bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rooting depth and specific leaf area modify the impact of experimental drought duration on temperate grassland species
Authors: Künzi Yvonne , Zeiter Michaela , Fischer Markus , Stampfli Andreas 
Published: January 2025

Abstract

Due to climate change, temperate grasslands are being exposed to increasingly severe droughts. Concurrently, land‐use intensification is altering grasslands' functional composition by promoting fast‐growing, resource‐acquisitive species with high specific leaf area (SLA).

How SLA affects the ability of grassland species to resist and recover from increasingly severe droughts and if deep roots improve their drought performance remains unclear. To investigate this, we established a common‐garden field experiment including temperate grassland species with SLAs of 17.9–39.3 mm2 g−1 and maximal rooting depths of 16–252 cm. After 1.5 years, we simulated droughts for 0, 79, 134, 177 and 220 days.

Drought effects on plant performance increased with drought length, reducing the survival of green tissue and annual biomass by up to ~50% across all 32 species considered. As plant‐available water remained in deep soil layers by the end of all treatments, deep roots mitigated the negative effect of increasing drought length on productivity in the later stage of drought and favoured productivity after a longer drought. The low‐to‐high SLA trait gradient among the 16 graminoid species seemed to represent alternative survival strategies ranging from dehydration tolerance to dehydration avoidance, rather than drought sensitivity. Variable drought responses along the SLA gradient of forbs imply that multiple other traits are related to drought resistance across evolutionarily distant species.

Synthesis. Our results suggest that deep roots are beneficial for temperate grassland species subjected to longer periods without rainfall when plant‐available water is lacking in shallow soil layers but remaining in deep soil layers. In the face of increasing drought severity, we thus recommend (1) fostering deep‐rooted species in intensive grasslands on deep, productive soil and (2) directing further studies towards identifying management practices that support deep rooting in semi‐natural grasslands.
Proximity‐Ligation Metagenomic Sequence Analysis Reveals That the Antibiotic Resistome Makes Significant Transitions During Municipal Wastewater Treatment
Authors: McCorison Cassandra B. , Kim Taegyu , Donato Justin J. , LaPara Timothy M. 
Published: January 2025

ABSTRACTShotgun and proximity‐ligation metagenomic sequencing were used to generate thousands of metagenome assembled genomes (MAGs) from the untreated wastewater, activated sludge bioreactors, and anaerobic digesters from two full‐scale municipal wastewater treatment facilities. Analysis of the antibiotic resistance genes (ARGs) in the pool of contigs from the shotgun metagenomic sequences revealed significantly different relative abundances and types of ARGs in the untreated wastewaster compared to the activated sludge bioreactors or the anaerobic digesters (p < 0.05). In contrast, these results were statistically similar when comparing the ARGs in the pool of MAGs, suggesting that proximity‐ligation metagenomic sequencing is particularly useful for pairing ARGs with their hosts but less adept at discerning quantitative differences in ARG types and relative abundances. For example, numerous MAGs of the genera Acinetobacter, Enterococcus, Klebsiella and Pseudomonas were identified in the untreated wastewater, many of which harboured plasmid‐borne and/or chromosomal‐borne ARGs; none of these MAGs, however, were detected in the activated sludge bioreactors or anaerobic digesters. In conclusion, this research demonstrates that the antibiotic resistome undergoes significant transitions in both the relative abundance and the host organisms during the municipal wastewater treatment process.
WTAP‐Mediated m6A Modification of TRAIL‐DR4 Suppresses MH7A Cell Apoptosis
Authors: Cui Xiaoya , Xu Fengxia , Pang Xue , Fan Chang , Jiang Hui 
Published: January 2025

