bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease
Authors: Spencer Paige N , Wang Jiawei , Smith Erin P , Spiga Luisella , Simmons Alan J , Kim Taewoo , Kim William , Brown Monica E , Yang Yilin , Kaur Harsimran , Xu Yanwen , Kang Seung Woo , Helou Matthew D , Lee Mason A , Zheng Lin , Arceneaux Deronisha , Tasneem Naila , Mueller Katherine D , Kuddar Ozge S , Harned Mariah H , Ro James , Li Jing , Banerjee Amrita , Markham Nicholas O , Wilson Keith T , Coburn Lori A , Goettel Jeremy A , Liu Qi , Washington M. Kay , Valdivia Raphael H , Zhu Wenhan , Lau Ken S
Published: January 2025

The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF–overexpressing Crohn′s disease (CD) model (TnfΔARE/+), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the host′s immune susceptibility to drive region–specific disease. We identifiedChlamydia muridarum, an intracellular bacterium and murine counterpart to the human sexually transmittedC. trachomatis, as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD. Disease manifestation in the AC depends on indoleamine 2,3-dioxygenase (IDO1) activity induced by hypersensitive surface secretory cells in genetically susceptible hosts. Single–cell and microbial analyses of human specimens also implicates this pathobiont–epithelial IDO1 pathway in patients with a history of CD in the AC. Our findings demonstrate that genetic and microbial factors can independently drive region–specific disease and provide a unique model to study CD specific to the AC.
The Evolutionary History of Metallothioneins in Horseshoe Crabs, Scorpions, Spiders and other Chelicerate Species
Authors: Palacios Òscar , Capdevila Mercè , Albalat Ricard
Published: January 2025

Metallothioneins (MTs) are a heterogenous family of proteins involved in metal homeostasis and detoxification, playing a crucial role in the adaptation of organisms to varying conditions of metal bioavailability across ecosystems. Despite their significance, MT characterization across animal groups remains uneven. While MTs have been extensively studied in vertebrates and gastropods, their presence and function in many arthropods, particularly within the Chelicerata subphylum, remain largely unexplored. Chelicerates, comprising thousands of species of spiders, scorpions and ticks, are a highly diverse group of animals inhabiting a wide range of environments. Identifying and characterizing their MTs is therefore essential for understanding how they manage metal availability of diverse habitats. In this study, we have identified over 400 chelicerate MTs, classifying them into three distinct types –types 1, 2, and 3– each exhibiting significant structural and phylogenetic differences. Our findings have revealed that most chelicerate MTs are bidomain proteins, with notable exceptions of monodomain forms and larger variants. Evolutionary analysis suggests that type 1 MTs represent the ancestral form, while types 2 and 3 likely emerged during the evolution of spiders. These results pave the way of a deeper understanding of the metal homeostasis and detoxification in chelicerates, laying the groundwork for future studies on the origin, evolution and functional diversification of MTs in arthropods and other metazoan lineages.
A data-driven modeling framework for mapping genotypes to synthetic microbial community functions
Authors: Qian Yili , Menon Sarvesh D , Quinn-Bohmann Nick , Gibbons Sean M , Venturelli Ophelia S
Published: January 2025

Microbial communities play a central role in transforming environments across Earth, driving both physical and chemical changes. By harnessing these capabilities, synthetic microbial communities, assembled from the bottom up, offer valuable insights into the mechanisms that govern community functions. These communities can also be tailored to produce desired outcomes, such as the synthesis of health-related metabolites or nitrogen fixation to improve plant productivity. Widely used computational models predict synthetic community functions using species abundances as inputs, making it impossible to predict the effects of species not included in the training data. We bridge this gap using a data-driven community genotype function (dCGF) model. By lifting the representation of each species to a high-dimensional genetic feature space, dCGF learns a mapping from community genetic feature matrices to community functions. We demonstrate that dCGF can accurately predict communities in a fixed environmental context that are composed in part or entirely from new species with known genetic features. In addition, dCGF facilitates the identification of species roles for a community function and hypotheses about how specific genetic features influence community functions. In sum, dCGF provides a new data-driven avenue for modeling synthetic microbial communities using genetic information, which could empower model-driven design of microbial communities.
Spatial dissimilarity analysis in single cell transcriptomics
Authors: Shi Quan , Kristiansen Karsten
Published: January 2025

The spatial dissimilarity method is a new statistical tool to uncover complex bivariate relationships in single cells and spatial transcriptomics data, thereby addressing unresolved issues such as alternative splicing and allele-specific gene expression. By applying our spatial dissimilarity analysis method on datasets of neurons, tumor, and normal cells, we identified thousands of alternatively spliced genes and instances of allele-specific gene expression. This is particularly evident in the analysis of quiescent and transitioning cell states, where our method reveals the nuanced gene expression dynamics associated with these states. Notably, our findings highlight how allele-specific genetic variants can provide insights into the subclone architecture of normal cells and cancer cells, offering a more comprehensive understanding of cellular heterogeneity and a new insight to understand gene function at specific cell types. The spatial dissimilarity analysis method deepens our comprehension of cellular complexity and gene expression dynamics during cell state transitions.
Dynamics of neuropeptide release and activity post-bloodmeal in the female mosquito, Aedes aegypti
Authors: Sajadi Farwa , Di Scipio Chiara , Snan Lulia , Paluzzi Jean-Paul V.
Published: January 2025

