bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA EPLET Frequencies Are Similar in Six Population Groups and Are Expressed by the Most Common HLA Alleles
Authors: Mangiola Massimo , Ellison Mitchell , Marrari Marilyn , Xu Qingyong , Mankowski Michal , Sese Doreen , Lonze Bonnie E. , Montgomery Robert A. , Zeevi Adriana 
Published: December 2024

ABSTRACTThe degree of immunological compatibility between donors and recipients greatly impacts allograft survival. In the United States kidney allocation system, HLA antigen‐level matching has been shown to cause ethnic disparities and thus, has been de‐emphasised. However, priority points are still awarded for antigen‐level zero‐ABDR matching, zero‐DR matching and one‐DR matching. Recently, the degree of HLA molecular (eplet) mismatch has emerged as a more accurate measure of immunological risk, and eplet mismatch load has gained attention as a possible biomarker to improve HLA compatibility. However, little is known about the frequency of eplets in population groups, which is a necessary step to ensure that candidates from any ethnical background can have similar chances at a well‐matched organ. Eplet frequencies were estimated using HLA alleles in the Common, Intermediate and Well‐Documented (CIWD) 3.0.0 catalogue for six population groups: African‐American (AFA), Asian‐Pacific Islander (API), European/European descent (EURO), Middle East/North Coast of Africa (MENA), Hispanic/Latino (HIS) and Native‐American (NAM). We determined that 98.6% (484 out of 491) of HLA eplets are expressed by the common HLA alleles in all population groups. Of the seven eplets that were expressed by less common HLA alleles, six were Class I eplets and one was expressed by HLA‐DQB1 alleles and most were expressed by HLA alleles that were more commonly observed in European/European descent populations. Our observations indicate that HLA eplets will not cause any significant disparity if applied to HLA molecular compatibility, regardless of the ethnic origin of both recipients and donors.
Student Medical Education Masterclasses: Diversifying the Academic Pipeline
Authors: Collin Victoria , Brown Megan , Alsafi Zaid , Sylvan Nicholas , Parekh Ravi , Kumar Sonia 
Published: December 2024

ABSTRACTBackgroundThere remains a lack of diversity among those pursuing clinical academic careers. Structural inequalities, discrimination and a paucity of relatable role models can disadvantage minoritised students, hindering their educational experiences and career opportunities. Innovative and effective approaches are needed at an undergraduate level to address this problem, ensuring the pipeline is representative, diverse and inclusive.ApproachTo help address this challenge, in 2021, we developed a free online ‘medical education masterclass series’ for 250 UK medical students, with students from minoritised backgrounds particularly encouraged to apply. The masterclasses explored topical themes in medical education through seminars and workshops featuring diverse guest speakers.EvaluationTo evaluate the programme, students were invited to submit an anonymised reflection and complete a semi‐structured interview exploring how their perceptions of medical education may have changed following attendance of the masterclasses. A total of 18% responded, and data were thematically analysed.ResultsStudents reflected on how the sessions broadened their understanding of medical education beyond their own curriculum experiences. Students described acquiring skills and building networks to further develop their interest in medical education. The desire to make medical education more inclusive was identified as a key priority for students, and students felt empowered to advocate for positive change within their own institutions.ImplicationsProviding students with opportunities to explore medical education through such masterclasses has the potential to raise awareness and address some of the barriers experienced by minoritised students. We would advocate for similar initiatives to be developed in other clinical academic areas to increase diversity.
An LLM‐Based Method for Quality Information Extraction From Web Text for Crowed‐Sensing Spatiotemporal Data
Authors: Huang Zongcai , Peng Peng , Lu Feng , Zhang He 
Published: December 2024

