bluuebunny/crossref_metadata_2025_split huggingface dataset:
Painting Peptides with Antimicrobial Potency through Deep Reinforcement Learning
Authors: Dong Ruihan , Cao Qiushi , Song Chen 
Published: January 2025

AbstractIn the post-antibiotic era, antimicrobial peptides (AMPs) serve as ideal drug candidates for their lower likelihood of inducing resistance. Computational models offer an efficient way to design novel AMPs. However, current optimization and generation approaches are tailored for different application scenarios. To address this challenge, we propose a novel AMP design model named AMPainter. Based on deep reinforcement learning, AMPainter integrates both optimization and generation tasks in a unified framework. We apply AM-Painter to three types of peptides, including known AMPs, signal peptides (SPs), and random sequences. AMPainter outperforms ten related models in enhancing the activity of known AMPs, and evolves effective AMPs from membrane-active SPs with a success rate of 80%. Furthermore, severalde novodesigned AMPs from random sequences are validated along with their evolutionary paths. Therefore, AMPainter contributes topaintantimicrobial potency to diverse peptides, assisting in expanding the AMP sequence space and discovering novel antimicrobial agents.
ERGA-BGE genome ofStigmatoteuthis arcturiRobson, 1948: the jewelled squid
Authors: Fernández-Álvarez Fernando Ángel , Bernal-Bajo Ainhoa , Escudero Nuria , Conejero María , Riesgo Ana , Fernández Rosa , Monteiro Rita , Böhne Astrid , Aguilera Laura , Gut Marta , Alioto Tyler S. , Ferreira Francisco Câmara , Cruz Fernando , Gómez-Garrido Jèssica , Brown Tom 
Published: January 2025

AbstractTheStigmatoteuthis arcturireference genome offers a valuable resource for understanding the evolutionary patterns of oceanic squids, who perform important ecological roles as both predators and prey in mesopelagic and deep-sea environments, while their genomes remain understudied. The entirety of the genome sequence was assembled into 46 contiguous chromosomal pseudomolecules. This chromosome-level assembly encompasses 3.25 Gb, composed of 1,268 contigs and 497 scaffolds, with contig and scaffold N50 values of 11.0 Mb and 74.6 Mb, respectively.
Deletion of themoeA gene inFlavobacteriumIR1 drives structural color shift from green to blue and alters polysaccharide metabolism
Authors: Escobar Doncel Álvaro , Patinios Constantinos , Campos Alexandre , Walter Costa Maria Beatriz , Turkina Maria V. , Murace Maria , Staals Raymond H.J. , Vignolini Silvia , Dutilh Bas E. , Ingham Colin J. 
Published: January 2025

ABSTRACTStructural colors (SC), generated by light interacting with nanostructured materials, is responsible for the brightest and most vivid coloration in nature. Despite being widespread within the tree of life, there is little knowledge of the genes involved. Partial exceptions are someFlavobacteriiain which genes involved in a number of pathways, including gliding motility and polysaccharide metabolism, have been linked to SC. A previous genomic analysis of SC and non-SC bacteria suggested that the pterin pathway is involved in the organization of bacteria to form SC. Thus here, we focus on themoeA molybdopterin molybdenum transferase. When this gene was deleted fromFlavobacteriumIR1, the knock-out mutant showed a strong blue shift in SC of the colony, different from the green SC of the wild-type. ThemoeA mutant showed a particularly strong blue shift when grown on kappa-carrageenan and was upregulated for starch degradation. To further analyze the molecular changes, proteomic analysis was performed, showing the upregulation of various polysaccharide utilization loci, which supported the link betweenmoeA and polysaccharide metabolism in SC. Overall, we demonstrated that single-gene mutations could change the optical properties of bacterial SC, which is unprecedented when compared to multicellular organisms where structural color is the result of several genes and can not yet be addressed genetically.
A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide’s Effects on Energy Balance
Authors: Ludwig Mette Q. , Coester Bernd , Gordian Desiree , Hassan Shad , Tomlinson Abigail J. , Toure Mouhamadoul Habib , Christensen Oliver P. , Moltke-Prehn Anja , Brown Jenny M. , Rausch Dylan M. , Gowda Anika , Wu Iris , Kernodle Stace , Dong Victoria , Ayensu-Mensah Mike , Sabatini Paul V. , Shin Jae Hoon , Kirigiti Melissa , Egerod Kristoffer L. , Le Foll Christelle , Lundh Sofia , Gerstenberg Marina Kjærgaard , Lutz Thomas A. , Kievit Paul , Secher Anna , Raun Kirsten , Myers Martin G. , Pers Tune H. 
Published: January 2025

AbstractAmylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate the suppression of food intake and body weight. To understand the molecular and neural mechanisms of cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across the rat, mouse, and non-human primate caudal brainstem. We then integrated spatial profiling to reveal neuron distribution in the rat DVC. Furthermore, we compared the acute and long-term transcriptional responses to cagrilintide across DVC neurons of rats, which exhibit strong cagrilintide responsiveness, and mice, which respond poorly to cagrilintide over the long term. We found that cagrilintide promoted long-term transcriptional changes, including increased prolactin releasing hormone (Prlh) expression, in the nucleus of the solitary tract (NTS)Calcr/Prlhcells in rats, but not in mice, suggesting the importance of NTSCalcr/Prlhcells for sustained weight loss. Indeed, activating rat area postremaCalcrcells briefly reduced food intake but failed to decrease food intake or body weight over the long term. Overall, these results not only provide a cross-species and spatial atlas of DVC cell populations but also define the molecular and neural mediators of acute and long-term cagrilintide action.
Embedding muscle fibers in hydrogel improves viability and preserves contractile function during prolongedex vivoculture
Authors: Vonk Leander A. , Esen Osman , Hoomoedt Daan , Balesar Rajvi M.N. , Ottenheijm Coen A. C. , Kirby Tyler J. 
Published: January 2025

AbstractEx vivoculture of isolated muscle fibers can serve as an important model forin vitroresearch on mature skeletal muscle fibers. Nevertheless, this model has limitations for long-term studies due to structural loss and dedifferentiation following prolonged culture periods. This study aimed to investigate howex vivoculture affects muscle fiber contraction and to improve the culture system to preserve muscle fiber morphology and sarcomere function. Additionally, we sought to determine which culture-induced changes can negatively affect muscle fiber contraction. We cultured isolated flexor digitorum brevis (FDB) muscle fibers in several conditions for up to 7 days, and investigated viability, morphology, the unloaded sarcomere shortening in intact fibers, along with force generation in permeabilized muscle fibers. In addition, we examined changes to the microtubule network. We found a time-dependent decrease in contractility and viability in muscle fibers cultured for 7 days in a 2D environment. Conversely, we found that culturing FDB muscle fibers in a low-serum, 3D culture environment reduces markers of muscle fiber dedifferentiation (i.e. sprouting), improves viability and retains contractility over time. We discovered that the loss of contractility of cultured muscle fibers was not the direct result of reduced sarcomere function but could be partially explained by changes to the microtubule network. Collectively, our findings highlight the importance of providing muscle fibers with a 3D environment duringex vivoculture, particularly when testing pharmacological or genetic interventions to study viability or contractile function.SummaryIn this work, the authors demonstrate that a low-serum, 3Dex vivoculture model preserves muscle fiber viability and contractility while reducing dedifferentiation. This model system can be utilized to conduct prolongedex vivopharmacological or genetic interventions to study fundamental muscle fiber processes or disease mechanisms.
Functional analysis of promoter element 2 within the viral polymerase gene of an emerging paramyxovirus, Sosuga virus
Authors: Akter Lipi , Kawasaki Junna , Rakib Tofazzal Md. , Okura Takashi , Kato Fumihiro , Kojima Shohei , Oda Kosuke , Matsumoto Yusuke 
Published: January 2025

