bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin‐degrading enzyme inhibition increases the unfolded protein response and favours lipid accumulation in the liver
Authors: Andres Marine , Hennuyer Nathalie , Zibar Khamis , Bicharel‐Leconte Marie , Duplan Isabelle , Enée Emmanuelle , Vallez Emmanuelle , Herledan Adrien , Loyens Anne , Staels Bart , Deprez Benoit , van Endert Peter , Deprez‐Poulain Rebecca , Lancel Steve 
Published: May 2024

Background and PurposeNonalcoholic fatty liver disease refers to liver pathologies, ranging from steatosis to steatohepatitis, with fibrosis ultimately leading to cirrhosis and hepatocellular carcinoma. Although several mechanisms have been suggested, including insulin resistance, oxidative stress, and inflammation, its pathophysiology remains imperfectly understood. Over the last decade, a dysfunctional unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress emerged as one of the multiple driving factors. In parallel, growing evidence suggests that insulin‐degrading enzyme (IDE), a highly conserved and ubiquitously expressed metallo‐endopeptidase originally discovered for its role in insulin decay, may regulate ER stress and UPR.Experimental ApproachWe investigated, by genetic and pharmacological approaches, in vitro and in vivo, whether IDE modulates ER stress‐induced UPR and lipid accumulation in the liver.Key ResultsWe found that IDE‐deficient mice display higher hepatic triglyceride content along with higher inositol‐requiring enzyme 1 (IRE1) pathway activation. Upon induction of ER stress by tunicamycin or palmitate in vitro or in vivo, pharmacological inhibition of IDE, using its inhibitor BDM44768, mainly exacerbated ER stress‐induced IRE1 activation and promoted lipid accumulation in hepatocytes, effects that were abolished by the IRE1 inhibitors 4μ8c and KIRA6. Finally, we identified that IDE knockout promotes lipolysis in adipose tissue and increases hepatic CD36 expression, which may contribute to steatosis.Conclusion and ImplicationsThese results unravel a novel role for IDE in the regulation of ER stress and development of hepatic steatosis. These findings pave the way to innovative strategies modulating IDE to treat metabolic diseases.
YTHDF3 phase separation regulates HSPA13‐dependent clear cell renal cell carcinoma development and immune evasion
Authors: Dai Chenyun , Cao Jianfu , Tang Yuangui , Jiang Yuxiao , Luo Chenghua , Zheng Junfang 
Published: May 2024

AbstractInsufficient understanding about the immune evasion mechanism leads to the inability in predicting current immunotherapy effects in clear cell renal cell carcinoma (ccRCC) and sensitizing ccRCC to immunotherapy. RNA binding proteins (RBPs) can promote tumor progression and immune evasion. However, research on RBPs, particularly m6A reader YTHDF3, in ccRCC development and immune evasion is limited. In this study, we found that YTHDF3 level was downregulated in ccRCC and was an independent prognostic biomarker for ccRCC. Decreased YTHDF3 expression was correlated with the malignancy, immune evasion, and poor response to anti‐programmed death ligand 1 (PD‐L1)/CTLA‐4 in ccRCC. YTHDF3 overexpression restrained ccRCC cell malignancy, PD‐L1 expression, CD8+ T cell infiltration and activities in vivo, indicating its inhibitory role in ccRCC development and immune evasion. Mechanistically, YTHDF3 WT was found to have phase separation characteristics and suppress ccRCC malignancy and immune evasion. Whereas YTHDF3 mutant, which disrupted phase separation, abolished its function. YTHDF3 enhanced the degradation of its target mRNA HSPA13 by phase separation and recruiting DDX6, resulting in the downregulation of the downstream immune checkpoint PD‐L1. HSPA13 overexpression restored ccRCC malignancy and immune evasion suppressed by YTHDF3 overexpression. In all, our results identify a new model of YTHDF3 in regulating ccRCC progression and immune evasion through phase separation.
Quantitative systems pharmacology modeling of macrophage‐targeted therapy combined with PD‐L1 inhibition in advanced NSCLC
Authors: Wang Hanwen , Arulraj Theinmozhi , Anbari Samira , Popel Aleksander S. 
Published: May 2024

