bluuebunny/crossref_metadata_2025_split huggingface dataset:
BioInstruct: instruction tuning of large language models for biomedical natural language processing
Authors: Tran Hieu , Yang Zhichao , Yao Zonghai , Yu Hong 
Published: June 2024

Abstract

Objectives
To enhance the performance of large language models (LLMs) in biomedical natural language processing (BioNLP) by introducing a domain-specific instruction dataset and examining its impact when combined with multi-task learning principles.

Materials and Methods
We created the BioInstruct, comprising 25 005 instructions to instruction-tune LLMs (LLaMA 1 and 2, 7B and 13B version). The instructions were created by prompting the GPT-4 language model with 3-seed samples randomly drawn from an 80 human curated instructions. We employed Low-Rank Adaptation (LoRA) for parameter-efficient fine-tuning. We then evaluated these instruction-tuned LLMs on several BioNLP tasks, which can be grouped into 3 major categories: question answering (QA), information extraction (IE), and text generation (GEN). We also examined whether categories (eg, QA, IE, and generation) of instructions impact model performance.

Results and Discussion
Comparing with LLMs without instruction-tuned, our instruction-tuned LLMs demonstrated marked performance gains: 17.3% in QA on average accuracy metric, 5.7% in IE on average F1 metric, and 96% in Generation tasks on average GPT-4 score metric. Our 7B-parameter instruction-tuned LLaMA 1 model was competitive or even surpassed other LLMs in the biomedical domain that were also fine-tuned from LLaMA 1 with vast domain-specific data or a variety of tasks. Our results also show that the performance gain is significantly higher when instruction fine-tuning is conducted with closely related tasks. Our findings align with the observations of multi-task learning, suggesting the synergies between 2 tasks.

Conclusion
The BioInstruct dataset serves as a valuable resource and instruction tuned LLMs lead to the best performing BioNLP applications.
Polychrome Bone Fluorescence: A Valuable Diagnostic Tool for Fourth-Degree Calvarial Burns. A Case Report
Authors: Malan Annemarie Martha , Öhlbauer Markus , Bader Rolf-Dieter , Wallner Britta 
Published: June 2024

Abstract
Fourth-degree calvarial burns are complex in management with regard to determining bone vitality and subsequent choice of defect coverage. Distinguishing viable and nonviable bone can be challenging. Tetracycline bone fluorescence is well described and in common use in maxillofacial patients with bisphosphonate osteonecrosis and has been reported in septic orthopedic surgery specifically periprosthetic joint infection. On the basis of viable bone fluoresces, the concept of polychrome fluorescence was extrapolated as a diagnostic tool for calvarial burns. Bone fluorescence presents an efficient, non-invasive, and cost-effective diagnostic tool delineating exact necrotic margins in fourth-degree burns ensuring targeted bone-sparing debridement. This report describes the use of polychrome bone fluorescence as an intraoperative tool including a single-center case report with fourth-degree calvarial burns.
The role of GDF5 in regulating enthesopathy development in the Hyp mouse model of XLH
Authors: Sorsby Melissa , Almardini Shaza , Alayyat Ahmad , Hughes Ashleigh , Venkat Shreya , Rahman Mansoor , Baker Jiana , Rana Rakshya , Rosen Vicki , Liu Eva S 
Published: June 2024

Abstract
X-linked hypophosphatemia (XLH) is caused by mutations in PHEX, leading to rickets and osteomalacia. Adults affected with XLH develop a mineralization of the bone-tendon attachment site (enthesis), called enthesopathy, which causes significant pain and impaired movement. Entheses in mice with XLH (Hyp) have enhanced bone morphogenetic protein (BMP) and Indian hedgehog (IHH) signaling. Treatment of Hyp mice with the BMP signaling blocker palovarotene attenuated BMP/IHH signaling in Hyp entheses, thus indicating that BMP signaling plays a pathogenic role in enthesopathy development and that IHH signaling is activated by BMP signaling in entheses. It was previously shown that mRNA expression of growth/differentiation factor 5 (Gdf5) is enhanced in Hyp entheses at P14. Thus, to determine a role for GDF5 in enthesopathy development, Gdf5 was deleted globally in Hyp mice and conditionally in Scx + cells of Hyp mice. In both murine models, BMP/IHH signaling was similarly decreased in Hyp entheses, leading to decreased enthesopathy. BMP/IHH signaling remained unaffected in WT entheses with decreased Gdf5 expression. Moreover, deletion of Gdf5 in Hyp entheses starting at P30, after enthesopathy has developed, partially reversed enthesopathy. Taken together, these results demonstrate that while GDF5 is not essential for modulating BMP/IHH signaling in WT entheses, inappropriate GDF5 activity in Scx + cells contributes to XLH enthesopathy development. As such, inhibition of GDF5 signaling may be beneficial for the treatment of XLH enthesopathy.
The role of conflict in the formation and maintenance of variant sex chromosome systems in mammals
Authors: Hughes Jonathan J , Lagunas-Robles German , Campbell Polly 
Published: June 2024