Female Aedes aegypti secrete urine rapidly post-bloodmeal ingestion, with diuresis beginning immediately for removal of excess salts and water. This post-prandial diuresis includes a peak, post-peak, and late phase, involving the combined actions of multiple hormones, including diuretic and anti-diuretic factors. Calcitonin-like diuretic hormone 31 (DH31) and kinin peptides stimulate diuresis through actions on their cognate receptors localized in the Malpighian "renal" tubules (MTs). In contrast, the anti-diuretic neurohormone, CAPA, inhibits secretion by MTs stimulated by select diuretic hormones, including DH31. While DH31 and kinin are critical in achieving post-prandial diuresis, and CAPA functions as an important anti-diuretic hormone, the kinetics of their release and haemolymph levels remain unknown. Herein, using heterologously expressed A. aegypti DH31, CAPA, and kinin receptors, we investigated the titres of these hormones in the haemolymph of female mosquitoes at different time points after blood feeding. Haemolymph extracts from female mosquitoes contained levels of diuretic peptides, specifically kinin and DH31, that increased immediately post-bloodmeal, with levels peaking at 2 and 5 min, respectively, while DH31 levels remained elevated for 15 min. Comparatively, levels of CAPA peptides in the haemolymph steadily increase 15 min post-blood feeding, with levels peaking at 30 min. Synergistic actions were observed between DH31 and a kinin-like peptides on the MTs, providing a physiological context for the rapid release of these peptides into the female haemolymph. Altogether, these results demonstrate that DH31 and kinin are released immediately post-bloodmeal and, along with CAPA peptides, have a coordinative action on the MTs to maintain haemolymph homeostasis through regulation of primary urine secretion.
Decoding the Molecular Language of Proteins with Evola
Authors: Zhou Xibin , Han Chenchen , Zhang Yingqi , Su Jin , Zhuang Kai , Jiang Shiyu , Yuan Zichen , Zheng Wei , Dai Fengyuan , Zhou Yuyang , Tao Yuyang , Wu Dan , Yuan Fajie
Published: January 2025

Proteins, nature’s intricate molecular machines, are the products of billions of years of evolution and play fundamental roles in sustaining life. Yet, deciphering their molecular language - that is, understanding how protein sequences and structures encode and determine biological functions - remains a cornerstone challenge in modern biology. Here, we introduce Evola, an 80 billion frontier protein-language generative model designed to decode the molecular language of proteins. By integrating information from protein sequences, structures, and user queries, Evola generates precise and contextually nuanced insights into protein function. A key innovation of Evola lies in its training on an unprecedented AI-generated dataset: 546 million protein question-answer pairs and 150 billion word tokens, designed to reflect the immense complexity and functional diversity of proteins. Post-pretraining, Evola integrates Direct Preference Optimization (DPO) to refine the model based on preference signals and Retrieval-Augmented Generation (RAG) for external knowledge incorporation, improving response quality and relevance. To evaluate its performance, we propose a novel framework, Instructional Response Space (IRS), demonstrating that Evola delivers expert-level insights, advancing research in proteomics and functional genomics while shedding light on the molecular logic encoded in proteins. The online demo is available athttp://www.chat-protein.com/.
Mitochondria as Indispensable Yet Replaceable Components of Germ Plasm: Insights into Primordial Germ Cell Specification in Non-Teleost Sturgeons
Authors: Gao Linan , Franěk Roman , Tichopád Tomáš , Rodina Marek , Gela David , Šindelka Radek , Saito Taiju , Pšenička Martin
Published: January 2025

While it is widely recognized that mitochondria are components of germ plasm, their specific role in the formation and specification of primordial germ cells (PGCs) remains poorly understood. Furthermore, it has not been established whether mitochondria in germ plasm possess unique characteristics essential for their function. In this study, we demonstrate that mitochondria are indispensable for PGCs development in non-teleost fishes and that their role is not dependent on their origin from germ plasm. Using sturgeon embryos, we showed that UV radiation applied to the vegetal pole effectively eliminates germ plasm, including mitochondria, and prevents PGCs formation. Remarkably, we restored germ plasm function and PGCs development by injecting mitochondria derived from donor eggs, even when these mitochondria were not originally part of the germ plasm. Transplanted mitochondria were successfully identified in larval PGCs using a fluorescent PKH26 tracer, and in interspecies transplantation experiments, their presence was confirmed using species-specific mtDNA and mtRNA primers in larvae and individual PGCs. Our findings reveal that mitochondria are critical but not germ plasm-specific determinants of PGCs formation. This study provides novel insights into the developmental pathways of germ cells and establishes a previously unrecognized flexibility in mitochondrial functionality within the germline. These findings also offer a potential method for conserving matrilineal genetics in critically endangered species like sturgeons, while simultaneously opening new avenues for studying germlines with high interspecies mitochondrial heteroplasmy and contributing to broader evolutionary and conservation biology.
An unexpected mode of whole-body regeneration from reaggregated cell suspension inHydractinia(Cnidaria, Hydrozoa)
Authors: Curantz Camille , Krasovec Gabriel , Horkan Helen R , Ryan Laura , Varley Áine , Frank Uri
Published: January 2025

