bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenome‐Wide Association Study of Asthma Exacerbations in Europeans
Authors: Martin‐Gonzalez Elena , Perez‐Garcia Javier , Herrera‐Luis Esther , Martin‐Almeida Mario , Kebede‐Merid Simon , Hernandez‐Pacheco Natalia , Lorenzo‐Diaz Fabian , González‐Pérez Ruperto , Sardón Olaia , Hernández‐Pérez José M. , Poza‐Guedes Paloma , Sánchez‐Machín Inmaculada , Mederos‐Luis Elena , Corcuera Paula , López‐Fernández Leyre , Román‐Bernal Berta , Toncheva Antoaneta A. , Harner Susanne , Wolff Christine , Brandstetter Susanne , Abdel‐Aziz Mahmoud Ibrahim , Hashimoto Simone , Vijverberg Susanne J. H. , Kraneveld Aletta D. , Potočnik Uroš , Kabesch Michael , Maitland‐van der Zee Anke H. , Villar Jesús , Melén Erik , Pino‐Yanes Maria
Published: February 2025

Background

Asthma exacerbations (AEs) represent the major contributor to the global asthma burden. Although genetic and environmental factors have been associated with AEs, the role of epigenetics remains uncovered.

Objective

This study aimed to identify whole blood DNA methylation (DNAm) markers associated with AEs in Europeans.

Methods

DNAm was assessed in 406 blood samples from Spanish individuals using the Infinium MethylationEPIC microarray (Illumina). An epigenome‐wide association study was conducted to test the association of DNAm with AEs at differentially methylated positions, regions, and epigenetic modules. CpGs suggestively associated with AEs (false discovery rate [FDR] < 0.1) were followed up for replication in 222 European individuals, and the genome‐wide significance (p < 9 × 10−8) was declared after meta‐analyzing the discovery and replication samples. Additional assessment was performed using nasal tissue DNAm data from 155 Spanish individuals. The effects of genetic variation on DNAm were assessed through cis‐methylation quantitative trait loci (meQTL) analysis. Enrichment analyses of previous EWAS signals were conducted.

Results

Four CpGs were associated with AEs, and two were replicated and reached genomic significance in the meta‐analysis (annotated to ZBTB16 and BAIAP2). Of those, CpG cg25345365 (ZBTB16) was cross‐tissue validated in nasal epithelium (p= 0.003) and associated with five independent meQTLs (FDR < 0.05). Additionally, four differentially methylated regions and one module were significantly associated with AEs. Enrichment analyses revealed an overrepresentation of prior epigenetic associations with prenatal and environmental exposures, immune‐mediated diseases, and mortality.

Conclusions

DNAm in whole blood and nasal samples may contribute to AEs in Europeans, capturing genetic and environmental risk factors.
Medication adherence and hospitalizations in older patients with coronary heart disease in Vietnam
Authors: Nguyen Tan Van , Nguyen Hang Thi Thuy , Truong Dung Ngoc , Nguyen Viet Quoc , Nguyen Huy Quang , Nguyen Huy Quoc , Ngo Trinh Thi Kim , Amsalu Erkihun , Wong Wei Jin , Nguyen Tu Ngoc
Published: February 2025

Aims

This study aimed to assess medication adherence among older people with coronary heart disease and its relationship with hospitalizations.

Methods

This is a prospective cohort study conducted at the outpatient clinics of a major hospital in Vietnam from November 2022 to June 2023. Consecutive older patients with coronary heart disease were recruited and followed for 6 months. Medication adherence was defined using the five‐item Medication Adherence Report Scale (MARS‐5). Multivariable logistic regression models were applied to examine the impact of medication adherence on hospitalization due to cardiovascular disease (CVD) and all‐cause hospitalization.

Results

There were 643 participants, mean age 73 ± 8 years, 74.3% were male. Overall, 76.4% (491/643) were classified as ‘adherent’. Over 6 months follow‐up, 23.3% of the participants were admitted to hospital and of these hospitalizations, 9.2% were due to CVD. The CVD‐related hospitalization rate was significantly higher in the non‐adherent group compared to the adherent group (13.8% vs. 7.7%, P = 0.023, respectively). In logistic regression models, medication adherence was associated with significantly reduced odds of CVD‐related hospitalization (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.27–0.86). Medication adherence was also associated with a trend of reduced all‐cause hospitalization (adjusted OR 0.75, 95% CI 0.49–1.15).

Conclusions

This study showed a positive relationship between medication adherence and reduced risk of CVD‐related hospitalization in older people with coronary heart disease. Healthcare providers should consider incorporating adherence assessment into the long‐term care for older patients with coronary heart disease.
Advances in Bruton tyrosine kinase (Btk) inhibition are steered by Bruton tyrosine kinase phylogeny
Authors: Minotti Giorgio , Camilli Massimiliano , Salvatorelli Emanuela , Menna Pierantonio
Published: February 2025

Bruton tyrosine kinase (Btk) has long been known to play a key role in chronic lymphatic leukaemia, Waldenström macroglobulinaemia and other B‐cell proliferative disorders. An impressive programme of drug discovery and clinical development led to the approval of covalent and non‐covalent Btk inhibitors that became pillars of treatment of such malignancies. However, both a risk of cardiovascular events and the emergence of an elusive mutational landscape seem to complicate the clinical use of each Btk inhibitor. In this plain language mini‐review, we show that the search for better Btk inhibitors is challenged by the ancestral origin of Btk, its homology with innocent kinases in cardiovascular system and unique phylogenetic‐like modalities with which Btk can mutate upon exposure to one inhibitor or another. Whereas basic and clinical pharmacology is already at work to explore new avenues of Btk inhibition, phylogeny remains behind the curtain to steer achievements and failures in this field.
Automation and asymmetric international spillovers of technological shocks
Authors: Momoda Shohei , Ogawa Takayuki , Shimizu Ryosuke
Published: February 2025

