bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Coronoid Process as a Free Graft for Condylar Reconstruction in a Patient With Condylar Osteoma: A Condylar Reconstruction Technical Note (Technical Strategy)
Authors: Yehia Mahmoud , Ahmed Mostafa Ezz Elarab , El Fadly Mahmoud Abd El Aziz
Published: January 2025

Osteoma is a rare, asymptomatic, and slowly growing benign tumor of bone. Upon reviewing the literature, only 21 cases were previously reported in the mandibular condyle. A 19-year-old male patient presented to the Department of Oral and Maxillofacial Surgery of Ain Shams University complaining of hypomobility and facial asymmetry involving the lower jaw. He stated that he was involved in a road traffic accident (RTA) and sustained a traumatic injury to the head a few years ago. Upon examination, it was noticed that the chin deviated to the right side with some discomfort during function. Computed tomography scans revealed the presence of a hyperdense mass medial to the right condylar pole. Condylectomy was carried out using a preauricular approach. A diagnosis of osteoma was confirmed histopathologically. The defect was reconstructed using the coronoid process as an autogenous-free graft.
Posterior Peroral Endoscopic Myotomy With Versus Without Sparing of the Oblique/Sling Fibers: A Meta-analysis
Authors: Diab Abdul-Rahman F. , Sujka Joseph A. , Patel Heena , Jegathesan Saarangan , Cruz Bou Alessandra , Docimo Salvatore , DuCoin Christopher G.
Published: January 2025

Background and Aims:

Several studies have hypothesized that sparing the oblique/sling fibers during posterior peroral endoscopic myotomy (POEM) may reduce the incidence of gastroesophageal reflux disease (GERD) and reflux esophagitis without compromising the established safety and efficacy of the procedure. This study compares perioperative, postoperative motility-related, and postoperative GERD-related outcomes between posterior oblique/sling fibers-sparing POEM (OFS-POEM) and conventional posterior POEM through a pairwise meta-analysis of comparative studies.

Methods:

We conducted a systematic literature review following PRISMA guidelines to identify articles directly comparing posterior OFS-POEM with conventional posterior POEM. A pairwise meta-analysis was performed using a random-effects model. Effect sizes were calculated as odds ratios for dichotomous data and mean differences for continuous data.

Results:

No significant differences were observed in perioperative outcomes, including mean gastric myotomy length, mean operative time, and incidence of adverse events. Similarly, no significant differences were noted in postoperative motility-related outcomes, such as mean Eckardt score and mean integrated relaxation pressure. However, a statistically significant reduction in the incidence of symptomatic GERD was observed in favor of OFS-POEM, with a number needed to treat (NNT) of 10 (95% CI: 6-49). Interestingly, no significant differences were found in the incidence of objectively diagnosed postoperative GERD, such as the number of patients with DeMeester scores >14 or the incidence of reflux esophagitis.

Conclusions:

This study suggests that OFS-POEM may reduce the incidence of symptomatic GERD following POEM, without affecting the incidence of GERD diagnosed by pH studies (DeMeester score >14) or by endoscopy (reflux esophagitis). Future studies with larger sample sizes are needed to further investigate the impact of OFS-POEM on GERD incidence as determined by pH studies and endoscopic findings. Given the limitations of this study, no definitive conclusions can be drawn. Multicenter randomized controlled trials with larger sample sizes are required to reach more reliable conclusions. Furthermore, stratifying data according to the type and class of achalasia would provide valuable information on whether there are differences in outcomes among the various types and classes of achalasia.
Mean mares? Habitat features influence female aggression in response to social instability in the feral horse (
Equus caballus
)
Authors: Nuñez Cassandra M. V. , Adelman James S.
Published: January 2025

It is unclear how habitat features alter animal responses to social instability. Only by uncovering such interactions can we fully understand the evolutionary drivers and fitness consequences of sociality. We capitalize on a management-induced manipulation of social stability in an island population of free-ranging feral horses (
Equus caballus
), living across three distinct habitat types. We tested whether female group-changing behaviour (a reliable measure of social instability) affected (i) female–female aggression, (ii) rank within female dominance hierarchies, (iii) stability of female hierarchies (in the groups they joined and/or left), and (iv) how habitat characteristics shaped these responses. Female group-changing behaviour positively predicted aggression from other females, but only when habitat features such as visibility and freshwater distribution were considered. We found no strong association among female group-changing behaviour and the aggression initiated, female rank or the stability of female dominance hierarchies. Our work reveals that animal responses to social instability are nuanced and impacted by the surrounding habitat. A better understanding of these impacts can help elucidate evolutionary drivers of sociality and mitigate unintended effects of management practices.
RNA splicing: a split consensus reveals two major 5′ splice site classes
Authors: Parker Matthew T. , Fica Sebastian M. , Simpson Gordon G.
Published: January 2025

The established consensus sequence for human 5′ splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5′ splice site classes are separable in genome sequences, sensitized by specific genotypes and associated with splicing complexity. The two classes reflect the commitment to 5′ splice site usage occurring primarily during 5′ splice site transfer to U6 snRNA. Separating the human 5′ splice site consensus into its two major constituents can help us understand fundamental features of eukaryote genome architecture and splicing mechanisms and inform treatment design for diseases caused by genetic variation affecting splicing.
A simple inland culture system provides insights into ascidian post-embryonic developmental physiology
Authors: Mathiesen Birthe Thuesen , Ohta Mayu , Magalhaes Boris Pinto De , Castelletti Chiara , Perria Vincenzo , Schuster Keaton , Christiaen Lionel , Ohta Naoyuki
Published: January 2025

