bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-nucleus multiple-organ chromatin accessibility mapping in the rat
Authors: Li Ronghai , Yuan Yue , Duan Shanshan , Deng Qiuting , Ma Wen , Liu Chang , Gao Peng , Lu Li , Liu Chuanyu
Published: November 2024

The chromatin accessibility landscape is the basis of cell-specific gene expression. We generated a multiorgan, single-nucleus chromatin accessibility landscape from the model organismRattus norvegicus. For this single-cell atlas, we constructed 25 libraries via snATAC-seq from nine organs in the rat, with a total of over 110,000 cells. Cell classification integrating gene activity scores with known marker genes identified 77 cell types, which were strongly correlated with those in published mouse single-cell transcriptome atlases. We further investigated the enrichment of cell type- and organ-specific transcription factors (TFs), the dynamics of T-cell developmental trajectories across organs, and the conservation and specificity of gene expression patterns across species. These findings provide a foundation for further investigations of the cell composition and gene regulatory networks throughout the rat body.

Highlights

Generation of a single-cell atlas of chromatin accessibility in nine organs of the rat

Characterization of cell type- and organ-specific transcription factors (TFs)

Dynamics of chromatin accessibility in developing T cells revealed by cross-organ analysis

Conservation and specificity of gene expression patterns among humans, mice, and rats revealed by cross-species analysis
Increased preference for lysine over arginine in spike proteins of SARS-CoV-2 BA.2.86 variant and its daughter lineages
Authors: Bozic Anze , Podgornik Rudolf
Published: November 2024

The COVID-19 pandemic offered an unprecedented glimpse into the evolution of its causative virus, SARS-CoV-2. It has been estimated that since its outbreak in late 2019, the virus has explored all possible alternatives in terms of missense mutations for all sites of its polypeptide chain. Spike protein of the virus exhibits the largest sequence variation in particular, with many individual mutations impacting target recognition, cellular entry, and endosomal escape of the virus. Moreover, recent studies unveiled a significant increase in the total charge on the spike protein during the evolution of the virus in the initial period of the pandemic. While this trend has recently come to a halt, we perform a sequence-based analysis of the spike protein of 2665 SARS-CoV-2 variants which shows that mutations in ionizable amino acids continue to occur with the newly emerging variants, with notable differences between lineages from different clades. What is more, we show that within mutations of amino acids which can acquire positive charge, the spike protein of SARS-CoV-2 exhibits a prominent preference for lysine residues over arginine residues. This lysine-to-arginine ratio increased at several points during spike protein evolution, most recently with BA.2.86 and its sublineages, including the recently dominant JN.1, KP.3, and XEC variants. The increased ratio is a consequence of mutations in different structural regions of the spike protein and is now among the highest among viral species in the Coronaviridae family. The impact of high lysine-to-arginine ratio in the spike proteins of BA.2.86 and its daughter lineages on viral fitness remains unclear; we discuss several potential mechanisms that could play a role and that can serve as a starting point for further studies.
Different alterations in mRNP composition trigger an increase in harmful R-loops
Authors: Mérida-Cerro José Antonio , Chevreux Guillaume , Palancade Benoit , Rondón Ana G. , Aguilera Andrés
Published: November 2024

Understanding how the assembly of nascent mRNA into a ribonucleoprotein (mRNP) influences R-loop homeostasis is crucial for gaining insight into the cellular mechanisms that prevent genome instability. Here, we identify three RNA-binding proteins, Rie1, Rim4 and She2, whose stoichiometry is important to limit R-loop accumulation and, thus, to prevent DNA damage. Interestingly, Rim4 and She2 are overrepresented in mRNPs assembled in the absence of THO. In addition, we found that an excess of Dis3 impairs exosome function, promoting R-loops, particularly from non-coding RNAs, which cause genomic instability. Our results indicate that mRNP assembly is a precise process that, when perturbed by changes in the availability of different RBPs or RNAs, causes R-loop-mediated DNA damage in the cell. These results may help to understand the mechanism that promotes cancer, as several RBPs are overexpressed in different types of tumors.

Author summary

R-loops are three-stranded structures formed by a DNA-RNA hybrid and the displaced ssDNA. The accumulation of R-loops damages the genome, highlighting the need for their tight regulation. One of the mechanisms that prevents R-loop formation is the co-transcriptional assembly of the nascent RNA into a messenger ribonucleoprotein (mRNP). Our study reveals that mRNP biogenesis is highly sensitive to perturbations. Not only the absence of mRNP components, but also the overexpression of specific RNA-binding proteins (RBPs) or the persistence of unstable transcripts, significantly stresses mRNP assembly, resulting in R-loop accumulation and consequent DNA damage. R-loops are involved in a number of neurodegenerative diseases and cancer, highlighting the importance of understanding the cellular processes that mitigate their accumulation.
Apoplast metabolomics reveals thatplant-pathogencrosstalk is modulated by nitrogen supply
Authors: Jeridi Roua , Davière Antoine , Jolivet Sylvie , Zarattini Marco , Clement Gilles , Soulie Marie-Christine , Landoulsi Ahmed , Fagard Mathilde
Published: November 2024

