bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of Xuanhuang Pill in protecting against alcohol liver disease using ultra-performance liquid chromatography/time-of-flight mass spectrometry and network pharmacology
Authors: Cui Xuejie , Du Maobo , Wei Kunhua , Dai Chen , Yang Rachel Y. H. , Zhou Bingxue , Luo Zhaojing , Yang Xiaonan , Yu Yi , Lin Wei , Wu Yi , Liu Yuhong 
Published: April 2023

IntroductionXuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism.MethodsThe hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology.ResultsThe current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP’s effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment.ConclusionIn summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease.
Evaluating the performance of a web-based vehicle blind zone estimation application: Validation and policy implications
Authors: Drake Juwon , Vennema Alessandra , Slonim Lily , Englin Eric , Brodeur Alyssa , Epstein Alexander K. , Fisher Donald L. 
Published: April 2023

Pedestrian fatalities have been increasing in the United States over the past decade; in 2021 they reached a 40-year high and together with an increasing number of bicyclist fatalities surged to over 8,400 vulnerable road users (VRUs) killed by motor vehicle crashes. There is widespread recognition of the link between passenger fleets transitioning from sedans to SUVs and pick-up trucks and the increase in vulnerable road user fatalities. Larger light-duty vehicles generally have larger blind zones, and larger blind zones are prominently linked to crashes with vulnerable road users. Heavy-duty commercial trucks, which comprise only four percent of vehicles on the road, are disproportionally associated with over eight percent of vulnerable road user deaths. With direct vision unregulated in the United States, there is a limited domestic market for large trucks with high direct vision despite research showing that one-quarter of the approximately 620 annual truck-involved pedestrian and bicyclist fatalities result from low-speed maneuvers with impaired direct vision and could be prevented by higher vision truck cabs. Communicating the seriousness of this problem is critical. This methods article presents an easy-to-use tool designed to give the public and fleet managers information to assess vehicle safety by quantifying driver blind zones using whatever driver eye positions are thought to be most applicable and with the option to standardize said eye position. Previously, measures of the percentage of volume surrounding the vehicle that cannot be seen or the number of people outside the vehicle that can fit in the blind zone could only be made with specialized instrumentation. The web-based application described, VIEW or visibility in elevated wide vehicles, can be used by anyone with a camera and access to the internet to obtain within approximately 15 min a reasonably accurate measure of the blind zone size, considerably faster than manual measurement methods. This article details the app usage procedure as well as the validation work conducted. In summary, the safety culture around SUVs, pickup trucks, and heavy-duty commercial trucks may change if drivers had an easy-to-use method to determine how much situational awareness they would be missing before they purchased a particular vehicle.
Transcranial direct current stimulation regulates phenotypic transformation of microglia to relieve neuropathic pain induced by spinal cord injury
Authors: Tan Mingliang , Feng Zhou , Chen Hui , Min Lingxia , Wen Huizhong , Liu Hongliang , Hou Jingming 
Published: April 2023

ObjectiveNeuropathic pain is a common complication after spinal cord injury (SCI). Transcranial direct current stimulation (tDCS) has been confirmed to be effective in relieving neuropathic pain in patients with SCI. The aim of this study is to investigate the effect of tDCS on neuropathic pain induced by SCI and its underlying mechanism.Materials and methodsThe SCI model was induced by a clip-compression injury and tDCS stimulation was performed for two courses (5 days/each). The motor function was evaluated by Basso-Beattie-Bresnahan (BBB) score, and the thermal withdrawal threshold was evaluated by the thermal radiation method. The effects of tDCS on the cerebral cortex, thalamus, midbrain, and medulla were detected by the enzyme-linked immunosorbent assay (ELISA) and immunofluorescence.ResultsThe results showed that SCI reduced the thermal withdrawal threshold and increased the concentration of inflammatory cytokines in the cortex, thalamus, midbrain, and medulla, including the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In addition, the activation of microglia and the proportion of M1 phenotypic polarization increased significantly in the ventral posterolateral (VPL), ventral tegmental (VTA), and periaqueductal gray (PAG) regions after SCI. After tDCS treatment, the thermal withdrawal threshold and motor function of SCI rats were significantly improved compared to the vehicle group. Meanwhile, tDCS effectively reduced the concentration of pro-inflammatory cytokines in the cortex, thalamus, midbrain, and medulla and increased the concentration of anti-inflammatory cytokines interleukin-10 (IL-10) in the thalamus. In addition, tDCS reduced the proportion of the M1 phenotype of microglia in VPL, VTA, and PAG regions and increase the proportion of the M2 phenotype.ConclusionThe results suggest that tDCS can effectively relieve SCI-induced neuropathic pain. Its mechanism may be related to regulating the inflammatory and anti-inflammatory cytokines in corresponding brain regions via promoting the phenotypic transformation of microglia.
Subacute myoclonic measles encephalitis – An opportunistic HIV-associated infection
Authors: Ene Luminita , Duiculescu Dan , Radoi Roxana , Lazar Mihaela , Tardei Gratiela , Ungureanu Eugenia , Ruta Simona , Vinters Harry V. , Letendre Scott , Grant Igor , Ellis Ronald J. , Achim Cristian L. 
Published: April 2023