Maintenance and breeding of experimental organisms are fundamental to life sciences, but both initial and running costs, and hands-on zootechnical demands can be challenging for many laboratories. Here, we first aimed to further develop a simple protocol for reliable inland culture of tunicate model species of the
Ciona
genus. We cultured both
Ciona robusta
and
Ciona intestinalis
in controlled experimental conditions, with a focus on dietary variables, and quantified growth and maturation parameters. From statistical analysis of these standardized datasets, we gained insights into the post-embryonic developmental physiology of
Ciona
and inferred an improved diet and culturing conditions for sexual maturation. We showed that body length is a critical determinant of both somatic and sexual maturation, which suggests the existence of systemic control mechanisms of resource allocation towards somatic growth or maturation and supports applying size selection as a predictor of reproductive fitness in our inland culture to keep the healthiest animals at low density in the system. In the end, we successfully established a new protocol, including size selection, to promote both sperm and egg production. Our protocol using small tanks will empower researchers to initiate inland
Ciona
cultures with low costs and reduced space constraints.
The smallest
Zosterophyllum
plant from the Lower Devonian of South China and the divergent life-history strategies in zosterophyllopsids
Authors: Huang Pu , Wang Jia-Shu , Wang Yi-Ling , Liu Lu , Zhao Jing-Yu , Xue Jin-Zhuang
Published: January 2025

Plants have evolved different life-history strategies to overcome limited amounts of available resources; however, when and how divergent strategies of sexual reproduction evolved in early land plants are not well understood. As one of the notable and vital components of early terrestrial vegetation, the Zosterophyllopsida and its type genus
Zosterophyllum
reached maximum species diversity during the Pragian (Early Devonian;
ca
410.8–407.6 million years ago). Here we describe a new species,
Zosterophyllum baoyangense
sp. nov., based on well-preserved specimens from the Pragian-aged Mangshan Group of Duyun, Guizhou Province, China. The new plant is characterized by its small size, K-shaped branching and tiny spikes with 5–10 sporangia. This plant is most likely
r
-selected, completing its whole lifespan in a short time, and such a strategy contributes to reproduction in a suitable window time. In contrast, most other species of
Zosterophyllum
and the zosterophyllopsids on a broader scale are larger in body size and have greater investments in fertile tissues, reflected in the size and total number of sporangia. We argue that the zosterophyllopsids probably benefited from the divergence of various life-history strategies and thus constituted a major part of the Early Devonian floras.
Pseudomonas retamae sp. nov., a novel endophytic bacterium with plant growth-promoting potential, isolated from root nodules of Retama monosperma in Northwestern Algeria
Authors: Selami Nawel , Zitouni-Haouar Fatima El-Houaria , Zerouki Chahira , Aibeche Chahrazed , Draou Nassima , Khelil Omar , Choubane Slimane , Maatallah Makaoui , Madani Ikram , Ouenzar Khadidja , Zemmour Assia , Kerkoud Mohamed , Mnasri Bacem , Moumen Bouziane , Vriet Cécile , Djabeur Abderrezak
Published: January 2025

A thorough polyphasic taxonomic study, integrating genome-based taxonomic approaches, was carried out to characterize the RB5T strain isolated from root nodules of Retama monosperma growing on the coastal dunes of Bousfer Beach (Oran, Algeria). The 16S rRNA gene sequence analysis revealed that strain RB5T had the highest similarity to Pseudomonas granadensis LMG27940T (98.94%) and Pseudomonas gozinkensis IzPS32dT (98.73%). Phylogenetic studies, including both 16S rRNA gene sequence and multilocus sequence analysis using 16S rRNA, gyrB and rpoD housekeeping genes, positioned RB5T in a distinct branch alongside its closest relative, P. granadensis LMG27940T. Phylogenomic analysis using the Bac120 marker set and Type (Strain) Genome Server confirmed the unique position of RB5T and its close relationship with P. granadensis LMG27940T. Similarly, genomic comparisons using average nucleotide identity based on blast (ANIb) and digital DNA–DNA hybridization (dDDH) revealed values of 92.85 and 59.3%, respectively, when compared with its closest relative, P. granadensis LMG27940T. Both values fall below the established species delimitation thresholds of 95–96% for ANIb and 70% for dDDH, providing strong genomic evidence that strain RB5T represents a novel species. Further average nucleotide identity comparisons with unclassified Pseudomonas spp. (384 genomes) and metagenomic-derived genomes from the Genome Taxonomy Database (GTDB) showed values between 84.27 and 89.2%, indicating that strain RB5T belongs to a unique evolutionary line. The genome of RB5T, with a size of 6 311 310 bp and a G+C content of 60%, harbours several key genes associated with plant growth-promoting traits, making it a promising candidate for sustainable agriculture. Phenotypically, RB5T strain is an aerobic, rod-shaped, Gram-negative, non-spore-forming bacterium that is motile with a single polar flagellum. It grows under a wide range of temperature (4–42 °C) and pH (5–10) conditions and tolerates up to 6% (w/v) NaCl. The main cellular fatty acid composition of RB5T includes C16:0, C17:0 cyclo and the summed features 3 consisting of C16:1 ω7c/C16:1 ω6c. Based on the phylogenetic, phenotypic, chemotaxonomic and genome comparison analyses, strain RB5T was identified as a novel species of the genus Pseudomonas, for which the name Pseudomonas retamae sp. nov. is proposed. The type strain is RB5T (=DSM 117471T=LMG 33633T=CIP 112482T).
Global DNA methylomes reveal oncogenic-associated 5-hydroxylmethylated cytosine (5hmC) signatures in the cell-free DNA of cancer patients
Authors: Rech Gabriel E. , Lau Alyssa C. , Goldfeder Rachel L. , Maurya Rahul , Danilov Alexey V. , Wei Chia-Lin
Published: January 2025

