bluuebunny/crossref_metadata_2025 huggingface dataset:
Reuse, remanufacturing and recycling in the steel sector
Authors: Davis C. , Hall R. , Hazra S. , Debattista K. , Zhuang S. , Duan J. , Li Z. , Shenton J. , Panni D. , Halfpenny A.
Published: November 2024

The global steel sector is undergoing a transition from being a major CO
2
emitter to a more sustainable circular material service provider, moving towards (near) net zero CO
2
through combined strategies of reuse, remanufacturing, recycling and changes to primary steelmaking. This paper considers the transition using the UK as an example, based on the current sector state and future plans/opportunities. Some key enablers/barriers have been identified, and case studies are presented on the current state of knowledge and technology developments. For example, increasing reuse/remanufacturing requires data on the component’s remaining life at the end-of-product life; in this work use of in-service monitoring for steel-intensive applications in the transport sector is discussed identifying sensor types/locations for fatigue loading assessment for different use conditions to feed into material/product passports for reuse/remanufacturing decisions. Increased recycling of obsolete scrap has implications for composition control with increases in residual elements, such as Cu, Sn, Cr and Ni inevitable. Current and future approaches to recycling and scrap sorting are discussed along with case studies for how residual elements affect microstructural development during steel processing, including effects on recrystallization, phase transformation and fine-scale precipitation, which potentially could be exploited to give increases in product strength.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
SymScore: Machine Learning Accuracy Meets Transparency in a Symbolic Regression-Based Clinical Score Generator
Authors: Cawiding Olive R. , Lee Sieun , Jo Hyeontae , Kim Sungmoon , Suh Sooyeon , Joo Eun Yeon , Chung Seockhoon , Kim Jae Kyoung
Published: November 2024

Self-report questionnaires play a crucial role in healthcare for assessing disease risks, yet their extensive length can be burdensome for respondents, potentially compromising data quality. To address this, machine learning-based shortened questionnaires have been developed. While these questionnaires possess high levels of accuracy, their practical use in clinical settings is hindered by a lack of transparency and the need for specialized machine learning expertise. This makes their integration into clinical workflows challenging and also decreases trust among healthcare professionals who prefer interpretable tools for decision-making. To preserve both predictive accuracy and interpretability, this study introduces the Symbolic Regression-Based Clinical Score Generator (SymScore). SymScore produces score tables for shortened questionnaires, which enable clinicians to estimate the results that reflect those of the original questionnaires. SymScore generates the score tables by optimally grouping responses, assigning weights based on predictive importance, imposing necessary constraints, and fitting models via symbolic regression. We compared SymScore’s performance with the machine learning-based shortened questionnaires MCQI-6 (n= 310) and SLEEPS (n= 4257), both renowned for their high accuracy in assessing sleep disorders. SymScore’s questionnaire demonstrated comparable performance (MAE = 10.73,R2= 0.77) to that of the MCQI-6 (MAE = 9.94,R2= 0.82) and achieved AU-ROC values of 0.85-0.91 for various sleep disorders, closely matching those of SLEEPS (0.88-0.94). By generating accurate and interpretable score tables, SymScore ensures that healthcare professionals can easily explain and trust its results without specialized machine learning knowledge. Thus, Sym-Score advances explainable AI for healthcare by offering a user-friendly and resource-efficient alternative to machine learning-based questionnaires, supporting improved patient outcomes and workflow efficiency.
Participant experience of Scottish Ballet’s dance-based long COVID support programme: A mixed methods study
Authors: Philip Keir EJ , Burton Alexandra , Lewis Adam , Buttery Sara C , Williams Parris J , Polkey Michael I , Fancourt Daisy , Hopkinson Nicholas S
Published: November 2024

Objectives

To explore participant experience and perceived impacts of an online dance-based long COVID support programme.

Design

Mixed-methods study using thematic analysis of semi-structured interviews and structured observations, and ordinal scale questionnaire responses.

Setting

Online, community-based, with participants in Scotland and England.

Participants

26 people with self-reported long COVID who participated in the final block of 10 sessions were invited to participate in this study. 13 of these consented, 12 female, 7 White British, 10 English as first language, mean(range) age 57yrs (38-77), symptom duration 27months (17 – 35), and live sessions attended 9.2 (4-17). Two dance leaders also participated in the study.

Interventions

An online dance-based long COVID support programme of live sessions, provided in morning and afternoon slots, 30 to 45 minute duration, and online materials to promote wellbeing and self-management strategies, developed by Scottish Ballet, people with long COVID and healthcare professionals. The block of 10 sessions, from which participants were recruited, ran in September-November 2023. Potential participants were required to confirm they were well enough to participate in the programme.

Results

Responses to closed questions regarding self-reported impacts demonstrated perceived physical and mental health improvements, the programme surpassed participant expectations, and participants would recommend the programme. Qualitatively, we identified four themes 1. Improved experience of symptoms; 2. Increased confidence regarding movement and physical activity; 3. Feeling calm and refreshed; 4: Valuing time spent in a safe space. Facilitators of impact related to content, logistics, and delivery. Few barriers were described. Dance leaders’ responses aligned with those of programme participants.

Conclusions

A remotely delivered dance-based intervention for supporting people with long COVID is feasible, with participants consistently reporting that they found it enjoyable and beneficial to their health and wellbeing. Further research to assess impact on clinically validated measures is required.

