bluuebunny/crossref_metadata_2025 huggingface dataset:
An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors
Authors: Zhang Xuan , Song Baobao , Carlino Maximillian J. , Li Guangyuan , Ferchen Kyle , Chen Mi , Thompson Evrett N. , Kain Bailee N. , Schnell Dan , Thakkar Kairavee , Kouril Michal , Jin Kang , Hay Stuart B. , Sen Sidharth , Bernardicius David , Ma Siyuan , Bennett Sierra N. , Croteau Josh , Salvatori Ornella , Lye Melvin H. , Gillen Austin E. , Jordan Craig T. , Singh Harinder , Krause Diane S. , Salomonis Nathan , Grimes H. Leighton
Published: March 2024

Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.
A Dataset of Electrical Components for Mesh Segmentation and Computational Geometry Research
Authors: Scheffler Benedikt , Bründl Patrick , Nguyen Huong Giang , Stoidner Micha , Franke Jörg
Published: March 2024

Data quality is of crucial importance in the field of automated or digitally assisted assembly. This paper presents a comprehensive data set of triangle meshes representing electrical and electronic components obtained by scraping Computer Aided Design (CAD) models from the Internet. Consisting of a total of 234 triangle meshes with labelled vertices, this data set was specifically created for segmentation tasks. Its versatility for multimodal tasks is underscored by the presence of various labels, including vertex labels, categories, and subcategories. This paper presents the data set and provides a thorough statistical analysis, including measures of shape, size, distribution, and inter-rater reliability. In addition, the paper suggests several approaches for using the data set, considering its multimodal characteristics. The data set and related findings presented in this paper are intended to encourage further research and advancement in the field of manufacturing automation, specifically spatial assembly.
An integrated multicriteria decision making framework for the selection of waste cement dust filled automotive brake friction composites
Authors: Singh Tej
Published: March 2024

This work discusses selecting optimal brake friction composite alternatives based on an integrated MABAC (multi-attributive border approximation area comparison) and AHP (analytic hierarchy process) approach. Therefore, non-asbestos automotive brake friction composites containing varying proportions of cement dust (50 to 0 wt%) and barium sulfate (0 to 50 wt%) were developed and tribo-evaluated on a Krauss machine following European regulations. Composite made up of 30 wt% cement dust and 20 wt% barium sulfate had the highest friction coefficient (0.361), lowest variability coefficient (0.598), and maximum recovery (123.27%). The composite with the least fading (15.36%) included 50 wt% cement dust, whereas the composite with the lowest wear (9.10 g) and the least frictional fluctuations (0.271) contained 50 wt% barium sulfate. By AHP, the friction coefficient (0.1989), fade (0.1696), recovery (0.1551), and wear (0.1412) were selected as the essential criteria in the performance assessment. Based on the MABAC ranking evaluation, the composite comprises 20 wt% barium sulfate and 30 wt% cement dust has the best tribological profile, whereas the composites of solely cement dust or barium sulfate have the poorest tribological profile. The acquired ranking results were confirmed using other decision-making models and subjected to sensitivity analysis to demonstrate their robustness.
A prospective multicenter assessor blinded pilot study using confocal laser endomicroscopy for intraoperative brain tumor diagnosis
Authors: Byun Yoon Hwan , Won Jae-Kyung , Hong Duk Hyun , Kang Ho , Kim Jang Hun , Yu Mi Ok , Kim Min-Sung , Kim Yong Hwy , Park Kyung-Jae , Jeong Min-Jae , Hwang Kyungmin , Kong Doo-Sik , Park Chul-Kee , Kang Shin-Hyuk
Published: March 2024

In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value < 0.005). These findings underscore cCeLL-Ex vivo's potential as a supplementary tool for intraoperative brain tumor diagnosis, with future studies anticipated to further validate its clinical utility.
Optimized machine learning model for air quality index prediction in major cities in India
Authors: Natarajan Suresh Kumar , Shanmurthy Prakash , Arockiam Daniel , Balusamy Balamurugan , Selvarajan Shitharth
Published: March 2024

Industrial advancements and utilization of large amount of fossil fuels, vehicle pollution, and other calamities increases the Air Quality Index (AQI) of major cities in a drastic manner. Major cities AQI analysis is essential so that the government can take proper preventive, proactive measures to reduce air pollution. This research incorporates artificial intelligence in AQI prediction based on air pollution data. An optimized machine learning model which combines Grey Wolf Optimization (GWO) with the Decision Tree (DT) algorithm for accurate prediction of AQI in major cities of India. Air quality data available in the Kaggle repository is used for experimentation, and major cities like Delhi, Hyderabad, Kolkata, Bangalore, Visakhapatnam, and Chennai are considered for analysis. The proposed model performance is experimentally verified through metrics like R-Square, RMSE, MSE, MAE, and accuracy. Existing machine learning models, like k-nearest Neighbor, Random Forest regressor, and Support vector regressor, are compared with the proposed model. The proposed model attains better prediction performance compared to traditional machine learning algorithms with maximum accuracy of 88.98% for New Delhi city, 91.49% for Bangalore city, 94.48% for Kolkata, 97.66% for Hyderabad, 95.22% for Chennai and 97.68% for Visakhapatnam city.
Diagnostic decisions of specialist optometrists exposed to ambiguous deep-learning outputs
Authors: Carmichael Josie , Costanza Enrico , Blandford Ann , Struyven Robbert , Keane Pearse A. , Balaskas Konstantinos
Published: March 2024

