bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationships between breast cancer risk factors based on mammographic features
Authors: Ye Zhoufeng , Nguyen Tuong L. , Dite Gillian S. , MacInnis Robert J. , Schmidt Daniel F. , Makalic Enes , Al-Qershi Osamah M. , Bui Minh , Esser Vivienne F. C. , Dowty James G. , Trinh Ho N. , Evans Christopher F. , Tan Maxine , Sung Joohon , Jenkins Mark A. , Giles Graham G. , Southey Melissa C. , Hopper John L. , Li Shuai 
Published: October 2023

AbstractBackgroundMammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology.MethodsWe used digitised mammograms for 371 monozygotic twin pairs, aged 40–70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method.ResultsThe mammogram risk scores were correlated within twin pairs and with each other (r = 0.22–0.81; allP < 0.005). We estimated that 28–92% of the associations between the risk scores could be attributed to causal relationships between the scores, with the rest attributed to familial confounders shared by the scores. There was consistent evidence for positive causal effects: of Cirrus, light areas, and bright areas on the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively); and of light areas and bright areas on Cirrus (accounting for 37% and 28%, respectively).ConclusionsIn a mammogram, the lighter (less dense) areas have a causal effect on the brightest (highly dense) areas, including through a causal pathway via textural features. These causal relationships help us gain insight into the relative aetiological importance of different mammographic features in breast cancer. For example our findings are consistent with the brightest areas being more aetiologically important than lighter areas for screen-detected breast cancer; conversely, light areas being more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. These findings highlight the utility of ICE FALCON and family data in decomposing the associations between intercorrelated disease biomarkers into distinct biological pathways.
[1, 8]-Naphthyridine derivatives as dual inhibitor of alkaline phosphatase and carbonic anhydrase
Authors: Alrokayan Salman , Hussain Tajamul , Alamery Salman , Mohammed Arif Ahmed , Mahmood Abid , Ejaz Syeda Abida , Langer Peter , Iqbal Jamshed 
Published: October 2023

Abstract[1,8]-Naphthyridine derivatives have been reported to possess important biological activities and may serve as attractive pharmacophores in the drug discovery process. [1,8]-Naphthyridine derivatives (1a-1l) were evaluated for inhibitory potential for isozymes of carbonic anhydrase (CA) and alkaline phosphatase (ALP). CAs have been reported to carry out reversible hydration of CO2 into HCO3−, secretion of electrolytes, acid–base regulation, bone resorption, calcification, and biosynthetic reactions. Whereas ALPs hydrolyze monophosphate esters with the release of inorganic phosphate and play an important role in bone mineralization. Both enzymes have been found to be over-expressed and raised functional activities in patients suffering from rheumatoid arthritis. The discovery of dual inhibitors of these enzymes may provide a synergistic effect to cure bone disorders such as rheumatoid arthritis and ankylosing spondylitis. Among the test compounds, the most potent inhibitors for CA-II, CA-IX, and CA-XII were 1e, 1g, and 1a with IC50 values of 0.44 ± 0.19, 0.11 ± 0.03 and 0.32 ± 0.07 µM, respectively. [1,8]-Naphthyridine derivatives (1a–1l) were approximately 4 folds more potent than standard CA inhibitor acetazolamide. While in the case of ALPs, the most potent compounds for b-TNAP and c-IAP were 1b and 1e with IC50 values of 0.122 ± 0.06 and 0.107 ± 0.02 µM, respectively. Thus, synthesized derivatives proved to be 100 to 800 times more potent as compared to standard inhibitors of b-TNAP and c-IAP (Levamisole and L-phenyl alanine, respectively). In addition, selectivity and dual inhibition of [1,8]-Naphthyridine derivatives confer precedence over known inhibitors. Molecular docking and molecular simulation studies were also conducted in the present studies to define the type of interactions between potential inhibitors and enzyme active sites.
Maternal pre-pregnancy obesity modifies the association between first-trimester thyroid hormone sensitivity and gestational Diabetes Mellitus: a retrospective study from Northern China
Authors: Sun Honglin , Zhou Yibo , Liu Jia , Wang Ying , Wang Guang 
Published: October 2023

Abstract
Background
Contradictory relationships have been observed between thyroid function and gestational diabetes mellitus (GDM). Previous studies have indicated that pre-pregnancy BMI (pBMI) could modify their relationships. Few studies have illustrated the role of thyroid hormone sensitivity on GDM. We aimed to explore the effect of pre-pregnancy obesity on the association between early pregnancy thyroid hormone sensitivity and GDM in euthyroid pregnant women.

