bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of an Open Central American Seaway on Ocean Circulation and the Oxygen Minimum Zone in the Tropical Pacific From Model Simulations
Authors: Khon V. C. , Hoogakker B. A. A. , Schneider B. , Segschneider J. , Park W.
Published: October 2023

The tectonic closure of the Central American Seaway (CAS) during the mid‐Miocene to mid‐Pliocene (∼16–3 Ma BP) is thought of as a key interval for the onset of the present‐day tropical Pacific oxygen minimum zone (OMZ). In this study we investigate the impact of an open CAS on the ocean circulation and the OMZ in the tropical Pacific. We perform a series of sensitivity experiments with the Kiel Climate Model, where we vary the CAS sill depth from shallow to deep. We find that the eastern tropical Pacific OMZ was less developed during the period of an open CAS. This is driven mainly by an enhanced eastward subsurface current that facilitated an increased oxygen supply from the western tropical Pacific. In addition, a small decrease in net marine primary production and subsequent weaker export of particulate organic carbon induced less subsurface oxygen consumption in the Eastern Equatorial Pacific.
The Influence of Southeastern South American Rainfall on Weather Patterns Over the Tropical Atlantic, Northwestern Africa and Western Europe
Authors: Zhao Siyu , Fu Rong , Wang Hui , Jin Fei‐Fei
Published: October 2023

During boreal winter (December–February), the South American monsoon system (SAMS) reaches its annual maximum when upper‐tropospheric westerly winds prevail over the equatorial Atlantic. Atmospheric dynamic model simulations suggest that Rossby waves generated over South America can propagate to and potentially influence weather patterns in the Northern Hemisphere (NH). However, observational evidence has been absent previously. Here we focus on southeastern South American (SESA) precipitation anomalies, which can characterize intraseasonal rainfall variability of the SAMS. Since tropical “westerly duct” and convective heating are important factors for cross‐equatorial propagation of Rossby wave (CEPRW), we identify two groups of events based on the two factors. By comparing the events associated with both SESA rainfall and tropical westerlies to the events associated with tropical westerlies only, we find that an anomalous Rossby wave train is triggered by precipitation anomalies over SESA, propagates in the southwest–northeast direction, and subsequently crosses the equator. Over a period of 4 days, near‐surface temperature over northwestern Africa and western Europe becomes warmer, accompanied by increased surface downward longwave radiation and precipitable water. The equatorward propagating Eliassen–Palm flux anomalies originated from SESA support the evidence of CEPRW. Simulations using a time‐dependent linear barotropic model forced by prescribed divergence anomalies over SESA further confirm that SESA rainfall can influence the NH weather patterns through CEPRW. Knowledge of this study will help us better understand and model interhemispheric teleconnections over the American–Atlantic–African/European sector.
Slopes of Lunar Crater Size‐Frequency Distributions at Copernican‐Aged Craters
Authors: Oetting A. , Schmedemann N. , Hiesinger H. , van der Bogert C. H.
Published: October 2023

Craters on the lunar surface can provide valuable information about the timing and sequence of surface‐forming processes on the Moon. A commonly used method for age determination is the analysis of the crater size‐frequency distribution (CSFD) to which a production function (PF) is fitted that represents the size‐frequency distribution of the impactors. However, the commonly used PF of Neukum (1983) is valid for crater diameters between 10 m and 300 km. Neukum et al. (2001, https://doi.org/10.1007/978-94-017-1035-0_3) revised the PF for crater diameters of 100 m–200 km. However, it is suggested to also be valid for the diameter range of 10 m–300 km as well. To assess whether we can extend a PF to craters ≤10 m in diameter, we investigated the slopes of the CSFDs of small craters formed on ejecta of young Copernican‐aged craters Giordano Bruno, Moore F, North Ray, and South Ray. A PF for smaller diameters would allow dating of young geological units, which are typically small, and would reduce the statistical error in age determinations, since smaller craters are more abundant. However, small craters are strongly influenced by geological factors, such as target properties, crater degradation, and secondary craters. For craters between 10 and 20 m we obtain a steeper CSFD slope than Neukum's proposed −3 slope (cumulative), whereas for craters ≤10 m the slope is about −3. We conclude that the PF of Neukum (1983) provides a reasonable CSFD slope for smaller craters, although it was not developed for this crater diameter range.
Anthropogenic Perturbations Change the Quality and Quantity of Terrestrial Carbon Flux to the Coastal Ocean
Authors: Wei Bingbing , Mollenhauer Gesine , Kusch Stephanie , Hefter Jens , Grotheer Hendrik , Schefuß Enno , Geibert Walter , Ransby Daniela , Jia Guodong
Published: October 2023

