bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical activity, metabolites, and breast cancer associations
Authors: Watts Eleanor L. , Moore Steven C. , Abar Leila , Hong Hyokyoung G. , Saint-Maurice Pedro F. , O’Connell Caitlin , Matthews Charles E. , Loftfield Erikka 
Published: May 2024

AbstractBackgroundThe effects of habitual physical activity on physiology and disease prevention are not fully understood. We examined the associations between physical activity, metabolites in systemic circulation, and breast cancer risk.MethodsTotal physical activity levels were assessed using doubly labeled water, accelerometers, and previous day recalls in the IDATA study (N=707 participants, ages 50-74 years, 51% women). Assessments occurred 1-6 times over a 12-month period and blood samples were collected twice. Partial Spearman correlations were used to estimate associations between physical activity and 843 serum metabolites, corrected for multiple testing using the false discovery rate (p-adj<0.05). Associations between physical activity-associated metabolites and breast cancer were explored in a prospective cohort (621 cases, 621 controls) using conditional logistic regression.ResultsPhysical activity was associated with 164 metabolites, spanning a wide range of pathways, including many amino acid pathways, glucose homeostasis, and bile acid metabolism. Nine physical activity-associated metabolites were also associated with postmenopausal breast cancer risk. Key metabolites were N-acetylthreonine, isovalerylglycine, 2-methylbutyroylcarnitine (amino acids and derivatives), androsteroid monosulfate C19H28O6S (1), and X-21310. These metabolites were consistent with a protective role of physical activity on breast cancer prevention and particularly implicated a role for branched chain amino acid catabolism. Sphingomyelin (d18:1/20:1, d18:2/20:0) levels were lower in participants with higher physical activity energy expenditure and were also associated with lower breast cancer risk.ConclusionPhysical activity is associated with a broad range of metabolites, some of which are also associated with reduced breast cancer risk, highlighting potential metabolic pathways for cancer prevention.
Using fibre-optic sensing for non-invasive, continuous dendrometry of mature tree trunks
Authors: van den Ende Martijn , Oberlé Eléonore , Améglio Thierry , Ardito Robin , Gâteblé Gildas 
Published: May 2024

AbstractDendrometry is the main non-invasive macroscopic technique commonly used in plant physiology and ecophysysiology studies. Over the years several types of dendrometric techniques have been developed, each with their respective strengths and drawbacks. Automatic and continuous monitoring solutions are being developed, but are still limited, particularly for non-invasive monitoring of large-diameter trunks. In this study, we propose a new type of automated dendrometer based on distributed fibre-optic sensing that continuously measures the change in stem circumference, is non-invasive, and has no upper limit on the trunk diameter on which it can be installed. We perform a three-month validation experiment during which we deploy a fibre-optic cable at three localities around the trunks of two specimens ofBrachychiton. We verify the accuracy of this new method through comparison against a conventional point-dendrometer, and we observe a consistent time lag between the various measurement locations that varies with the meteorological conditions. Finally, we discuss the feasibility of the fibre-based dendrometer in the context of existing dendrometric techniques and practical experimental considerations.
Three cytochrome P450 fromNicotiana attenuataplay key roles in triterpene biosynthesis
Authors: Yang Caiqiong , Halitschke Rayko , O’Connor Sarah E. , Baldwin Ian T. 
Published: May 2024

AbstractPentacyclic triterpenoids, recognized for their natural bioactivity, display complex spatiotemporal accumulation patterns within the ecological model plant,Nicotiana attenuata. Despite their ecological significance, the underlying biosynthetic enzymes and functional attributes of triterpenoid synthesis inN. attenuataremain unexplored. Three multifunctional cytochrome P450 monooxygenases (NaCYP716A419, NaCYP716C87, NaCYP716E107) fromN. attenuatawere shown to oxidize the pentacyclic triterpene skeleton as evidenced by heterologous expression inNicotiana benthamiana. NaCYP716A419 catalyzed a consecutive three-step oxidation reaction at the C28 position of β-amyrin/lupeol/lupanediol, yielding the corresponding alcohol, aldehyde, and carboxylic acid. NaCYP716C87 hydroxylated the C2α position of β-amyrin/lupeol/lupanediol/erythrodiol/oleanolic acid/betulinic acid, while NaCYP716E107 hydroxylated the C6β position of β-amyrin/oleanolic acid. Three CYP716 enzymes are highly expressed in flowers and respond to induction by ABA, MeJA, SA, GA3, and abiotic stress treatments. Using VIGS technology, we revealed that silencing of NaCYP716A419 affects the growth and reproduction ofN. attenuata, suggesting the ecological significance of these specialized metabolite biosynthetic steps.One-sentence summaryThree CYP716 enzymes diversifyN. attenuata’striterpenoid sector with potential roles in growth and development.
Monitoring multi-pathogens and SARS-CoV-2 variants in aircraft and airport wastewater
Authors: Tay Martin , Lee Benjamin , Ismail Muhammad Hafiz , Yam Jerald , Maliki Dzulkhairul , Gin Karina Yew-Hoong , Chae Sae-Rom , Ho Zheng Jie Marc , Teoh Yee Leong , Ng Lee Ching , Wong Judith Chui Ching 
Published: May 2024

