bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between antifungal clinical practices and a new clinical decision support system ANTIFON-CLIC® for the treatment of invasive candidiasis: a retrospective multicentre study
Authors: Bienvenu Anne-Lise , Cour Martin , Pavese Patricia , Guichon Céline , Leray Véronique , Chapuis Claire , Dureault Amélie , Mohkam Kayvan , Gallet Salomé , Bourget Stéphanie , Kahale Elham , Chaabane Wajih , Subtil Fabien , Maucort-Boulch Delphine , Talbot François , Dode Xavier , Richard Jean-Christophe , Leboucher Gilles 
Published: April 2024

Abstract

Background
Invasive candidiasis is still recognized as a major cause of morbidity and mortality. To support clinicians in the optimal use of antifungals for the treatment of invasive candidiasis, a computerized decision support system (CDSS) was developed based on institutional guidelines.

Objectives
To evaluate the correlation of this newly developed CDSS with clinical practices, we set-up a retrospective multicentre cohort study with the aim of providing the concordance rate between the CDSS recommendation and the medical prescription (NCT05656157).

Patients and methods
Adult patients who received caspofungin or fluconazole for the treatment of an invasive candidiasis were included. The analysis of factors associated with concordance was performed using mixed logistic regression models with department as a random effect.

Results
From March to November 2022, 190 patients were included from three centres and eight departments: 70 patients from centre A, 84 from centre B and 36 from centre C. Overall, 100 patients received caspofungin and 90 received fluconazole, mostly (59%; 112/190) for empirical/pre-emptive treatment. The overall percentage of concordance between the CDSS and medical prescriptions was 91% (173/190) (confidence interval 95%: 82%–96%). No significant difference in concordance was observed considering the centres (P &gt; 0.99), the department of inclusion (P = 0.968), the antifungal treatment (P = 0.656) or the indication of treatment (P = 0.997). In most cases of discordance (n = 13/17, 76%), the CDSS recommended fluconazole whereas caspofungin was prescribed. The clinical usability evaluated by five clinicians was satisfactory.

Conclusions
Our results demonstrated the high correlation between current antifungal clinical practice and this user-friendly and institutional guidelines-based CDSS.
A comprehensive study on Geranium robertianum L. antibacterial potential
Authors: Stanković Marina M , Ristivojević Petar M , Ivković Đurđa D , Milutinović Milena G , Terzić Jelena N , Stefanović Olgica D 
Published: April 2024

Abstract

Aims
The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined.

Methods and results
Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml−1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml−1 for ethanol extract, and 958.01 ± 6.14 µg ml−1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts.

Conclusions
The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.
Large language models for biomedicine: foundations, opportunities, challenges, and best practices
Authors: Sahoo Satya S , Plasek Joseph M , Xu Hua , Uzuner Özlem , Cohen Trevor , Yetisgen Meliha , Liu Hongfang , Meystre Stéphane , Wang Yanshan 
Published: April 2024

Abstract

Objectives
Generative large language models (LLMs) are a subset of transformers-based neural network architecture models. LLMs have successfully leveraged a combination of an increased number of parameters, improvements in computational efficiency, and large pre-training datasets to perform a wide spectrum of natural language processing (NLP) tasks. Using a few examples (few-shot) or no examples (zero-shot) for prompt-tuning has enabled LLMs to achieve state-of-the-art performance in a broad range of NLP applications. This article by the American Medical Informatics Association (AMIA) NLP Working Group characterizes the opportunities, challenges, and best practices for our community to leverage and advance the integration of LLMs in downstream NLP applications effectively. This can be accomplished through a variety of approaches, including augmented prompting, instruction prompt tuning, and reinforcement learning from human feedback (RLHF).

Target Audience
Our focus is on making LLMs accessible to the broader biomedical informatics community, including clinicians and researchers who may be unfamiliar with NLP. Additionally, NLP practitioners may gain insight from the described best practices.

Scope
We focus on 3 broad categories of NLP tasks, namely natural language understanding, natural language inferencing, and natural language generation. We review the emerging trends in prompt tuning, instruction fine-tuning, and evaluation metrics used for LLMs while drawing attention to several issues that impact biomedical NLP applications, including falsehoods in generated text (confabulation/hallucinations), toxicity, and dataset contamination leading to overfitting. We also review potential approaches to address some of these current challenges in LLMs, such as chain of thought prompting, and the phenomena of emergent capabilities observed in LLMs that can be leveraged to address complex NLP challenge in biomedical applications.
The Impact of Mammographic, Radiologist, and Patient Factors on the Likelihood of Probably Benign (BI-RADS 3) Assessment at Diagnostic Mammography
Authors: Chesebro Allyson L , Abbasi Nooshin , Lacson Ronilda , Chikarmane Sona A , Licaros Andro R L , Giess Catherine S 
Published: April 2024

Abstract

Objective
To evaluate the association of mammographic, radiologist, and patient factors on BI-RADS 3 assessment at diagnostic mammography in patients recalled from screening mammography.