Artificial intelligence (AI) has great potential in ophthalmology. We investigated how ambiguous outputs from an AI diagnostic support system (AI-DSS) affected diagnostic responses from optometrists when assessing cases of suspected retinal disease. Thirty optometrists (15 more experienced, 15 less) assessed 30 clinical cases. For ten, participants saw an optical coherence tomography (OCT) scan, basic clinical information and retinal photography (‘no AI’). For another ten, they were also given AI-generated OCT-based probabilistic diagnoses (‘AI diagnosis’); and for ten, both AI-diagnosis and AI-generated OCT segmentations (‘AI diagnosis + segmentation’) were provided. Cases were matched across the three types of presentation and were selected to include 40% ambiguous and 20% incorrect AI outputs. Optometrist diagnostic agreement with the predefined reference standard was lowest for ‘AI diagnosis + segmentation’ (204/300, 68%) compared to ‘AI diagnosis’ (224/300, 75% p = 0.010), and ‘no Al’ (242/300, 81%, p =  < 0.001). Agreement with AI diagnosis consistent with the reference standard decreased (174/210 vs 199/210, p = 0.003), but participants trusted the AI more (p = 0.029) with segmentations. Practitioner experience did not affect diagnostic responses (p = 0.24). More experienced participants were more confident (p = 0.012) and trusted the AI less (p = 0.038). Our findings also highlight issues around reference standard definition.
Epidemiology and field efficacy of anthelmintic drugs associated with gastrointestinal nematodes of sheep in Nejo district, Oromia, Ethiopia
Authors: Solomon Latera , Haile Geremew , Ahmed Nejash A. , Abdeta Debela , Galalcha Workineh , Hailu Yacob
Published: March 2024

Gastrointestinal nematodes (GINs) are major constraints to health and productivity of small ruminants. Methods of their control relies mainly on anthelmintic drugs; however, the indiscriminate use of these drugs could lead to the development of anthelmintic resistance (AR). This study aimed to investigate the epidemiology of GINs infection, and field evaluation of anthelmintic efficacy in sheep. The epidemiological data were collected using a cross-sectional study design while a farm-based field study design was employed for the evaluation of anthelminthic efficacy. Furthermore, standard parasitological techniques were employed for qualitative and quantitative worm identification. The overall prevalence indicated 50.3%. Six genera of GINs (Haemonchus, Trichostrongylus, Oesophagostomum/Chabertia, Trichuris, Teladosargia/Ostertagia and Nematodirus) were identified. Among the identified genera, Haemonchus (25.4%) and Trichostrongylus (24.8%) were the dominant genera followed by mixed infection (21.8%), Oesophagostomum/Chabertia (10.4%), Trichuris (7.8%), Teladosargia (Ostertagia) (5.7%) and Nematodirus (4.1%). Mixed infections consisted either of double infections with Haemonchus and Trichostrongylus, or triple infections with Haemonchus, Trichostrongylus and Trichuris. The McMaster egg counting results showed that the mean EPG of infected sheep was 845.6. The results also showed 66 (34.2%), 101 (52.3%) and 26 (13.5%) sheep had low, moderate and heavy worm burden, respectively. Albendazole and Ivermectin showed low efficacy (percentage reductions = 90% and 92%; 95% lower confidence limit = 82.1% and 83.6% respectively) whereas Tetramisole was effective (FECR% = 96.8%; 95% LCL = 93.4%). Factors such as age, body condition, management system and past deworming history of sheep were found to have a statistically significant (p < 0.05) influence on the occurrence and burden of the worms. This is further explained as the highest prevalence and worm burden was detected in sheep of young age (p = 0.008; OR = 0.58; 95% CI = 0.39–0.87), poor body condition (p = 0.001; OR = 0.08; 95% CI = 0.04–0.16) and sheep kept under semi-intensive (p = 0.04; OR = 1.53; 95% CI = 1.02–2.29) with no deworming history for the last two months (p = 0.001; OR = 2.97; 95% CI = 1.94–4.56). The study results revealed that nematode infections were among sheep health constraints that could hurt their productivity while low efficacy of Albendazole and Ivermectin were detected. Therefore, the appropriate management techniques of GIN infections should be designed and implemented. Moreover, a further study involving more sensitive techniques (e.g. Mini-FLOTAC, molecular, and serological techniques) should be conducted by considering different host and environmental risk factors such as production level and seasons.
The neural basis of naturalistic semantic and social cognition
Authors: Thye Melissa , Hoffman Paul , Mirman Daniel
Published: March 2024