ABSTRACTBackgroundN6‐methyladenosine (m6A) is one of the most conserved internal RNA modifications, which has been implicated in many biological processes, such as apoptosis and proliferation. Wilms tumor 1‐associating protein (WTAP), as a key component of m6A methylation, is a nuclear protein that has been associated with the regulation of proliferation and apoptosis. Rheumatoid arthritis (RA), a systemic, infiltrating autoimmune disease, is characterized by synovial hyperplasia. However, little is known about the precise role of WTAP in RA. This study investigated the role of the WTAP‐mediated m6A modification of TNF‐related apoptosis‐inducing ligand death receptor 4 (TRAIL‐DR4) in RA.MethodMethyltransferase WTAP overexpression plasmids and small interfering RNAs were constructed and transfected into MH7A cells. Immunofluorescence (IF) staining, quantitative reverse transcription polymerase chain reaction (RT‐qPCR), and Western blot were used to detect changes in the expression of WTAP, the B‐cell lymphoma 2 (BCL2) gene family, BCL2‐associated X (BAX) and TRAIL‐DR4 expression, and the effects of WTAP overexpression on cell viability, cell cycle, apoptosis, and proliferation were assessed by a cell counting kit‐8 (CCK‐8), flow cytometry, and transmission electron microscopy (TEM). The m6A modification of TRAIL‐DR4 was verified by m6A methylated RNA immunoprecipitation‐qPCR (MeRIP‐qPCR) and its stability was assessed by an actinomycin D assay.ResultsOverexpression of WTAP not only increased the levels of WTAP and BCL2, and decreased the levels of BAX and TRAIL‐DR4, but also significantly inhibited MH7A cell apoptosis and promoted cell viability and proliferation, while WTAP silencing led to the opposite trend. The SRAMP online database predicted that TRAIL‐DR4 has multiple potential methylation‐binding sites, and fluorescence in situ hybridization (FISH) combined with IF showed that WTAP and TRAIL‐DR4 were mainly expressed in both the nucleus and cytoplasm. MeRIP‐qPCR and actinomycin D analysis experiments revealed that WTAP could promote the m6A level of TRAIL‐DR4, decrease the stability of TRAIL‐DR4 mRNA, and subsequently inhibit apoptosis.ConclusionThis study suggests that WTAP‐mediated m6A modification of TRAIL‐DR4 suppresses MH7A cell apoptosis. This discovery offers a new focus and avenue for the clinical treatment of RA, while also extending our understanding of the pathophysiology of RA from the standpoint of m6A alteration.
The ability of lacewing larvae to predate two pest caterpillars in relation to the prey defensive behaviour and body size
Authors: Samková Alena , Raška Jan , Opletalová Ivana , Zouhar Miloslav , Skuhrovec Jiří 
Published: January 2025

Abstract
Predatory larvae of the lacewing Chrysoperla carnea (Neuroptera: Chrysopidae) represent an important biocontrol agent, as they prey on a wide range of prey, including economically important crop pests. However, some prey use active defensive behaviours that may reduce the effectiveness of these predators in biological control.
In this study, we aimed to investigate the anti‐predator defensive behaviour of two economically important pests, Scrobipalpa cf. ocellatella and Autographa cf. gamma (Lepidoptera: Gelechiidae and Noctuidae, respectively), and the effectiveness of this behaviour in combination with their body size.
During our laboratory experiments, the caterpillars of these species defended themselves against predators using body tremors, striking the predator with the anterior part of the body and secretion (for A. cf. gamma) or regurgitation (for S. cf. ocellatella).
Interestingly, the defensive behaviour itself had no effect on hunting success. Instead, the killing of caterpillars depended mainly on the variance in their body size.
Our results suggest that predatory lacewing larvae can be effective predators of the caterpillars S. cf. ocellatella and A. cf. gamma due to their ability to overcome their defensive behaviour. However, field experiments will be necessary to determine the effectiveness of lacewings as biocontrol agent.
Morphology of the Soft Palate Tonsil Mucosa of Collared Peccary (Pecari tajacu, Linnaeus, 1758)
Authors: Tomiate André Neri , de Oliveira Moacir Franco , da Silva José Roberto Rodrigues , Camargo Paula Oliveira , Ciena Adriano Polican 
Published: January 2025

ABSTRACTCollared Peccary (Pecari tajacu, Linnaeus, 1758) is a mammalian Tayassuidae species from tropical to semi‐arid areas. The morphological features of the oral cavity in this species were identified and described. Tonsils are secondary lymphoid organs essential for contact with antigens due to food and air intake. This study aimed to describe histological characteristics and three‐dimensional morphology of the soft palate tonsil mucosa. Therefore, the samples (n = 10) were analysed by stereomicroscope for morphology, light microscopy (n = 4) for structural characterisation, and scanning electron microscopy (n = 6) to reveal three‐dimensional aspects of the epithelial surface and connective tissue cores (CTC). Our findings revealed a pair of soft palate tonsils separated by a median raphe. A keratinised squamous stratified epithelium characterised the tonsil. The epithelial surface had several orifices, and these were associated with a lymph nodule organisation. After epithelial removal, the three‐dimensional aspect of the lamina propria was evidenced by conical projections throughout the region, even on the crypt's edge and inside them. The soft palate tonsils mucosa was like the previous description; however, the revealed CTC had a conical morphology, a new feature in this organ.
Proteinuria and tubular cells: Plasticity and toxicity
Authors: Faivre Anna , Verissimo Thomas , de Seigneux Sophie 
Published: January 2025