In the present study, we analyzed the role played by the apoplast in the crosstalk between biotic and abiotic stress conditions. In particular, we studied the crosstalk between nitrogen (N) limitation and infection of the model plantArabidopsis thalianabyE. amylovora, an apoplastic bacterium. Our previous findings indicated that low N (LN) conditions increaseE. amylovora in plantatiters and expression of virulence factors. In this work, we extracted the apoplast wash fluids (AWF) from plants grown under low N or high N (HN) conditions and applied them to bacteriain vitro. We observed that LN-AWF induced stronger virulence gene expression than HN-AWF. Metabolomic analysis of both apoplast extracts revealed the presence of common metabolites, however, their proportions were distinct, indicating a direct effect of N availability on apoplast content. Interestingly, changes in the apoplast metabolite proportions were also observed early after bacterial infection, but only in plants grown under LN conditions. To evaluate the effect of single metabolites on virulence gene expression, we selected 43 metabolites and observed that 29 of them were activators whereas two, GABA and citrate, acted as repressors. This study shows that environmental constraints, such as N availability, impact plant-pathogen interactions by altering the apoplastic content.
ELOVL6 as a Therapeutic Target: Disrupting c-MYC-Driven Lipid Metabolism to Enhance Chemotherapy in Pancreatic Cancer
Authors: García García Ana , Ferrer Aporta María , Vallejo Palma Germán , Giráldez Trujillo Antonio , Castillo-González Raquel , Calzón Lozano David , Mora Perdiguero Alberto , Muñoz Velasco Raúl , Colina Castro Miguel , de Simone Benito Elena , Torres-Ruiz Raul , Rodriguez-Perales Sandra , Dehairs Jonas , V Swinnen Johannes , Garcia-Cañaveras Juan Carlos , Lahoz Agustín , Montalvo Quirós Sandra , del Pozo-Rojas Carlos , Luque Rioja Clara , Monroy Francisco , Herráez-Aguilar Diego , Alonso Riaño Marina , Rodríguez Peralto José Luis , Sánchez-Arévalo Lobo Víctor Javier
Published: November 2024

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, marked by a survival rate of only 12%. Consequently, the exploration of novel therapeutic strategies becomes a critical clinical imperative. Among the genetic alterations contributing to PDAC, c-MYC overexpression arises due to upstream mutations, amplifications, and copy number alterations. c-MYC serves as a key regulator in the tumor’s metabolic reprogramming, playing a pivotal role in proliferation, migration, and metastasis. This study delves into the investigation of the role of the elongase ELOVL6 in c-MYC-induced cell transformation and its potential as a therapeutic target in PDAC. Here, we demonstrate that c-MYC regulates lipid elongation to promote cell transformation, offering a new avenue for therapeutic intervention. Initially, we show the direct regulation of ELOVLs expression by c-MYC in various PDAC mouse models and cell lines, elucidating its upregulation during transformation and tumor progression. Genetic or chemical inhibition of ELOVL6 results in decreased proliferation and migration, accompanied by alterations in fatty acid elongation. These changes in fatty acid composition led to modifications in membrane rigidity, permeability, and thickness, which collectively affect micropinocytosis and macropinocytosis. Importantly, we observe an increase in Abraxane uptake and a synergistic effect when combined with ELOVL6 interferencein vitro.In vivovalidation demonstrates that ELOVL6 inhibition significantly reduces tumor growth and enhances the response to Abraxane, thereby increasing overall survival. Altogether, these results position ELOVL6 as a promising therapeutic target in the treatment of PDAC.
Correlative humoral and cellular immunity to genetically attenuated malaria parasites in humans
Authors: Colstrup Emil , Nakajima Rie , Krol Jelte M. M. , Lamers Olivia A. C. , de Assis Rafael R. , Jain Aarti , Jasinskas Algis , Iliopoulou Eva , de Bes-Roeleveld Helena M. , Franke-Fayard Blandine M. D. , Roestenberg Meta , Felgner Philip L. , Murugan Rajagopal
Published: November 2024

Malaria caused byPlasmodium falciparumremains one of the major infectious diseases with a high burden in Sub-Saharan Africa. In spite of the advancements made in vaccine development and implementation in endemic countries, sterile and durable protection has not been achieved. Recently, we have shown the superior protective capacity of whole sporozoites attenuated to arrest late but not early during the liver stage development in a controlled human malaria infection study. Here we report the breadth of antigens targeted by hitherto understudied parasite liver stage immunity and convey the coherence between humoral and cellular immunity observed in our clinical study. Our findings uncover the underlying immunogenic differences between early- and late-liver stage arresting parasites and identify key liver-stage antigens for future vaccine development focused on inducing sterile immunity to malaria.
Synthetic gene circuits that selectively target RAS-driven cancers
Authors: Senn Gabriel , Nissen Leon , Benenson Yaakov
Published: November 2024