Decoding social environments and engaging meaningfully with other people are critical aspects of human cognition. Multiple cognitive systems, including social and semantic cognition, work alongside each other to support these processes. This study investigated shared processing between social and semantic systems using neuroimaging data collected during movie-viewing, which captures the multimodal environment in which social knowledge is exchanged. Semantic and social content from movie events (event-level) and movie transcripts (word-level) were used in parametric modulation analyses to test (1) the degree to which semantic and social information is processed within each respective network and (2) engagement of the same cross-network regions or the same domain-general hub located within the semantic network during semantic and social processing. Semantic word and event-level content engaged the same fronto-temporo-parietal network and a portion of the semantic hub in the anterior temporal lobe (ATL). Social word and event-level content engaged the supplementary motor area and right angular gyrus within the social network, but only social words engaged the domain-general semantic hub in left ATL. There was evidence of shared processing between the social and semantic systems in the dorsolateral portion of right ATL which was engaged by word and event-level semantic and social content. Overlap between the semantic and social word and event results was highly variable within and across participants, with the most consistent loci of overlap occurring in left inferior frontal, bilateral precentral and supramarginal gyri for social and semantic words and in bilateral superior temporal gyrus extending from ATL posteriorly into supramarginal gyri for social and semantic events. These results indicate a complex pattern of shared and distinct regions for social and semantic cognition during naturalistic processing.

Protocol registration

The stage 1 protocol for this Registered Report was accepted in principle on October 11, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/ACWQY.
Phototoxicity of low doses of light and influence of the spectral composition on human RPE cells
Authors: Françon Anaïs , Delaunay Kimberley , Jaworski Thara , Lebon Cécile , Picard Emilie , Youale Jenny , Behar-Cohen Francine , Torriglia Alicia
Published: March 2024

Light is known to induce retinal damage affecting photoreceptors and retinal pigment epithelium. For polychromatic light, the blue part of the spectrum is thought to be the only responsible for photochemical damage, leading to the establishment of a phototoxicity threshold for blue light (445 nm). For humans it corresponds to a retinal dose of 22 J/cm2. Recent studies on rodents and non-human primates suggested that this value is overestimated. In this study, we aim at investigating the relevance of the current phototoxicity threshold and at providing new hints on the role of the different components of the white light spectrum on phototoxicity. We use an in vitro model of human induced pluripotent stem cells (hiPSC)-derived retinal pigment epithelial (iRPE) cells and exposed them to white, blue and red lights from LED devices at doses below 22 J/cm2. We show that exposure to white light at a dose of 3.6 J/cm2 induces an alteration of the global cellular structure, DNA damage and an activation of cellular stress pathways. The exposure to blue light triggers DNA damage and the activation of autophagy, while exposure to red light modulates the inflammatory response and inhibits autophagy.
Experimental and computational evidence that Calpain-10 binds to the carboxy terminus of NaV1.2 and NaV1.6
Authors: Arratia Luis Manuel , Bermudes-Contreras Juan David , Juarez-Monroy Jorge Armando , Romero-Macías Erik Alan , Luna-Rojas Julio Cesar , López-Hidalgo Marisol , Vega Ana Victoria , Zamorano-Carrillo Absalom
Published: March 2024

Voltage-gated sodium channels (NaV) are pivotal proteins responsible for initiating and transmitting action potentials. Emerging evidence suggests that proteolytic cleavage of sodium channels by calpains is pivotal in diverse physiological scenarios, including ischemia, brain injury, and neuropathic pain associated with diabetes. Despite this significance, the precise mechanism by which calpains recognize sodium channels, especially given the multiple calpain isoforms expressed in neurons, remains elusive. In this work, we show the interaction of Calpain-10 with NaV's C-terminus through a yeast 2-hybrid assay screening of a mouse brain cDNA library and in vitro by GST-pulldown. Later, we also obtained a structural and dynamic hypothesis of this interaction by modeling, docking, and molecular dynamics simulation. These results indicate that Calpain-10 interacts differentially with the C-terminus of NaV1.2 and NaV1.6. Calpain-10 interacts with NaV1.2 through domains III and T in a stable manner. In contrast, its interaction with NaV1.6 involves domains II and III, which could promote proteolysis through the Cys-catalytic site and C2 motifs.
High-temperature tensile strength of C/SiC composite under laser-induced high heating flux in an aerobic environment
Authors: Wang Jiawei , Li Bin , Wang Shanshan , Zhang Shunlei , Yang Pengling , Wei Chenghua , Shen Yanlong
Published: March 2024

Based on the advantages of laser high brightness, a high-temperature mechanical property measuring device has been developed, which can measure the high-temperature strength of C/SiC composites under the condition of short-term high-temperature rise rate and solve the problem of over-oxidation of materials in conventional high-temperature mechanical properties experiments. The experimental results show that the maximum temperature rise rate is 260 ℃/s at the initial heating stage, and the test time is controlled within 35 s. The tensile strength of the prepared C/SiC composites decreased first and then increased at high temperatures and laser-induced high temperatures. The experimental results are similar to those in the literature under the inert atmosphere. Oxidation has less of an effect on the mechanical characteristics of materials under conditions of rapid temperature rise. The system can be used to test the mechanical properties of composite materials at high temperatures and as a simulation platform for the thermal response of specific thermal protection systems subjected to a constant heat flux. This study can provide a new idea for testing ultra-high temperature mechanical properties of C/SiC materials and provide key technical support for the engineering application and high-temperature testing of C/SiC materials in high-temperature environments.
An event-oriented diffusion-refinement method for sparse events completion
Authors: Zhang Bo , Han Yuqi , Suo Jinli , Dai Qionghai
Published: March 2024

