bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Evaluation of Machine Learning Models for the Detection of Emergency Department Patients with Opioid Misuse from Clinical Notes
Authors: Shahid Usman , Parde Natalie , Smith Dale L. , Dickinson Grayson , Bianco Joseph , Thorpe Dillon , Hota Madhav , Afshar Majid , Karnik Niranjan S. , Chhabra Neeraj 
Published: December 2024

AbstractObjectivesThe accurate identification of Emergency Department (ED) encounters involving opioid misuse is critical for health services, research, and surveillance. We sought to develop natural language processing (NLP)-based models for the detection of ED encounters involving opioid misuse.MethodsA sample of ED encounters enriched for opioid misuse was manually annotated and clinical notes extracted. We evaluated classic machine learning (ML) methods, fine-tuning of publicly available pretrained language models, and a previously developed convolutional neural network opioid classifier for use on hospitalized patients (SMART-AI). Performance was compared to ICD-10-CM codes. Both raw text and text transformed to the United Medical Language System were evaluated. Face validity was evaluated by term feature importance.ResultsThere were 1123 encounters used for training, validation, and testing. Of the classic ML methods, XGBoost had the highest AU_PRC (0.936), accuracy (0.887), and F1 score (0.863) which outperformed ICD-10-CM codes [accuracy 0.870; F1 0.830]. Logistic regression, support vector machine, and XGBoost models had higher AU_PRC using transformed text, while decision trees performed better using raw text. Excluding XGBoost, fine-tuned pre-trained language models outperformed classic ML methods. The best performing model was the fine-tuned SMART-AI based model with domain adaptation [AU_PRC 0.948; accuracy 0.882; F1 0.851]. Explainability analyses showed the most predictive terms were ‘heroin’, ‘opioids’, ‘alcoholic intoxication, chronic’, ‘cocaine’, ‘opiates’, and ‘suboxone’.ConclusionsNLP-based models outperform entry of ICD-10-CM diagnosis codes for the detection of ED encounters with opioid misuse. Fine tuning with domain adaptation for pre-trained language models resulted in improved performance.
Protective role of dietary antioxidant intake on long-term effects of extreme PM2.5exposure on respiratory health
Authors: Govindaraju Thara , Smith Catherine L , Ikin Jillian , Owen Alice J , Carroll Matthew , Borg Brigitte M. , Gao Caroline X , Brown David , Poland David , Allgood Shantelle , Abramson Michael J , Walker-Bone Karen , McCaffrey Tracy A , Lane Tyler J 
Published: December 2024

AbstractObjectiveEvidence for the protective effects of dietary antioxidants on respiratory health following exposure to smoke from landscape fires is scarce. This study assessed whether the long-term respiratory effects of fine particulate matter (PM2.5) from the 2014 Hazelwood coal mine fire were moderated by dietary antioxidants, 8.5 years later.MethodsWe conducted a cross-sectional analysis of data collected 8.5 years after the mine fire from 282 residents of Morwell (a highly exposed town adjacent to the mine) and 166 residents from the nearby unexposed town of Sale. Coal mine fire-related PM2.5was the primary exposure and meeting recommended dietary intake for antioxidants including vitamins (A, E and C), minerals (zinc, magnesium and selenium) and omega-3 fatty acids assessed through the Australian Eating Survey (AES) was the moderator. Respiratory symptoms were the primary outcome. Analyses used logistic regression models, adjusting for potential confounders.ResultsVitamins A and E, magnesium, and zinc attenuated the association between fire-related PM2.5and prevalence of chronic cough; three of the four (except magnesium) attenuated the association between fire-related PM2.5and chronic phlegm. Omega-3 fatty acids attenuated the association between PM2.5and COPD.ConclusionMeeting recommended intakes of vitamins, A and E, magnesium and zinc may provide protection against the long-term adverse effects of exposure to particulate matter from other medium duration but extreme exposure events. Advocating incorporation of fruits and vegetables in daily diet could offer more than the conventional health benefits due to their high antioxidant content.Highlights➢ A coal mine fire exposed a regional Victorian community to extreme levels of PM2.5.➢ We examined if dietary antioxidants mitigated PM2.5effects on respiratory health.➢ Vitamins A and E and Zinc reduced PM2.5effects on chronic cough and chronic phlegm.
Sex Differences in Non-Acute Myocardial Infarction Cardiogenic Shock: Insights from the Northwell-Shock Registry
Authors: Li Shuojohn , Adi Abduljabar , Miller Marcy , Sakr Fouad , Jnani Jack , Rodriguez Emily A. , Tan Samuel , Mokhtari Moein Bayat , Ramsis Ramsis , Smoller Rebecca , Stevens Gerin R. , Hernandez-Montfort Jaime , Griffin Matthew , Pierce Matthew , Villela Miguel Alvarez 
Published: December 2024