Hydrozoan cnidarians are among the few animals that can regenerate whole bodies from reaggregated cell dissociations but the cellular and molecular mechanisms that control this ability and how it is related to embryonic development are not well understood. Furthermore, the evolution of this type of regeneration is enigmatic since it does not occur naturally. Here, we show that aggregate regeneration inHydractinia symbiolongicarpusproceeds through several, consistent stages that include the formation of an epidermal layer, followed by migration, proliferation, and differentiation of adult pluripotent stem cells, known as i-cells. Migration of i-cells is controlled by sphingosine-1-phosphate signaling. Single-cell transcriptomics revealed, surprisingly, that the newly regenerated individual derives nearly exclusively from i-cell progeny rather than from recycled somatic cells, as seen in other hydrozoans. Given the similarity of this phenomenon to embryogenesis, we propose that the ability ofHydractiniacell aggregates to regenerate is a side effect of the animal’s i-cell-mediated development.
Ultraviolet damage and repair maps inDrosophilareveal the impact of domain-specific changes in nucleosome repeat length on repair efficiency
Authors: Morledge-Hampton Benjamin , Selvam Kathiresan , Chauhan Manish , Goodman Alan G. , Wyrick John J.
Published: January 2025

Cyclobutane pyrimidine dimers (CPDs) are formed in DNA following exposure to ultraviolet (UV) light and are mutagenic unless repaired by nucleotide excision repair (NER). It is known that CPD repair rates vary in different genome regions owing to transcription-coupled NER and differences in chromatin accessibility; however, the impact of regional chromatin organization on CPD formation remains unclear. Furthermore, nucleosomes are known to modulate UV damage and repair activity, but how these damage and repair patterns are affected by the overarching chromatin domains in which these nucleosomes are located is not understood. Here, we generated a new CPD damage map inDrosophilaS2 cells using CPD-seq and analyzed it alongside existing excision repair-sequencing (XR-seq) data to compare CPD damage formation and repair rates across five previously established chromatin types inDrosophila. This analysis revealed that repair activity varies substantially across different chromatin types, whereas CPD formation is relatively unaffected. Moreover, we observe distinct patterns of repair activity in nucleosomes located in different chromatin types, which we show is owing to domain-specific differences in nucleosome repeat length (NRL). These findings indicate that NRL is altered in different chromatin types inDrosophilaand that changes in NRL modulate the repair of UV lesions.
Toward an evolving framework for responsible AI for credit scoring in the banking industry
Authors: Mathen Manoj Philip , Paul Anindita
Published: January 2025

Purpose

The aim of this research is to conduct a systematic review of the literature on responsible artificial intelligence (RAI) practices within the domain of AI-based Credit Scoring (AICS) in banking. This review endeavours to map the existing landscape by identifying the work done so far, delineating the key themes and identifying the focal points of research within this field.

Design/methodology/approach

A database search of Scopus and Web of Science (last 20 years) resulted in 377 articles. This was further filtered for ABDC listing, and augmented with manual search. This resulted in a final list of 53 articles which was investigated further using the TCCM (Theory, Context, Characteristics and Methodology) review protocol.

Findings

The RAI landscape for credit scoring in the banking industry is multifaceted, encompassing ethical, operational and technological dimensions. The use of artificial intelligence (AI) in banking is widespread, aiming to enhance efficiency and improve customer experience. Based on the findings of the systematic literature review we found that past studies on AICS have revolved around four major themes: (a) Advances in AI technology; (b) Ethical considerations and fairness; (c) Operational challenges and limitations; and (d) Future directions and potential applications. The authors further propose future directions in RAI in credit scoring.

Originality/value

Earlier studies have focused on AI in banking, credit scoring in isolation. This review attempts to provide deeper insights, facilitating the development of this key field.
Halal standards practices in the food industry: the impact of halal assurance and operations
Authors: Othman Baharudin , Md Nawi Nurul Hudani
Published: January 2025

Purpose

The purpose of this study is to examine the effect of halal standards practices towards organizational performance. Additionally, the moderating role of organizational size on this association is explored for Malaysian halal industry so that the halal management practice in the future is expected to run well.

Design/methodology/approach

Regression analyses technique via Statistical Package For Social Science 27.0 is used to analyses the results of a self-administered questionnaire completed by 241 internal halal committee officers of multinational corporations and small and medium enterprises (SMEs) in Malaysia.

Findings

The results showed that halal standards practices give an effect that indicates 13.2% of the performance. In more detail, it only demonstrates the significant contribution of the halal assurance predictor to organizational performance compared to the halal operations (HOs) predictor. Additionally, organizational size also acts as a moderator between the relationships between halal standard practices (HO) and organizational performance. Besides, the study findings also show that there was a significant difference in organizational performance for multinationals and SMEs. This encouraging outcome is the result of organizational performance is influenced by a chain that interacts with each other starting from input, which then translates into process and ultimately results that are also supported by internal control of the organization for Malaysian halal industry.

Research limitations/implications

This study only focused on the Malaysian halal industry such as certain number of factors and limited measurement was used in this study. Only a few halal standards practices and organization performance measurements were considered.