Event cameras or dynamic vision sensors (DVS) record asynchronous response to brightness changes instead of conventional intensity frames, and feature ultra-high sensitivity at low bandwidth. The new mechanism demonstrates great advantages in challenging scenarios with fast motion and large dynamic range. However, the recorded events might be highly sparse due to either limited hardware bandwidth or extreme photon starvation in harsh environments. To unlock the full potential of event cameras, we propose an inventive event sequence completion approach conforming to the unique characteristics of event data in both the processing stage and the output form. Specifically, we treat event streams as 3D event clouds in the spatiotemporal domain, develop a diffusion-based generative model to generate dense clouds in a coarse-to-fine manner, and recover exact timestamps to maintain the temporal resolution of raw data successfully. To validate the effectiveness of our method comprehensively, we perform extensive experiments on three widely used public datasets with different spatial resolutions, and additionally collect a novel event dataset covering diverse scenarios with highly dynamic motions and under harsh illumination. Besides generating high-quality dense events, our method can benefit downstream applications such as object classification and intensity frame reconstruction.
Numerical performance of CO2 accumulation and droplet dispersion from a cough inside a hospital lift under different ventilation strategies
Authors: Chillón Sergio A. , Fernandez-Gamiz Unai , Zulueta Ekaitz , Ugarte-Anero Ainara , Blanco Jesus Maria
Published: March 2024

The impact of mechanical ventilation on airborne diseases is not completely known. The recent pandemic of COVID-19 clearly showed that additional investigations are necessary. The use of computational tools is an advantage that needs to be included in the study of designing safe places. The current study focused on a hospital lift where two subjects were included: a healthy passenger and an infected one. The elevator was modelled with a fan placed on the middle of the ceiling and racks for supplying air at the bottom of the lateral wall. Three ventilation strategies were evaluated: a without ventilation case, an upwards-blowing exhausting fan case and a downwards-blowing fan case. Five seconds after the elevator journey began, the infected person coughed. For the risk assessment, the CO2 concentration, droplet removal performance and dispersion were examined and compared among the three cases. The results revealed some discrepancies in the selection of an optimal ventilation strategy. Depending on the evaluated parameter, downward-ventilation fan or no ventilation strategy could be the most appropriate approach.
Characterization of diseased primary human hepatocytes in an all-human cell-based triculture system
Authors: Odanga Justin J. , Anderson Sharon M. , Breathwaite Erick K. , Presnell Sharon C. , LeCluyse Edward L. , Chen Jingsong , Weaver Jessica R.
Published: March 2024

Liver diseases, including NAFLD, are a growing worldwide health concern. Currently, there is a lack of suitable in vitro models that sustain basic primary human hepatocyte (PHH) morphology and functionality while supporting presentation of disease-associated phenotypic characteristics such as lipid accumulation and inflammasome activation. In TruVivo, an all-human triculture system (hTCS), basic metabolic functions were characterized in PHHs isolated from normal or diseased livers during two-weeks of culture. Decreases in albumin and urea levels and CYP3A4 activity were seen in diseased-origin PHHs compared to normal PHHs along with higher CYP2E1 expression. Positive expression of the macrophage markers CD68 and CD163 were seen in the diseased PHH preparations. Elevated levels of the pro-inflammatory cytokines IL-6 and MCP-1 and the fibrotic markers CK-18 and TGF-β were also measured. Gene expression of FASN, PCK1, and G6PC in the diseased PHHs was decreased compared to the normal PHHs. Further characterization revealed differences in lipogenesis and accumulation of intracellular lipids in normal and diseased PHHs when cultured with oleic acid and high glucose. TruVivo represents a promising new platform to study lipogenic mechanisms in normal and diseased populations due to the preservation of phenotypic differences over a prolonged culture period.
The value of marsh restoration for flood risk reduction in an urban estuary
Authors: Taylor-Burns Rae , Lowrie Christopher , Tehranirad Babak , Lowe Jeremy , Erikson Li , Barnard Patrick L. , Reguero Borja G. , Beck Michael W.
Published: March 2024

The use of nature-based solutions (NBS) for coastal climate adaptation has broad and growing interest, but NBS are rarely assessed with the same rigor as traditional engineering solutions or with respect to future climate change scenarios. These gaps pose challenges for the use of NBS for climate adaptation. Here, we value the flood protection benefits of stakeholder-identified marsh restoration under current and future climate change within San Francisco Bay, a densely urbanized estuary, and specifically on the shores of San Mateo County, the county most vulnerable to future flooding in California. Marsh restoration provides a present value of $21 million which increases to over $100 million with 0.5 m of sea level rise (SLR), and to about $500 million with 1 m of SLR. There are hotspots within the county where marsh restoration delivers very high benefits for adaptation, which reach $9 million/hectare with likely future sea level and storm conditions. Today’s investments in nature and community resilience can result in increasing payoffs as climate change progresses and risk increases.
Technical development and application of supercritical CO2 foaming technology in PCL foam production
Authors: Zhou Yujin , Tian Yingrui , Zhang Mengdong
Published: March 2024