Therapies targeting mutated RAS, the most frequently mutated oncogene in human cancers, could benefit millions of patients. Recently approved RAS inhibitors represent a breakthrough, but are limited to a specific KRASG12Cmutation and prone to resistance. Synthetic gene circuits offer a promising alternative by sensing and integrating cancer-specific biomolecular inputs, including mutated RAS, to selectively express therapeutic proteins in cancer cells. A key challenge for these circuits is achieving high cancer selectivity to prevent toxicity in healthy cells. To address this challenge, we present a novel approach combining multiple RAS sensors into RAS-targeting gene circuits, which allowed us to express an output protein in cells with mutated RAS with unprecedented selectivity. We implemented a modular design strategy and modelled the impact of individual circuit components on output expression. This enabled cell-line specific adaptation of the circuits to optimize selectivity and fine-tune expression. We further demonstrate the targeting capabilities of the circuits by employing them in different RAS-driven cancer cells. This work highlights the potential of synthetic gene circuits as a novel therapeutic strategy for RAS-driven cancers, advancing the application of synthetic biology in oncology.
Data and contemporary economics: role, paradox and
development
Authors: Jiang Hai-xi , Jiang Nan-ping
Published: November 2024

Purpose

A more accurate comprehension of data elements and the exploration of new
laws governing contemporary data in both theoretical and practical domains
constitute a significant research topic.

Design/methodology/approach

Based on the perspective of evolutionary economics, this paper re-examines
economic history and existing literature to study the following: changes in
the “connotation of production factors” in economics caused by
the evolution of production factors; the economic paradoxes formed by data
in the context of social production processes and business models, which
traditional theoretical frameworks fail to solve; the disruptive innovation
of classical theory of value by multiple theories of value determination and
the conflicts between the data market monopoly as well as the resulting
distribution of value and the real economic society. The research indicates
that contemporary advancements in data have catalyzed transformative
innovation within the field of economics.

Findings

The research indicates that contemporary advancements in data have catalyzed
disruptive innovation in the field of economics.

Originality/value

This paper, grounded in academic research, identifies four novel issues
arising from contemporary data that cannot be adequately addressed within
the confines of the classical economic theoretical framework.
Driving corporate digitization with reliable data through the A3 approach: an Italian case study
Authors: Cantini Alessandra , Costa Federica , Portioli-Staudacher Alberto
Published: November 2024

Purpose

Pursuing digital transformation is a valuable strategy to attain companies’ operational excellence and sustainable development. However, installing digital technologies and software is insufficient for achieving a successful digital transformation. Equally vital is providing digital solutions with reliable input data, which is a hard task in companies where information is gathered through manual or non-standardized processes. The lack of reliable data prevents technologies and software from operating at their best, hindering their ability to process information and derive correct insights for improvement. To avoid this, companies should embrace structured problem-solving approaches to evaluate current data retrieval processes, identify error sources and formulate countermeasures. This paper aims to provide an empirical study to substantiate A3 as a winning approach for advancing input data acquisition in companies.

Design/methodology/approach

A case study research is proposed, investigating the application of A3 in an ink manufacturing company, and checking how A3 improves data collection and company performance.

Findings

The case study corroborates A3 as an effective approach, allowing the removal of inefficiencies that previously went unnoticed and reaching a 10% productivity improvement.

Practical implications

Pursuing digital transformation is a valuable strategy to attain companies’ operational excellence and sustainable development. However, installing digital technologies and software is insufficient for achieving a successful digital transformation. Equally vital is providing digital solutions with reliable input data, which is a hard task in companies where information is gathered through manual or non-standardized processes.

Originality/value

The originality of this paper lies in the application scope and aim of the A3 approach. A3 is a mature paradigm but often coined for production and still endowed with unexplored potential. This paper proposes the application of A3 for improving companies’ data retrieval processes, focusing for the first time on information reliability and its importance in ensuring the functioning of digital technologies and software.
Discovering current trends and forecasting future research directions in FinTech by way of co-word-burst analyses
Authors: Duan Carson
Published: November 2024

Purpose

The purpose of this study is to identify the existing research themes and future directions of the FinTech field by analyzing the dynamics of co-word burst.

Design/methodology/approach

A dataset of 1792 SCI or SSCI articles retrieved from the Web of Science database. First, the paper conducted a scientific production analysis. Then, using bibliometric analysis, the paper conducts co-word-burst analyses for keywords, title, abstract and Keywords Plus to detect the emerging trends. Based on these trends, future research directions were forecasted.

Findings

The study detected six research themes: the knowledge of FinTech, FinTech applications, FinTech technologies, COVID-19, FinTech ecosystem and FinTech implications for research. These six FinTech research themes were further conceptualized as a six-dimensional analytical framework for FinTech investigations. Then, the study forecasts that these six themes and related conversations will be an ongoing focus of Fintech research, particularly COVID-19 effects on FinTech.

Originality/value

This study is the first attempt to review FinTech literature based on quantitative and qualitative analyses of co-word burst. It overcomes the limitation of individual/group determinant(s) studies and presents a holistic view of current research themes and future research directions in FinTech field.
Institutional investors’ impact on sustainability disclosure: exploring the moderating role of financial performance
Authors: Alkurdi Amneh , Bataineh Hanady , Al Tarawneh Essa Mahmoud , Khatib Saleh F.A.
Published: November 2024

Purpose

This paper aims to investigate the relationship between institutional investors and sustainability disclosure, specifically examining the impact of financial performance as a moderator variable on the relationship between institutional investors and sustainability disclosure.

