bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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

AbstractCharacterization 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

AbstractLukenya 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

ABSTRACTKnown 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

AbstractIntroductionPrehabilitation 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.MethodsPrehab4Cancer (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.ResultsA 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).ConclusionsThe 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

AbstractEnzymes 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

AbstractThroughout 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

AbstractAdenosine 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.TeaserStructures 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

AbstractAdoptive 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

AbstractOverweight-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.HighlightsPolygenic 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

AbstractBackgroundThe 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.ResultsHere 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.ConclusionARGfore 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

AbstractBackground 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.