bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferenceless coded aperture correlation holography for five-dimensional imaging of 3D space, spectrum and polarization
Authors: Joshi Narmada , Tiwari Vipin , Kahro Tauno , Xavier Agnes Pristy Ignatius , Tahara Tatsuki , Kasikov Aarne , Kukli Kaupo , Juodkazis Saulius , Tamm Aile , Rosen Joseph , Anand Vijayakumar
Published: January 2025

Interferenceless coded aperture correlation holography (I-COACH) is a robust imaging technique for recovering three-dimensional object information using incoherent holography without two-beam interference. In this study, five-dimensional (5D) imaging along 3D space, spectrum and polarization in I-COACH is proposed and experimentally demonstrated for the first time. The proposed technique exploits the polarization-dependent light modulation characteristics of spatial light modulators to record polarization-dependent intensity distributions, which are distinguished by significant blurring between orthogonal polarization states. 5D I-COACH is implemented by inter-connecting all five dimensions in a single frame, and image recovery is attempted from different configurations of recorded point spread intensity distributions and response-to-object intensity distributions along 5D using recently developed deconvolution techniques. The simulation and experimental results confirm the 5D imaging capabilities of I-COACH. The proposed technique can be a useful tool for birefringence microscopy, and functional and structural imaging applications.
Constitutive modelling of non-crystalline solids using Van der Waals Potential
Authors: Kumar Raj , Mahata Paritosh
Published: January 2025

Non-crystalline solid materials have significant applications in the domains of science and engineering. This study focuses on the use of fundamental concepts of molecular interactions to develop a constitutive equation that can predict the stress-stretch behaviors of these materials. The strain energy density function of the material is derived using Helmholtz free energy of van der Waals potential. It is obtained in terms of excluded volume and number density of the molecules. To make consistent with continuum approximation, the excluded volume and number density are defined in terms of strain invariants of right Cauchy-Green deformation tensor. Finally, the constitutive model is represented in the form of Cauchy stress tensor. The current model is used for predicting finite deformation of non-crystalline solid phase of material. The results derived from the current model are also compared with the experimental results of polyurethane foam and poly vinyl alcohol gel materials. The current constitutive model can also be used for predicting the deformation characteristics of micro/nano components used in engineering systems. This study can provide a basis for the future scope of the constitutive modelling for the non-crystalline solid materials considering their complex molecular structures.
High performance energy-saving electrocatalysts for hydrogen evolution reaction: a minireview on the influence of structure and support
Authors: Zuo Chunyan , Hu Hengyuan , Han Meisheng , Qiu Yejun , Tao Guohua
Published: January 2025

Generating hydrogen from water electrolysis is a promising clean energy strategy that may help alleviate energy crisis, which stimulates tremendous research interests in searching high performance catalysts with low energy consumption. Here, we review recent progresses on the development of high performance electrocatalysts for hydrogen evolution reaction (HER) from the energy consumption perspective. A universal energy label based on energy conversion efficiency (ECE) is proposed to evaluate the HER performance, and a global design strategy incorporating both catalyst and support in the same integrated framework is advocated. In particular, the structural influence on the ECE and the stability of HER electrocatalysts is discussed, and the role of support carriers in forming energy-saving catalytic systems with minimized non-HER energy loss, which are vital for practical processes, is highlighted. This paper provides new insights into the structure-property relationship and the support effect in developing highly efficient and durable electrocatalysts for HER.
Nipple Position and Clinical Outcomes Following Nipple-Sparing Mastectomy: An Examination of Prepectoral and Subpectoral Implant-Based Reconstruction Utilizing 3D Imaging
Authors: Stern Carrie S , Graziano Francis D , White Donovan R , Shammas Ronnie L , Plotsker Ethan L , Smith-Montes Elizabeth , Boe Lillian , Levy Jacob , Moo Tracy-Ann , Sacchini Virgilio , Allen Robert J , Mehrara Babak J , Nelson Jonas A
Published: January 2025

Background

Nipple-sparing mastectomy (NSM) has become increasingly popular in recent years. However, the impact of prepectoral vs subpectoral implant reconstruction on nipple position, clinical outcomes, and patient-reported outcomes (PROs) after NSM remains unknown.

