bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraspecific variation of two duckweed species influences response to microcystin-LR exposure
Authors: Rzodkiewicz Lacey D. , Turcotte Martin M. 
Published: June 2023

AbstractCyanotoxins produced by harmful cyanobacteria blooms can damage freshwater ecosystems and threaten human health. Floating macrophytes may be used as a means of biocontrol by limiting light and resources available to cyanobacteria. However, genetic variation in macrophyte sensitivity to cyanotoxins could influence their suitability as biocontrol agents. We investigated the influence of such intraspecific variation on the response of two rapidly growing duckweed species,Lemna minorandSpirodela polyrhiza, often used in nutrient and metal bioremediation. We assessed two biomarkers related to productivity (biomass and chlorophyll A production) and two related to fitness measures (population size and growth rate). Fifteen genetic lineages of each species were grown in media containing common cyanotoxin microcystin-LR at ecologically relevant concentrations or control media for a period of twelve days. Genotype identity had a strong impact on all biomarker responses. Microcystin concentration did impact the final population sizes of both macrophyte species with a marginal effect on growth rate ofL. minorand the chlorophyll A production ofS. polyrhiza, but overall these species were very tolerant of microcystin. The strong tolerance supports the potential use of these plants as bioremediators of cyanobacterial blooms. The differential impact of microcystin exposure discovered in single lineage models among genotypes indicates a potential for cyanotoxins to act as selective forces and reduce local macrophyte genetic diversity.HighlightsEcotoxicology often uses standard genotypes of plants in testing.We tested the influence of clonal variation in duckweeds on their response to common cyanotoxin, microcystin-LR.Microcystin impacts were often masked by genotypic variation in response.Results imply that genotype identity may be important to bioremediation and local evolutionary dynamics.
Improving patient clustering by incorporating structured label relationships in similarity measures
Authors: Lambert Judith , Leutenegger Anne-Louise , Baudot Anaïs , Jannot Anne-Sophie 
Published: June 2023

AbstractContextPatient stratification is the cornerstone of numerous health studies, serving to enhance medicine efficacy estimation and facilitate patient matching. To stratify patients, similarity measured between patients can be computed from medical health records databases, such as medico-administrative databases. Importantly, the variables included in medico-administrative databases can be associated with labels, which can be organized in ontologies or other classification systems. However, to the best of our knowledge, the relevance of considering such label classification in the computation of patient similarity measures has been poorly studied.ObjectiveWe propose and evaluate several weighted versions of the Cosine similarity that consider structured label relationships to compute patient similarities from a medico-administrative database.Material and MethodsAs a use case, we analyze medicine reimbursements contained in theÉchantillon Généraliste des Bénéficiaires, a French medico-administrative database. We compute the standard Cosine similarity between patients based on their medicine reimbursement. In addition, we computed a weighted Cosine similarity measure that includes variable frequencies and two weighted Cosine similarity measures that consider label relationships. We construct patient networks from each similarity measure and identify clusters of patients. We evaluate the performance of the different similarity measures with enrichment tests using information on chronic diseases.ResultsThe similarity measures that include label relationships perform better to identify similar patients. Indeed, using these weighted measures, we identify distinct patient clusters with a higher number of chronic disease enrichments as compared to the other measures. Importantly, the enrichment tests provide clinically interpretable insights into these patient clusters.ConclusionConsidering label relationships when computing patient similarities improves stratification of patients regarding their health status.
Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis
Authors: An De-Wei , Hansen Tine W. , Aparicio Lucas S. , Chori Babangida , Huang Qi-Fang , Wei Fang-Fei , Cheng Yi-Bang , Yu Yu-Ling , Sheng Chang-Sheng , Gilis-Malinowska Natasza , Boggia José , Wojciechowska Wiktoria , Niiranen Teemu J. , Tikhonoff Valérie , Casiglia Edoardo , Narkiewicz Krzysztof , Stolarz-Skrzypek Katarzyna , Kawecka-Jaszcz Kalina , Jula Antti M. , Yang Wen-Yi , Woodiwiss Angela J. , Filipovský Jan , Wang Ji-Guang , Rajzer Marek W. , Verhamme Peter , Nawrot Tim S. , Staessen Jan A. , Li Yan ,   The International Database of Central Arterial Properties for Risk Stratification Investigators
Published: June 2023

