bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial changes of systemic ventricular function and atrioventricular valve function in patients with failing Fontan
Authors: Matsubara Muneaki , Dahmen Vincent , Gaebert Paula , Palm Jonas , Niedermaier Carolin , Osawa Takuya , Schaeffer Thibault , Heinisch Paul Philipp , Röhlig Christoph , Piber Nicole , Hager Alfred , Ewert Peter , Hörer Jürgen , Ono Masamichi 
Published: January 2025

Abstract

OBJECTIVES
This study investigated the longitudinal changes in ventricular function and atrioventricular valve function to clarify the timing and the mechanisms of failing Fontan.

METHODS
Patients who underwent total cavopulmonary connection between 1994 and 2023 were reviewed, and longitudinal echocardiographic examinations of ventricular function and atrioventricular valve regurgitation were analysed.

RESULTS
A total of 650 patients were included. The most frequent primary diagnosis was hypoplastic left heart syndrome in 175 patients. Dominant right ventricle was observed in 337 patients (51.8%). The median age at total cavopulmonary connection was 2.3 (1.8–3.3) years. Failing Fontan was observed in 78 patients (12%) during the median follow-up of 6.2 years. Among them, dominant right ventricle was observed in 51 patients (65.4%). Patients with protein-losing enteropathy or plastic bronchitis (n = 37) developed Fontan failure early (median 2.6 years post-total cavopulmonary connection). Still, patients maintained ventricular function (93.1% normal at 5 years) and atrioventricular valve competence (no case of moderate/severe regurgitation at 5 years) over time. Patients who developed failing Fontan associated with progression of heart failure (n = 41) had later onset (median 8.3 years post-total cavopulmonary connection) but indicated progressive ventricular dysfunction (68.3% normal at 5 years, 53.8% normal at 10 years) and atrioventricular valve regurgitation (12.3% moderate/severe at 5 years, 15.3% moderate/severe at 10 years).

CONCLUSIONS
Patients with failing Fontan indicated different serial ventricular and atrioventricular valve function profiles. Ventricular function was preserved in failing Fontan patients with protein-losing enteropathy or plastic bronchitis, whereas progressive ventricular dysfunction was observed in failing Fontan patients with heart failure.
Functional test of a naturally occurred tumor modifier gene provides insights to melanoma development
Authors: Garcia-Olazabal Mateo , Adolfi Mateus Contar , Wilde Brigitta , Hufnagel Anita , Paudel Rupesh , Lu Yuan , Meierjohann Svenja , Rosenthal Gil G , Schartl Manfred 
Published: January 2025

Abstract
Occurrence of degenerative interactions is thought to serve as a mechanism underlying hybrid unfitness in most animal systems. However, the molecular mechanisms underpinning the genetic interaction and how they contribute to overall hybrid incompatibilities are limited to only a handful of examples. A vertebrate model organism, Xiphophorus, is used to study hybrid dysfunction, and it has been shown from this model that diseases, such as melanoma, can occur in certain interspecies hybrids. Melanoma development is due to hybrid inheritance of an oncogene, xmrk, and loss of a co-evolved tumor modifier. It was recently found that adgre5, a G protein-coupled receptor involved in cell adhesion, is a tumor regulator gene in naturally hybridizing Xiphophorus species Xiphophorus birchmanni (X. birchmanni) and Xiphophorus malinche (X. malinche). We hypothesized that 1 of the 2 parental alleles of adgre5 is involved in regulation of cell growth, migration, and melanomagenesis. Accordingly, we assessed the function of adgre5 alleles from each parental species of the melanoma-bearing hybrids using in vitro cell growth and migration assays. In addition, we expressed each adgre5 allele with the xmrk oncogene in transgenic medaka. We found that cells transfected with the X. birchmanni adgre5 exhibited decreased growth and migration compared to those with the X. malinche allele. Moreover, X. birchmanni allele of adgre5 completely inhibited melanoma development in xmrk-transgenic medaka, while X. malinche adgre5 expression did not exhibit melanoma suppressive activity in medaka. These findings provide evidence that adgre5 is a natural melanoma suppressor and provide new insight in melanoma etiology.
Now is the time to introduce new innovative assisted reproduction methods to implement accessible, affordable, and demonstrably successful advanced infertility services in resource-poor countries
Authors: Ombelet Willem , Van Blerkom Jonathan , Boshoff Gerhard , Huyser Carin , Lopes Federica , Nargund Geeta , Sallam Hassan , Vanmechelen Koen , Campo Rudi 
Published: January 2025

