bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic-based patient stratification in Alzheimer’s disease
Authors: Hernández-Lorenzo Laura , García-Gutiérrez Fernando , Solbas-Casajús Ana , Corrochano Silvia , Matías-Guiu Jordi A. , Ayala Jose L. 
Published: May 2024

AbstractAlzheimer's disease (AD) shows a high pathological and symptomatological heterogeneity. To study this heterogeneity, we have developed a patient stratification technique based on one of the most significant risk factors for the development of AD: genetics. We addressed this challenge by including network biology concepts, mapping genetic variants data into a brain-specific protein–protein interaction (PPI) network, and obtaining individualized PPI scores that we then used as input for a clustering technique. We then phenotyped each obtained cluster regarding genetics, sociodemographics, biomarkers, fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, and neurocognitive assessments. We found three clusters defined mainly by genetic variants found in MAPT, APP, and APOE, considering known variants associated with AD and other neurodegenerative disease genetic architectures. Profiling of these clusters revealed minimal variation in AD symptoms and pathology, suggesting different biological mechanisms may activate the neurodegeneration and pathobiological patterns behind AD and result in similar clinical and pathological presentations, even a shared disease diagnosis. Lastly, our research highlighted MAPT, APP, and APOE as key genes where these genetic distinctions manifest, suggesting them as potential targets for personalized drug development strategies to address each AD subgroup individually.
Novel applications of Convolutional Neural Networks in the age of Transformers
Authors: Ersavas Tansel , Smith Martin A. , Mattick John S. 
Published: May 2024

AbstractConvolutional Neural Networks (CNNs) have been central to the Deep Learning revolution and played a key role in initiating the new age of Artificial Intelligence. However, in recent years newer architectures such as Transformers have dominated both research and practical applications. While CNNs still play critical roles in many of the newer developments such as Generative AI, they are far from being thoroughly understood and utilised to their full potential. Here we show that CNNs can recognise patterns in images with scattered pixels and can be used to analyse complex datasets by transforming them into pseudo images with minimal processing for any high dimensional dataset, representing a more general approach to the application of CNNs to datasets such as in molecular biology, text, and speech. We introduce a pipeline called DeepMapper, which allows analysis of very high dimensional datasets without intermediate filtering and dimension reduction, thus preserving the full texture of the data, enabling detection of small variations normally deemed ‘noise’. We demonstrate that DeepMapper can identify very small perturbations in large datasets with mostly random variables, and that it is superior in speed and on par in accuracy to prior work in processing large datasets with large numbers of features.
The role of RUNX1/NF-κB in regulating PVAT inflammation in aortic dissection
Authors: Wang Ao , Dong Shengjun , Liu Baohui , Liu Dianxiao , Zou Mingrui , Han Yuexin , Yang Lijuan , Wang Yujiu 
Published: May 2024

AbstractThe pathogenesis of aortic dissection (AD), an aortic disease associated with high mortality, involves significant vascular inflammatory infiltration. However, the precise relationship between perivascular adipose tissue (PVAT) and aortic dissection remains incompletely understood. The objective of this study is to investigate the role of PVAT inflammation in the pathogenesis of aortic dissection and identify novel therapeutic targets for this disease. The mouse model of aortic dissection was established in this study through intraperitoneal injection of Ang II and administration of BAPN in drinking water. Additionally, control groups were established at different time points including the 2-week group, 3-week group, and 4-week group. qPCR and immunohistochemistry techniques were employed to detect the expression of inflammatory markers and RUNX1 in PVAT surrounding the thoracic aorta in mice. Additionally, an aortic dissection model was established using RUNX1 knockout mice, and the aforementioned indicators were assessed. The 3T3-L1 cells were induced to differentiate into mature adipocytes in vitro, followed by lentivirus transfection for the knockdown or overexpression of RUNX1. The study aimed to investigate the potential cell-to-cell interactions by co-culturing 3T3-L1 cells with A7r5 or RAW264.7 cells. Subsequently, human aortic PVAT samples were obtained through clinical surgery and the aforementioned indicators were detected. In comparison to the control group, the aortic dissection model group exhibited decreased expression of MMP-2 and NF-κB in PVAT, while TNF-α and RUNX1 expression increased. Suppression of RUNX1 expression resulted in increased MMP-2 and NF-κB expression in PVAT, along with decreased TNF-α expression. Overexpression of RUNX1 upregulated the expression levels of NF-Κb, MMP-2, and TNF-α in adipocytes, whereas knockdown of RUNX1 exerted an opposite effect. Macrophages co-cultured with adipocytes overexpressing RUNX1 exhibited enhanced CD86 expression, while vascular smooth muscle cells co-cultured with these adipocytes showed reduced α-SMA expression. In human samples, there was an increase in both RUNX1 and MMP-2 expression levels, accompanied by a decrease in TNF-α and NF-Κb expression. The presence of aortic dissection is accompanied by evident inflammatory alterations in the PVAT, and this phenomenon appears to be associated with the involvement of RUNX1. It is plausible that the regulation of PVAT's inflammatory changes by RUNX1/NF-κB signaling pathway plays a role in the pathogenesis of aortic dissection.
Atlas of phytoplankton phenology indices in selected Eastern Mediterranean marine ecosystems
Authors: Kournopoulou Antonia , Kikaki Katerina , Varkitzi Ioanna , Psarra Stella , Assimakopoulou Georgia , Karantzalos Konstantinos , Raitsos Dionysios E. 
Published: May 2024

