bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal and Geographic Variability of International Urinary Phthalates in Humans: A Systematic Review and Meta-Analysis of Biomonitoring Data
Authors: Acevedo Jonathan M. , Kahn Linda G. , Pierce Kristyn A. , Albergamo Vittorio , Carrasco Anna , Manuel Robbie S.J. , Singer Rosenberg Marissa , Trasande Leonardo 
Published: November 2024

AbstractPhthalates are endocrine-disrupting chemicals (EDCs) that alter hormone functions throughout the lifespan. Growing awareness of the adverse health effects of phthalate exposure has led to regulating certain phthalates in the United States, Canada, and Europe. However, international comparisons of urinary phthalate metabolite concentrations as biomarkers of exposure are sparse, and few studies have controlled for cohort-specific variables like pregnancy.We aimed to examine trends in urinary phthalate monoester metabolite concentrations in non-occupationally exposed populations globally, excluding locations where representative data are already available at the country level.We systematically reviewed studies published between 2000 and 2023 that reported urinary phthalate monoester concentrations. We examined changes in metabolite concentrations across time, controlling for region, age, and pregnancy status, using mixed-effects meta-regression models with and without a quadratic term for time. We identified heterogeneity using Cochran’s Q-statistic and I2index, adjusting for it with the trim-and-fill method.The final analytic sample consisted of 216 studies. Significant differences in phthalate metabolite concentrations were observed across regions, age groups, and between pregnant and non-pregnant cohorts. Our meta-regression identified a significant non-linear trend with time for Mono-n-butyl phthalate and Mono-isononyl phthalate concentration internationally and in Eastern and Pacific Asia (EPA). We also observed significant non-linear associations between time and Mono(2-ethyl-5-hydroxyhexyl) phthalate, Mono(2-carboxymethylhexyl) phthalate, and Mono(3-carboxypropyl) phthalate concentration internationally and/or in EPA, along with Mono(2-ethylhexyl) phthalate, Mono-carboxy-isononyl phthalate, and Mono-ethyl phthalate. Additionally, Mono-ethyl phthalate concentration showed a significant negative linear association with time in Latin America and Africa. Heterogeneity was high, indicating potential bias in our results.Our findings indicate the need for increased awareness of phthalate exposure. Further analysis of the attributable disease burden and cost at regional and international levels, especially in low- and middle-income countries, is essential to understanding these and other EDCs impact on population health and the economy.HighlightsSome phthalate levels significantly differed by region, age, and pregnancy status.Many phthalates had non-linear associations internationally from 2000 to 2023.MnBP and MiNP levels increased, driven by Eastern and Pacific Asia results.Most phthalate metabolites’ levels declined overall and region-specific over time.There was insufficient data on phthalate metabolite levels for many regions.
Wearable Focal Muscle Vibration Improves Upper Limb Function in People with Sub-acute Stroke
Authors: Niazi Imran Khan , Amjad Imran , Farooq Irum , Shafi Hina , Rashid Usman , Kumari Nitika , Shaikh Nusratnaaz , Jochumsen Mads , Holt Kelly , Haavik Heidi , Farmer Simon F. , Pujari Amit N. 
Published: November 2024