Methods
This study included 1310 women with singleton gestation. Subjects were classified into pre-pregnancy obese and non-obese subgroups by pBMI levels with a cutoff of 25 kg/m2. Sensitivity to thyroid hormone was evaluated by Thyroid Feedback Quartile-Based Index (TFQI), Chinese-referenced parametric TFQI (PTFQI), TSH Index (TSHI) and Thyrotrophic T4 Resistance Index (TT4RI). The associations between these composite indices and GDM were analyzed using multivariate regression models in the two subgroups, respectively.

Results
In pre-pregnancy non-obese group, early pregnancy TFQI, PTFQI, TSHI and TT4RI levels were higher in subjects with incident GDM compared to those without GDM (all P < 0.05). By contrast, obese women with GDM exhibited lower levels of those indices (all P < 0.05). The occurrence of GDM were increased with rising TFQI, PTFQI, TSHI and TT4RI quartiles in non-obese women ( all P for trend < 0.05), while exhibited decreased trend across quartiles of those indices in obese women (all P for trend < 0.05). Further logistic analysis indicated contrary relationships between thyroid hormone sensitivity and the occurrence of GDM in the two groups, respectively. The OR of the fourth versus the first quartile of TFQI for GDM was 1.981 (95% CI 1.224, 3.207) in pre-pregnancy non-obese group, while was 0.131 (95% CI 0.036, 0.472) in pre-pregnancy obese group. PTFQI and TSHI yielded similar results.

Conclusions
The association between maternal sensitivity to thyroid hormones during early gestation and the occurrence of GDM was modified by pre-pregnancy obesity.
Regulatory mechanism of LncRNAs in gonadal differentiation of hermaphroditic fish, Monopterus albus
Authors: Hu Qiaomu , Xia Xueping , Lian Zitong , Tian Haifeng , Li Zhong 
Published: October 2023

Abstract
Background
Monopterusalbus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism of the sex reversal was unknown.

Methods
We produced transcriptomes containing mRNAs and lncRNAs in the crucial stages of the gonad, including the ovary, ovotestis and testis. The expression of the crucial lncRNAs and their target genes was detected using qRT‒PCR and in situ hybridization. The methylation level and activity of the lncRNA promoter were analysed by applying bisulfite sequencing PCR and dual-luciferase reporter assays, respectively.

Results
This effort revealed that gonadal development was a dynamic expression change. Regulatory networks of lncRNAs and their target genes were constructed through integrated analysis of lncRNA and mRNA data. The expression and DNA methylation of the lncRNAs MSTRG.38036 and MSTRG.12998 and their target genes Psmβ8 and Ptk2β were detected in developing gonads and sex reversal gonads. The results showed that lncRNAs and their target genes exhibited consistent expression profiles and that the DNA methylation levels were negatively regulated lncRNA expression. Furthermore, we found that Ptk2β probably regulates cyp19a1 expression via the Ptk2β/EGFR/STAT3 pathway to reprogram sex differentiation.

Conclusions
This study provides novel insight from lncRNA to explore the potential molecular mechanism by which DNA methylation regulates lncRNA expression to facilitate target gene transcription to reprogram sex differentiation in M.albus, which will also enrich the sex differentiation mechanism of teleosts.
Peer support interventions in maternal and child healthcare delivery in sub-Saharan Africa: protocol for a realist review
Authors: Dugle Gordon , Antwi John , Quentin Wilm 
Published: October 2023

Abstract
Background
Peer support has been proposed as a promising policy intervention for addressing adverse maternal and child healthcare (MCH) outcomes in sub-Saharan Africa (SSA). Existing reviews on peer support largely draw on evidence from high-income countries or focus on single services like breastfeeding, nutrition or postnatal care. In contrast, this review aims to provide a comprehensive overview of the empirical literature on peer support interventions across various MCH services in sub-Saharan Africa. Specifically, we aim to understand how, why, for whom, and in what circumstances different forms of MCH peer support interventions contribute to improving healthcare outcomes in sub-Saharan Africa.