AbstractBackgroundAs global travel resumed in COVID-19 endemicity, the potential of aircraft wastewater monitoring to provide early warning of disease trends for SARS-CoV-2 variants and other infectious diseases, particularly at international air travel hubs, was recognized. We therefore assessed and compared the feasibility of testing wastewater from inbound aircraft and airport terminals for 18 pathogens including SARS-CoV-2 in Singapore, a popular travel hub in Asia.MethodsWastewater samples collected from inbound medium- and long-haul flights and airport terminals were tested for SARS-CoV-2. Next Generation Sequencing (NGS) was carried out on positive samples to identify SARS-CoV-2 variants. Airport and aircraft samples were further tested for 17 other pathogens through quantitative reverse transcription polymerase chain reaction (RT-qPCR).ResultsThe proportion of SARS-CoV-2-positive samples and the average virus load was higher for wastewater samples from aircraft as compared to airport terminals. Cross-correlation analyses indicated that viral load trends from airport wastewater led local COVID-19 case trends by two to five days. A total of ten variants (44 sub-lineages) were successfully identified from aircraft wastewater and airport terminals, and four variants of interest (VOIs) and one variant under monitoring (VUM) were detected in aircraft and airport wastewater 18-31 days prior to detection in local clinical cases. The detection of five respiratory and four enteric viruses in aircraft wastewater samples further underscores the potential to expand aircraft wastewater to monitoring pathogens beyond SARS-CoV-2.ConclusionOur findings demonstrate the feasibility of aircraft wastewater testing for monitoring infectious diseases threats, potentially detecting signals before clinical cases are reported. The triangulation of similar datapoints from aircraft wastewater of international travel nodes could therefore serve as a useful early warning system for global health threats.
United States Provider Experiences with Telemedicine for Hepatitis C Treatment: A Nationwide Survey
Authors: Patel Pruthvi , Wells Martin T. , Wethington Elaine , Shapiro Martin , Parvez Yasir , Kapadia Shashi N , Talal Andrew H 
Published: May 2024

AbstractBackgroundHepatitis C virus (HCV) elimination requires treatment access expansion, especially for underserved populations. Telehealth has the potential to improve HCV treatment access, although data are limited on its incorporation into standard clinical practice.MethodsWe conducted a cross-sectional, e-mail survey of 598 US HCV treatment providers who had valid email addresses and 1) were located in urban areas and had written ≥20 prescriptions for HCV treatment to US Medicare beneficiaries in 2019-20 or 2) were located in non-urban areas and wrote any HCV prescriptions in 2019-20. Through email, we notified providers of a self-administered electronic 28-item survey of clinical strategies and attitudes about telemedicine for HCV.ResultsWe received 86 responses (14% response rate), of which 75 used telemedicine for HCV in 2022. Of those 75, 24% were gastroenterologists/hepatologists, 23% general medicine, 17% infectious diseases, and 32% non-physicians. Most (82%) referred patients to commercial laboratories, and 85% had medications delivered directly to patients. Overwhelmingly, respondents (92%) felt that telehealth increases healthcare access, and 76% reported that it promotes or is neutral for treatment completion. Factors believed to be “extremely” or “very” important for telehealth use included patient access to technology (86%); patients’ internet access (74%); laboratory access (76%); reimbursement for video visits (74%) and audio-only visits (66%). Non-physician licensing and liability statutes were rated “extremely” or “very” important by 43% and 44%, respectively.ConclusionsProviders felt that telehealth increases HCV treatment access. Major limitations were technological requirements, reimbursement, and access to ancillary services. These findings support the importance of digital equity and literacy to achieve HCV elimination goals.
Association of body water balance, nutritional risk, and sarcopenia with outcome in patients with acute ischemic stroke
Authors: Akimoto Takayoshi , Tasaki Kenta , Ishihara Masaki , Hara Makoto , Nakajima Hideto 
Published: May 2024