Strengths and Limitations of the study

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This is the first known study to explore participant experience in a dance-based support programme for people with long COVID.

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The study provides insights into participant perspectives on their experience of movement and ways it might be incorporated into long COVID management.

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Small number of participants limits generalisability of the conclusions.

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Participants were self-selecting both in accessing the program and the evaluation described here.

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Further research is required to assess impact on clinically validated outcome measures.
Structure determinants of DANGEROUS MIX 3, an alpha/beta hydrolase, for triggering NLR-mediated genetic incompatibility in plants
Authors: Kim Gijeong , Wan Wei-Lin , Kim Nayun , Tan Yi Yun , Charoennit Nuri , Lee Rachelle R. Q. , Liew Yin Yin , Ng Shen Kai , Zhang Yizhong , Song Ji-Joon , Chae Eunyoung
Published: November 2024

Genetic incompatibility occurs when a mismatched pair of plant immune components mounts autoimmune responses in hybrids. Highly diversified NLR receptors are main culprits of the genetic conflict, recognizing host proteins from different origin as immune trigger. Here, we report the molecular mechanism underlying a DANGEROUS MIX (DM) autoimmunity, comprising DM2h/RPP1 NLR and its incompatible partner DM3, an alpha/beta hydrolase. Cryo-electron microscopy reveals the oligomeric nature of two natural DM3 variants in a trimer of dimer configuration. The polymorphism triggering autoimmunity is located at the dimer interface, resulting in drastic structural differences such that dimerizing helix and loop reinforcing the interface is lost and disordered. Structure-function analysis shows that integrity of the dimer interface, but neither maintenance of hexamer nor its enzymatic activity, is the key factor contributing to autoimmunity. Our finding pinpoints checkpoints embedded in the oligomeric configuration of a host enzyme that controls the switching mechanism of NLR activity.
Error rates inQST–FSTcomparisons depend on genetic architecture and estimation procedures
Authors: Liu Junjian J. , Edge Michael D.
Published: November 2024

Genetic and phenotypic variation among populations is one of the fundamental subjects of evolutionary genetics. One question that arises often in data on natural populations is whether differentiation among populations on a particular trait might be caused in part by natural selection. For the past several decades, researchers have usedQST–FSTapproaches to compare the amount of trait differentiation among populations on one or more traits (measured by the statisticQST) with differentiation on genome-wide genetic variants (measured byFST). Theory says that under neutrality,FSTandQSTshould be approximately equal in expectation, soQSTvalues much larger thanFSTare consistent with local adaptation driving subpopulations’ trait values apart, andQSTvalues much smaller thanFSTare consistent with stabilizing selection on similar optima. At the same time, investigators have differed in their definitions of genome-wideFST(such as “ratio of averages” vs. “average of ratios” versions ofFST) and in their definitions of the variance components inQST. Here, we show that these details matter. Different versions ofFSTandQSThave different interpretations in terms of coalescence time, and comparing incompatible statistics can lead to elevated type I error rates, with some choices leading to type I error rates near one when the nominal rate is 5%. We conduct simulations under varying genetic architectures and forms of population structure and show how they affect the distribution ofQST. When many loci influence the trait, our simulations support procedures grounded in a coalescent-based framework for neutral phenotytpic differentiation.
Microbial lysates as low-cost serum replacements in cellular agriculture media formulation
Authors: Dolgin James , Chakravarty Damayanti , Sullivan Sean F. , Cai Yiming , Lim Taehwan , Yamaguchi Pomaikaimaikalani , Balkan Joseph E. , Xu Licheng , Olawoyin Aaron D. , Lee Kyongbum , Kaplan David L. , Nair Nikhil U.
Published: November 2024

Cultivated meat, the process of generating meat in vitro without sacrificing animals, is a promising alternative to the traditional practice of livestock agriculture. However, the success of this field depends on finding sustainable and economical replacements for animal-derived and expensive fetal bovine serum (FBS) that is typically used in cell culture processes. Here, we outline an effective screening process to vet the suitability of microbial lysates to support the growth of immortalized bovine satellite cells (iBSCs) and mackerel (Mack1) cells. We show that easily producible, low-cost whole-cell lysates fromVibrio natriegenscan be used to create serum-free media for the long-term growth of iBSCs. The optimized medium, named “VN40” (basal B8 media containing Vibrio natriegens lysate proteins at 40 µg/mL), outperforms previously established serum-free media while maintaining cell phenotype and myogenicity. Overall, this study shows a novel approach to producing serum-free media for cultivated meat production using microbially-derived lysates.
Spatial Profiling of Patient-Matched HER2 Positive Gastric Cancer Reveals Resistance Mechanisms to Trastuzumab and Trastuzumab Deruxtecan
Authors: Sheng Taotao , Sundar Raghav , Srivastava Supriya , Ong Xuewen , Tay Su Ting , Ma Haoran , Uchihara Tomoyuki , Lian Benedict Shi Xiang , Hagihara Takeshi , Xu Chang , Ho Shamaine Wei Ting , Huang Kie Kyon , Tan Angie Lay Keng , NG Michelle Shu Wen , Clara Ng Shi Ya , Nasca Vincenzo , Pircher Chiara Carlotta , Randon Giovanni , Giordano Silvia , Corso Simona , Lum Jeffrey Huey Yew , Teh Ming , So Jimmy Bok Yan , Gasparello Jessica , Fassan Matteo , Pietrantonio Filippo , Tan Patrick
Published: November 2024

PURPOSE

HER2-positive gastric cancer (HER2+ GC) exhibits significant intra-tumoral heterogeneity and frequent development of resistance to HER2-targeted therapies. This study aimed to characterize the spatial tumor microenvironment (TME) in HER2+ GC and identify mechanisms of resistance to HER2 blockade including trastuzumab and trastuzumab deruxtecan (T-DXd), with the goal of informing novel therapeutic strategies.