Objective

We hypothesized that prepectoral reconstruction would lead to a more anatomic nipple position and improved clinical outcomes and PROs when compared to subpectoral reconstruction following NSM.

Methods

Surgical characteristics, complications, and PROs in NSM patients with implant-based reconstruction from 2018 to 2021 were prospectively collected. Nipple displacement from baseline was analyzed with 3-dimensional (3D) surface imaging.

Results

In total 216 patients underwent 391 NSMs, separated into subpectoral (n = 96) and prepectoral (n = 120) cohorts. There were no differences in demographics or comorbidities between cohorts. Prepectoral placement showed a greater incidence of short-term return to the operating room (21% vs 10%, P = .026). Three-dimensional analysis of 96 patients and 175 nipple positions was conducted. Compared to preoperative baseline, 3D imaging at 12 months postoperatively showed that the subpectoral cohort had greater straight-line distance between the nipples (23.1 mm vs 17.3 mm, P < .001) and more lateral nipple displacement (9.2 mm vs 6.1 mm, P < .001) when compared to the prepectoral cohort. Regression analysis found no relationship between incision pattern and nipple displacement. No postoperative differences were seen in PROs.

Conclusions

Subpectoral NSM reconstruction was found to have more lateralized nipple displacement when compared to prepectoral patients, regardless of the incision pattern employed. Nipple displacement after NSM can play a significant role in postoperative aesthetic appearance and should be considered when deciding implant plane.

Level of Evidence: 3 (Therapeutic)
Territorial-sneaker games with non-uniform interactions and female mate choice
Authors: Sherratt Thomas N , Beatty Christopher D , Dewan Ian , Di Iorio Katherine , Finkelstein Isaac , Loeffler-Henry Karl , Miller Marrissa , Para Falisha , Raposo Megan , Sherratt Frances
Published: January 2025

Male territorial-sneaker polymorphisms are common in nature. To understand how these polymorphisms evolve, we developed a game theoretical model analogous to the classical Hawk-Dove model, but with two important differences. First, we allowed non-uniform interaction rates of strategies to account for the possibility that some interactions between male strategies are disproportionately more frequent than others. Second, we allowed females to exhibit a preference for one type of male and thereby choose mates adaptively. Selection dynamics were modeled using coupled replicator equations. The model confirms that there is a broad range of conditions under which a male polymorphism will arise. We applied the model to understand the genetic polymorphism in adult male Mnais damselflies (Zygoptera). Here, orange-winged adult males defend oviposition sites and mate with females when they arrive, while clear-winged ‘sneaker’ males are typically non-territorial and opportunistically mate with females. Intriguingly, in allopatry, the males of Mnais costalis and M. pruinosa both exhibit the same orange-clear winged polymorphism but where the species co-occur, males of M. costalis evolve orange wings while males of M. pruinosa tend to evolve clear wings. To understand this phenomenon and evaluate the importance of female choice in mediating it, we extended our game-theoretical model to two interacting species. While both competitive and reproductive interference can explain the male monomorphisms in sympatry, reproductive interference explains the phenomenon under a wider set of conditions. When females of the rarer species change their male preferences to facilitate species discrimination, it can generate runaway selection on male phenotypes.
Multimodal artificial intelligence models for radiology
Authors: Tariq Amara , Banerjee Imon , Trivedi Hari , Gichoya Judy
Published: January 2025