AbstractPhytoplankton is a fundamental component of marine food webs and play a crucial role in marine ecosystem functioning. The phenology (timing of growth) of these microscopic algae is an important ecological indicator that can be utilized to observe its seasonal dynamics, and assess its response to environmental perturbations. Ocean colour remote sensing is currently the only means of obtaining synoptic estimates of chlorophyll-a (a proxy of phytoplankton biomass) at high temporal and spatial resolution, enabling the calculation of phenology metrics. However, ocean colour observations have acknowledged weaknesses compromising its reliability, while the scarcity of long-term in situ data has impeded the validation of satellite-derived phenology estimates. To address this issue, we compared one of the longest available in situ time series (20 years) of chlorophyll-a concentrations in the Eastern Mediterranean Sea (EMS), along with concurrent remotely-sensed observations. The comparison revealed a marked coherence between the two datasets, indicating the capability of satellite-based measurements in accurately capturing the phytoplankton seasonality and phenology metrics (i.e., timing of initiation, duration, peak and termination) in the studied area. Furthermore, by studying and validating these metrics we constructed a satellite-derived phytoplankton phenology atlas, reporting in detail the seasonal patterns in several sub-regions in coastal and open seas over the EMS. The open waters host higher concentrations from late October to April, with maximum levels recorded during February and lowest during the summer period. The phytoplankton growth over the Northern Aegean Sea appeared to initiate at least a month later than the rest of the EMS (initiating in late November and terminating in late May). The coastal waters and enclosed gulfs (such as Amvrakikos and Maliakos), exhibit a distinct seasonal pattern with consistently higher levels of chlorophyll-a and prolonged growth period compared to the open seas. The proposed phenology atlas represents a useful resource for monitoring phytoplankton growth periods in the EMS, supporting water quality management practices, while enhancing our current comprehension on the relationships between phytoplankton biomass and higher trophic levels (as a food source).
Proximity tracking using ultra-wideband technology for equine social behaviour research
Authors: Torres Borda Laura , Roth Peter , Lumetzberger Jennifer , Auer Ulrike , Jenner Florien 
Published: May 2024

AbstractSociopositive interactions with conspecifics are essential for equine welfare and quality of life. This study aimed to validate the use of wearable ultra-wideband (UWB) technology to quantify the spatial relationships and dynamics of social behaviour in horses by continuous (1/s) measurement of interindividual distances. After testing the UWB devices’ spatiotemporal accuracy in a static environment, the UWB measurement validity, feasibility and utility under dynamic field conditions was assessed in a group of 8 horses. Comparison of the proximity measurements with video surveillance data established the measurement accuracy and validity (r = 0.83, p < 0.0001) of the UWB technology. The utility for social behaviour research was demonstrated by the excellent accordance of affiliative relationships (preferred partners) identified using UWB with video observations. The horses remained a median of 5.82 m (95% CI 5.13–6.41 m) apart from each other and spent 20% (median, 95% CI 14–26%) of their time in a distance ≤ 3 m to their preferred partner. The proximity measurements and corresponding speed calculation allowed the identification of affiliative versus agonistic approaches based on differences in the approach speed and the distance and duration of the resulting proximity. Affiliative approaches were statistically significantly slower (median: 1.57 km/h, 95% CI 1.26–1.92 km/h, p = 0.0394) and resulted in greater proximity (median: 36.75 cm, 95% CI 19.5–62 cm, p = 0.0003) to the approached horse than agonistic approaches (median: 3.04 km/h, 95% CI 2.16–3.74 km/h, median proximity: 243 cm, 95% CI 130–319 cm), which caused an immediate retreat of the approached horse at a significantly greater speed (median: 3.77 km/h, 95% CI 3.52–5.85 km/h, p < 0.0001) than the approach.
A facile DNA coacervate platform for engineering wetting, engulfment, fusion and transient behavior
Authors: Liu Wei , Deng Jie , Song Siyu , Sethi Soumya , Walther Andreas 
Published: May 2024