AbstractParamyxovirus genomes carry bipartite promoters at the 3’ ends of both their genome and antigenome, thereby initiating RNA synthesis, which requires the viral polymerase to recognize two elements: the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2). We have previously shown that the antigenomic PE2 (agPE2) in many viruses in theRubulavirinaesubfamily is located within the coding region of the viral RNA polymerase L gene. Sosuga virus (SOSV), belonging to theRubulavirinaesubfamily, is highly pathogenic to humans, thus necessitating high-level containment facilities for infectious virus research. The use of a minigenome system permits studies of viral RNA synthesis at lower biosafety levels. Because minigenomes of negative-strand RNA viruses generally comprise only the untranslated regions, agPE2 within the L coding region—such as those found inRubulavirinaelike SOSV—are typically omitted. However, generating an SOSV minigenome that retains agPE2 led to a pronounced increase in activity, enabling a detailed examination of the role of agPE2 in SOSV replication. In manyRubulavirinae, the agPE2 not only acts as a promoter but also encodes part of the L protein, resulting in a distinct motif at the C-terminus of the L protein. We have further shown that this motif is preserved even inRubulavirinaethat no longer contain the agPE2 within the L gene.ImportanceParamyxoviruses are classified into three major subfamilies:Orthoparamyxovirinae,AvulavirinaeandRubulavirinae. All paramyxovirus genomes and antigenomes possess bipartite promoters, comprising two elements: promoter element 1 (PE1) at the 3’ end and promoter element 2 (PE2) located internally. We previously revealed that, in manyRubulavirinae, the antigenomic PE2 lies within the coding region of the viral RNA polymerase L gene. In this study, we used Sosuga virus, a member of theRubulavirinaesubfamily, to elucidate the role of antigenomic PE2 in viral replication. Because the PE2 region encodes part of the L protein, its presence leads to a distinctive motif at the C-terminus of L protein. Notably, this motif is conserved in allRubulavirinae, including those that do not harbor the antigenomic PE2 within their L gene, indicating its importance in viral propagation.
Understanding the barriers and facilitators to delivering peer support effectively in England: a qualitative interview study
Authors: Foye Una , Lyons Natasha , Shah Prisha , Mitchell Lizzie , Machin Karen , Chipp Beverley , Jeffreys Stephen , Jeynes Tamar , Persaud Karen , Nicholls Vicky , Cooper Ruth E , Grundy Andrew , Pemovska Tamara , Ahmed Nafiso , Appleton Rebecca , Repper Julie , Johnson Sonia , Lloyd-Evans Brynmor , Simpson Alan 
Published: January 2025

AbstractBackgroundPeer support roles within mental health services are rapidly increasing in number and scope in the UK and internationally. This paper explores the facilitators and barriers to delivering peer support effectively, as experienced by Peer Support Workers (PSWs) in a range of services and settings.MethodsWe conducted semi-structured qualitative interviews with paid mental health PSWs working across a range of settings in England. We took a collaborative, participatory approach. Interviews were carried out by researchers with experience of living with and/or supporting others with mental health conditions, and for some having experience delivering peer support themselves, and data were analysed using methods guided by general principles of thematic analysis.ResultsWe interviewed 35 PSWs. Their roles were varied, spanning a range of mental health areas, and regions, but overarching facilitators and barriers were identified that appeared important across roles and settings. These included the need for roles to have flexibility with some structure and boundaries; the need for support, supervision and training to ensure PSWs are skilled in delivering the unique elements of their job; the importance of working with a strong team and leaders who support and value PSWs to help navigate the challenging personal aspects of being a PSW; the complexity of working in mental health systems where systemic factors such as funding, pay and progression can have a considerable effect both on the personal experience of PSWs and on the value placed on PSWs in the wider organisation.ConclusionOur findings highlight the complexity of PSWs, with a wide variety both of facilitators allowing them to carry out roles effectively and barriers to doing so. As PSWs numbers and the scope of their roles increase, awareness of barriers and facilitators needs to inform PSW job roles, support systems and integration into teams and mental health systems.
Multi-molecular phenotyping in a self-sampling population
Authors: Dahl Leo , Bendes Annika , Bueno Álvez María , Albrecht Vincent , Aghelpasand Hooman , Björkander Sophia , Kebede Merid Simon , Mezger Anja , Käller Max , Fredolini Claudia , Torinsson Naluai Åsa , Beck Olof , Melén Erik , Bauer Stefan , Gisslén Magnus , Roxhed Niclas , Schwenk Jochen M 
Published: January 2025