ABSTRACTBACKGROUNDAortic pulse wave velocity (PWV) predicts cardiovascular events (CVE) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using two populations studies, respectively, for derivation (IDCARS) and replication (MONICA).METHODSA risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mmHg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI).RESULTSIn well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomical pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (HR [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both endpoints was ∼0.75. IDI was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas NRI was not for any outcome.CONCLUSIONSPWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person’s lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.
Mosquito surveillance on U.S military installations as part of a Japanese encephalitis virus detection program: 2016 to 2021
Authors: Olson Mark F. , Brooks Caroline , Kakazu Akira , Promma Ploenphit , Sornjai Wannapa , Smith Duncan R. , Davis Timothy J. 
Published: June 2023

AbstractJapanese encephalitis virus (JEV) continues to circulate throughout Southeast Asia and the Western Pacific where approximately 3 billion people in 24 countries are at risk of infection. Surveillance targeting the mosquito vectors of JEV was conducted at four military installations on Okinawa, Japan, between 2016 and 2021. Out of a total of 10,426 mosquitoes from 20 different species, zero were positive for JEV. The most abundant mosquito species collected wereAedes albopictus(36.4%) followed byCulex sitiens(24.3%) andArmigeres subalbatus(19%). Statistically significant differences in mosquito species populations according to location were observed. Changes in land use over time appear to be correlated with the species and number of mosquitoes trapped in each location. Japanese encephalitis virus appears to be absent from mosquito populations on Okinawa, but further research on domestic pigs and ardeid birds is warranted.Author summaryJapanese encephalitis (JE) is a vector borne disease of significant public health importance for over one third of the earth’s population. While JE was first reported in Japan, the most significant outbreaks today are occurring in China and India. Since 2015, Japanese encephalitis vaccine became mandatory for United States military personnel assigned to Japan or South Korea. In an effort to evaluate the risk of JE infection to service members stationed on Okinawa, mosquito surveillance was conducted at four military installations between 2016 and 2021. Over ten thousand mosquitoes were collected, identified to species, and subjected to PCR testing. None of these samples were positive for Japanese encephalitis virus, but further research is still necessary.
Comprehensive repertoire of the chromosomal alteration and mutational signatures across 16 cancer types from 10,983 cancer patients
Authors: Everall Andrew , Tapinos Avraam , Hawari Aliah , Cornish Alex , Sud Amit , Chubb Daniel , Kinnersley Ben , Frangou Anna , Barquin Miguel , Jung Josephine , Church David N ,   Genomics England Research Consortium, Alexandrov Ludmil , Houlston Richard , Gruber Andreas J. , Wedge David C. 
Published: June 2023

ABSTRACTWhole genome sequencing (WGS) allows exploration of the complete compendium of oncogenic processes generating characteristic patterns of mutations. Mutational signatures provide clues to tumour aetiology and highlight potentially targetable pathway defects. Here, alongside single base substitution (SBS), double base substitution (DBS), small insertions and deletions (ID) and copy number aberration (CN) signatures covered by the Catalogue of Somatic Mutations in Cancer (COSMIC) we report signatures from an additional mutation type, structural variations (SV), all extractedde-novofrom WGS in 10,983 patients across 16 tumour types recruited to the 100,000 genomes project. Across the five mutation classes we report 137 signatures, with 29 signatures new to COSMIC, including the first COSMIC SV signature reference set. We relate the signatures to clinical outcomes and likely response to therapy, demonstrating the role of signature analysis in delivering the vision of precision oncology.
Trajectory of plasma lipidomes associated with the risk of late-onset Alzheimer’s disease pathogenesis: a longitudinal study in the ADNI cohort
Authors: Wang Tingting , Arnold Matthias , Huynh Kevin , Weinisch Patrick , Giles Corey , Mellett Natalie A , Duong Thy , Marella Bharadwaj , Nho Kwangsik , De Livera Alysha , Han Xianlin , Blach Colette , Saykin Andrew J , Kastenmüller Gabi , Meikle Peter J , Kaddurah-Daouk Rima ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2023