Characterization of tumor epigenetic aberrations is integral to understanding the mechanisms of tumorigenesis and provide diagnostic, prognostic, and predictive information of high clinical relevance. Among the different tumor-associated epigenetic signatures, 5 methyl-cytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the two most well-characterized DNA methylation alterations linked to cancer pathogenesis. 5hmC has a tissue-specific distribution and its abundance is subjected to changes in tumor DNA, making it a promising biomarker. Detecting tumor-related DNA methylation alterations in tissues is highly invasive, while the analysis of the cell-free DNA (cfDNA) is poised to supplement, if not replace, surgical biopsies. Despite many studies attempted to identify new epigenetic targets for liquid biopsy assays, little is known about the regulatory roles of 5hmC, its impacts on the molecular phenotypes in tumors. Most importantly, whether the oncogenic-associated 5hmC signatures found in tumor tissues can be recapitulated in patients’ cfDNA. In this study, we performed the unbiased and simultaneous detection of 5mC and 5hmC whole-genome DNA modifications at base-resolution from two distinct cancer cohorts, from patients with bladder cancer or B-Cell lymphoma, their corresponding normal tissues, and cfDNAs from plasma. We analyzed tissue-specific methylation patters and searched for signatures in gene coding and regulatory regions linked to cancerous states. We then looked for methylation signatures in patients’ cfDNA to determine if they were consistent with the tumor-specific patterns. We determined the functional significance of 5hmC in tissue specific transcription and uncovered hundreds of tumor-associated 5hmC signatures. These tumor-associated 5hmC changes, particularly in genes and enhancers, were functionally significant in tumorigenesis pathways and correlated with tumor specific gene expression. To investigate if cfDNA is a faithful surrogate for tumor-associated 5hmC, we devised a targeted capture strategy to examine the alterations of 5hmC in cfDNA from patients with bladder cancer and lymphoma with sufficient sensitivity and specificity and confirmed that they recapitulated the patterns we observed in tumor tissues. Our results provide analytic validation of 5hmC as a cancer-specific biomarker. The methods described here for systematic characterization of 5hmC at functional elements open new avenues to discover epigenetic markers for non-invasive diagnosis, monitoring, and stratifying cancer.
Planting 10 Million Trees with Lukenya University in Kenya: Methodology and Preliminary Observations and Forecasts
Authors: Kyalo Protus , Kungurtsev Vyacheslav , Muli Esther , Pietsch Stephan , Mugo Kennedy , Kaigongi Margrate , Muasa Martin , Wafula Judith , Muvela Sammy , Mutua Charles
Published: January 2025

Lukenya University has recently begun implementing a Ten Million Tree Growing Initiative, as part a larger national multi-institutional country-wide tree growing program. In this paper we describe the methods used as far as tree selection and the planting itself. Note that most of the trees are not planted directly by the institution by given to farmers to plant on their land, with instruction as to how to choose a location and how to technically perform the planting and maintenance to ensure greater success for the tree and the environment surrounding it. This knowledge arises out of years of experience as far as both the biology of planting and the social interaction with smallholder farmer communities. We kept track of the survival and growth of a subsample of a number of different tree species. After about two years of operation, we performed a statistical analysis on preliminary data. We observe statistically significant advantages to survival and relative growth volume to indigenous trees and the aforementioned comprehensive instruction before plotting, among other observations we relate from the hypothesis tests performed. Finally, we present estimates of the carbon sequestration and economic value of the trees to the community. Summarizing, the paper presents a comprehensive transparent display of a tree growing initiative, a common endeavor motivated to maximize social welfare and climate change resilience, and in so doing can develop the knowledge of best practices for these purposes.
New reproduction numbers for the visible and real epidemic dynamics
Authors: Nesteruk Igor
Published: January 2025

Known basic and effective reproduction numbers are based on registered (visible) cases despite that asymptomatic and unregistered patients are characteristic of almost all infection diseases. New reproduction numbers - the ratios of the real numbers of infectious persons (symptomatic and asymptomatic) at different moments of time and a simple method of their estimation with the use of visible (registered) cases only were proposed. The novel general SIR (susceptible-infectious-removed) model was used and the results of calculations for the pertussis epidemic in England are presented. New approach could help to control different epidemics, in particular new waves of COVID-19.
Feasibility, acceptability and clinical outcomes of a real-world, regional lung cancer prehabilitation programme for patients undergoing curative intent radiotherapy
Authors: Gourlay Ewan , Banfill Kathryn , Merchant Zoe , Goodley Patrick , Brown Louise , Murphy Jack , Moore John , Evison Matthew
Published: January 2025

Introduction

Prehabilitation improves both physiological measurements and clinical outcomes for patients undergoing surgery for lung cancer. The feasibility, acceptability and efficacy of prehabilitation for patients having curative-intent radiotherapy for lung cancer is uncertain.