PATIENTS AND METHODS

We performed spatial transcriptomics on pre-and post-treatment samples from patients with HER2+ metastatic GC who received trastuzumab-based therapy. We also established patient-derived organoids (PDOs) to investigate mechanisms of trastuzumab resistancein vitro.

RESULTS

ERBB2-high tumor regions were found to be "immune cold", characterized by lowPD-L1expression and reduced lymphocyte infiltration. We identified two distinct mechanisms of acquired trastuzumab resistance: epithelial-mesenchymal transition (EMT) and upregulation of the endoplasmic reticulum-associated protein degradation (ERAD) pathway. EMT-positive tumors showed increased expression of immune checkpoints, includingPD-L1, and the chemokineCCL2. Non-EMT tumors exhibited upregulation of the ERAD pathway, highlighting it as a potential therapeutic target. Importantly, we observed increased expression of the promising therapeutic target CLDN18.2, in trastuzumab-resistant tumors. Additionally, loss of HLA was identified as a potential mechanism of resistance to trastuzumab deruxtecan (T-DXd).

CONCLUSION

Our spatial profiling study reveals distinct TME features and resistance mechanisms in HER2+ GC, providing a valuable resource for future research and therapeutic development. The identification of potential therapeutic targets, such as CLDN18.2, may pave the way for novel treatment strategies to overcome resistance and improve outcomes for patients with HER2+ GC.
Transcriptional phenotype of the anti-parasitic benzodiazepine meclonazepam on the blood flukeSchistosoma mansoni
Authors: Henthorn Clair R. , McCusker Paul , Clec’h Winka Le , Chevalier Frédéric D. , Anderson Timothy J.C. , Zamanian Mostafa , Chan John D.
Published: November 2024

There are limited control measures for the disease schistosomiasis, despite the fact that infection with parasitic blood flukes affects hundreds of millions of people worldwide. The current treatment, praziquantel, has been in use since the 1980’s and there is a concern that drug resistance may emerge with continued monotherapy. Given the need for additional antischistosomal drugs, we have re-visited an old lead, meclonazepam. In comparison to praziquantel, there has been relatively little work on its antiparasitic mechanism. Recent findings indicate that praziquantel and meclonazepam act through distinct receptors, making benzodiazepines a promising chemical series for further exploration. Previous work has profiled the transcriptional changes evoked by praziquantel treatment. Here, we examine in detail schistosome phenotypes evoked byin vitroandin vivomeclonazepam treatment. These data confirm that meclonazepam causes extensive tegument damage and directly kills parasites, as measured by pro-apoptotic caspase activation.In vivomeclonazepam exposure results in differential expression of many genes that are divergent in parasitic flatworms, as well as several gene products implicated in blood feeding and regulation of hemostasis in other parasites. Many of these transcripts are also differentially expressed with praziquantel exposure, which may reflect a common schistosome response to the two drugs. However, despite these similarities in drug response, praziquantel-resistant parasites retain susceptibility to meclonazepam’s schistocidal effects. These data provide new insight into the mechanism of antischistosomal benzodiazepines, resolving similarities and differences with the current frontline therapy, praziquantel.
Compensatory Evolution to DNA Replication Stress is Robust to Nutrient Availability
Authors: Natalino Mariana , Fumasoni Marco
Published: November 2024

Evolutionary repair refers to the compensatory evolution that follows perturbations in cellular processes. While evolutionary trajectories are often reproducible, other studies suggest they are shaped by genotype-by-environment (GxE) interactions. Here, we test the predictability of evolutionary repair in response to DNA replication stress—a severe perturbation impairing the conserved mechanisms of DNA synthesis, resulting in genetic instability. We conducted high-throughput experimental evolution on Saccharomycescerevisiaeexperiencing constitutive replication stress, grown under different glucose availabilities. We found that glucose levels impact the physiology and adaptation rate of replication stress mutants. However, the genetics of adaptation show remarkable robustness across environments. Recurrent mutations collectively recapitulated the fitness of evolved lines and are advantageous across macronutrient availability. We also identified a novel role of the mediator complex of RNA polymerase II in adaptation to replicative stress. Our results highlight the robustness and predictability of evolutionary repair mechanisms to DNA replication stress and provide new insights into the evolutionary aspects of genome stability, with potential implications for understanding cancer development.
Population genomics of the invasive Argentine ant (Linepithema humile) – adaptive evolution in the introduced supercolonies despite low genetic diversity
Authors: Holmberg Ida , Paviala Jenni , Pedersen Jes Søe , Helanterä Heikki , Viljakainen Lumi
Published: November 2024