Abstract
Nearly 200 million people worldwide suffer from infertility. Disparities exist between developed and developing countries due to differences in the availability of infertility care, different reimbursement policies and socio-cultural differences surrounding procreation. In low- and middle-income countries, specialized infertility centres are either scarce or non-existent, mostly in private settings, and accessible only to the fortunate few who can afford them. The success and sustainability of ARTs will depend on our ability to optimize these techniques in terms of availability, affordability, and effectiveness. A low-cost, simplified IVF system has been developed and shown to be safe, cost-effective, and widely applicable to low-resource settings. Combined with inexpensive mild ovarian stimulation protocols, this could become a truly effective means of treating infertility and performing assisted reproduction at affordable prices, but only if such programmes are sincerely desired and supported by all relevant stakeholders. A receptive political, governmental, and clinical community is essential.
Boundedness of Stable Minimal Models With KLT Singularities
Authors: Zhu Minzhe 
Published: January 2025

Abstract
We investigate the singularities and boundedness of a special kind of algebraic varieties so-called stable minimal models, which are constructed and studied by Birkar in [6, 8]. Given a klt stable minimal model with bounded relative volume, if we fix the dimension, Iitaka volume, and a DCC set controlling coefficients, then we show that the singularities of the klt stable minimal model can be controlled uniformly. Furthermore, we prove that with certain bounded data, stable minimal models with klt singularities form a bounded family.
Intimate partner violence and maternal antenatal care utilization: is there a dose-response relationship? Findings from the Ethiopian National Demographic and Health Survey
Authors: Mekonnen Bazie , Gebremariam Abebe , Deyessa Negussie , Cranmer John N 
Published: January 2025

Abstract

Background
Maternal mortality in sub-Saharan Africa (SSA) is an enduring public health challenge. Adequate utilization of antenatal care (ANC) services is one strategy to mitigate the problem by identifying and managing pregnancy risks early. Yet, in SSA, uptake of ANC remains low. Intimate partner violence (IPV) may be a deterrent to ANC uptake. We measured the dose–response relationship between IPV and adequate ANC utilization (defined as four or more visits [ANC-4]) using data from the Ethiopia Demographic and Health Survey (EDHS) 2016.

Methods
We used complex sample logistic regression to measure the impact of three IPV subscales (emotional, sexual and physical) on ANC-4 while controlling for sociodemographic, obstetric and women empowerment factors.

Results
A total of 2599 (weighted) currently married or in-union women were included. There was a significant dose–response relationship between IPV and ANC utilization. Emotional (adjusted odds ratio [aOR] 0.78 [confidence interval {CI} 0.64 to 0.97]) and sexual (aOR 0.68 [CI 0.50 to 0.92]) violence decreased ANC-4 uptake while controlling for the covariates.

Conclusions
IPV is common, yet often invisible, in Ethiopia. Health workers may begin directly screening pregnant women for IPV in order to increase targeted support of ANC uptake. This is the first known study to confirm IPV has a dose–response relationship with ANC-4 uptake.
Individualization of piperacillin dosage based on therapeutic drug monitoring with or without model-informed precision dosing: a scenario analysis
Authors: Haefliger David , Mina Lynn , Guidi Monia , Marzolini Catia , Thoueille Paul , Rothuizen Laura E , Thoma Yann , Decosterd Laurent A , Guery Benoit , Girardin François R , Buclin Thierry 
Published: January 2025

Abstract

Background
Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.

Objectives
To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.