Methods

Prehab4Cancer (P4C) is a regional, community-based prehabilitation service for patients with cancer in Greater Manchester in the United Kingdom. We present an evaluation of the P4C service for patients undergoing curative-intent radiotherapy for lung cancer over a 2-year period. Feasibility was evaluated against prespecified key performance indicators. Objective physiological and subjective functional assessments were recorded before and after completion. Effects on mortality in comparison to a non-prehab cohort were assessed in an exploratory regression analysis.

Results

A total of 381 patients were referred to P4C via a web-based portal. 86% (329/381) were contacted by phone and 73% (279/381) completed an initial assessment. 45% (172/381) completed the prehab programme with a median of 7 (IQR 3-11) sessions during a median time to commencing treatment of 23 days (IQR 16 – 34). Median time from referral to assessment was 4 days (IQR 3 – 6) and 86% (239/279) were completed within 7 days of referral. Six-minute Walk Tests improved by an average of 30m (95% CI 20.6–41m, p=<0.001). 16% (n = 21/132) of participants initially score “Medium” or “High” on IPAQ for weekly physical activity, improving to 52% (n = 66/132) on programme completion. Participants had a median reduction in score of −2.5 (95% CI −3.0 - −1.5) in WHODAS 2.0. There was an 8% reduction in 1-year mortality in patients completing prehab (11%, 17/160) vs those that did not complete prehab (19%, 30/158, OR 0.5, 95% CI 0.24–1.00, p=0.054 after adjustment for age, gender, performance status and cancer staging).

Conclusions

The P4C programme has demonstrated feasibility, acceptability and effectiveness in patients with lung cancer undergoing curative-intent radiotherapy.
ADe NovoDesign Strategy to Convert FAcD from Dimer to Active Monomer
Authors: Chen Ke-Wei , Wang Cui-zhen , Huang Hui-si , Wu Xing , Chen Jia-Nan , Qiu Jia-He , HOI Kin Kuan , Sun Tian-Yu , Wang Jian-bo , Wu Yun-Dong
Published: January 2025

Enzymes largely exist in various oligomeric states, but monomeric enzymes are more conducive to industrial applications. Converting an oligomeric enzyme into an active monomer is a significant challenge. In this study, we present ade novodesign strategy to convert fluoroacetate dehalogenase (FAcD) from its native dimeric form to an active monomer. Using the AI-based method ProteinMPNN, we identified critical protein-protein interaction (PPI) sites at the dimer interface. ArDCA, another AI tool, was employed to pinpoint catalytic hotspots. Six mutants,Mu1-Mu6, were designed. Molecular dynamics (MD) simulations, coupled with mass spectrometry, confirmed that these mutants form stable monomers. The pre-reaction state (PRS) model predicted that three of these mutants exhibited catalytic activity. In particular,Mu5with 11 mutations from the wild-type, was predicted to have high catalytic activity, and was subsequently confirmed by kinetics experiment, with akcatof 672.2 min-1and a T5030> 100 °C, comparable to the wild-type enzyme (kcat= 676.3 min-1, T5030= 84 °C). Notably, the Y149M mutation increased catalytic activity nearly forty-fold, demonstrating the effectiveness of our design strategy.
Phylogenetically distant but cohabiting: Fungal communities of fine roots inDiphasiastrum complanatum,Pinus sylvestris, andVaccinium myrtillusin a Lithuanian pine forest
Authors: Kuprina Kristina , Wirth Moana , Luque Maria Sanchez , Heklau Heike , Rimgailė-Voicik Radvilė , Bog Manuela , Schnittler Martin
Published: January 2025

Throughout evolution, distinct plant lineages independently established mutualistic relationships with various fungal taxa. However, the extent to which these relationships are conserved across different plant and fungal lineages remains unclear. In this study, we compared fungal communities associated with the fine roots of three phylogenetically distant yet cohabiting plant species:Diphasiastrum complanatum, a member of lycophytes, the most basal extant vascular plant lineages;Pinus sylvestris,a gymnosperm; andVaccinium myrtillus, an angiosperm, an evolutionary relatively young lineage. To minimize environmental variability, fine roots of three species were collected from each of 19 five-square-meter plots within a Scots pine forest in Lithuania. Using metabarcoding and microscopic techniques, we observed significant differences in the fungal community composition and diversity among the three plant species. We detected no signs of arbuscular mycorrhiza in any species. Samples ofD. complanatumshowed significantly higher taxonomical diversity, whileP. sylvestrisshowed lowest diversity, with ectomycorrhizal fungi being most abundant. Samples ofV. myrtillushad a prevalence of putative ericoid mycorrhiza taxa, classes Sebacinales and Trechisporales, likely forming hyphal coils detected through microscopy. In contrast, no mycorrhiza was detected inD. complanatumsporophytes. This, along with the presence of well-developed root hairs and similarity to the fungal community inhabiting soil suggests a low dependency on mycorrhizal associations and a more opportunistic fungi-plant relationship. This is the first study of fungi associated with the sporophytes ofD. complanatum.Our findings provide valuable insights into the complex interactions between fungi and plants from diverse phylogenetic lineages in natural environments.
Molecular basis of ligand binding and receptor activation at the human A3 adenosine receptor
Authors: Zhang Liudi , Mobbs Jesse I. , Bennetts Felix M. , Venugopal Hariprasad , Nguyen Anh T.N. , Christopoulos Arthur , van der Es Daan , Heitman Laura H. , May Lauren T. , Glukhova Alisa , Thal David M.
Published: January 2025

Adenosine receptors (ARs: A1AR, A2AAR, A2BAR, and A3AR) are crucial therapeutic targets, yet developing selective, efficacious drugs remains challenging. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of the human A3AR in three distinct functional states: bound to the endogenous agonist adenosine, the clinically relevant agonist Piclidenoson, and the covalent antagonist LUF7602. These structures, complemented by mutagenesis and pharmacological studies, reveal a unique A3AR activation mechanism involving an extensive hydrogen bond network from the extracellular surface down to the orthosteric binding site. In addition, we identify a cryptic pocket that accommodates the N6-iodobenzyl group of Piclidenoson through a ligand-dependent conformational change of M1745.35. Our comprehensive structural and functional characterization of A3AR advances understanding of adenosine receptor pharmacology and establishes a foundation for developing more selective therapeutics for various disorders including inflammatory diseases, cancer, and glaucoma.