The Argentine ant (Linepithema humile), native to South America, has spread globally over the past 150 years, forming extremely large supercolonies in its introduced range. For example, the European Main supercolony spans over 6,000 km along the Mediterranean coastline. Despite the recent demographic history, including founder effects, Argentine ants thrive in the introduced range and displace native ant species. We took a comprehensive approach to investigate this highly invasive species’ recent demographic history and genome evolution, primarily focusing on introduced supercolonies. We used pooled whole genome sequence data of 100 workers from the species native range and each of the three invasive supercolonies – European Main, Catalonia, and Chile. Invasive supercolonies were highly differentiated from each other and harboured low genetic diversity. Despite this, we could detect signs of positive selection in their genomes – both supercolony-specific and shared patterns. Positively selected genes overlapped the most across invasive supercolonies, indicating altered and shared selective pressure in new habitats. These included, e.g., genes implicated in neurobiological functions. Moreover, we found balancing selection, both supercolony-specific and shared patterns, including many chemical signalling genes. We conclude that introduced Argentine ant supercolonies evolve adaptively, indicating that founder effects and low genetic diversity do not always hamper adaptability.
Evaluating a Cassava Crop Growth Model by Optimizing Genotypic-Specific Parameters Using Multi-environment Trial Breeding Data
Authors: Okoma Pamelas M. , Kayondo Siraj S. , Rabbi Ismail Y. , Moreno-Cadena Patricia L. , Hoogenboom Gerrit , Jannink Jean-Luc
Published: November 2024

Cassava (Manihot esculentaCrantz) is a critical food security crop for sub-Saharan Africa. Efforts to improve cassava through breeding have expanded over the past decade. At the same time, crop growth models (CGM) are becoming common place in breeding efforts to expand the inference of evaluations of breeding germplasm to environments that have not been tested and to prepare for breeding for adaptation to future climates. We parameterized a CGM, the CROPGRO-MANIHOT-Cassava model in the DSSAT family of models, using data on 67 clones from the International Institute of Tropical Agriculture cassava breeding program evaluated from 2017 to 2020 and over eight locations in Nigeria using trial and error parameter adjustments and the General Likelihood Uncertainty Estimation method. Our objectives were to assess the feasibility of this large-scale calibration in the context of a cassava breeding program and to identify systematic biases of the model. For each cultivar we calculated the Pearson correlation between model prediction and observation across the environments, as well as root mean squared error and d statistics. As a result of calibration, the correlation coefficient increased from −0.03 to +0.08, the RMSE dropped from 21 t ha-1to 5 t ha-1while d increased from 0.23 to 0.44. We found that the model underestimated root yield in dry environments (low precipitation and high temperature) and overestimated root yield in wet environments (high precipitation and low temperature). Our experience suggests both that CGM calibration could become a routine component of the cassava breeding data analysis cycle and that there are opportunities for model improvement.
How reliably can species co-occurrence be inferred from occupancy models?
Authors: Louvrier Julie , Fidino Mason , Stuardo Josefa Vergara , Gimenez Olivier
Published: November 2024

Interspecific interactions, such as predation, competition, and mutualism, are fundamental to the structure and function of any biotic community. Understanding these interactions provides valuable insights into community dynamics and informs conservation efforts. One common approach to studying these interactions is through co-occurrence patterns, which remain essential for understanding species relationships. Occupancy models have emerged as powerful tools to investigate these patterns, offering a flexible framework for ecological questions. Among these models, the co-occurrence framework developed by Rota et al. (2016) has seen widespread applications across various species and habitats.

In this study, we used simulations to evaluate the performance of the Rota et al. (2016) co-occurrence model under different study designs and species interaction scenarios. Specifically, we examined how the bias and precision of species occupancy estimates are influenced by the presence or absence of another species, varying the number of sampling units surveyed and the number of temporal replicates per unit. Additionally, we compared the co-occurrence model’s performance with a simpler model that does not account for species interactions to determine when statistically significant co-occurrence patterns emerge.

We observed that occupancy parameters become more precise as the intensity of species avoidance increased, and while the number of sampling sites significantly influenced precision, the number of temporal replicates did not. Notably, the co-occurrence model outperformed the non-interaction model only when species avoidance was strong and at least 150 sites were sampled. Based on these results, we recommend a minimum of 150 sampling sites when applying the Rota et al. (2016) model to evaluate co-occurrence between two potentially interacting species. Our study emphasizes the need for further development of methods capable of detecting interaction signals, even at low to moderate interaction levels, and in studies with fewer sampling sites.
Single-Cell Atlas of AML Reveals Age-Related Gene Regulatory Networks in t(8;21) AML
Authors: Whittle Jessica , Meyer Stefan , Lacaud Georges , Baker Syed Murtuza , Iqbal Mudassar
Published: November 2024

Background

Acute myeloid leukemia (AML) is characterized by cellular and genetic heterogeneity, which correlates with clinical course. Although single-cell RNA sequencing (scRNA-seq) reflect this diversity to some extent, the low sample numbers in individual studies limit the analytic potential of comparisons of specific patient groups.

