bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico identification and ex vivo evaluation of Toxoplasma gondii peptides restricted to HLA-A*02, HLA-A*24 and HLA-B*35 alleles in human PBMC from a Colombian population
Authors: Vargas-Montes Mónica , Valencia-Jaramillo María Camila , Valencia-Hernández Juan David , Gómez-Marín Jorge Enrique , Arenas Ailan Farid , Cardona Néstor 
Published: December 2024

AbstractToxoplasma gondii infects approximately 30% of the population, and there is currently no approved vaccine. Identifying immunogenic peptides with high affinity to different HLA molecules is a promising vaccine strategy. This study used an in silico approach using artificial neural networks to identify T. gondii peptides restricted to HLA-A*02, HLA-A*24, and HLA-B*35 alleles. Proteomes from seven T. gondii strains and transcriptomic data of overexpressed genes from T. gondii-RH in human PBMC were also used. Parasite protein sequences were analyzed with R ‘Epitope Prediction’ library. Peptide candidates were evaluated in the artificial neural networks based on the probabilities of output neurons (p > 0.5). The IFN-γ responses in PBMC from T. gondii seronegative and seropositive individuals were evaluated by ELISpot. Peptides with higher IFN-γ induction were evaluated to identify cytotoxic response in CD8+ T cells (CD107a). In silico analysis identified 36 peptides from T. gondii proteins with predicted affinity to HLA-A*02, A*24, and B*35 alleles. Experiments with PBMCs revealed that a peptide restricted to HLA-A02 (P1: FLFAWITYV) induced a significant increase in IFN-γ-producing cells (p = 0.004). For HLA-A24, a peptide (P8: VFAFAFAFFLI) also induced a significant IFN-γ response (p = 0.004), while for the HLA-B*35 allele, the P6 peptide (YPIAPSFAM) induced a response that differed significantly from the control (p = 0.05). These peptides induced also a significant percentage of central memory CD8 + T cells expressing the degranulation marker CD107a (p < 0.05). Finally, we identified three T. gondii peptides that induced IFN-γ response, and a cytotoxic response measured by CD107a expression on CD45RAneg-CD8 cells. These peptides could be considered part of a multi-epitope vaccine against toxoplasmosis in humans.
Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells
Authors: Gultom Mitra , Lin Lin , Brandt Camilla Blunk , Milusev Anastasia , Despont Alain , Shaw Jane , Döring Yvonne , Luo Yonglun , Rieben Robert 
Published: December 2024

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of acute respiratory syndrome (ARDS) and the mortality of COVID-19 infection. Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection. Here, we investigated the interaction of SARS-CoV-2 spike protein with human ECs from aortic (HAoEC) and pulmonary microvascular (HPMC) origins, cultured under physiological flow conditions. We showed that the SARS-CoV-2 spike protein triggers prolonged expression of cell adhesion markers in both ECs, similar to the effect of TNF-α. SARS-CoV-2 spike treatment also led to the release of various cytokines and chemokines observed in severe COVID-19 patients. Moreover, increased binding of leucocytes to the endothelial surface and a procoagulant state of the endothelium were observed. Transcriptomic profiles of SARS-CoV-2 spike-activated HPMC and HAoEC showed prolonged upregulation of genes and pathways associated with responses to virus, cytokine-mediated signaling, pattern recognition, as well as complement and coagulation pathways. Our findings support experimental and clinical observations of the vascular consequences of SARS-CoV-2 infection and highlight the importance of EC protection as one of the strategies to mitigate the severe effects as well as the possible post-acute complications of COVID-19 disease.
The Design and Implementation of an Educational Chatbot with Personalized Adaptive Learning Features for Project Management Training
Authors: Chen Da-Lun , Aaltonen Kirsi , Lampela Hannele , Kujala Jaakko 
Published: December 2024

