStb6 as a proof of concept that this method could quickly recover single candidate virulence genes. We subjected the avirulent Z. tritici strain IPO323, which carries the recognized AvrStb6 allele, to ultraviolet (UV) mutagenesis and generated a library of over 66,000 surviving spores. We screened these survivors on leaves of the resistant wheat variety Cadenza in mixtures (soups) ranging from 100 to 500 survivors per soup. We identified five soups with a gain-of-virulence (GoV) phenotype relative to the IPO323 parental strain and re-sequenced 18 individual isolates, including four control isolates and two isolates lacking virulence, when screened individually. Of the 12 confirmed GoV isolates, one had a single nucleotide polymorphism (SNP) in the AvrStb6 coding region. The other 11 GoV isolates exhibited large (approximately 70 kb) deletions at the end of chromosome 5, including the AvrStb6 locus. Our findings demonstrate the efficiency of this forward genetic approach in elucidating the genetic basis of qualitative resistance to Z. tritici and the potential to rapidly identify other, currently unknown, Avr genes in this pathogen. [Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
White matter hyperintensity genetic risk factor TRIM47 regulates autophagy in brain endothelial cells
Authors: Yeung Sunny Hoi‐Sang , Lee Ralph Hon‐Sun , Cheng Gerald Wai‐Yeung , Ma Iris Wai‐Ting , Kofler Julia , Kent Candice , Ma Fulin , Herrup Karl , Fornage Myriam , Arai Ken , Tse Kai‐Hei 
Published: September 2024

AbstractWhite matter hyperintensity (WMH) is strongly correlated with age‐related dementia and hypertension, but its pathogenesis remains obscure. Genome‐wide association studies identified TRIM47 at the 17q25 locus as a top genetic risk factor for WMH formation. TRIM family is a class of E3 ubiquitin ligase with pivotal functions in autophagy, which is critical for brain endothelial cell (ECs) remodeling during hypertension. We hypothesize that TRIM47 regulates autophagy and its loss‐of‐function disturbs cerebrovasculature. Based on transcriptomics and immunohistochemistry, TRIM47 is found highly expressed by brain ECs in human and mouse, and its transcription is upregulated by artificially induced autophagy while downregulated in hypertension‐like conditions. Using in silico simulation, immunocytochemistry and super‐resolution microscopy, we predicted a highly conserved binding site between TRIM47 and the LIR (LC3‐interacting region) motif of LC3B. Importantly, pharmacological autophagy induction increased Trim47 expression on mouse ECs (b.End3) culture, while silencing Trim47 significantly increased autophagy with ULK1 phosphorylation induction, transcription, and vacuole formation. Together, we demonstrate that TRIM47 is an endogenous inhibitor of autophagy in brain ECs, and such TRIM47‐mediated regulation connects genetic and physiological risk factors for WMH formation but warrants further investigation.
Liver disease in primary antibody deficiencies
Authors: Bez Patrick , Warnatz Klaus 
Published: September 2024

Purpose of review
Liver disease has emerged as a major risk factor for increased mortality in patients with common variable immunodeficiency (CVID). This is mostly due to presinusoidal portal hypertension (PHTN) frequently secondary to nodular regenerative hyperplasia (NRH). Its pathogenesis is still poorly understood and treatment strategies for its various stages are often guided by trial and error. This review summarizes the most recent findings in the light of previous literature

Recent findings
In the last 2 years, different groups have addressed pathology, diagnostics, treatment, and liver transplantation. Histological examinations seem to support the pathogenetic sequence of T-cell mediated infiltration and damage of the sinusoidal space with secondary development of NRH, pericellular fibrosis, and the manifestation of PHTN. While markers of the early phase – beyond slight elevation of cholestatic enzymes – are still missing, elevated liver stiffness and splenomegaly above 16 cm longitudinal diameter have been suggested as warning signs for PHTN in CVID patients. Data on immunosuppressive treatment of this manifestation is still very heterogeneous, but a recent report on liver transplantation was encouraging for end stage liver disease

Summary
Liver disease deserves higher attention in the management of CVID. More studies are needed to understand its pathogenesis and optimal treatment.
Preliminary study of the mechanism of isolinderalactone inhibiting the malignant behavior of bladder cancer
Authors: Wang Qun , Xu Wenkai , Ying Lu , Shi Hongjin , Sun Yuxin , Feng Wei , Xu Haole , Xie Jun , Wei Hairong , Yang Zhao , Wang Haifeng 
Published: September 2024

Abstract

Background
Isolinderalactone (ILL), extracted from the dried tubers of Linderae aggregate, has multiple functions, such as antioxidation, antitumor, and anti-infection effects. However, there have been few studies on ILL's antitumor role and no reports on its role in bladder cancer (BC).