Polycaprolactone (PCL) has the advantages of good biocompatibility, appropriate biodegradability, non-toxicity, flexibility, and processability. As a result, PCL-based foams can successfully work in bone tissue engineering, medical patches, drug delivery, reinforcing materials, and other applications. A promising technology for producing PCL foam products is supercritical CO2 (ScCO2) foaming technology, which avoids using organic solvents, is green, and has low foaming agent costs. However, due to the limitations of ScCO2 foaming technology, it is no longer possible to use this technology alone to meet current production requirements. Therefore, ScCO2 foaming technology must combine with other technologies to develop PCL foam products with better performance and matching requirements. This paper systematically reviews the technological development of ScCO2 foaming in producing PCL foams. The molding process of ScCO2 foaming and the conventional preparation process of PCL foam products are discussed comprehensively, including the preparation process, advantages, and disadvantages, challenges faced, etc. Six combined technologies for ScCO2 foaming in the production of PCL foams and the applications of PCL foams are presented. Finally, the future remaining research for producing PCL foams by ScCO2 foaming is analyzed.
Linking alterations in estrogen receptor expression to memory deficits and depressive behavior in an ovariectomy mouse model
Authors: Baek Dong-Cheol , Kang Ji-Yun , Lee Jin-Seok , Lee Eun-Jung , Son Chang-Gue
Published: March 2024

The high risk of neurological disorders in postmenopausal women is an emerging medical issue. Based on the hypothesis of altered estrogen receptors (ERα and β) after the decline of estrogen production, we investigated the changes in ERs expressions across brain regions and depressive/amnesic behaviors. C57BL/6J female mice were ovariectomized (OVX) to establish a menopausal condition. Along with behavior tests (anxiety, depression, and memory), the expression of ERs, microglial activity, and neuronal activity was measured in six brain regions (hippocampus, prefrontal cortex, striatum, raphe nucleus, amygdala, and hypothalamus) from 4 to 12 weeks after OVX. Mice exhibited anxiety- and depressive-like behaviors, as well as memory impairment. These behavioral alterations have been linked to a suppression in the expression of ERβ. The decreased ERβ expression coincided with microglial-derived neuroinflammation, as indicated by notable activations of Ionized calcium-binding adapter molecule 1 and Interleukin-1beta. Additionally, the activity of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus, decreased in a time-dependent manner from 4 to 12 weeks post-OVX. Our study provides evidence shedding light on the susceptibility to memory impairment and depression in women after menopause. This susceptibility is associated with the suppression of ERβ and alteration of ERα in six brain regions.
Evaluating screening for autism spectrum disorder using cluster randomization
Authors: Jonsdottir Sigridur Loa , Saemundsen Evald , Thorarinsdottir Elin Astros , Rafnsson Vilhjalmur
Published: March 2024

We evaluated the rate of autism spectrum disorder (ASD) in a group invited to a screening program compared to the rates in two groups who received usual care. The population eligible for screening was all children in Iceland registered for their 30-month well-child visits at primary healthcare centers (PHCs) from March 1, 2016, to October 31, 2017 (N = 7173). The PHCs in the capital area of Reykjavik were the units of cluster randomization. Nine PHCs were selected for intervention (invited group), while eight PHCs received usual care (control group 1). PHCs outside the capital area were without randomization (control group 2). An interdisciplinary team, including a pediatrician contributing with physical and neurological examination, a psychologist evaluating autism symptoms using a diagnostic instrument, and a social worker interviewing the parents, reached a consensus on the clinical diagnosis of ASD according to the ICD-10 diagnostic system. Children in the population were followed up for at least two years and 119 cases were identified. The overall cumulative incidence of ASD was 1.66 (95% confidence interval (CI): 1.37, 1.99). In the invited group the incidence rate was 2.13 (95% CI: 1.60, 2.78); in control group 1, the rate was 1.83 (95% CI: 1.31, 2.50); and in control group 2, the rate was 1.02 (95% CI: 0.66, 1.50). Although the rate of ASD was higher in the invited group than in the control groups, the wide confidence intervals prevented us from concluding definitively that the screening detected ASD more readily than usual care.
Position-specific isomers of monohydroxy fatty acids in the land-atmosphere interface: identification and quantification
Authors: Niu Mutong , An Na , Zhang Wenxin , Hu Wei , Fu Xiaoli , Kawamura Kimitaka , Feng Yuqi , Zhu Quanfei , Fu Pingqing
Published: March 2024