Abstract
The XX/XY sex chromosome system is deeply conserved in therian mammals, as is the role of Sry in testis determination, giving the impression of stasis relative to other taxa. However, the long tradition of cytogenetic studies in mammals documents sex chromosome karyotypes that break this norm in myriad ways, ranging from fusions between sex chromosomes and autosomes to Y chromosome loss. Evolutionary conflict, in the form of sexual antagonism or meiotic drive, is the primary predicted driver of sex chromosome transformation and turnover. Yet conflict-based hypotheses are less considered in mammals, perhaps because of the perceived stability of the sex chromosome system. To address this gap, we catalog and characterize all described sex chromosome variants in mammals, test for family-specific rates of accumulation, and consider the role of conflict between the sexes or within the genome in the evolution of these systems. We identify 152 species with sex chromosomes that differ from the ancestral state and find evidence for different rates of ancestral to derived transitions among families. Sex chromosome-autosome fusions account for 79% of all variants whereas documented sex chromosome fissions are limited to three species. We propose that meiotic drive and drive suppression provide viable explanations for the evolution of many of these variant systems, particularly those involving autosomal fusions. We highlight taxa particularly worthy of further study and provide experimental predictions for testing the role of conflict and its alternatives in generating observed sex chromosome diversity.
Sorry you asked? Mayo, Myriad, and the battles over patent-eligibility
Authors: Cook-Deegan Robert , Geary Janis , Hapke Kara , Skvarkova Zuzana , Filipek Marina , Leaver Jillian 
Published: June 2024

Abstract
Genetic testing for inherited cancer risk changed dramatically when the US Supreme Court handed down unanimous rulings in Mayo v. Prometheus (2012) and Myriad v. Association for Molecular Pathology (2013). Those decisions struck down claims to methods based on ‘laws of nature’ (Mayo) and DNA molecules corresponding to sequences found in nature (Myriad). Senators Thom Tillis (R-NC) and Christopher Coons (D-DE) introduced legislation that would abrogate those decisions and specify narrow statutory exclusions to patent-eligibility in §101 of the US Patent Act. What would be the consequences of doing so? The Supreme Court decisions coincided with changes in how genetic tests were performed, reimbursed and regulated. Multi-gene sequencing supplanted oligo-gene testing as the cost of sequencing dropped 10,000-fold. Payers dramatically changed reimbursement practices. Food and Drug Administration regulation was proposed and remains in prospect. Databases for clinical interpretation made data freely available, augmenting a knowledge commons. The spectacular implosion of Theranos tempered investment in molecular diagnostics. These factors all complicate explanations of why venture capital funding for molecular diagnostics dropped relative to other sectors. Restoring patent-eligibility would put renewed pressure on other patent doctrines, such as obviousness, enablement and written description, that were not raised in the Supreme Court cases.
Please Mind the Gap: Indel-Aware Parsimony for Fast and Accurate Ancestral Sequence Reconstruction and Multiple Sequence Alignment Including Long Indels
Authors: Iglhaut Clara , Pečerska Jūlija , Gil Manuel , Anisimova Maria 
Published: June 2024