Human activities have increasingly changed terrestrial particulate organic carbon (POC) export to the coastal ocean since the Industrial Age (19th century). However, the influence of human perturbations on the composition and flux of terrestrial biospheric and petrogenic POC sub‐pools remains poorly constrained. Here, we examined 13C and 14C compositions of bulk POC and source‐specific biomarkers (fatty acids, FA) from two nearshore sediment cores collected in the Pearl River‐derived mudbelt, to determine the impacts of human perturbations of the Pearl River watershed on the burial of terrestrial POC in the coastal ocean over the last century. Our results show that although agricultural practices and deforestation during the 1930s–1950s increased C4 plant coverage in the watershed, the export fluxes of terrestrial biospheric and petrogenic POC remained rather unchanged; however, added perturbations since 1974, including increasing coal consumption, embankment and dam constructions caused massive export of both petrogenic POC and relatively fresh terrestrial biospheric POC from the river delta. Our data reveal that human activities substantially enhance the transfer of petrogenic POC and fresh biospheric POC to the coastal ocean after ca. 1974, with the latter process acting as an important sink for anthropogenic CO2.
Tropical Cyclones and Equatorial Waves in a Convection‐Permitting Aquaplanet Simulation With Off‐Equatorial SST Maximum
Authors: Rios‐Berrios Rosimar , Davis Christopher A. , Martinez Jonathan
Published: October 2023

Tropical weather phenomena—including tropical cyclones (TCs) and equatorial waves—are influenced by planetary‐to‐convective‐scale processes; yet, existing data sets and tools can only capture a subset of those processes. This study introduces a convection‐permitting aquaplanet simulation that can be used as a laboratory to study TCs, equatorial waves, and their interactions. The simulation was produced with the Model for Prediction Across Scales‐Atmosphere (MPAS‐A) using a variable resolution mesh with convection‐permitting resolution (i.e., 3‐km cell spacing) between 10°S and 30°N. The underlying sea‐surface temperature is given by a zonally symmetric profile with a peak at 10°N, which allows for the formation of TCs. A comparison between the simulation and satellite, reanalysis, and airborne dropsonde data is presented to determine the realism of the simulated phenomena. The simulation captures a realistic TC intensity distribution, including major hurricanes, but their lifetime maximum intensities may be limited by the stronger vertical wind shear in the simulation compared to the observed tropical Pacific region. The simulation also captures convectively coupled equatorial waves, including Kelvin waves and easterly waves. Despite the idealization of the aquaplanet setup, the simulated three‐dimensional structure of both groups of waves is consistent with their observed structure as deduced from satellite and reanalysis data. Easterly waves, however, have peak rotation and meridional winds at a slightly higher altitude than in the reanalysis. Future studies may use this simulation to understand how convectively coupled equatorial waves influence the multi‐scale processes leading to tropical cyclogenesis.
MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1
Authors: Zhang Chen , Ye Weilong , Zhao Mengyao , Long Lujue , Xia Dengsheng , Fan Zhipeng
Published: October 2023

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), βIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.
Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm
Authors: Cui Ming , Hu Ya , Zhang Zejian , Chen Tianqi , Dai Menghua , Xu Qiang , Guo Junchao , Zhang Taiping , Liao Quan , Yu Jun , Zhao Yupei
Published: October 2023

Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.
Association of polygenic risk for bipolar disorder with grey matter structure and white matter integrity in youth
Authors: Jiang Xinyue , Zai Clement C. , Kennedy Kody G. , Zou Yi , Nikolova Yuliya S. , Felsky Daniel , Young L. Trevor , MacIntosh Bradley J. , Goldstein Benjamin I.
Published: October 2023

There is a gap in knowledge regarding the polygenic underpinnings of brain anomalies observed in youth bipolar disorder (BD). This study examined the association of a polygenic risk score for BD (BD-PRS) with grey matter structure and white matter integrity in youth with and without BD. 113 participants were included in the analyses, including 78 participants with both T1-weighted and diffusion-weighted MRI images, 32 participants with T1-weighted images only, and 3 participants with diffusion-weighted images only. BD-PRS was calculated using PRS-CS-auto and was based on independent adult genome-wide summary statistics. Vertex- and voxel-wise analyses examined the associations of BD-PRS with grey matter metrics (cortical volume [CV], cortical surface area [CSA], cortical thickness [CTh]) and fractional anisotropy [FA] in the combined sample, and separately in BD and HC. In the combined sample of participants with T1-weighted images (n = 110, 66 BD, 44 HC), higher BD-PRS was associated with smaller grey matter metrics in frontal and temporal regions. In within-group analyses, higher BD-PRS was associated with lower CTh of frontal, temporal, and fusiform gyrus in BD, and with lower CV and CSA of superior frontal gyrus in HC. In the combined sample of participants with diffusion-weighted images (n = 81, 49 BD, 32 HC), higher BD-PRS was associated with lower FA in widespread white matter regions. In summary, BD-PRS calculated based on adult genetic data was negatively associated with grey matter structure and FA in youth in regions implicated in BD, which may suggest neuroimaging markers of vulnerability to BD. Future longitudinal studies are needed to examine whether BD-PRS predicts neurodevelopmental changes in BD vs. HC and its interaction with course of illness and long-term medication use.
The role of sphingosine-1-phosphate in autophagy and related disorders
Authors: Xiao Siqi , Peng Kaixin , Li Congxin , Long Yuanyuan , Yu Qin
Published: October 2023