Results

We performed large scale integration of published scRNA-seq datasets to create a unique single-cell transcriptomic atlas for AML (AML scAtlas), totaling 748,679 cells, from 159 AML patients and 44 healthy donors from 20 different studies. This is the largest single-cell data resource for AML to our knowledge, publicly available athttps://cellxgene.bmh.manchester.ac.uk/AML/. This AML scAtlas, allowed exploration of the clinical importance of age in t(8;21) AML to an unprecedented level, given thein-uteroorigin of pediatric disease. We uncovered age-associated gene regulatory network (GRN) signatures, which we validated using bulk RNA sequencing data to delineate distinct groups with divergent biological characteristics. Furthermore, using an additional multiomic dataset (scRNA-seq and scATAC-seq), we created a de-noised GRN reflecting the previously defined age-related signatures.

Conclusions

Applying integrated data analysis of the AML scAtlas, we reveal age-dependent gene regulation in t(8;21), perhaps reflecting immature/fetal HSC origin in prenatal origin disease vs postnatal origin. Our analysis revealed that BCLAF1, which is particularly enriched in t(8;21) pediatric AML of inferredin-uteroorigin, is a promising prognostic indicator. The AML scAtlas provides a powerful resource to investigate molecular mechanisms underlying different AML subtypes.
Tools for intersectional optical and chemical tagging on cell surfaces
Authors: Innes-Gold Sarah , Cheng Hanzeng , Liu Luping , Cohen Adam E.
Published: November 2024

We present versatile tools for intersectional optical and chemical tagging of live cells. Photocaged tetrazines serve as “photo-click” adapters between recognition groups on the cell surface and diverse chemical payloads. We describe two new functionalized photocaged tetrazine structures which add a light-gating step to three common cell-targeting chemical methods: HaloTag/chloroalkane labeling, nonspecific primary amine labeling, and antibody labeling. We demonstrate light-gated versions of these three techniques in live cultured cells. We then explore two applications: monitoring tissue flows on the surface of developing zebrafish embryos, and combinatorial multicolor labeling and sorting of optically defined groups of cells. Photo-click adapters add optical control to cell tagging schemes, with modularity in both tag and cell attachment chemistry.
Isotonic medium treatment limits burn wound microbial colonization and improves tissue repair
Authors: Horn Adam , Wagner Andrew S. , Hou Yiran , Zajac Jocelyn C. , Fister Alexandra M. , Chen Zhili , Pashaj Joana , Junak Mary , Mercado Soto Nayanna M. , Gibson Angela , Huttenlocher Anna
Published: November 2024

Burn injuries undergo a complex healing process in which progressive spreading of epithelial damage can lead to secondary complications such as wound infection, which is a major driver of mortality among burn patients. We recently reported that burning larval zebrafish triggers dysregulated keratinocyte dynamics compared to mechanical injury. Here, we investigate keratinocyte behavior following burn injury and the subsequent potential for microbial colonization of burn wounds over time. Real-time imaging, coupled with tracking of photoconverted cells, revealed that early keratinocyte motility contributes to the spread of epithelial damage beyond the initial site of burn injury and that increased epithelial damage was associated with wound colonization by the fungal pathogenCandida albicans. Modulating osmotic balance by treating larval zebrafish with isotonic medium limited the spread of epithelial damage and reduced microbial colonization of burn wounds. Using cultured human skin, we found that topical treatment with isotonic solution (saline) similarly prevented the spread of epithelial damage over time. These findings indicate that keratinocyte behavior contribute to burn wound progression in larval zebrafish and link keratinocyte dynamics to microbial colonization of burn wounded tissue.
Exogenous ephrin-A3 administration restores vaginal epithelial barrier function in progestin-treated mice
Authors: Liu Mohan , Miguel Rodolfo D Vicetti , Aceves Kristen , Cherpes Thomas L
Published: November 2024

Desmosomes are junctional complexes that confer mechanical strength and enhance epithelial barrier function at mucosal surfaces by anchoring intermediate filaments to plasma membrane. While these roles are less explored in vaginal vs. cutaneous epithelium, we previously reported that treating mice with the progestin depot medroxyprogesterone acetate (DMPA) reduces vaginal epithelial levels of the desmosomal cadherins desmoglein-1 (DSG1) and desmocollin-1 (DSC1) and weakens vaginal epithelial barrier function. We also showed these effects were avoided by treating mice with DMPA and a conjugated equine estrogen vaginal cream. The current investigation further explored the effects of sex steroids on vaginal epithelial integrity, identifying ephrin-A3 (EFNA3) as a key regulator of desmosomal cadherin gene expression. We observed topical administration of recombinant EFNA3 (rEFNA3) promotes vaginal DSG1 expression in a biphasic dose-dependent manner and partially reverses the loss of vaginal epithelial barrier function induced by DMPA treatment. Consistent with this effect, morbidity and mortality elicited by genital herpes simplex virus type 2 infection were delayed, but not prevented, in mice administered DMPA and rEFNA3 vs. DMPA and vehicle. Together, these studies identify EFNA3 as an important regulator of desmosomal function in vaginal epithelium and improve current understanding of sex steroid-mediated mechanisms that control vaginal epithelial barrier function.
Golden eagles regularly use gravity waves to soar in the Alps: new insights from high-resolution weather data
Authors: Carrard Tom , Nourani Elham , Jansing Lukas , Zimmermann Tim , Sumasgutner Petra , Tschumi Matthias , Jenny David , Wikelski Martin , Safi Kamran , Sprenger Michael , Scacco Martina
Published: November 2024

