bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a GRGPI model for predicting the prognostic and treatment outcomes in head and neck squamous cell carcinoma
Authors: Han Fei , Wang Hong-Zhi , Chang Min-Jing , Hu Yu-Ting , Liang Li-Zhong , Li Shuai , Liu Feng , He Pei-Feng , Yang Xiao-Tang , Li Feng 
Published: January 2023

BackgroundHead and neck squamous cell carcinoma (HNSCC) is among the most lethal and most prevalent malignant tumors. Glycolysis affects tumor growth, invasion, chemotherapy resistance, and the tumor microenvironment. Therefore, we aimed at identifying a glycolysis-related prognostic model for HNSCC and to analyze its relationship with tumor immune cell infiltrations.MethodsThe mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), while glycolysis-related genes were obtained from the Molecular Signature Database (MSigDB). Bioinformatics analysis included Univariate cox and least absolute shrinkage and selection operator (LASSO) analyses to select optimal prognosis-related genes for constructing glycolysis-related gene prognostic index(GRGPI), as well as a nomogram for overall survival (OS) evaluation. GRGPI was validated using the Gene Expression Omnibus (GEO) database. A predictive nomogram was established based on the stepwise multivariate regression model. The immune status of GRGPI-defined subgroups was analyzed, and high and low immune groups were characterized. Prognostic effects of immune checkpoint inhibitor (ICI) treatment and chemotherapy were investigated by Tumor Immune Dysfunction and Exclusion (TIDE) scores and half inhibitory concentration (IC50) value. Reverse transcription-quantitative PCR (RT-qPCR) was utilized to validate the model by analyzing the mRNA expression levels of the prognostic glycolysis-related genes in HNSCC tissues and adjacent non-tumorous tissues.ResultsFive glycolysis-related genes were used to construct GRGPI. The GRGPI and the nomogram model exhibited robust validity in prognostic prediction. Clinical correlation analysis revealed positive correlations between the risk score used to construct the GRGPI model and the clinical stage. Immune checkpoint analysis revealed that the risk model was associated with immune checkpoint-related biomarkers. Immune microenvironment and immune status analysis exhibited a strong correlation between risk score and infiltrating immune cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis showed typical immune pathways. Furthermore, the GRGPIdel showed excellent predictive performance in ICI treatment and drug sensitivity analysis. RT-qPCR showed that compared with adjacent non-tumorous tissues, the expressions of five genes were significantly up-regulated in HNSCC tissues.ConclusionThe model we constructed can not only be used as an important indicator for predicting the prognosis of patients but also had an important guiding role for clinical treatment.
Osteocalcin serum concentrations and markers of energetic metabolism in pediatric patients. Systematic review and metanalysis
Authors: Rodríguez-Narciso Silvia , Martínez-Portilla Raigam Jafet , Guzmán-Guzmán Iris Paola , Careaga-Cárdenas Gabriela , Rubio-Navarro Brenda Jazmin , Barba-Gallardo Luis Fernando , Delgadillo-Castañeda Rodolfo , Villafan-Bernal José Rafael 
Published: January 2023