S1P, also referred to as sphingosine-1-phosphate, is a lipid molecule with bioactive properties involved in numerous cellular processes such as cell growth, movement, programmed cell death, self-degradation, cell specialization, aging, and immune system reactions. Autophagy is a meticulously controlled mechanism in which cells repurpose their elements to maintain cellular balance. There are five stages in autophagy: initiation, nucleation, elongation and maturation, fusion, and degradation. New research has provided insight into the complex connection between S1P and autophagy, uncovering their interaction in both normal and abnormal circumstances. Gaining knowledge about the regulatory mechanism of S1P signaling on autophagy can offer a valuable understanding of its function in well-being and illness, potentially leading to innovative therapeutic concepts for diverse ailments. Hence, this review analyzes the essential stages in mammalian autophagy, with a specific emphasis on recent research exploring the control of each stage by S1P. Additionally, it sheds light on the roles of S1P-induced autophagy in various disorders.
A spatial sequencing atlas of age-induced changes in the lung during influenza infection
Authors: Kasmani Moujtaba Y. , Topchyan Paytsar , Brown Ashley K. , Brown Ryan J. , Wu Xiaopeng , Chen Yao , Khatun Achia , Alson Donia , Wu Yue , Burns Robert , Lin Chien-Wei , Kudek Matthew R. , Sun Jie , Cui Weiguo
Published: October 2023

Influenza virus infection causes increased morbidity and mortality in the elderly. Aging impairs the immune response to influenza, both intrinsically and because of altered interactions with endothelial and pulmonary epithelial cells. To characterize these changes, we performed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and bulk RNA sequencing (bulk RNA-seq) on lung tissue from young and aged female mice at days 0, 3, and 9 post-influenza infection. Our analyses identified dozens of key genes differentially expressed in kinetic, age-dependent, and cell type-specific manners. Aged immune cells exhibited altered inflammatory, memory, and chemotactic profiles. Aged endothelial cells demonstrated characteristics of reduced vascular wound healing and a prothrombotic state. Spatial transcriptomics identified novel profibrotic and antifibrotic markers expressed by epithelial and non-epithelial cells, highlighting the complex networks that promote fibrosis in aged lungs. Bulk RNA-seq generated a timeline of global transcriptional activity, showing increased expression of genes involved in inflammation and coagulation in aged lungs. Our work provides an atlas of high-throughput sequencing methodologies that can be used to investigate age-related changes in the response to influenza virus, identify novel cell-cell interactions for further study, and ultimately uncover potential therapeutic targets to improve health outcomes in the elderly following influenza infection.
Sonogenetic control of multiplexed genome regulation and base editing
Authors: Liu Pei , Foiret Josquin , Situ Yinglin , Zhang Nisi , Kare Aris J. , Wu Bo , Raie Marina N. , Ferrara Katherine W. , Qi Lei S.
Published: October 2023

Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, and tunable strategy for controlling the expression of multiple endogenous genes both in vitro and in vivo, utilizing ultrasound as the stimulus. By engineering a hyper-efficient dCas12a and effector under a heat shock promoter, we demonstrate a system that can be inducibly activated through thermal energy produced by ultrasound absorption. This system allows versatile thermal induction of gene activation or base editing across cell types, including primary T cells, and enables multiplexed gene activation using a single guide RNA array. In mouse models, localized temperature elevation guided by high-intensity focused ultrasound effectively triggers reporter gene expression in implanted cells. Our work underscores the potential of ultrasound as a clinically viable approach to enhance cell and gene-based therapies via precision genome and epigenome engineering.
Subcycle surface electron emission driven by strong-field terahertz waveforms
Authors: Li Shaoxian , Sharma Ashutosh , Márton Zsuzsanna , Nugraha Priyo S. , Lombosi Csaba , Ollmann Zoltán , Márton István , Dombi Péter , Hebling János , Fülöp József A.
Published: October 2023

The advent of intense terahertz (THz) sources opened a new era when the demonstration of the acceleration and manipulation of free electrons by THz pulses became within reach. THz-field-driven electron emission was predicted to be confined to a single burst due to the single-cycle waveform. Here we demonstrate the confinement of single-cycle THz-waveform-driven electron emission to one of the two half cycles from a solid surface emitter. Either the leading or the trailing half cycle was active, controlled by reversing the field polarity. THz-driven single-burst surface electron emission sources, which do not rely on field-enhancement structures, will impact the development of THz-powered electron acceleration and manipulation devices, all-THz compact electron sources, THz waveguides and telecommunication, THz-field-based measurement techniques and solid-state devices.
The SMN complex drives structural changes in human snRNAs to enable snRNP assembly
Authors: Pánek Josef , Roithová Adriana , Radivojević Nenad , Sýkora Michal , Prusty Archana Bairavasundaram , Huston Nicholas , Wan Han , Pyle Anna Marie , Fischer Utz , Staněk David
Published: October 2023