Artificial intelligence (AI) models in medicine often fall short in real-world deployment due to inability to incorporate multiple data modalities in their decision-making process as clinicians do. Clinicians integrate evidence and signals from multiple data sources like radiology images, patient clinical status as recorded in electronic health records, consultations from fellow providers, and even subtle clues using the appearance of a patient, when making decisions about diagnosis or treatment. To bridge this gap, significant research effort has focused on building fusion models capable of harnessing multi-modal data for advanced decision making. We present a broad overview of the landscape of research in multimodal AI for radiology covering a wide variety of approaches from traditional fusion modelling to modern vision-language models. We provide analysis of comparative merits and drawbacks of each approach to assist future research and highlight ethical consideration in developing multimodal AI. In practice, the quality and quantity of available training data, availability of computational resources, and clinical application dictates which fusion method may be most suitable.
Physicians’ required competencies in AI-assisted clinical settings: a systematic review
Authors: Schuitmaker Lotte , Drogt Jojanneke , Benders Manon , Jongsma Karin
Published: January 2025

Background

Utilizing Artificial Intelligence (AI) in clinical settings may offer significant benefits. A roadblock to the responsible implementation of medical AI is the remaining uncertainty regarding requirements for AI users at the bedside. An overview of the academic literature on human requirements for the adequate use of AI in clinical settings is therefore of significant value.

Sources of data

A systematic review of the potential implications of medical AI for the required competencies of physicians as mentioned in the academic literature.

Areas of agreement

Our findings emphasize the importance of physicians’ critical human skills, alongside the growing demand for technical and digital competencies.

Areas of controversy

Concrete guidance on physicians' required competencies in AI-assisted clinical settings remains ambiguous and requires further clarification and specification. Dissensus remains over whether physicians are adequately equipped to use and monitor AI in clinical settings in terms of competencies, skills and expertise, issues of ownership regarding normative guidance, and training of physicians’ skills.

Growing points

Our review offers a basis for subsequent further research and normative analysis on the responsible use of AI in clinical settings.

Areas timely for developing research

Future research should clearly outline (i) how physicians must be(come) competent in working with AI in clinical settings, (ii) who or what should take ownership of embedding these competencies in a normative and regulatory framework, (iii) investigate conditions for achieving a reasonable amount of trust in AI, and (iv) assess the connection between trust and efficiency in patient care.
Brain microstructure alterations in subjective cognitive decline: a multi-component T2 relaxometry study
Authors: Rivas-Fernández Miguel Ángel , Bouhrara Mustapha , Canales-Rodríguez Erick J , Lindín Mónica , Zurrón Montserrat , Díaz Fernando , Galdo-Álvarez Santiago
Published: January 2025

Previous research has revealed patterns of brain atrophy in subjective cognitive decline, a potential preclinical stage of Alzheimer’s disease. However, the involvement of myelin content and microstructural alterations in subjective cognitive decline has not previously been investigated. This study included three groups of participants recruited from the Compostela Aging Study project: 53 cognitively unimpaired adults, 16 individuals with subjective cognitive decline and hippocampal atrophy and 70 with subjective cognitive decline and no hippocampal atrophy. Group differences were analysed across five MRI biomarkers derived from multi-component T2 relaxometry, each sensitive to variations in cerebral composition and microstructural tissue integrity. Although no significant differences in myelin content were observed between groups, the subjective cognitive decline with hippocampal atrophy group exhibited a larger free-water fraction, and reduced fraction and relaxation times of the intra/extracellular water compartment in frontal, parietal and medial temporal lobe brain regions and white matter tracts as compared with the other groups. Moreover, both subjective cognitive decline groups displayed lower total water content as compared with the control group and the subjective cognitive decline with hippocampal atrophy group showed lower total water content as compared with the subjective cognitive decline without hippocampal atrophy group. These changes are likely related to microstructural tissue differences related to neuroinflammation, axonal degeneration, iron accumulation or other physiologic variations, calling for further examinations.
Dehydroamino acids and their crosslinks in Alzheimer’s disease aggregates
Authors: Markovich Samuel W , Frey Brian L , Scalf Mark , Shortreed Michael R , Smith Lloyd M
Published: January 2025