Design/methodology/approach

This paper used a panel data set of 51 firms from the industrial sector listed in the Amman Stock Exchange, with a total of 459 observations during 2013–2021. Multiple regression models were used to test the direct and moderating relationships.

Findings

The findings of this paper indicate that institutional investors exhibit varying attitudes toward sustainability disclosure. Institutional investors have a positive and significant impact on firm sustainability disclosure. Furthermore, the relationship between institutional investors and sustainability disclosure is significantly influenced by financial performance.

Social implications

The study’s findings encourage regulators to enhance firms’ awareness of sustainability disclosures by balancing the economic, social and environmental pillars. This can be achieved by conserving natural resources, protecting the environment and promoting social justice for future generations.

Originality/value

The paper’s insights can be valuable for policymakers’ sustainable practices by encouraging institutional investors to support sustainability activities actively.
A committed brand facing moral dilemma crises: the role of inferred goodwill and self-brand connection in consumer regret
Authors: Jang Jisu , Kang Jiyun , Huan Christine
Published: November 2024

Purpose

In an era of blurred moral boundaries, brands face “moral dilemma crises”, which are distinguished from traditional crises. Based on expectancy violations theory, this study aims to explore how consumers interpret (inferred goodwill) and evaluate (consumer regret) the precrisis committed brands, reinforced by corporate ability and responsibility (expectancies) during moral dilemma crises and whether self-brand connection moderates this relationship.

Design/methodology/approach

The main study used a scenario-based online survey with a purchased beauty brand, analyzed via structural equation modeling and PROCESS macro, to examine the effects of corporate ability and responsibility on regret, mediated by inferred goodwill and moderated by self-brand connection. A validation study with a fictitious brand used an online experimental design, analyzed with t-tests and ANCOVAs.

Findings

When corporate ability and corporate responsibility are considered together, corporate ability negatively impacts inferred goodwill (boomerang effect), whereas corporate responsibility positively impacts inferred goodwill (buffering effect). Inferred goodwill acts as a mediator that reduces regret. The negative impact of corporate ability on inferred goodwill and regret becomes stronger among consumers with strong self-brand connections. However, self-brand connection does not moderate the relationship between corporate responsibility and inferred goodwill.

Originality/value

This research extends the application of expectancy violations theory to moral dilemma crises, differentiates between the effects of corporate ability and responsibility, highlights the role of inferred goodwill and regret and explores the moderating effects of self-brand connection, providing tailored insights for brand management.
Green consumption: the role of perceived symbolic value and personal innovativeness
Authors: Hasudungan Albert , Saragih Harriman Samuel
Published: November 2024

Purpose

This study aims to explore the relationship between personal innovativeness, perceived symbolic value and green purchase intentions within the context of sustainable consumption. Specifically, it investigates how personal innovativeness influences both green purchase intentions and perceived symbolic value and examines whether perceived symbolic value mediates the relationship between personal innovativeness and green purchase intentions.

Design/methodology/approach

Using a survey-based quantitative approach, data were collected from a sample of Indonesian consumers using online panels via SurveyMonkey®. The study used Rogers’ diffusion theory to conceptualize personal innovativeness and drew on theories of symbolic consumption to frame perceived symbolic value. Partial least square structural equation modeling was used to test the proposed hypotheses and explore the relationships among the constructs.

Findings

The results indicate that personal innovativeness positively affects green purchase intentions and enhances the perceived symbolic value of green products. Moreover, perceived symbolic value influences green purchase intentions and partially mediates the relationship between personal innovativeness and green purchase intentions. These findings underscore the critical role of symbolic value in the adoption of green products and highlight personal innovativeness as a key driver in sustainable consumer behavior.

Originality/value

This research contributes to the sustainable consumption literature by integrating personal innovativeness with symbolic value considerations in green purchasing decisions, offering a novel insight into how individual traits and product symbolism interact to influence consumer behavior in the context of environmental sustainability.
A comprehensive meta-analysis of the impact of intervention programmes on psychological capital development: post-intervention and longer-term effects
Authors: Loghman Saeed , Ramirez-Perez Mauricio , Bohle Philip , Martin Angela
Published: November 2024

Purpose

This paper presents the most up-to-date comprehensive meta-analysis of the effectiveness of interventions to enhance psychological capital (PsyCap). It also reports the first meta-analytic examination of longer-term effects (beyond the immediate post-intervention period).

Design/methodology/approach

This meta-analysis followed PRISMA 2020 guidelines and utilised the methodologies of Hunter and Schmidt (2004) and Borenstein et al. (2009). The search period was from 2006 until February 2023. A total of 40 studies (N = 4,207) were included in the meta-analyses. The analyses were performed using the Comprehensive Meta-Analysis (CMA) Version 4 software programme.

Findings

The results indicate that the impacts of interventions on PsyCap and each of its component resources are greater than those reported in a previous meta-analysis (Lupșa et al., 2020), with the strongest impacts on hope and optimism. Interventions had sustained positive effects on PsyCap, hope, resilience and optimism, but not efficacy, and the frequency of intervention sessions influenced the effectiveness of interventions on hope, efficacy and optimism. Interestingly, specific PsyCap-focussed interventions did not have the greatest impact on PsyCap or its component resources.