Methods
This Institutional Review Board–approved retrospective study of consecutive unique diagnostic mammography examinations in asymptomatic patients recalled from screening mammography March 5, 2014, to December 31, 2019, was conducted in a single large United States health care institution. Mammographic features (mass, calcification, distortion, asymmetry), breast density, prior examination, and BI-RADS assessment were extracted from reports by natural language processing. Patient age, race, and ethnicity were extracted from the electronic health record. Radiologist years in practice, recall rate, and number of interpreted diagnostic mammograms were calculated. A mixed effect logistic regression model evaluated factors associated with likelihood of BI-RADS 3 compared with other BI-RADS assessments.

Results
A total of 12 080 diagnostic mammography examinations were performed during the study period, yielding 2010 (16.6%) BI-RADS 3 and 10 070 (83.4%) other BI-RADS assessments. Asymmetry (odds ratio [OR] = 6.49, P &lt;.001) and calcification (OR = 5.59, P &lt;.001) were associated with increased likelihood of BI-RADS 3 assessment; distortion (OR = 0.20, P &lt;.001), dense breast parenchyma (OR = 0.82, P &lt;.001), prior examination (OR = 0.63, P = .01), and increasing patient age (OR = 0.99, P &lt;.001) were associated with decreased likelihood. Mass, patient race or ethnicity, and radiologist factors were not significantly associated with BI-RADS 3 assessment. Malignancy rate for BI-RADS 3 lesions was 1.6%.

Conclusion
Asymmetry and calcifications had an increased likelihood of BI-RADS 3 assessment at diagnostic evaluation with low likelihood of malignancy, while radiologist features had no association.
N6-methyladenosine promotes TNF mRNA degradation in CD4+ T lymphocytes
Authors: van Vroonhoven Ellen C N , Picavet Lucas W , Scholman Rianne C , Sijbers Lyanne J P M , Kievit Corlinda R E , van den Dungen Noortje A M , Mokry Michal , Evers Anouk , Lebbink Robert J , Mocholi Enric , Coffer Paul J , Calis Jorg J A , Vastert Sebastiaan J , van Loosdregt Jorg 
Published: April 2024

Abstract
N6-methyladenosine (m6A) is a RNA modification that can regulate post-transcriptional processes including RNA stability, translation, splicing, and nuclear export. In CD4+ lymphocytes, m6A modifications have been demonstrated to play a role in early differentiation processes. The role of m6A in CD4+ T cell activation and effector function remains incompletely understood. To assess the role of m6A in CD4+ T lymphocyte activation and function, we assessed the transcriptome-wide m6A landscape of human primary CD4+ T cells by methylated RNA immunoprecipitation sequencing. Stimulation of the T cells impacted the m6A pattern of hundreds of transcripts including tumor necrosis factor (TNF). m6A methylation was increased on TNF messenger RNA (mRNA) after activation, predominantly in the 3′ untranslated region of the transcript. Manipulation of m6A levels in primary human T cells, the directly affected the expression of TNF. Furthermore, we identified that the m6A reader protein YTHDF2 binds m6A-methylated TNF mRNA, and promotes its degradation. Taken together, this study demonstrates that TNF expression in CD4+ T lymphocytes is regulated via m6A and YTHDF2, thereby providing novel insight into the regulation of T cell effector functions.
Antibacterial activity of Cymbopogon species essential oils against Xanthomonas citri and their use in post-harvest treatment for citrus canker management
Authors: Marin Vítor Rodrigues , Zamuner Caio Felipe Cavicchia , Hypolito Giovane Böerner , Ferrarezi Juliano Henrique , Alleoni Natália , Caccalano Mario Nicolas , Ferreira Henrique , Sass Daiane Cristina 
Published: April 2024

Abstract
Citrus canker is a disease caused by the gram-negative bacterium Xanthomonas citri subp. citri (X. citri), which affects all commercially important varieties of citrus and can lead to significant losses. Fruit sanitization with products such as chlorine-based ones can reduce the spread of the disease. While effective, their use raises concerns about safety of the workers. This work proposes essential oils (EOs) as viable alternatives for fruit sanitization. EOs from Cymbopogon species were evaluated as to their antibacterial activity, their effect on the bacterial membrane, and their ability to sanitize citrus fruit. The in vitro assays revealed that the EOs from C. schoenanthus and C. citratus had a lower bactericidal concentration at 312 mg L−1, followed by 625 mg L−1 for C. martini and C. winterianus. Microscopy assay revealed that the bacterial cell membranes were disrupted after 15 min of contact with all EOs tested. Regarding the sanitizing potential, the EOs with higher proportions of geraniol were more effective in sanitizing acid limes. Fruit treated with C. shoenanthus and C. martini showed a reduction of ∼68% in the recovery of viable bacterial cells. Therefore, these EOs can be used as viable natural alternatives in citrus fruit disinfection.
Biobank donation in search of public benefits and the potential impact of intellectual property rights over access to health-technologies developed: A focus on the bioethical implications
Authors: McMahon Aisling M , Kolawole Opeyemi I 
Published: April 2024