1

Soaring flight developed as a result of behavioural and morphological adaptations that allow birds to reduce the metabolic cost of flight by harnessing the energy available in the atmosphere. Despite an increased attention given in the last decades to the physics and ecology that allow soaring flight, its study has been limited by the generally low spatio-temporal resolution of available atmospheric data. This constrained our ability to quantify the atmospheric conditions that allow soaring, and limited our understanding of its flexibility in different uplift conditions. While the use of updraughts such as thermals and orographic lifting are well described in the literature (albeit only quantified through atmospheric proxies), the use of others, such as gravity waves, was hypothesised but largely undocumented. Recent advancements in high-resolution atmospheric modelling, with hourly output available at the kilometer-scale grid spacing, offer new opportunities to investigate the flexibility of soaring flight in response to complex atmospheric dynamics. In this study, we used a combination of a high-resolution atmospheric analysis and high-resolution GPS tracking data to characterise the updraught sources used by golden eagles,Aquila chrysaetos, in the European Alps. We document that golden eagles in this region repeatedly use gravity waves, and that while thermals were still the main updraught source used for soaring, gravity waves were involved in at least 19% of the inspected soaring segments. In winter, when thermals were more scarce, the quasi-totality of soaring events were powered by gravity waves or orographic lifting, largely expanding the environmental energy available to soaring birds and therefore the landscape connectivity in topographically complex regions. Our results also emphasise the difficulty to distinguish between convective (thermals) and dynamic updraught sources, as these co-occur within the boundary layer over complex terrain.
Do short-term responses to product manipulation health warnings predict subsequent quitting-related behaviours? Findings from an Australian cohort study
Authors: Brennan Emily , Gascoyne Claudia , Dunstone Kimberley , Thrasher James F , Hoek Janet , Wakefield Melanie , Durkin Sarah
Published: November 2024

Background

Pictorial health warnings on tobacco packs can stimulate short-term cognitive and emotional responses that lead to quit attempts. We tested novel product attribute health warnings (PAHWs) that corrected misperceptions about harm created by the use of filter-venting, menthol and roll-your-own tobacco. PAHWs uniquely influenced outcomes assessing knowledge of industry manipulation of cigarettes, industry-centric negative emotional responses, and product-specific smoking dissonance. In this study, we examined if these unique short-term responses predicted subsequent quitting-related behaviours.

Method

We analysed follow-up data from a between-subjects online experiment that assessed effects of new PAHWs. Participants were randomised to view PAHWs alone (PAHW condition) or with a complementary video (PAHW+Video), and exposure occurred during a baseline session and then repeatedly each day for 7 days. Short-term PAHW responses were measured at 8-day follow-up (N=712). Quitting-related behaviours were measured at 4-week follow-up (N=301). Covariate-adjusted logistic regression models examined associations between short-term PAHW responses and subsequent quitting-related behaviours.

Results

Two of the short-term responses – knowledge of industry manipulation of cigarettes, and product-specific smoking dissonance – significantly and positively predicted all three quitting-related outcomes: smoke-limiting micro-behaviours (e.g., foregoing cigarettes), quit attempts, and 7-day sustained abstinence. Additionally, industry-centric negative emotional responses significantly and positively predicted smoke-limiting micro-behaviours and 7-day sustained abstinence, but not quit attempts.

Conclusion

PAHWs featuring corrective information about the tobacco industry’s manipulation of tobacco products elicited short-term responses that predicted subsequent engagement in smoke-limiting micro-behaviours, quit attempts, and sustained quit attempts. PAHWs can complement other health warnings featuring the health risks of smoking and may help motivate people who smoke to quit and stay quit.
Sperm sequencing reveals extensive positive selection in the male germline
Authors: Neville Matthew DC , Lawson Andrew RJ , Sanghvi Rashesh , Abascal Federico , Pham My H , Cagan Alex , Nicola Pantelis A , Bayzetinova Tetyana , Baez-Ortega Adrian , Roberts Kirsty , Lensing Stefanie V. , Widaa Sara , Alcantara Raul E , García María Paz , Wadge Sam , Stratton Michael R , Campbell Peter J , Small Kerrin , Martincorena Iñigo , Hurles Matthew E , Rahbari Raheleh
Published: November 2024

Mutations that occur in the cell lineages of sperm or eggs can be transmitted to offspring. In humans, positive selection of driver mutations during spermatogenesis is known to increase the birth prevalence of certain developmental disorders. Until recently, characterising the extent of this selection in sperm has been limited by the error rates of sequencing technologies. Using the duplex sequencing method NanoSeq, we sequenced 81 bulk sperm samples from individuals aged 24 to 75 years. Our findings revealed a linear accumulation of 1.67 (95% CI = 1.41-1.92) mutations per year per haploid genome, driven by two mutational signatures associated with human ageing. Deep targeted and exome NanoSeq of sperm samples identified over 35,000 germline coding mutations. We detected 40 genes (31 novel) under significant positive selection in the male germline, implicating both activating and loss-of-function mechanisms and diverse cellular pathways. Most positively selected genes are associated with developmental or cancer predisposition disorders in children, while four genes that exhibit elevated frequencies of protein-truncating variants in healthy populations. We find that positive selection during spermatogenesis drives a 2-3 fold elevated risk of known disease-causing mutations in sperm, resulting in 3-5% of sperm from middle-aged to elderly individuals carrying a pathogenic mutation across the exome. These findings shed light on the dynamics of germline mutations and highlight a broader increased disease risk for children born to fathers of advanced age than previously appreciated.
Device-measured moderate-to-vigorous physical activity and prognosis of inflammatory bowel disease
Authors: He Zixuan , Sun Yuhao , Huang Hanyi , Liu Yilong , Dan Lintao , Ruan Xixian , Fu Tian , Li Zhaoshen , Wang Xiaoyan , Chen Jie , Bai Yu
Published: November 2024

Importance

Evidence on physical activity recommendations for inflammatory bowel disease (IBD) patients is limited, with concerns about high-intensity activity.