AbstractThe breakthrough in generative artificial intelligence (AI) has unlocked new possibilities for higher education. There are many studies on educational chatbots in the fields of science, technology, engineering, and mathematics; however, studies on designing and leveraging chatbots in a multidisciplinary field like project management have been scarce. Although some studies have incorporated elements to facilitate personalized or adaptive learning experience, more research on the design and evaluation of personalized adaptive learning chatbots is needed to offer learners more engaging learning experiences and help them achieve better outcomes. This study applies the concept of personalized adaptive learning, investigating how to design a personalized chatbot for training project management skills in higher education. By leveraging chatbot technology and generative AI, we built PMTutor, with personalized adaptive learning features, integrating it into a project management course. The results suggest that this type of chatbot can complement learning and engage learners by providing customized feedback during an exercise. This study provides insights into the design and usability of personalized adaptive learning chatbots for project management training.
Using Learning Analytics to Support Self-Regulated Learning in Primary Education – A Learning Design Perspective
Authors: Paavilainen Teija , López-Pernas Sonsoles , Väisänen Sanna , Kontkanen Sini , Hirsto Laura 
Published: December 2024

AbstractIn digitalized learning processes, learning analytics (LA) can help teachers make pedagogically sound decisions and support pupils’ self-regulated learning (SRL). However, research on the role of the pedagogical dimensions of learning design (LD) in influencing the possibilities of LA remains scarce. Primary school presents a unique LA context characterized by blended learning environments and pupils’ various abilities to regulate their learning, underscoring teachers’ vital importance. This study explores how pedagogically diverse LDs influence pupils’ SRL behaviors and learning management system (LMS) usage, as well as how this is reflected in LA visualizations. Two LDs were designed and implemented in two primary school classes of fifth (n = 30) and sixth (n = 22) graders within authentic pedagogical and technological contexts. We used sequence analysis to examine the pupils’ SRL actions during LDs, using LMS log data and observation data to contextualize these actions. The results show that LA offers less accurate feedback in more open, collaborative LDs as pupils tend to rely less on the LMS to regulate their learning. Furthermore, the teacher powerfully influences LMS usage in blended primary school classrooms. To maximize the potential of using LA to support SRL, its design needs to be grounded in the LD through an understanding of how the regulation of learning is promoted in diverse learning processes.
Assessing the Power of the HEXACO to Predict Professional Burnout Among Catholic Priests in Italy
Authors: Crea Giuseppe , Francis Leslie J. , McKenna Ursula 
Published: December 2024

AbstractThis study tests the application of the HEXACO among Catholic priests and the power of this six factor model of personality to predict scores on the Francis Burnout Inventory among priests. Data provided by 264 priests serving in Italy lead to two conclusions. In this population three of the six scales of the HEXACO failed to display adequate levels of internal consistency reliability (emotionality, agreeableness, openness to experience). High scores of extraversion and conscientiousness predicted higher scores of satisfaction in ministry. Low scores of extraversion, conscientiousness, and honesty and humility predicted higher scores of emotional exhaustion in ministry. The role of the honesty and humility factor in predicting negative affect but not positive affect supports the balanced affect model of professional burnout that views positive and negative affect as partly independent systems.
A review of structural and functional connectivity studies in European forests
Authors: Martínez-Richart Ana Isabel , Zolles Anita , Oettel Janine , Petermann Jana S. , Essl Franz , Lapin Katharina 
Published: December 2024

Abstract

Context
Ecological connectivity is key to mitigating global change impacts such as isolation and climate change effects on populations, especially in historically modified biomes such as European forests. The term connectivity is widely used in conservation, but the multiple methods for measuring it, as well as the scales and objects of study to which it can be applied, make it difficult to understand and compare research results.

Objectives
Our aim was to enhance the understanding of connectivity studies in European forests to inform conservation efforts, guide future research, and identify potential knowledge gaps, through a systematic review of connectivity studies in European forests.

Methods
We did a systematic review on the literature of connectivity studies in European forests. We classified the studies according to the methods used. Then, we extracted information on study characteristics and context relevant for our purpose.

Results
Our literature search identified 142 relevant articles, more than half of these studied connectivity through structural measures (based only on landscape attributes). The three most used measures were area-based methods, Euclidean distances, and spatial indices (structural), followed by species and graph theory-based models (functional measures, including species data). Most studies focused on large Western European countries, and birds and mammals as focal taxa. Generally, functional measures were more frequent in publications that had the study of connectivity as a primary objective.