Methods
This review follows five iterative steps for undertaking realist reviews (1) defining the review scope; (2) developing initial programme theories; (3) searching for evidence; (4) selecting and appraising evidence; and (5) extracting, analysing and synthesising evidence. Four databases–Cochrane Library, PubMed, CINAHL, and EMBASE–were repeatedly searched between March and June 2021. From a large volume of records retrieved from the database and citation search, 61 papers have been selected for review. We will conduct a second search of the same database covering June 2021 to the present before the final extraction and synthesis. The final list of selected papers will be imported into NVivo 12 software and organised, extracted, analysed and synthesised iteratively to examine and illustrate the causal links between contexts, mechanisms and outcomes of MCH peer support interventions in SSA. We have drawn on the existing literature on peer support in healthcare generally to develop initial programme theories. We will then use the empirical literature on MCH peer support interventions in SSA, inputs from a stakeholders’ workshop in Ghana and a conference presentation to refine the initial programme theory.

Discussion
The review will develop an explicit theory of peer support intervention in healthcare delivery and provide insights for developing evidence-informed policy on the intervention. Drawing lessons from the different national contexts and diverse areas of MCH in SSA, the review will provide an analytically generalizable programme theory that can guide intervention design and implementation. While focusing on MCH peer support interventions in SSA, the review contributes to evolving conversations on the use of theory for health policy planning and complex intervention design and implementation globally.

Trial registration
PROSPERO registration ID: CRD42023427751.
Universal approximation property of a continuous neural network based on a nonlinear diffusion equation
Authors: Honda Hirotada 
Published: October 2023

AbstractRecently, differential equation-based neural networks have been actively studied. This paper discusses the universal approximation property of a neural network that is based on a nonlinear partial differential equation (PDE) of the parabolic type.Based on the assumption that the activation function is non-polynomial and Lipschitz continuous, and applying the theory of the difference method, we show that an arbitrary continuous function on any compact set can be approximated using the output of the network with arbitrary precision. Additionally, we present an estimate of the order of accuracy with respect to △t and △x.
Attachment insecurity and breadcrumbing engagement in young adults: a cross-sectional, cross-country study in India and Spain
Authors: Khattar Vivek , Huete Nuria , Navarro Raúl 
Published: October 2023

AbstractBackgroundBreadcrumbing, defined as the act of sending out flirtatious, but non-committal text messages to lure a sexual/romantic partner without expending much effort, has gained attention in popular culture and the media due to its relevance to contemporary dating dynamics. However, there is lack of evidence of the association between attachment insecurity and breadcrumbing This study aims to uncover the potential relationship between breadcrumbing engagement and attachment insecurity among Indian and Spanish young adults.MethodsData were collected through an anonymous online survey answered by 334 adults in India and by 348 adults in Spain aged between 18 and 40 years old. A linear regression model in both countries was run to examine breadcrumbing engagement and its relationship with the set of sociodemographic variables included in the study (participants’ age and sex, sexual orientation, relationship status and educational level) and the two dimensions of attachment insecurity (anxious and avoidant).ResultsThe results showed that insecure attachment, both anxious and avoidant, were associated with engaging in breadcrumbing in both the countries. However, there was a stronger association between anxious attachment and breadcrumbing in India compared to Spain, where the association was stronger between avoidant attachment and breadcrumbing.ConclusionsFindings from this study offer insight into an under-studied practice in the context of interpersonal relationships (i.e., breadcrumbing behaviour) and show the importance of attachment theoretical framework to hypothesize and analyse expectations regarding strategies to negotiate intimate relationships and the breadcrumbing experience particularly.
The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760
Authors: Cacanyiova Sona , Cebova Martina , Simko Fedor , Baka Tomas , Bernatova Iveta , Kluknavsky Michal , Zorad Stefan , Krskova Katarina , Shaman Ezgi , Zemancikova Anna , Barta Andrej , Aydemir Basak G. , Berenyiova Andrea 
Published: October 2023

Abstract
Background
Angiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN).

Results
Zofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect.