BackgroundOsteocalcin plays a role in glucose metabolism in mice, but its relevance in human energetic metabolism is controversial. Its relationship with markers of energetic metabolism in the pediatric population has not been systematically addressed in infants and adolescents.ObjectiveThis study aims to assess the mean differences between tOC, ucOC, and cOC among healthy children and children with type 1 or type 2 diabetes (T1D or T2D) and the correlation of these bone molecules with metabolic markers.MethodsA systematic review and metanalysis were performed following PRISMA criteria to identify relevant observational studies published in English and Spanish using PubMed, Scopus, EBSCO, and Web of Science databases. The risk of bias was assessed using New Castle–Ottawa scale. Effect size measures comprised standardized mean difference (SMD) and Pearson correlations. Heterogeneity and meta-regressions were performed.ResultsThe 20 studies included were of high quality and comprised 3,000 pediatric patients who underwent tOC, cOC, or ucOC measurements. Among healthy subjects, there was a positive correlation of ucOC with WC and weight, a positive correlation of tOC with FPG, HDL-c, WC, height, and weight, and a negative correlation between tOC and HbA1c. Among diabetic subjects, a negative correlation of ucOC with HbA1c and glycemia in both T1D and T2D was found and a negative correlation between tOC and HbA1c in T1D but not in T2D. The ucOC concentrations were lower in T2D, T1D, and patients with abnormal glucose status than among controls. The serum concentrations of tOC concentrations were lower among T1D than in controls. The patient's age, altitude, and HbA1c influenced the levels of serum tOC.ConclusionOsteocalcin is involved in energy metabolism in pediatric subjects because it is consistently related to metabolic and anthropometric parameters.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42019138283.
Efficacy and safety of Chinese herbal medicine in the treatment of chronic pruritus: A systematic review and meta-analysis of randomized controlled trials
Authors: Wang Jie , Chen Yuhang , Yang Xinwei , Huang Jianli , Xu Yihua , Wei Wei , Wu Xianbo 
Published: January 2023

Background: Chronic pruritus (CP) is a common and aggravating symptom associated with skin and systemic diseases. Although clinical reports suggest that Chinese herbal medicine (CHM) is safe and effective in Chronic pruritus treatment, evidence to prove it is lacking. Therefore, in this review, we evaluated the therapeutic effects and safety of Chinese herbal medicine for the treatment of Chronic pruritus.Methods: Nine databases were searched for relevant randomized controlled trials (RCTs) from the inception of the database to 20 April 2022. The randomized controlled trials that compared the treatment of Chinese herbal medicine or a combination of Chinese herbal medicine and conventional western medicine treatment (WM) with western medicine treatment intervention for patients with Chronic pruritus were selected. We evaluated the effects of treatment with Chinese herbal medicine on the degree of pruritus, the Dermatology Life Quality Index (DLQI) score, response rate, recurrence rate, and incidence of adverse events in patients with Chronic pruritus. The risk of bias in each trial was evaluated using the Cochrane Collaboration tool. The RevMan software (version 5.3) was used for performing meta-analyses to determine the comparative effects.Results: Twenty-four randomized controlled trials were included, compared with placebo, moderate-quality evidence from one study showed that Chinese herbal medicine was associated with reduced visual analogue scale (VAS) (MD: −2.08; 95% CI = −2.34 to −1.82). Compared with western medicine treatment, low-to moderate-quality evidence from 8 studies indicated that Chinese herbal medicine was associated with reduced visual analogue scale, 4 studies indicated that Chinese herbal medicine was associated with reduced Dermatology Life Quality Index (MD = −1.80, 95% CI = −2.98 to −.62), and 7 studies indicated that Chinese herbal medicine was associated with improved Effective rate (RR: 1.26; 95% CI = 1.19–1.34). Compared with combination of Chinese herbal medicine and western medicine treatment, 16 studies indicated that Chinese herbal medicine was associated with reduced visual analogue scale, 4 studies indicated that Chinese herbal medicine was associated with reduced Dermatology Life Quality Index (MD = −2.37, 95% CI = −2.61 to −2.13), and 13 studies indicated that Chinese herbal medicine was associated with improved Effective rate (RR: 1.28; 95% CI = 1.21–1.36). No significant difference in the occurrence of adverse events in using Chinese herbal medicine or western medicine treatment was reported.Conclusion: The efficacy of Chinese herbal medicine used with or without western medicine treatment was better than western medicine treatment in treating chronic pruritus. However, only a few good studies are available regarding Chronic pruritus, and thus, high-quality studies are necessary to validate the conclusions of this study.
Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach
Authors: Michelet Robin , Bindellini Davide , Melin Johanna , Neumann Uta , Blankenstein Oliver , Huisinga Wilhelm , Johnson Trevor N. , Whitaker Martin J. , Ross Richard , Kloft Charlotte 
Published: January 2023