Originality/value

This study contributes to emerging research on wellbeing-oriented HRM and provides valuable insights into more effective design and implementation of interventions to enhance PsyCap and its component resources. These interventions are a promising form of investment in employees which may bring mutual gains for individuals and organisations. The present findings extend those of previous studies and specifically respond to the call for further research on the persistence of PsyCap intervention effects.
Indirect comparison of deucravacitinib and other systemic treatments for moderate to severe plaque psoriasis in Asian populations: A systematic literature review and network meta‐analysis
Authors: Tsai Tsen‐Fang , Tada Yayoi , Kung Camy , Zhong Yichen , Cichewicz Allie , Borkowska Katarzyna , Westley Tracy , Kisa Renata M. , Huang Yu‐Huei , Gao Xing‐Hua , Jo Seong‐Jin , Armstrong April W.
Published: November 2024

Expanding the systemic treatment options for patients with psoriasis, deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor is approved in the United States, European Union, China, Japan, Taiwan, Korea, and other countries for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Evidence suggests the comparative efficacy of systemic therapies may be different in Asian versus White patients. This systematic review and network meta‐analysis (NMA) evaluated the clinical efficacy associated with deucravacitinib and other biologic or non‐biologic systemic treatments for moderate to severe plaque psoriasis in Asian populations. Electronic databases were searched to identify randomized trials of the interventions of interest. Multinomial random effects models adjusting for baseline placebo risk were used to estimate Psoriasis Area and Severity Index (PASI) responses at weeks 10–16. Of 8596 studies identified, 20 were included in the NMA. The estimated PASI 75 and 90 (95% credible interval) response rates for deucravacitinib were estimated to be 66% (49%–80%) and 40% (24%–58%) in Asian populations, notably higher than placebo (6% [4%–9%] and 1% [0.8–2%]) and apremilast (24% [12%–40%] and 9% [4%–20%]). No statistically significant difference was observed in PASI 75 and 90 responses between deucravacitinib and adalimumab, certolizumab pegol, infliximab, ustekinumab, and tildrakizumab. Deucravacitinib demonstrated robust efficacy in the Asian population, with PASI 75 and 90 responses comparable to some biologics. Deucravacitinib provides a convenient oral therapy with efficacy similar to several biologic therapies.
Clinicopathological features of epithelioid hemangioma of 43 patients with long‐term follow‐up: A two‐center retrospective study
Authors: Luo Si‐Yu , Zhou Kai‐Yi , Wang Qin‐Xiao , Feng Lin , Fang Sheng
Published: November 2024

Epithelioid hemangioma (EH) is a rare angioproliferative disorder for which histopathology is the main approach to diagnosis. The tendency to recur is of concern to clinicians and patients. The factors associated with recurrence have been sporadically reported and a large‐scale cohort study has been lacking. This study aims to investigate the clinicopathological characteristics and long‐term clinical outcomes of EH patients from two tertiary care hospitals. A two‐center retrospective cohort study of 43 patients with a diagnosis of EH between 2013 and 2023 was evaluated at follow‐up. A comprehensive and detailed review of clinical and pathological data with long‐term follow‐up was performed. Information on prognosis was available for 43, and 8 (8/43, 18.6%) experienced local recurrence. Facial (Cramer's V = 0.405, P = 0.029) and multiple (relative risk [RR] 4.306, 95% confidence interval [CI] 1.213, 15.282, Phi = 0.369, P = 0.016) lesions, subcutaneous involvement (RR 5.063, 95% CI 1.157, 22.151, Phi = 0.374, P = 0.014), and the presence of lymphoid follicles (RR 9.750, 95% CI 3.853, 24.671, Phi = 0.670, P < 0.001) were associated with higher recurrence rates. According to the presence or absence of well‐differentiated angiogenesis, EH can be pathologically classified into vascular, cellular, and intermediate types, while the depth, degree, and pattern of inflammation, tissue eosinophilia, eosinophilic microabscesses, and hobnail endothelial cells differed significantly between cellular and vascular types. The characteristics of EH are distinguished by different pathological subtypes. This study provides insight into the clinicopathological features and outcome of EH to assist clinicians in the diagnosis and management of this rare condition.
Lack of Evidence for Transmission of Atypical H‐Type Bovine Spongiform Encephalopathy Prions (H‐BSE Prions) by Intracranial and Oral Challenges to Nonhuman Primates
Authors: Shibata Hiroaki , Ono Fumiko , Sato Yuko , Ohto Keiko , Nakano Nozomi , Imamura Morikazu , Horiuchi Motohiro , Tobiume Minoru , Hagiwara Ken'ichi
Published: November 2024