This study examines international spillover effects of technological shocks using a dynamic open economy model in which production tasks are automated by robots. A concentration of robot production in a few countries worldwide is essential to understanding automation advances and robot price declines in a globalized economy. Technological improvements in robot‐producing countries decrease world robot prices and affect automation advances in other countries specializing in non‐robot production; however, the reverse is not true. The welfare effects are also asymmetric and depend on the type of technological shocks. For example, by improving the productivity of investment in robots, the non‐robot producing countries suffer from the deteriorated terms of trade and may become worse off depending on the global wealth distribution.
Genome‐Wide Association Study Reveals Genetic Architecture of Common Epilepsies
Authors: Thakran Sarita , Guin Debleena , Singh Priyanka , Uppili Bharathram , Ramachandran Srinivasan , Kushwaha Suman S. , Kukreti Ritushree
Published: February 2025

Epilepsy, affecting approximately 50 million individuals worldwide, exhibits a genetic heritability of 32%. While several genes/loci associated with epilepsy have been identified through candidate and genome‐wide association studies (GWAS), exploration of population‐specific markers remains underexplored. We conducted the first GWAS in north Indian population (~1500 samples) to identify genetic variants/loci associated with epilepsy risk, validated using targeted next‐generation sequencing (NGS). Our GWAS revealed 30 variants across seven loci associated with epilepsy risk, including six novel loci. Subtype analysis based on etiology and seizure types, identified 57 variants across 11 loci, 10 of which are novel. Gene‐set analysis unveiled enrichment in genes associated with glutathione synthesis and recycling and regulation of dopaminergic neuron differentiation pivotal in epilepsy pathophysiology. Furthermore, PRS analysis revealed a significant genetic contribution to the epilepsy with an R2 of 0.00573. Additionally, targeted NGS showed ~95% concordance with GSA genotypes. Our study highlights six novel loci rs17031055/4q31.3(DCHS2), rs73182224/3q27.2(DGKG), rs9322462/6q25.2(CNKSR3), rs75328617/8q24.23(RNU1‐35P), rs2938010/10q26.13(CTBP2) and rs11652575/17p11.2(SLC5A10) associated with epilepsy risk. These findings offer valuable insights into the genetic landscape of epilepsy in the north Indian population, providing foundation for future exploratory studies.
Loss of 18q Alters TGFβ Signalling Affecting Anteroposterior Neuroectodermal Fate in Human Embryonic Stem Cells
Authors: Lei Yingnan , Duong Mai Chi , Krivec Nuša , Janssens Charlotte , Regin Marius , Huyghebaert Anfien , Couvreu de Deckersberg Edouard , Sermon Karen , Al Delbany Diana , Spits Claudia
Published: February 2025

Chromosomal abnormalities acquired during cell culture can compromise the differentiation potential of human pluripotent stem cells (hPSCs). In this work, we identified a diminished differentiation capacity to retinal progenitor cells in human embryonic stem cells (hESCs) with complex karyotypes that had in common the loss of part of chromosome 18q. Time‐course gene‐expression analysis during spontaneous differentiation and single‐cell RNA sequencing found that these variant cell lines poorly specified into anterior neuroectoderm, and, when progressing through differentiation, they yielded poorly pigmented cells, with proliferating and pluripotent cell populations. The variant cell lines showed dysregulation of TGFβ signalling during differentiation, and chemical modulation of the TGFβ pathways showed that the basis of the improper specification was due to imbalances in the anteroposterior neuroectodermal fate commitment.
Pharmacokinetics of a Novel Piperaquine Dispersible Granules Formulation Under Fasting and Various Fed Conditions Versus Piperaquine Tablets When Fasted in Healthy Tanzanian Adults: A Randomized, Phase I Study
Authors: Milando Florence A. , Jongo Said , Abdulla Salim , Nyaulingo Gloria , Tumbo Anneth‐Mwasi , Mswata Sarah , Tiago Juliether , Bongole Beatus S. , Mirambo Ashura , Kassimu Kamaka , Mbarak Hussein , Rashid Mohammed A. , Hamad Ali , Mihayo Michael , Ndanzi Tunu , Zuberi Omary , Saadia Naima , Somboka Mariam , Yamba‐Yamba Mariam , Ngonyani Theresia , Nditi Amina , Msuya Margaret , Mwalimu Bakari , Msuya Hajirani M. , Awadh Khamis , Ali Ali , Marrast Anne Claire , Gossen Denis , Neequaye Alice , El‐Gaaloul Myriam , Ramachandruni Hanu , Borghini‐Fuhrer Isabelle
Published: February 2025