2.AbstractBackgroundPrevious studies had explored the role of patients’ sex in defining clinical presentation, management, and outcomes among patients with acute myocardial infarction (AMI) related cardiogenic shock (CS). However, the effect of sex among patients with non-acute myocardial infarction related CS (nonAMI-CS) is less well defined.MethodAdult patients treated for CS (International Classification of Diseases, Tenth Revision, [ICD-10] code R57.0) between 2016 and 2022 across eleven hospitals within our health system, all utilizing a shared electronic medical record, were included. CS etiologies were defined as AMI, nonAMI and others. For nonAMI-CS patients, stratification by sex was performed to compare the incidence of specific etiologies, baseline characteristics, management and outcomes between men and women. Comparisons were conducted using t-tests, Wilcoxon rank-sum tests or chi-square tests. Logistic regression models were developed to examine the effect of sex on in-hospital mortality, management strategies, and mortality predictors.Result2,256 patients admitted for nonAMI-CS were identified. Women comprised 36% of the study cohort and were older and had more medical comorbidities. There was no significant difference in presenting CS severity as measured by Society for Cardiovascular Angiography and Interventions (SCAI) stages, APACHE scores or in-hospital mortality. There were significant differences in the specific etiologies of nonAMI-CS, where women had more valvular cardiogenic shock. Women received fewer invasive interventions including pulmonary artery catheter (PAC) and intra-aortic balloon pump (IABP) when compared to men but similar rates of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO). Lastly, women were more likely to be discharged to skilled nursing facilities while men more likely to home.ConclusionSignificant sex-specific differences exist in nonAMI-CS including specific etiologies, management strategies, and factors associated with mortality. Despite older age, more comorbidities and lower rates of invasive management procedures, women had similar survival to men but higher need for skilled facilities upon discharge.
Uncertainty in blacklisting potential Pacific plant invaders using species distribution models
Authors: Holle Valén , Rönnfeldt Anna , Schifferle Katrin , Cabral Juliano Sarmento , Craven Dylan , Knight Tiffany , Seebens Hanno , Weigelt Patrick , Zurell Damaris 
Published: December 2024

