bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic cyclic peptide for promoting antigen presentation and immune activation
Authors: Zhang Jiahui , Madge Harrison Y. R. , Mahmoud Asmaa , Lu Lantian , Wang Wanyi , Huang Wenbin , Koirala Prashamsa , Gonzalez Cruz Jazmina L. , Kong Wei Yang , Bashiri Sahra , Shalash Ahmed O. , Hussein Waleed M. , Khalil Zeinab G. , Wells James W. , Toth Istvan , Stephenson Rachel J. 
Published: January 2025

Abstract
Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action. We identified a potential universal delivery platform, not only capable of adjuvanting different peptide epitopes (e.g., NS1 and 88/30 from group A Streptococcus, gonadotropin hormone releasing hormone [GnRH]), but also protein antigens (e.g., bovine serum albumin [BSA], receptor binding domain (RBD) of the SARS-CoV-2 protein responsible for COVID-19 infection [SARS-CoV-2 RBD]) and small molecular haptens (e.g., cocaine). All vaccine candidates self-assembled into sub-500 nm nanoparticles and induced high antigen-specific systemic IgG titers and opsonic potential compared to the antigen co-administered with a commercial adjuvant, complete Freund’s adjuvant. Notably, presence of the cyclic decapeptide in this vaccine increased accumulation in the draining inguinal lymph nodes, facilitating cellular uptake of peptide antigens. Furthermore, the lipoamino acid promoted dendritic cell activation, acting as both toll-like receptors 2 and 4 -targeting moiety. Our study revealed the importance of the cyclic decapeptide and lipoamino acid presence in antigen presentation and immune response activation, leading onto the development of a fully synthetic, self-assembled, and promising platform for the delivery of subunit vaccines and anti-drug vaccines.
Continental influx and pervasive matrilocality in Iron Age Britain
Authors: Cassidy Lara M. , Russell Miles , Smith Martin , Delbarre Gabrielle , Cheetham Paul , Manley Harry , Mattiangeli Valeria , Breslin Emily M. , Jackson Iseult , McCann Maeve , Little Harry , O’Connor Ciarán G. , Heaslip Beth , Lawson Daniel , Endicott Phillip , Bradley Daniel G. 
Published: January 2025

Abstract
Roman writers found the relative empowerment of Celtic women remarkable1. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods2. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male. Such a matrilocal pattern is undescribed in European prehistory, but when we compare mitochondrial haplotype variation among European archaeological sites spanning six millennia, British Iron Age cemeteries stand out as having marked reductions in diversity driven by the presence of dominant matrilines. Patterns of haplotype sharing reveal that British Iron Age populations form fine-grained geographical clusters with southern links extending across the channel to the continent. Indeed, whereas most of Britain shows majority genomic continuity from the Early Bronze Age to the Iron Age, this is markedly reduced in a southern coastal core region with persistent cross-channel cultural exchange3. This southern core has evidence of population influx in the Middle Bronze Age but also during the Iron Age. This is asynchronous with the rest of the island and points towards a staged, geographically granular absorption of continental influence, possibly including the acquisition of Celtic languages.
Prolonged persistence of mutagenic DNA lesions in somatic cells
Authors: Spencer Chapman Michael , Mitchell Emily , Yoshida Kenichi , Williams Nicholas , Fabre Margarete A. , Ranzoni Anna Maria , Robinson Philip S. , Kregar Lori D. , Wilk Matthias , Boettcher Steffen , Mahbubani Krishnaa , Saeb Parsy Kourosh , Gowers Kate H. C. , Janes Sam M. , Ng Stanley W. K. , Hoare Matt , Green Anthony R. , Vassiliou George S. , Cvejic Ana , Manz Markus G. , Laurenti Elisa , Martincorena Iñigo , Stratton Michael R. , Nangalia Jyoti , Coorens Tim H. H. , Campbell Peter J. 
Published: January 2025