Piperaquine tetraphosphate (PQP), a long‐acting antimalarial, is being considered in a combination for chemoprevention. Dihydroartemisinin‐piperaquine tablets (hard and dispersible) approved for the treatment of acute uncomplicated malaria should be administered in a fasted state, as PQP bioavailability increases with food. A new taste‐masked dispersible granules PQP formulation aims to minimize the impact of food on drug exposure. This randomized, open label, parallel group, Phase I pilot study was conducted between 24th July 2023, and 3rd January 2024, at the Ifakara Health Institute, Bagamoyo, Tanzania in 60 healthy African adults (five cohorts of 12). Single‐dose pharmacokinetics and relative systemic exposure of the oral PQP dispersible granules formulation prototype (320 mg) was compared to the hard tablet when fasted and PQP granules in three different fed conditions. In the fasted state, the relative exposure of PQP granules versus the tablet was 73.9% (90% CI 48.3, 113.0) for Cmax and 86.5% (68.2, 109.6) for AUC0‐t. Following a typical East African low‐fat meal, a standard high‐fat meal, or 250 mL whole milk, the relative exposure of PQP granules versus the fasted state was 202% (90% CI 132, 311), 275% (193, 391), and 294% (203, 425) for Cmax and 164% (124, 217), 184% (148, 228), and 195% (147, 259) for AUC0‐t, respectively. Both formulations were well tolerated with one drug‐related adverse event (moderate migraine). No severe or serious adverse events or clinically relevant laboratory or electrocardiograph changes were observed. PQP dispersible granules had lower systemic exposures versus the tablet when fasted, whereas various meals increased drug exposure.
Learning by Example: Does Positive Nonverbal Behavior Reduce Children's Racial Bias?
Authors: Gonzalez Antonya M. , Skinner Allison L. , Baron Andrew Scott
Published: February 2025

Nonverbal behavior is a ubiquitous, everyday cue that is often used as a basis for social evaluation. Numerous studies indicate that children are sensitive to these signals and form evaluative judgments after viewing positive or negative nonverbal cues directed toward a target. Furthermore, they generalize these judgments to other members of a targets’ social group, indicating that nonverbal behavior displays can influence intergroup bias. However, no studies thus far have directly examined whether exposure to positive nonverbal behavior cues can reduce children's implicit and explicit racial bias. In the current study, we exposed White and Asian children ages 9–11 to positive nonverbal behavior displayed by a White expresser toward a Black target, drawn from children's television shows. Children demonstrated a pro‐White/anti‐Black bias implicitly, but explicitly preferred Black over White characters. Additionally, children judged Black characters from the clips and novel Black characters positively. We found that there was no difference in implicit or explicit racial bias between children who viewed positive nonverbal behavior demonstrated by a White expresser to a Black target as compared to children who were only exposed to a Black target (and no nonverbal cues) or unrelated video clips. Future research examining the influence of positive nonverbal behavior on children's racial bias should consider using more overt or prolonged demonstrations of positive nonverbal behavior or increasing children's familiarity with the characters presented.
Mismanagement amid resource abundance: Sovereign risk, private sector credit rationing, and economic stagnation in Colombia, 1861‒98
Authors: Primmer Andrew
Published: February 2025

This article examines the relationship between national politics, sovereign default, credit rationing, and their effects on fiscal revenues and exports in nineteenth‐century Colombia. Using quantitative and qualitative analysis, it challenges existing narratives on Colombia's lack of sustained nineteenth‐century export‐led development, showing that sovereign default was a political choice with long‐term negative impacts. The study highlights how credit rationing and technological backwardness hindered economic growth. It argues that these policies caused Colombia's economic stagnation, leading to boom‐and‐bust cycles in export crop production. It identifies substantial growth during the liberal era and minimal growth during the regeneración period.
Investigation of the Initiation of Composite Mode I/II Crack in Gas‐Bearing Rock Caused by Nonuniformly Distributed Heat Flux
Authors: Li Wei , Chen Wenhua
Published: February 2025

To investigate the patterns of rock crack initiation caused by the nonuniformly distributed heat flux resulting from fracture air‐vapor pressure, the fracture air‐vapor pressure control equation was deduced, and five spatial distribution forms of heat flux were established. The crack initiation criterion considering nonuniform heat flux conditions was proposed based on the modified maximum tangential stress criterion, the theory was validated using FEM and FE‐FEM numerical methods. The results show that the peak value of nonuniform heat flux determines the maximum value of the crack surface temperature, and the distribution form determines the range of high‐temperature and low‐temperature regions on the crack surface. Axisymmetric heat flux induces centrosymmetric cracking, and nonaxisymmetric heat flux induces noncentrosymmetric cracking. It was observed that when qmax = 5000 mW/m2, there is a mutation line in the critical crack initiation angle, which mutates from −90° to 90°. The position of the mutation line decreases with increasing heat flux.
Local‐ and Regional‐Scale Climate Variability Drives Complex Patterns of Growth Synchrony and Asynchrony in Deep‐Sea Snappers Across the Indo‐Pacific
Authors: Widdrington Joseph B. , Reis‐Santos Patrick , Macdonald Jed I. , Moore Bradley R. , Nicol Simon J. , Morrongiello John R. , Gillanders Bronwyn M.
Published: February 2025