AbstractInvasive alien species pose a growing threat to global biodiversity, necessitating evidence-based prevention measures. Species distribution models (SDMs) are a useful tool for quantifying the potential distribution of alien species in non-native areas and deriving blacklists based on establishment risk. Yet, uncertainties due to different modelling decisions may affect predictive accuracy and the robustness of such blacklists. We thus aim to assess the relevance of three distinct sources of uncertainty in SDM-based blacklists: species data, environmental data and SDM algorithms.Focusing on 82 of the most invasive plant species on the Hawaiian Islands, we built SDMs to quantify their establishment potential in the Pacific region. We considered two different species datasets (native vs. global occurrences), two environmental predictor sets (climatic vs. edapho-climatic), and four different SDM algorithms. Based on SDM predictions, we derived blacklists using three distinct blacklisting definitions and quantified the variance in blacklist rankings associated with each source of uncertainty.On average, SDMs showed fair predictive performance. SDM algorithm choice resulted in the largest variation in blacklist ranks while the relevance of species and environmental data was lower and varied across blacklist definitions. Nevertheless, using only native occurrences led to a clear underestimation of the establishment potential for certain species and to lower predictive performance, including high-ranking species on blacklists.SDMs can serve as a robust decision support tool to plan preventive management strategies. To establish robust model-aided blacklists, we recommend ensemble models using multiple SDM algorithms that rely on global rather than native occurrences only. The relevance of environmental predictors additional to climate should be carefully considered and weighed against spatial coverage of those data to ensure sufficiently large sample sizes and predictive accuracy. We advocate for explicit assessment of uncertainty to increase confidence in blacklists and allow more reliable decision-making.
Two strains of Toscana virus show different virulence and replication capacity in mice and cell culture models
Authors: Roy Marlène , Lacôte Sandra , Desloire Sophie , Thiesson Adrien , Pulido Coralie , Aurine Noémie , Mathieu Cyrille , Pain Bertrand , Marianneau Philippe , Arnaud Frédérick , Ratinier Maxime 
Published: December 2024

AbstractToscana virus (TOSV), belonging toPhenuiviridaefamily, is circulating in most Mediterranean countries and is transmitted to humans by infected female sand flies. While most infections are asymptomatic, TOSV is considered as a leading cause of meningitis and encephalitis in humans during summer. Three TOSV genotypes (named A, B, and C) have been identified, although no virus strain belonging to lineage C has been isolated so far. To date, the relationship between TOSV genetic diversity and viral pathogenicity or replication capacity remains unknown. This study aimed to compare two TOSV strains from either lineage A (TOSV-A) or B (TOSV-B) in several cell culture and two mouse models. We showed that TOSV-A replicated more efficiently in BSR and A549 cells while TOSV-B had a replication advantage in human induced pluripotent stem cells differentiated in neural cells and LL-5 sand fly cells.In vivo, we were unable to detect any virus in the brains of immunocompetent C57BL/6JRj mice infected with either strain of TOSV. On the contrary, we showed that TOSV-A disseminated to the central nervous system of 129/Svifnar-/-mice unlike TOSV-B, despite higher viremia of TOSV-B and a greater dissemination of this strain in other organs. The reasons for these differences are not yet known, although we showed that the presence of TOSV neutralizing antibodies in serum was slightly delayed in TOSV-A-infected mice. Altogether, the data presented in this study provide new avenues to study TOSV-induced pathogenesis and ultimately unveil molecular viral determinants modulating TOSV replication capacity.Author SummaryToscana virus is a sand fly-borne phlebovirus with tropism for the human central nervous system (CNS) and the causal agent of aseptic meningitis and encephalitis during summer in countries surrounding the Mediterranean Sea. The pathogenesis induced by TOSV is still poorly understood as well as the correlation between TOSV genetic diversity and viral pathogenicity or replication capacity. In this study, we characterised two TOSV strains belonging to two different genetic lineages (named A and B) in severalin vitro,ex vivoandin vivomodels of infection. We showed that the biological properties of these two strains is strikingly different and, importantly, we identified 129/Svifnar-/-mice as a suitable model to study the mechanism of TOSV invasion of the CNS and viral pathogenesis. Our comparative study also highlights the importance of strengthening our efforts to identify molecular viral determinants modulating TOSV-induced pathogenesis and vector transmission, in order to better characterise the epidemiological risk posed by circulating strains.
Both tobacco TA29 and sesame GN13 promoters provide anther-specific GUS expression in transgenic sesame (Sesamum indicumL.)
Authors: Debnath Anirban Jyoti , Basu Debabrata , Sikdar Samir Ranjan 
Published: December 2024