Teaser

Structures of the A3AR in different conformations reveal a unique activation mechanism and cryptic binding pocket.
Enforced E-selectin ligand installation enhances homing and efficacy of adoptively transferred T cells
Authors: Hou Yingqin , Ye Jinfeng , Qin Ke , Cui Leigh-Ann , Chung Shereen , Chapla Digantkumar Gopaldas , Wang Wenjian , Shi Yujie , Chen Mingkuan , Moremen Kelley. W. , Sackstein Robert , Wu Peng
Published: January 2025

Adoptive T-cell transfer has revolutionized the treatment of hematological malignancies. However, this approach has had very limited success in treating solid tumors, largely due to inadequate infiltration of vascularly administered T cells at tumor sites. The shear-resistant interaction between endothelial E-selectin and its cognate ligand expressed on leukocytes, sialyl Lewis X (sLeX), is an essential prerequisite for extravasation of circulating leukocytes. Here, we report that enforced E-selectin ligand expression (enforced sLeXdisplay) on antigen-specific T cells can be achieved by fucosylating cells via cell surface treatment with the human α1-3-fucosyltransferase, FUT6 (“exofucosylation”), or via Golgi-targeted FUT6 overexpression (“Golgi-fucosylation”). However, despite comparable E-selectin binding, only sLeX-modified T cells engendered by exofucosylation, not by Golgi-fucosylation, exhibited enhanced parenchymal infiltration of target malignant sites. This heightened homing yielded significantly improved therapeutic efficacy in various murine syngeneic and xenograft cancer models, including subcutaneous solid tumors, lymphoma and leukemia, as well as lung and bone marrow metastases. Therefore, exofucosylation represents a promising strategy to improve the efficacy of adoptive T-cell therapy, particularly in the treatment of solid tumors and metastatic disease.
An Integrative Polygenic and Epigenetic Risk Score for Overweight-Related Hypertension in Chinese Population
Authors: Zhang Yaning , Zheng Qiwen , Qian Qili , Yuan Na , Liu Tianzi , Gao Xingjian , Fan Xiu , Bi Youkun , Ji Guangju , Jia Peilin , Wang Sijia , Liu Fan , Zeng Changqing
Published: January 2025

Overweight-related hypertension (OrH), defined by the coexistence of excess body weight and hypertension (HTN), is an increasing health concern elevating cardiovascular disease risks. This study evaluates the prediction performance of polygenic risk scores (PRS) and methylation risk scores (MRS) for OrH in 7,605 Chinese participants from two cohorts: the Chinese Academy of Sciences (CAS) and the National Survey of Physical Traits (NSPT). In CAS cohort, which predominantly consists of academics, males showed significantly higher prevalence of obesity, hypertension (HTN), and OrH, along with worse metabolic syndrome indicators, compared to females. This disparity was less pronounced in NSPT cohort and in broader Chinese studies. Among ten PRS methods, PRScsx was the most effective, enhancing prediction accuracy for obesity (AUC = 0.75), HTN (AUC = 0.74), and OrH (AUC = 0.75), compared to baseline models using only age and sex (AUC = 0.55–0.71). Similarly, Lasso-based MRS models improved prediction accuracies for obesity (AUC = 0.70), HTN (AUC = 0.73), and OrH (AUC = 0.78). Combining PRS and MRS further boosted prediction accuracy to the AUC of 0.77, 0.76, and 0.80, respectively. These models stratified individuals into high (> 0.6) or low (< 0.1) risk categories, covering 59.95% for obesity, 31.75% for HTN, and 43.89% for OrH, respectively. Our findings highlight a higher OrH risk among male academics, emphasize the influence of metabolic and lifestyle factors on MRS predictions, and highlight the value of multi-omics approaches in enhancing risk stratification.

Highlights

Polygenic risk scores and methylation risk scores were systematically evaluated in predicting the risk of obesity, hypertension, and overweight related hypertension in Chinese participants. PRScsx demonstrated robust accuracy in PRS profiling, while Lasso-based MRS showed superior performance in MRS profiling. Moreover, integrating multi-omics analyses further improved disease risk profiling for these conditions, highlighting their potential for personalized care and prevention strategies.

Gender disparity in the prevalence of metabolism-related disorders largely changed in recent three decades in China. Male to female prevalence ratio for obesity, hypertension, and overweight related hypertension reached striking high as 3.8, 2.9 and 4.7 among academics. These differences are likely influenced by the complex interplay among epigenetic factors, lifestyle and metabolic health.
ARGfore: A multivariate framework for forecasting antibiotic resistance gene abundances using time-series metagenomic datasets
Authors: Choi Joung Min , Rumi Monjura Afrin , Vikesland Peter J. , Pruden Amy , Zhang Liqing
Published: January 2025

Background

The global spread of antibiotic resistance presents a significant threat to human, animal, and plant health. Metagenomic sequencing is increasingly being utilized to profile antibiotic resistance genes (ARGs) in various environments, but presently a mechanism for predicting future trends in ARG occurrence patterns is lacking. Capability of forecasting ARG abundance trends could be extremely valuable towards informing policy and practice aimed at mitigating the evolution and spread of ARGs.