Conclusions
Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.
In silico analysis of missense SNPs in GABRA1, GABRB1, and GABRB3 genes associated with some diseases in neurodevelopmental disorders
Authors: Manaz Mehmet , Karasakal Ömer Faruk , Özkan Oktay Ebru , Karahan Mesut 
Published: October 2023

Abstract
Background
Neurodevelopmental disorders are disorders that are generally seen in the early developmental period of an individual's life and involve more than one disease that causes disruptions in the central nervous system. These disorders can be given as examples of diseases such as autism, mental retardation, some epileptic disorders, communication disorders, and mental retardation. The aim of this study is to determine the possible harmful effects of missense single nucleotide polymorphisms (SNPs) in the GABRA1, GABRB1, and GABRB3 genes, which are associated with neurodevelopmental disorders, on the structure and stabilization of the protein, using in silico methods. Software tools SIFT, PolyPhen-2 HumVar, PolyPhen-2 HumDiv, PROVEAN, SNAP2, PHD-SNP, SNP&GO, PANTHER, and Meta-SNP were used to predict harmful SNPs. I-Mutant and MUpro software tools were used to predict the effects of predicted harmful SNPs on protein stabilization. The STRING software tool was used for protein–protein interactions, the GeneMANIA software tool for gene–gene interactions, and the Project HOPE software tool for three-dimensional modeling examples.

Results
As a result of the bioinformatics analysis, rs121434579, rs139163545, and rs267600530 in the GABRA1 gene; rs74608570, rs75612351, rs78815529 in the GABRB1 gene, and rs7819600779, rs1719850690, rs7819600779, rs171985060690, rs7819600779, rs1719850600779, rs149963014 in the GABRB3 gene were predicted as harmful SNPs.

Conclusions
In this study, protein structure, function, and stabilization of SNPs known to cause amino acid substitutions in GABRA1, GABRB1, and GABRB3 genes associated with some diseases in neurodevelopmental disorders were investigated using bioinformatics tools. As a result of the results obtained in our study, it is thought that it will benefit experimental studies and bioinformatics studies.
Fabrication and characterization of multiphase bituminous materials for cold region pavements
Authors: Wang Di , Cannone Falchetto Augusto , Zhang Fan , Riccardi Chiara , Sun Yuxuan 
Published: October 2023

AbstractIn this study, the low temperature creep properties of multiphase bituminous materials (binder, mastic, Fine Aggregate Matrix—FAM, and mixture) were experimentally evaluated, and the impact of size effect on FAM and mixture specimen was also assessed. First, the mix design of mastic and FAM was performed based on the reference mixture Asphalt Concrete (AC) 22 TS. The mathematical adaptation to the boundary sieve method was applied to calculate FAM gradation and binder content. Next, a preparation method was proposed to produce Fine Aggregate Matrix (FAM) in a laboratory environment, and scale-up slab samples were also fabricated for FAM and mixture specimens to evaluate the size effect phenomenon. Finally, three-point bending (3 PB) creep tests were conducted on the multiphase bituminous specimens with different dimensions at -6 °C, -12 °C, and -18 °C with a modified Bending Beam Rheometer (BBR) device and a dynamic loading machine, depending on the sample size. Results indicate that the creep stiffness of the FAM was close to mixtures and much higher than the one observed in binder and mastic. The proposed fabrication approach provides a satisfactory method for preparing a representative FAM phase in the mixture, while the air voids can be easily adjusted during the slab compaction procedure. This study supports the idea of using FAM to discriminate asphalt mixtures for cold regions. The correlation between up-scaled FAM and mixture specimens should be further investigated, including different mixture types and corresponding FAM.
Transformative technologies in medicine: a primer for psychiatrists
Authors: Mayfield Neil , Ker Suzy , Steele Rachel , Wright Stephen 
Published: October 2023

SUMMARYAcross medicine, key scientific advances in the past couple of decades have deepened knowledge of fundamental mechanisms of disease, leading to new treatments and the possibility of increased personalisation of care. Some of the most important developments in fields as diverse as immunology, the microbiome, genetics, stem cells and artificial intelligence are summarised in this article to raise awareness among psychiatrists and to help understand the opportunities and challenges they may present for mental healthcare in the future.