bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging shapes infection profiles of influenza A virus and SARS-CoV-2 in human lung slices
Authors: Brügger Melanie , Machahua Carlos , Zumkehr Beatrice , Cismaru Christiana , Jandrasits Damian , Dorn Patrick , Marti Thomas M. , Zimmer Gert , Thiel Volker , Funke-Chambour Manuela , Alves Marco P. 
Published: April 2024

ABSTRACTThe recent coronavirus disease 2019 (COVID-19) outbreak revealed the susceptibility of elderly patients to respiratory virus infections, showing cell senescence or subclinical persistent inflammatory profiles and favouring the development of severe pneumonia. In our study, we evaluated the potential influence of lung aging on the efficiency of replication of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as determined the pro-inflammatory and antiviral responses of the distal lung tissue. Using precision-cut lung slices (PCLS) from donors of different ages, we found that pandemic H1N1 and avian H5N1 IAV replicated in the lung parenchyma with high efficacy. In contrast to these IAV strains, SARS-CoV-2 early isolate and Delta variant of concern (VOC) replicated less efficiently in PCLS. Interestingly, both viruses showed reduced replication in PCLS from older compared to younger donors, suggesting that aged lung tissue represents a sub-optimal environment for viral replication. Regardless of the age-dependent viral loads, PCLS responded to infection with both viruses by an induction of IL-6 and IP-10/CXCL10 mRNAs, being highest for H5N1. Finally, while SARS-CoV-2 infection was not causing detectable cell death, IAV infection caused significant cytotoxicity and induced significant early interferon responses. In summary, our findings suggest that aged lung tissue might not favour viral dissemination, pointing to a determinant role of dysregulated immune mechanisms in the development of severe disease.New & NoteworthyPCLS from donors of varying ages were exposed to SARS-CoV-2 or IAV. Notably, the latter exhibited the highest replication efficacy, triggering early interferon responses, elevated IL-6 and IP-10/CXCL10 mRNAs expression, and significant cell death compared to SARS-CoV-2. Overall, across all age groups, the pulmonary environment showed sustained immunocompetence. For both viruses, older donor-derived PCLS displayed reduced viral permissiveness, suggesting aged lung tissue might not favour viral dissemination, implying other factors contribute to severe disease development.
Assessment and phenotypic identification of millet germplasm (Setaria italica[L.]) in Liaoning, China
Authors: Xin-tong Li , Wei-Feng He , Hong-hao Wang , Min Xu 
Published: April 2024

AbstractAimsThis study evaluated millet germplasms in Liaoning Province to support the collection, preservation and innovation of millet germplasm resources.MethodsThe study was conducted from 2018 to 2020, involved the selection of 105 millet germplasm resources from the Germplasm Bank of the Liaoning Academy of Agricultural Sciences (LAAS), the observation and recording of 31 traits, and the application of multivariate analysis methods to assess phenotypic diversity.ResultsFrom the diversity analysis and correlation analysis, it was found that the tested traits had abundant diversity and complex correlations among them. principal component analysis (PCA) comprehensively analyzed all quantitative traits and extracted 7 principal components. Grey relational analysis (GRA) highlighted the varied contributions of different traits to yield. Through systematic cluster analysis, the resources were categorized into six groups at Euclidean distance of 17.09. K-mean cluster analysis determined the distribution interval and central value of each trait, then identified resources with desirable traits.ConclusionThe results revealed resources that possess characteristics such as upthrow seedling leaves, more tillers and branches, larger and well-formed ears, and lodging resistance prefer to higher grain yield. It was also discovered that the subear internode length (SIL) could be an indicator for maturity selection. Four specific resources, namely, Dungu No. 1, Xiao-li-xiang, Basen Shengu, and Yuhuanggu No. 1, were identified for further breeding and practical applications.
Behavioral Repertoire of lab-reared early juveniles of the Mexican four-eyed octopus:Octopus maya
Authors: González-Navarrete D.A. , Vergara-Ovalle F. , García-Andaluz P. , Ayala-Guerrero F. , Rosas C. , Vázquez-León P. , Paz-Trejo D.B. , Sánchez-Castillo H. 
Published: April 2024

