bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four glycosyltransferase genes are responsible for synthesis and accumulation of different flavonol glycosides in apple tissues
Authors: Zhu Xiaoping , Chen Ying , Jiao Ju , Zhao Shanshan , Yan Yanfang , Ma Fengwang , Yao Jia‐Long , Li Pengmin 
Published: June 2024

SUMMARYFlavonols are widely synthesized throughout the plant kingdom, playing essential roles in plant physiology and providing unique health benefits for humans. Their glycosylation plays significant role in improving their stability and solubility, thus their accumulation and function. However, the genes encoding the enzymes catalyze this glycosylation remain largely unknown in apple. This study utilized a combination of methods to identify genes encoding such enzymes. Initially, candidate genes were selected based on their potential to encode UDP‐dependent glycosyltransferases (UGTs) and their expression patterns in response to light induction. Subsequently, through testing the in vitro enzyme activity of the proteins produced in Escherichia coli cells, four candidates were confirmed to encode a flavonol 3‐O‐galactosyltransferase (UGT78T6), flavonol 3‐O‐glucosyltransferase (UGT78S1), flavonol 3‐O‐xylosyltransferase/arabinosyltransferase (UGT78T5), and flavonol 3‐O‐rhamnosyltransferase (UGT76AE22), respectively. Further validation of these genes' functions was conducted by modulating their expression levels in stably transformed apple plants. As anticipated, a positive correlation was observed between the expression levels of these genes and the content of specific flavonol glycosides corresponding to each gene. Moreover, overexpression of a flavonol synthase gene, MdFLS, resulted in increased flavonol glycoside content in apple roots and leaves. These findings provide valuable insights for breeding programs aimed at enriching apple flesh with flavonols and for identifying flavonol 3‐O‐glycosyltransferases of other plant species.
Prevalence of presumed endplate junction failure at the lumbosacral intervertebral junction in dogs on computed tomography
Authors: Tellegen Anna R. , Beukers Martijn , Meij Björn P. , Tryfonidou Marianna A. , Veraa Stefanie 
Published: June 2024

AbstractLumbosacral intervertebral disc herniation (IVDH) is a common cause of lower back pain in dogs and humans. In humans, the vertebral endplate to annulus fibrosus (AF) attachment was implicated as an alternative failure site besides rupture through the dorsal AF (AFF). Endplate junction failure (EPJF) is characterized by IVDH, accompanied by endplate irregularities (type A), rim avulsions (type B), or larger bony avulsions on one (type C) or both endplates (type D), associated with an adjacent endplate defect. This retrospective study reports the CT prevalence of presumed EPJF in dogs and its associations with signalment and other lumbosacral CT abnormalities. CT scans, including the lumbosacral spine of dogs obtained at two institutions, were assessed, yielding 324 scans. Presumed EPJF was found in 69 dogs (21%) and AFF in 68 dogs (21%), commonly at the caudal endplate of the last lumbar vertebra (71%). The remaining 187 dogs did not show presumed EPJF or AFF. Presumed EPJF type A occurred in 49/69, type B in 19/69, and type C in 1/69 dogs. Univariable logistic regression showed that presumed EPJF was associated with significantly higher IVDH grades than AFF. In the multiple regression model, presumed EPJF and AFF remained associated with increasing age and spondylosis deformans. Presumed EPJF was associated with vertebral endplate sclerosis and AFF with zygapophyseal joint osteoarthritis. In conclusion, presumed EPJF was observed on CT in 21% of dogs with lumbosacral IVDH. Prospective studies correlating EPJF on CT with clinical, surgical, and histopathological findings are needed for a better understanding of the underlying pathology and clinical relevance.
Molecular characterization of rabies virus from wild and domestic animals in the Sultanate of Oman
Authors: Ali Haytham , Ali Ahmed , Al Mawly Julanda , Tohamy Hossam G. , El‐Neweshy Mahmoud S. 
Published: June 2024