Abstract
DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment1–3. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours3,4, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium5–12. Persistent DNA lesions occurred at increased rates, with distinctive mutational signatures, in donors exposed to tobacco or chemotherapy, suggesting that they can arise from exogenous mutagens. In haematopoietic stem cells, persistent DNA lesions, probably from endogenous sources, generated the characteristic mutational signature SBS1913; occurred steadily throughout life, including in utero; and endured for 2.2 years on average, with 15–25% of lesions lasting at least 3 years. We estimate that on average, a haematopoietic stem cell has approximately eight such lesions at any moment in time, half of which will generate a mutation with each cell cycle. Overall, 16% of mutations in blood cells are attributable to SBS19, and similar proportions of driver mutations in blood cancers exhibit this signature. These data indicate the existence of a family of DNA lesions that arise from endogenous and exogenous mutagens, are present in low numbers per genome, persist for months to years, and can generate a substantial fraction of the mutation burden of somatic cells.
Autoactive CNGC15 enhances root endosymbiosis in legume and wheat
Authors: Cook Nicola M. , Gobbato Giulia , Jacott Catherine N. , Marchal Clemence , Hsieh Chen Yun , Lam Anson Ho Ching , Simmonds James , del Cerro Pablo , Gomez Pilar Navarro , Rodney Clemence , Cruz-Mireles Neftaly , Uauy Cristobal , Haerty Wilfried , Lawson David M. , Charpentier Myriam 
Published: January 2025

Abstract
Nutrient acquisition is crucial for sustaining life. Plants develop beneficial intracellular partnerships with arbuscular mycorrhiza (AM) and nitrogen-fixing bacteria to surmount the scarcity of soil nutrients and tap into atmospheric dinitrogen, respectively1,2. Initiation of these root endosymbioses requires symbiont-induced oscillations in nuclear calcium (Ca2+) concentrations in root cells3. How the nuclear-localized ion channels, cyclic nucleotide-gated channel (CNGC) 15 and DOESN’T MAKE INFECTIONS1 (DMI1)4 are coordinated to specify symbiotic-induced nuclear Ca2+ oscillations remains unknown. Here we discovered an autoactive CNGC15 mutant that generates spontaneous low-frequency Ca2+ oscillations. While CNGC15 produces nuclear Ca2+ oscillations via a gating mechanism involving its helix 1, DMI1 acts as a pacemaker to specify the frequency of the oscillations. We demonstrate that the specificity of symbiotic-induced nuclear Ca2+ oscillations is encoded in its frequency. A high frequency activates endosymbiosis programmes, whereas a low frequency modulates phenylpropanoid pathways. Consequently, the autoactive cngc15 mutant, which is capable of generating both frequencies, has increased flavonoids that enhance AM, root nodule symbiosis and nutrient acquisition. We transferred this trait to wheat, resulting in field-grown wheat with increased AM colonization and nutrient acquisition. Our findings reveal a new strategy to boost endosymbiosis in the field and reduce inorganic fertilizer use while sustaining plant growth.
Massively parallel characterization of transcriptional regulatory elements
Authors: Agarwal Vikram , Inoue Fumitaka , Schubach Max , Penzar Dmitry , Martin Beth K. , Dash Pyaree Mohan , Keukeleire Pia , Zhang Zicong , Sohota Ajuni , Zhao Jingjing , Georgakopoulos-Soares Ilias , Noble William S. , Yardımcı Galip Gürkan , Kulakovskiy Ivan V. , Kircher Martin , Shendure Jay , Ahituv Nadav 
Published: January 2025

Abstract
The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states1. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.7% of these sequences were active. By testing sequences in both orientations, we find promoters to have strand-orientation biases and their 200-nucleotide cores to function as non-cell-type-specific ‘on switches’ that provide similar expression levels to their associated gene. By contrast, enhancers have weaker orientation biases, but increased tissue-specific characteristics. Utilizing our lentiMPRA data, we develop sequence-based models to predict cCRE function and variant effects with high accuracy, delineate regulatory motifs and model their combinatorial effects. Testing a lentiMPRA library encompassing 60,000 cCREs in all three cell types further identified factors that determine cell-type specificity. Collectively, our work provides an extensive catalogue of functional CREs in three widely used cell lines and showcases how large-scale functional measurements can be used to dissect regulatory grammar.
Self-isolation of adolescents after Covid-19 pandemic between social withdrawal and Hikikomori risk in Italy
Authors: Cerbara Loredana , Ciancimino Giulia , Corsetti Gianni , Tintori Antonio 
Published: January 2025