Materials and methods
Human BC cell lines T24 and EJ-1 were treated with different concentrations of ILL (0, 10, 20, 50, 100, 200, 400, 600, 800, and 1000 μmol/L), and the cell proliferation inhibition rate was analyzed using the CCK-8 assay. The effect of ILL on T24 and EJ-1 cell cycle inhibition and apoptosis was examined using flow cytometry. Immunoblotting was used to detect the levels of apoptosis-related proteins, BAX, BAK1, and CYCS, in BC cells of the control and ILL-treated groups, and quantitative PCR experiments were performed to detect the apoptosis-related gene expression of CASP10, CYCS, BAX, BCL-2, CASP8, and BAK1. T24 and EJ-1 tumor-bearing mouse models were established and divided into vehicle control, low-dose (10 mg/kg) and high-dose (20 mg/kg) groups, with 5 mice in each group. Hematoxylin and eosin staining and immunohistochemistry were used to detect changes in apoptosis-related proteins in vivo.

Results
The CCK-8 assay showed that in vitro, ILL significantly inhibited the proliferation of the T24 and EJ-1 BC cell lines. Flow cytometry and immunoblotting results showed that ILL increased mitochondrial permeability by upregulating proapoptotic proteins BAK1 and BAX, promoting CYCS release and significantly inducing cell cycle arrest at G0/G1 phase. In vivo, on day 25 of administration, tumor inhibition rates in T24 and EJ-1 tumor-bearing mice were up to 75.24% and 47.43%, respectively, in the ILL high-dose–treated and 71.58% and 43.89%, respectively, in the ILL low-dose–treated groups.

Conclusions
Isolinderalactone controls BC progression by inducing apoptosis, suggesting that ILL may be an effective drug for the treatment of BC.
Beyond size: A comprehensive overview of small-volume benign prostatic hyperplasia
Authors: Xu Junhao , Han Bangmin , Xia Shujie , Jing Yifeng 
Published: September 2024

Abstract
Benign prostatic hyperplasia (BPH) is one of the most frequently diagnosed benign disorders that cause dysuria in middle-aged and elderly men. Some patients with BPH have relatively small prostates (referred to as small-volume BPH) but still experience the lower urinary tract infection. Medication treatment is typically not successful in these patients. In addition, their pathophysiologic pathways deviate from those previously observed. Furthermore, as there is no accepted protocol for the diagnosis and treatment of small-volume BPH, patients can experience great difficulties in managing surgical complications such as bladder neck contracture. Thus, we reviewed the features of small-volume prostates, preoperative assessment, surgical technique, and management of complications.
State Schooling Policies and Cognitive Performance Trajectories: A Natural Experiment in a National US Cohort of Black and White Adults
Authors: Kim Min Hee , Liu Sze Yan , Brenowitz Willa D. , Murchland Audrey R. , Nguyen Thu T. , Manly Jennifer J. , Howard Virginia J. , Thomas Marilyn D. , Hill-Jarrett Tanisha , Crowe Michael , Murchison Charles F. , Glymour M. Maria 
Published: September 2024

Background:
Education is strongly associated with cognitive outcomes at older ages, yet the extent to which these associations reflect causal effects remains uncertain due to potential confounding.

Methods:
Leveraging changes in historical measures of state-level education policies as natural experiments, we estimated the effects of educational attainment on cognitive performance over 10 years in 20,248 non-Hispanic Black and non-Hispanic White participants, aged 45+ in the Reasons for Geographic and Racial Disparities in Stroke cohort (2003–2020) by (1) using state- and year-specific compulsory schooling laws, school-term length, attendance rate, and student-teacher ratio policies to predict educational attainment for US Census microsample data from 1980 and 1990, and (2) applying policy-predicted years of education (PPYEd) to predict memory, verbal fluency, and a cognitive composite. We estimated overall and race- and sex-specific effects of PPYEd on level and change in each cognitive outcome using random intercept and slope models, adjusting for age, year of first cognitive assessment, and indicators for state of residence at age 6.

Results:
Each year of PPYEd was associated with higher baseline cognition (0.11 standard deviation [SD] increase in composite measure for each year of PPYEd, 95% confidence interval [CI] = 0.07, 0.15). Subanalyses focusing on individual cognitive domains estimate the largest effects of PPYEd on memory. PPYEd was not associated with the rate of change in cognitive scores. Estimates were similar across Black and White participants and across sex.

Conclusions:
Historical policies shaping educational attainment are associated with better later-life memory, a major determinant of dementia risk.
Oral agents for lowering lipoprotein(a)
Authors: Nicholls Stephen J. , Nelson Adam J. , Michael Laura F. 
Published: September 2024

Purpose of review
To review the development of oral agents to lower Lp(a) levels as an approach to reducing cardiovascular risk, with a focus on recent advances in the field.