AbstractComprehensive lipidomic studies have demonstrated strong cross-sectional associations between the blood lipidome and late-onset Alzheimer’s disease (AD) and its risk factors. However, the longitudinal relationship between the lipidomic variations and progression of AD remains unknown. Here, we employed longitudinal lipidomic profiling on 4,730 plasma samples from 1,517 participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort to investigate the temporal evolution of lipidomes among diagnostic groups. At baseline, there were 1,393 participants including 437 cognitively normal (CN), 713 with mild cognitive impairment (MCI), and 243 AD cases. During follow up, 329 individuals (29 CN and 300 MCI) developed clinical AD (AD converters). We developed an AD-CN classification model to stratify the non-converting MCI group into AD-like and non AD-like MCI based on their lipidomics profiles at baseline. Longitudinal analysis identified associations between the change in ether lipid species (including alkylphosphatidylcholine, alkenylphosphatidylcholine, lysoalkylphosphatidylcholine, and lysoalkenylphosphatidylcholine) in converters relative to non-converting CN and MCI groups. Further, the AD-CN model efficiently classified MCI into low AD risk and high AD risk, with the high AD risk group having two times higher risk of conversion to AD than the low risk group. These findings suggest that the lipidomic profile can serve as a potential biomarker to identify individuals at higher risk for progressing to AD.
Outcome Prediction in Aneurysmal Subarachnoid Hemorrhage with World Federation of Neurological Societies grade V(OPAS-V)
Authors: Yamada Shuhei , Nishida Takeo , Takenaka Tomofumi , Yamazaki Hiroki , Nakagawa Ryota , Takagaki Masatoshi , Yano Yoshihiro , Nakamura Hajime , Toyota Shingo , Fujinaka Toshiyuki , Taki Takuyu , Fujita Toshiaki , Kishima Haruhiko 
Published: June 2023

AbstractBackgroundAneurysmal subarachnoid hemorrhage (aSAH) with World Federation of Neurological Societies (WFNS) grade V has a high mortality rate and poor prognosis. Some patients with WFNS grade V aSAH have had good outcomes after aggressive treatment; however, outcome predictions based on routine examinations and findings obtained at admission are yet to be reported. This study aimed to develop a decision tree model for predicting outcomes of patients with WFNS grade V aSAH to aid decision-making for treatment strategy.MethodsA multicenter study with retrospective and prospective data collected from 201 (derivation cohort) and 12 (validation cohort) patients with WFNS grade V aSAH, respectively, was conducted. Clinical outcomes were divided into good (Modified Rankin Scale [mRS] score at the time of discharge: 0–2) and poor (mRS score: 3–6) outcomes. A decision tree model was developed for the derivation cohort using the classification and regression tree method with clinical data including laboratory findings; it was named OPAS-V (Outcome Prediction in Aneurysmal Subarachnoid hemorrhage with WFNS grade V). The performance of the model was evaluated by area under the curve (AUC) and overall accuracy in both cohorts.ResultsOPAS-V comprised 3 metrics; the percentage of lymphocytes (<49.9% or not), age (>50 yrs or not), and glucose to potassium ratio (≥3.2 or not). The model achieved an AUC of 0.828 (95% confidence interval: 0.712–0.944) and overall accuracy of 0.930. Moreover, the model performed well in the validation cohort with an AUC of 0.700 (95% confidence interval: 0.200–1) and overall accuracy of 0.833.ConclusionsThis study developed the first decision tree model for predicting outcomes of patients with WFNS grade V aSAH, based on simple findings obtained at admission. This may aid clinicians in determining treatment strategies for severe conditions such as WFNS grade V aSAH.
Fostering transparent medical image AI via an image-text foundation model grounded in medical literature
Authors: Kim Chanwoo , Gadgil Soham U. , DeGrave Alex J. , Cai Zhuo Ran , Daneshjou Roxana , Lee Su-In 
Published: June 2023

AbstractBuilding trustworthy and transparent image-based medical AI systems requires the ability to interrogate data and models at all stages of the development pipeline: from training models to post-deployment monitoring. Ideally, the data and associated AI systems could be described using terms already familiar to physicians, but this requires medical datasets densely annotated with semantically meaningful concepts. Here, we present a foundation model approach, named MONET (Medical cONcept rETriever), which learns how to connect medical images with text and generates dense concept annotations to enable tasks in AI transparency from model auditing to model interpretation. Dermatology provides a demanding use case for the versatility of MONET, due to the heterogeneity in diseases, skin tones, and imaging modalities. We trained MONET on the basis of 105,550 dermatological images paired with natural language descriptions from a large collection of medical literature. MONET can accurately annotate concepts across dermatology images as verified by board-certified dermatologists, outperforming supervised models built on previously concept-annotated dermatology datasets. We demonstrate how MONET enables AI transparency across the entire AI development pipeline from dataset auditing to model auditing to building inherently interpretable models.
Myeloid-derived suppressor cells exacerbate poly(I:C)-induced lung inflammation in mice with renal injury and older mice
Authors: Xie Zhiqi , Zhou Haoyang , Obana Masanori , Fujio Yasushi , Okada Naoki , Tachibana Masashi 
Published: June 2023