Abstract
Despite having important biological implications, insertion, and deletion (indel) events are often disregarded or mishandled during phylogenetic inference. In multiple sequence alignment, indels are represented as gaps and are estimated without considering the distinct evolutionary history of insertions and deletions. Consequently, indels are usually excluded from subsequent inference steps, such as ancestral sequence reconstruction and phylogenetic tree search. Here, we introduce indel-aware parsimony (indelMaP), a novel way to treat gaps under the parsimony criterion by considering insertions and deletions as separate evolutionary events and accounting for long indels. By identifying the precise location of an evolutionary event on the tree, we can separate overlapping indel events and use affine gap penalties for long indel modeling. Our indel-aware approach harnesses the phylogenetic signal from indels, including them into all inference stages. Validation and comparison to state-of-the-art inference tools on simulated data show that indelMaP is most suitable for densely sampled datasets with closely to moderately related sequences, where it can reach alignment quality comparable to probabilistic methods and accurately infer ancestral sequences, including indel patterns. Due to its remarkable speed, our method is well suited for epidemiological datasets, eliminating the need for downsampling and enabling the exploitation of the additional information provided by dense taxonomic sampling. Moreover, indelMaP offers new insights into the indel patterns of biologically significant sequences and advances our understanding of genetic variability by considering gaps as crucial evolutionary signals rather than mere artefacts.
Ethical Considerations in Co-Authoring Research with Music Therapy Stakeholders
Authors: Devlin Kerry , Meadows Anthony , Johnston Morgan , Johnston Cheryl 
Published: June 2024

Abstract
While stakeholders provide invaluable perspectives about music therapy, particularly through the lens of their expertise as participants in music therapy encounters, their perspectives are rarely amplified in the context of full participation in research teams. In support of stakeholder participation in music therapy research, this article introduces and explores ethical considerations related to co-authorship. These ethical considerations are approached in three ways: (1) describing how co-authorship has been undertaken with music therapy stakeholders, specifically disabled children and adults, in a range of contexts, (2) Identifying ethical considerations related to our team’s own research project (Devlin, K., Johnston, M., & Johnston, C. [2024]. Making mistakes together: therapy participant, parent, and therapist perspectives on music therapy in two different settings. Music Therapy Perspectives) with two coauthors who are also stakeholders, and (3) providing guidelines for music therapists interested in coauthoring research with stakeholders. In doing so, the importance of co-authorship as an accessible, equitable research practice is emphasized.
Plain language abstract This article is about planning, doing, and writing research with people who are usually studied in music therapy research. We call this co-research. We talk about: •How to keep people safe •How to make decisions together •How to work and write as a team •If we should use our real names
Distinct SARS-CoV-2 populational immune backgrounds tolerate divergent RBD evolutionary preferences
Authors: Ma Wentai , Fu Haoyi , Jian Fanchong , Cao Yunlong , Li Mingkun 
Published: June 2024

ABSTRACT
Immune evasion is a pivotal force shaping the evolution of viruses. Nonetheless, the extent to which virus evolution varies among populations with diverse immune backgrounds remains an unsolved mystery. Prior to the widespread SARS-CoV-2 infections in December 2022 and January 2023, the Chinese population possessed a markedly distinct (less potent) immune background due to its low infection rate, compared to countries experiencing multiple infection waves, presenting an unprecedented opportunity to investigate how the virus has evolved under different immune contexts. We compared the mutation spectrum and functional potential of the newly derived mutations that occurred in BA.5.2.48, BF.7.14 and BA.5.2.49—variants prevalent in China—with their counterparts in other countries. We found that the emerging mutations in the receptor-binding-domain region in these lineages were more widely dispersed and evenly distributed across different epitopes. These mutations led to a higher angiotensin-converting enzyme 2 (ACE2) binding affinity and reduced potential for immune evasion compared to their counterparts in other countries. These findings suggest a milder immune pressure and less evident immune imprinting within the Chinese population. Despite the emergence of numerous immune-evading variants in China, none of them outcompeted the original strain until the arrival of the XBB variant, which had stronger immune evasion and subsequently outcompeted all circulating variants. Our findings demonstrated that the continuously changing immune background led to varying evolutionary pressures on SARS-CoV-2. Thus, in addition to viral genome surveillance, immune background surveillance is also imperative for predicting forthcoming mutations and understanding how these variants spread in the population.
Framework for standardizing digital health in resource-constrained settings: a case study of Uganda’s digital health communication infrastructure
Authors: Alunyu Egwar Andrew , Amiyo Mercy Rebekah , Nabukenya Josephine 
Published: June 2024