Due to a wide variety and similar physicochemical properties of monohydroxy saturated fatty acids (OH-FAs) isomers as biomarkers, previously reported OH-FAs in environmental samples were mainly restricted to the α-, β-, (ω-1)- and ω-OH-FA isomers. Here, N,N-dimethylethylenediamine (DMED) labeling coupled with ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis with multiple reaction monitoring mode (MRM) was developed to screen, identify and quantify position-specific isomers of OH-FAs (C8-C18). An identification strategy of positional isomers of OH-FAs, including α-, β-, 4 to (ω-2)-, (ω-1)- and ω-OH-FAs, was established by integrating the characteristics of peak intensity ratios of product ions based on the library of OH-FAs. Meanwhile, d4-DMED-labeled OH-FA standards as internal standards were adopted for the relative quantification of positional isomers. The extraction processes were optimized for different interface-environmental samples. Our method offers a promising tool to investigate position-specific isomers of OH-FAs in the land-atmosphere interface.
Large language models and multimodal foundation models for precision oncology
Authors: Truhn Daniel , Eckardt Jan-Niklas , Ferber Dyke , Kather Jakob Nikolas
Published: March 2024

The technological progress in artificial intelligence (AI) has massively accelerated since 2022, with far-reaching implications for oncology and cancer research. Large language models (LLMs) now perform at human-level competency in text processing. Notably, both text and image processing networks are increasingly based on transformer neural networks. This convergence enables the development of multimodal AI models that take diverse types of data as an input simultaneously, marking a qualitative shift from specialized niche models which were prevalent in the 2010s. This editorial summarizes these developments, which are expected to impact precision oncology in the coming years.
Deep learning on tertiary lymphoid structures in hematoxylin-eosin predicts cancer prognosis and immunotherapy response
Authors: Chen Ziqiang , Wang Xiaobing , Jin Zelin , Li Bosen , Jiang Dongxian , Wang Yanqiu , Jiang Mengping , Zhang Dandan , Yuan Pei , Zhao Yahui , Feng Feiyue , Lin Yicheng , Jiang Liping , Wang Chenxi , Meng Weida , Ye Wenjing , Wang Jie , Qiu Wenqing , Liu Houbao , Huang Dan , Hou Yingyong , Wang Xuefei , Jiao Yuchen , Ying Jianming , Liu Zhihua , Liu Yun
Published: March 2024

Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models’ discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis.
Digital twins for health: a scoping review
Authors: Katsoulakis Evangelia , Wang Qi , Wu Huanmei , Shahriyari Leili , Fletcher Richard , Liu Jinwei , Achenie Luke , Liu Hongfang , Jackson Pamela , Xiao Ying , Syeda-Mahmood Tanveer , Tuli Richard , Deng Jun
Published: March 2024

The use of digital twins (DTs) has proliferated across various fields and industries, with a recent surge in the healthcare sector. The concept of digital twin for health (DT4H) holds great promise to revolutionize the entire healthcare system, including management and delivery, disease treatment and prevention, and health well-being maintenance, ultimately improving human life. The rapid growth of big data and continuous advancement in data science (DS) and artificial intelligence (AI) have the potential to significantly expedite DT research and development by providing scientific expertise, essential data, and robust cybertechnology infrastructure. Although various DT initiatives have been underway in the industry, government, and military, DT4H is still in its early stages. This paper presents an overview of the current applications of DTs in healthcare, examines consortium research centers and their limitations, and surveys the current landscape of emerging research and development opportunities in healthcare. We envision the emergence of a collaborative global effort among stakeholders to enhance healthcare and improve the quality of life for millions of individuals worldwide through pioneering research and development in the realm of DT technology.
Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections
Authors: Cao Pengxing , Kho Steven , Grigg Matthew J. , Barber Bridget E. , Piera Kim A. , William Timothy , Poespoprodjo Jeanne R. , Jang Ihn Kyung , Simpson Julie A. , McCaw James M. , Anstey Nicholas M. , McCarthy James S. , Britton Sumudu
Published: March 2024

Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we developed mathematical models that capture parasite and matrix PvLDH dynamics in ex vivo culture and the human host. We estimated key biological parameters characterising in vivo PvLDH dynamics based on longitudinal data of parasitemia and PvLDH concentration collected from P. vivax-infected humans, with the estimates informed by the ex vivo data as prior knowledge in a Bayesian hierarchical framework. We found that the in vivo accumulation rate of intraerythrocytic PvLDH peaks at 10–20 h post-invasion (late ring stage) with a median estimate of intraerythrocytic PvLDH mass at the end of the life cycle to be 9.4 × 10−3ng. We also found that the median estimate of in vivo PvLDH half-life was approximately 21.9 h. Our findings provide a foundation with which to advance our quantitative understanding of P. vivax biology and will facilitate the improvement of PvLDH-based diagnostic tools.
Emergence and clonal expansion of a qacA-harbouring sequence type 45 lineage of methicillin-resistant Staphylococcus aureus
Authors: Nong Yi , Steinig Eike , Pollock Georgina L. , Taiaroa George , Carter Glen P. , Monk Ian R. , Pang Stanley , Daley Denise A. , Coombs Geoffrey W. , Forde Brian M. , Harris Patrick N. A. , Sherry Norelle L. , Howden Benjamin P. , Pasricha Shivani , Baines Sarah L. , Williamson Deborah A.
Published: March 2024