ABSTRACTKnowledge‐driven GIS increasingly requires multi‐source, multi‐type, and multi‐model crowd‐sensing spatiotemporal data, whose data quality is difficult to guarantee and determine. Hence, extracting quality indicator information, widely present in various unstructured web texts, is crucial to providing supplementary quality information for crowd‐sensing spatiotemporal data. Recent advances in large language models show potential in extracting quality indicator information. However, it is still hard to get accurate results from large language models that use different quality indicators for crowd‐sensing spatiotemporal data. Therefore, we have designed a large language model that is fine‐tuned for the extraction of spatiotemporal quality information from quality description text (LLMFT‐STQIE). Firstly, we establish a quality indicator vocabulary to determine whether the text includes quality indicator information from the spatiotemporal data. Then, we create a two‐stage prompt model with QILE and QIVE prompts that include input text, task type, instructions, the quality indicator vocabulary, output format, and a reference case. This model is based on the fine‐tuning technology of large language models. The results show that our LLMFT‐STQIE achieves an accuracy of 91% and a recall rate of 80%, respectively, representing improvements of 23% and 38% compared to untuned large language models. These results further show that the suggested method easily and accurately extracts quality indicator information from web texts for crowd‐sensing spatiotemporal data. The study helps investigate strategies for optimizing huge language models for specific scenarios or task specifications.
Precision in Parsing: Evaluation of an Open‐Source Named Entity Recognizer (NER) in Veterinary Oncology
Authors: Pinard Christopher J. , Poon Andrew C. , Lagree Andrew , Wu Kuan‐Chuen , Li Jiaxu , Tran William T. 
Published: December 2024

ABSTRACTIntegrating Artificial Intelligence (AI) through Natural Language Processing (NLP) can improve veterinary medical oncology clinical record analytics. Named Entity Recognition (NER), a critical component of NLP, can facilitate efficient data extraction and automated labelling for research and clinical decision‐making. This study assesses the efficacy of the Bio‐Epidemiology‐NER (BioEN), an open‐source NER developed using human epidemiological and medical data, on veterinary medical oncology records. The NER's performance was compared with manual annotations by a veterinary medical oncologist and a veterinary intern. Evaluation metrics included Jaccard similarity, intra‐rater reliability, ROUGE scores, and standard NER performance metrics (precision, recall, F1‐score). Results indicate poor direct translatability to veterinary medical oncology record text and room for improvement in the NER's performance, with precision, recall, and F1‐score suggesting a marginally better alignment with the oncologist than the intern. While challenges remain, these insights contribute to the ongoing development of AI tools tailored for veterinary healthcare and highlight the need for veterinary‐specific models.
Root of unity quantum cluster algebras and discriminants
Authors: Nguyen Bach , Trampel Kurt , Yakimov Milen 
Published: December 2024

AbstractWe describe a connection between the subjects of cluster algebras, polynomial identity algebras, and discriminants. For this, we define the notion of root of unity quantum cluster algebras and prove that they are polynomial identity algebras. Inside each such algebra we construct a (large) canonical central subalgebra, which can be viewed as a far reaching generalization of the central subalgebras of big quantum groups constructed by De Concini, Kac, and Procesi and used in representation theory. Each such central subalgebra is proved to be isomorphic to the underlying classical cluster algebra of geometric type. When the root of unity quantum cluster algebra is free over its central subalgebra, we prove that the discriminant of the pair is a product of powers of the frozen variables times an integer. An extension of this result is also proved for the discriminants of all subalgebras generated by the cluster variables of nerves in the exchange graph. These results can be used for the effective computation of discriminants. As an application we obtain an explicit formula for the discriminant of the integral form over of each quantum unipotent cell of De Concini, Kac, and Procesi for arbitrary symmetrizable Kac–Moody algebras, where is a root of unity.
High Effectiveness Tip Cooling Using Inclined Slots
Authors: Mutekwa Macdonald , Vieira Joao , Farfaras Maximilian G. , Coull John D. , Bacic Marko , Ireland Peter T. 
Published: December 2024