Methods
Measurements from 80 courses of intermittent piperacillin infusions, each with two TDM samples, were retrospectively submitted to our MIPD software TUCUXI. We considered six dosage adjustment strategies: identical dosage for all (4000 mg q8h), actual initial dosage (chart-based), actual empirical adjustment following first TDM, a priori MIPD-based dosage, a posteriori MIPD-based adjustment after first TDM and MIPD including both TDM measurements. Dosing strategies were compared regarding daily dosage, trough levels distribution and PTA (with target trough 8–32 mg/L).

Results
Median trough concentration fell within 8–32 mg/L for all strategies except a priori MIPD-based dosage (42 mg/L). Distributions of trough concentrations predicted with the six dosage adjustment strategies showed significant differences, with both a posteriori MIPD-based strategies best reducing their standard deviation (P &lt; 0.001). PTA of 32%, 32%, 55%, 29%, 83% and 94% were estimated, respectively for the six strategies (P &lt; 0.001). Poor performance of a priori MIPD-based dosage did not hinder a posteriori MIPD-based strategies from significantly improving target attainment.

Conclusions
Whilst empirical TDM improves exposure standardization and target attainment compared with no TDM, MIPD can still bring further improvement. Prospective trials remain warranted to confirm MIPD benefits not only on target attainment but also on clinical endpoints.
Semi-supervised learning from small annotated data and large unlabeled data for fine-grained Participants, Intervention, Comparison, and Outcomes entity recognition
Authors: Chen Fangyi , Zhang Gongbo , Fang Yilu , Peng Yifan , Weng Chunhua 
Published: January 2025

Abstract

Objective
Extracting PICO elements—Participants, Intervention, Comparison, and Outcomes—from clinical trial literature is essential for clinical evidence retrieval, appraisal, and synthesis. Existing approaches do not distinguish the attributes of PICO entities. This study aims to develop a named entity recognition (NER) model to extract PICO entities with fine granularities.

Materials and Methods
Using a corpus of 2511 abstracts with PICO mentions from 4 public datasets, we developed a semi-supervised method to facilitate the training of a NER model, FinePICO, by combining limited annotated data of PICO entities and abundant unlabeled data. For evaluation, we divided the entire dataset into 2 subsets: a smaller group with annotations and a larger group without annotations. We then established the theoretical lower and upper performance bounds based on the performance of supervised learning models trained solely on the small, annotated subset and on the entire set with complete annotations, respectively. Finally, we evaluated FinePICO on both the smaller annotated subset and the larger, initially unannotated subset. We measured the performance of FinePICO using precision, recall, and F1.

Results
Our method achieved precision/recall/F1 of 0.567/0.636/0.60, respectively, using a small set of annotated samples, outperforming the baseline model (F1: 0.437) by more than 16%. The model demonstrates generalizability to a different PICO framework and to another corpus, which consistently outperforms the benchmark in diverse experimental settings (P-value &lt; .001).

Discussion
We developed FinePICO to recognize fine-grained PICO entities from text and validated its performance across diverse experimental settings, highlighting the feasibility of using semi-supervised learning (SSL) techniques to enhance PICO entities extraction. Future work can focus on optimizing SSL algorithms to improve efficiency and reduce computational costs.

Conclusion
This study contributes a generalizable and effective semi-supervised approach leveraging large unlabeled data together with small, annotated data for fine-grained PICO extraction.
Automating pharmacovigilance evidence generation: using large language models to produce context-aware structured query language
Authors: Painter Jeffery L , Chalamalasetti Venkateswara Rao , Kassekert Raymond , Bate Andrew 
Published: January 2025

Abstract

Objective
To enhance the accuracy of information retrieval from pharmacovigilance (PV) databases by employing Large Language Models (LLMs) to convert natural language queries (NLQs) into Structured Query Language (SQL) queries, leveraging a business context document.

Materials and Methods
We utilized OpenAI’s GPT-4 model within a retrieval-augmented generation (RAG) framework, enriched with a business context document, to transform NLQs into executable SQL queries. Each NLQ was presented to the LLM randomly and independently to prevent memorization. The study was conducted in 3 phases, varying query complexity, and assessing the LLM’s performance both with and without the business context document.