AbstractImmune checkpoint inhibitors remained the standard‐of‐care treatment for advanced non‐small cell lung cancer (NSCLC) for the past decade. In unselected patients, anti‐PD‐(L)1 monotherapy achieved an overall response rate of about 20%. In this analysis, we developed a pharmacokinetic and pharmacodynamic module for our previously calibrated quantitative systems pharmacology model (QSP) to simulate the effectiveness of macrophage‐targeted therapies in combination with PD‐L1 inhibition in advanced NSCLC. By conducting in silico clinical trials, the model confirmed that anti‐CD47 treatment is not an optimal option of second‐ and later‐line treatment for advanced NSCLC resistant to PD‐(L)1 blockade. Furthermore, the model predicted that inhibition of macrophage recruitment, such as using CCR2 inhibitors, can potentially improve tumor size reduction when combined with anti‐PD‐(L)1 therapy, especially in patients who are likely to respond to anti‐PD‐(L)1 monotherapy and those with a high level of tumor‐associated macrophages. Here, we demonstrate the application of the QSP platform on predicting the effectiveness of novel drug combinations involving immune checkpoint inhibitors based on preclinical or early‐stage clinical trial data.
Rapid molecular profiling utilising minimal quantities of endobronchial ultrasound‐guided aspirates for the detection of Epidermal Growth Factor Receptor, KRAS, ALK, ROS1, RET, NTRK and MET gene alterations from patients with non‐small‐cell lung carcinomas on the Biocartis Idylla™ platform
Authors: Haragan Alexander , Lee Robert 
Published: May 2024

AbstractObjectivesComprehensive molecular analysis for patients with non‐small‐cell lung carcinoma (NSCLC) is essential for managing modern targeted therapies. This study sought to establish the feasibility of utilising real‐time PCR to perform rapid and comprehensive profiling on minimal amounts of endobronchial ultrasound‐guided (EBUS) aspirates as a fast, tissue‐sparing route of predictive profiling.MethodsA volume of 500 μL of EBUS aspirate and fixative from patients with NSCLC was decanted, and 80 μL (<1% of total specimen received) was utilised for analysis. Biocartis Idylla™ cartridges for epidermal growth factor receptor (EGFR) mutations, KRAS mutations and a GeneFusion cartridge (ALK, ROS1, RET, NTRK1/2/3 rearrangements & MET 14 exon skipping) were analysed for each case to provide molecular data on the main clinically relevant targets as per UK guidelines.ResultsA total of 62 cases were included; all of which had successful DNA analysis (EGFR and KRAS cartridges). RNA analysis (GeneFusion cartridge) was successful for 42 of 51 (82%) with initial approach, with 11 of 11 (100%) achieving a successful result with modified protocol. In all, 23 KRAS mutations (37%), 5 EGFR mutations (8%) and 1 ROS fusion (2%) were identified. Average time from specimen receipt to molecular read‐out was 5 h.ConclusionReal‐time PCR utilising the Idylla™ platform is rapid, utilises minimal amounts of tissue and provides accurate results. We propose this is a useful ancillary method to utilise alongside next‐generation sequencing (NGS) in cases of urgent clinical requirement or EBUS aspirates with inadequate quantities of tissue for NGS.
Effects of biochar versus film mulching on soil hydrothermal properties and wheat crop performance in semi‐arid loess
Authors: Wang Huan , Fan Jun , Shao Ming'an , Wang Xi , Wang Jia , Hao Mingde 
Published: May 2024