IntroductionAn unusual cluster of myoclonic epilepsy was observed in a Romanian pediatric HIV cohort concurrent with measles outbreaks. We describe this particular form of subacute measles encephalitis (SME) in a group of HIV-infected children and adolescents with severe immunosuppression.MethodsThis is a single-center study, starting in 1997 and covering 4 measles outbreaks in Romania. The presumptive diagnosis of subacute myoclonic measles encephalitis (SMME) was based on: (1) epidemiological data, previous measles episode or presumed contact with measles virus (MV), (2) clinical presentation with initial localized myoclonic jerks with rapid extension and subsequent motor deficit with preserved mental status, and (3) neuroimaging studies revealing cortical gray matter lesions. Definitive diagnosis was based on a neuropathological exam and immunohistochemistry of brain tissues, and measles RNA detection in the cerebrospinal fluid (CSF).ResultsThirty-six patients were diagnosed with a particular form of SME during consecutive measles outbreaks in Romania: 1996–1998 (22); 2005–2008 (12); 2010–2011 (1) and 2016-2018 (1). Most children were born in the late 80s and had parenterally acquired HIV infection in early childhood. Before the episode of SMME, 11 patients had confirmed measles, while the rest, without typical rash, had a respiratory tract infection and/or presumed previous measles contact. In all patients, the clinical onset was sudden, with unilateral myoclonus. MRI findings revealed mainly focal cortical gray matter lesions. Neurologic symptoms progressed rapidly to coma and death in most patients. Three patients survived SMME, they had higher CD4 count at onset, slower progression of neurological symptoms, and benefit of immune recovery with cART. Immunocytochemistry studies revealed MV in the brain with a pattern suggesting an ascending viral neural infection. MV was isolated from CSF in 7 out of 8 patients. Sequence analysis of MV RNA from both nasopharyngeal swabs and CSF was available for one patient with similar N-450 strain characteristics.ConclusionDuring an outbreak of measles, neurological manifestations, especially myoclonus in immunosuppressed patients, can be related to measles even in the absence of an acute episode. This particular form of subacute myoclonic measles encephalitis is an opportunistic fatal disease. Immune recovery due to effective antiretroviral treatment might increase survival.
Effects of transcranial combined with peripheral repetitive magnetic stimulation on limb spasticity and resting-state brain activity in stroke patients
Authors: Qin Yin , Liu Xiaoying , Zhang Yinxin , Wu Jiwei , Wang Xiaoyang 
Published: April 2023