ABSTRACTBehavioral studies have predominantly focused on organisms within the phyla Craniata and Arthropoda. Yet, there has been a growing interest in studying the behavior of organisms from alternative phyla, such as mollusks, owing to the research opportunities they offer. Among mollusks, cephalopods have emerged as a prominent subject of inquiry. However, behavioral research on Mexico’s endemic species,Octopus maya (Om), remains conspicuously scarce.Omexhibits favorable attributes for utilization as a standardized animal model in neuroscience research, primarily due to its adaptability to laboratory settings and the successful raising of multiple generations. A comprehensive understanding ofOm’s behavior within laboratory environments is essential to harness its potential as a research model. Thus, the main goal of this study was to establish a comprehensive behavioral catalog forOmunder laboratory conditions. ThirteenOmsubjects (6 to 20 grams) were housed in controlled tank environments. Our findings reveal thatOmexhibits a diverse behavioral repertoire, comprising a minimum of twenty-one distinct behaviors categorized into six behavioral classes. Additionally,Omdisplays discernable diurnal and nocturnal activity patterns, with increased activity levels, altered behavior distributions, and varying activity frequencies predominantly during daylight hours. This expanded knowledge ofOm’s behavior enhances its suitability as a research model organism.
Gastrula-premarked posterior enhancer primes posterior tissue development through cross-talk with TGF-β signaling pathway
Authors: Chen Yingying , Tan Fengxiang , Fang Qing , Zhang Lin , Liao Jiaoyang , Shen Penglei , Qian Yun , Wen Mingzhu , Song Rui , Fu Yonggao , Xu He Jax , Wang Ran , Li Cheng , Shao Zhen , Li Jinsong , Jing Naihe , Yang Xianfa 
Published: April 2024

AbstractThe regulatory mechanisms governing cell fate determination, particularly lineage diversification during mammalian embryonic development, remain poorly understood with in-depth regulatory paradigms yet to be fully elucidated. Here, leveraging the epigenetic landscape of mouse gastrula, we identified p-Enh, a pre-marked enhancer in primitive streak region, as pivotal regulator for posterior tissue development in mouse embryos. Morphological and single-cell transcriptomic analyses confirmed embryonic lethality phenotype with disrupted posterior tissue development trajectories in p-Enh-KO embryos. Molecularly, apart from regulating the neighboring coding-geneCdx2 in cis, our findings suggest that p-Enh also modulate the global transcriptome and epigenomic landscape, which might through the transient production of eRNAin trans. Further investigation revealed p-Enh participate in the regulatory cascades of TGF-β signaling. Chemical modulation of TGF-β signaling can largely rescue the posterior development deficiency inin vitrogastruloids through aCdx2-independent mechanism. Thus, we propose a potential model in which the broadly distributed p-Enh transcripts within the nucleus could serve as essential cross-modular coordinators, priming the posterior development of mouse embryo.
Enhancing system empathy within a UK Emergency Department: A feasibility interprofessional priority setting exercise
Authors: Howick Jeremy , Ward Andy , Grantham Charlotte , Bennett-Weston Amber 
Published: April 2024

ABSTRACTBackgroundSystem-level barriers inhibit empathy in healthcare, and this can harm patients and practitioners. The barriers include burnout-inducing administrative workloads, burdensome protocols, lack of wellbeing spaces, un-empathic leadership, and not emphasising empathy as an institutional value. A workshop aimed at enhancing empathic systems was successfully delivered in Canada but has not been tested in the UK National Health Service (NHS) setting.AimTo test the feasibility of an empathic systems workshop within the UK NHS setting.MethodsWe conducted an interprofessional group of an emergency department (ED). We used a modified nominal group technique to prioritise actions to enhance empathy in the ED system. Satisfaction with the workshop and confidence that the workshop would lead to change were measured on a 10-point Likert scale.ResultsTwenty-eight participants representing the following stakeholder groups attended the workshop: leaders, consultants, nurses, security, and porters. The group agreed to generating a better wellbeing action plan and implementing an effective secondary triage system. Seventy-three percent (73%) rated their satisfaction with the workshop as 8 or higher out of ten, and 63% reported being confident that the workshop would lead to positive change.LimitationsA doctors strike limited the range of stakeholders who were able to attend, and long-term follow up was not conducted.ConclusionsParticipants in a UK setting were satisfied with a previously developed system empathy workshop and reported being confident that it would lead to positive change. Participants were able to prioritise changes that would improve system empathy and were confident that the changes would be effective.
Inhospital Mortality, Readmission, and Prolonged Length of Stay Risk Prediction Leveraging Historical Electronic Health Records
Authors: Bopche Rajeev , Gustad Lise Tuset , Afset Jan Egil , Ehrnström Birgitta , Damås Jan Kristian , Nytrø Øystein 
Published: April 2024