Practical implications

Halal food producers should engender greater commitment to Halal standard practice involving acts, standards, regulations and guidelines that can be used to comply halal requirements needed by halal certification bodies especially halal committee members to control internally. It also serves as a valuable resource for policymakers and practitioners aiming to identify effective practices for comprehensive halal standards management to enhance organizational performance, particularly for micro-scale enterprises within the Malaysian halal industry.

Originality/value

This study considerably advances the existing body of knowledge by applying standard halal practices model to explain their relationship, with organization size serving as a moderating to variable and provide direction for researchers in subsequent studies. They also offer valuable insights for practitioners seeking to continually enhance organizational performance through the implementation of effective halal standards management practices within the Malaysian halal industry.
Disentangling Timing Uncertainty of Event‐Driven Connectedness Among Oil‐Based Energy Commodities
Authors: Kočenda Evžen , Bartušek Daniel
Published: January 2025

Reported news events frequently influence the pricing dynamics of oil‐based commodities. We analyse almost 900 oil‐related events from 1987 to 2022, categorising them based on recurring characteristics. We quantify dynamic connectedness among energy commodities and apply a novel bootstrap‐after‐bootstrap testing procedure to identify 21 statistically significant historical events that triggered abrupt and enduring increases in volatility connectedness. Geopolitical events are more consistently associated with elevated connectedness than economic events, while natural events do not exhibit a similar impact. Events share prevailing characteristics: their negativity, unexpected nature and the introduction of concerns about oil supply shortages.
Exploring Paramedicine Models of Care: A Novel Macro Analysis Using the RESPIGHT Framework
Authors: Weber Anthony , Devenish Scott , Lam Louisa
Published: January 2025

Objective

To evaluate the alignment of undergraduate paramedicine curricula in Australia with the RESPIGHT model, focusing on diverse aspects such as emergency response, community engagement and governance.

Design

Deductive thematic analysis was conducted to assess the alignment of curricula from 16 Australian universities with the RESPIGHT framework.

Setting

The study reviewed undergraduate pre‐registration paramedicine programmes across Australian universities.

Participants

The study included a comprehensive analysis of curricula from 16 universities offering undergraduate paramedicine programmes.

Main Outcome Measure

The degree of alignment of paramedicine curricula with the RESPIGHT categories: emergency response, community engagement, situated practice, primary healthcare, integration with health services, governance, leadership and treatment and transport.

Results

The analysis revealed varying degrees of alignment across the RESPIGHT categories, with notable discrepancies in areas such as community engagement and governance. Some universities demonstrated strong alignment in emergency response and treatment, while others showed weaker integration with primary healthcare and community engagement.

Conclusion

The study highlights significant disparities in the preparedness of paramedicine students for the broad scope of practice required in modern healthcare. The findings underscore the need for curriculum reform to better prepare students for community care models and the evolving healthcare landscape, ensuring a more comprehensive and integrated approach to paramedicine education in Australia.
mRNA‐laden lipid nanoparticle‐enabled humanized CD19 CAR‐T‐cell engineering for the eradication of leukaemic cells
Authors: Chen Zhaozhao , Ren Anqi , Li Yingying , Shu Jinhui , Wu Jianghua , Huang Hekuan , Wang Jingming , Hu Yu , Mei Heng
Published: January 2025

Chimeric antigen receptor T‐cell (CAR‐T) therapy has shown transformative potential in treating malignant tumours, with increasing global approval of CAR‐T products. However, high‐production costs and risks associated with viral vector‐based CAR‐T cells—such as insertional mutagenesis and secondary tumour formation—remain challenges. Our study introduces an innovative CAR‐T engineering approach using mRNA delivered via lipid nanoparticles (LNPs), aiming to reduce costs and enhance safety while maintaining strong anti‐tumour efficacy. We developed an LNP‐based transfection protocol for efficient delivery of mRNA encoding full‐human CAR constructs, achieving high CAR expression and significant cytotoxicity against leukaemic cells in vitro. Co‐culture with Raji cells showed increased cytokine secretion and tumour cell killing by mRNA‐LNP CAR‐T cells. Therapeutic efficacy was further demonstrated in an NOD‐scid‐IL2Rγnull (NSG) mouse model with Raji engraftment, where treated mice exhibited marked tumour regression and extended survival. These findings underscore the potential of mRNA‐LNPs as a non‐viral, effective CAR‐T engineering platform, offering a promising alternative to traditional methods that could improve CAR‐T safety, efficacy and accessibility in clinical cancer immunotherapy.
Dexmedetomidine Inhibits Ferroptosis by Regulating the SRY‐Box Transcription Factor 9/Divalent Metal Transporter‐1 Axis to Alleviate Cerebral Ischemia/Reperfusion Injury
Authors: Liu Zhen , Liu Qionghua , Zhang Xuekang , Li Gan
Published: January 2025