Alzheimer’s disease is characterized by the accumulation of protein aggregates, which are thought to be influenced by posttranslational modifications. Dehydroamino acids are rarely observed posttranslational modifications that contain an electrophilic alkene capable of forming protein-protein crosslinks, which may lead to protein aggregation. We report here the discovery of dehydroamino acids in the protein aggregates from Alzheimer’s disease, constituting an unknown and previously unsuspected source of extensive proteomic complexity. We used mass spectrometry-based proteomics to discover 404 sites of dehydroamino acid formation in 171 proteins from protein aggregate-enriched human brain samples, 6-fold more sites than observed in the soluble protein fractions. The dehydroamino acid modifications are observed both directly and in the form of conjugates after reacting with abundant cellular nucleophiles or crosslinking to nucleophilic amino acid residues. We report 11 such crosslinks, including three in the Tau protein, which are 10-fold more abundant in Alzheimer’s disease samples compared to age-matched controls. Many of the proteins found to contain dehydroamino acids and their conjugates are involved in protein aggregation or pathways dysregulated in Alzheimer’s disease. Dehydroamino acids are prevalent modifications in the Alzheimer’s disease brain proteome and give rise to protein crosslinks that may contribute to protein aggregation.
‘I don’t worry about going outside anymore’: a patient’s journey with recalcitrant lupus pernio responsive to adalimumab
Authors: Duff Eimear , Feighery Cliona
Published: January 2025

This powerful patient viewpoint article details the journey of an individual with recalcitrant lupus pernio, whose disease improved considerably following treatment with adalimumab, initially combined with methotrexate. The patient shares how successful therapy transformed their quality of life, allowing them to regain confidence and freedom in their daily activities.
YOLO-fall: a YOLO-based fall detection model with high precision, shrunk size, and low latency
Authors: Zhang Xiaoyang , Bai Jian , Qiao Guanchao , Xiao Xiao , Meng Liwei , Hu Shaogang
Published: January 2025

According to recent research statistics, falling has become an important factor affecting the health and safety of the elderly. To reduce the computational cost of hardware and meet the demand for real-time fall detection, we propose a lightweight fall detection network called YOLO-fall oriented for mobile and small edge computing devices. We have made the following improvements based on you only look once (YOLO). First, the backbone network is designed to be lightweight. Then, the convolution module is reparameterized and the C3 structure is improved to ensure the balance between speed and accuracy. Finally, a 5 × 5 depth convolution is added to the detection head to improve the detection ability of large targets. The proposed YOLO-fall is trained and validated on the E-FPDS public dataset and achieves a 78.4% mean average precision (mAP) with 2.45 M parameters and 12.2 GFLOPs. Compared with YOLOv5s, YOLO-fall has a 6.1% improvement in mAP and a 65.1% reduction in parameters. Although Yolov9s has a higher mAP of 82.9%, YOLO-fall reduces the parameters and calculation quantities by 74.8 and 69.2%, respectively. Therefore, the proposed YOLO-fall has the potential to accurately perform real-time fall detection on mobile and small edge computing devices.
Cardiac strangulation with chronic ab-extrinseco occlusion of the left-circumflex artery from an epicardial lead: a case report
Authors: Giarletta Lorenzo , Moliterno Eleonora , Perna Francesco , Marano Riccardo
Published: January 2025

Background

Cardiac strangulation (CS) from epicardial pacing leads (EPLs) is a rare and potentially lethal mechanical complication associated with epicardial pacemaker (PM) implantation.

Case summary

We report a case of a 44-year-old-female patient presenting with chest and left shoulder pain in the absence of reported trauma with history of congenital atrioventricular block treated with epicardial PM implantation during the childhood and subsequent transvenous reimplantation over the years. Troponin I resulted within normal values and ECG, transthoracic echocardiography and chest X-ray documented no acute cardiopulmonary findings. After 3 months the patient underwent coronary computed tomography angiography (CCTA) documenting the presence of solid and focally calcified tissue grown along the course of the EPLs, determining multiple focal impressions on the left ventricular epicardial edge and a segmental occlusion of the middle left-circumflex artery (LCX) due to ab-extrinseco compression. After 10 days, the patient was admitted at the emergency department with atypical chest pain and underwent invasive coronary angiography (ICA), which confirmed chronic occlusion of the mid-LCX with complete collateral circulation; a stress echocardiography ruled out myocardial ischaemia and the patient was uneventfully discharged.