AbstractObjectiveThe aim of this study was to investigate predictive capabilities of historical records of patients maintained at hospitals towards predicting an impending adverse outcomes such as, mortality, readmission, and prolonged length of stay (PLOS).MethodsLeveraging a de-identified dataset from a tertiary care university hospital, we developed a eXplainable Artificial Intelligence (XAI) framework combining tree-based and traditional ML models with interpretations, and statistical analysis of predictors of mortality, readmission, and PLOS.ResultsOur framework demonstrated exceptional predictive performance with notable Area Under the Receiver Operating Characteristic (AUROC) of 0.9625 and Area Under the Precision-Recall Curve (AUPRC) of 0.8575 for 30-day mortality at discharge and an AUROC of 0.9545 and AUPRC of 0.8419 at admission. For the readmission and PLOS risk the highest AUROC achieved were 0.8198 and 0.9797 repectively. The tree-based machine learning (ML) models consistently outperformed the traditional ML models in all the four prediction tasks. The key predictors were age, derived temporal features, routine laboratory tests, and diagnostic and procedural codes.ConclusionThe study underscores the potential of leveraging medical history for enhanced predictive analytics in hospitals. We present a accurate and intuitive framework for early warning models that can be easily implemented in the current and developing digital health platforms to accurately predict adverse outcomes.
Design of antigens to present a tumor-specific cryptic epitope
Authors: Xu Huafeng , Palpant Timothy , Wang Qi , Shaw David E. 
Published: April 2024

AbstractIn many cancers, the epidermal growth factor receptor (EGFR) gene is amplified, mutated, or both. The monoclonal antibody mAb806 binds selectively to cancer cells that overexpress EGFR or express the truncated mutant EGFRvIII, but not to normal cells. This suggests that a promising avenue for developing cancer vaccines may be to design antigens that elicit mAb806-like antibodies. In this study, we designed antigens that present the mAb806-binding epitope in the same conformation as in overexpressed or truncated EGFR. We first used molecular dynamics simulations to identify conformations of EGFR in which the residues of the mAb806-binding epitope are accessible. We then designed antigens by substituting that epitope in place of a structurally similar loop in a different protein and generating mutants that could potentially stabilize the mAb806-binding conformation in this new context. Two mutants in which the epitope remained stable in subsequent simulations were chosen for evaluation in vitro. Binding kinetics experiments with these designed antigens provided strong evidence that the epitope was successfully stabilized in the mAb806-binding conformation, suggesting that they could potentially form the basis of vaccines that elicit cancer-selective antibodies.
GōMartini 3: From large conformational changes in proteins to environmental bias corrections
Authors: Souza Paulo C. T. , Borges-Araújo Luís , Brasnett Chris , Moreira Rodrigo A. , Grünewald Fabian , Park Peter , Wang Liguo , Razmazma Hafez , Borges-Araújo Ana C. , Cofas-Vargas Luis Fernando , Monticelli Luca , Mera-Adasme Raúl , Melo Manuel N. , Wu Sangwook , Marrink Siewert J. , Poma Adolfo B. , Thallmair Sebastian 
Published: April 2024

ABSTRACTCoarse-grained modeling has become an important tool to supplement experimental measurements, allowing access to spatio-temporal scales beyond all-atom based approaches. The GōMartini model combines structure- and physics-based coarse-grained approaches, balancing computational efficiency and accurate representation of protein dynamics with the capabilities of studying proteins in different biological environments. This paper introduces an enhanced GōMartini model, which combines a virtual-site implementation of Gō models with Martini 3. The implementation has been extensively tested by the community since the release of the new version of Martini. This work demonstrates the capabilities of the model in diverse case studies, ranging from protein-membrane binding to protein-ligand interactions and AFM force profile calculations. The model is also versatile, as it can address recent inaccuracies reported in the Martini protein model. Lastly, the paper discusses the advantages, limitations, and future perspectives of the Martini 3 protein model and its combination with Gō models.
Relaxin Modulates the Genomic Actions and Biological Effects of Estrogen in the Myometrium
Authors: Tripathy Sudeshna , Nagari Anusha , Chiu Shu-Ping , Nandu Tulip , Camacho Cristel V. , Mahendroo Mala , Lee Kraus W. 
Published: April 2024

AbstractEstradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ERα). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explored the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild-type or mutant ERα (hTERT-HM-ERα cells). Our results indicate that Rln modulates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation of ERα on serine 118 (S118), as well as by reducing the E2-dependent binding of ERα across the genome. These effects were associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of some genes and enhanced expression of others. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ERα required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ERα signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes.
Comparative accuracy of five screening tools for sarcopenia in community older adults:a systematic review and a network meta-analysis
Authors: Li Jie , Yang Yujie , Gao Menglin , Yuan Huaihong 
Published: April 2024