Bovine spongiform encephalopathy (BSE) is a prion disease in cattle caused by classical‐type (C‐), L‐type (L‐), or H‐type (H‐) BSE prions. While C‐BSE prions are zoonotic agents responsible for variant Creutzfeldt–Jakob disease, L‐ and H‐BSE prions are believed not to be connected to human prion diseases. However, L‐BSE prions have been shown to transmit to cynomolgus monkeys (Macaca fascicularis), suggesting they may have zoonotic potential. In the present study, we examined whether H‐BSE prions are transmissible to cynomolgus monkeys. The monkeys were injected intracranially (n = 2) or given orally (n = 2) with brain homogenates from a cow infected with H‐BSE prions. After asymptomatic observation periods of 4–6 years, the monkeys were euthanized for autopsy. Histological examination of the brain did not reveal any pathological changes. Immunohistochemical and Western blot analyses did not detect disease‐associated forms of prion protein (PrPSc) in the brain, peripheral neurons, or lymphatic tissues. The unsuccessful transmission indicates an effective barrier against the transmission of cattle H‐BSE prions to cynomolgus monkeys. Based on the results obtained in this nonhuman primate model, we estimated that the potential transmission of H‐BSE prions to humans is substantially lower than C‐ and L‐BSE prions.
The lasting impact of historical residential security maps on experienced segregation
Authors: Aaronson Daniel , Han Joel Kaiyuan , Hartley Daniel A. , Mazumder Bhashkar
Published: November 2024

We study the impact of 1930s Residential Security maps on experienced segregation as measured by geolocation data. We compare adjacent neighborhoods with different creditworthiness grades. Using a sample of neighborhood boundaries, which, based on estimated propensity scores, were likely drawn for idiosyncratic reasons, residents of neighborhoods on the lower graded side of the boundary are more likely to visit other historically lower graded destination neighborhoods and neighborhoods that currently tend to have lower household income and lower educational attainment. Disparities in visits are not driven by work commutes, very local visits, or differences in income.
Associations of maternal serum ferritin levels across gestation with gestational diabetes mellitus: A longitudinal cohort study
Authors: Mo Huiqin , Wen Jingna , Qu Cuicui , Liu Xiaohua
Published: November 2024

Background

The longitudinal changes in maternal serum ferritin (SF) levels across gestation, which indirectly reflect iron supplementation, have not been extensively investigated in relation to gestational diabetes mellitus (GDM).

Methods

We conducted a retrospective cohort study at a tertiary maternal hospital in Shanghai. Women with SF concentration measurements at 8.0–13.6 weeks' gestation (GW), 29.0–31.6 GW, and an oral glucose tolerance test (OGTT) at 24–28 GW were included. We utilized logistic regression analysis to assess GDM association with maternal SF levels and longitudinal changes.

Results

The study included 17 560 women, with 2160 (12.3%) participants diagnosed with GDM. Adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for GDM across increasing quartiles of SF concentrations at 8.0–13.6 GW were 1.00 (reference), 1.139 (95% CI: 1.012–1.283), 1.093 (95% CI: 0.969–1.233), and 1.248 (95% CI: 1.111–1.403). Similarly, at 29.0–31.6 GW, increasing quartiles of SF concentrations were associated with higher adjusted ORs for GDM: 1.00 (reference), 1.165 (95% CI: 1.029–1.320), 1.335 (95% CI: 1.184–1.505), and 1.428 (95% CI: 1.268–1.607). Pregnant women with higher SF levels (upper 25th percentile) at 8.0–13.6 GW had a reduced GDM risk if their SF levels decreased to the lower 25th percentile at 29.0–31.6 GW. Conversely, the subgroup with higher SF levels (upper 25th percentile) at both time points had the highest incidence rate of GDM (15.3%, 1.235 [95% CI: 1.087–1.404]).

Conclusions

Maternal SF levels independently and positively associated with GDM risk during early and late gestational stages. Considering the increased GDM risk, routine iron supplementation for iron‐replete women is questionable.

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OGU: A Toolbox for Better Utilising Organelle Genomic Data
Authors: Wu Ping , Xue Ningning , Yang Jie , Zhang Qiang , Sun Yuzhe , Zhang Wen
Published: November 2024

Organelle genomes serve as crucial datasets for investigating the genetics and evolution of plants and animals, genome diversity, and species identification. To enhance the collection, analysis, and visualisation of such data, we have developed a novel open‐source software tool named Organelle Genome Utilities (OGU). The software encompasses three modules designed to streamline the handling of organelle genome data. The data collection module is dedicated to retrieving, validating and organising sequence information. The evaluation module assesses sequence variance using a range of methods, including novel metrics termed stem and terminal phylogenetic diversity. The primer module designs universal primers for downstream applications. Finally, a visualisation pipeline has been developed to present comprehensive insights into organelle genomes across different lineages rather than focusing solely on individual species. The performance, compatibility and stability of OGU have been rigorously evaluated through benchmarking with four datasets, including one million mixed GenBank records, plastid genomic data from the Lamiaceae family, mitochondrial data from rodents, and 308 plastid genomes sourced from various angiosperm families. Based on software capabilities, we identified 30 plastid intergenic spacers. These spacers exhibit a moderate evolutionary rate and offer practical utility comparable to coding regions, highlighting the potential applications of intergenic spacers in organelle genomes. We anticipate that OGU will substantially enhance the efficient utilisation of organelle genomic data and broaden the prospects for related research endeavours.
Exploration of the pattern of lymph node metastasis in esophageal cancer based on membrane anatomy theory
Authors: Yang Pengjie , Han Bater , Tian Ziqiang , Tang Peng , Yan Qin , Liu Weixin , Zhang Xuefeng , Yu Yongjun , Li Yong
Published: November 2024

Objective

To analyze the pattern of lymph node metastasis in esophageal cancer based on the theory of membrane anatomy.