AbstractThe recent COVID-19 pandemic has posed major health challenges. To expand our molecular understanding beyond those seeking medical care, we conducted a cross-sectional survey targeting random residents from Sweden’s two largest cities.Two thousand participants were invited during 2021 to self-sample dried blood spots (DBS) and provide health information. DBS samples were analysed for multiple anti-SARS-CoV-2 antibodies (Abs), auto-reactive antibodies (AAbs) against 23 interferons (IFNs), and for 502 circulating immune-related proteins. Data-driven methodologies characterised the DBS phenotypes in response to infections and vaccination.We received DBS samples from 437 (22%) volunteers aged 18-69, 60% females, and 50% per city. Multi-analyte serology distinguished self-reported infections (26%) and vaccination (40%), revealing a time-dependent discrepancy between reported and measured immunity. Anti-IFN Abs were detected in 21% of the donors and more frequent for type 1 IFNs alongside a natural infection. Integrating proteomics with antibody data provided additional insights into processes of cell-mediated immunity. Proteomics-centric analysis identified 24% of the participants to deviate in their phenotypes due to infection, immunity, respiratory distress, and age-related traits.Multi-molecular analysis of layperson samples uncovered heterogeneity and diversity of immunity and health phenotypes, complementing clinical investigations.
Cross-sectional Study on Sex Disparities among Japanese and Korean University School of Pharmacy Professors
Authors: Soh Hyunseo , Ohno Eri , Hashimoto Mayu , Han Euna , Maeda Hideki 
Published: January 2025

AbstractJapan and South Korea are ranked low in the Gender Gap Index, and the ratio of female faculty members at universities is low. The ratio of female professors at universities is assumed to be lower than the ratio of female medical professionals; however, the details remain unknown. Consequently, this study aimed to examine sex disparity among professors in the pharmacy departments of universities in Japan and South Korea. Furthermore, the characteristics of Japanese and South Korean pharmacy departments were examined to explore the differences and sex disparity.This study was conducted based on publicly available information from the websites of each university’s pharmacy department as of November 1, 2023. Sex was determined from first names or photographs. This study was conducted following the STROBE guidelines, and no ethical review or consent was required.This study included 73 universities in Japan and 35 universities in South Korea. The proportion of female professors in university pharmacy departments was 12.5% in Japan and 32.9% in South Korea. A total of 1,965 pharmacy professors were identified in Japan and South Korea. Of these, 1,527 were from Japan and 438 were from South Korea. The estimated ratio of professors to million individuals in Japan was 12.28, compared to 8.51 in South Korea. This indicated that Japan had approximately 1.4 times as many professors as South Korea after correction for population.The proportion of female professors in both countries was <50%. Japan had significantly fewer female professors than South Korea, suggesting that women’s advancement in university pharmacy departments was lagging in Japan. Additionally, South Korea’s higher number of female professors specializing in clinical research may suggest that women with clinical practice experience in hospitals or pharmacies were becoming university professors.
A Comparative Environmental Impact Analysis of Screening Tests for Colorectal Cancer
Authors: Rudrapatna Vivek A. , Wang Tzu An , Vazirnia Parsia , Wang Kaiyi , Alhalel Nathan , Slatter Shadera , Mattson Gunnar , Becker Amy , Oon Ching-Ying , Wang Shan , Karlon William , Pasternak Scott , Thiel Cassandra L. , Gandhi Seema , Woolen Sean 
Published: January 2025