Objective

To investigate the associations of accelerometer-measured moderate-to-vigorous physical activity (MVPA) with bowel resection risk and mortality among individuals with IBD.

Design, setting, and participants

This longitudinal cohort study collected data from 1,303 UK Biobank participants with IBD diagnosis and device-measured physical activity from 2013 to 2015, with follow-up data examined until 2022.

Exposures

MVPA was classified based on data measured by wrist-worn accelerometers over a 7-day period. MVPA patterns were defined as inactive (< 150 minutes/week), active weekend warrior (≥ 150 minutes/week, ≥50% of total MVPA achieved in 1-2 days), and regularly active (≥ 150 minutes/week, not active weekend warrior).

Main Outcomes and Measures

The bowel resection was identified through operational records from hospital inpatient data of the National Health Service. Deaths were documented through linkage to the national death register. Associations were estimated using multivariable Cox regression models and nonlinearity was assessed by restricted cubic spline.

Results

During a median follow-up of 7.8 years, 56 incident bowel resection cases and 86 deaths were documented. After multivariable adjustment, participants in the highest tertile of MVPA duration had lower risks of bowel resection (HR, 0.44; 95% CI, 0.22-0.86) and mortality (HR, 0.49; 95% CI, 0.27-0.89) compared to those in the lowest tertile. MVPA duration is linearly associated with bowel resection (Pnon-linear= 0.13) while its dose-response relationship with mortality plateaus at approximately 58 min/day (Pnon-linear= 0.02). Regarding MVPA patterns, the active weekend warrior pattern was inversely associated with bowel resection risk (HR, 0.28; 95% CI, 0.12-0.65), the regularly active pattern was inversely associated with both bowel resection risk (HR, 0.37; 95% CI, 0.19-0.69) and mortality (HR, 0.53; 95% CI, 0.31-0.91) compared to the inactive.

Conclusion and relevance

Longer accelerometer-measured MVPA was associated with reduced bowel resection risk and mortality. The regularly active pattern may be the optimal choice for individuals with IBD, while the active weekend warrior pattern still provides health benefits compared to being inactive.
Clinical Characteristics Associated with Functional Seizures in Individuals with Psychosis
Authors: Lake Allison M. , Reddy India A. , Havranek Robert , Davis Lea K. , Fox Jonah
Published: November 2024

Background and Hypothesis

Functional seizures (FS) are episodes characterized by seizure-like events that are not caused by hypersynchronous neuronal activity. Prior studies have suggested an increased prevalence of psychotic disorders among patients with FS, but results have been inconsistent. We hypothesize that FS are associated with psychosis and that among patients with psychosis, the presence of FS may influence patient clinical characteristics, mortality, and medical resource utilization.

Study Design

The association between FS and psychosis was assessed using electronic health records data from a total of 752,883 individuals receiving care at Vanderbilt University Medical Center between 1989 and 2023. Analyses of the association between FS and psychiatric outcomes, sexual trauma, healthcare utilization, and other clinical comorbidities were conducted in a subset of 5,239 patients with psychosis.

Study Results

Odds of FS were elevated among patients with psychosis compared to controls (OR=10.17, 95% CI=8.55-12.08, p<0.001). Among patients with psychosis, those with FS exhibited higher rates of suicidality (OR=1.98, 95% CI=1.40-2.8, p<0.001), catatonia (OR=1.95, 95% CI=1.23-3.09, p=0.03), sexual trauma history (OR=2.98, 95% CI=2.08-4.26, p<0.001) and had a greater numbers of antipsychotic trials (4.56 versus 3.37, beta=1.16, SE=0.16, p<0.001) than those without FS. Furthermore, patients with comorbid FS had a greater numbers of hospital presentations at one, three, five, and ten years after receiving a psychosis diagnosis (p<0.001).

Conclusions

FS are more common among patients with psychosis and are associated with increased healthcare utilization as well as an increased prevalence of suicidality, catatonia, and certain psychiatric and medical comorbidities.
Contrasting dissemination patterns of diploid cultivated cotton speciesGossypium herbaceumL. andG. arboreumL. in Antiquity
Authors: Viot Christopher R.
Published: November 2024

The textile use of cotton fibers from sister speciesGossypium arboreumL. (Tree Cotton) andG. herbaceumL. (Levant Cotton) began, respectively, in Asia in the eighth millennium BP and in Africa in the third millennium BP and probably earlier. Archaeological data show that cotton cultivation spread in the Antiquity over most tropical and subtropical regions suitable for agriculture in Afroeurasia. The geographical expansions of the two Old World cotton species appear very contrasted, in terms of their chronologies, in terms of the areas conquered, and as for their speed of diffusion.G. arboreumspread over humid or sub-humid regions of southern, western and eastern Asia atca. 0.8 to 1.7 km/yr, a rate close to that estimated for wheat from the Fertile Crescent to northwestern Europe during Antiquity, whileG. herbaceumspread over arid to sub-arid regions of Africa and western and central Asia, much later and more than five times faster thanG. arboreum. The very high speed of diffusion ofG. herbaceumcan be explained by the context and by the agricultural adaptations of this species but also leads to revisit the history of its domestication and beginning of cultivation.
Combined phylogenetic and geographic data can predict plant-pest interactions with high accuracy
Authors: Hernández-Gutiérrez Elvira , Nichols Richard A. , Kelly Laura J.
Published: November 2024