Cerebral ischemia/reperfusion injury (IRI) is pathologically associated with ferroptosis. Dexmedetomidine (Dex) exerts neuroprotective activity after cerebral IRI. Our work focused on probing the pharmacologic effect of Dex on ferroptosis during cerebral IRI and the mechanisms involved. Cerebral IRI models were established by oxygen–glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion (MCAO). 2,3,5‐Triphenyltetrazolium chloride (TTC) staining was utilized to detect cerebral infarct size and mNSS was performed to evaluate neurologic deficits. Brain pathologic changes were analyzed by HE staining. Lipid peroxidation level was detected by C11‐BODIPY staining, and Fe2+ and MDA levels were measured using the kits. Cell vitality was examined by CCK‐8 assay. Dual‐luciferase reporter and ChIP assays were adopted to determine the interaction between SOX9 and DMT1 promoter. Dex ameliorated ferroptosis and neuronal death induced by MCAO and OGD/R. SOX9 upregulation abolished the inhibitory effect of Dex on OGD/R‐induced ferroptosis and neuronal death in SH‐SY5Y cells. Our further trials showed that SOX9 transcriptionally activated DMT1 expression. As expected, DMT1 overexpression prevented Dex‐induced decrease in ferroptosis and neuronal death in OGD/R‐treated SH‐SY5Y cells. Dex inhibited ferroptosis to exert neuroprotection effects on cerebral IRI by inactivating the SOX9/DMT1 axis.
Invoking the Discourse of Children's Rights in Campaigns Around Public Space
Authors: Powell Rhian , Muddiman Esther , Power Sally , Taylor Chris
Published: January 2025

Increasing emphasis is being placed on the need to consider children's rights in planning decisions. However, the way these rights are claimed by adults can be problematic, especially when planning decisions are controversial and contested. Drawing on interview data with participants engaged in campaigning around the development of a green space in Cardiff, we show how the adult appropriation of children's rights to support such campaigns may not only be misleading but potentially damaging. We conclude by discussing the limits of age‐based rights claims and the need to ensure that children's rights are not appropriated for adult agendas.
Second Time Around: Increased Rate of Living Donation From Repeat Organ Donors
Authors: Sidoti Carolyn N. , Terlizzi Kelly , Donnelly Conor , Jaffe Ian S. , Motter Jennifer D. , Philosophe Benjamin , Jenkins Reed T. , Hussain Sarah , Colon Pedro , Tevar Amit D. , Lonze Bonnie E. , Orandi Babak J. , Levan Macey L. , Segev Dorry L. , Massie Allan B.
Published: January 2025

Introduction

Some living organ donors will decide to donate again at a later date. Evidence has indicated that this practice may have increased in recent years. We evaluated the incidence and outcomes of this practice to inform counseling of potential repeat donors.

Methods

Using SRTR data from 1994 to 2023, we identified 220 repeat living donors and their 415 recipients. We constructed donor comparison groups using weighting by the odds. We described clinical and lab results at 6 months, 1 year, and 2 years post‐donation separately for kidney‐second donors and liver‐second donors. We compared all‐cause graft failure for their recipients with those of comparison donors.

Results

The annual count of repeat living donors increased from 5 in 2018 to 25 in 2019 (p < 0.001). Of 220 donors, 159 were liver‐second donors (72.3%) and 55 were kidney‐second donors (25.0). The percentage of nondirected donations increased from 30.5% at first donation to 53.2% at second donation (p < 0.001). Liver‐second donors had one death approximately 2.5 years post‐donation. Seventeen were re‐admitted and 20 experienced complications requiring an interventional procedure or re‐operation. Among kidney‐second donors, no deaths, re‐admissions, or post‐donation complications were reported. Post‐donation outcomes in both groups were comparable when evaluated against organ‐specific comparison donors. Recipients of repeat living donors experienced graft survival similar to recipients of comparison donors.

Conclusions

Repeat living donation may be a safe practice for carefully selected living donors in the short term; however, long term safety is unknown. Outcomes for recipients are similar to recipients of comparison donors.
Leaf Dry Matter Content Is Phylogenetically Conserved and Related to Environmental Conditions, Especially Wildfire Activity
Authors: Dai Dachuan , Yu Dongli , Gao Wuchao , Perry George L. W. , Paterson Adrian M. , You Chengming , Zhou Shixing , Xu Zhenfeng , Huang Congde , Cao Dongyu , Curran Timothy J. , Cui Xinglei
Published: January 2025

Leaf dry matter content (LDMC) is an important determinant of plant flammability. Investigating global patterns of LDMC could provide insights into worldwide plant flammability patterns, informing wildfire management. We characterised global patterns of LDMC across 4074 species from 216 families, revealing that phylogenetic and environmental constraints influence LDMC. LDMC varied across growth forms and taxonomic groups, displaying phylogenetic niche conservatism. Temperature, precipitation, aridity index, soil total nitrogen content and wildfire activity affected LDMC, and the effect of wildfire activity was stronger than other environmental factors across species with postfire regeneration abilities. Such species had higher LDMC, and their LDMC was less phylogenetically conserved and more strongly associated with fire activity. Our results suggest that, although LDMC shows phylogenetic niche conservatism, LDMC is determined by environmental factors, especially wildfire activity. Wildfire has likely acted as a selective pressure towards high LDMC across species that persist through fire using postfire regeneration.
How well is the female population represented in clinical trials with infusion therapies for Parkinson's disease? A systematic review and metanalysis
Authors: Smilowska Katarzyna , Carvalho Vanessa , Szejko Natalia , Costa João , Moro Elena , Antonini Angelo
Published: January 2025

Background

Parkinson's disease (PD) is a neurodegenerative disorder affecting both sexes, but differences exist between male and female in clinical manifestations, functional impact of symptoms and hormonal influences. Therefore, representativeness of females in PD trials indirectly determines the external validity of the clinical research in this field.