Introduction: Hydrocortisone is the standard of care in cortisol replacement therapy for congenital adrenal hyperplasia patients. Challenges in mimicking cortisol circadian rhythm and dosing individualization can be overcome by the support of mathematical modelling. Previously, a non-linear mixed-effects (NLME) model was developed based on clinical hydrocortisone pharmacokinetic (PK) pediatric and adult data. Additionally, a physiologically-based pharmacokinetic (PBPK) model was developed for adults and a pediatric model was obtained using maturation functions for relevant processes. In this work, a middle-out approach was applied. The aim was to investigate whether PBPK-derived maturation functions could provide a better description of hydrocortisone PK inter-individual variability when implemented in the NLME framework, with the goal of providing better individual predictions towards precision dosing at the patient level.Methods: Hydrocortisone PK data from 24 adrenal insufficiency pediatric patients and 30 adult healthy volunteers were used for NLME model development, while the PBPK model and maturation functions of clearance and cortisol binding globulin (CBG) were developed based on previous studies published in the literature.Results: Clearance (CL) estimates from both approaches were similar for children older than 1 year (CL/F increasing from around 150 L/h to 500 L/h), while CBG concentrations differed across the whole age range (CBGNLME stable around 0.5 μM vs. steady increase from 0.35 to 0.8 μM for CBG PBPK). PBPK-derived maturation functions were subsequently included in the NLME model. After inclusion of the maturation functions, none, a part of, or all parameters were re-estimated. However, the inclusion of CL and/or CBG maturation functions in the NLME model did not result in improved model performance for the CL maturation function (ΔOFV &gt; −15.36) and the re-estimation of parameters using the CBG maturation function most often led to unstable models or individual CL prediction bias.Discussion: Three explanations for the observed discrepancies could be postulated, i) non-considered maturation of processes such as absorption or first-pass effect, ii) lack of patients between 1 and 12 months, iii) lack of correction of PBPK CL maturation functions derived from urinary concentration ratio data for the renal function relative to adults. These should be investigated in the future to determine how NLME and PBPK methods can work towards deriving insights into pediatric hydrocortisone PK.
Identification of a novel P2X7 antagonist using structure-based virtual screening
Authors: Pasqualetto Gaia , Zuanon Marika , Brancale Andrea , Young Mark T. 
Published: January 2023

P2X4 and P2X7 receptors are ATP-gated ion channels, which play important roles in neuropathic and inflammatory pain, and as such they are important drug targets in diseases of inflammatory origin. While several compounds targeting P2X4 and P2X7 receptors have been developed using traditional high-throughput screening approaches, relatively few compounds have been developed using structure-based design. We initially set out to develop compounds targeting human P2X4, by performing virtual screening on the orthosteric (ATP-binding) pocket of a molecular model of human P2X4 based on the crystal structure of the Danio rerio receptor. The screening of a library of approximately 300,000 commercially available drug-like compounds led to the initial selection of 17 compounds; however, none of these compounds displayed a significant antagonist effect at P2X4 in a Fluo-4 ATP-induced calcium influx assay. When the same set of compounds was tested against human P2X7 in an ATP-stimulated Yo-Pro1 dye uptake assay, one compound (an indeno(1,2-b)pyridine derivative; GP-25) reduced the response by greater than 50% when applied at a concentration of 30 µM. GP-25 displayed an IC50 value of 8.7 μM at human P2X7 and 24.4 μM at rat P2X7, and was confirmed to be active using whole-cell patch clamp electrophysiology and not cytotoxic. Schild analysis suggested that mode of action of GP-25 was orthosteric. Screening of a further 16 commercially available analogues of GP-25 led to the discovery of five additional compounds with antagonist activity at human P2X7, enabling us to investigate the structure-activity relationship. Finally, docking of the R- and S-enantiomers of GP-25 into the orthosteric pocket of molecular models of human P2X4 and human P2X7 revealed that, while both enantiomers were able to make multiple interactions between their carboxyl moieties and conserved positively charged amino-acids in human P2X7, only the S-enantiomer of GP-25 was able to do this in human P2X4, potentially explaining the lack of activity of GP-25 at this receptor.
Steering thermal photoassociation of magnesium atoms by two time-delayed femtosecond laser pulses
Authors: Zhang Rong , Hu Jin-Wei , Han Yong-Chang , Fu Bina , Shundalau Maksim 
Published: January 2023