AbstractAimsRabies virus (RV) is endemic in some Arabian countries. However, it is difficult to control RV without understanding the epidemiological evolution of endemic RV isolates. The current study aimed to characterize RV from domestic and wild animal clinical cases in Oman.Methods and ResultsTwelve brain samples from domestic (Five camels, three goats and one cattle) and wild animals (Two foxes and one honey badger) were investigated from different locations in Oman between 2017 and 2020. All samples were confirmed by RV nucleoprotein (N) gene‐specific primers. Seven out of the 12 amplified samples were successfully sequenced and subjected to sequence and phylogenetic analysis. The detected RVs shared an in‐between 96.8%–98.7% and 96.9%–99% nucleotide and amino acid identities, respectively. However, the wild animal RVs shared only 92.6%–93.9% and 95.9% nucleotide and amino acid identities with the domestic animal RVs, respectively. Negri bodies were detected histologically in six brain samples from camels (n = 3), goats (n = 1) and foxes (n = 2). The RVs from domestic animals shared 97%–98.7% and 98%–100% nucleotide and amino acid identities with the previously published fox RVs from Oman and Gulf countries. Phylogenetic analysis suggested that all RV sequences belong to a distinct clade confined to the previously reported clade V within the Middle Eastern Cluster.ConclusionsAs indicated by the analysis of RVs from different locations between 2017 and 2020, a genetic variant isolated to the Gulf region may exist within the Middle East clade. Moreover, it appears that new RV lineages are emerging rapidly within this region. Therefore, a comprehensive genomic and phylogenetic analysis of the circulating RV is important for the development of future prevention and control strategies.
Health net-outcome objectives and approaches for spatial planning and development: a scoping review protocol
Authors: Stewart-Evans James , Wilson Emma , Langley Tessa , Hands Angela , Leonardi-Bee Jo 
Published: June 2024

Objective:
The objective of this scoping review is to review the body of knowledge on net gain and no net loss (net-outcome) objectives and approaches applicable to health in spatial planning and development policies and practice.

Introduction:
There is an established body of academic and gray literature addressing environmental net-outcome objectives, such as biodiversity net gain, in spatial planning policies and practice. A “health net gain” objective has recently been proposed as a driver for health protection and the realization of health. Such an objective and approach are yet to be scoped and defined.

Inclusion criteria:
This review will consider sources in the scientific and gray literature that describe health net-outcome objectives that can be implemented in spatial planning and development policies and practice. Source contexts will not be limited to specific countries, geographical areas, or settings. All types of evidence will be considered.

Methods:
This review will follow the JBI methodology for scoping reviews. Databases to be searched include PsycINFO, Embase, HMIC Health Management Information Consortium, MEDLINE (Ovid), Scopus, and selected databases from the ProQuest Social Science Premium Collection. Sources of gray literature to be searched include ProQuest Dissertations and Theses, TRIP Pro, and BASE. No language or date restrictions will be applied. Two independent reviewers will retrieve and review full-text studies and extract data. The results will be presented in tabular or diagrammatic format with a narrative summary.

Review registration:
Open Science Framework https://osf.io/4dbcm
Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1‐G93A mice
Authors: Deutsch Andrew J. , Elbasiouny Sherif M. 
Published: June 2024

AbstractPersistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)‐G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS. To fill this gap, we measured the net and individual PIC and POC components of wild‐type (WT) and SOD MNs in current clamp and voltage clamp during disease progression (assessed by neuroscores). We show that SOD MNs of symptomatic mice experience a much larger net PIC, relative to WT cells from age‐matched littermates. Specifically, the Na+ and Ca2+ PICs are larger, whereas the lasting SK‐mediated (SKL) POC is smaller than WT (Na+ PIC is the largest and SKL POC is the smallest components in SOD MNs). We also show that PIC dysregulation is present at symptom onset, is sustained throughout advanced disease stages and is proportional to SOD MN cell size (largest dysregulation is in the largest SOD cells, the most vulnerable in ALS). Additionally, we show that studying disease progression using neuroscores is more accurate than using SOD mouse age, which could lead to misleading statistics and age‐based trends. Collectively, this study contributes novel PIC and POC data, reveals ionic mechanisms contributing to the vulnerability differential among MN types/sizes, and provides insights on the roles PIC and POC mechanisms play in MN excitability dysfunction in ALS.
imageKey points
Individual persistent inward currents (PICs) and persistent outward currents (POCs) have never been examined before in spinal motoneurons (MNs) of symptomatic amyotrophic lateral sclerosis (ALS) mice. Thus, we contribute novel PIC and POC data to the ALS literature.
Male SOD MNs of symptomatic mice have elevated net PIC, with larger Na+ and Ca2+ PICs but reduced SKL POC vs. wild‐type littermates. Na+ PIC is the largest and SKL POC is the smallest current in SOD cells.
The PIC/POC dysregulation is present at symptom onset. PIC dysregulation is sustained throughout advanced disease, and is proportional to SOD MN size (largest dysregulation is in the largest cells, the most vulnerable in ALS). Thus, we reveal ionic mechanisms contributing to the vulnerability differential among MN types/sizes in ALS.
Studying disease progression using SOD mice neuroscores is more accurate than using age, which could distort the statistical differences between SOD and WT PIC/POC data and the trends during disease progression.
Views of emergency care providers in providing healthcare for asylum seekers and refugees
Authors: Doherty Cal , Quinn Joanna , Lowe David John , Khanolkar Amal R 
Published: June 2024