Abstract
Social withdrawal is a widespread phenomenon among adolescents, presenting significant challenges in understanding its aetiology and dynamics. This study, drawing on data from two cross-sectional surveys conducted in 2019 and 2022 on students in public upper secondary schools, investigates the trend of self-isolation among Italian adolescents before and after the COVID-19 pandemic. The two nationally representative samples comprise 3273 and 4288 participants, respectively, with 46.3% and 41.2% identifying as female, ranging in age from 14 to 19 years. Using Multiple Correspondence Analysis (MCA) and Hierarchical Cluster Analysis (HCA), three distinct profiles of social withdrawal were identified among adolescents: “Social Butterflies”, “Friendship-Centric”, and “Lone Wolves”. Notably, the discovery of a subgroup within the Lone Wolves, composed of adolescents who never meet their friends and whose number has doubled post-pandemic, highlights the chronic nature of the phenomenon that demands urgent intervention. These findings shed light on the increase of self-isolation in Italy, showing the interplay of socio-demographic, psychological, and sociological factors underlying this phenomenon.
Validation of mixed reality in planning orbital reconstruction with patient-specific implants
Authors: Dubron K. , Shaheen E. , Jacobs R. , Politis C. , Willaert R. 
Published: January 2025

Abstract
This study aims to evaluate and compare the usability and performance of mixed reality (MR) technology versus conventional methods for preoperative planning of patient-specific reconstruction plates for orbital fractures. A crossover study design was used to compare MR technology with conventional three-dimensional (3D) printing approaches in the planning of maxillofacial traumatology treatments. The primary focus was on user-friendliness and the accuracy of patient-specific reconstruction planning. Secondary outcomes included investigating time differences between the two approaches and evaluating the potential effects on the learning curve. Participants were asked to complete questionnaires assessing various aspects, such as visualization, interaction, segmentation, treatment planning, and evaluation. Objective endpoints were evaluated blindly, while subjective endpoints were analyzed through a double-blind process. The total workflow time for MR technology was significantly shorter compared to the conventional method. Moreover, treatment planning using MR was significantly more accurate (p = .028), with participants reporting a higher mean global satisfaction score compared to the conventional group (80.6% vs. 72.5%). This study sheds light on the potential benefits of employing MR technology in maxillofacial orbital reconstruction. This preoperative method allows for faster and more precise design of patient-specific implants for orbital reconstruction, potentially leading to improved long-term cost-effectiveness.
Implications for the diagnosis of aspiration and aspergillosis in critically ill patients with detection of galactomannan in broncho-alveolar lavage fluids
Authors: Dubler Simon , Etringer Michael , Lichtenstern Christoph , Brenner Thorsten , Zimmermann Stefan , Schnitzler Paul , Budeus Bettina , Rengier Fabian , Kalinowska Paulina , Hoo Yuan Lih , Weigand Markus A. 
Published: January 2025