AbstractBiomolecular coacervates are emerging models to understand biological systems and important building blocks for designer applications. DNA can be used to build up programmable coacervates, but often the processes and building blocks to make those are only available to specialists. Here, we report a simple approach for the formation of dynamic, multivalency-driven coacervates using long single-stranded DNA homopolymer in combination with a series of palindromic binders to serve as a synthetic coacervate droplet. We reveal details on how the length and sequence of the multivalent binders influence coacervate formation, how to introduce switching and autonomous behavior in reaction circuits, as well as how to engineer wetting, engulfment and fusion in multi-coacervate system. Our simple-to-use model DNA coacervates enhance the understanding of coacervate dynamics, fusion, phase transition mechanisms, and wetting behavior between coacervates, forming a solid foundation for the development of innovative synthetic and programmable coacervates for fundamental studies and applications.
Immunogenomics and spatial proteomic mapping highlight distinct neuro-immune architectures in melanoma vs. non-melanoma-derived brain metastasis
Authors: Mendoza-Valderrey Alberto , Dettmann Ethan , Hanes Douglas , Kessler Daria M. , Danilova Ludmila , Rau Kai , Quan Yueqin , Stern Stacey , Barkhoudarian Garni , Bifulco Carlo , Margolin Kim , Kolker Steven , Ascierto Maria L. 
Published: May 2024

Abstract
Background
Brain metastases (BrMs) are a devastating complication of solid tumours. A better understanding of BrMs biology is needed to address their challenging clinical management.

Methods
Immunogenomic and digital spatial analyses were applied to interrogate the peripheral blood and tumour specimens derived from 53 unique patients with BrMs originating from different solid tumours.

Results
At craniotomy time, patients with melanoma-derived brain metastasis (MBM) displayed in the periphery lower neutrophil–lymphocyte ratio (NLR) compared to non-melanoma-derived brain metastasis (non-MBM). Regardless of the primary tumour source, higher NLR was associated with reduced overall survival (OS). Tumour MicroEnviroment genomic evaluations revealed higher expression of genes identifying NK, CD8 and B cells in MBM vs. non-MBM. Moreover, MBM patients with longer OS displayed increased CD8+ cell infiltration. Spatial proteomic analysis further highlighted enriched infiltration of CD8+ cells, antigen-presenting cells, T-cell agonists and B cells in MBM. Conversely, increased expression of genes and proteins associated with neurodevelopment, cell–cell adhesion and neutrophil infiltration were observed in non-MBM.

Conclusions
These findings reveal an increased immunogenicity of MBM vs non-MBM and highlight the presence of a unique neuro-immune interplays in MBM vs non-MBM, suggesting that a balance between neuro-immune architectures might be associated with diverging clinical outcome of patients with BrMs.
Mime-seq 2.0: a method to sequence microRNAs from specific mouse cell types
Authors: Mandlbauer Ariane , Sun Qiong , Popitsch Niko , Schwickert Tanja , Spanova Miroslava , Wang Jingkui , Ameres Stefan L , Busslinger Meinrad , Cochella Luisa 
Published: May 2024