AbstractAimProteinuria is the most robust predictive factors for the progression of chronic kidney disease (CKD), and interventions targeting proteinuria reduction have shown to be the most effective nephroprotective treatments to date. While glomerular dysfunction is the primary source of proteinuria, its consequences extend beyond the glomerulus and have a profound impact on tubular epithelial cells. Indeed, proteinuria induces notable phenotypic changes in tubular epithelial cells and plays a crucial role in driving CKD progression. This comprehensive review aims to elucidate the mechanisms involved in the tubular handling of proteins and explore the potential effects of proteinuria on the function of tubular epithelial cells.MethodsThis paper is a narrative review. Litterature review was performed on PubMed from its inception until 2024, focusing on the effects of proteinuria on tubular cells.ResultsThe review highlights the toxic effects of plasma proteins on tubular epithelial cells through signal transduction pathways, as well as endoplasmic reticulum stress activation, oxidative stress, and metabolic alterations. Additionally, it provides an updated understanding of the dynamic phenotypic changes occurring within the nephron in response to proteinuria.ConclusionsBy examining the intricate interplay between proteinuria and tubular epithelial cells, this review sheds light on key factors contributing to CKD progression and unveils potential targets for therapeutic interventions.
The pleiotropic effects of PCSK9 in cardiovascular diseases beyond cholesterol metabolism
Authors: Liu Gang , Yu Xiatian , Cui Chaochu , Li Xiao , Wang Tianyun , Palade Philip T. , Mehta Jawahar L. , Wang Xianwei 
Published: January 2025

AbstractCardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally, with elevated low‐density lipoprotein cholesterol (LDL‐C) levels being a major risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating LDL‐C levels by promoting the degradation of hepatic low‐density lipoprotein receptors (LDLR) responsible for clearing LDL‐C from the circulation. PCSK9 inhibitors are novel lipid‐modifying agents that have demonstrated remarkable efficacy in reducing plasma LDL‐C levels and decreasing the incidence of CVD. However, the broader clinical impacts of PCSK9 functions beyond cholesterol metabolism, including both desired and undesired effects from therapeutic PCSK9 inhibition, underscore the urgent necessity to elucidate the underlying mechanisms. Recent studies have shown that local PCSK9 in the vascular system can interact with other receptors such as CD36, LRP‐1, and ABCA1. This provides new evidence supporting the potential contribution of PCSK9 to CVD through LDLR‐independent signaling pathways. Therefore, this review aimed to outline the diverse effects of PCSK9 on CVD and discuss the underlying mechanisms in non‐cholesterol‐related processes, which will provide a rational basis for its long‐term pharmacological inhibition in the clinic.
Use of a Non‐Endoscopic Capsule‐Sponge Triage Test for Reflux Symptoms: Results From the NHS England Prospective Real‐World Evaluation
Authors: Gourgiotis Vlasios , Graham Charlotte , Foerster Kristen ,   NHS England Pilot and NHS England Oversight Group, Fitzgerald Rebecca C. , Harvey Rory , Morris Danielle L. 
Published: January 2025