By solving the full-dimensional time-dependent Schrödinger equation with the thermal-random-phase wavepacket method, we investigate the photoassociation (PA) process of hot (1000 K) magnesium atoms induced by two time-delayed femtosecond laser pulses. Driven by the 840 nm fs laser pulses, the Mg2 molecules can be formed on the four excited states, (1)1Πg, (1)1Πu, (2)1Πu, and (2)1Σu+, from the initial electronic ground state X1Σg+. It is found that the three-photon couplings between X1Σg+ and the three ungerade states [(1)1Πu (2)1Πu, and (2)1Σu+], play dominant roles in the population transfer process. By scanning the pulse duration τ from 50 to 200 fs, and varying the delay time δt0 from 0 to 2τ fs, we find that the final PA population is strongly dependent on the two parameters. For a given δt0, the parameter τ can induce a significant variation (2 ∼ 6.8 times) for the final PA population transfer, and for a given τ, one can also obtain a significant variation (2.7 ∼ 3.5 times) of the final PA population by varying δt0. Additionally, the dynamics of the coherently vibrational wavepackets of the four excited states are also influenced by the two parameters.
Modeling of the potential geographical distribution of naked oat under climate change
Authors: Qin Mingxing , Gao Xinyue , Feng Meichen , Jin Ning , Wang Chao , Cheng Wenjuan 
Published: January 2023

IntroductionNaked oat (Avena sativa L.), is an important miscellaneous grain crop in China, which is rich in protein, amino acids, fat and soluble dietary fiber. The demand for functional foods is gradually increasing as living standards rise, and the output of minor cereals in China is increasing annually. The planting layout of naked oat is scattered and lacks planning, which seriously restricts the development of the naked oat industry. The increase in miscellaneous grain production will not only be impacted by cultivation methods and management techniques, but the potential impact of global climate change needs to be considered. North China is the main area for naked oat production, worldwide.MethodsIn this study, the potential distribution range of naked oat in North China was forecast based on historical distribution data and the Maxent model under climate change conditions. The performance of the model was relatively high.ResultsThe results indicated that the most suitable area for the potential geographic distribution of naked oat in North China was 27.89×104 km2, including central and northeastern Shanxi, and northeastern and western Hebei and Beijing, gradually moving northward. The core suitable area increased, and the distribution of naked oat had an obvious regional response to climate warming; the main environmental factors affecting the potential geographic distribution were precipitation factor variables (precipitation seasonality (variation coefficient)), terrain factor variables (elevation) and temperature factor variables (temperature seasonality (Standard Deviation*100)).DiscussionIn this study, the Maxent model was used to analyze and predict suitable areas for naked oat in North China, and the distribution of suitable areas was accurately divided, and the main climatic factors affecting the distribution of naked oat were identified. This research provides data support and theoretical support for the optimal planting zone of naked oat in North China.
Vessels in a Rhododendron ferrugineum (L.) population do not trace temperature anymore at the alpine shrubline
Authors: Piccinelli Silvia , Francon Loïc , Corona Christophe , Stoffel Markus , Slamova Lenka , Cannone Nicoletta 
Published: January 2023

IntroductionMean xylem vessel or tracheid area have been demonstrated to represent powerful proxies to better understand the response of woody plants to changing climatic conditions. Yet, to date, this approach has rarely been applied to shrubs.MethodsHere, we developed a multidecadal, annually-resolved chronology of vessel sizes for Rhododendron ferrugineum shrubs sampled at the upper shrubline (2,550 m asl) on a north-facing, inactive rock glacier in the Italian Alps.Results and DiscussionOver the 1960-1989 period, the vessel size chronology shares 64% of common variability with summer temperatures, thus confirming the potential of wood anatomical analyses on shrubs to track past climate variability in alpine environments above treeline. The strong winter precipitation signal recorded in the chronology also confirms the negative effect of long-lasting snow cover on shrub growth. By contrast, the loss of a climate-growth relation signal since the 1990s for both temperature and precipitation, significantly stronger than the one found in radial growth, contrasts with findings in other QWA studies according to which stable correlations between series of anatomical features and climatic parameters have been reported. In a context of global warming, we hypothesize that this signal loss might be induced by winter droughts, late frost, or complex relations between increasing air temperatures, permafrost degradation, and its impacts on shrub growth. We recommend future studies to validate these hypotheses on monitored rock glaciers.
Intestinal metabolites and the risk of autistic spectrum disorder: A two-sample Mendelian randomization study
Authors: Liu Deyang , Bu Dengyin , Li Hong , Wang Qingsong , Ding Xudong , Fang Xiaolu 
Published: January 2023