The past decade has seen an increase in the prevalence of sequence type (ST) 45 methicillin-resistant Staphylococcus aureus (MRSA), yet the underlying drivers for its emergence and spread remain unclear. To better understand the worldwide dissemination of ST45 S. aureus, we performed phylogenetic analyses of Australian isolates, supplemented with a global population of ST45 S. aureus genomes. Our analyses revealed a distinct lineage of multidrug-resistant ST45 MRSA harbouring qacA, predominantly found in Australia and Singapore. Bayesian inference predicted that the acquisition of qacA occurred in the late 1990s. qacA was integrated into a structurally variable region of the chromosome containing Tn552 (carrying blaZ) and Tn4001 (carrying aac(6’)-aph(2”)) transposable elements. Using mutagenesis and in vitro assays, we provide phenotypic evidence that qacA confers tolerance to chlorhexidine. These findings collectively suggest both antimicrobial resistance and the carriage of qacA may play a role in the successful establishment of ST45 MRSA.
Tissue damaging toxins in snake venoms: mechanisms of action, pathophysiology and treatment strategies
Authors: Bittenbinder Mátyás A. , van Thiel Jory , Cardoso Fernanda C. , Casewell Nicholas R. , Gutiérrez José-María , Kool Jeroen , Vonk Freek J.
Published: March 2024

Snakebite envenoming is an important public health issue responsible for mortality and severe morbidity. Where mortality is mainly caused by venom toxins that induce cardiovascular disturbances, neurotoxicity, and acute kidney injury, morbidity is caused by toxins that directly or indirectly destroy cells and degrade the extracellular matrix. These are referred to as ‘tissue-damaging toxins’ and have previously been classified in various ways, most of which are based on the tissues being affected (e.g., cardiotoxins, myotoxins). This categorisation, however, is primarily phenomenological and not mechanistic. In this review, we propose an alternative way of classifying cytotoxins based on their mechanistic effects rather than using a description that is organ- or tissue-based. The mechanisms of toxin-induced tissue damage and their clinical implications are discussed. This review contributes to our understanding of fundamental biological processes associated with snakebite envenoming, which may pave the way for a knowledge-based search for novel therapeutic options.
Interplay of biotic and abiotic factors shapes tree seedling growth and root-associated microbial communities
Authors: Chamard Joey , Faticov Maria , Blanchet F. Guillaume , Chagnon Pierre-Luc , Laforest-Lapointe Isabelle
Published: March 2024

Root-associated microbes can alleviate plant abiotic stresses, thus potentially supporting adaptation to a changing climate or to novel environments during range expansion. While climate change is extending plant species fundamental niches northward, the distribution and colonization of mutualists (e.g., arbuscular mycorrhizal fungi) and pathogens may constrain plant growth and regeneration. Yet, the degree to which biotic and abiotic factors impact plant performance and associated microbial communities at the edge of their distribution remains unclear. Here, we use root microscopy, coupled with amplicon sequencing, to study bacterial, fungal, and mycorrhizal root-associated microbial communities from sugar maple seedlings distributed across two temperate-to-boreal elevational gradients in southern Québec, Canada. Our findings demonstrate that soil pH, soil Ca, and distance to sugar maple trees are key drivers of root-associated microbial communities, overshadowing the influence of elevation. Interestingly, changes in root fungal community composition mediate an indirect effect of soil pH on seedling growth, a pattern consistent at both sites. Overall, our findings highlight a complex role of biotic and abiotic factors in shaping tree-microbe interactions, which are in turn correlated with seedling growth. These findings have important ramifications for tree range expansion in response to shifting climatic niches.
Contrasting segregation patterns among endogenous retroviruses across the koala population
Authors: Lillie Mette , Pettersson Mats , Jern Patric
Published: March 2024

Koalas (Phascolarctos cinereus) have experienced a history of retroviral epidemics leaving their trace as heritable endogenous retroviruses (ERVs) in their genomes. A recently identified ERV lineage, named phaCin-β, shows a pattern of recent, possibly current, activity with high insertional polymorphism in the population. Here, we investigate geographic patterns of three focal ERV lineages of increasing estimated ages, from the koala retrovirus (KoRV) to phaCin-β and to phaCin-β-like, using the whole-genome sequencing of 430 koalas from the Koala Genome Survey. Thousands of ERV loci were found across the population, with contrasting patterns of polymorphism. Northern individuals had thousands of KoRV integrations and hundreds of phaCin-β ERVs. In contrast, southern individuals had higher phaCin-β frequencies, possibly reflecting more recent activity and a founder effect. Overall, our findings suggest high ERV burden in koalas, reflecting historic retrovirus-host interactions. Importantly, the ERV catalogue supplies improved markers for conservation genetics in this endangered species.
Earthquakes unveil the global-scale fractality of the lithosphere
Authors: Perinelli Alessio , Ricci Leonardo , De Santis Angelo , Iuppa Roberto
Published: March 2024