Abstract
Invasive infections with Aspergillus fumigatus in ICU patients are linked to high morbidity and mortality. Diagnosing invasive pulmonary aspergillosis (IPA) in non-immunosuppressed patients is difficult, as Aspergillus antigen (galactomannan [GM]) may have other causes. This retrospective study analyzed 160 ICU surgical patients with positive GM in broncho-alveolar lavage fluid (BALF), classifying them based on AspICU criteria for suspected IPA (pIPA) or aspiration. Patients with pIPA had higher disease severity than those with aspiration, including higher dialysis rates, organ transplantation, corticosteroid use, and Sequential Organ Failure Assessment (SOFA) score. Aspergillus culture was positive in 47.0% of pIPA cases but only 2.6% of aspiration cases (p < 0.001). SOFA score at first positive GM in BALF independently predicted 28-day mortality. In surgical patients with a positive GM in BALF, aspiration is more likely if there’s no corticosteroid therapy, negative Aspergillus culture, and a history of aspiration events. Diagnosis of pIPA requires Aspergillus culture or prior corticosteroid therapy in this cohort of critically ill patients.
Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity
Authors: Mougari Said , Favède Valérie , Predella Camilla , Reynard Olivier , Durand Stephanie , Mazelier Magalie , Pizzioli Edoardo , Decimo Didier , Bovier Francesca T. , Lapsley Lauren M. , Castagna Candace , Lieberman Nicole A. P. , Noel Guillaume , Mathieu Cyrille , Malissen Bernard , Briese Thomas , Greninger Alexander L. , Alabi Christopher A. , Dorrello N. Valerio , Marot Stéphane , Marcelin Anne-Geneviève , Zarubica Ana , Moscona Anne , Porotto Matteo , Horvat Branka 
Published: January 2025

Abstract
We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants. Prolonged administration of high-dose lipopeptides has neither adverse effects nor impairs peptide efficacy in subsequent SARS-CoV-2 challenges. The peptide-protected mice develop cross-reactive neutralizing antibodies against both SARS-CoV-2 used for the initial infection and recently circulating variants, and are completely protected from a second lethal infection, suggesting that they developed SARS-CoV-2-specific immunity. This strategy provides an additional antiviral approach in the global effort against COVID-19 and may contribute to development of rapid responses against emerging pathogenic viruses.
Unified study of viscoelasticity and sound damping in hard and soft amorphous solids
Authors: Mizuno Hideyuki , Saitoh Kuniyasu , Hara Yusuke , Ikeda Atsushi 
Published: January 2025

Abstract
Amorphous solids are diverse materials that take on various forms such as structural glasses, granular materials, foams, emulsions, and biological systems. Recent research has made significant progress in understanding non-phonon vibrational modes universally present in amorphous materials, which have been observed as excess vibrational modes over the Debye law, known as boson peak, as well as quasi-localized vibrational modes. These vibrational modes are crucial to explaining material properties of a wide range of amorphous materials, from “hard" solids like structural glasses to “soft" solids like foams and emulsions. However, we still lack a theoretical framework that can comprehensively explain them in a unified manner. Here, we propose a unified theory for viscoelasticity and sound damping which are significantly different between hard and soft amorphous solids but are ultimately determined by non-Debye scaling laws of the non-phonon vibrational modes. Our theory can explain acoustic properties of structural glasses, which have been measured experimentally with light, inelastic X-ray, and neutron scattering techniques, on one hand, and viscoelastic properties of foams and emulsions, which have been measured by various macrorheology and microrheology techniques, on the other. We thus provide a comprehensive explanation for these experimental measurements of two distinct types of amorphous solids.
Depression symptom-specific genetic associations in clinically diagnosed and proxy case Alzheimer’s disease
Authors: Gilchrist Lachlan , Spargo Thomas P. , Green Rebecca E. , Coleman Jonathan R. I. , Howard David M. , Thorp Jackson G. , Adey Brett N. , Lord Jodie , Davies Helena L. , Mundy Jessica , ter Kuile Abigail R. , Davies Molly R. , Hübel Christopher , Bristow Shannon , Lee Sang Hyuck , Rogers Henry , Curtis Charles , Kakar Saakshi , Malouf Chelsea M. , Kalsi Gursharan , Arathimos Ryan , Corbett Anne , Ballard Clive , Brooker Helen , Creese Byron , Aarsland Dag , Hampshire Adam , Velayudhan Latha , Eley Thalia C. , Breen Gerome , Iacoangeli Alfredo , Kõks Sulev , Lewis Cathryn M. , Proitsi Petroula 
Published: January 2025