AbstractBackgroundBioelectrical impedance analysis (BIA) can serve to evaluate body water balance and muscle mass. The present study aimed to explore the interrelationships among body water balance, nutritional risk, sarcopenia, and outcome after acute ischemic stroke (AIS).MethodsThis single-center, prospective study included 111 patients with AIS and a premorbid modified Rankin Scale score (mRS) ≤2. Overhydration, indicating a body water balance abnormality, was defined as an extracellular fluid/total body water ratio >0.390. The geriatric nutritional risk index (GNRI) was used as nutrition marker, a GNRI <92 was considered low. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia criteria. Poor outcome was defined as an mRS ≥3 at discharge.ResultsIn the overall cohort, including 40 women, the median age was 77 years, 43 had poor prognosis, 31 overhydration, 25 low GNRI, and 44 sarcopenia. Patients with poor outcome had significantly higher National Institutes of Health Stroke Scale (NIHSS) scores, and significantly more common with overhydration, low GNRI, and sarcopenia (P <0.001 for all). Increasing concomitance of overhydration, low GNRI, and sarcopenia was associated with a heightened rate of poor outcomes. Especially, poor outcome was observed in 19 of 23 patients with low muscle mass and overhydration. In multivariate analysis, overhydration (odds ratio [OR] 5.504, 95% confidence interval [CI] 1.717–17.648; P = 0.004), age (OR 1.062, 95%CI 1.010–1.117; P = 0.020) and NIHSS score (OR 1.790, 95%CI 1.307–2.451; P < 0.001) were independent poor prognostic factors.ConclusionsBody water balance and muscle mass assessment using BIA was useful in predicting AIS outcome. Overhydration was particularly associated with poor outcome. The combination of overhydration and low muscle mass could specifically predict poor outcomes after AIS.Graphical Abstract
Variant rs9644568 in the intergenic region downstream of the LPL gene is associated with high LDL cholesterol levels among Filipinos
Authors: Cutiongco–de la Paz Eva Maria C. , Nevado Jose B. , Santos Lourdes Ella G. , Aman Aimee Yvonne Criselle L. , Magno Jose Donato A. , Reganit Paul Ferdinand M. , Tiongco Richard Henry P. , Ona Deborah Ignacia D. , Punzalan Felix Eduardo R. , Llanes Elmer Jasper B. , Aherrera Jaime Alfonso M. , Fernandez Carla Mae O. , Abrahan Lauro L. , Agustin Charlene F. , Bejarin Adrian John P. , Sy Rody G. 
Published: May 2024

AbstractHigh blood level of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although genetic variants linked to high LDL-C have been studied in other populations, there have been no previous studies among Filipinos. This study aims to determine the association of candidate genetic variants to high LDL-C. We performed an age- and sex-matched case-control study that compared Filipino participants with high LDL-C levels (n=60) with controls (n=60). DNA was extracted from blood samples and genotyped for candidate SNPs using a customized microarray chip. Logistic regression analyses were used to determine the composite association of genetic and clinical variables to the condition. Of the initial eleven SNPs associated with high LDL-C in univariate analyses, only the variant rs9644568 in the intergenic region downstream of theLPLgene remained significantly associated with high LDL-C levels on multiple regression analysis and variable selection after adjustment for hypertension. The G allele was observed as the risk allele in a recessive model. The variant rs9644568-G in theLPLgene was associated with high blood LDL-C levels among Filipinos. In combination with hypertension, this genetic profile may identify individuals who are susceptible to develop high LDL-C in this population.
Full-length tRNAs lacking a functional CCA tail are selectively sorted into the lumen of extracellular vesicles
Authors: Scheepbouwer Chantal , Aparicio-Puerta Ernesto , Gómez-Martin Cristina , van Eijndhoven Monique A.J. , Drees Esther E.E. , Bosch Leontien , de Jong Daphne , Wurdinger Thomas , Zijlstra Josée M. , Hackenberg Michael , Gerber Alan , Pegtel D. Michiel 
Published: May 2024