Climatic variation can play a critical role in driving synchronous and asynchronous patterns in the expression of life history characteristics across vast spatiotemporal scales. The synchronisation of traits, such as an individual's growth rate, under environmental stress may indicate a loss of phenotypic diversity and thus increased population vulnerability to stochastic deleterious events. In contrast, synchronous growth under favourable ecological conditions and asynchrony during unfavourable conditions may help population resilience and buffer against the negative implications of future environmental variability. Despite the significant implications of growth synchrony and asynchrony to population productivity and persistence, little is known about its causes and consequences either within or among fish populations. This is especially true for long‐lived deep‐sea species that inhabit environments characterised by large‐scale interannual and decadal changes, which could propagate growth synchrony across vast distances. We developed otolith growth chronologies for three deep‐sea fishes (Etelis spp.) over 65° of longitude and 20° of latitude across the Indo‐Pacific region. Using reconstructed time series of interannual growth from six distinct Exclusive Economic Zones (EEZs), we assessed the level of spatial synchrony at the individual‐, population‐ and species‐scale. Across five decades of data, complex patterns of synchronous and asynchronous growth were apparent for adult populations within and among EEZs of the Pacific Ocean, mediated by shifts in oceanographic phenomena such as the Pacific Decadal Oscillation. Overall, our results indicate that the degree of synchrony in biological traits at depth depends on life history stage, spatiotemporal scales of environmental variability and the influence of ecological factors such as competition and dispersal. By determining the magnitude and timing of spatially synchronous growth at depth and its links to environmental variability, we can better understand fluctuations in deep‐sea productivity and its vulnerability to future environmental stressors, which are key considerations for sustainability.
Soil Moisture Threshold of Methane Uptake in Alpine Grassland Ecosystems
Authors: Wang Peiyan , Wang Jinsong , Wang Song , D'Imperio Ludovica , Elberling Bo , Ambus Per , Zhang Zhen , Ito Akihiko , Li Yang , Pan Junxiao , Song Lei , Liu Ning , Zhang Ruiyang , Chen Weinan , Niu Shuli
Published: February 2025

Methane (CH4) uptake in alpine ecosystems is an important component of the global CH4 sink. However, large uncertainties remain regarding the magnitude and spatial patterns of CH4 uptake, owing to its extensive spatial variability, diverse controlling factors, and limited regional‐scale observations. Here, we investigated field ecosystem CH4 uptake along a 3200‐km transect across various alpine grasslands on the Qinghai–Tibetan Plateau (QTP). We found a substantial spatial variation in in situ CH4 uptake among alpine grasslands, with the highest rates in drier regions of the mid‐western QTP. Soil moisture was the most important factor controlling CH4 uptake, exhibiting a remarkably low threshold of 6.2 ± 0.1 v/v %. Below this threshold, CH4 uptake was constrained by soil moisture, moisture‐induced nitrogen limitation, and high temperatures. Above this threshold, CH4 uptake was mainly limited by gas diffusion and low temperatures. By integrating grid predictors with a random forest model trained on 1851 field measurements encompassing both our observations and a regional synthesis across the QTP, we estimated a regional CH4 uptake of 0.88 ± 0.020 Tg CH4 year−1 from all alpine grasslands on the QTP. This higher estimate, primarily driven by alpine steppes, was significantly greater than current regional estimates from global CH4 models. Our findings highlight the importance of CH4 sink in dry alpine ecosystems characterized by low soil moisture, suggesting that the contribution of CH4 sink in drylands may have been substantially underestimated in the current global CH4 budget.
Relationship between decreased activities of daily living, decreased physical strength and future weight loss in community‐dwelling older adults
Authors: Hoshi Kazuhiro , Shibasaki Koji , Yakabe Mitsutaka , Hosoi Tatsuya , Matsumoto Shoya , Yamada Shizuru , Hashimoto Seiji , Akishita Masahiro , Ogawa Sumito
Published: February 2025

Aim

Weight loss is among the diagnostic criteria for frailty and is associated with increased mortality among older people. This study aimed to identify factors associated with future weight loss among community‐dwelling older people.

Methods

A multidimensional questionnaire‐based prospective cohort study was carried out. The questionnaire included the Kihon Checklist, instrumental activities of daily living (IADL) scale, Activity Scale for the Elderly, Fall Risk Index‐21 and Dietary Variety Score. The associations among the scores of the scales and the 3‐year weight change from study entry were assessed. The participants were categorized into the non‐weight loss group, <4.5‐kg weight loss group and >4.5‐kg weight loss group.

Results

In total, 982 participants completed the follow up. Their mean age was 73.4 ± 5.1 years, and 545 (55.5%) participants were women. Among the IADL questionnaire subitems, depositing and withdrawing money from the bank, walking, interacting with people, taking medication, and cooking were associated with 3‐year weight loss. Furthermore, cooking was strongly associated with weight loss. However, there was no association between eating frequency and weight loss. Finally, low IADL and physical function scores were associated with a doubled risk of future weight loss.

Conclusions

An association was found between 3‐year weight loss and physical fitness and IADL, such as walking, among community‐dwelling older people. Future weight loss in older people can be caused by a decline in IADL and physical fitness before a decline in dietary intake. Furthermore, maintaining IADL and physical fitness can prevent future weight loss and frailty. Geriatr Gerontol Int 2025; ••: ••–••.
The Protein Kinase aPKC as Well as the Small GTPases RhoA and Cdc42 Regulates Neutrophil Chemotaxis Partly by Recruiting the ROCK Kinase to the Leading Edge
Authors: Naito Atsushi , Kamakura Sachiko , Hayase Junya , Kohda Akira , Niiro Hiroaki , Akashi Koichi , Sumimoto Hideki
Published: February 2025