AbstractViral pneumonia is a global health burden with a high mortality rate, especially in the elderly and in patients with underlying diseases. Recent studies have found that myeloid-derived suppressor cells (MDSCs) are abundant in these patient groups; however, their roles in the progression of viral pneumonia remain unclear. In this study, we observed a substantial increase in MDSCs in a mouse model of renal ischemia/reperfusion (I/R) injury and in older mice. When intranasal polyinosinic- polycytidylic acid (poly(I:C)) administration was used to mimic viral pneumonia, we found that mice with renal I/R injury exhibited more severe lung inflammation than sham mice when challenged with poly(I:C). In addition, MDSC depletion attenuated lung inflammation in mice with I/R injury. Similar results were obtained in older mice compared with those in young mice. Furthermore, we found that the adoptive transfer ofin vitro-differentiated MDSCs exacerbated poly(I:C)-induced lung inflammation. Taken together, these experimental results suggest that the increased proportion of MDSCs in mice with renal I/R injury and in older mice exacerbates poly(I:C)-induced lung inflammation. These findings have important implications for the treatment and prevention of severe lung inflammation caused by viral pneumonia.
Proteomic insights into mental health status: plasma markers in young adults
Authors: Afonin Alexey M. , Piironen Aino-Kaisa , de Sousa Maciel Izaque , Ivanova Mariia , Alatalo Arto , Whipp Alyce M , Pulkkinen Lea , Rose Richard J , van Kamp Irene , Kaprio Jaakko , Kanninen Katja M. 
Published: June 2023

AbstractGlobal emphasis on enhancing prevention and treatment strategies necessitates increased understanding of biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the “general psychopathology factor”, is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography–tandem mass spectrometry, 14 proteins with a significant connection with the p-factor were identified, 9 of which were linked to epidermal growth factor receptor (EGFR) signalling. This exploratory study provides new insight into biological alterations associated with mental health status in young adults.
Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer
Authors: Zhang Linan , Cascio Sandra , Mellors John W , Buckanovich Ronald J , Osmanbeyoglu Hatice Ulku 
Published: June 2023

AbstractHigh-grade serous ovarian carcinoma (HGSOC) is a heterogeneous disease, and a high stromal/desmoplastic tumor microenvironment (TME) is associated with a poor outcome. Stromal cell subtypes, including fibroblasts, myofibroblasts, and cancer-associated mesenchymal stem cells, establish a complex network of paracrine signaling pathways with tumor-infiltrating immune cells that drive effector cell tumor immune exclusion and inhibit the antitumor immune response. Single-cell transcriptomics of the HGSOC TME from public and in-house datasets revealed a distinct transcriptomic landscape for immune and non-immune cells in high-stromal vs. low-stromal tumors. High-stromal tumors had a lower fraction of certain T cells, natural killer (NK) cells, and macrophages and increased expression of CXCL12 in epithelial cancer cells and cancer-associated mesenchymal stem cells (CA-MSCs). Analysis of cell-cell communication indicated that epithelial cancer cells and CA-MSCs secreted CXCL12 that interacted with the CXCR4 receptor, which was overexpressed on NK and CD8+T cells. CXCL12 and/or CXCR4 antibodies confirmed the immunosuppressive role of CXCL12-CXCR4 in high-stromal tumors.
Dopamine activation modulates oscillatory synchrony in the hippocampal-prefrontal cortex circuitry
Authors: de Oliveira-Júnior Benedito Alves , Leite João Pereira , Ruggiero Rafael Naime 
Published: June 2023

AbstractInteraction between brain networks forms the functional unit that sustains cognition and behavior. It has been proposed that oscillatory activity can synchronize distant neuronal populations. One crucial aspect to elucidate brain function and its emergent properties is to understand how functional connectivity is modulated in different time scales according to environmental or physiological demand. Modulatory neurotransmitters such as dopamine have been implicated in changes in membrane excitability, modulation of oscillatory power, and coherence in crucial circuits for cognition, such as the hippocampus-prefrontal cortex (HPC-PFC) pathway. However, it is not known how dopaminergic release modulates specifically the phase synchrony of HPC-PFC or which specific dopaminergic receptors are responsible for the effects. In this context, our objective was to investigate the influence of dopaminergic activity on HPC-PFC synchrony and to assess whether the observed effects are receptor-specific. Our results show that dopamine induces HPC-PFC theta synchrony dose-dependently. This effect is not reproduced by apomorphine unspecific agonism or by SKF and quinpirole agonists, which act respectively on D1- and D2-like receptors. Additionally, we observed a late effect with peak activity between 30 and 40 minutes after dopamine 100 nmol, apomorphine 0.75 mg/kg, or quinpirole administration in which the HPC-PFC delta synchrony increased. Together, these results evidence the participation of dopaminergic neurotransmission in regulating HPC-PFC oscillatory dynamics, Influencing the synchronization in slow frequency oscillation and long-distant brain communication.