AbstractBackgroundSarcopenia, a prevalent and serious condition among community older adults, often remains unnoticed. The use of systematic screening has the potential to enhance detection rates; however, there is currently no consensus on the most effective approach. This study ai med to assess the diagnostic test accuracy of five simple sarcopenia screening tools and determine which test has the highest accuracy.ObjectiveTo assess and compare the accuracy of five screening tools for sarcopenia in community older adults.DesignA systematic review and a network meta analysis.MethodsA systematic search was conducted in various databases including Pubmed, The Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and Sinomed up to September 2023. Studies reporting on the accuracy of diagnostic testing for sarcopenia in community-dwelling older adults using one or more of the following sarcopenia screening tools were included: Sarcopenia Simple Five-Item Rati ng Scale (SARC-F), SARC-F combined with calf circumference (SA RC-CalF), SARC-F combined with older adults and BMI (SARC-F+ EBM), Mini sarcopenia risk assessment-5 (MSRA-5), and Mini sarcopenia risk assessment-7 (MSRA-7). The reference standard was the Asian Working Group on Sarcopenia (AWGS), the European Working Group on Sarcopenia on Older People (EWGSOP), the Foundation for National Institutes of Health (FNIH), or the International Working Group on Sarcopenia (IWGS). Random-effects bivariate binomial model meta-analyses, meta-regressions and a network meta-analysis were used to estimate the pooled and relative sensitivities and specificities.ResultsWe identified and evaluated 22 papers focused on SARC-F, S ARC-CalF, MSRA-5, and MSRA-7. Traditional meta-analysis sorting results showed summary sensitivities of 0.25, 0.59, 0.43, 0.82, and 0.51, summary specificities of 0.94, 0.82, 0.81, 0.39, and 0.85, summary AUC of 0.80, 0.76, 0.70, 0.68, and 0.75, and summary DOR of 5, 7, 3, 3, and 6. The network meta-analysis ranking results showed that MRSA-5 had the highest sensitivity (92.27) and SARC-F had the highest specificity (99.81) under the cumulative ranking.Linking evidence to actionThe MSRA can be used as a tool for screening sarcopenia in community older adults, while the SARC-F can be used for first-time diagnosis of sarcopenia in this population. However, it is important to interpret the results with caution due to the variability among different studies analyzing the accuracy of this diagnostic test. Future research should focus on obtaining additional evidence from large sample sizes and high-quality studies.
Highly Pathogenic Avian Influenza A (H5N1) clade 2.3.4.4b Virus detected in dairy cattle
Authors: Hu Xiao , Saxena Anugrah , Magstadt Drew R. , Gauger Phillip C. , Burrough Eric , Zhang Jianqiang , Siepker Chris , Mainenti Marta , Gorden Patrick J. , Plummer Paul , Li Ganwu 
Published: April 2024

AbstractThe global emergence of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses poses a significant global public health threat. Until March 2024, no outbreaks of this virus clade had occurred in domestic cattle. We genetically characterize HPAI viruses from dairy cattle showing an abrupt drop in milk production. They share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. B3.13 viruses underwent two reassortment events since 2023 and exhibit critical mutations in HA, M1, and NS genes but lack critical mutations in PB2 and PB1 genes, which enhance virulence or adaptation to mammals. The PB2 E627K mutation in a human case underscores the potential for rapid evolution post-infection, highlighting the need for continued surveillance to monitor public health threats.
The Natural Material Evolution and Stage-wise Assembly of Silk Along the Silk Gland
Authors: Brookstein Ori , Shimoni Eyal , Eliaz Dror , Dezorella Nili , Biran Idan , Rechav Katya , Sivan Ehud , Kozell Anna , Shimanovich Ulyana 
Published: April 2024

AbstractSilk fibers, with their highly ordered structure and mechanically superb properties, are produced in arthropod glands at minimal energy input and ambient conditions, a remarkable feat yet to be achieved synthetically. Due to the high instability and shear sensitivity of the silk protein feedstock, understanding silk fiber formation has been largely limited toin-vitrostudies of certain gland sections, offering only a fragmented view of this process. Here, we monitor the whole silk feedstock processingin-situ, at the nano- to micron-scales, through imaging its progressive macromolecular assemblies and phase transitions along the entireBombyx morisilkworm silk gland. This is done by combining state-of-the-art microscopy techniques, such as cryogenic sample preparation, fixation, and imaging. Our work reveals that fibroin assembles into micron-sized spherical storage “compartments” in the posterior and middle gland sections, a state that ensures its stability and avoids premature fibrillation. These compartments undergo several structural transformations along the gland and eventually disassemble at the entry to the anterior section, before the silk feedstock spinning begins. The spinning itself commences via a series of structural transitions, from the alignment of protein chains in liquid feedstock, through the formation of several fibrillated nano-structures and, in the final stage, a network of cross-linked nano-bundles, which determines the structure and properties of the final microfiber. Importantly, the length of the anterior section of the silk gland enables such gradual and balanced structural transitions. This direct imaging of silk’s natural formation process can help formulate a template for the transformation of fibrillar proteins into synthetic bio-fibers.DedicationThis work is dedicated to the memory of Dr. Eyal Shimoni, who was a valued colleague and a dear friend. Eyal was a vital part of this research and was essential in shaping its direction. He will be deeply missed for his intellect, mindfulness, creativity, and unwavering dedication to scientific development. Though he is no longer with us, his influence and spirit continue to inspire us in our scientific pursuits. May his passion for discovery and commitment to excellence live on through this work.