The small GTPases RhoA and Cdc42 and their effector proteins play crucial roles in neutrophil chemotaxis. However, endogenous localization and regulation of these proteins have remained largely unknown. Here, we show, using a trichloroacetic acid fixation method, that endogenous RhoA and Cdc42 are preferentially accumulated at the F‐actin‐rich leading edge (pseudopod) during chemotaxis of human neutrophil‐like PLB‐985 cells in response to the chemoattractant C5a. Interestingly, the enrichment of RhoA is impaired by knockdown of Cdc42, indicating a positive regulation by Cdc42. Depletion of Cdc42 or RhoA each induces the formation of multiple pseudopods, confirming their significance in cell polarization with an organized actin network at the front. The Rho‐associated kinase ROCK is also recruited to the leading edge during chemotaxis in a manner dependent on not only RhoA and Cdc42 but also aPKC, a Cdc42‐interacting kinase that can also bind to ROCK. ROCK promotes phosphorylation of the myosin light chain at the front, possibly regulating pseudopod contractility. Knockdown of aPKC suppresses neutrophil chemotaxis by disturbing pseudopod orientation without forming multiple protrusions. An incorrectly oriented pseudopod is also observed in ROCK‐depleted cells. Thus, aPKC, as well as RhoA and Cdc42, likely regulates neutrophil chemotaxis partly by recruiting ROCK to the leading edge for correct directionality.
Regulation of Gut Starvation Responses Through DrosophilaNP3253 Neurons
Authors: Nguyen Quang‐Dat , Fujii Kiho , Ishibashi Kentaro , Hashiba Haruka , Ohtsubo Wakako , Kitazawa Haruki , Tanimoto Hiromu , Fuse Naoyuki , Kurata Shoichiro
Published: February 2025

The “gut–brain axis,” a bidirectional communication system between the gastrointestinal tract and the central nervous system, plays a crucial role in regulating complex physiological functions in response to nutrients, pathogens, and microbiota. However, the cellular and molecular mechanisms governing this regulation remain poorly understood. Using Drosophila melanogaster as a model organism, we previously identified NP3253 neurons, located in both the brain and gut, as key contributors to gut homeostasis during oral bacterial infection. Here, we found a novel role of NP3253 neurons in regulating starvation resistance. We observed that a subset of NP3253 neurons in the gut were activated during starvation. To investigate downstream effect, we conducted RNA‐Seq analysis on the gut of adult flies with genetically silenced NP3253 neurons, comparing gene expression under starved and fed conditions. This analysis identified 26 genes differentially expressed in response to both starvation and NP3253 neuronal activity. Among these, CG12643, encoding an uncharacterized short peptide, was found to be essential for starvation resistance in the gut. Our findings demonstrate that NP3253 neurons modulate the gut gene expression in response to starvation, thereby supporting physiological adaptation to environmental stressors.
The prevalence and clinical significance of residual occult breast cancer after neoadjuvant chemotherapy: reassessing surgical pathology in cases initially described as pathological complete response
Authors: Ai Di , Arrey Eliel N , Postlewait Lauren M , Gao Yuan , Li Xiaoxian
Published: February 2025

Aims

Evaluation of pathological complete response (pCR) [no residual invasive carcinoma in the breast (RIC) or lymph node metastases (LNM) in surgical specimens following therapy] is typically based on evaluation of one level of haematoxylin and eosin (H&E) section. Not achieving pCR is associated with worse outcomes, and additional therapy may ensue. This study of patients with triple‐negative (TNBC) or human epidermal growth factor receptor 2 (HER2)‐positive (HER2+) breast cancer who underwent neoadjuvant therapy aims to assess whether occult residual disease (ORD) can be identified in deeper sections of tumour beds and lymph nodes in cases originally reported as pCR and whether ORD is associated with worse outcomes.

Methods and results

In 84 cases of pCR (2009–17) at our institution, deeper‐level recuts were assessed for ORD. Oncological and survival outcomes were compared. ORD was identified in seven of 40 TNBC (17.5%; five RIC; one LMN; one RIC and LMN) and four of 44 HER2+ (9.1%; three RIC; one LMN) cases (all residual cancer burden I). Median follow‐up was 46.7 months for TNBC (one local recurrence, four distant metastases and two deaths) and 86.8 months for HER2+ (no local recurrence, three distant metastases and two deaths). All recurrence and death events occurred in patients with pCR without ORD, with no recurrence events in patients with ORD.

Conclusions

In patients with TNBC and HER2+ breast cancer with pCR by standard pathological assessment, occult residual disease is not uncommon. Occult disease was not associated with worse oncological or survival outcomes, suggesting standard pathological assessment is sufficient to identify clinically meaningful disease.
FoxO1 mediates odontoblast differentiation of hDPSCs via B cell‐derived ANGPTL1 in dental caries: A laboratory investigation
Authors: Zhan Peimeng , Huang Zhu , Xie Zhuo , Zhang Xinfang , Shen Zongshan , Chen Lingling , Huang Shuheng , Huang Qiting , Lin Zhengmei , Wang Runfu
Published: February 2025

Aim

Clinical and in vitro evidence indicates that chronic inflammatory responses initiated by dental caries can persist in the dental pulp even after treatment, necessitating the formation of reparative dentin to restore tissue homeostasis and health. Human dental pulp stem cells (hDPSCs) serve as crucial precursors in this reparative process. This study explores the role of B cells and their secreted factor, Angiopoietin Like 1 (ANGPTL1), in promoting hDPSCs differentiation into odontoblasts under carious conditions, with a particular focus on the activation of Forkhead box O1 (FoxO1).

Methodology

Single‐cell RNA sequencing (scRNA‐Seq) data from the GEO database were analysed to explore cellular interactions and molecular mechanisms in dental pulp. Immunofluorescence staining was used to investigate the expression patterns of B cells or hDPSCs in dental pulp and hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds. The expression levels of ANGPTL1 were quantified using enzyme‐linked immunosorbent assay (ELISA). Odontoblast differentiation capacity was assessed by alkaline phosphatase activity, alizarin red S staining, and western blotting analysis. hDPSCs were overexpressed or knocked down FoxO1 with lentiviruses. The regulatory interaction between FoxO1 and the DSPP promoter was evaluated through dual‐luciferase reporter assay and chromatin immunoprecipitation assay. Statistical analyses were conducted using Student's t‐test or one‐way analysis of variance (anova) with a p‐value of <.05 considered statistically significant.