Spliceosomal snRNPs are multicomponent particles that undergo a complex maturation pathway. Human Sm-class snRNAs are generated as 3′-end extended precursors, which are exported to the cytoplasm and assembled together with Sm proteins into core RNPs by the SMN complex. Here, we provide evidence that these pre-snRNA substrates contain compact, evolutionarily conserved secondary structures that overlap with the Sm binding site. These structural motifs in pre-snRNAs are predicted to interfere with Sm core assembly. We model structural rearrangements that lead to an open pre-snRNA conformation compatible with Sm protein interaction. The predicted rearrangement pathway is conserved in Metazoa and requires an external factor that initiates snRNA remodeling. We show that the essential helicase Gemin3, which is a component of the SMN complex, is crucial for snRNA structural rearrangements during snRNP maturation. The SMN complex thus facilitates ATP-driven structural changes in snRNAs that expose the Sm site and enable Sm protein binding.
Infection- or AZD1222 vaccine-mediated immunity reduces SARS-CoV-2 transmission but increases Omicron competitiveness in hamsters
Authors: Port Julia R. , Yinda Claude Kwe , Riopelle Jade C. , Weishampel Zachary A. , Saturday Taylor A. , Avanzato Victoria A. , Schulz Jonathan E. , Holbrook Myndi G. , Barbian Kent , Perry-Gottschalk Rose , Haddock Elaine , Martens Craig , Shaia Carl. I. , Lambe Teresa , Gilbert Sarah C. , van Doremalen Neeltje , Munster Vincent J.
Published: October 2023

Limited data is available on the effect of vaccination and previous virus exposure on the nature of SARS-CoV-2 transmission and immune-pressure on variants. To understand the impact of pre-existing immunity on SARS-CoV-2 airborne transmission efficiency, we perform a transmission chain experiment using naïve, intranasally or intramuscularly AZD1222 vaccinated, and previously infected hamsters. A clear gradient in transmission efficacy is observed: Transmission in hamsters vaccinated via the intramuscular route was reduced over three airborne chains (approx. 60%) compared to naïve animals, whereas transmission in previously infected hamsters and those vaccinated via the intranasal route was reduced by 80%. We also find that the Delta B.1.617.2 variant outcompeted Omicron B.1.1.529 after dual infection within and between hosts in naïve, vaccinated, and previously infected transmission chains, yet an increase in Omicron B.1.1.529 competitiveness is observed in groups with pre-existing immunity against Delta B.1.617.2. This correlates with an increase in the strength of the humoral response against Delta B.1.617.2, with the strongest response seen in previously infected animals. These data highlight the continuous need to improve vaccination strategies and address the additional evolutionary pressure pre-existing immunity may exert on SARS-CoV-2.
Arctic weather variability and connectivity
Authors: Meng Jun , Fan Jingfang , Bhatt Uma S. , Kurths Jürgen
Published: October 2023

The Arctic’s rapid sea ice decline may influence global weather patterns, making the understanding of Arctic weather variability (WV) vital for accurate weather forecasting and analyzing extreme weather events. Quantifying this WV and its impacts under human-induced climate change remains a challenge. Here we develop a complexity-based approach and discover a strong statistical correlation between intraseasonal WV in the Arctic and the Arctic Oscillation. Our findings highlight an increased variability in daily Arctic sea ice, attributed to its decline accelerated by global warming. This weather instability can influence broader regional patterns via atmospheric teleconnections, elevating risks to human activities and weather forecast predictability. Our analyses reveal these teleconnections and a positive feedback loop between Arctic and global weather instabilities, offering insights into how Arctic changes affect global weather. This framework bridges complexity science, Arctic WV, and its widespread implications.
Metabolic fingerprinting on retinal pigment epithelium thickness for individualized risk stratification of type 2 diabetes mellitus
Authors: Yang Shaopeng , Zhu Zhuoting , Chen Shida , Yuan Yixiong , He Mingguang , Wang Wei
Published: October 2023

The retina is an important target organ of diabetes mellitus, with increasing evidence from patients and animal models suggesting that retinal pigment epithelium (RPE) may serve as an early marker for diabetes-related damages. However, their longitudinal relationship and the biological underpinnings remain less well understood. Here, we demonstrate that reduced in vivo measurements of RPE thickness (RPET) represents a significant risk factor for future type 2 diabetes mellitus (T2DM) and its microvascular phenotypes. After performing systematic analyses of circulating plasma metabolites using two complementary approaches, we identify a wide range of RPET metabolic fingerprints that are independently associated with reduced RPET. These fingerprints hold their potential to improve predictability and clinical utility for stratifying future T2DM and related microvascular phenotypes beyond traditional clinical indicators, providing insights into the promising role of retinas as a window to systemic health.
The ClpX protease is essential for inactivating the CI master repressor and completing prophage induction in Staphylococcus aureus
Authors: Thabet Mohammed A. , Penadés José R. , Haag Andreas F.
Published: October 2023