Results

Here we propose ARGfore, a multivariate forecasting model for predicting ARG abundances from time-series metagenomic data. ARGfore extracts features that capture inherent relationships among ARGs and is trained to recognize patterns in ARG trends and seasonality.

Conclusion

ARGfore outperformed standard time-series forecasting methods, such as N-HiTS, LSTM, and ARIMA, exhibiting the lowest mean absolute percentage error when applied to different wastewater datasets. Additionally, ARGfore demonstrated enhanced computational efficiency, making it a promising candidate for a variety of ARG surveillance applications. The rapid prediction of future trends can facilitate early detection and deployment of mitigation efforts if necessary. ARGfore is publicly available athttps://github.com/joungmin-choi/ARGfore.
Understory low compositional stability enhances functional stability in response to bull kelp removal in southern Chile
Authors: Fica-Rojas Eliseo , López Daniela N. , Pérez-Matus Alejandro , Valdivia Nelson
Published: January 2025

Background and Aims.

Ecological stability is central to understand the ability of natural systems to respond to disturbances, especially when these occur directly over important species within communities, such as foundational species. The bull kelpDurvillaea incurvatais common in intertidal and shallow subtidal rocky shores, supporting a diverse understory. The direct harvesting ofDurvillaeaconstitute a common practice along the Chilean coast able to disrupts the abundances of the understory community and as well aggregated properties such as overall community biomass. Thus, we investigated the resistance, resilience, and recovery of the understory community ofDurvillaeasubjected to an experimental kelp removal in two sites from the temperate Chilean coast.

Methods.

We simulated a pulse removal ofDurvillaeacause by direct harvesting, by removing once all the individuals within experimental plots and then we monitored the composition and biomass of the sessile and mobile understory community for 25 months.

Key Results.

After the disturbance we observed a rapid recovery ofDurvillaeacover and varying stability responses of the understory community. Community composition showed a low resistance to the disturbance but returned rapidly within 5 – 7 months to pre disturbance levels (high resilience), however showed an incomplete recovery compared to controls. While community biomass displayed high resistance to the disturbance and then remained constant across time (resilience = 0), showing a complete recovery compared to control communities.

Conclusions.

Differing fromDurvillaeadominated communities from other regions, our analyzed communities showed rapid recovery dynamics in compositional and functional aspects, resulting highly resilient to the type of disturbance applied. In addition, since varying stability responses reported, we encourage the use of multiple dimensions of stability to exhaustively characterize the responses ofDurvillaeadominated communities and other kelps, when exposed to disturbances.
Painting Peptides with Antimicrobial Potency through Deep Reinforcement Learning
Authors: Dong Ruihan , Cao Qiushi , Song Chen
Published: January 2025

In the post-antibiotic era, antimicrobial peptides (AMPs) serve as ideal drug candidates for their lower likelihood of inducing resistance. Computational models offer an efficient way to design novel AMPs. However, current optimization and generation approaches are tailored for different application scenarios. To address this challenge, we propose a novel AMP design model named AMPainter. Based on deep reinforcement learning, AMPainter integrates both optimization and generation tasks in a unified framework. We apply AM-Painter to three types of peptides, including known AMPs, signal peptides (SPs), and random sequences. AMPainter outperforms ten related models in enhancing the activity of known AMPs, and evolves effective AMPs from membrane-active SPs with a success rate of 80%. Furthermore, severalde novodesigned AMPs from random sequences are validated along with their evolutionary paths. Therefore, AMPainter contributes topaintantimicrobial potency to diverse peptides, assisting in expanding the AMP sequence space and discovering novel antimicrobial agents.
ERGA-BGE genome ofStigmatoteuthis arcturiRobson, 1948: the jewelled squid
Authors: Fernández-Álvarez Fernando Ángel , Bernal-Bajo Ainhoa , Escudero Nuria , Conejero María , Riesgo Ana , Fernández Rosa , Monteiro Rita , Böhne Astrid , Aguilera Laura , Gut Marta , Alioto Tyler S. , Ferreira Francisco Câmara , Cruz Fernando , Gómez-Garrido Jèssica , Brown Tom
Published: January 2025

TheStigmatoteuthis arcturireference genome offers a valuable resource for understanding the evolutionary patterns of oceanic squids, who perform important ecological roles as both predators and prey in mesopelagic and deep-sea environments, while their genomes remain understudied. The entirety of the genome sequence was assembled into 46 contiguous chromosomal pseudomolecules. This chromosome-level assembly encompasses 3.25 Gb, composed of 1,268 contigs and 497 scaffolds, with contig and scaffold N50 values of 11.0 Mb and 74.6 Mb, respectively.
Deletion of themoeA gene inFlavobacteriumIR1 drives structural color shift from green to blue and alters polysaccharide metabolism
Authors: Escobar Doncel Álvaro , Patinios Constantinos , Campos Alexandre , Walter Costa Maria Beatriz , Turkina Maria V. , Murace Maria , Staals Raymond H.J. , Vignolini Silvia , Dutilh Bas E. , Ingham Colin J.
Published: January 2025