Objective

To estimate the representativeness of female in infusion therapy trials for advanced PD.

Methods

PubMed and EMBASE databases were searched (1980 to September 2023), along with congress abstracts, to identify controlled clinical trials and large non‐controlled studies on infusion therapies in PD enrolling >100 patients. Random‐effect meta‐analysis was conducted to estimate mean pooled prevalence of females included in the studies. Subgroup analyses were conducted accordingly to study design and intervention.

Results

We included 15 studies (six studies on levodopa‐carbidopa intestinal gel, six on subcutaneous levodopa, two on subcutaneous apomorphine, and one on levodopa‐carbidopa‐entacapone intestinal gel). Sex was not a randomisation stratification factor in any of these studies. Only one study explored differences in the outcome estimated according to sex. Overall, the proportion of female included was 38% (95% CI:33%–43%; I2 = 74%), without differences between studies assessing different type of interventions (p = 0.72) or between study design (p = 0.35). In two studies, females represented the majority of included patients.

Conclusion

Female with advanced PD are underrepresented in infusion therapy trials. Most trials have overlooked sex‐based biological differences that can impact clinical and functional outcomes, raising concerns about the generalizability of these findings to real‐world contexts.
The environmental impact of extracellular matrix preparation
Authors: Chen Ying , Ke Zihao , Wang Haiyang , Zhang Rui , Zhou Yingjie , Marsili Enrico , Mei Jin
Published: January 2025

The extracellular matrix (ECM) is a network of proteins and other molecules that encase and support cells and tissues in the body. As clinical and biotechnological uses of ECM are expanding, it is essential to assess the environmental impact associated with its production. Due to high levels of customization, various laboratories employ distinct methods; therefore, this study evaluates three common protocols. Life cycle assessment (LCA) methodology has been developed to evaluate the environmental impacts of products produced through diverse processes. Despite its widespread application in the pharmaceutical industry, LCA has seldom been utilized to estimate the environmental effects of laboratory protocols. This Viewpoint applies LCA to assess the functionality and environmental impacts of ECM produced via P1, P2, and P3. The results of this assessment indicate that the protocol with the highest impact generates approximately 43 times more CO2‐equivalent emissions (CO2 eq) than that with the lowest impact, while the ECM produced using the least impactful protocol demonstrates the highest biocompatibility. Additional environmental indicators such as eutrophication, photochemical oxidation, and acidification also vary among the tested protocols. This work underscores the need to factor environmental impact in the development of novel biomedical materials.
Investigating the Effects of Thermal Variability and Heatwaves on Pond Zooplankton Communities and Physiological Traits
Authors: Bonadonna Christine C. , Moffett Emma R. , Symons Celia C.
Published: January 2025

To understand the impacts of climate change, we must understand the consequences of multiple and interacting timescales of temperature change. While much is known about rising mean temperatures, less is understood about the influence of projected thermal variability and extreme events like heatwaves on biological communities. This study investigates the interaction of short‐term (experimental) and long‐term (historic) thermal variability with heatwaves on zooplankton communities and physiological traits.

We performed a fully factorial mesocosm experiment with three factors: (1) historic thermal variation (four source ponds with similar average temperature but different daily thermal ranges including 3.7°C, 5.9°C, 9.1°C, and 10.7°C); (2) experimental thermal variation (insulated and non‐insulated tanks); and (3) a 4‐day heatwave treatment (+3.5°C) halfway through the experiment. We sampled the zooplankton community throughout the experiment and assayed the upper thermal limit (CTmax) and metabolic rate of Daphnia dentifera and Leptodiaptomus signicauda immediately before and after the heatwave.

Zooplankton community composition responded minimally to thermal variability and the heatwave. For both species, CTmax response to the heatwave varied by experimental thermal variability, increasing in individuals from low‐variability tanks and decreasing in individuals from high‐variability tanks. Metabolic rate did not vary significantly by any of the treatments.

D. dentifera and L. signicauda's upper thermal limit seems to be unaffected by their historic thermal history, while their CTmax response to a heatwave seems to rely only on their short‐term thermal variability history. Metabolic rate, on the other hand, is unaffected by thermal history or heatwaves of this magnitude. In spite of the physiological responses at the individual level, zooplankton community structure seems to be buffered and overall unaffected by heatwaves and thermal variability at this magnitude.

Our experiment provides new insight on the effects of thermal variability at both short‐ and long‐term scales combined with an acute heatwave to understand the effects of a changing climate in a more realistic manner. The data supports that individuals from recently thermally stable backgrounds may be better equipped to positively respond physiologically to heatwaves and zooplankton community structure in this system could be unaffected by warming at this magnitude.
Effects of exercise on cognitive function and glycated hemoglobin A1c among patients with type 2 diabetes mellitus and cognitive impairment: A systematic review and meta‐analysis
Authors: Li Xiaoxue , Chen Bin , Liu Xinyuan , Ma Jingya
Published: January 2025

Aim

To evaluate the effects of exercise versus without‐exercise group on global cognitive function, executive function, glycated hemoglobin A1c (HbA1c) and fasting plasma glucose in patients with type 2 diabetes mellitus and cognitive impairment.