Recent findings
Extensive evidence implicates Lp(a) in the causal pathway of atherosclerotic cardiovascular disease and calcific aortic stenosis. There are currently no therapies approved for lowering of Lp(a). The majority of recent therapeutic advances have focused on development of injectable agents that target RNA and inhibit synthesis of apo(a). Muvalaplin is the first, orally administered, small molecule inhibitor of Lp(a), which acts by disrupting binding of apo(a) and apoB, in clinical development. Nonhuman primate and early human studies have demonstrated the ability of muvalaplin to produce dose-dependent lowering of Lp(a). Ongoing clinical trials will evaluate the impact of muvalaplin in high cardiovascular risk and will ultimately need to determine whether this strategy lowers the rate of cardiovascular events.

Summary
Muvalaplin is the first oral agent, developed to lower Lp(a) levels. The ability of muvalaplin to reduce cardiovascular risk remains to be investigated, in order to determine whether it will be a useful agent for the prevention of cardiovascular disease.
Designing a Website to Support a Multisite, International Clinical Trial
Authors: Pasek Tracy Ann , Napolitano Natalie , Cassidy Amy , Kalvas Laura Beth , Curley Martha A.Q. 
Published: September 2024

Background
Safe and reliable implementation of complex study protocols in multisite clinical trials requires that all study personnel have 24/7 access to up-to-date study materials. Study websites can serve as an electronic manual of operations (eMOO) to support trial conduct.

Objective
We describe the development, organization, and maintenance of a study website and eMOO to facilitate quick and efficient communication during conduct of a complex, multisite, international clinical trial.

Methods
We worked closely with our information technology department to develop and maintain our study website, which includes a public home page, a section for parents and families, and three password-protected portals that serve as an eMOO for (a) study sites, (b) study site investigators, and (c) the operations team (e.g., clinical coordination center, data coordination center).

Results
The public home page is helpful for families contemplating study participation and for nonparticipating sites considering joining our trial. The patient and family education section supports family participation in the study. The study site portal contains all information needed for local study teams to safely manage a study patient. The investigator portal provides access to research-specific materials needed to lead the study at each site. The operations team portal supports overall study management. For other scientists considering use of a study website for their multisite research, we recommend close collaboration with information technology for development and maintenance, limited and clearly defined roles for version control, and use of unmodifiable file formats to prevent unapproved alterations of study materials.

Discussion
Although investment in development and maintenance has been significant, we have appreciated marked value to our operations team and study sites. Our study website development process is relevant to other scientists conducting multisite clinical research.
Effect of knee strengthening exercises and lifestyle modifications through mobile phone support in people suffering from knee osteoarthritis
Authors: Garg Nikhil , Gupta Nikhil , Khatri Kavin , Kanwal Abhinav , Hussain Zeeshan , Sachdeva Jimmy 
Published: September 2024

ABSTRACT

Objective
The study aimed to evaluate the effectiveness of mobile phone-based support in improving exercise adherence and outcomes in knee OA.

Designs
A prospective comparative cohort study was conducted with a follow-up at 3, 6, and 12 weeks, involving 210 participants allocated into intervention and control groups. The intervention group received knee exercise flyers and mobile phone-based adherence support, while the control group received only standard instructions after physiotherapy. Outcome measures included Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, numeric rating scale pain scores, and quality of life assessments at baseline and follow-ups at 3, 6 and 12 weeks.

Results
The intervention group exhibited significant reductions in WOMAC scores, pain scores and improvement in quality of life over the 12-week follow-up compared to baseline. The intervention group exhibited significantly greater improvements in the outcomes as compared to control group.

Conclusion
A combined intervention of knee exercises leaflets and SMS/phone-call adherence support led to significant improvements in pain, functional outcomes and quality of life among individuals with knee OA. These findings underscore the potential of mobile phone-based interventions as effective adjuncts to traditional therapies for knee OA.
The emergence of letermovir and maribavir drug-resistant mutations: from clinical trials to real-world studies
Authors: Zhu Violet Z. , Horton Miles B. , Haeusler Gabrielle M. , Yong Michelle K. 
Published: September 2024

Purpose of review
Cytomegalovirus (CMV) infection is associated with severe clinical disease and high morbidity in immunocompromised hosts. Letermovir and maribavir, are two recently developed antiviral drugs used in the prevention and treatment of resistant and refractory CMV. Following the publication of landmark randomized trials and increased use, both clinical trial data and real-world experience has reported the development of antiviral drug resistance. The aim of this review was to comprehensively review the published literature on letermovir and maribavir drug resistance and to describe the clinical scenarios in which they may emerge.

Recent findings
For letermovir, the most frequently detected resistance mutations occur in the UL56 gene (C325Y/W/F) and confer total resistance. Maribavir resistance mutations most often occur in the UL97 gene and resistance-associated variants (RAVs) T409M, H411Y, C480F have all been detected. The clinical context in which letermovir and maribavir resistance occurs include high viral loads at initiation, intensified immunosuppression, subtherapeutic drug exposure because of poor adherence, drug interactions, and inadequate central nervous system (CNS) penetration. Emergence of resistance mutations generally occurs within the first 3 months of initiation.

Summary
The detection of letermovir and maribavir resistance mutations highlights an ongoing clinical challenge in the management of CMV.