Background and objectiveTranscranial magnetic stimulation and peripheral repetitive magnetic stimulation (rPMS), as non-invasive neuromodulation techniques, can promote functional recovery in patients with post-stroke spasticity (PSS), but the effects of transcranial magnetic stimulation combined with peripheral magnetic stimulation on PSS remain largely unknown. Therefore, we examined the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) combined with rPMS on PSS patients and its potential neural correlates to behavioral improvements.MethodsForty-nine PSS patients were divided randomly into three groups: a combined group (n = 20), a LF-rTMS group (n = 15), and a control group (n = 14). The combined group received LF-rTMS and rPMS treatment, the rTMS group received LF-rTMS treatment, and the control group received only routine rehabilitation. All patients underwent Ashworth Spasm Scale (MAS), upper extremity Fugl-Meyer (FMA-UE), and modified Barthel Index (MBI) assessments before and after intervention. In addition, resting-state functional magnetic resonance imaging data were collected pre- and post-treatment to observe changes in the amplitude of low-frequency fluctuation (ALFF).ResultsThe MAS score was decreased, FMA-UE score and MBI scores were increased in the three groups after therapy than before therapy (all P &lt; 0.05). In particular, the combined group showed significant effect on improved motor function and relieved spasticity in PSS (P &lt; 0.01). Moreover, the combined treatment increased ALFF values mainly in the right supplementary motor area, right middle frontal gyrus, and right cerebellum, while reduced ALFF values mainly in the right post-central gyrus compared with pre-treatment. Compared with the LF-rTMS and control groups, the combined treatment increased ALFF values in the right cerebellum and reduced ALFF values mainly in the frontoparietal cortex. Improvements in the MAS score were positively correlated with the change in ALFF values in the right cerebellum (r = 0.698, P = 0.001) and the right supplementary motor area (r = 0.700, P = 0.001) after combined treatment.ConclusionTranscranial combined with peripheral repetitive magnetic stimulation could improve spastic state and motor function in PSS patients, and this effect may be associated with altered cerebellar and frontoparietal cortical activity.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR1800019452.
n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not: NHANES 2007–2016
Authors: Zeng Guixing , You Dongxin , Ye Lingyan , Wu Yuchi , Shi Hualin , Lin Jiarong , Jiang Ziyan , Wei Junping 
Published: April 2023

Background and aimsGout, the most prevalent inflammatory arthritis, has undesirable effects on the quality of life. Omega-3 polyunsaturated fatty acids (n-3 PUFA) has a strong link with anti-inflammatory impacts. However, whether the harmful effects of seafood in relation to gout may vary owing to different levels of n-3 PUFA in seafood is still unclear. It was the goal of this study to examine the relationship between n-3 PUFA poor/rich seafood consumption and gout.MethodsBetween 2007 and 2016, five NHANES cycles were performed, with 12,505 subjects having complete data for gout and two 24-h dietary intake interviews. The 24-h dietary recalls were utilized to evaluate dietary habits. Gout was defined based on questionnaires. Weighted logistic regression models were conducted to investigate the association between n-3 PUFA poor/rich seafood consumption and gout. Moreover, subgroup analysis was utilized to estimate the stability of results. Covariates including age, gender, race/ethnicity, income, education, body mass index, chronic kidney disease, diabetes mellitus, hypertension, smoking status, and drinking status were stratified in different models.ResultsIn the fully adjusted model, each unit of increase of n-3 PUFA poor seafood intake was associated with an 8.7% increased risk of gout (OR = 1.087, 95% CI: 1.039, 1.138, P &lt; 0.001), whereas, no correlation was found between n-3 PUFA rich seafood consumption and gout. It also provided a proof-of-concept regarding the potential for n-3 PUFA rich seafood to counteract harmful effects of purines in relation to gout. A dose-response analysis showed that there was a non-linear relationship between n-3 PUFA rich seafood intake and the risk of gout in the female group.ConclusionFindings suggest that n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not.
Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer
Authors: Feliciano Josephine Louella , McLoone Dylan , Xu Yingxin , Quek Ruben G.W. , Kuznik Andreas , Pouliot Jean-Francois , Gullo Giuseppe , Rietschel Petra , Guyot Patricia , Konidaris Gerasimos , Chan Keith , Keeping Sam , Wilson Florence R. , Freemantle Nick 
Published: April 2023

ObjectivesIn randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression.MethodsPatients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring).ResultsIn the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction—the most suitable method based on published guidelines and trial characteristics—produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction.ConclusionsAfter adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.
Investigating miR-9 as a mediator in laryngeal cancer health disparities
Authors: Gobin Christina , Inkabi Samuel , Lattimore Chayil C. , Gu Tongjun , Menefee James N. , Rodriguez Mayrangela , Kates Heather , Fields Christopher , Bian Tengfei , Silver Natalie , Xing Chengguo , Yates Clayton , Renne Rolf , Xie Mingyi , Fredenburg Kristianna M. 
Published: April 2023