Results

scRNA‐Seq data indicated a significant increase in B cells and ANGPTL1 expression in carious dental pulp. Functional analyses confirmed that ANGPTL1 secreted by B cells activated FoxO1 expression in hDPSCs, enhancing their differentiation into odontoblast‐like cells. Blocking ANGPTL1 signalling with a specific antibody reduced FoxO1 expression, indicating a regulatory link between ANGPTL1 and FoxO1. Overexpression of FoxO1 in hDPSCs promoted their differentiation into odontoblasts and facilitated mineralized matrix formation. Mechanistic studies revealed that FoxO1 directly binds to the DSPP promoter, thereby inducing its expression.

Conclusions

Our study reveals a novel mechanism in which ANGPTL1 secreted by B cells in a carious environment promotes the odontoblast differentiation of hDPSCs by upregulating FoxO1. This finding highlights a potential therapeutic target for enhancing dental pulp repair and regeneration.
Enhanced properties of (TaNbTiV)C high‐entropy carbide ceramics through controlled structure and morphology of high‐entropy carbide powders
Authors: Li Haitao , Chen Ruoyu , Liu Feng , Li Chengxin , Yang Xiaoyan , Li Saisai , Jia Wenbao
Published: February 2025

Submicron high‐entropy carbide (HEC) (TaNbTiV)C powders with various morphologies and properties were prepared using the molten salt method by adjusting structures and graphitization of carbon sources. Subsequently, the HEC ceramics were sintered at 1900°C using spark plasma sintering. Compared to traditional carbon sources (carbon black and flake graphite), powders synthesized using graphitic carbon microspheres with a spherical shape exhibited a smaller particle size of 0.45 µm, a larger specific surface area of 14.46 m2/g, and a larger lattice constant of 0.4451 nm. Moreover, the HEC powders prepared using graphitic carbon microspheres enhanced the sintering of the HEC matrix, leading to improved mechanical properties and oxidation resistance of the HEC ceramics compared to those prepared using other carbon sources. Unlike the precursor method used to adjust the HEC powder structure, the molten salt method is a low‐cost and straightforward approach to regulating the HEC powder structure by controlling the structure of raw material.
Microwave rapid synthesis of LiNi0.85Mn0.10Co0.05O2 positive electrode materials for lithium‐ion batteries
Authors: Koshika Yuki , Kaneda Haruki , Furuichi Yuki
Published: February 2025

Ni‐rich (Ni ≥80 atom%) layered oxides are promising candidates of positive electrode materials for lithium‐ion batteries because of high specific capacity, and reducing energy consumption during synthesis is important for mass production to reduce environmental impact. Microwave heating of Ni‐rich layered oxide is anticipated to enable much faster and more effective synthesis than conventional method; however, only a few studies have been reported. In this study, LiNi0.85Mn0.10Co0.05O2 (NMC85) positive electrode materials were prepared by preheating the mixture of Ni0.85Mn0.10Co0.05(OH)2 precursor and LiOH, followed by microwave heating at a rate of 28.3°C min−1 and holding at 850°C for 1 h. The specific discharge capacity in half‐cell of NMC85 synthesized by microwave heating was 190.0 mAh g−1. Although the capacity was still inferior to that of NMC85 synthesized by conventional heating method, which was one of the highest values among Ni‐rich layered oxide by microwave synthesis, owing to high crystallinity. Furthermore, much improvement of the electrochemical properties is expected by increasing uniformity during the microwave heating, because inhomogeneous crystal growth and cation mixing were observed. This study indicates the possibility to apply microwave heating for the synthesis of Ni‐rich layered oxide and improve the energy efficiency considerably.
Influence of Trainees' Transfer Beliefs, Intentions, and Commitment on Transfer Readiness: Variable and Person‐Oriented Analyses
Authors: González‐Ortiz de Zárate Aitana , Roig‐Ester Helena , Robalino Guerra Paulina E. , Garone Anja , Quesada‐Pallarès Carla
Published: February 2025

Transfer beliefs are understudied in the training transfer field, whereas structural equation modelling (SEM) has been a widely used technique to study transfer models. New methodologies are needed to study training transfer and network analysis (NA) has emerged as a new approach that provides a visual representation of a given network. We explored the relation of transfer beliefs, intentions, commitment, and implementation intentions, and transfer using variable (SEM) and person‐oriented approaches (NA) according to groups of trainees based on their transfer readiness. The longitudinal design measured T1 before the training and T2 after the training (268 participants). T1 measured trainees' beliefs about transfer, commitment to transfer, and intention to transfer; T2 measured self‐reported transfer and implementation intention actions. The results of the NA confirmed the structure of the exploratory factor analysis. The NA model offered the visual representation of the network complimentary to the results obtained via SEM. Differentiating NA and SEM multigroup by cluster showed differences in models and architectures between clusters. We discussed the relations between beliefs and transfer, and also the implications of the combined use of the SEM and NA as novel approaches to study transfer.
The impact of Ta2O5 in multinucleating agents on chemically strengthened MgO–Al2O3–SiO2 transparent glass‐ceramics
Authors: Xu Guoliang , Li Mengyong , Wang Fu , Liao Qilong , Gu Yuxin , Liu Laibao , Dong Junwei , Chen Jiajia , Li Guanghua , Li Lisheng
Published: February 2025