Conclusions
Research priorities and recommendations to guide future studies were identified such as the inclusion of structural and functional measures to bridge the gap between approaches, retaining the benefits of both and helping to uncover relationships between them; and as the need to address temporal connectivity, especially for less mobile species.
SeqMatcher: efficient genome sequence matching with AVX-512 extensions
Authors: Espinosa Elena , Quislant Ricardo , Larrosa Rafael , Plata Oscar 
Published: December 2024

AbstractThe recent emergence of long-read sequencing technologies has enabled substantial improvements in accuracy and reduced computational costs. Nonetheless, pairwise sequence alignment remains a time-consuming step in common bioinformatics pipelines, becoming a bottleneck in de novo whole-genome assembly. Speeding up this step requires heuristics and the development of memory-frugal and efficient implementations. A promising candidate for all of the above is Myers’ algorithm. However, the state-of-the-art implementations face scalability challenges when dealing with longer reads and large datasets. To address these challenges, we propose SeqMatcher, a fast and memory-frugal genomics sequence aligner. By leveraging the long registers of AVX-512, SeqMatcher reduces the data movement and memory footprint. In a comprehensive performance evaluation, SeqMatcher achieves speedups of up to 12.32x for the unbanded version and 26.70x for the banded version compared to the non-vectorized implementation, along with energy footprint reductions of up to 2.59x. It also outperforms state-of-the-art implementations by factors of up to 29.21x, 17.56x, 13.47x, 9.12x, and 8.81x compared to Edlib, WFA2-lib, SeqAn, BSAlign, and QuickEd, while improving energy consumption with reductions of up to 6.78x.
A fixed-point approach to control problems for Kolmogorov type second-order equations and systems
Authors: Hofman Alexandru , Precup Radu 
Published: December 2024

AbstractIn this paper, the second-order differential equations and systems of Kolmogorov type are defined. With reference to population dynamics models, unlike the first-order equations which give the expression of the per capita rate, in the case of the second-order equations, the law of change of the per capita rate is given. Several control problems with fixed final time and fixed final state, with additive and multiplicative control, are studied. Their controllability is proved with fixed-point methods, the theorems of Banach, Schauder, Krasnoselskii, Avramescu and Perov.
Morphometric and taxonomic studies of Senna ser. Coriaceae (Leguminosae, Caesalpinioideae, Cassieae), including a new species from Chapada Diamantina, Bahia, Brazil
Authors: de Lima Alexandre Gibau , de Freitas Mansano Vidal , Trovó Marcelo , Bacon Christine D. 
Published: December 2024

AbstractSenna sect. Chamaefistula ser. Coriaceae is restricted to Brazil and is predominantly distributed in savanna habitat. The species are morphologically characterized by their shrub or treelet habit, usually reniform stipules, extrafloral nectaries usually positioned on the middle or distal part of the petiole, zygomorphic corolla and laterally compressed fruits with the seeds parallel to the fruit valves. Previous taxonomic studies have recognized only three species and one variety, nevertheless, they provided the groundwork for a more comprehensive treatment, presented here. Based on fieldwork and on the analysis of herbarium specimens, we recognize five species belonging to Senna ser. Coriaceae including one new species from the seasonally dry areas in the Chapada Diamantina, Senna diamantinensis. We carried out a morphometric analyses and here recognize S. caesia as a distinct species rather than a variety of S. corifolia. We propose a new combination for Cassia kuhlmannii and recognize it under the genus Senna. In addition, we propose two first-step lectotypifications and one second-step lectotypification. The taxonomic treatment provided here includes an identification key, morphological descriptions, taxonomic notes, illustrations, preliminary conservation assessments, and habitat and phenology data for each species.
Apothecia trump setae: Paratricharia belongs in the Aulaxina clade and is distant from Tricharia (lichenized Ascomycota: Gomphillaceae)
Authors: Lücking Robert , Chaves-Chaves José Luis , Moncada Bibiana 
Published: December 2024