Structural colors (SC), generated by light interacting with nanostructured materials, is responsible for the brightest and most vivid coloration in nature. Despite being widespread within the tree of life, there is little knowledge of the genes involved. Partial exceptions are someFlavobacteriiain which genes involved in a number of pathways, including gliding motility and polysaccharide metabolism, have been linked to SC. A previous genomic analysis of SC and non-SC bacteria suggested that the pterin pathway is involved in the organization of bacteria to form SC. Thus here, we focus on themoeA molybdopterin molybdenum transferase. When this gene was deleted fromFlavobacteriumIR1, the knock-out mutant showed a strong blue shift in SC of the colony, different from the green SC of the wild-type. ThemoeA mutant showed a particularly strong blue shift when grown on kappa-carrageenan and was upregulated for starch degradation. To further analyze the molecular changes, proteomic analysis was performed, showing the upregulation of various polysaccharide utilization loci, which supported the link betweenmoeA and polysaccharide metabolism in SC. Overall, we demonstrated that single-gene mutations could change the optical properties of bacterial SC, which is unprecedented when compared to multicellular organisms where structural color is the result of several genes and can not yet be addressed genetically.
A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide’s Effects on Energy Balance
Authors: Ludwig Mette Q. , Coester Bernd , Gordian Desiree , Hassan Shad , Tomlinson Abigail J. , Toure Mouhamadoul Habib , Christensen Oliver P. , Moltke-Prehn Anja , Brown Jenny M. , Rausch Dylan M. , Gowda Anika , Wu Iris , Kernodle Stace , Dong Victoria , Ayensu-Mensah Mike , Sabatini Paul V. , Shin Jae Hoon , Kirigiti Melissa , Egerod Kristoffer L. , Le Foll Christelle , Lundh Sofia , Gerstenberg Marina Kjærgaard , Lutz Thomas A. , Kievit Paul , Secher Anna , Raun Kirsten , Myers Martin G. , Pers Tune H.
Published: January 2025

Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate the suppression of food intake and body weight. To understand the molecular and neural mechanisms of cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across the rat, mouse, and non-human primate caudal brainstem. We then integrated spatial profiling to reveal neuron distribution in the rat DVC. Furthermore, we compared the acute and long-term transcriptional responses to cagrilintide across DVC neurons of rats, which exhibit strong cagrilintide responsiveness, and mice, which respond poorly to cagrilintide over the long term. We found that cagrilintide promoted long-term transcriptional changes, including increased prolactin releasing hormone (Prlh) expression, in the nucleus of the solitary tract (NTS)Calcr/Prlhcells in rats, but not in mice, suggesting the importance of NTSCalcr/Prlhcells for sustained weight loss. Indeed, activating rat area postremaCalcrcells briefly reduced food intake but failed to decrease food intake or body weight over the long term. Overall, these results not only provide a cross-species and spatial atlas of DVC cell populations but also define the molecular and neural mediators of acute and long-term cagrilintide action.
Embedding muscle fibers in hydrogel improves viability and preserves contractile function during prolongedex vivoculture
Authors: Vonk Leander A. , Esen Osman , Hoomoedt Daan , Balesar Rajvi M.N. , Ottenheijm Coen A. C. , Kirby Tyler J.
Published: January 2025

Ex vivoculture of isolated muscle fibers can serve as an important model forin vitroresearch on mature skeletal muscle fibers. Nevertheless, this model has limitations for long-term studies due to structural loss and dedifferentiation following prolonged culture periods. This study aimed to investigate howex vivoculture affects muscle fiber contraction and to improve the culture system to preserve muscle fiber morphology and sarcomere function. Additionally, we sought to determine which culture-induced changes can negatively affect muscle fiber contraction. We cultured isolated flexor digitorum brevis (FDB) muscle fibers in several conditions for up to 7 days, and investigated viability, morphology, the unloaded sarcomere shortening in intact fibers, along with force generation in permeabilized muscle fibers. In addition, we examined changes to the microtubule network. We found a time-dependent decrease in contractility and viability in muscle fibers cultured for 7 days in a 2D environment. Conversely, we found that culturing FDB muscle fibers in a low-serum, 3D culture environment reduces markers of muscle fiber dedifferentiation (i.e. sprouting), improves viability and retains contractility over time. We discovered that the loss of contractility of cultured muscle fibers was not the direct result of reduced sarcomere function but could be partially explained by changes to the microtubule network. Collectively, our findings highlight the importance of providing muscle fibers with a 3D environment duringex vivoculture, particularly when testing pharmacological or genetic interventions to study viability or contractile function.

In this work, the authors demonstrate that a low-serum, 3Dex vivoculture model preserves muscle fiber viability and contractility while reducing dedifferentiation. This model system can be utilized to conduct prolongedex vivopharmacological or genetic interventions to study fundamental muscle fiber processes or disease mechanisms.
Functional analysis of promoter element 2 within the viral polymerase gene of an emerging paramyxovirus, Sosuga virus
Authors: Akter Lipi , Kawasaki Junna , Rakib Tofazzal Md. , Okura Takashi , Kato Fumihiro , Kojima Shohei , Oda Kosuke , Matsumoto Yusuke
Published: January 2025