AbstractYield improvement is one of the most concerning areas of the “Queen of Oilseed” sesame (Sesamum indicumL.) for its successful commercialisation. Heterosis breeding is an alternate approach for improving sesame compared to the time- and labour-consuming conventional breeding. However, tedious hand emasculation and pollination processes restrict the implementation of commercial heterosis on sesame. The unavailability of male sterile, restorer, and maintainer lines further complicates the problem. Biotechnological gene manipulation can silence anther-specific vital gene(s) leading to male sterility. Anther-specific gene study is therefore crucial to reach such a goal. In this study, we have cloned two established anther-specific promoters: sesame SiBGproplus (hereafter GN13, NCBI accession no.KT246471) and tobacco TA29 (NCBI accession no.X52283) in the plant expression vector pCAMBIA2301 producing respective GN13::GUS and TA29::GUS chimeric vectors. We recovered putatively transgenic T0 sesame lines using conventionalAgrobacterium-mediated transformation with 1.76% and 1.71% frequencies, respectively. The T0 lines were segregated at the 3:1 Mendelian segregation ratio for kanamycin resistance and generated T1 transgenic lines by self-fertilisation. Most of the T1 transgenics had a single copy of transgene integration. The histological assay revealed the tapetum-specific GUS expression in the T1 transgenic lines; GUS expression was undetected in other tested plant parts. The results depict successful anther/tapetum-specific expression of two promoters in transgenic sesame lines. In further research, these promoters could be used for anther-specific cytotoxic gene expression, RNAi, or CRISPR-mediated mutational approaches to destroy androecium selectively and exhibit male sterility in sesame, resulting in heterosis-mediated improvement.
Cold stress involves CBF dependent regulatory pathway to remodel wood formation inEucalyptus gunniihybrids
Authors: Bachir Ines Hadj , Ployet Raphael , San Clemente Hélène , Aguilar Marielle , Dupas Annabelle , Ladouce Nathalie , Martinez Yves , Grima-Pettenati Jacqueline , Teulières Chantal , Cassan-Wang Hua , Mounet Fabien 
Published: December 2024

AbstractWhile being the most planted tree worldwide, mostEucalyptusspecies are sensitive to frost. Long-term exposure to cold temperatures, among other abiotic cues, triggers modification of secondary xylem differentiation inEucalyptus, but the molecular mechanisms behind it remain unknown. Overexpression of key players of cold signalling pathway, the CRT-repeat binding factors (CBF), not only causes the expected increase in freezing tolerance but also remodels wood in a similar trend to cold acclimation, making it a good candidate for wood functional adaptation to cold stress. To gain insight in CBF role in cold-induced secondary cell wall (SCW) remodelling, we used both targeted and untargeted methodologies to show that chilling and freezing temperatures induced the deposition of a thick SCW with alterations in lignin and polysaccharides composition as well as modifications of wood anatomy in aEucalyptuscold-tolerant hybrid. Using co-expression network approaches, we identified CBF transcription factors (TFs) as a regulatory hub in xylem cold response. Direct targets of the CBF TFs were identified by DAPseq and unravelled promising candidates involved in SCW deposition and hormonal signalling pathways. Our results shed new light on the interplay between cold response and wood formation, bringing new evidence for the role of the cell wall in trees tolerance to abiotic stresses.
Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities
Authors: Farghli Alaa R. , Chan Marina , Sherman Marc S. , Dickerson Lindsay K. , Shui Bo , Nukaya Manabu , Stephanou Andreas , Ma Rosanna K. , Pepe-Mooney Brian J. , Smith Colton J. , Long Donald , Munn Paul R. , McNairn Adrian , Grenier Jennifer K. , Karski Michael , Ronnekleiv-Kelly Sean M. , Pillarisetty Venu G. , Goessling Wolfram , Gujral Taranjit S. , Vakili Khashayar , Sethupathy Praveen 
Published: December 2024

AbstractFibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant markers and pathways in FLC. However, a significant drawback of these efforts is that they were conducted on bulk tumor samples. Consequently, identities and roles of distinct cell types within the tumor milieu, and the patterns of intercellular communication, have yet to be explored. In this study we unveil cell-type specific gene signatures, transcription factor networks, and super-enhancers in FLC using a multi-omics strategy that leverages both single-nucleus ATAC-seq and single-nucleus RNA-seq. We also infer completely rewired cell-to-cell communication patterns in FLC including signaling mediated by SPP1-CD44, MIF-ACKR3, GDF15-TGFBR2, and FGF7-FGFR. Finally, we validate findings with loss-of-function studies in several models including patient tissue slices, identifying vulnerabilities that merit further investigation as candidate therapeutic targets in FLC.
Cross-disease modeling of peripheral blood identifies biomarkers of type 2 diabetes predictive of Alzheimer’s disease
Authors: Ball Brendan K. , Park Jee Hyun , Proctor Elizabeth A. , Brubaker Douglas K. 
Published: December 2024

ABSTRACTType 2 diabetes (T2D) is a significant risk factor for Alzheimer’s disease (AD). Despite multiple studies reporting this connection, the mechanism by which T2D exacerbates AD is poorly understood. It is challenging to design studies that address co-occurring and comorbid diseases, limiting the number of existing evidence bases. To address this challenge, we expanded the applications of a computational framework called Translatable Components Regression (TransComp-R), initially designed for cross-species translation modeling, to perform cross-disease modeling to identify biological programs of T2D that may exacerbate AD pathology. Using TransComp-R, we combined peripheral blood-derived T2D and AD human transcriptomic data to identify T2D principal components predictive of AD status. Our model revealed genes enriched for biological pathways associated with inflammation, metabolism, and signaling pathways from T2D principal components predictive of AD. The same T2D PC predictive of AD outcomes unveiled sex-based differences across the AD datasets. We performed a gene expression correlational analysis to identify therapeutic hypotheses tailored to the T2D-AD axis. We identified six T2D and two dementia medications that induced gene expression profiles associated with a non-T2D or non-AD state. Finally, we assessed our blood-based T2DxAD biomarker signature in post-mortem human AD and control brain gene expression data from the hippocampus, entorhinal cortex, superior frontal gyrus, and postcentral gyrus. Using partial least squares discriminant analysis, we identified a subset of genes from our cross-disease blood-based biomarker panel that significantly separated AD and control brain samples. Our methodological advance in cross-disease modeling identified biological programs in T2D that may predict the future onset of AD in this population. This, paired with our therapeutic gene expression correlational analysis, also revealed alogliptin, a T2D medication that may help prevent the onset of AD in T2D patients.
Assembly of hierarchical multiphase condensates using designer surfactant proteins
Authors: Guan Muyang , Hammer Daniel A. , Good Matthew C. 
Published: December 2024

AbstractBiomolecular condensates are complex fluids formed by liquid-liquid phase separation of macromolecules. Similar to other types of soft matter, they feature a range of biophysical properties that distinguish them from the cellular milieu. As a separate phase, they have an identifiable interface that dictates their interaction with the cytoplasm and other membraneless organelles. In this work, we engineer the interface of condensates to build novel hierarchical mesoscale structures from two immiscible disordered proteins: the RGG domain of LAF-1, a RNA-processing protein involved in germ granule assembly and the low complexity domain (LC) of FUS, an RNA binding protein whose aggregation is implicated in age-related neurodegeneration. RGG and FUS LC do not co-partition with one another and instead form discrete protein-rich condensed phases. Despite their apparent immiscibility, we identified conditions that can promote hierarchical assembly, either kinetically trapping one phase in the other, or using a designer surfactant protein that reduces the interfacial tension between the two phases. In addition, we studied factors that impact condensate miscibility and structure formation, including surface properties and viscoelasticity. This study probes the principles that underlie formation and assembly of complex structures from biomolecular condensates and provides a strategy for designing synthetic multiphasic materials capable of spatial partitioning.