MgO–Al2O3–SiO2 (MAS) glass‐ceramics are significant due to their excellent mechanical properties. However, most of these glass‐ceramics are opaque and lack chemically strengthened capabilities. In this study, chemically strengthened transparent MAS glass‐ceramics were successfully synthesized by employing SnO2 + ZrO2 + Ta2O5 as a multinucleating agent. Systematic investigation was conducted using differential scanning calorimetry (DSC), X‐ray diffraction (XRD), transmission electron microscope (TEM), field emission scanning electron microscope (FE‐SEM), Scattered Light Photoelastic Stress Meter (SLP), and Vickers hardness measurements. The results show that Ta2O5 exhibits a good nucleation effect. With the increase of Ta2O5 content from 0 mol% to 0.5 mol%, the exothermic peak temperature of the precipitated crystals decreased from 976.3°C to 937.6°C. The primary crystalline phases precipitated in the MAS system were MgAl₂O₄ (PDF#21‐1152) and ZnAl₂O₄ (PDF#05‐0669), with secondary phases including SnO2 (PDF#46‐1088), ZrO2 (PDF#50‐1089), and Ta2O5 (PDF#21‐1198). TEM‐tested interplanar spacing data and electron diffraction ring data further confirmed the presence of these crystalline phases. At 0.5 mol% Ta2O5 content, after crystallization at 920°C, the average grain size was approximately 40.34 nm, with 86.57% transmittance at 550 nm. The Vickers hardness of the parent glass increased from 6.68 GPa to 7.17 GPa after heat treatment at 920°C. Following 5 h of ion exchange, Vickers hardness increased to 7.97 GPa, with surface compressive stress (CS) of 150.29 MPa and depth of layer (DOLzero) of 80.96 µm. After 24 h of ion exchange, Vickers hardness reached 8.16 GPa, with CS of 239.86 MPa and DOLzero of 93.28 µm. The conclusions provide new insights for further study of the MAS system and broaden its application field such as in cover materials.
Institutionalized Policy Evaluation within the Democratic System: Why? When? How?
Authors: Fumagalli Corrado
Published: February 2025

Philosophers have expressed concerns about elite capture at various stages of the democratic decision‐making process. However, there has been no sustained normative analysis of government‐driven feedback platforms that enable different actors to formulate recommendations for revising or canceling existing laws and policies. My article addresses and fills this gap. I contend that government‐driven feedback platforms serve a dual purpose of influencing the policy‐making process and demonstrating that decisions are open to revision. I also argue that these feedback platforms are intended to generate a normatively salient, forward‐looking, and balanced integration of technical knowledge and local knowledge, establishing the epistemic foundation for future deliberation. I then provide three normative standards that serve as a guide to balance expert knowledge with citizens' experience and values.
A Systematic Review of the Recent Research on the Usefulness of Chatbots for Language Education
Authors: Şahin Kızıl Aysel , Klimova Blanka , Pikhart Marcel , Parmaxi Antigoni
Published: February 2025

Background

The rise of intelligent chatbots powered by artificial intelligence and machine learning has ignited interest in their potential for revolutionising second language (L2) acquisition and foreign language learning (FLL). While their potential seems vast, understanding their actual impact on learning outcomes requires comprehensive analysis. Also required is the continuous evaluation of this technology due to the rapid pace of advancements in chatbots, highlighting the need for a fresh look using the latest research. This systematic review aims to address this need by investigating the effectiveness of modern chatbots in L2 learning and FLL, offering valuable insights for language educators and researchers.

Objectives

This study systematically reviews existing research to assess the usefulness of chatbots in L2 acquisition and FLL, identifying key areas of improvement and future research directions.

Methods

Following the PRISMA methodology, 33 relevant studies published between 2020 and May 2024 were analysed. Thematic analysis was employed to identify key themes related to chatbot applications, language skills impacted, and learning outcomes achieved.

Results

The findings clearly reveal specific language skills (i.e., speaking) and language knowledge (i.e., vocabulary) that have a significant impact on enhancing students' learning outcomes by using chatbots, while pointing out insufficient research in this area. The results also show major benefits of chatbots for FLL, such as individualised learning, immediate feedback, enhancing willingness to communicate, and increased interaction.

Conclusions

This systematic review highlights specific practical implications and suggestions that have a direct impact on the usefulness of chatbots in FLL and L2 acquisition, and a need to investigate further variables such as age, language skills, personality traits, or teacher's role with respect to the use of chatbots in foreign language classes. Further implications are also raised in terms of learning design considerations when such a technology is incorporated in the FLL classroom.
Beyond the Pipeline (Problem): Examining Racial and Ethnic Representation in 21st Century High Technology Self‐employment
Authors: Atkins Rachel Marie Brooks , Burrage April
Published: February 2025

Is the racial variation in the tech labor force and tech entrepreneurship associated with differences in STEM degree attainment? Using data from the American Community Survey, we examine whether racial disparities in tech employment and entrepreneurship reflect differences in STEM degree attainment within the labor force, a challenge known as the tech pipeline problem. We document that White workers are overrepresented in tech entrepreneurship, while Black, Hispanic, and Asian workers are underrepresented in tech entrepreneurship. Notably, Black workers are the only group underrepresented in tech employment relative to their share of the STEM‐‐educated labor force. Our findings suggest that gaps in STEM degree attainment account for only a small portion of the racial disparity in the tech labor force. We also find important differences in the relationship between STEM degree attainment, tech employment, and tech entrepreneurship by race. We conclude the paper with a proposed research agenda for further study.
Adverse Effects of Ultrasonic Instrumentation and Air Polishing on Dental Restorations: A Systematic Review of Laboratory Studies
Authors: Esati Jeronim , Amran Tarek , Weiger Roland , Alsulaimani Lujain , Blatz Markus B. , Eggmann Florin
Published: February 2025

Objective

The aim of this systematic review was to evaluate the effects of ultrasonic instrumentation and air polishing on surface roughness and marginal integrity of dental restorations, addressing their potential adverse impacts on various biomaterials.