Abstract
The tip of the high-pressure turbine blade is critical for gas turbine performance. Hot gas leaking through the tip gap tends to oxidize and erode the blade while generating significant aerodynamic loss. Squealer tips are often used to maximize efficiency, but the thin rims are thermally vulnerable and difficult to cool. The resultant degradation often limits engine life, turbine entry temperatures, and thermal efficiency. This work considers means to improve the cooling of squealer tips to minimize degradation. Compared to conventional, cylindrical-hole designs, a step-change improvement in cooling effectiveness can be achieved using near-tip slots. In this configuration, coolant is ejected in an approximately streamwise direction along the pressure side rim, cooling a large area with high effectiveness. Experiments characterizing cooling and aerodynamics are performed in a representative linear cascade on an inclined slot design developed to enhance manufacturability while retaining high cooling effectiveness. This design is shown to more than double the cooling effectiveness on the pressure side rim compared to a conventional discrete-hole baseline. Improved coolant shielding is retained for varying mass flowrates, tip clearances, and density ratios. Aerodynamic measurements show that the slot design can outperform the baseline provided the coolant mass fraction between the slots is suitably optimized.
Engineering a live-attenuated porcine reproductive and respiratory syndrome virus vaccine to prevent RNA recombination by rewiring transcriptional regulatory sequences
Authors: Li Liwei , Chen Jinxia , Cao Zhengda , Guo Ziqiang , Liu Jiachen , Zhou Yanjun , Tong Guangzhi , Gao Fei 
Published: December 2024

ABSTRACT

Recombination is a significant factor driving the evolution of RNA viruses. The prevalence and variation of porcine reproductive and respiratory syndrome virus (PRRSV) in China have been increasing in complexity due to extensive interlineage recombination. When this recombination phenomenon occurs in live vaccine strains, it becomes increasingly difficult to prevent and control PRRSV. Reverse genetic manipulation to engineer a different transcriptional regulatory sequence (TRS) circuit introduces genetic traps into the viral genome that are lethal to recombinant RNA progeny viruses. In this study, major interlineage recombination patterns were identified between lineage 1 (L1) PRRSVs and lineage 8 (L8) PRRSVs in China, from 2019 to 2023. The recombinant mutant virus, vA-TRSall, was constructed and successfully rescued by rewiring the entire TRS circuit without changing the amino acid-coding sequence in the genome of the PRRSV live vaccine strain vHuN4-F112. The vA-TRSall, with a brand new TRS circuit, provided effective immune protection against the highly pathogenic L8 PRRSV (vHuN4) and epidemic NADC30-like L1 PRRSV (vZJqz21). Recombination analysis
in vitro
and
in vivo
showed that, compared with the vHuN4-F112 and vZJqz21 co-infection groups, the incidence rates of mutation breakpoints and template-switching recombination in the vA-TRSall and vZJqz21 co-infected groups were effectively reduced. The results have enriched our understanding of the critical role of TRS circuits in PRRSV recombination mechanisms and indicate a successful redesign that can endow PRRSV live vaccines with recombination-resistant capabilities.

IMPORTANCE
Porcine reproductive and respiratory syndrome viruses (PRRSVs) are genetically diverse, and this is due in part to their extensive recombination. Live vaccines are widely used to prevent and control PRRS in China. However, owing to the wide variety of live vaccines, non-standard use, and the wild viruses prevalent on pig farms, new strains, generated via RNA recombination, are continuously emerging. Vaccine strains are also involved in PRRSV recombination, which leads to the emergence of new variants and alterations in virulence and pathogenesis. A recombination-resistant genome was engineered by rewiring the entire transcriptional regulatory sequence (TRS) circuit of the live PRRSV vaccine strain. Theoretically, after clinical application, once the virus recombines with the genome of the epidemic strain, the base pairing between the two sets of TRS circuits should be disrupted, resulting in a fatal genetic trap for the generation of an RNA recombinant progeny virus. Therefore, the remodeled PRRSV TRS mutant generated in this study can serve as a recombination-resistant platform for the rational design of safe PRRS vaccines in the future.
Autophagy protein Atg7 is essential for maintaining malaria parasite cellular homeostasis and organelle biogenesis
Authors: Mishra Akancha , Rajput Suryansh , Srivastava Pratik Narain , Shabeer Ali H. , Mishra Satish 
Published: December 2024

ABSTRACT

Plasmodium
parasites have a complex life cycle that transitions between mosquito and mammalian hosts, and undergo continuous cellular remodeling to adapt to various drastic environments. Following hepatocyte invasion, the parasite discards superfluous organelles for intracellular replication, and the remnant organelles undergo extensive branching and mature into hepatic merozoites. Autophagy is a ubiquitous eukaryotic process that permits the recycling of intracellular components. Here, we show that the
Plasmodium berghei
autophagy-related E1-like enzyme Atg7 is expressed in the blood, sporozoites, and liver stages, localized to the parasite cytosol, and is essential for the localization of Atg8 on the membrane and the development of parasite blood and liver forms. We found that depleting Atg7 abolishes Atg8 lipidation, exocytosis of micronemes, organelle biogenesis, and the formation of merozoites during liver-stage development. Overall, this study establishes the essential functions of Atg7 in
Plasmodium
blood and liver stages, and highlights its role in maintaining the parasite’s cellular homeostasis and organelle biogenesis.