Methods

A systematic search of Cqvip, SinoMed, Wanfang Data, CINAHL, Cochrane, Embase, Pubmed, Lippincott, Web of Science and Scopus was carried out. Randomized control trials were selected. The risk of bias was evaluated using the Cochrane Risk of Bias tool. The random‐effects model was used to obtain the pooled estimates.

Results

Eight trials with 884 participants were included. Exercise could significantly improve global cognitive function (standardized mean difference 0.82, 95% CI 0.53–1.12), executive function measured by the Trail‐Marking Test part B (mean difference −20.43, 95% CI −36.20, −4.66), glycated hemoglobin A1c (%; mean difference −0.58, 95% CI −0.88, −0.29) and fasting plasma glucose (mg/dL; mean difference −17.61, 95% CI −32.67, −2.54).

Conclusions

Exercise can improve cognitive function, glycated hemoglobin A1c and fasting plasma glucose among type 2 diabetes mellitus patients with cognitive impairment. Additional studies with higher methodological quality are expected to draw more definite conclusions. This finding could provide a reference for clinical decision‐making and guide future research initiatives. Geriatr Gerontol Int 2025; 25: 148–159.
Confounders: A threat to the interpretation of research findings in endodontics
Authors: Farajollahi Mehran , Saber Tahan Shima , Keshtkar Abbasali , Peters Ove A.
Published: January 2025

Confounding is a significant challenge in endodontic research, as it can blur the true effect and relationship between exposure and outcomes, potentially compromising the internal validity of research findings. Confounding variables can create apparent differences between study groups when no actual difference exists or fail to reveal true differences when they are present. Additionally, confounding can lead to either an underestimation or an overestimation of the effect of exposure on the outcome. This narrative review aims to (i) define confounder variables and explain how to identify them, (ii) elaborate methods for controlling confounders, and (iii) discuss how confounders can obscure any causal relationship. Confounding variables can be controlled through study design such as randomization, matching and restriction, or adjusted using statistical methods like stratification and multivariable models. However, inadequate control of confounding can result in residual confounding, which poses a significant threat to the interpretation of findings in endodontic research.
Three challenges of social protection in sub‐Saharan Africa: informality, climate change and pandemics
Authors: Delpy Léo
Published: January 2025

This article provides an overview of social protection challenges in sub‐Saharan Africa. It explores three main challenges: the integration of informal workers, the management of climate change and pandemics. Despite the proliferation of social protection programmes in sub‐Saharan Africa, effective coverage remains low. About 76.3% of the population is not covered by any formal social protection mechanisms. Following the principle of qualitative comparative analysis, this article offers a twofold contribution. Firstly, it provides an overview of the diversity of social protection mechanisms in sub‐Saharan Africa. This article proposes to describe the three categories of social protection using the concept of social protection mix: formal, semi‐formal and informal. Secondly, using this concept, this study explores three major challenges of the social protection mix in sub‐Saharan Africa. Finally, this article suggests ways to strengthen social protection systems that address new challenges and incorporate the diversity of social protection mechanisms.
Racial disparity in preoperative C‐reactive protein level for predicting prognosis of patients with non‐metastatic clear cell renal cell carcinoma: INMARC study
Authors: Chen Wei , Tanaka Hajime , Kobayashi Masaki , Fukuda Shohei , Nakayama Akinori , Meagher Margaret F. , Yoshida Soichiro , Derweesh Ithaar H. , Master Viraj A. , Hirakawa Akihiro , Fujii Yasuhisa , Saito Kazutaka
Published: January 2025

Background

C‐reactive protein (CRP) is a prognostic biomarker for clear cell renal cell carcinoma (ccRCC). However, there may be potential racial heterogeneity in distribution and prognostic impact of CRP level. We investigated potential racial differences in distribution and prognostic impact of preoperative CRP among Asian (AS), African American (AA), and Caucasian (CAUC) patients with non‐metastatic ccRCC (nmccRCC).

Methods

We retrospectively analyzed 1991 nmccRCC cases (AS/AA/CAUC: n = 968/223/800) undergoing nephrectomy from the international multi‐institutional database. We investigated CRP distributions and optimal cut‐off values for predicting recurrence‐free survival (RFS) and overall survival (OS) using Cox regressions for each racial group. Subgroup analyses considered comorbidities, pathological T stage, and Fuhrman grade.

Results

Preoperative CRP distributions differed significantly among the races, with median values of 0.90 mg/L (interquartile range, 0.40–2.33) for AS, 5.00 mg/L (1.98–12.20) for AA, and 3.55 mg/L (1.41–8.48) for CAUC (p < 0.01). Optimal cut‐off values for RFS were 1.2 mg/L in AS, 2.8 mg/L in AA, and 1.7 mg/L in CAUC, showing C‐indices of 0.77, 0.71, and 0.77, respectively. For OS, they were 1.6 mg/L in AS, 8.3 mg/L in AA, and 9.3 mg/L in CAUC, yielding C‐indices of 0.77, 0.70, and 0.74, respectively. Subgroup analyses revealed varying reference ranges of CRP levels among races (1.1–2.2/2.7–5.0/1.5–3.4 mg/L for RFS, and AS/AA/CAUC: 0.9–3.0/8.0–12.7/8.0–10.4 mg/L for OS, respectively).