Methods

A retrospective analysis was conducted on 143 patients who underwent esophageal surgery at the Cancer Hospital of the Chinese Academy of Medical Sciences from March 2021 to March 2022. Lymph node metastasis was observed and categorized according to postoperative T staging. The characteristics and patterns of lymph node metastasis in different regions were observed, and the lymph node metastasis patterns in patients with clinical T3 esophageal cancer were analyzed using membrane anatomy theory.

Results

Among the 143 patients with esophageal squamous cell carcinoma, 21 were treated with surgery alone, while the rest received preoperative adjuvant therapy. A total of 5456 lymph nodes were cleared from the 143 patients, with 204 positive lymph nodes, resulting in a positive rate of 3.74%. In the thoracic lymph node dissection, the metastatic rates exceeded 5% for the following regions: 106recR (17.36%), 106recL (12.5%), 107 (10.42%), and 108 (5.56%) station. When analyzing the abdominal lymph node metastasis, the metastatic rates exceeded 5% for regions 7 (13.19%), 3a (7.64%), 2 (6.94%), and 1 (6.25%) station. Group analysis of patients with esophageal squamous cell carcinoma before postoperative pathological T3 stage revealed an increasing trend in tumor lymph node metastasis rate with later T staging. Lymph node metastasis in region 106recR can occur early, with a metastasis rate of 18.37% in T1 tumors. Analysis of lymph node metastasis characteristics in 103 patients clinically staged as T3 showed that 3966 lymph nodes were cleared, with 186 positive nodes, resulting in a positive rate of 4.69%. Lymph node metastasis rates were higher in regions 106recL, 106recR, 107, 108, 110, 1, 2, 3a, and 7, all exceeding 5%.

Conclusion

The theory of membrane anatomy can effectively explain the pattern of lymph node metastasis in esophageal cancer.
Industrial water pollution and farmer adaptation: Evidence from rice farming in Jiangsu, China
Authors: Marchand Sébastien , Barro Maimouna , Xiong Hang , Guo Huanxiu
Published: November 2024

The shift of industrial water pollution from urban to rural areas during industrialization can impact agricultural production and stimulate farmers’ adaptive behavior. As an illustration, this study examines the impact of industrial water pollution from manufacturing firms on rice production in Jiangsu, China. By combining data from the China Rural Fixed Point Survey with the China Environmental Statistics Database, we employ an extended translog production function to distinguish between the effects of industrial water pollution and farmers’ adaptation behaviors. Our results demonstrate that industrial chemical oxygen demand (COD) has a direct biological effect on paddy rice growth, reducing rice yields by 3.76 to 4.17 percent. This detrimental effect is most pronounced within a radius of 5 kg from the village center. Additionally, farmers increase their operating inputs to mitigate the adverse effects of industrial water pollution. These findings underscore the need for stringent environmental regulations and enhanced environmental education in rural areas to promote the sustainable development of both manufacturing industry and agriculture in developing countries.
In Desperate Need: Public Sanitation in Contemporary London
Authors: Habermehl Victoria , McFarlane Colin
Published: November 2024

There has been a collapse in the number of public toilets in UK cities. Austerity cuts, a lack of legal requirements, and a failure to prioritise sanitation has led to significant health and equality impacts. Research on public toilets in the Global North focuses on their historical production, contemporary design, or on the experience of particular social groups, with less work bringing governance and social experience together. We argue for a focus on the “ungoverning” of sanitation, on how residents “learn” sanitation in the city, and on the need for radical transformation in sanitation approaches and delivery. Drawing on research in London, we set out the challenges for public toilet provision and make a case for a sanitation revolution in British cities. We focus on the experience of delivery drivers and residents with health concerns in order to illustrate the inequalities in provision and their consequences.
Impact of the mare colostral immunoglobulins on the expression of TLR3, TLR4, and TLR7 in foals
Authors: Migdał Anna , Migdał Łukasz , Oczkowicz Maria , Tombarkiewicz Barbara , Okólski Adam
Published: November 2024

Colostrum contains substances such as hormones, enzymes, polyamides, nucleic acid derivatives, and amino acid derivatives and also includes immunomodulating substances, proline‐rich polypeptides, immunoglobulins (Ig) as well as bacteriostatic compounds. The aim of the study was to evaluate the impact of colostral Ig on the level of expression of selected Toll‐like receptor genes (TLR3, TLR4, and TLR7). The experiments were conducted on 25 Polish Pony foals. Blood samples were collected according to the following scheme: before first suckling, at the 1st, 3rd, 5th, 10th, 20th, and 30th, day of age. Colostrum was obtained before the first suckling, 24 hr, and 3 days after the delivery. Gene expression analyses were performed on Illumina Eco using a commercial kit TaqMan®MGB probes. The quality of colostrum was assessed via refractometer and BRIX value. The total Ig level was calculated from the spectrophotometric method. IgG levels were measured using ELISA assay. The quality of colostrum significantly correlated with TLR4 and TLR7 expression. Foals that ingested colostrum with low Ig content displayed a higher level of TLR4 gene expression, while in the case of TLR7 the opposite trend was shown. This result indicates that colostrum may play an important role in shaping the mechanisms of building the immune system's response to bacterial pathogens.
Autonomy and prevention: From conflicting to complementary aims of prenatal screening
Authors: Dondorp Wybo , de Wert Guido , Becking Ellis C. , Scheffer Peter G. , Bekker Mireille , Henneman Lidewij
Published: November 2024