IMPORTANCE

The malaria life cycle involves two hosts, mosquitoes and vertebrates.
Plasmodium
parasites undergo complex intracellular and extracellular stages during this transition. Here, we report that an autophagy-related E1-like enzyme Atg7 is required to conjugate Atg8 on the apicoplast membrane. Atg7 depletion in
Plasmodium berghei
resulted in the loss of Atg8 lipidation and multiple defects like clearance of micronemes, organelle biogenesis, and maturation of hepatic schizonts during liver-stage development. The essentiality of
Plasmodium
Atg7 in blood and liver stages suggests it is a prospective target for developing autophagy-specific inhibitors. These results highlight the importance of autophagy in malaria parasite development.
Phage-mediated virulence loss and antimicrobial susceptibility in carbapenem-resistant
Klebsiella pneumoniae
Authors: Yu Yanshuang , Wang Mengzhu , Ju Liuying , Li Minchun , Zhao Mengshi , Deng Hui , Rensing Christopher , Yang Qiu E. , Zhou Shungui 
Published: December 2024

ABSTRACT

Bacteriophages, known for their ability to kill bacteria, are hampered in their effectiveness because bacteria are able to rapidly develop resistance, thereby posing a significant challenge for the efficacy of phage therapy. The impact of evolutionary trajectories on the long-term success of phage therapy remains largely unclear. Herein, we conducted evolutionary experiments, genomic analysis, and CRISPR-mediated gene editing, to illustrate the evolutionary trajectory occurring between phages and their hosts. Our results illustrate the ongoing “arms race” between a lytic phage and its host, a carbapenem-resistant
Klebsiella pneumoniae
clinical strain Kp2092, suggesting their respective evolutionary adaptations that shape the efficacy of phage therapy. Specifically, Kp2092 rapidly developed resistance to phages through mutations in a key phage receptor (
galU
) and bacterial membrane defenses such as LPS synthesis, however, this evolution coincides with unexpected benefits. Evolved bacterial clones not only exhibited increased sensitivity to clinically important antibiotics but also displayed a loss of virulence in an
in-vivo
model. In contrast, phages evolved under the selection pressure against Kp2092 mutants and exhibited enhanced bacterial killing potency, targeting mutations in phage tail proteins gp12 and gp17. These parallel evolutionary trajectories suggest a common genetic mechanism driving adaptation, ultimately favoring the efficacy of phage therapy. Overall, our findings highlight the potential of phages not only as agents for combating bacterial resistance, but also a driver of evolution outcomes that could lead to more favorable clinical outcomes in the treatment of multidrug resistance pathogens.

IMPORTANCE

Carbapenem-resistant
Klebsiella pneumoniae
represents one of the leading pathogens for infectious diseases. With traditional antibiotics often being ineffective, phage therapy has emerged as a promising alternative. However, phage predation imposes a strong evolutionary pressure on the rapid evolution of bacteria, challenging treatment efficacy. Our findings illustrate how co-evolution enhances phage lytic capabilities through accumulated mutations in the tail proteins gp12 and gp17, while simultaneously reducing bacterial virulence and antibiotic resistance. These insights advance our understanding of phage-host interactions in clinical settings, potentially inspiring new approaches akin to an “arms race” model to combat multidrug-resistant crises effectively.
The protein structurome of Orthornavirae and its dark matter
Authors: Mutz Pascal , Camargo Antonio Pedro , Sahakyan Harutyun , Neri Uri , Butkovic Anamarija , Wolf Yuri I. , Krupovic Mart , Dolja Valerian V. , Koonin Eugene V. 
Published: December 2024