Materials and Methods

A search of five databases, supplemented by manual searches, identified relevant laboratory studies. Forty‐two studies met the inclusion criteria, with data on surface roughness and marginal quality extracted for analysis. The RoBDEMAT tool was used to assess risk of bias.

Results

Ultrasonic instrumentation significantly increased roughness, particularly in resin‐modified glass ionomer cements and resin‐based composites, whereas zirconia and lithium disilicate were less affected. Air polishing, especially with sodium bicarbonate and calcium carbonate powders, also increased roughness. Erythritol and glycine powders were the least abrasive. Both ultrasonic scaling and air polishing negatively impacted marginal quality. The RoBDEMAT assessments revealed shortcomings in randomization, sample size justification, and blinding.

Conclusions

Ultrasonic instrumentation and air polishing can adversely affect dental restorations, with the degree of impact varying by biomaterial and debridement method. Low‐abrasive powders, such as erythritol and glycine, are recommended. Methodological refinements and clinical studies are needed to enhance the applicability of these findings to patient care.

Clinical Significance

This review highlights the critical need to choose appropriate debridement methods to minimize iatrogenic damage to dental restorations. Low‐abrasive air polishing powders, such as erythritol and glycine, are recommended for the removal of soft deposits and stains to preserve surface smoothness and marginal integrity.
Associations of Accelerometer‐Measured Physical Activity With Dementia, Anxiety, and Depression Among Older Adults
Authors: Stulberg Eric L. , Chou Lin‐Na , Gore Shweta , Conroy Molly B. , Majersik Jennifer J. , Hunzinger Katherine J. , LaPoint Alexander , Kaur Sandhu Mandeep , Schneider Andrea L. C. , Kumar Amit
Published: February 2025

Background

Higher physical activity (PA) is associated with better neuropsychiatric health, but prior studies have been limited by cross‐sectional designs, self‐reported PA measures, and small numbers of older individuals. We examined associations between baseline and changes in accelerometer‐measured moderate‐vigorous PA (MVPA) with neuropsychiatric health among individuals aged ≥ 70 years in the National Health and Aging Trends Study.

Methods

We used the average daily minutes of accelerometer‐measured MVPA above a validated threshold of 2184 counts per minute as a continuous measure at baseline for the exposure variable. For longitudinal analyses, we categorized change in MVPA as follows: an increase of > 20 min/day over 1 year, a decrease of > 20 min/day over 1 year, and staying within 20 min/day over 1 year. Our outcomes were possible/probable dementia and anxiety or depression. Associations were estimated using confounder‐adjusted logistic regressions.

Results

In our survey‐weighted analytic sample of 639 individuals aged ≥ 70 years, 56% were ≥ 75 years, and 53% were female. After adjusting for confounders, a 20‐min/day higher baseline MVPA was significantly associated with lower odds of possible/probable dementia 1 year later (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.83–0.96) but not with depression and anxiety symptoms. Compared to no change in PA over 1 year, an increase in MVPA by > 20 min/day was associated with decreased odds of depression and anxiety symptoms (OR = 0.06, 95% CI = 0.03–0.14) but not with possible/probable dementia. Compared to no change in MVPA over 1 year, a decrease in MVPA by > 20 min/day was associated with higher odds of possible/probable dementia (OR = 3.82, 95% CI = 1.34–10.87) but not with depression and anxiety symptoms.

Conclusions

Higher and increasing MVPA over time is associated with better neuropsychiatric health in individuals aged ≥ 70 years. Future studies should prioritize evaluating detailed PA trajectories to better understand how different doses, intensities, and modalities of PA impact neuropsychiatric decline in older adults.
Postpartum period according to Roy adaptation model: Assessment of fatigue, self‐esteem, functional status, and dyadic adjustment
Authors: Ataş Ayşe Nur , Özçalik Habibe Bay , Özerdoğan Nebahat
Published: February 2025

Objective

The study was conducted to examine the relationship between fatigue, self‐esteem, functional status, and dyadic adjustment in the postpartum period and the factors affecting them.

Methods

The study was designed in cross‐sectional type. It was carried out in the postpartum follow‐up clinic of a hospital in the Central Anatolian Region of Turkey between November 2021 and July 2022. Responses from a total of 328 mothers in the first 6 months postpartum were analyzed. Data were collected using a “Descriptive Information Form,” the “Chalder Fatigue Scale,” the “Rosenberg Self‐Esteem Scale,” the “Inventory of Functional Status after Childbirth,” and the “Revised Dyadic Adjustment Scale.”

Results

The mean scores of the mothers participating in the study on the total Chalder fatigue scale, Rosenberg self‐esteem scale, Inventory of functional status after childbirth, and Revised dyadic adjustment scale were 13.65 ± 6.13, 1.33 ± 1.33, 10.57 ± 2.02, and 51.51 ± 9.49, respectively. It was determined that fatigue had a positive effect and dyadic adjustment had a negative effect on the postpartum self‐esteem levels of the mothers. The progress of the postpartum period affects the functional status of mothers positively and significantly.

Conclusions

According to the results of the research, the decrease in fatigue and the increase in dyadic adjustment in women positively affect the increase in self‐esteem.