Bacteriophages (phages) are the most abundant biological entities on Earth, exerting a significant influence on the dissemination of bacterial virulence, pathogenicity, and antimicrobial resistance. Temperate phages integrate into the bacterial chromosome in a dormant state through intricate regulatory mechanisms. These mechanisms repress lytic genes while facilitating the expression of integrase and the CI master repressor. Upon bacterial SOS response activation, the CI repressor undergoes auto-cleavage, producing two fragments with the N-terminal domain (NTD) retaining significant DNA-binding ability. The process of relieving CI NTD repression, essential for prophage induction, remains unknown. Here we show a specific interaction between the ClpX protease and CI NTD repressor fragment of phages Ф11 and 80α in Staphylococcus aureus. This interaction is necessary and sufficient for prophage activation after SOS-mediated CI auto-cleavage, defining the final stage in the prophage induction cascade. Our findings unveil unexpected roles of bacterial protease ClpX in phage biology.
Microgravity studies of solidification patterns in model transparent alloys onboard the International Space Station
Authors: Akamatsu S. , Bottin-Rousseau S. , Witusiewicz V. T. , Hecht U. , Plapp M. , Ludwig A. , Mogeritsch J. , Şerefoğlu M. , Bergeon N. , Mota F. L. , Sturz L. , Zimmermann G. , McFadden S. , Sillekens W.
Published: October 2023

We review recent in situ solidification experiments using nonfaceted model transparent alloys in science-in-microgravity facilities onboard the International Space Station (ISS), namely the Transparent Alloys (TA) apparatus and the Directional Solidification Insert of the DEvice for the study of Critical Liquids and Crystallization (DECLIC-DSI). These directional-solidification devices use innovative optical videomicroscopy imaging techniques to observe the spatiotemporal dynamics of solidification patterns in real time in large samples. In contrast to laboratory conditions on ground, microgravity guarantees the absence or a reduction of convective motion in the liquid, thus ensuring a purely diffusion-controlled growth of the crystalline solid(s). This makes it possible to perform a direct theoretical analysis of the formation process of solidification microstructures with comparisons to quantitative numerical simulations. Important questions that concern multiphase growth patterns in eutectic and peritectic alloys on the one hand and single-phased, cellular and dendritic structures on the other hand have been addressed, and unprecedented results have been obtained. Complex self-organizing phenomena during steady-state and transient coupled growth in eutectics and peritectics, interfacial-anisotropy effects in cellular arrays, and promising insights into the columnar-to-equiaxed transition are highlighted.
Mediation and longitudinal analysis to interpret the association between clozapine pharmacokinetics, pharmacogenomics, and absolute neutrophil count
Authors: Lock Siobhan K. , Legge Sophie E. , Kappel Djenifer B. , Willcocks Isabella R. , Helthuis Marinka , Jansen John , Walters James T. R. , Owen Michael J. , O’Donovan Michael C. , Pardiñas Antonio F.
Published: October 2023

Clozapine is effective at reducing symptoms of treatment-resistant schizophrenia, but it can also induce several adverse outcomes including neutropenia and agranulocytosis. We used linear mixed-effect models and structural equation modelling to determine whether pharmacokinetic and genetic variables influence absolute neutrophil count in a longitudinal UK-based sample of clozapine users not currently experiencing neutropenia (N = 811). Increased daily clozapine dose was associated with elevated neutrophil count, amounting to a 133 cells/mm3 rise per standard deviation increase in clozapine dose. One-third of the total effect of clozapine dose was mediated by plasma clozapine and norclozapine levels, which themselves demonstrated opposing, independent associations with absolute neutrophil count. Finally, CYP1A2 pharmacogenomic activity score was associated with absolute neutrophil count, supporting lower neutrophil levels in CYP1A2 poor metabolisers during clozapine use. This information may facilitate identifying at-risk patients and then introducing preventative interventions or individualised pharmacovigilance procedures to help mitigate these adverse haematological reactions.
A benchmark dataset for machine learning in ecotoxicology
Authors: Schür Christoph , Gasser Lilian , Perez-Cruz Fernando , Schirmer Kristin , Baity-Jesi Marco
Published: October 2023

The use of machine learning for predicting ecotoxicological outcomes is promising, but underutilized. The curation of data with informative features requires both expertise in machine learning as well as a strong biological and ecotoxicological background, which we consider a barrier of entry for this kind of research. Additionally, model performances can only be compared across studies when the same dataset, cleaning, and splittings were used. Therefore, we provide ADORE, an extensive and well-described dataset on acute aquatic toxicity in three relevant taxonomic groups (fish, crustaceans, and algae). The core dataset describes ecotoxicological experiments and is expanded with phylogenetic and species-specific data on the species as well as chemical properties and molecular representations. Apart from challenging other researchers to try and achieve the best model performances across the whole dataset, we propose specific relevant challenges on subsets of the data and include datasets and splittings corresponding to each of these challenge as well as in-depth characterization and discussion of train-test splitting approaches.
IRIDIA-AF, a large paroxysmal atrial fibrillation long-term electrocardiogram monitoring database
Authors: Gilon Cédric , Grégoire Jean-Marie , Mathieu Marianne , Carlier Stéphane , Bersini Hugues
Published: October 2023