AbstractThe phylogenetic relationships of the monospecific genus Paratricharia, with the single species P. paradoxa, within the family Gomphillaceae are resolved using newly generated sequences of the mtSSU and nuLSU markers for three specimens collected in Costa Rica. The results support placement as sister to the genus Caleniopsis, the two genera sister to a clade containing the genera Aulaxina and Aulaxinella. This placement confirms earlier studies based on cladistic analysis of phenotype characters and phenotype-based phylogenetic binning, suggesting that apothecial features are more informative for the phylogenetic placement of taxa within Gomphillaceae than thallus characteristics.
Liquid Structure of Iron and Iron–Nitrogen–Carbon Alloys Within the Cores of Small Terrestrial Bodies
Authors: Pease Allison , Liu Jiachao , Lv Mingda , Piper Jack , Kono Yoshio , Dorfman Susannah M. 
Published: December 2024

AbstractNitrogen has been proposed to be stored within planetary cores, but its effects on the structure and density of molten Fe–alloys have not been explored experimentally. Using energy‐dispersive X‐ray diffraction, we determined the structure of Fe–N(–C) liquids at core conditions (1–7 GPa and 1700–1900°C) within a Paris‐Edinburgh press. Variation of N up to 7 wt.% and C up to 1.5 wt.% results in near‐linear changes in Fe–Fe atom distances and structure factor with increasing light element content. We did not observe a significant pressure‐driven structural transition in Fe–N(–C) liquids. We model the expansion of the Fe–Fe bonds using a modified Birch‐Murnaghan equation of state. With this model, we demonstrate that N or C contamination could lead to an overestimation of the Fe–Fe distances of pure Fe. We observe that the incorporation of 1 wt.% N or C into Fe results in a change in Fe–Fe distances that is twice as significant as the effect of 1 GPa. By approximating the change in volume, we infer that N and C incorporated in liquid iron could contribute to the density deficit observed in the cores of terrestrial bodies.
Power-free plasma separation based on negative magnetophoresis for rapid biochemical analysis
Authors: Zeng Lin , Liu Chao , Yang Yi , Hu Shi , Li Ruihan , Tan Xiaotian , Shen Jienan , Zhang Yi , Huang Shaohui , Yang Hui 
Published: December 2024

AbstractWe present a versatile platform for label-free magnetic separation of plasma, tailored to accommodate diverse environments. This innovative device utilizes an advanced long-short alternating double Halbach magnetic array, specifically engineered for optimal magnetic separation. The array’s adaptability allows for seamless integration with separation channels of varying sizes, enabling static separation of whole blood. The platform has a highly flexible processing throughput, spanning from 100 μL to 3 mL per separation cycle without sacrificing separation efficiency. A key aspect of this device is its power-free operation throughout the separation process, obviating the complexity of conventional separation devices. Its effectiveness is demonstrated by the extraction of 40 μL of plasma from 100 μL of rat whole blood within 8 min. The separated plasma proved effective for subsequent analysis of antibody concentration and size in the separated plasma for pharmacokinetic investigations, yielding results on par with those obtained via centrifugation. Furthermore, the device’s high-throughput capability was validated using human whole blood, achieving 3 mL of plasma separation in just 1 min. In a follow-up study on COVID-19 IgG antibody detection, the results matched those from centrifugation. The device demonstrates a separation efficiency of 99.9% for cells larger than 1 μm in both rat and human blood samples, with a plasma recovery rate of 72.7%. In summary, our magnetic separation device facilitates rapid plasma extraction from whole blood, with a capacity of up to 3 mL per minute in human blood, without compromising subsequent plasma-based analyses, thereby highlighting its broad applicability across diverse settings.
Unraveling the associations between voice pitch and major depressive disorder: a multisite genetic study
Authors: Di Yazheng , Rahmani Elior , Mefford Joel , Wang Jinhan , Ravi Vijay , Gorla Aditya , Alwan Abeer , Kendler Kenneth S. , Zhu Tingshao , Flint Jonathan 
Published: December 2024