BackgroundObservational studies have reported a strong association between autistic spectrum disorder (ASD) and intestinal metabolites. However, it is unclear whether this correlation is causally or violated by confounding or backward causality. Therefore, this study explored the potential causal relationship between intestinal metabolites and dependent metabolites on ASD.MethodsWe used a two-sample Mendelian random analysis and selected variants closely related to intestinal flora-dependent metabolites as instrumental variables. MR-Egger, inverse variance weighted (IVW), MR-PRESSO, maximum likelihood, and weighted median were performed to reveal their causal relationships. Ten metabolites were studied, which included trimethylamine-N-oxide, betaine, carnitine, choline, glutamate, kynurenine, phenylalanine, serotonin, tryptophan, and tyrosine. Sensitivity tests were also performed to evaluate the robustness of the MR study.ResultsThe IVW method revealed that serotonin may increase the ASD risk (OR 1.060, 95% CI: 1.006–1.118), while choline could decrease the ASD risk (OR 0.925, 95% CI: 0.868–0.988). However, no definite causality was observed between other intestinal metabolites (e.g., trimethylamine-N-oxide, betaine, and carnitine) with ASD. Additionally, neither the funnel plot nor the MR-Egger test showed horizontal pleiotropy, and the MR-PRESSO test found no outliers. Cochran’s Q test showed no significant heterogeneity among the studies, suggesting the robustness of the study.ConclusionOur study found potential causality from intestinal metabolites on ASD. Clinicians are encouraged to offer preventive measures to such populations.
Case report: Amnestic mild cognitive impairment in multiple domains associated with neurofascin 186 autoantibodies: Case series with follow-up and review
Authors: Hansen Niels , Sagebiel Anne , Rentzsch Kristin , Hirschel Sina , Wiltfang Jens , Schott Björn H. , Claudia Bartels 
Published: January 2023

BackgroundNeurofascin 186 autoantibodies are known to occur with a diseased peripheral nervous system. Recently, also additional central nervous system (CNS) involvement has been reported in conjunction with neurofascin 186 autoantibodies. Our case enlarges the spectrum of neurofascin 186 antibody-related disease to include mild cognitive impairment (MCI).MethodsWe report here a case after having examined the patient files retrospectively, including diagnostics such as blood and cerebrospinal fluid (CSF) analysis involving the determination of neural autoantibodies, brain magnetic resonance imaging (MRI), brain fluorodesoxyglucose positron emission tomography (FDG-PET), and extensive neuropsychological testing.ResultsWe report on two patients with MCI. Brain MRI showed cerebral microangiopathy in both patients, but brain FDG-PET demonstrated pathology in the right prefrontal cortex, in the right inferior parietal cortex, and in both lateral occipital cortices in one patient. Neurofascin 186 antibodies were detected in serum in both patients, and neurofascin 186 autoantibodies were also detected in the CSF of one of these patients. At follow-up six month later, neurofascin 186 autoantibodies disappeared in one patient while persisting in the other.ConclusionWe report on two individuals presenting MCI associated with neurofascin 186 antibodies, thus expanding the potential spectrum of neurofascin 186-associated disease. This report supports the recommendation to consider also neurofascin 186 autoantibodies in not just peripheral nerve disease, but also in disorders involving CNS autoimmunity. More studies are needed to clarify the lack of association between neurofascin 186 autoantibodies and cognitive decline.