Conclusion

The preoperative CRP distributions and their optimal cut‐off values for predicting patient prognosis differed significantly among the races. Using race‐specific cut‐off values, CRP demonstrated consistently high‐prognostic accuracies, which may improve tailored patient management in nmccRCC.
Facilitators and Barriers of Large Language Model Adoption Among Nursing Students: A Qualitative Descriptive Study
Authors: Ma Yingzhuo , Liu Tong , Qi Jianwei , Gan Yiling , Cheng Qiongyao , Wang Jun , Xiao Mingzhao
Published: January 2025

Aim

To explore nursing students' perceptions and experiences of using large language models and identify the facilitators and barriers by applying the Theory of Planned Behaviour.

Design

A qualitative descriptive design.

Method

Between January and June 2024, we conducted individual semi‐structured online interviews with 24 nursing students from 13 medical universities across China. Participants were recruited using purposive and snowball sampling methods. Interviews were conducted in Mandarin. Data were analysed through directed content analysis.

Results

Analysis revealed 10 themes according to 3 constructs of the Theory of Planned Behaviour: (a) attitude: perceived value and expectations were facilitators, while perceived caution posed barriers; (b) subjective norm: media effects and role model effectiveness were described as facilitators, whereas organisational pressure exerted by medical universities, research institutions and hospitals acted as a barrier to usage; (c) perceived behavioural control: the design of models and free access were strong incentives for students to use, while geographic access restrictions and digital literacy deficiencies were key factors hindering adoption.

Conclusion

This study explored nursing students' attitudes, subjective norms and perceived behavioural control regarding the use of large language models. The findings provided valuable insights into the factors that hindered or facilitated nursing students' adoption.

Implications for the Profession

Through the lens of this study, we have enhanced knowledge of the journey of nursing students using large language models, which contributes to the implementation and management of these tools in nursing education.

Impact

There is a gap in the literature regarding nursing students' views and perceptions of large language models and the factors that influence their usage, which this study addresses. These findings could provide evidence‐based support for nurse educators to formulate management strategies and guidelines.

Reporting Method

Reporting adheres to the consolidated criteria for reporting qualitative research (COREQ) checklist.

Public Contribution

No patient or public contribution.
A comparative study of AI‐generated and human‐crafted learning objectives in computing education
Authors: Doyle Aidan , Sridhar Pragnya , Agarwal Arav , Savelka Jaromir , Sakr Majd
Published: January 2025

Background

In computing education, educators are constantly faced with the challenge of developing new curricula, including learning objectives (LOs), while ensuring that existing courses remain relevant. Large language models (LLMs) were shown to successfully generate a wide spectrum of natural language artefacts in computing education.

Objectives

The objective of this study is to evaluate if it is feasible for a state‐of‐the‐art LLM to support curricular design by proposing lists of high‐quality LOs.

Methods

We propose a simple LLM‐powered framework for the automatic generation of LOs. Two human evaluators compare the automatically generated LOs to the human‐crafted ones in terms of their alignment with course goals, meeting the SMART criteria, mutual overlap, and appropriateness of ordering.

Results

We found that automatically generated LOs are comparable to LOs authored by instructors in many respects, including being measurable and relevant while exhibiting some limitations (e.g., sometimes not being specific or achievable). LOs were also comparable in their alignment with the high‐level course goals. Finally, auto‐generated LOs were often deemed to be better organised (order, non‐overlap) than the human‐authored ones.

Conclusions

Our findings suggest that LLM could support educators in designing their courses by providing reasonable suggestions for LOs.
A Retrospective Study of Stabilizing Bridges in Patients With Stages III and IV Periodontitis: Up to 35 Years of Clinical Audit
Authors: Fardal Øystein , Grytten Jostein
Published: January 2025

Background/Aim

Studies on large cross‐arch bridges in patients with severe periodontitis show that such bridges can stabilize the periodontal condition. However, it is not known if these bridges will reduce long‐term tooth loss and what factors are important for their long‐term survival. The aim of the study was to study all patients with Stages III/IV periodontitis who received cross‐arch bridges for up 35 years in a private practice.

Materials and Methods

All patients referred for periodontal treatment from 1986 who received cross‐arch bridges with observation period of minimum 7 years were assessed. All dropouts were accounted for.

Results

Ninety‐eight patients (1.7% of the patient population) with 111 bridges were observed (57 females and 37 males). Age at bridge construction was 55.4 years (SD = 7.1, range 39–79). Failure rate was 14.4% at 16.1 years (SD = 4.0 range 10–22). Reasons for failure were poor oral hygiene (p = 0.0093) and complications such as caries, endontics, porcelain fractures and gingival retractions during maintenance therapy (p = 0.0059). Fewer abutment teeth were lost from the bridges than teeth from the same and opposing arches (8.8% vs. 34.4% and 25.4%) (p < 0.0001).

Conclusion

Cross‐arch bridges constructed for patients with Stages III and IV periodontitis were successful in terms of longevity, low failure rates, tooth preservation and patient satisfaction.