ABSTRACT

Metatranscriptomics is uncovering more and more diverse families of viruses with RNA genomes comprising the viral kingdom Orthornavirae in the realm Riboviria. Thorough protein annotation and comparison are essential to get insights into the functions of viral proteins and virus evolution. In addition to sequence- and hmm profile‑based methods, protein structure comparison adds a powerful tool to uncover protein functions and relationships. We constructed an Orthornavirae “structurome” consisting of already annotated as well as unannotated (“dark matter”) proteins and domains encoded in viral genomes. We used protein structure modeling and similarity searches to illuminate the remaining dark matter in hundreds of thousands of orthornavirus genomes. The vast majority of the dark matter domains showed either “generic” folds, such as single α-helices, or no high confidence structure predictions. Nevertheless, a variety of lineage-specific globular domains that were new either to orthornaviruses in general or to particular virus families were identified within the proteomic dark matter of orthornaviruses, including several predicted nucleic acid-binding domains and nucleases. In addition, we identified a case of exaptation of a cellular nucleoside monophosphate kinase as an RNA-binding protein in several virus families. Notwithstanding the continuing discovery of numerous orthornaviruses, it appears that all the protein domains conserved in large groups of viruses have already been identified. The rest of the viral proteome seems to be dominated by poorly structured domains including intrinsically disordered ones that likely mediate specific virus-host interactions.

IMPORTANCE
Advanced methods for protein structure prediction, such as AlphaFold2, greatly expand our capability to identify protein domains and infer their likely functions and evolutionary relationships. This is particularly pertinent for proteins encoded by viruses that are known to evolve rapidly and as a result often cannot be adequately characterized by analysis of the protein sequences. We performed an exhaustive structure prediction and comparative analysis for uncharacterized proteins and domains (“dark matter”) encoded by viruses with RNA genomes. The results show the dark matter of RNA virus proteome consists mostly of disordered and all-α-helical domains that cannot be readily assigned a specific function and that likely mediate various interactions between viral proteins and between viral and host proteins. The great majority of globular proteins and domains of RNA viruses are already known although we identified several unexpected domains represented in individual viral families.
Targets of influenza human T-cell response are mostly conserved in H5N1
Authors: Sidney John , Kim A-Reum , de Vries Rory D. , Peters Bjoern , Meade Philip S. , Krammer Florian , Grifoni Alba , Sette Alessandro 
Published: December 2024

ABSTRACT

Frequent recent spillovers of subtype H5N1 clade 2.3.4.4b highly pathogenic avian influenza (HPAI) virus into poultry and mammals, especially dairy cattle, including several human cases, increased concerns over a possible future pandemic. Here, we performed an analysis of epitope data curated in the Immune Epitope Database (IEDB). We found that the patterns of immunodominance of seasonal influenza viruses circulating in humans and H5N1 are similar. We further conclude that a significant fraction of the T-cell epitopes is conserved at a level associated with cross-reactivity between avian and seasonal sequences, and we further experimentally demonstrate extensive cross-reactivity in the most dominant T-cell epitopes curated in the IEDB. Based on these observations, and the overall similarity of the neuraminidase (NA) N1 subtype encoded in both HPAI and seasonal H1N1 influenza virus as well as cross-reactive group 1 HA stalk-reactive antibodies, we expect that a degree of pre-existing immunity is present in the general human population that could blunt the severity of human H5N1 infections.

IMPORTANCE
Influenza A viruses (IAVs) cause pandemics that can result in millions of deaths. The highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype is presently among the top viruses of pandemic concern, according to the WHO and the National Institute of Allergy and Infectious Diseases (NIAID). Previous exposure by infection and/or vaccination to a given IAV subtype or clade influences immune responses to a different subtype or clade. Analysis of human CD4 and CD8 T-cell epitope conservation between HPAI H5N1 and seasonal IAV sequences revealed levels of identity and conservation conducive to T cell cross-reactivity, suggesting that pre-existing T cell immune memory should, to a large extent, cross-recognize avian influenza viruses. This observation was experimentally verified by testing responses from human T cells to non-avian IAV and their HPAI H5N1 counterparts. Accordingly, should a more widespread HPAI H5N1 outbreak occur, we hypothesize that cross-reactive T-cell responses might be able to limit disease severity.