Atrial fibrillation (AF) is the most common sustained heart arrhythmia in adults. Holter monitoring, a long-term 2-lead electrocardiogram (ECG), is a key tool available to cardiologists for AF diagnosis. Machine learning (ML) and deep learning (DL) models have shown great capacity to automatically detect AF in ECG and their use as medical decision support tool is growing. Training these models rely on a few open and annotated databases. We present a new Holter monitoring database from patients with paroxysmal AF with 167 records from 152 patients, acquired from an outpatient cardiology clinic from 2006 to 2017 in Belgium. AF episodes were manually annotated and reviewed by an expert cardiologist and a specialist cardiac nurse. Records last from 19 hours up to 95 hours, divided into 24-hour files. In total, it represents 24 million seconds of annotated Holter monitoring, sampled at 200 Hz. This dataset aims at expanding the available options for researchers and offers a valuable resource for advancing ML and DL use in the field of cardiac arrhythmia diagnosis.
Optimal heat emissivity control of n population system based on individual size-distribution
Authors: Ba Zhenggang , Wang Ye
Published: October 2023

This paper generalizes a class of controllability problems based on the scale structure population system model. Based on the comparison principle of linear systems, the solution of the nonlinear system model is obtained by referring to the fixed point theorem. The non-negative, boundedness, existence, and uniqueness of the solution of the system model are established. The optimality condition is described in detail by means of a normal cone and conjugate system under the condition of proving the continuous dependence of the state environment on the solution to control variables.
Correlation analysis of obesity phenotypes with leptin and adiponectin
Authors: Aisike Guliqiekeran , Kuerbanjiang Maierheba , Muheyati Dina , Zaibibuli Kaibinuer , Lv Mei-Xia , Han Jia
Published: October 2023

Obesity can be categorized as metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). However, individuals with MHO are characterized by the absence of metabolic syndrome (MS) and appear to have lower inflammation levels compared to MUO. This study aimed to investigate the association of obesity phenotypes with leptin (LEP) and adiponectin (ADP). According to the inclusion and exclusion criteria, we selected 178 subjects from the previous cross-sectional survey. Based on the body mass index (BMI) and diagnostic criteria of MS, we divided the individuals into three groups, including healthy control group (HC group), metabolically healthy obesity group (MHO group) and metabolically unhealthy obesity group (MUO group). The concentrations of LEP and ADP in serum were measured, and the association of these two cytokines with different obesity phenotypes were subsequently analyzed. Compared to both the HC and MHO groups, the MUO group showed significantly higher BMI, waist circumference (WC), waist-hip ratio (WHR), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (Homa-IR) and blood pressure (P < 0.05). In contrast, serum high-density lipoprotein cholesterol (HDL-C) was notably lower in the MUO group (P < 0.05). ADP was found to have a positive correlation with systolic blood pressure (SBP) and a negative correlation with FPG in the MHO group. In the MUO group, LEP demonstrated a positive correlation with fasting insulin (FINS) and Homa-IR, while ADP showed a positive correlation with TC and SBP. Linear regression analysis further indicated that SBP (β = 0.234, P = 0.043), TG (β = − 0.292, P = 0.001) and LDL-C (β = 0.626, P = 0.000) were independently correlated with ADP, and BMI (β = 0.398, P = 0.002) was independently correlated with LEP in obese individuals. In conclusion, ADP and LEP were closely related with glucose and lipid metabolism in obese individuals, these two cytokines might play critical roles in obesity-associated metabolic disorders.
An empirical comparison of deep learning explainability approaches for EEG using simulated ground truth
Authors: Sujatha Ravindran Akshay , Contreras-Vidal Jose
Published: October 2023

Recent advancements in machine learning and deep learning (DL) based neural decoders have significantly improved decoding capabilities using scalp electroencephalography (EEG). However, the interpretability of DL models remains an under-explored area. In this study, we compared multiple model explanation methods to identify the most suitable method for EEG and understand when some of these approaches might fail. A simulation framework was developed to evaluate the robustness and sensitivity of twelve back-propagation-based visualization methods by comparing to ground truth features. Multiple methods tested here showed reliability issues after randomizing either model weights or labels: e.g., the saliency approach, which is the most used visualization technique in EEG, was not class or model-specific. We found that DeepLift was consistently accurate as well as robust to detect the three key attributes tested here (temporal, spatial, and spectral precision). Overall, this study provides a review of model explanation methods for DL-based neural decoders and recommendations to understand when some of these methods fail and what they can capture in EEG.
Relative lateral wall thickness is an improved predictor for postoperative lateral wall fracture after trochanteric femoral fracture osteosynthesis
Authors: van Knegsel Kenneth P. , Hsu C.-E. , Huang K.-C. , Benca Emir , Pastor Torsten , Ganse Bergita , Varga Peter , Gueorguiev Boyko , Knobe Matthias
Published: October 2023