AbstractMany microRNAs (miRNAs) are expressed with high spatiotemporal specificity during organismal development, with some being limited to rare cell types, often embedded in complex tissues. Yet, most miRNA profiling efforts remain at the tissue and organ levels. To overcome challenges in accessing the microRNomes from tissue-embedded cells, we had previously developed mime-seq (miRNome by methylation-dependent sequencing), a technique in which cell-specific miRNA methylation in C. elegans and Drosophila enabled chemo-selective sequencing without the need for cell sorting or biochemical purification. Here, we present mime-seq 2.0 for profiling miRNAs from specific mouse cell types. We engineered a chimeric RNA methyltransferase that is tethered to Argonaute protein and efficiently methylates miRNAs at their 3′-terminal 2′-OH in mouse and human cell lines. We also generated a transgenic mouse for conditional expression of this methyltransferase, which can be used to direct methylation of miRNAs in a cell type of choice. We validated the use of this mouse model by profiling miRNAs from B cells and bone marrow plasma cells.
The Effects of Light Level and Signal-to-Noise Ratio on the Task-Evoked Pupil Response in a Speech-in-Noise Task
Authors: Baldock Jennifer , Kapadia Sarosh , van Steenbrugge Willem , McCarley Jason 
Published: May 2024

Purpose:
There is increasing interest in the measurement of cognitive effort during listening tasks, for both research and clinical purposes. Quantification of task-evoked pupil responses (TEPRs) is a psychophysiological method that can be used to study cognitive effort. However, light level during cognitively demanding listening tasks may affect TEPRs, complicating interpretation of listening-related changes. The objective of this study was to examine the effects of light level on TEPRs during effortful listening across a range of signal-to-noise ratios (SNRs).

Method:
Thirty-six adults without hearing loss were asked to repeat target sentences presented in background babble noise while their pupil diameter was recorded. Light level and SNRs were manipulated in a 4 × 4 repeated-measures design. Repeated-measures analyses of variance were used to measure the effects.

Results:
Peak and mean dilation were typically larger in more adverse SNR conditions (except for SNR −6 dB) and smaller in higher light levels. Differences in mean and peak dilation between SNR conditions were larger in dim light than in brighter light.

Conclusions:
Brighter light conditions make TEPRs less sensitive to variations in listening effort across levels of SNR. Therefore, light level must be considered and reported in detail to ensure sensitivity of TEPRs and for comparisons of findings across different studies. It is recommended that TEPR testing be conducted in relatively low light conditions, considering both background illumination and screen luminance.

Supplemental Material:

https://doi.org/10.23641/asha.25676538
AMICO galaxy clusters in KiDS-DR3: Measuring the splashback radius from weak gravitational lensing
Authors: Giocoli Carlo , Palmucci Lorenzo , Lesci Giorgio F. , Moscardini Lauro , Despali Giulia , Marulli Federico , Maturi Matteo , Radovich Mario , Sereno Mauro , Bardelli Sandro , Castignani Gianluca , Covone Giovanni , Ingoglia Lorenzo , Romanello Massimiliano , Roncarelli Mauro , Puddu Emanuella 
Published: May 2024

Context. Weak gravitational lensing offers a powerful method to investigate the projected matter density distribution within galaxy clusters, granting crucial insights into the broader landscape of dark matter on cluster scales.
Aims. In this study, we make use of the large photometric galaxy cluster data set derived from the publicly available Third Data Release of the Kilo-Degree Survey, along with the associated shear signal. Our primary objective is to model the peculiar sharp transition in the cluster profile slope, that is what is commonly referred to as the splashback radius. The data set under scrutiny includes 6962 galaxy clusters, selected by AMICO (an optimised detection algorithm of galaxy clusters) on the KiDS-DR3 data, in the redshift range of 0.1 ≤ z ≤ 0.6, all observed at a signal-to-noise ratio greater than 3.5.
Methods. Employing a comprehensive Bayesian analysis, we model the stacked excess surface mass density distribution of the clusters. We adopt a model from recent results on numerical simulations that capture the dynamics of both orbiting and infalling materials, separated by the region where the density profile slope undergoes a pronounced deepening.
Results. We find that the adopted profile successfully characterizes the cluster masses, consistent with previous works, and models the deepening of the slope of the density profiles measured with weak-lensing data up to the outskirts. Moreover, we measure the splashback radius of galaxy clusters and show that its value is close to the radius within which the enclosed overdensity is 200 times the mean matter density of the Universe, while theoretical models predict a larger value consistent with a low accretion rate. This points to a potential bias of optically selected clusters preferentially characterized by a high density at small scales compared to a pure mass-selected cluster sample.
Comprehensive Strategies for the Synthesis of 1,3-Enyne Derivatives
Authors: Hazra Chinmoy Kumar , Malakar Chandi C. , Kant Kamal , Patel Chandresh Kumar , Reetu Reetu , Teli Yaqoob Ahmed , Naik Priyadarshini , Some Sanjukta , Aljaar Nayyef , Atta Ananta K. 
Published: May 2024