ABSTRACTBackgroundAcid reflux is a common presentation in primary care leading to a high volume of referrals to endoscopy that are often normal.AimsTo determine whether a non‐endoscopic capsule sponge biomarker test could triage patients with low‐risk reflux symptoms, reduce endoscopy waiting lists and identify Barrett's oesophagus in a real‐world setting.MethodsPatients with reflux symptoms on NHS endoscopy waiting lists who were offered a capsule sponge (test group) between February 2021 and August 2022 were included in this national multicentre prospective cohort study and compared with eligible patients on the standard endoscopy pathway (counterfactual group).ResultsTwo thousand one hundred seventy patients from 23 hospitals undertook a capsule sponge triage test and submitted follow‐up data, of whom 1694 (78%) were discharged without endoscopy and 476 (22%) were referred for endoscopy. In a detailed subgroup analysis 1411/1549 (92%) attended and successfully swallowed the capsule of whom 307/1411 (21.8%) required endoscopy. Of 111 patients with positive capsule sponge biomarker results who had endoscopy, 19.8% had Barrett's oesophagus. In comparison, in patients with negative sponge biomarkers who were referred for endoscopy due to ongoing symptoms, none had Barrett's oesophagus (p = 0.0002). Eighty‐two percent surveyed (267/357) were satisfied with the alternative pathway.ConclusionsCapsule sponge triage is feasible, safe and acceptable. It substantially reduces the endoscopy burden for routine reflux referrals with a favourable diagnostic yield for Barrett's oesophagus. Longer term follow‐up will help to confidently assess the impact of the programme and place of capsule sponge in the diagnostic pathway.
Effects of pasture‐burning management on anuran communities in subtropical Brazilian grasslands
Authors: Cansan Guilherme , Moser Camila Fernanda , de Oliveira Juliano Morales , Tozetti Alexandro Marques 
Published: January 2025

AbstractAnthropogenic fire is a worldwide event that affects many ecosystems and organisms. In Southern Brazil, grassland management with fire has been highly employed since the mid‐18th century. Although the practice is regulated by federal law (prescribed fire), there is no detailed information about the impacts of this practice on the small, non‐volant fauna. We evaluated the effect of fire management on anuran species richness and community composition in Brazilian grassland areas that have adopted this practice for more than 15 years. Our results show that burning practices lead to a reduction of anuran richness. About 37% of the species occur exclusively in sites free of fire. Sites with fire management have low densities of taller grass and shrubs, which could reduce habitat availability for some anuran species. Nestedness and turnover components of beta diversity did not differ within and between treatments, but there was a tendency for a nestedness organization of the community in burned sites, suggesting that sites with fire management are a subsample of sites where fire is absent. Our results pointed out that prescribed fire practices have potentially negative effects on the anuran diversity. These results suggest that the changes in vegetation, in particular percentages of shrub cover, affect habitat suitability for some species. Therefore, anuran communities tend to become less diverse and lack arboreal species where fire occurs.Abstract in Portuguese is available with online material.
Comparison of 11C‐Acetate and 18F‐FDG PET/CT for Immune Infiltration and Prognosis in Hepatocellular Carcinoma
Authors: Xu Hao , Wang Hao , Jiang Dong‐Lang , Wu Yan‐Fei , Xie Sun‐Zhe , Su Ying‐Han , Guan Yi‐Hui , Xie Fang , Zhu Wen‐Wei , Qin Lun‐Xiu 
Published: January 2025

ABSTRACTImmunotherapy has revolutionized cancer treatment, making it a challenge to noninvasively monitor immune infiltration. Metabolic reprogramming in cancers, including hepatocellular carcinoma (HCC), is closely linked to immune status. In this study, we aimed to evaluate the ability of carbon‐11 acetate (11C‐acetate) and fluorine‐18 fluorodeoxyglucose (18F‐FDG) PET/CT findings in predicting overall survival (OS) and immune infiltration in HCC patients. Totally 32 patients who underwent preoperative 18F‐FDG and 11C‐acetate PET/CT, followed by liver resection for HCC, were prospectively enrolled at authors' institute between January 2019 and October 2021. Tracer uptake was qualified. Densities of CD3+, CD8+, and granzyme B+ CD8+ immune cells were assessed and the Immunoscore was defined by combining the densities of CD3+ and CD8+ in tumor interior (TI) and invasion margin (IM). Patients with avid HCCs in 11C‐acetate PET/CT demonstrated a longer OS. Those with only 11C‐acetate‐avid HCCs exhibited a longer OS compared to those with only 18F‐FDG uptake. In contrast to 18F‐FDG uptake, 11C‐acetate uptake was positively associated with CD3+, CD8+, and granzyme B+ CD8+ cell infiltration. Patients with a higher Immunoscore exhibited a longer OS and an increased uptake of 11C‐acetate rather than 18F‐FDG. The sensitivity of 11C‐acetate PET/CT in the detection of patients with immune infiltration was superior to that of 18F‐FDG PET/CT (88% [21 of 24] vs. 58% [14 of 24]). These data show that preoperative 11C‐acetate PET/CT may be a promising approach for the evaluation of immune status and postoperative outcome of HCCs.
Local excision for T1 rectal cancer: A population‐based study of practice patterns and oncological outcomes
Authors: Brennan Kelly E. , Farooq Ameer O. , Mckechnie Tyler J. , Wiseman Vanessa H. , Kong Weidong , Bankhead Clare R. , Heneghan Carl J. , Rai Mandip S. , Patel Sunil V. 
Published: January 2025