ABSTRACTBACKGROUNDHealthcare is a major contributor to global greenhouse gas emissions. Colorectal cancer (CRC) screening is one of the most widely used healthcare services in the US, indicated for approximately 134 million adults. Recommended screening options include fecal immunochemical tests (FITs) every year, CT colonographies (CTCs) every 5 years, or colonoscopies every 10 years. We compared the environmental impacts of these tests and identified opportunities for impact reduction.METHODSWe conducted a comparative life cycle assessment of three CRC screening strategies at the University of California, San Francisco. We performed on site audits to document the materials and energy used for each screening test. We used the ReCiPe 2016 method to estimate the environmental impacts of these procedures, measured by global warming potential (GWP) and damage to human health. We estimated the 10-year cumulative impacts of each screening strategy using a Markov reward model. We accounted for model uncertainty using hierarchical Monte Carlo simulations.FINDINGSFIT-based screening had the lowest environmental impacts, with a roughly 20% margin of superiority over colonoscopies, and this finding was robust in sensitivity analyses. Across tests, the biggest cause of environmental harm was car-based transportation of patients and staff. Prioritizing FITs over screening colonoscopies in the US could enhance population health by roughly 5.2 million disability adjusted life years per decade. Transitioning to electric vehicles could reduce the GWP of all screening tests by 15-20%.INTERPRETATIONGiven the similar efficacy and safety of these tests, payors should prioritize FITs for low-risk patients. Government initiatives to decarbonize transportation, incentivize telehealth, and mandate environmental product declarations will help reduce the environmental impacts of healthcare more generally. Our results call for a closer look at resource-intensive preventative health strategies, which could result in more harm than good if applied to a low-risk population.FUNDINGNIH, UCSF
Privacy-preserving AUC Computation in Distributed Machine Learning with PHT-meDIC
Authors: de Arruda Botelho Herr Marius , Baykara Cem Ata , Ünal Ali Burak , Pfeifer Nico , Akgün Mete 
Published: January 2025

AbstractEnsuring privacy in distributed machine learning while computing the Area Under the Curve (AUC) is a significant challenge because pooling sensitive test data is often not allowed. Although cryptographic methods can address some of these concerns, they may compromise either scalability or accuracy. In this paper, we present two privacy-preserving solutions for secure AUC computation across multiple institutions: (1) an exact global AUC method that handles ties in prediction scores and scales linearly with the number of samples, and (2) an approximation method that substantially reduces runtime while maintaining acceptable accuracy. Our protocols leverage a combination of homomorphic encryption (modified Paillier), symmetric and asymmetric cryptography, and randomized encoding to preserve the confidentiality of true labels and model predictions. We integrate these methods into the Personal Health Train (PHT)-meDIC platform, a distributed machine learning environment designed for healthcare, to demonstrate their correctness and feasibility. Results using both real-world and synthetic datasets confirm the accuracy of our approach: the exact method computes the true AUC without revealing private inputs, and the approximation provides a balanced trade-off between computational efficiency and precision. All relevant code is publicly available athttps://github.com/PHT-meDIC/PP-AUC, facilitating straightforward adoption and further development within broader distributed learning ecosystems.Author summaryA commonly used metric to evaluate the performance of machine learning models is the Area Under the Curve (AUC). Calculating the AUC in distributed machine learning settings is challenging because data cannot be shared between institutions due to privacy concerns. To address this, we developed two privacy-preserving methods: one that calculates the exact AUC securely and another that provides faster approximations with high accuracy. These methods use advanced encryption techniques to protect sensitive data while enabling secure collaboration. We tested them in a real-world healthcare platform called PHT-meDIC and demonstrated their effectiveness. The code is publicly available athttps://github.com/PHT-meDIC/PP-AUCto support wider adoption.
Specialized response of default mode subnetworks and multiple-demand regions to transitions of person, place and time
Authors: Zhou Ashley X , Duncan John , Mitchell Daniel J 
Published: January 2025

AbstractThis study used functional MRI data from theStudyForrestdataset to investigate the role of subnetworks of the default mode network (DMN) during naturalistic stimulus transitions of different types and magnitudes. We found distinct activation profiles within the DMN: the dmPFC subnetwork was specifically associated with character and location transitions, the MTL subnetwork preferred location and temporal transitions, while the Core DMN subnetwork responded to all three transition types. The multiple-demand network instead responded selectively to temporal transitions. These distinct response profiles appeared largely invariant to the semantic distance implied by the transitions. All subnetworks also responded significantly, and in a graded manner, to subjective event boundaries. Results suggest specific roles of the DMN subnetworks in perceiving and segmenting naturalistic events, supporting the view that DMN subnetworks cooperate in interpreting continuous external events and maintaining an updated contextual model of the world.