Discussion

The diagnosis of CS in patients with epicardial PM leads remains challenging, especially in adults with atypical clinical presentation; thus, any clinical or instrumental clue should prompt further higher-level imaging investigations, such as CCTA or ICA. It is also important to disclose that sometimes CS can be only a collateral finding with no relationship with the patient’s symptoms.
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

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

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

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

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

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

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 < 0.001). PTA of 32%, 32%, 55%, 29%, 83% and 94% were estimated, respectively for the six strategies (P < 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

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 < .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

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

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

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

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 (<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 (<2 years) and 1.4% after late relapse (>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

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

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.
An Expanding Universe of Mutational Signatures and Its Rapid Evolution in Single-Stranded RNA Viruses
Authors: Yang Yue , Zhang Xinyi , Chen Tingting , Wu Fengyuan , Huang Yu S , Qu Yanhua , Xu Miao , Ma Liang , Liu Mo , Zhai Weiwei
Published: January 2025

The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array of endogenous and exogenous factors associated with somatic changes. However, the overall landscape of mutational processes in germline mutations across the tree of life and associated evolutionary driving forces are rather unclear. In this study, we analyzed mutational processes in single-stranded RNA (ssRNA) viruses which are known to jump between different hosts with divergent exogenous environments. We found that mutational spectra in different ssRNA viruses differ significantly and are mainly associated with their genetic divergence. Surprisingly, host environments contribute much less significantly to the mutational spectrum, challenging the prevailing view that the exogenous cellular environment is a major determinant of the mutational spectrum in viruses. To dissect the evolutionary forces shaping viral spectra, we selected two important scenarios, namely the inter-host evolution between different viral strains as well as the intra-host evolution. In both scenarios, we found mutational spectra change significantly through space and time, strongly correlating with levels of natural selection. Combining the mutations across all ssRNA viruses, we identified a suite of mutational signatures with varying degrees of similarity to somatic signatures in humans, indicating universal and divergent mutational processes across the tree of life. Taken together, we unraveled an unprecedented dynamic landscape of mutational processes in ssRNA viruses, pinpointing important evolutionary forces shaping fast evolution of mutational spectra in different species.
The serum amyloid A to C-reactive protein ratio is lower in men than in women because of higher C-reactive protein concentrations in men
Authors: Uda Hiroshi , Katayama Michihito , Maeda Keiji , Saiki Osamu
Published: January 2025

Objectives

We previously found that discrepancy between serum amyloid A (SAA) and C-reactive protein (CRP) levels linked to the difference of SAA/CRP ratio in patients with early rheumatoid arthritis, and the ratio varied among different patients. This study aimed to determine why the SAA/CRP ratio differed among different patients.

Methods

The patients (n = 466) with most of inflammatory diseases were enrolled. After examined CRP and SAA concentrations, we compared the SAA/CRP ratio, and SAA and CRP concentrations in men and women.

Results

The SAA/CRP ratio varied dramatically among different patients (33.6–0.140). The 10 highest SAA/CRP ratios were all in women, and half of the 10 lowest ratios were found in men. The loge SAA/CRP ratio was significantly higher in women than in men (P < .0001). The loge SAA concentration was not different between women and men (P = .174), but the loge CRP concentration was significantly higher in men (P < .0001).

Conclusions

The SAA/CRP ratio varies considerably among different patients. The SAA/CRP ratio in women is higher than in men because loge CRP but not SAA concentrations in men are higher than in women. The finding is against the conventional view and suggests that the reference range of CRP concentrations in women should be assessed lower than in men.