The relationship between the magnitude of earthquakes and their spatial and temporal distribution has been observed to exhibit a scale invariance hypothesised to originate from self-organized critical regimes. However, the fractality of earthquake distributions has been mostly established in circumscribed areas, despite the fact that the self-organized criticality of the lithosphere should only emerge at global or continental level. Here, we analyze seismic observations occurring over the whole Earth between 2004–2020 to investigate the fractal correlation dimension of earthquakes distribution. We find that the distribution of earthquakes is fractal on a global scale, as well as approximately magnitude-independent and stationary over decadal time scales. Our results set a primary constraint on the spatial scaling properties of lithosphere dynamics. We suggest that macroscopic models should fulfil this constraint to correctly replicate the features of seismicity, and potentially improve seismic hazard assessment.
Manipulating the insulating post arrangement in DC-biased AC-iEK devices to improve microparticle separations
Authors: Nasir Ahamed Nuzhet Nihaar , Mendiola-Escobedo Carlos A. , Perez-Gonzalez Victor H. , Lapizco-Encinas Blanca H.
Published: March 2024

This study proposes a strategy for improving the separation resolution of binary microparticle mixtures by modifying the post array arrangement in insulator-based electrokinetic devices.
First-principles study of multifunctional Mn2B3 materials with high hardness and ferromagnetism
Authors: Xu Chunhong , Bao Kuo , Wang Sheng , Wu Gang , Ma Shuailing , Li Liangliang , Chu Paul K. , Liu Chao
Published: March 2024

Transition metal boride TM2B3 is widely studied in the field of physics and materials science.
Proposals for gas-detection improvement of the FeMPc monolayer towards ethylene and formaldehyde by using bimetallic synergy
Authors: Ma Yingying , Xiong Huihui , Zhang Jianbo
Published: March 2024

Development and fabrication of a novel gas sensor with superb performance are crucial for enabling real-time monitoring of ethylene (C2H4) and formaldehyde (H2CO) emissions from industrial manufacture.
The effect of a polymer capping agent on electrodeposited silver nanoparticles in a silver deposition-based electrochromic device
Authors: Uji Shun , Nakamura Kazuki , Kobayashi Norihisa
Published: March 2024

By introducing PVP to the Ag deposition-based EC device, PVP prevented the coalescence of Ag nanoparticles due to its capping effect. This work provides a novel method for controlling the morphology of electrodeposited metal nanoparticles using additives.
Exploring the large chemical space in search of thermodynamically stable and mechanically robust MXenes via machine learning
Authors: Park Jaejung , Kim Minseon , Kim Heekyu , Lee Jaejun , Lee Inhyo , Park Haesun , Lee Anna , Min Kyoungmin , Lee Seungchul
Published: March 2024

A high-throughput MXene screening framework that combines machine learning and density functional theory calculations was proposed to expeditiously evaluate the thermodynamic stability of various MXenes and to explore their mechanical properties.
In situ Sr–Nd isotope analysis of vesuvianite by LA-MC-ICP-MS: methodology and application
Authors: Wei Qin-Di , Yang Yue-Heng , Wang Hao , Wu Shi-Tou , Yang Ming , Huang Chao , Xu Lei , Xie Lie-Wen , Yang Jin-Hui , Wu Fu-Yuan
Published: March 2024

Methodology and application for in situ Sr–Nd isotope analyses of vesuvianite were presented using LA-MC-ICP-MS.
Effective synthesis of diethyl carbonate over Mg–Y composite oxides via alcoholysis of ethyl carbamate
Authors: Wang Peixue , Liu Shimin , Cui Xinjiang , Wu Yang , Shi Feng
Published: March 2024

Effective synthesis of diethyl carbonate from ethyl carbamate and ethanol using Mg–Y composite oxides.
Recent advancements in the specific determination of carcinoembryonic antigens using MOF-based immunosensors
Authors: Karimzadeh Zahra , Mahmoudpour Mansour , Rahimpour Elaheh , Jouyban Abolghasem
Published: March 2024

Carcinoembryonic antigens (CEAs) are prominent cancer biomarkers that enable the early detection of numerous cancers.
Braiding, twisting, and weaving microscale fibers with capillary forces
Authors: Sherif Ahmed , Faaborg Maya Winters , Zeng Cheng , Brenner Michael P. , Manoharan Vinothan N.
Published: March 2024

We present a 3D-printed machine that uses repulsive capillary forces to programmably braid, twist, and weave micrometer-scale fibers.
Ammonium persulfate assisted synthesis of ant-nest-like hierarchical porous carbons derived from chitosan for high-performance supercapacitors and zinc-ion hybrid capacitors
Authors: Chen Gui , Chen Shaozhen , Wu Xiaoyan , Wu Caijuan , Xiao Yong , Dong Hanwu , Yu Xiaoyuan , Liang Yeru , Hu Hang , Zheng Mingtao
Published: March 2024

A novel strategy is developed for the preparation of chitosan-derived ant-nest-like hierarchical porous carbons (AH-PCs), which exhibit excellent electrochemical performances both for supercapacitors and zinc-ion hybrid capacitors.