Abstract
Depression is a risk factor for the later development of Alzheimer’s disease (AD), but evidence for the genetic relationship is mixed. Assessing depression symptom-specific genetic associations may better clarify this relationship. To address this, we conducted genome-wide meta-analysis (a genome-wide association study, GWAS) of the nine depression symptom items, plus their sum score, on the Patient Health Questionnaire (PHQ-9) (GWAS-equivalent N: 224,535–308,421) using data from UK Biobank, the GLAD study and PROTECT, identifying 37 genomic risk loci. Using six AD GWASs with varying proportions of clinical and proxy (family history) case ascertainment, we identified 20 significant genetic correlations with depression/depression symptoms. However, only one of these was identified with a clinical AD GWAS. Local genetic correlations were detected in 14 regions. No statistical colocalization was identified in these regions. However, the region of the transmembrane protein 106B gene (TMEM106B) showed colocalization between multiple depression phenotypes and both clinical-only and clinical + proxy AD. Mendelian randomization and polygenic risk score analyses did not yield significant results after multiple testing correction in either direction. Our findings do not demonstrate a causal role of depression/depression symptoms on AD and suggest that previous evidence of genetic overlap between depression and AD may be driven by the inclusion of family history-based proxy cases/controls. However, colocalization at TMEM106B warrants further investigation.
A neural coding method based on feature sensing
Authors: He Dongbin , Hu Aiqun , Sheng Kaiwen 
Published: January 2025

AbstractThe novel network contains many sensors, which greatly heightens data transmission burdens. Some networks require the data perceived by sensors for a period to make decisions. Drawing inspiration from the human neural conduction mechanism, a waveform data encoding method called feature sensing neural coding (FSNC) is proposed to enhance network data transmission efficiency. It involves feature decomposition of information and subsequent non‐linear encoding of feature coefficients for data transmission. This approach exploits the unique neuronal responses to diverse stimuli and the inherent non‐linear characteristics of human neural coding. Finally, taking the speech signal and seismic wave signal as examples, the effectiveness of FSNC is verified by simulating the auditory nerve conduction process with frequency as a feature according to the mechanism of travelling wave motion of the basilar membrane in the cochlea. Moreover, experiments on seismic waveform signals have demonstrated the wide applicability of FSNC. Compared with traditional speech coding schemes, the FSNC bit rate is only 6.4 kbps, which greatly reduces the amount of data transmitted. Not only that, FSNC also has a certain fault tolerance, and parallel transmission can also greatly increase the transmission rate. This research provides new ideas for efficient data transmission over new networks.
Knowledge distillation approach for skin cancer classification on lightweight deep learning model
Authors: Saha Suman , Hemal Md. Moniruzzaman , Eidmum Md. Zunead Abedin , Mridha Muhammad Firoz 
Published: January 2025

AbstractOver the past decade, there has been a global increase in the incidence of skin cancers. Skin cancer has serious consequences if left untreated, potentially leading to more advanced cancer stages. In recent years, deep learning based convolutional neural network have emerged as powerful tools for skin cancer detection. Generally, deep learning approaches are computationally expensive and require large storage space. Therefore, deploying such a large complex model on resource‐constrained devices is challenging. An ultra‐light and accurate deep learning model is highly desirable for better inference time and memory in low‐power‐consuming devices. Knowledge distillation is an approach for transferring knowledge from a large network to a small network. This small network is easily compatible with resource‐constrained embedded devices while maintaining accuracy. The main aim of this study is to develop a deep learning‐based lightweight network based on knowledge distillation that identifies the presence of skin cancer. Here, different training strategies are implemented for the modified benchmark (Phase 1) and custom‐made model (Phase 2) and demonstrated various distillation configurations on two datasets: HAM10000 and ISIC2019. In Phase 1, the student model using knowledge distillation achieved accuracies ranging from 88.69% to 93.24% for HAM10000 and from 82.14% to 84.13% on ISIC2019. In Phase 2, the accuracies ranged from 88.63% to 88.89% on HAM10000 and from 81.39% to 83.42% on ISIC2019. These results highlight the effectiveness of knowledge distillation in improving the classification performance across diverse datasets and enabling the student model to approach the performance of the teacher model. In addition, the distilled student model can be easily deployed on resource‐constrained devices for automated skin cancer detection due to its lower computational complexity.