Lateral wall thickness is a known predictor for postoperative stability of trochanteric femoral fractures and occurrence of secondary lateral wall fractures. Currently, the AO/OTA classification relies on the absolute lateral wall thickness (aLWT) to distinguish between stable A1.3 and unstable A2.1 fractures that does not take interpersonal patient differences into account. Thus, a more individualized and accurate measure would be favorable. Therefore, we proposed and validated a new patient-specific measure—the relative lateral wall thickness (rLWT)—to consider individualized measures and hypothesized its higher sensitivity and specificity compared with aLWT. First, in 146 pelvic radiographs of patients without a trochanteric femoral fracture, the symmetry of both caput-collum-diaphyseal angle (CCD) and total trochanteric thickness (TTT) was assessed to determine whether the contralateral side can be used for rLWT determination. Then, data of 202 patients were re-evaluated to compare rLWT versus previously published aLWT. Bilateral symmetry was found for both CCD and TTT (p ≥ 0.827), implying that bone morphology and geometry of the contralateral intact side could be used to calculate rLWT. Validation revealed increased accuracy of the rLWT compared with the gold standard aLWT, with increased specificity by 3.5% (Number Needed to Treat = 64 patients) and sensitivity by 1% (Number Needed to Treat = 75 patients). The novel rLWT is a more accurate and individualized predictor of secondary lateral wall fractures compared with the standard aLWT. This study established the threshold of 50.5% rLWT as a reference value for predicting fracture stability in trochanteric femoral fractures.
Machine learning risk estimation and prediction of death in continuing care facilities using administrative data
Authors: Shahidi Faezehsadat , Rennert-May Elissa , D’Souza Adam G. , Crocker Alysha , Faris Peter , Leal Jenine
Published: October 2023

In this study, we aimed to identify the factors that were associated with mortality among continuing care residents in Alberta, during the coronavirus disease 2019 (COVID-19) pandemic. We achieved this by leveraging and linking various administrative datasets together. Then, we examined pre-processing methods in terms of prediction performance. Finally, we developed several machine learning models and compared the results of these models in terms of performance. We conducted a retrospective cohort study of all continuing care residents in Alberta, Canada, from March 1, 2020, to March 31, 2021. We used a univariable and a multivariable logistic regression (LR) model to identify predictive factors of 60-day all-cause mortality by estimating odds ratios (ORs) with a 95% confidence interval. To determine the best sensitivity–specificity cut-off point, the Youden index was employed. We developed several machine learning models to determine the best model regarding performance. In this cohort study, increased age, male sex, symptoms, previous admissions, and some specific comorbidities were associated with increased mortality. Machine learning and pre-processing approaches offer a potentially valuable method for improving risk prediction for mortality, but more work is needed to show improvement beyond standard risk factors.
AST/ALT-to-platelet ratio (AARPRI) predicts gynaecological cancers: a 8-years follow-up study in 653 women
Authors: Crudele Lucilla , De Matteis Carlo , Graziano Giusi , Novielli Fabio , Petruzzelli Stefano , Piccinin Elena , Gadaleta Raffaella Maria , Cariello Marica , Moschetta Antonio
Published: October 2023

Non-alcoholic fatty liver disease (NAFLD), specifically liver steatosis and fibrosis with steatohepatitis (NASH), is often associated with visceral adiposopathy, whose pathogenetic features have been proposed as tumorigenic triggers. We performed a prospective analysis in 653 metabolic women to reveal any conditions that may predict and concur to cancer development during a 8-years period of follow-up. Among clinical and biochemical variables, only AST and non-invasive liver fibrosis scores (AARPRI, APRI, FIB-4, mFIB4) significantly distinguished cancer-developer women (n = 62, 9.5%) from those who did not develop cancer (p < 0.001). In ROC analysis, these scores also showed good sensitivity and specificity in differentiating women who developed cancer (all p < 0.001). We then calculated OR for these indexes finding that increased AARPRI was associated with the highest risk (OR = 6, p < 0.001) of gynaecological cancers development. We further validated these cut-off values in women who had developed other types of cancer, confirming that AARPRI is able to identify the risk for cancer development (OR = 5, p < 0.001). Our findings support the hypothesis that NAFLD, more than obesity per se, is directly associated with the clinical and pathogenic metabolic scenario of gynaecological cancers and encourage the use of liver fibrosis indexes to detect risk of cancer onset in women. Preventing adiposopathy and NAFLD through lifestyle and therapies may represent an instrumental strategy for cancer prevention and/or co-treatment in oncology.
Real-world treatment patterns of rheumatoid arthritis in Brazil: analysis of DATASUS national administrative claims data for pharmacoepidemiology studies (2010–2020)
Authors: Birck Marina G. , Ferreira Rafaela , Curi M. , Krueger Whitney S. , Julian Guilherme S. , Liede Alexander
Published: October 2023