ABSTRACTSmall extracellular vesicles (sEVs) are heterogenous lipid membrane particles typically less than 200 nm in size and secreted by most cell types either constitutively or upon activation signals. sEVs isolated from biofluids contain RNAs, including small non-coding RNAs (ncRNAs), that can be either encapsulated within the EV lumen or bound to the EV surface. EV-associated microRNAs (miRNAs) are, despite a relatively low abundance, extensively investigated for their selective incorporation and their role in cell-cell communication. In contrast, the sorting of highly-structured ncRNA species is understudied, mainly due to technical limitations of traditional small RNA sequencing protocols. Here, we adapted ALL-tRNAseq to profile the relative abundance of highly structured and potentially methylated small ncRNA species, including transfer RNAs (tRNAs), small nucleolar RNAs (snoRNAs), and Y RNAs in bulk EV preparations. We determined that full-length tRNAs, typically 75 to 90 nucleotides in length, were the dominant small ncRNA species (>60% of all reads in the 18-120 nucleotides size-range) in all cell culture-derived EVs, as well as in human plasma-derived EV samples, vastly outnumbering 21 nucleotides-long miRNAs. Nearly all EV-associated tRNAs were protected from external RNAse treatment, indicating a location within the EV lumen. Strikingly, the vast majority of luminal-sorted, full-length, nucleobase modification-containing EV-tRNA sequences, harbored a dysfunctional 3’ CCA tail, 1 to 3 nucleotides truncated, rendering them incompetent for amino acid loading. In contrast, in non-EV associated extracellular particle fractions (NVEPs), tRNAs appeared almost exclusively fragmented or ‘nicked’ into tRNA-derived small RNAs (tsRNAs) with lengths between 18 to 35 nucleotides. We propose that in mammalian cells, tRNAs that lack a functional 3’ CCA tail are selectively sorted into EVs and shuttled out of the producing cell, offering a new perspective into the physiological role of secreted EVs and luminal cargo-selection.
A dissection of the genomic antimicrobial resistance epidemiology ofSalmonellaTyphimurium
Authors: Kaur Sandeep , Payne Michael , Partridge Sally R. , Sintchenko Vitali , Lan Ruiting 
Published: May 2024

AbstractSalmonellaTyphimurium (STm) is a globally prevalent pathogen. We compiled a dataset comprising ∼65,000 publicly available STm isolates and analysed the predicted-resistance to 15 key antibiotics. Additionally, we typed all isolates using a standardized typing method, multilevel genome typing (MGT), and characterised the resistance profiles by MGT sequence types (ST). We identified 407 MGT STs wherein at least 80% of the isolates were non-susceptible to at least one antibiotic. For the key antibiotics prescribed for severe salmonellosis, we identified three ciprofloxacin non-susceptible MGT STs, and eight cefotaxime non-susceptible MGT STs in the last two years of the dataset (2021-2022). While the ciprofloxacin non-susceptible MGT STs comprised isolates predominantly from the UK; only one cefotaxime non-susceptible MGT ST comprised isolates predominantly from UK and associated with swine, with others from USA, and associated with cattle and poultry. Integration of AMR predictions with MGT strain typing provides sharable, standardised, and specific identification and tracking of resistant isolates. This integrated analysis presents a unique approach for the global surveillance of antimicrobial resistance and resistant strains.
The NHR-23-regulated putative protease inhibitormlt-11gene is necessary forC. eleganscuticle structure and function
Authors: Ragle James Matthew , Turzo Ariela , Jackson Anton , Vo An A. , Pham Vivian T. , Ward Jordan D. 
Published: May 2024

ABSTRACTC. elegansmolting offers a powerful entry point to understanding developmentally programmed apical extracellular matrix remodeling. However, the gene regulatory network controlling this process remains poorly understood. Focusing on targets of NHR-23, a key transcription factor that drives molting, we confirmed the Kunitz family protease inhibitor genemlt-11as an NHR-23 target. Through reporter assays, we identified NHR-23-binding sites that are necessary and sufficient for epithelial expression. We generated a translational fusion and demonstrated that MLT-11 is localized to the cuticle and lined openings to the exterior (vulva, rectum, mouth). We created a set of strains expressing varied levels of MLT-11 by deleting endogenouscis-regulatory element sequences. Combined deletion of twocis-regulatory elements caused developmental delay, motility defects, and failure of the cuticle barrier. Inactivation ofmlt-11by RNAi produced even more pronounced defects.mlt-11is necessary to pattern every layer of the adult cuticle, suggesting a broad patterning role prior to the formation of the mature cuticle. Together these studies provide an entry point into understanding how individualcis-regulatory elements function to coordinate expression of oscillating genes involved in molting and how MLT-11 ensures proper cuticle assembly.
“Galacturonic acid oxidation: a radical way to stick together”
Authors: Grandjean Cyril , Voxeur Aline , Chabout Salem , Boutet Stéphanie , Pelloux Jérôme , Bouton Sophie , Mouille Grégory 
Published: May 2024