Biological invasions are a major threat to biodiversity, often having destructive ecological and economic consequences. It is therefore essential to concentrate the limited resources available on managing the most serious risks. We build a robust Bayesian model to predict host species at risk fromAgrilus, a genus of plant-feeding beetles that includes one of the world’s most destructive tree pests. The model uses the interplay of phylogenetic and geographic distance between known and potential hosts to estimate the probability of newAgrilus-host interactions. We assess the risk these beetles pose toQuercusspecies (oaks), their most common host, and find that our model can assign the status of known hosts with an accuracy of 83.6% in leave-one-out analyses. We employ this model to identify oak species at risk fromAgrilus,providing data to inform more targeted efforts to prevent novelAgrilusintroductions. Our model correctly identifies recently acquired novel hosts ofAgrilusspecies that have invaded new areas, providing further evidence of its ability to accurately predict future potential interactions. Our approach makes use of readily available phylogenetic and geographic occurrence data and could be widely implemented to assess other potential invasive species, and help to prioritise counter measures against different threats worldwide.
NuclampFISH enables cell sorting based on nuclear RNA expression for chromatin analysis
Authors: Liu Yifang , Qiu Yuchen , Nian Keqing , Rouhanifard Sara H.
Published: November 2024

Transcriptional bursts refer to periods when RNA polymerase interacts with a DNA locus, leading to active gene transcription. This bursting activity can vary across individual cells, and analyzing the differences in transcription sites can help identify key drivers of gene expression for a specific target. Scaffolding methods based on fluorescence in situ hybridization (FISH) have been widely used to amplify the fluorescent signal of mRNAs and sort cells based on mRNA expression levels. However, these methods are inefficient at targeting nuclear RNA, including transcription sites, due to the probes’ limited accessibility through cellular compartment membranes and crosslinked proteins. Additionally, the required formaldehyde fixation interferes with downstream analysis of chromatin and protein-binding interactions. To address these challenges, a platform that integrates amplified FISH with reversible crosslinkers and allows access to the nucleus is needed. In response, we developed nuclear clampFISH (nuclampFISH). This method amplifies the fluorescent signal of mRNAs using a reversible crosslinker, enabling the sorting of cells based on nuclear RNA expression and compatible with downstream biochemical analysis. This assay demonstrates that transcriptionally active cells have more accessible chromatin for a respective gene. Notably, the tools developed are highly accessible and do not require specialized computation or equipment.
Investigating Short-Chain Fatty Acids Effects on Extracellular Vesicles Production in Colorectal Cancer
Authors: Macedo D. , Abalde-Cela S. , Diéguez L. , Preto A. , Honrado C.
Published: November 2024

Colorectal cancer (CRC) is the third most diagnosed and the second leading cause of cancer-related deaths globally, often due to late detection and limited treatment options. Recent studies have linked alterations in gut microbiota to CRC, particularly emphasizing the role of short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate in shaping the tumor microenvironment (TME). SCFAs contribute to CRC pathogenesis by inducing lysosomal membrane permeabilization, cell cycle arrest, and apoptosis in cancer cells. Extracellular vesicles (EVs) are membrane-bound vesicles that facilitate intercellular communication and have gained attention as promising non-invasive biomarkers for cancer diagnosis and treatment monitoring. EVs participate in cellular response mechanisms to external stimuli by transferring proteins, lipids, and nucleic acids between cells, thus modulating target cell behavior and promoting coordinated responses to stress and environmental challenges. This process is essential for cellular adaptation and plays a significant role in pathophysiological processes, including tumor progression and immune modulation, making EVs highly relevant in clinical research. This study examined the impact of SCFAs on EV production and phenotype in CRC cells. The results indicated a notable increase in EV-sized particles following SCFA treatment of colorectal cell lines, particularly in the SW480 CRC cell line. For CRC cell lines, while co-precipitated protein levels remained stable, there was a slight decrease in cellular DNA and an increase in EV-associated DNA. KRAS-mutant SW480 cells exhibited the most pronounced response, emphasizing their heightened sensitivity to SCFA. Notably, microsatellite instability - a key biomarker for immunotherapy in CRC - was detected in both small and large EV populations from BRAF-mutant RKO cells after SCFA treatment, even at low DNA concentrations. These findings underscore the potential of EVs for non-invasive detection of molecular markers, paving the way for further exploration of their role in precision oncology.

Abstract Figure

Graphical Abstract.

Effects of SCFA on EV production and characteristics in CRC cells. Treatment with SCFA led to a significant increase in the number of EV-sized particles, a decrease in cellular DNA and a corresponding increase in EV-DNA. This study also identified MSI in both s-EV and L-EV, even following SCFA treatment and at low DNA concentrations. Created using BioRender.