Abstract
Uganda has several digital health interventions, but most are not interoperable, failing the goal of digitizing the healthcare environment. One major reason for this failure is that the implementations are not based on a common set of standards formally agreed upon by the country’s health ministry. Therefore, Uganda and other countries that have fallen behind in standardizing their health systems need to implement and fast-track the formulation of contextual digital health standards. This study followed a design science approach to develop a framework for standardizing the digital health communication infrastructure. The design went through three cycles of design and improvement. Results show that 17 digital health stakeholders in Uganda who evaluated the framework agreed that they are suitable to guide standardization activities in Uganda. This study argues that other countries with digital health challenges similar to those in Uganda can adopt the framework.
The m6A reader ECT8 is an abiotic stress sensor that accelerates mRNA decay in Arabidopsis
Authors: Cai Zhihe , Tang Qian , Song Peizhe , Tian Enlin , Yang Junbo , Jia Guifang 
Published: June 2024

Abstract
N 6-methyladenosine (m6A) is the most abundant mRNA modification and plays diverse roles in eukaryotes, including plants. It regulates various processes, including plant growth, development, and responses to external or internal stress responses. However, the mechanisms underlying how m6A is related to environmental stresses in both mammals and plants remain elusive. Here, we identified EVOLUTIONARILY CONSERVED C-TERMINAL REGION 8 (ECT8) as an m6A reader protein and showed that its m6A-binding capability is required for salt stress responses in Arabidopsis (Arabidopsis thaliana). ECT8 accelerates the degradation of its target transcripts through direct interaction with the decapping protein DECAPPING 5 within processing bodies. We observed a significant increase in the ECT8 expression level under various environmental stresses. Using salt stress as a representative stressor, we found that the transcript and protein levels of ECT8 rise in response to salt stress. The increased abundance of ECT8 protein results in the enhanced binding capability to m6A-modified mRNAs, thereby accelerating their degradation, especially those of negative regulators of salt stress responses. Our results demonstrated that ECT8 acts as an abiotic stress sensor, facilitating mRNA decay, which is vital for maintaining transcriptome homeostasis and enhancing stress tolerance in plants. Our findings not only advance the understanding of epitranscriptomic gene regulation but also offer potential applications for breeding more resilient crops in the face of rapidly changing environmental conditions.
Partner-switching components PmgA and Ssr1600 regulate high-light acclimation in Synechocystis sp. PCC 6803
Authors: Nakamura Riku , Takahashi Yuji , Tachibana Shogo , Terada Arisa , Suzuki Kakeru , Kondo Kumika , Tozawa Yuzuru , Hihara Yukako 
Published: June 2024

Abstract
Photomixotrophic growth A (PmgA) is a pleiotropic regulator essential for growth under photomixotrophic and prolonged high-light (HL) conditions in the cyanobacterium Synechocystis sp. PCC 6803. The overall similarity with the antisigma factor of the bacterial partner-switching system indicates that PmgA exerts a regulatory function via phosphorylation of its target proteins. In this study, we performed an in vitro phosphorylation assay and protein–protein interaction analysis and found that PmgA interacts with 4 antisigma antagonist homologs, Ssr1600, Slr1856, Slr1859, and Slr1912, but specifically phosphorylates Ssr1600. Phenotypic analyses using the set of gene disruption and overexpression strains of pmgA and ssr1600 revealed that phosphorylation by PmgA is essential for the accumulation of Ssr1600 protein in vivo. The ssr1600-disrupted mutant showed similar phenotypes as those previously reported for the pmgA-disrupted mutant, namely, no obvious phenotype just after the shift to HL, but higher chlorophyll content, 5-aminolevulinic acid synthesis activity, and psaAB transcript levels than those in the wild type after 6 h. These findings indicate that the phosphorylated form of Ssr1600 works as the output of the partner-switching system to coordinately repress chlorophyll biosynthesis and accumulation of photosystem I during HL acclimation.
Nonnegligible cascading impacts of global urban expansion on net primary productivity
Authors: Liu Kangyao , Pei Fengsong , Liu Xiaoping , Zeng Zhenzhong , Zhu Peng , Fang Chuanglin , Xu Xiaocong , Wang Shaojian , Mao Jiafu , Chen Xiuzhi , Wu Changjiang , Cai Yiling , Zeng Li , Shi Qian , Li Xia 
Published: June 2024