BackgroundThe number of asylum seekers awaiting decisions on their claims in the UK has more than tripled since 2014. How we meet international obligations to provide appropriate healthcare to asylum seekers and refugees (ASRs) is therefore an increasingly important issue. The views of frontline healthcare workers are vital to ensure the development of sustainable and effective health policy when it comes to caring for this group.MethodA single-centre qualitative study in the form of semistructured interviews was conducted at the Queen Elizabeth University Hospital ED in Glasgow, Scotland, between January and March 2023. Volunteering ED care providers (EDCPs)—doctors and nurses—working in the ED were interviewed and the data analysed and presented through a thematic analytical framework.Results12 semistructured interviews were conducted—6 doctors and 6 nurses. Analysis revealed four themes: (1) ‘staff attitudes’ highlighted in particular the positive views of the participants in providing care for ASRs; (2) ‘presentation patterns’ revealed significant variations in opinion, with one-third of participants, for example, believing there was no difference in presentations compared with the general population; (3) ‘challenges to optimal care’ outlines multiple subthemes which impact care including the unique challenge of the ED triage system; and (4) ‘transition in care’ discusses participant concerns regarding arranging safe and appropriate follow-up for ASR patients. Ethical dilemmas in providing care, as highlighted in previous studies, did not feature heavily in discussions in this study.ConclusionThis study provides an insight into the views of EDCPs in providing care to ASRs in the ED. Study findings can potentially contribute to the development of ED-specific guidelines as well as inform wider health policy and provide a focus and direction for further research.
Protein O-fucosyltransferase 1 promotes PD-L1 stability to drive immune evasion and directs liver cancer to immunotherapy
Authors: Li Qianyu , Guo Wenyun , Qian Yifei , Li Songling , Li Linfeng , Zhu Zijun , Wang Fan , Tong Yu , Xia Qiang , Liu Yanfeng 
Published: June 2024

Background and aimsThe immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy.MethodsDe novoMYC/Trp53−/−liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underlying mechanism of POFUT1-mediated immune evasion.ResultsWe identified POFUT1 as a crucial promoter of immune evasion in liver cancer. Notably, POFUT1 promoted HCC progression and inhibited T-cell infiltration in the xenograft tumor and de novo MYC/Trp53−/−mouse liver tumor models. Mechanistically, we demonstrated that POFUT1 stabilized programmed death ligand 1 (PD-L1) protein by preventing tripartite motif containing 21-mediated PD-L1 ubiquitination and degradation independently of its protein-O-fucosyltransferase activity. In addition, we further demonstrated that PD-L1 was required for the tumor-promoting and immune evasion effects of POFUT1 in HCC. Importantly, inhibition of POFUT1 could synergize with anti-programmed death receptor 1 therapy by remodeling TME in the xenograft tumor mouse model. Clinically, POFUT1 high expression displayed a lower response rate and worse clinical outcome to ICB therapies.ConclusionsOur findings demonstrate that POFUT1 functions as a novel regulator of tumor immune evasion and inhibition of POFUT1 may be a potential therapeutic strategy to enhance the efficacy of immune therapy in HCC.
Complex immune microenvironment of chordoma: a road map for future treatment
Authors: Niu Hua-Qing , Zheng Bo-Yv , Zou Ming-Xiang , Zheng Bo-Wen 
Published: June 2024

BackgroundChordoma, a rare bone tumor, presents limited treatment options and patients typically exhibit poor survival outcomes. While immunotherapy has shown promising results in treating various tumors, research on the immune microenvironment of chordomas is still in its early stages. Therefore, understanding how the immune microenvironment of chordomas influences the outcomes of immunotherapy is crucial.MethodsWe employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, CellChat, gene set variation analysis, as well as calculation of immune features to further dissect the complex immune microenvironment of chordoma.ResultsPrevious research by van Oostet alargued that compared with other sarcomas, chordomas typically exhibit an immunologically “hot” microenvironment, a conclusion with which we concur based on their research findings. Additionally, the authors suggest that T cell-mediated immunotherapy is feasible for the majority of chordomas. However, we are inclined to categorize them as an immune-excluded phenotype according to the latest classification methods, rather than persisting with the concepts of “cold” and “hot”. Unlike them, we explored immune infiltration scores (IS), T lymphocyte scoring (TLS), and human leucocyte antigen class I (HLA-I) using Bulk RNA-seq data from 126 chordoma patients and found that higher IS, TLS, and higher HLA-I expression were associated with poorer patient prognosis. Additionally, CellChat analysis of scRNA-seq results from six chordoma patients revealed no direct interaction between T cells and tumor cells.ConclusionsThese findings suggested that the efficacy of T cell-based immunotherapy may be limited or even ineffective for patients with chordoma.
Circulating receptor activator of nuclear factor kappa-B ligand (RANKL) levels predict response to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC)
Authors: Iuliani Michele , Simonetti Sonia , Cristofani Leonardo , Cavaliere Silvia , Cortellini Alessio , Russano Marco , Vincenzi Bruno , Tonini Giuseppe , Santini Daniele , Pantano Francesco 
Published: June 2024

BackgroundReceptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment and immune cell responses. This study aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy.MethodsPlasma RANKL levels were measured in 100 patients with advanced NSCLC without bone metastases undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. To establish the optimal cut-off value, we used the Cutoff Finder package in R. Survival curves for four distinct patient groups, according to their RANKL and PDL1 levels (high or low), were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS).ResultsThe optimal RANKL cut-off was established at 280.4 pg/mL, categorizing patients into groups with high or low RANKL levels. A significant association was observed between increased RANKL concentrations and decreased survival rates at 24 months, only within the subgroup expressing high levels of PDL1 (p=0.002). Additionally, low RANKL levels in conjunction with elevated PDL1 expression correlated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, p=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, p=0.003), indicating RANKL’s potential as an indicator of adverse prognosis in these patients. Multivariate analysis identified RANKL as an independent negative prognostic factor for both PFS and OS, regardless of other clinicopathological features.ConclusionThese results highlight the prognostic and predictive value of RANKL specifically in patients with high PDL1 expression.
Assessing water position through distributed temperature sensing using Rayleigh-based optical frequency-domain reflectometry: a laboratory feasibility study
Authors: Acharya Ashis , Tanimura Daiki , Zhang Chao , Ito Fumihiko , Sakaki Toshihiro , Komatsu Mitsuru , Doi Issei , Kogure Tetsuya 
Published: June 2024

This study demonstrates the ability of the Rayleigh-based phase-noise compensated optical frequency-domain reflectometry (PNC-OFDR) sensing method to monitor the distributed temperature field with an ultra-short data acquisition period of 2 ms, a spatial resolution of 2 cm, and a temperature resolution of 0.1 °C. A heating cable (H-cable) was embedded within a cylindrical concrete mortar specimen and subjected to various heating powers. A sensing optical cable (temperature measurement cable) was placed adjacent to the H-cable to monitor the temperature distribution continuously. Two water-holding boxes were installed along the specimen at two positions to retain water. The study’s results indicated that the PNC-OFDR technique demonstrated a high sensitivity to even small temperature changes, enabling it to pinpoint water locations at two distinct points accurately. The research determined the minimal heating power required to successfully locate the water positions. The magnitude of the heating power exerted a significant impact on the temperature change. Three distinct phases of temperature increment were observed for a given heating period: rapid, fast, and gentle increase. The insights gained from this study have the potential to be applied in natural fields, allowing for the detection of groundwater and seepage phenomena in vulnerable slopes.
Background gravitational waves as signature of the adiabatic expansion of a black body that represents the dark universe
Authors: Cruz Cláudio Nassif , Amaro de Faria Jr. A.C. 
Published: June 2024

We propose a toy model of a spherical universe made up of an exotic dark gas with temperature T in thermal equilibrium with a black body in adiabatic expansion. Each particle of this exotic gas mimics a kind of particle of dark energy represented by the vacuum energy, being quantized into virtual particles with extremely small masses that form such gas representing the own tissue of the expanding space–time governed by a negative pressure whose origin is the equation of state of vacuum, i.e., p = −ρ, where ρ is the vacuum energy density. So, each vacuum particle occupies a tiny area of space so-called Planck area [Formula: see text], which represents the minimum area of the whole space–time given by the spherical surface with area [Formula: see text], where RH is the Hubble radius. We realize that such spherical surface is the surface of the black body for representing the dark universe as if it were the surface of an expanding balloon. Thus, we are able to derive the law of universal gravitation, thus leading us to understand the cosmological anti-gravity. We estimate the very small order of magnitude of the cosmological constant and the acceleration of expansion of the dark sphere. In this toy model, as the dark universe can be thought of as a large black body, when we obtain its power and frequency of emission of radiation, we find very low values. We conclude that such radiation and frequency of the black body made up of dark energy is a background gravitational wave with very low frequency in the order of 10−17Hz due to the slight stretching of the fabric of space–time.
A Survey of General-purpose Polyhedral Compilers
Authors: Thangamani Arun , Loechner Vincent , Genaud Stéphane 
Published: June 2024

Since the 1990s, many implementations of polyhedral compilers have been written and distributed, either as source-to-source translating compilers or integrated into wider-purpose compilers. This article provides a survey on those various available implementations as of today, 2024.
First, we list and describe most commonly available polyhedral schedulers and compiler implementations. Then, we compare the general-purpose polyhedral compilers using two main criteria—robustness and performance—on the PolyBench/C set of benchmarks.