AbstractFilm mulching and biochar have been applied as effective measures for increasing crop yields in arid and semi‐arid areas for many years. However, the effects of the temporal and spatial distributions of soil hydrothermal properties on crop yields are still unclear under film mulching and biochar addition. Thus, we conducted a field experiment with winter wheat on the Loess Plateau of China for two years (2020–2022) with three treatments: control, film mulching, and biochar. The results demonstrated that film mulching and biochar addition increased the average soil temperature in the 0–50 cm soil depth throughout the whole growth period and the influence depth exceeded 50 cm. Biochar addition only significantly increased soil temperature in the overwintering stage (p < 0.05). Film mulching increased the maximum and minimum temperatures in the 0–50 cm soil depth at seedling stage. Film mulching and biochar increased average ≥10°C accumulated soil temperature by increasing the ≥10°C accumulated soil temperature in the daytime and nighttime, and the number of days with a daily soil temperature ≥10°C during the whole growth period. Film mulching improved soil water storage in the 0–300 cm soil depth in each growth stage during both years, and also increased the wheat grain yield, aboveground biomass, and water use efficiency. Biochar addition increased the wheat grain yield and aboveground biomass of two years compared with control, but the increases were not significant (p > 0.05). In addition, correlation analysis showed that adequate temperatures in the 0–50 cm soil depth during the seedling and overwintering stages, and suitable soil moisture conditions in the 0–300 cm soil depth before sowing, jointing, and filling stages were important factors for increasing wheat grain yields under film mulching. In summary, film mulching mainly regulated the soil temperature in the 0–50 cm soil depth and moisture conditions in the 0–300 cm soil depth during different growth stages to increase grain yields. Film mulching has more obvious effects on moisture regulation, temperature regulation, and yield increases than biochar addition. Some environmentally friendly measures (such as conservation agriculture) with the same yield improving effect as mulching are also recommended to explore and promote in theLoess Plateau region.
Derivation of physically based soil hydraulic parameters in New Zealand by combining soil physics and hydropedology
Authors: Pollacco J. A. P. , Fernández‐Gálvez J. , Webb T. , Vickers S. , Robertson B. , McNeill S. , Lilburne L. , Rajanayaka C. , Chau H. W. 
Published: May 2024

AbstractField‐characterised soil morphological data (to 1 m depth) and modelled soil water release characteristics are recorded in the S‐map database for soils covering approximately 40% of New Zealand's soil area. This paper shows the development of the Smap‐Hydro database that estimates hydraulic parameters by synergising soil morphologic data recorded in S‐map and soil physics. The Smap‐Hydro parameters were derived using the bi‐modal Kosugi hydraulic function. The validity of the Smap‐Hydro parameters was tested by applying them within an uncalibrated physically based hydrological model (HyPix) and comparing results with soil water content, θ, measured with Aquaflex soil moisture probes (0–40 cm deep) at 24 sites across New Zealand. The HyPix model provided an excellent fit with observed soil water content for 25% of the sites, a good fit for 33% of the sites and a poor fit for 42% of the sites. Applying the model to all soils in the S‐map database required adjustments for the occurrence of rock fragments, hydraulic discontinuities caused by soil pans and required the addition of boundary conditions for water tables and the occurrence of impermeable rock. A discussion on how we can further synergise the development of pedotransfer functions with knowledge of soil physics is provided.
Recently acquired HCV infection in men who have sex with men in Germany in the direct‐acting antivirals era and during the COVID‐19 pandemic
Authors: Ingiliz Patrick , Lutz Thomas , Schewe Knud , Baumgarten Axel , Krznaric Ivanka , Mauss Stefan , Christensen Stefan , Bickel Markus , Schmidt Axel J. , Sabranski Michael , He Feng , Jain Sonia , Martin Nastasha K. , Rockstroh Jürgen K. , Boesecke Christoph 
Published: May 2024

AbstractIntroductionDirect‐acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co‐infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro‐elimination despite high treatment rates.MethodsThe cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented.ResultsA total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39–52), and the median CD4 count was 660/mm3 (IQR 527–835).The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro‐elimination. The reinfection incidence was 15.5 per 100 patient‐years (95% confidence interval 12.6–18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre‐exposure prophylaxis.ConclusionsHigh treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID‐19 restrictions, led to micro‐elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals.
Post‐operative pain in non‐surgical root canal treatment after sealer‐based obturation versus warm vertical compaction: A randomized clinical trial
Authors: Alzoubi Fahad , Alajmi Samhan , Alkandari Abdullah , Alqahtani Saad , Alanezi Amer , Setzer Frank C. 
Published: May 2024