Abstract
Accelerated global urban expansion not only directly occupies surrounding ecosystems, but also induces cascading losses of natural vegetation elsewhere through cropland displacement. Yet, how such effects alter the net primary productivity (NPP) worldwide remains unclear. Here, we quantified the direct and cascading impacts of global urban expansion on terrestrial NPP from 1992 to 2020 and projected the impacts under the shared socioeconomic pathways framework by 2100. We found that global urban expansion caused a cascading loss of 29.2 to 63.9 Tg C/year of terrestrial NPP in the historical period (1992–2020), accounting for 13–29% of the total direct NPP loss. Instead, our projections indicate that during 2020–2100, mainly due to the increased relocation of displaced croplands to low-productive ecosystems, the cascading impacts gradually change from negative to positive, leading to a net NPP increase. Such an increase may offset up to 7% of the total direct NPP loss, better balancing crop compensation with NPP maintenance. Our findings highlight the unexpected large cascading impacts of urban expansion on the carbon cycle and stress the importance of regulating land transitions to curtail land-use emissions.
Enhancing social cohesion with cooperative bots in societies of greedy, mobile individuals
Authors: Shi Lei , He Zhixue , Shen Chen , Tanimoto Jun 
Published: June 2024

Abstract
Addressing collective issues in social development requires a high level of social cohesion, characterized by cooperation and close social connections. However, social cohesion is challenged by selfish, greedy individuals. With the advancement of artificial intelligence (AI), the dynamics of human–machine hybrid interactions introduce new complexities in fostering social cohesion. This study explores the impact of simple bots on social cohesion from the perspective of human–machine hybrid populations within network. By investigating collective self-organizing movement during migration, results indicate that cooperative bots can promote cooperation, facilitate individual aggregation, and thereby enhance social cohesion. The random exploration movement of bots can break the frozen state of greedy population, help to separate defectors in cooperative clusters, and promote the establishment of cooperative clusters. However, the presence of defective bots can weaken social cohesion, underscoring the importance of carefully designing bot behavior. Our research reveals the potential of bots in guiding social self-organization and provides insights for enhancing social cohesion in the era of human–machine interaction within social networks.
Genotypic and phenotypic spectrum of maple syrup urine disease in Zhejiang of China
Authors: Yang X , Yang R , Zhang T , Tan D J , Pan R , Chen Z , Wu D , Chen C , Xu Y , Zhang L , Li X , Shu Q , Hu L 
Published: June 2024

Abstract

Background
Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder originating from defects in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex encoded by BCKDHA, BCKDHB and DBT. This condition presents a spectrum of symptoms and potentially fatal outcomes. Although numerous mutations in the BCKDH complex genes associated with MSUD have been identified, the relationship between specific genotypes remains to be fully elucidated.

Aim
Our objective was to predict the pathogenicity of these genetic mutations and establish potential links between genotypic alterations and the clinical phenotypes of MSUD.

Design
Retrospective population-based cohort.

Methods
We analyzed 20 MSUD patients from the Children’s Hospital at Zhejiang University School of Medicine (Hangzhou, China), recorded from January 2010 to December 2023. Patients’ blood samples were collected by heel-stick through neonatal screening, and amino acid profiles were measured by tandem mass spectrometry. In silico methods were employed to assess the pathogenicity, stability and biophysical properties. Various computation tools were utilized for assessment, namely PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf and SNP effect.

Results
We detected 25 distinct mutations, including 12 novel mutations. The BCKDHB gene was the most commonly affected (53.3%) compared to the BCKDHA gene (20.0%) and DBT gene (26.7%). In silico webservers predicted all novel mutations were disease-causing.

Conclusions
This study highlights the genetic complexity of MSUD and underscores the importance of early detection and intervention. Integrating neonatal screening with advanced sequencing methodologies is pivotal in ensuring precise diagnosis and effective management of MSUD, thereby significantly improving the prognosis for individuals afflicted with this condition.