Results
Our approach significantly improved NLQ-to-SQL accuracy, increasing from 8.3% with the database schema alone to 78.3% with the business context document. This enhancement was consistent across low, medium, and high complexity queries, indicating the critical role of contextual knowledge in query generation.

Discussion
The integration of a business context document markedly improved the LLM’s ability to generate accurate SQL queries (ie, both executable and returning semantically appropriate results). Performance achieved a maximum of 85% when high complexity queries are excluded, suggesting promise for routine deployment.

Conclusion
This study presents a novel approach to employing LLMs for safety data retrieval and analysis, demonstrating significant advancements in query generation accuracy. The methodology offers a framework applicable to various data-intensive domains, enhancing the accessibility of information retrieval for non-technical users.
Environmental stress differentially affects phenotypic modularity and fluctuating asymmetry in generalist and specialist cactophilic Drosophila
Authors: Vrdoljak Juan , Soto Ignacio María , Carreira Valeria Paula , Padró Julian 
Published: January 2025

Abstract
Modularity and developmental (in)stability have the potential to influence phenotype production and, consequently, the evolutionary trajectories of species. Depending on the environmental factors involved and the buffering capacity of an organism, different developmental outcomes are expected. Cactophilic Drosophila species provide an established eco-evolutionary model with well-studied ecological conditions, making them ideal for studying these phenomena. Here, we investigated how variations in larval diet and exposure to alkaloids on primary and secondary host plants affect the degree of integration/modularity and fluctuating asymmetry (FA, a proxy for developmental instability) of wing shape in two sibling species with different degrees of specialisation: Drosophila buzzatii (generalist) and Drosophila koepferae (specialist). Additionally, we compared the anterior–posterior modular configuration with a recently proposed proximal–distal modular configuration. Our results revealed greater independence among proximal–distal modules compared to anterior–posterior modules. Moreover, we observed sex-specific responses, with males exhibiting greater susceptibility to stressful environments than females. Each species showed a particular trait pattern across treatments: D. buzzatii showed increased integration and FA when reared in a nutrient-poor, alkaloid-rich secondary host, while D. koepferae displayed similar responses in novel environments characterised by double doses of alkaloids on the secondary host plant. These findings align with the generalist-specialist paradigm, suggesting that specialists may be challenged by novel environments, whereas generalists may be more affected by stressful conditions. Our study highlights the importance of considering each part of the proximal–distal wing axis independently, and the need to consider ecological-evolutionary history when investigating the relationship between complex phenotypic traits and environmental stress.
The Effect of Asset Encumbrance on Bank Behavior: Evidence from the Introduction of Covered Bonds in Norway
Authors: Cao Jin , Juelsrud Ragnar E , Sondershaus Talina 
Published: January 2025

Abstract
We use the introduction of covered bonds in Norway in 2007 together with administrative and supervisory data at the bank and loan level to investigate the effect of asset encumbrance, that is, pledging assets as collateral, on the composition of bank balance sheets and bank risk. We show that covered bonds—despite being collateralized with mortgages—lead to a shift in bank lending from mortgages to corporate loans. The marginal corporate borrower is young and low-rated, suggesting that overall credit risk increases. At the same time, we find that balance sheet liquidity increases. Overall, the beneficial effects of increased liquidity on bank risk outweighs any negative effects of increased credit risk, ultimately reducing risk premia on total and unsecured funding. The effects are driven by banks with initially low net holdings of liquid assets and low firm credit risk in their lending portfolios.
Incidence and prognostic implications of prostate-specific antigen persistence and relapse after radical prostatectomy: population-based study
Authors: Scilipoti Pietro , Garmo Hans , Gedeborg Rolf , Robinson David , Stattin Pär , Westerberg Marcus 
Published: January 2025

Abstract

Background
There has been a wide range in incidence of prostate-specific antigen (PSA) persistence and relapse after radical prostatectomy (RP) for prostate cancer (PCa). We aimed to describe incidence and prognostic implications of PSA persistence and relapse.

Methods
Register-based cohort study in Sweden of men diagnosed with PCa between 2007 and 2020 who underwent RP. Risks were estimated using competing risk cumulative incidence curves. Treatment after persistence or relapse and risk of PCa death and other causes were stratified according to persistence, European Association of Urology relapse risk groups, time to relapse, and life expectancy based on age and comorbidities.