Abstract
The availability of biomaterials is a key component of health research and the development of new health-technologies (including, diagnostics, medicines, and vaccines). People are often encouraged by biobanks to donate samples altruistically to such biobanks. While empirical evidence suggests many donors are motivated by the desire to contribute towards developing new health-technologies for society. However, a tension can arise as health-technologies whose development is contributed to by donors’ biomaterials will often be protected by intellectual property rights (IPRs), including patents. Patents give rightsholders control over how patented technologies are used and can be used in a way that impedes public access to technologies developed. Yet, there are no binding European legal obligations mandating disclosure to donors of how IPRs can operate over downstream health-technologies and how they could impact access to health-technologies developed, nor are there legally binding obligations to ensure public accessibility of technologies developed. Focusing on the bioethical implications posed, this article argues that the current situation can impact donors’ autonomy and dignity interests. A more holistic approach is needed for biobank donation, which embeds a consideration of donors’ expectations/interests from the point of donation through to how such samples are used and how health-technologies developed are accessed. We put forward avenues that seek to address such issues.
Comparing transit spectroscopy pipelines at the catalogue level: evidence for systematic differences
Authors: Mugnai Lorenzo V , Swain Mark R , Estrela Raissa , Roudier Gael M 
Published: April 2024

ABSTRACT
The challenge of inconsistent results from different data pipelines, even when starting from identical data, is a recognized concern in exoplanetary science. As we transition into the JWST era and prepare for the ARIEL space mission, addressing this issue becomes paramount because of its implications on our understanding of exoplanets. Although comparing pipeline results for individual exoplanets has become more common, this study is the first to compare pipeline results at the catalogue level. We present a comprehensive framework to statistically compare the outcomes of data analysis reduction on a population of exoplanets and we leverage the large number of observations conducted using the same instrument configured with HST-WFC3. We employ three independent pipelines: Iraclis, excalibur, and CASCADe. Our combined findings reveal that these pipelines, despite starting from the same data and planet system parameters, yield substantially different spectra in some cases. However, the most significant manifestations of pipeline differences are observed in the compositional trends of the resulting exoplanet catalogues. We conclude that pipeline-induced differences lead to biases in the retrieved information, which are not reflected in the retrieved uncertainties. Our findings underscore the critical need to confront these pipeline differences to ensure the reproducibility, accuracy, and reliability of results in exoplanetary research. Our results demonstrate the need to understand the potential for population-level bias that pipelines may inject, which could compromise our understanding of exoplanets as a class of objects.
Multiscale accretion in dense cloud cores and the delayed formation of massive stars
Authors: Vázquez-Semadeni Enrique , Gómez Gilberto C , González-Samaniego Alejandro 
Published: April 2024

ABSTRACT
The formation mechanism of massive stars remains one of the main open problems in astrophysics, in particular the relationship between the mass of the most massive stars and that of the cores in which they form. Numerical simulations of the formation and evolution of molecular clouds, within which dense cores and stars form self-consistently, show that the core mass increases in time, and also that the most massive stars tend to appear later than lower mass stars. We present an idealized model that incorporates accretion onto the cores as well as onto the stars, in which the core mass growth is regulated by a ‘gravitational choking’ mechanism that does not involve any form of support. This process is of purely gravitational origin, and causes some of the mass accreted onto cores to stagnate there, rather than being transferred to the stars. In addition, we estimate the mass of the most massive allowed star before its photoionizing radiation is capable of overcoming the accretion flow. This model constitutes a proof of concept for the simultaneous growth of the gas reservoir and the stellar mass, the delay in the formation of massive stars observed in numerical simulations, the need for massive, dense cores in order to form massive stars, and the observed correlation between the mass of the most massive star and the mass of the cluster it resides in. Also, our model implies that by the time massive stars begin to form in a core, a number of low-mass stars are expected to have already formed.
A JWST investigation into the bar fraction at redshifts 1 ≤ z ≤ 3
Authors: Le Conte Zoe A , Gadotti Dimitri A , Ferreira Leonardo , Conselice Christopher J , de Sá-Freitas Camila , Kim Taehyun , Neumann Justus , Fragkoudi Francesca , Athanassoula E , Adams Nathan J 
Published: April 2024