AbstractAimPost‐operative pain may occur after non‐surgical root canal treatment (NSRCT). The root filling technique and choice of sealer may be contributing factors. This randomized controlled clinical trial compared post‐operative pain and analgesics intake after NSRCT using a sealer‐based obturation technique (SBO) with single‐cone gutta‐percha and calcium silicate sealer (CSS) versus a warm‐vertical compaction (WVC) technique with gutta‐percha and a resin‐based sealer (RBS).MethodologyThis study was designed as a parallel‐two arm, double‐blind, randomized superiority clinical trial registered at www.clinicaltrials.gov (NCT04753138). Patients referred for NSRCT fulfilling the inclusion criteria participated in this study. Pre‐operative periapical radiographs and CBCT scans were taken and numerical rating scale (NRS) pain scores were recorded. Upon completion of canal instrumentation, participants were randomly allocated to either Group SBO: SBO with CSS or Group WVC: Warm‐vertical compaction with RBS. Post‐operative pain and analgesics intake were recorded at 1, 3 and 7 days after endodontic treatment completion. Non‐parametric Mann–Whitney U and Friedman tests and a generalized estimating equation were used to assess differences in pain scores between the groups, within each treatment group at different time points and for correlations, respectively.ResultsThe study included 195 participants (212 teeth). One participant declined to submit the NRS form. Therefore, 194 participants (211 teeth) were included in the final analysis (99.5% response rate). No statistically significant differences in post‐operative pain or analgesic intake existed between the two groups at any time point (p > .05). Age, pre‐operative pain, apical diagnosis and post‐operative analgesic intake were significantly related to post‐operative pain (p < .05).ConclusionsSealer‐based obturation technique with CSS was associated with similar post‐operative pain levels and analgesics intake as WVC with RBS. Regarding post‐operative pain, SBO with CSSs may be a suitable clinical alternative.
Academic discourse socialization in a “bilingual” undergraduate course: Group work among students with diverse cultural and linguistic backgrounds
Authors: Itoi Kiyu , Mizukura Ryo 
Published: May 2024

AbstractWith the growth of internationalization in higher education, there is a need to examine students’ experiences in increasingly diverse classrooms. This study explores students’ academic discourse socialization (ADS), within a context where the majority of students are non‐native speakers, in a course designed to enhance intercultural communication skills by providing students with both theoretical knowledge and practical experiences to collaborate with a diverse group of peers. We aim to answer the following questions: (1) Does native‐speakerism ideology impact Japanese students’ comprehension of intercultural communication with non‐native speakers, and if so, how? (2) How does the understanding of intercultural communication affect students’ interactions and group work with international peers? We conducted qualitative semistructured interviews with Japanese and international students at a private Japanese university. Our findings show that despite the absence of specific language instruction in the course, the group work predominantly utilized English and Japanese. Furthermore, the results revealed a unique ADS process in this context, with no clear dichotomy between experts and novices. Instead, all students negotiated their participation and language use within the academic community, with native‐speakerism ideology influencing the ADS process. These results enrich the research on ADS in non‐English‐speaking countries and development of new conceptual frameworks to better comprehend its dynamics.
Integrating health–life balance, job satisfaction and family–work interference among housemaids: Insights through Social Exchange Theory
Authors: Krishnakumar Sheeja 
Published: May 2024