AbstractMajor depressive disorder (MDD) often goes undiagnosed due to the absence of clear biomarkers. We sought to identify voice biomarkers for MDD and separate biomarkers indicative of MDD predisposition from biomarkers reflecting current depressive symptoms. Using a two-stage meta-analytic design to remove confounds, we tested the association between features representing vocal pitch and MDD in a multisite case-control cohort study of Chinese women with recurrent depression. Sixteen features were replicated in an independent cohort, with absolute association coefficients (beta values) from the combined analysis ranging from 0.24 to 1.07, indicating moderate to large effects. The statistical significance of these associations remained robust, with P values ranging from 7.2 × 10–6 to 6.8 × 10–58. Eleven features were significantly associated with current depressive symptoms. Using genotype data, we found that this association was driven in part by a genetic correlation with MDD. Significant voice features, reflecting a slower pitch change and a lower pitch, achieved an AUC-ROC of 0.90 (sensitivity of 0.85 and specificity of 0.81) in MDD classification. Our results return vocal features to a more central position in clinical and research work on MDD.
An isothermal calorimetry assay for determining steady state kinetic and Ensitrelvir inhibition parameters for SARS-CoV-2 3CL-protease
Authors: Mazzei Luca , Ranieri Sofia , Silvestri Davide , Greene-Cramer Rebecca , Cioffi Christopher , Montelione Gaetano T. , Ciurli Stefano 
Published: December 2024

Abstract
This manuscript details the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CLpro, the main protease from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CLpro is essential for producing the proteins necessary for viral infection, which led to the COVID-19 pandemic. The ITC-based assay provided rapid and reliable measurements of 3CLpro activity, allowing for the direct derivation of the kinetic enzymatic constants K

M
and k

cat
by monitoring the thermal power required to maintain a constant temperature as the substrate is consumed. The manuscript highlights several advantages of the proposed ITC-based assay over traditional methods used to study 3CLpro, such as Förster Resonance Energy Transfer (FRET) and Liquid Chromatography-Mass Spectrometry (LC–MS) and overcomes the need for non-biological substrates or discontinuous post-reaction steps. The ease of application of the ITC method allowed for the determination of the temperature dependence of the catalytic constants, enabling the estimation of the reaction activation energy. Additionally, the assay was used to determine the inhibition mode and kinetic parameters for 3CLpro inhibition by Ensitrelvir. This molecule was revealed to act as a slow- and tight-binding inhibitor that forms an initial E•I complex (K

I
= 9.9 ± 0.7 nM) quickly transitioning to a tighter E•I* assembly (K

I
* = 1.1 ± 0.2 nM). This versatile calorimetric method is proposed for general use in the discovery and development of drugs targeting 3CLpro.
Evolution of SARS-CoV-2 spike trimers towards optimized heparan sulfate cross-linking and inter-chain mobility
Authors: Froese Jurij , Mandalari Marco , Civera Monica , Elli Stefano , Pagani Isabel , Vicenzi Elisa , Garcia-Monge Itzel , Di Iorio Daniele , Frank Saskia , Bisio Antonella , Lenhart Dominik , Gruber Rudolf , Yates Edwin A. , Richter Ralf P. , Guerrini Marco , Wegner Seraphine V. , Grobe Kay 
Published: December 2024

AbstractThe heparan sulfate (HS)-rich extracellular matrix (ECM) serves as an initial interaction site for the homotrimeric spike (S) protein of SARS-CoV-2 to facilitate subsequent docking to angiotensin-converting enzyme 2 (ACE2) receptors and cellular infection. More recent variants, notably Omicron, have evolved by swapping several amino acids to positively charged residues to enhance the interaction of the S-protein trimer with the negatively charged HS. However, these enhanced interactions may reduce Omicron’s ability to move through the HS-rich ECM to effectively find ACE2 receptors and infect cells, raising the question of how to mechanistically explain HS-associated viral movement. In this work, we show that Omicron S proteins have evolved to balance HS interaction stability and dynamics, resulting in enhanced mobility on an HS-functionalized artificial matrix. This property is achieved by the ability of Omicron S-proteins to cross-link at least two HS chains, allowing direct S-protein switching between chains as a prerequisite for cell surface mobility. Optimized HS interactions can be targeted pharmaceutically, as an HS mimetic significantly suppressed surface binding and cellular infection specifically of the Omicron variant. These findings suggest a robust way to interfere with SARS-CoV-2 Omicron infection and potentially future variants.