Our study assessed DATASUS as a potential source for pharmacoepidemiologic studies in rheumatoid arthritis (RA) in the Brazilian population focusing on treatment patterns and determinants of initiating or switching to a novel therapy. This was a descriptive database study of RA patients with at least one claim of RA and ≥ 2 claims of disease-modifying anti-rheumatic drug (DMARD); conventional synthetic (cs), biologic (b) or targeted synthetic (ts) DMARD with more than 6 months of follow-up from 01-Jan-2010 to 31-Dec-2020. Analyses were stratified for SUS-exclusive and SUS+ private user cohorts. We identified 250,251 patients with RA in DATASUS: mean age of 58.4 years, majority female (83%) and white (58%). 62% were SUS-exclusive and 38% SUS+ private. Most common bDMARDs were adalimumab and etanercept. Age (adjusted odds ratio 1.78 [50+]; 95% CI 1.57–2.01), SUS exclusive status (0.53; 0.47–0.59), distance to clinic [160+ km] (0.57; 0.45–0.72), and pre-index csDMARD claims (1.23; 1.08–1.41) were independent predictors of initiating a novel oral tsDMARD. Switching from bDMARD to tsDMARD, associations were similar, except for the direction of associations for SUS exclusive status (adjusted hazard ratio 1.10; 1.03–1.18), distance to clinic (1.18; 1.03–1.35), and number of previous bDMARD (0.15; 0.14–0.16). DATASUS is a source suitable for treatment-related analyses in RA reflecting the public health system in Brazil.
Prevalence of Cryptosporidium infection and associated risk factors in calves in Egypt
Authors: Gattan Hattan S. , Alshammari Ayed , Marzok Mohamed , Salem Mohamed , AL-Jabr Omar A. , Selim Abdelfattah
Published: October 2023

Cryptosporidium is one of the causative parasitic agents that causes gastrointestinal diseases in calves. The parasite poses a zoonotic risk to immunocompromised individuals and children. Thus, this study aimed to determine the prevalence of Cryptosporidium infection in calves in three Egyptian governorates situated in Nile Delta and assess the associated risk factors. The Cryptosporidium oocysts were detected in 81 out of 430 calves (18.84%). In addition, the univariant analysis showed that age, feeding source, hygienic status, presence of diarrhea and contact with other animals were significantly (P < 0.05) associated with Cryptosporidium prevalence in calves. Furthermore, the risk factors related with Cryptosporidium prevalence were age (OR 1.96, 95%CI 0.97–3.94), feeding on milk and pasture (OR 2.07, 95%CI 1.15–3.72), poor hygienic condition (OR 2.25, 95%CI 1.28–3.94), presence of diarrhea (OR 2.47, 95%CI 1.23–4.96) and contact with other domestic animals (OR 2.08, 95%CI 1.24–3.50). In addition, the PCR assay targeting 18srRNA showed that the most prevalent species among calves was C. parvum. Although additional researches are required to understand the most effective steps that farmers and veterinary professionals should take to decrease the occurrence of Cryptosporidium infection.
Mechanical properties and sustainable bacterial resistance effect of strontium-modified phosphate-based glass microfiller in dental composite resins
Authors: Go Hye-Bin , Lee Myung-Jin , Seo Ji-Young , Byun Sung-Yun , Kwon Jae-Sung
Published: October 2023

Dental composite resins are widely used in dental restorations. However, their clinical application is limited by the occurrence of secondary caries. Strontium-modified phosphate-based glass (Sr-PBG) is a material known to have a sustainable bacterial resistance effect. The mechanical properties (in particular, flexural strength, modulus of elasticity, and hardness) of dental materials determine their function. Therefore, this study aimed to investigate the mechanical and ion-releasing properties as well as the sustainable bacterial resistance effect of bioactive resin composites containing Sr-PBG. The data were analyzed by ANOVA and Tuckey’s tests (p < 0.05). We incorporated a Sr-PBG microfiller at 3, 6, and 9 wt.% concentrations into a commercially available composite resin and investigated the mechanical properties (flexural strength, elastic modulus, and micro hardness), ion release characteristics, and color of the resultant resins. In addition, we examined the antibacterial effects of the composite resins against Streptococcus mutans (S. mutans). The mechanical properties of the Sr-PBG groups differed only slightly from those of the control group (p > 0.05). However, the optical density at 600 nm of S. mutans incubated on the experimental group was significantly lower compared to that observed with the control (p < 0.05) both before and after thermocycling between 5 and 55 ℃ for 850 cycles (dwell time: 45 s). Therefore, strontium-modified resin materials exhibited a sustainable bacterial resistance effect in vitro while maintaining some of the mechanical properties of ordinary acrylic resins.