AbstractHousemaids play an essential role in the urban household and support their domestic chores so that urbanites go to work, indirectly contributing to the country's economy. Hence, this study has significance in understanding the impact of work–health balance, work–life balance, family–work interference, job satisfaction, marital status and parental status on job involvement within the framework of Social Exchange Theory among housemaids working in selected dwellings in Bangalore, India. This study aims to determine the influence of work–life and work–health balance on job satisfaction and the impact of moderators as well as the influence of family–work interference on work and health balance and mediators’ impact, finally, the impact of work and health balance, job satisfaction, family–work interference, parental and marital status on job involvement. The data was collected from 571 housemaids working in six apartments in East Bangalore. Attaining job satisfaction from work–health balance and work–life balance is proven true among housemaids. The moderators’ age and parental status have a moderating role. Work–health and work–life balance impact family–work interference and are mediated by employer support. Work–health balance, work–life balance and job satisfaction have a significant relationship with job involvement, whereas family–work interference and parental status are negatively related. Employers recognizing work–health and work–life balance enhance job satisfaction and job involvement among housemaids, benefiting both the housemaids and employers, which is proved in this study.
Strategies for genomic predictions of an indicine multi‐breed population using single‐step GBLUP
Authors: Londoño‐Gil Marisol , López‐Correa Rodrigo , Aguilar Ignacio , Magnabosco Claudio Ulhoa , Hidalgo Jorge , Bussiman Fernando , Baldi Fernando , Lourenco Daniela 
Published: May 2024

AbstractBrazilian livestock breeding programmes strive to enhance the genetics of beef cattle, with a strong emphasis on the Nellore breed, which has an extensive database and has achieved significant genetic progress in the last years. There are other indicine breeds that are economically important in Brazil; however, these breeds have more modest sets of phenotypes, pedigree and genotypes, slowing down their genetic progress as their predictions are less accurate. Combining several breeds in a multi‐breed evaluation could help enhance predictions for those breeds with less information available. This study aimed to evaluate the feasibility of multi‐breed, single‐step genomic best linear unbiased predictor genomic evaluations for Nellore, Brahman, Guzerat and Tabapua. Multi‐breed evaluations were contrasted to the single‐breed ones. Data were sourced from the National Association of Breeders and Researchers of Brazil and included pedigree (4,207,516), phenotypic (328,748), and genomic (63,492) information across all breeds. Phenotypes were available for adjusted weight at 210 and 450 days of age, and scrotal circumference at 365 days of age. Various scenarios were evaluated to ensure pedigree and genomic information compatibility when combining different breeds, including metafounders (MF) or building the genomic relationship matrix with breed‐specific allele frequencies. Scenarios were compared using the linear regression method for bias, dispersion and accuracy. The results showed that using multi‐breed evaluations significantly improved accuracy, especially for smaller breeds like Guzerat and Tabapua. The validation statistics indicated that the MF approach provided accurate predictions, albeit with some bias. While single‐breed evaluations tended to have lower accuracy, merging all breeds in multi‐breed evaluations increased accuracy and reduced dispersion. This study demonstrates that multi‐breed genomic evaluations are proper for indicine beef cattle breeds. The MF approach may be particularly beneficial for less‐represented breeds, addressing limitations related to small reference populations and incompatibilities between G and A22. By leveraging genomic information across breeds, breeders and producers can make more informed selection decisions, ultimately improving genetic gain in these cattle populations.
Synchronization of in vivo MacoNPV‐A baculovirus infection by analysis of individual Mamestra configurata larval guts
Authors: Donly B. Cameron , Theilmann David A. , Hegedus Dwayne D. , Baldwin Douglas , Erlandson Martin A. 
Published: May 2024

AbstractMany studies have examined the gene expression of baculoviruses during host infection by infecting cultured insect host cells; however, only a few have attempted to characterize the interaction between baculoviruses and insect larvae, which more accurately models the virus‐insect relationship. The greatest challenge in assessing gene expression profiles in vivo in the larval gut is the lack of infection synchronization compared to cultured cells. Working with bertha armyworm, Mamestra configurata, larvae infected with the baculovirus Mamestra configurata nucleopolyhedrovirus‐A (MacoNPV‐A), viral gene expression was measured using droplet‐digital PCR, showing that the rate of infection in individual insects varies extremely widely. Subsequent RNA‐Seq of individual guts revealed that gene expression patterns were consistent in individuals with similar levels of viral gene expression. Therefore, the best approach for analysing baculovirus gene expression in vivo is to use the expression of an early viral gene as a means to select individuals that are closely matched in infection progress to produce the most synchronized infection cohorts for measuring gene expression profiles. In this way, a profile of gene expression was identified very early in infection that would have been masked by the activity of a few very robustly infected individuals present in sample pools made up of multiple individuals.