AbstractAimLocal excision (LE) for T1 rectal cancer may be recommended in those with low‐risk disease, while resection is typically recommended in those with a high risk of luminal recurrence or lymph node metastasis. The aim of this work was to compare survival between resection and LE.MethodThis was a population‐based retrospective cohort study set in the Canadian province of Ontario. Patients were individuals with T1Nx rectal cancer between 2010 and 2014 and demographics, disease characteristics, treatments and outcomes were determined using linked administrative databases. This study does not include clinical information regarding individual patient treatment decisions. The main outcome measure was overall survival (OS).ResultsA total of 719 patients were identified, including 359 with upfront resection, 113 with LE and immediate resection (<90 days) and 247 with LE with definitive intent. The majority of LEs were performed via colonoscopy. Piecemeal excision (42% vs. 49%, p = 0.28) and positive margin (50% vs. 77%, p < 0.01) rates were high in both LE groups, with the highest rate in those with immediate resection. The prevalence of poor differentiation (<5%, p = 0.70) and lymphovascular invasion (LVI) (14%, p = 0.80) was similar across groups. In those with LE with definitive intent, 21% ultimately underwent resection (median 150 days, interquartile range 114–181 days) and 4% received radiation. There was no difference in 5‐year OS between groups (resection 83.2% vs. LE and immediate resection 82.3% vs. definitive LE 83.3%; p = 0.33). Adjusted analyses demonstrated no association between approach and survival [definitive intent LE hazard ratio (HR) 0.97 (95% CI 0.70–1.35), LE and immediate resection HR 0.97 (95% CI 0.60–1.45), upfront resection HR 1 (Ref); p = 0.98]. Differentiation, piecemeal excisions and LVI were not associated with OS in the LE groups.ConclusionThere were no observed differences in survival between those who underwent resection, LE and immediate resection and definitive intent LE. Although, these are observational data, they call into question the reflexive decision to offer radical resection for those with suspected T1 rectal cancer.
Safety, Tolerability, and Pharmacokinetics of NIM‐1324 an Oral LANCL2 Agonist in a Randomized, Double‐Blind, Placebo‐Controlled Phase I Clinical Trial
Authors: Leber Andrew , Hontecillas Raquel , Tubau‐Juni Nuria , Bassaganya‐Riera Josep 
Published: January 2025

ABSTRACTNIM‐1324 is an oral investigational new drug for autoimmune disease that targets the Lanthionine Synthetase C‐like 2 (LANCL2) pathway. Through activation of LANCL2, NIM‐1324 modulates CD4+ T cells to bias signaling and cellular metabolism toward increased immunoregulatory function while providing similar support to phagocytes. In primary human immune cells, NIM‐1324 reduces type I interferon and inflammatory cytokine (IL‐6, IL‐8) production. Oral NIM‐1324 was assessed for safety, tolerability and PK in normal healthy volunteers in a randomized, double‐blind, placebo‐controlled trial. Subjects (n = 57) were randomized into five single ascending dose (SAD) cohorts (250, 500, 750, 1000, 1500 mg, p.o.) and three multiple ascending dose (MAD) cohorts (250, 750, 1500 mg QD for 7 days, p.o.). NIM‐1324 did not increase total AE rates in individual cohorts or pooled active groups in SAD or MAD with no SAEs in the study. Oral NIM‐1324 dosing does not result in any clinically significant findings by biochemistry, coagulation, ECG, hematology, or urinalysis when compared to placebo. Plasma exposure, as measured by area under the curve from 0 to 24 h (AUC0‐24), scaled dose proportionally over 250–1000 mg. At 250 mg, NIM‐1324 successfully engaged the target with an upregulation of Lancl2 and key transcriptional biomarkers in whole blood. In conclusion, NIM‐1324 treatment is well‐tolerated up to daily oral doses of at least 1500 mg (nominal), a ≥ six‐fold margin over the anticipated therapeutic dose, and 1000 mg (maximum observed exposure), at least a four‐fold margin over the anticipated therapeutic dose with no dose limiting toxicities.