Results
Among 10 700 men, the 10-year risk of PSA persistence or relapse after RP was 34% (95% confidence interval = 32% to 35%). Within 12 months of persistence/relapse, 75% of men with persistence, high-risk relapse, or early relapse (&lt;2 years) received treatment. The 10-year risk of PCa death ranged from 12% for men with persistence to 2% in men with low-risk relapse, whereas death from other causes ranged from 11% to 16%. Risk of PCa death was 8.5% after early relapse (&lt;2 years) and 1.4% after late relapse (&gt;5 years).

Conclusions
This population-based study estimated that one-third of men would have PSA persistence or relapse within 10 years from RP. There was a wide range in risk of death from PCa according to cancer characteristics and time to relapse. Risk of death from other causes was substantial. These factors, along with life expectancy, should inform treatment decisions for men with persistence or relapse.
Resolving spatially distinct phytohormone response zones in Arabidopsis thaliana roots colonized by Fusarium oxysporum
Authors: Calabria Jacob , Wang Liu , Rast-Somssich Madlen I , Chen Hsiang-Wen , Watt Michelle , Persson Staffan , Andersen Tonni Grube , Idnurm Alexander , Somssich Marc 
Published: January 2025

Abstract
Jasmonic acid (JA), ethylene (ET), and salicylic acid (SA) are the three major phytohormones coordinating plant defense responses, and all three are implicated in the defense against the fungal pathogen Fusarium oxysporum. However, their distinct modes of action and possible interactions remain unknown, in part because all spatial information on their activity is lacking. Here, we set out to probe this spatial aspect of plant immunity by using live microscopy with newly developed fluorescence-based transcriptional reporter lines. We have created a GreenGate vector collection of Plant Immune system Promoters (GG-PIPs) that allow us to image local activation of immune pathways with single-cell resolution. Using this system, we demonstrated that SA and JA act spatially separately from each other in distinct sets of root cells neighboring the fungal colonization site, while ET contributed to both sets. SA and ET induced the hypersensitive response as a first line of defense, while JA and ET governed active defense against the pathogen in a separate, second line of defense. Such an approach to resolve plant immune responses on an individual cell level has been lacking, and this work demonstrates that this microscopy-based approach can contribute to understanding plant immune responses in detail.
Read Length Dominates Phylogenetic Placement Accuracy of Ancient DNA Reads
Authors: Bettisworth Ben , Psonis Nikolaos , Poulakakis Nikos , Pavlidis Pavlos , Stamatakis Alexandros 
Published: January 2025

Abstract
A common problem when analyzing ancient DNA data is to identify the species that corresponds to the recovered analyzing ancient DNA sequence(s). The standard approach is to deploy sequence similarity-based tools, such as BLAST. However, as analyzing ancient DNA reads may frequently stem from unsampled taxa due to extinction, it is likely that there is no exact match in any database. As a consequence, these tools may not be able to accurately place such reads in a phylogenetic context. Phylogenetic placement is a technique where a read is placed onto a specific branch of a phylogenetic reference tree, which allows for a substantially finer resolution when identifying reads. Prior applications of phylogenetic placement have deployed only on data from extant sources. Therefore, it is unclear how the analyzing ancient DNA damage affects phylogenetic placement’s applicability to analyzing ancient DNA data. To investigate how analyzing ancient DNA damage affects placement accuracy, we re-implemented a statistical model of analyzing ancient DNA damage. We deploy this model, along with a modified version of the existing assessment pipeline PEWO, to 7 empirical datasets with 4 leading tools: APPLES, EPA-Ng, pplacer, and RAPPAS. We explore the analyzing ancient DNA damage parameter space via a grid search in order to identify the analyzing ancient DNA damage factors that exhibit the largest impact on placement accuracy. We find that the frequency of DNA backbone nicks (and consequently read length) has the, by far, largest impact on analyzing ancient DNA read placement accuracy, and that other factors, such as misincorporations, have a negligible effect on overall placement accuracy.