BackgroundFor several decades, Black patients have carried a higher burden of laryngeal cancer among all races. Even when accounting for sociodemographics, a disparity remains. Differentially expressed microRNAs have been linked to racially disparate clinical outcomes in breast and prostate cancers, yet an association in laryngeal cancer has not been addressed. In this study, we present our computational analysis of differentially expressed miRNAs in Black compared with White laryngeal cancer and further validate microRNA-9-5p (miR-9-5p) as a potential mediator of cancer phenotype and chemoresistance.MethodsBioinformatic analysis of 111 (92 Whites, 19 Black) laryngeal squamous cell carcinoma (LSCC) specimens from the TCGA revealed miRNAs were significantly differentially expressed in Black compared with White LSCC. We focused on miR-9-5 p which had a significant 4-fold lower expression in Black compared with White LSCC (p&lt;0.05). After transient transfection with either miR-9 mimic or inhibitor in cell lines derived from Black (UM-SCC-12) or White LSCC patients (UM-SCC-10A), cellular migration and cell proliferation was assessed. Alterations in cisplatin sensitivity was evaluated in transient transfected cells via IC50 analysis. qPCR was performed on transfected cells to evaluate miR-9 targets and chemoresistance predictors, ABCC1 and MAP1B.ResultsNorthern blot analysis revealed mature miR-9-5p was inherently lower in cell line UM-SCC-12 compared with UM-SCC-10A. UM -SCC-12 had baseline increase in cellular migration (p &lt; 0.01), proliferation (p &lt; 0.0001) and chemosensitivity (p &lt; 0.01) compared to UM-SCC-10A. Increasing miR-9 in UM-SCC-12 cells resulted in decreased cellular migration (p &lt; 0.05), decreased proliferation (p &lt; 0.0001) and increased sensitivity to cisplatin (p &lt; 0.001). Reducing miR-9 in UM-SCC-10A cells resulted in increased cellular migration (p &lt; 0.05), increased proliferation (p &lt; 0.05) and decreased sensitivity to cisplatin (p &lt; 0.01). A significant inverse relationship in ABCC1 and MAP1B gene expression was observed when miR-9 levels were transiently elevated or reduced in either UM-SCC-12 or UM-SCC-10A cell lines, respectively, suggesting modulation by miR-9.ConclusionCollectively, these studies introduce differential miRNA expression in LSCC cancer health disparities and propose a role for low miR-9-5p as a mediator in LSCC tumorigenesis and chemoresistance.
Is cancer stage data missing completely at random? A report from a large population-based cohort of non-small cell lung cancer
Authors: Robinson Andrew G. , Nguyen Paul , Goldie Catherine L. , Jalink Matthew , Hanna Timothy P. 
Published: April 2023

IntroductionPopulation-based datasets are often used to estimate changes in utilization or outcomes of novel therapies. Inclusion or exclusion of unstaged patients may impact on interpretation of these studies.MethodsA large population-based dataset in Ontario, Canada of non-small cell lung cancer patients was examined to evaluate the characteristics and outcomes of unstaged patients compared to staged patients. Multivariable Poisson regression was used to evaluate differences in patient-level characteristics between groups. Kaplan-Meier estimates of survival and log-rank statistics were utilized.ResultsIn our Ontario cohort of 51,152 patients with NSCLC, 11.2% (n=5,707) were unstaged, and there was evidence that stage data was not missing completely at random. Those without assigned stage were more likely than staged patients to be older (RR [95%CI]), (70-79 vs. 20-59: 1.51 [1.38-1.66]; 80+ vs. 20-59: 2.87 [2.62-3.15]), have a higher comorbidity index (Score 1-2 vs 0: 1.19 [1.12-1.27]; 3 vs. 0: 1.49 [1.38-1.60]), and have a lower socioeconomic class (4 vs. 1 (lowest): 0.91 [0.84-0.98]; 5 vs. 1 (lowest): 0.89 [0.83-0.97]). Overall survival of unstaged patients suggested a mixture of early and advanced stage, but with a large proportion that are probably stage IV patients with more rapid death than those with reported stage IV disease.ConclusionIn this case study, evaluation of stage-specific health care utilization and outcomes for staged patients with stage IV disease at the population level may have a bias as a distinct subset of stage IV patients with rapid death are likely among those without a documented stage in administrative data.