From an ethical point of view, there is an important distinction between two types of prenatal screening. The first of these targets maternal or foetal conditions (e.g., infectious diseases, blood group sensitization) where early detection allows for interventions that improve the chances of a healthy pregnancy outcome. The second screens for foetal conditions such as Down syndrome, where a timely diagnosis in most cases only allows for a choice between preparation for a child with special needs or termination of the pregnancy. Whereas the former makes an easy fit with the prevention aim of most other population screening programmes, the latter does not. In order to steer clear from a possible eugenic reading of its aim, a wide international consensus has emerged for the view that prenatal screening of this type should have the atypical aim of helping women (couples) to make autonomous reproductive choices, rather than reducing the birth prevalence of the relevant disorders. However, keeping these types of prenatal screening apart may become increasingly difficult given the development of tests, such as the Non‐Invasive Prenatal Test, which cannot only be used for both types of screening but may also lead to interconnected findings on both sides of the divide. This makes it an urgent question: What the aim or aims of this new hybrid screening should be? As neither ‘prevention’ nor ‘autonomy’ will do, we argue for a normative framework that gives both aims their due, while recognizing the tensions between them.
Hydroxy‐wybutosine tRNA modifications as indicators of disease progression and therapeutic targets in leukaemia
Authors: Chen Xu , Gong Rui‐Ze , Mo Liu‐Ying , Cheng Ya‐Ting , Ma Yu , Qi Yi‐Tao , Yan Tong‐Meng , Jiang Zhi‐Hong
Published: November 2024

Therapeutic approaches for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) differ due to distinct diagnostic criteria and treatment strengths. However, reliable biomarkers to differentiate AML from MDS are needed. This study investigated transfer RNA (tRNA) modifications, particularly hydroxy‐wybutosine (OHyW), in the transition from MDS to AML. We found a significant decrease in OHyW and its biosynthetic enzyme leucine carboxyl methyltransferase 2 (LCMT2, alias symbol is TYW4) levels in AML compared to MDS. Mass spectrometric analysis revealed distinct tRNA modification patterns, with AML showing decreased OHyW and increased precursor levels, indicating a disrupted biosynthetic pathway. Lower LCMT2 expression correlated with reduced drug sensitivity and limited differentiation potential in AML cell lines. The results highlight the pivotal role of tRNA modifications in the progression from MDS to AML and suggest that targeting LCMT2 may enhance therapeutic outcomes in AML. By understanding these molecular mechanisms, we can develop new diagnostic markers and therapeutic strategies, potentially transforming the clinical management of AML and improving patient outcomes.
The underlying causes of differential migration: assumptions, hypotheses, and predictions
Authors: Paprocki Neil , Conway Courtney J.
Published: November 2024

Mechanisms governing the migratory decisions of birds have long fascinated ecologists and sparked considerable debate. Identifying factors responsible for variation in migration distance, also known as differential migration, has been a popular approach to understanding the mechanisms underlying migratory behaviour more generally. However, research progress has been slowed by the continued testing of overlapping, non‐mechanistic, and circular predictions among a small set of historically entrenched hypotheses. We highlight the body size hypothesis and suggest that the predictions commonly tested have impeded progress because body size relationships with migration distance are predictions made by several distinct hypotheses with contrasting mechanisms. The cost of migration itself has not been adequately accounted for in most hypotheses, and we propose two flight efficiency hypotheses with time‐ and energy‐minimizing mechanisms that allow individuals to mitigate the risks inherent to longer migrations. We also advance two conceptual versions of the social dominance hypothesis based on two distinct underlying mechanisms related to distance minimization and food maximization that will help clarify the role of competition in driving migratory decisions. Overall, we describe and refine 12 mechanistic hypotheses proposed to explain differential migration (along with several other special‐case hypotheses), seven of which have underlying mechanisms related to food limitation as past research has identified this to be an important driver of differential migration. We also thoroughly reviewed 145 publications to assess the amount of support for 10 critical assumptions underlying alternative hypotheses for differential migration in birds. Our review reveals that surprisingly few studies explicitly evaluate assumptions within a differential migration context. Generating and testing strong predictions and critical assumptions underlying mechanisms of alternative hypotheses will improve our ability to differentiate among these explanations of differential migration. Additionally, future intraspecific progress will be greatest if investigators continue to focus on mechanisms underlying variation in migration distance within rather than among demographic classes, as previous research has found differing mechanisms to be responsible for differential migration among demographic classes. Interspecifically, a thorough comparative analysis that seeks to explain variation in migration distance among species would broaden both our understanding of the mechanisms regulating current differential migration patterns and those that led to the evolution of migration more generally. Collectively, we provide a framework that, together with advances in animal‐borne tracking and other technology, can be used to advance our understanding of the causes of differential migration distance, and migratory decisions more generally.