AbstractThe synthesis of 1,3-enyne has widespread appeal in organic synthesis due to their proven adaptability as intermediates in routes to compounds of significant biological and material interest. A variety of methods have been designed to formulate 1,3-enynes from diverse substrates, such as alkynes, 1,3-diynes, alkynyl-substituted cyclopropanes, and propargyl alcohols. This review covers the synthesis of 1,3-enynes utilizing the homo- and cross-coupling of alkynes, nucleophilic metal/acid-induced cyclopropane ring opening, and rearrangement/dehydration of propargyl alcohols. A key concern in procedures starting from alkynes and 1,3-diynes is the management of regio-, stereo-, and, where fitting, chemoselectivity. In contrast, in cyclopropyl ring opening nucleophile orientation determines the 1,3-enynes formed. Efficient methods for the broad and selective synthesis of 1,3-enynes are highlighted and specific examples are given to demonstrate the efficacy of these processes.1	Introduction and Scope2	Synthesis2.1	Synthesis of 1,3-Enynes from Alkynes2.1.1	Metal-Catalyzed Cross-Coupling/Additions of Alkynes with Alkenes or Vinyl or Aryl Halides2.1.1.1	Palladium Catalysis2.1.1.2	Rhodium Catalysis2.1.1.3	Copper Catalysis2.1.1.4 I	ron Catalysis2.1.1.5	Nickel Catalysis2.1.1.6	Miscellaneous2.2	Synthesis of Enynes from Propargyl Alcohols2.3	Metal/Acid-Catalyzed Ring Opening of Cyclopropanes3	Conclusion
Research on time-value-oriented business model innovation path in life services enterprises and its impact on customer perceived value
Authors: Liu Xia , Sun Yanhan , Zhou Shengshi , Li Yu , Zhuang Shan 
Published: May 2024

AbstractIn the era of the digital economy, the acceleration of life pace has induced to a continuous increase in people’s sense of time scarcity. In order to satisfy consumers’ lifestyle changes and immediate needs, life service enterprises have carried out lots of business model innovation activities guided by value of time. However, it is still unclear what the time-value-oriented business model innovation path is and whether it can improve the perceived value of customers. Under such background, this paper aims to construct a time-value-oriented business model innovation path in life services enterprises and to discuss its relationship with customer perceived value. The study indicates that: Firstly, specific innovation paths of enterprises include putting forward the purpose of value of time proposition, designing standardized process based on time-oriented, constantly forming unique core resources such as big data, brand and supply chain, and updating the transaction method combining online and offline, and so on. Secondly, the questionnaire results indicate that time-value oriented business model innovation in four aspects – value proposition, key processes, core resources, and transaction methods – can effectively enhance customer perceived value. Thirdly, there are differences in the matching degree between time-value-oriented business model innovation and customer value perception among different types of enterprises in the life services industry. Among them, the express delivery industry has the highest enhancing degree and customer satisfaction. This is related to the heterogeneous characteristics of industries such as express delivery, transportation, catering, and retail. Overall, this study offers a comprehensive and practical perspective for enterprises to meet customer perceived value demands by presenting business model innovation paths and solutions.
Switch the click: Ultrafast photochemistry of photoDIBO-OH tracked by time-resolved IR spectroscopy
Authors: Denninger L. , Brunst H. , van Wilderen L. J. G. W. , Horz M. , Masood H. M. A. , McNitt C. D. , Burghardt I. , Popik V. V. , Bredenbeck J. 
Published: May 2024

Click chemistry refers to selective reactions developed for grafting of bio(macro)molecules in their biological media. Caged click compounds have been employed to spatiotemporally control click reactions. Here, we survey the uncaging of photo-dibenzocyclooctyne-OH (photoDIBO-OH) to its click-chemistry active form DIBO-OH, with particular attention to its conversion timescale and efficiency. Ultraviolet pump–infrared probe experiments reveal a stepwise decarbonylation: first, carbon monoxide (C≡O) is released within 1.8 ps, and then, it converts, within 10 ps, to DIBO-OH. Completion of uncaging is achieved with an efficiency of ∼50%. A successful demonstration of two-photon uncaging of photoDIBO-OH at long wavelength (700 nm) confers enhanced in vivo compatibility and proceeds on the same timescale.