Paramyxovirus genomes carry bipartite promoters at the 3’ ends of both their genome and antigenome, thereby initiating RNA synthesis, which requires the viral polymerase to recognize two elements: the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2). We have previously shown that the antigenomic PE2 (agPE2) in many viruses in theRubulavirinaesubfamily is located within the coding region of the viral RNA polymerase L gene. Sosuga virus (SOSV), belonging to theRubulavirinaesubfamily, is highly pathogenic to humans, thus necessitating high-level containment facilities for infectious virus research. The use of a minigenome system permits studies of viral RNA synthesis at lower biosafety levels. Because minigenomes of negative-strand RNA viruses generally comprise only the untranslated regions, agPE2 within the L coding region—such as those found inRubulavirinaelike SOSV—are typically omitted. However, generating an SOSV minigenome that retains agPE2 led to a pronounced increase in activity, enabling a detailed examination of the role of agPE2 in SOSV replication. In manyRubulavirinae, the agPE2 not only acts as a promoter but also encodes part of the L protein, resulting in a distinct motif at the C-terminus of the L protein. We have further shown that this motif is preserved even inRubulavirinaethat no longer contain the agPE2 within the L gene.

Importance

Paramyxoviruses are classified into three major subfamilies:Orthoparamyxovirinae,AvulavirinaeandRubulavirinae. All paramyxovirus genomes and antigenomes possess bipartite promoters, comprising two elements: promoter element 1 (PE1) at the 3’ end and promoter element 2 (PE2) located internally. We previously revealed that, in manyRubulavirinae, the antigenomic PE2 lies within the coding region of the viral RNA polymerase L gene. In this study, we used Sosuga virus, a member of theRubulavirinaesubfamily, to elucidate the role of antigenomic PE2 in viral replication. Because the PE2 region encodes part of the L protein, its presence leads to a distinctive motif at the C-terminus of L protein. Notably, this motif is conserved in allRubulavirinae, including those that do not harbor the antigenomic PE2 within their L gene, indicating its importance in viral propagation.
Understanding the barriers and facilitators to delivering peer support effectively in England: a qualitative interview study
Authors: Foye Una , Lyons Natasha , Shah Prisha , Mitchell Lizzie , Machin Karen , Chipp Beverley , Jeffreys Stephen , Jeynes Tamar , Persaud Karen , Nicholls Vicky , Cooper Ruth E , Grundy Andrew , Pemovska Tamara , Ahmed Nafiso , Appleton Rebecca , Repper Julie , Johnson Sonia , Lloyd-Evans Brynmor , Simpson Alan
Published: January 2025

Background

Peer support roles within mental health services are rapidly increasing in number and scope in the UK and internationally. This paper explores the facilitators and barriers to delivering peer support effectively, as experienced by Peer Support Workers (PSWs) in a range of services and settings.

Methods

We conducted semi-structured qualitative interviews with paid mental health PSWs working across a range of settings in England. We took a collaborative, participatory approach. Interviews were carried out by researchers with experience of living with and/or supporting others with mental health conditions, and for some having experience delivering peer support themselves, and data were analysed using methods guided by general principles of thematic analysis.

Results

We interviewed 35 PSWs. Their roles were varied, spanning a range of mental health areas, and regions, but overarching facilitators and barriers were identified that appeared important across roles and settings. These included the need for roles to have flexibility with some structure and boundaries; the need for support, supervision and training to ensure PSWs are skilled in delivering the unique elements of their job; the importance of working with a strong team and leaders who support and value PSWs to help navigate the challenging personal aspects of being a PSW; the complexity of working in mental health systems where systemic factors such as funding, pay and progression can have a considerable effect both on the personal experience of PSWs and on the value placed on PSWs in the wider organisation.

Conclusion

Our findings highlight the complexity of PSWs, with a wide variety both of facilitators allowing them to carry out roles effectively and barriers to doing so. As PSWs numbers and the scope of their roles increase, awareness of barriers and facilitators needs to inform PSW job roles, support systems and integration into teams and mental health systems.
Multi-molecular phenotyping in a self-sampling population
Authors: Dahl Leo , Bendes Annika , Bueno Álvez María , Albrecht Vincent , Aghelpasand Hooman , Björkander Sophia , Kebede Merid Simon , Mezger Anja , Käller Max , Fredolini Claudia , Torinsson Naluai Åsa , Beck Olof , Melén Erik , Bauer Stefan , Gisslén Magnus , Roxhed Niclas , Schwenk Jochen M
Published: January 2025

The recent COVID-19 pandemic has posed major health challenges. To expand our molecular understanding beyond those seeking medical care, we conducted a cross-sectional survey targeting random residents from Sweden’s two largest cities.

Two thousand participants were invited during 2021 to self-sample dried blood spots (DBS) and provide health information. DBS samples were analysed for multiple anti-SARS-CoV-2 antibodies (Abs), auto-reactive antibodies (AAbs) against 23 interferons (IFNs), and for 502 circulating immune-related proteins. Data-driven methodologies characterised the DBS phenotypes in response to infections and vaccination.

We received DBS samples from 437 (22%) volunteers aged 18-69, 60% females, and 50% per city. Multi-analyte serology distinguished self-reported infections (26%) and vaccination (40%), revealing a time-dependent discrepancy between reported and measured immunity. Anti-IFN Abs were detected in 21% of the donors and more frequent for type 1 IFNs alongside a natural infection. Integrating proteomics with antibody data provided additional insights into processes of cell-mediated immunity. Proteomics-centric analysis identified 24% of the participants to deviate in their phenotypes due to infection, immunity, respiratory distress, and age-related traits.

Multi-molecular analysis of layperson samples uncovered heterogeneity and diversity of immunity and health phenotypes, complementing clinical investigations.