SummaryThe middle lamellae (ML) of plant cells, enriched in Homogalacturonan (HG) is considered to function as a crucial ‘glue’ responsible for cell-cell cohesion (for review see1). Mutants with defective HG content exhibit cell adhesion defects2,3. Despite advances, the mechanisms governing cell adhesion during plant development remain elusive. We previously hypothesized that cell-cell cohesion relies on cell wall integrity signaling, yet the specifics remain undefined4. OligoGalacturonans (OG), degradation products of HG, are prime candidates for ‘informing’ cells about ML status and thereby influencing cell adhesion. This integrity signal is crucial for adhesion homeostasis4. OGs serve as signaling molecules, recognized by membrane-bound cell wall receptors. Notably, restoring adhesion inqua2-1mutants by modulating pectin response gene expression inesmd/qua2mutants underscores potential OGs’ importance4–6. Deciphering the diversity and role of endogenous OGs is imperative for understanding cell adhesion modulation. Our study aims to identify compounds in this signalling pathway that regulate cell adhesion. We focused on characterizing HG degradation products in dark-grown hypocotyls. Our findings highlight various oligomers, along with two key monomers: galacturonic acid and its oxidized form, galactaric acid. These monomers appear to play a pivotal role in controlling cell adhesion by indirectly enhancing the crosslinking of extensin, a cell wall structural protein. This crosslinking leads to the densification of extensin-based cell wall networks, ultimately restoring cell adhesion in defective mutants. Our research sheds light on the intricate interplay between HG degradation product monomer and cell adhesion mechanisms.
Finnish gyrate atrophy mutation OAT;c.1205C>T leads to accumulation of intracellular GABA
Authors: Sartori-Maldonado Rocio , Wartiovaara Kirmo 
Published: May 2024

AbstractHyperornithinaemia with gyrate atrophy of choroid and retina (HOGA) is a recessive metabolic disease caused by dysfunction of the ornithine aminotransferase (OAT) gene, leading to ornithine accumulation and a complex metabolic imbalance. This causes retinal degeneration that ultimately evolve to blindness. However, the mechanisms of this degeneration remain unknown. Here, we have conducted untargeted metabolomic analysis in patient-derived induced pluripotent stem cells and their isogenic counterparts. Mutant cells show altered levels of ornithine-related metabolites, including low creatine, proline and glutamate, and elevated arginine and citrulline. The untargeted metabolomics approach revealed changes in the urea cycle and polyamine synthesis pathways with a significant intracellular accumulation of gamma-aminobutyric acid (GABA). Hence, we propose GABA as a key player in the disease pathogenicity, potentially affecting neuronal function in the eye.
Comparative Analysis of Small Secreted Peptide Signaling during Defense Response: Insights from Vascular and Non-Vascular Plants
Authors: Lyapina Irina , Ganaeva Daria , Rogozhin Eugene A. , Ryabukhina Ekaterina V. , Ryazantsev Dmitry Yu. , Lazarev Vassili , Alieva Sabina E. , Mamaeva Anna , Fesenko Igor 
Published: May 2024

AbstractSmall secreted peptides (SSPs) play an important role in modulating immune responses in all land plants. However, the evolution of stress peptide signaling in different plant phyla remains poorly understood. Here, we compared the expression of SSP genes in the pathogen-induced transcriptomes of vascular and non-vascular plants. We found 13, 19, 15, and 28 SSP families that were differentially expressed during infection inPhyscomitrium patens,Zea mays,Brassica napus, andSolanum tuberosum, respectively. A comparative study of peptide motifs and predicted three-dimensional structures confirmed the similarity of SSPs across the examined plant species. In both vascular and non-vascular plants, however, only the RALF peptide family was differentially regulated under infection. We also found that EPFL peptides, which are involved in growth and development processes in angiosperms, were differentially regulated inP. patensin response to pathogen infection. The search for novel immune-specific peptides revealed a family of PSY-like peptides that are differentially regulated during infection inP. patens. The treatment with synthetic EPFL, MEG, PSY, and PSY-like peptides validated their roles in the immune response and growth regulation. Thus, our study showed the complex nature of SSP signaling and shed light on the regulation of SSPs in different plant lineages during infection.