ABSTRACT
The presence of a stellar bar in a disc galaxy indicates that the galaxy hosts in its main part a dynamically settled disc and that bar-driven processes are taking place in shaping its evolution. Studying the cosmic evolution of the bar fraction in disc galaxies is therefore essential to understand galaxy evolution in general. Previous studies have found, using the Hubble Space Telescope (HST), that the bar fraction significantly declines from the local Universe to redshifts near one. Using the first four pointings from the JWST Cosmic Evolution Early Release Science Survey and the initial public observations for the Public Release Imaging for Extragalactic Research, we extend the studies of the bar fraction in disc galaxies to redshifts 1 ≤ $z$ ≤ 3, that is, for the first time beyond redshift two. We only use galaxies that are also present in the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey on the Extended Groth Strip and Ultra Deep Survey HST observations. An optimized sample of 368 close-to-face-on galaxies is visually classified to find the fraction of bars in disc galaxies in two redshift bins: 1 ≤ $z$ ≤ 2 and 2 &lt; $z$ ≤ 3. The bar fraction decreases from $\approx 17.8^{+ 5.1}_{- 4.8}$ per cent to $\approx 13.8^{+ 6.5}_{- 5.8}$ per cent (from the lower to the higher redshift bin), but is about twice the bar fraction found using bluer HST filters. Our results show that bar-driven evolution might commence at early cosmic times and that dynamically settled discs are already present at a lookback time of ∼11 Gyr.
Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma
Authors: Zhou Yong , Mo Shanlan , Cui Heyang , Sun Ruifang , Zhang Weimin , Zhuang Xiaofei , Xu Enwei , Li Hongyi , Cheng Yikun , Meng Yongsheng , Liu Meilin , Yan Ting , Liu Huijuan , Zhang Ling , Yang Bin , Xi Yanfeng , Wang Shubin , Cheng Xiaolong , Li ShuaiCheng , Liu Zhihua , Zhan Qimin , Hu Zheng , Cui Yongping 
Published: April 2024

ABSTRACT
Esophageal squamous cell carcinoma (ESCC) is a poor-prognostic cancer type with extensive intra- and inter-patient heterogeneity in both genomic variations and tumor microenvironment (TME). However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2, accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the esophagus. Interestingly, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+ T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted therapy. Collectively, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.
Nicotinic Receptor Alpha-5 Subunit Gene Polymorphism is Associated With Heavy Smoking Under a Range of Nicotine Dosing Conditions
Authors: Zuo Yantao , Rose Jed E , Davis James M , Behrens Kelsey A , Golaub Aisha A , Chandra Upasana U , Aarons Emily K , Morgan-Glover Janiece D , Mukhin Alexey G 
Published: April 2024

Abstract

Introduction
This study aimed to assess the role of the rs16969968 variant of nicotinic receptor alpha-5 subunit in regulating smoking behavior and nicotine intake in response to nicotine manipulations among dependent smokers in a naturalistic environment.

Aims and Methods
Sixty-nine adults (19 females) smoking 10 or more cigarettes per day (CPD) were asked to complete four 2-week study phases during which they smoked exclusively one of two types of Spectrum nicotine research cigarettes (FTC nicotine yield 0.8 and 1.6 mg, respectively), their usual brand of cigarettes, or their usual brand of cigarettes while wearing a 21-mg nicotine patch. Measurements included rs16969968 genotype, number of CPD, smoking topography, and plasma cotinine.

Results
Compared to controls (G/G carriers), A allele carriers reported smoking 4 to 5 more CPD across all conditions (all ps &lt; .05). Mean total smoke volume per day and cotinine were greater in A allele carriers than in controls (ps = .05, .046, respectively). No significant genotype differences were found in smoking compensation indices for the switch from medium to high-nicotine-yield cigarettes. Nicotine patch-induced reductions in cigarettes smoked per day and total smoke volume per day showed significant interactions between genotype and pre-patch levels, with heavier smokers showing greater effects of genotype (p = .052 and p = .006, respectively).

Conclusions
Results suggest that the rs16969968 variants regulate the heaviness of smoking primarily by their impact on daily numbers of cigarettes smoked, but no genotype differences were found in smoking compensation after switching from medium to high-nicotine cigarettes.

Implications
The differences in daily cigarette consumption between rs16969968 risk-allele carriers and controls are shown to be consistent regardless of manipulations of cigarette nicotine content and transdermal nicotine supplementation and markedly greater among dependent smokers than those observed in the general smoker populations. G/G allele carriers, relative to A allele carriers, appeared to be more sensitive to the nicotine patch manipulation, reducing their smoking to a greater extent. These findings support continued efforts in the development of personalized intervention strategies to reduce the rs16969968-conveyed genetic propensity for heavy smoking.