AbstractThe objective of the study was to compare the effects of two focal muscle vibration (FMV) stimulation frequencies (60 Hz and 120 Hz), combined with conventional physical therapy (PT), on upper limb impairment and function in people with sub-acute stroke when FMV is delivered through a wearable FMV device.The study was a parallel group, randomized controlled trial conducted at the Rehabilitation Centre of Railway General Hospital, Rawalpindi, Pakistan. A total of 98 individuals with sub-acute stroke were randomly allocated to control group (eight weeks of conventional physical therapy, (PT)) or experimental groups (eight weeks of conventional physical therapy combined with focal muscle vibration (FMV) at 60 Hz (PT + FMV60 Hz) or 120 Hz (PT + FMV120 Hz)). Outcome measures included Fugl Meyer Scale for upper extremity (FMUE), Motor Assessment Scale (MAS), and Modified Ashworth Scale (MASh). They were collected at baseline and after eight weeks of treatment. Data were analysed using linear regression model. The study was registered on the National Institutes of HealthClinicalTrials.govclinical trial registry (IdentifierNCT04289766).At post-intervention time-point, FMUE scores varied across groups (F (2, 81) = 7.2, p = 0.001), MAS scores did not vary across groups (F (2, 81) = 0.2, p = 0.8) and MASh rank changes varied across groups (F (2, 81) = 3.3, p = 0.04). There were no differences between the PT + FMV60 Hz and the PT + FMV120 Hz groups.This study provides the evidence that wearable Focal Muscle Vibration (at 60 and 120 Hz) improves the motor outcome of sub-acute stroke patients. Thus, it can be used along with conventional physiotherapy as a valid intervention to promote upper limb function and reduce spasticity in sub-acute post-stroke patients.
MosCoverY: a new method to estimate mosaic Loss of Y chromosome from NGS sequencing coverage data
Authors: Timonina V. , Marchal A. , Abel L. , Cobat A. , Fellay J. 
Published: November 2024

ABSTRACTMosaic loss of the Y chromosome (mLOY) is the most common somatic event in men, strongly associated with aging and various health conditions. Current methods for detecting mLOY primarily rely on DNA genotyping arrays. Here, we present MosCoverY, a novel method for estimating mLOY from NGS sequencing data that can be applied to both exome and genome sequencing. MosCoverY addresses the challenges posed by the structure of the Y chromosome by focusing on single-copy genes and normalizing their coverage against autosomal exons matched by length and GC content. We validated MosCoverY using data from 212,062 male participants in the UK Biobank, comparing its results to those obtained using genotyping- or whole genome sequencing-based methods. MosCoverY identified mLOY in 5.6% of men, demonstrating performance that was comparable to the other methods. MosCoverY also replicated known associations between mLOY, age, smoking, all-cause mortality, and germline genetic loci, showing the strongest associations in many cases. MosCoverY offers a valuable tool for detecting mLOY from exome data in population-scale studies.
A regulator controls both DNA damage response and anti-phage defense networks inMoraxellaceae
Authors: Song Shuang , Zhong Shitong , Shi Qiucheng , Zheng Xiangkuan , Yao Yue , Wang Wenxiu , Chen Shanhou , Huang Zijun , An Dongyue , Xu Hong , Tian Bing , Zhao Ye , Wang Liangyan , Zhang Wei , Hua Xiaoting , Yu Yunsong , Lu Huizhi , Fan Lu , Hua Yuejin 
Published: November 2024

AbstractDNA damage chemicals, including many antibiotics, often induce prophage induction and phage outbreaks in microbial communities, a major threat to bacterial survival.Moraxellaceaecontains clinically highly relevant strains with outstanding antibiotic and radio resistance, yet their cellular-level regulation in DNA damage response and anti-phage defense is largely unknown. Here, we identified a WYL family protein that had replaced the ubiquitous SOS system in evolution and directly regulated a transcriptional network of both DNA repair genes and anti-phage defense genes under DNA damage stress. This study depicts a mechanism that how bacteria maintain immunity to phages without compromising on antibiotic resistance, and sheds light on controlling the resistance ofMoraxellaceaestrains in clinical practice.
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

SummaryThe 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.HighlightsGeneration of a single-cell atlas of chromatin accessibility in nine organs of the ratCharacterization of cell type- and organ-specific transcription factors (TFs)Dynamics of chromatin accessibility in developing T cells revealed by cross-organ analysisConservation and specificity of gene expression patterns among humans, mice, and rats revealed by cross-species analysis
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

AbstractUnderstanding 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 summaryR-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

ABSTRACTIn 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

ABSTRACTPancreatic 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

AbstractMalaria 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

AbstractTherapies 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

PurposeThe 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/approachA 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.FindingsThe 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/valueThis 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.