bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal vibration perception threshold alters the gait features in type 2 diabetes mellitus patients
Authors: Dong Lining , Hu Yanyun , Xu Lei , Zeng Hui , Shen Wenqi , Esser Patrick , Dawes Helen , Liu Fang 
Published: February 2023

ObjectiveIt is generally believed that gait characteristics of diabetic neuropathic patients differ from those of non-diabetic ones. However, it is still unclear how the abnormal foot sensation influences the gait during walking in type 2 diabetes mellitus (T2DM). For the purpose of gaining a better insight into the alterations of detailed gait parameters and figuring out important aspects in the gait indexes by peripheral neuropathy in elder T2DM patients, we compared the gait features in participants with normal glucose tolerance (NGT) controls and diabetic individuals complicated by peripheral neuropathy or not.Subjects and methodsGait parameters were observed during the 10-m walk on flat land among different conditions of diabetes in 1,741 participants from three clinical centers. Subjects were divided into four groups: persons with NGT were taken as the control group; patients with T2DM included three subgroups: DM control (no chronic complications), DM-DPN (DM complicated by only peripheral neuropathy), and DM-DPN+LEAD (DM complicated by both neuropathy and artery disease). The clinical characteristics and gait parameters were assessed and compared among these four groups. Analyses of variance were employed to verify possible differences of gait parameters between groups and conditions. Stepwise multivariate regression analysis was performed to reveal possible predictors of gait deficits. Receiver operating characteristic (ROC) curve analysis was employed to find any discriminatory power of diabetic peripheral neuropathy (DPN) for the step time.ResultsIn participants burdened with DPN, whether complicated by lower extremity arterial disease (LEAD) or not, step time increased sharply (p &lt; 0.05). Stepwise multivariate regression models showed that independent variables of gait abnormality were sex, age, leg length, vibration perception threshold (VPT), and ankle-brachial index (ABI) (p &lt; 0.01). Meanwhile, VPT was a significant independent predictor of step time, spatiotemporal variability (SDA), and temporal variability (SDB) (p &lt; 0.05). ROC curve analysis was explored to find the discriminatory power of DPN for the occurrence of increased step time. The area under the curve (AUC) value was 0.608 (95% CI: 0.562–0.654, p &lt; 0.01), and the cutoff point was 538.41 ms accompanied by a higher VPT. A significant positive association was observed between increased step time and the highest VPT group [odds ratio (OR) = 1.83, 95% CI: 1.32–2.55, p&lt; 0.01]. In female patients, this OR value elevated to 2.16 (95% CI: 1.25–3.73, p&lt; 0.01).ConclusionsIn addition to sex, age, and leg length, VPT was a distinct factor that associated with altered gait parameters. DPN is associated with increased step time, and the step time increases with worsening VPT in type 2 diabetes.
Prognostic RNA-editing signature predicts immune functions and therapy responses in gliomas
Authors: He Yi , Zhang Xingshu , Zhang Sen , Zhang Yi , Xie Bo , Huang Meng , Zhang Junjie , Shen Lili , Long Wenyong , Liu Qing 
Published: February 2023

Background: RNA-editing refers to post-transcriptional transcript alterations that lead to the formation of protein isoforms and the progression of various tumors. However, little is known about its roles in gliomas.Aim: The aim of this study is to identify prognosis-related RNA-editing sites (PREs) in glioma, and to explore their specific effects on glioma and potential mechanisms of action.Methods: Glioma genomic and clinical data were obtained from TCGA database and SYNAPSE platform. The PREs was identified with regression analyses and the corresponding prognostic model was evaluated with survival analysis and receiver operating characteristic curve. Functional enrichment of differentially expressed genes between risk groups was performed to explore action mechanisms. The CIBERSORT, ssGSEA, gene set variation analysis, and ESTIMATE algorithms were employed to assess the association between PREs risk score and variations of tumor microenvironment, immune cell infiltration, immune checkpoints, and immune responses. The maftools and pRRophetic packages were used to evaluate tumor mutation burden and predict drug sensitivity.Results: A total of thirty-five RNA-editing sites were identified as prognosis-related in glioma. Functional enrichment implied variation of immune-related pathways between groups. Notably, glioma samples with higher PREs risk score exhibited higher immune score, lower tumor purity, increased infiltration of macrophage and regulatory T cells, suppressed NK cell activation, elevated immune function score, upregulated immune checkpoint gene expression, and higher tumor mutation burden, all of which implied worse response to immune therapy. Finally, high-risk glioma samples are more sensitive to Z-LLNle-CHO and temozolomide, while the low-risk ones respond better to Lisitinib.Conclusion: We identified a PREs signature of thirty-five RNA editing sites and calculated their corresponding risk coefficients. Higher total signature risk score indicates worse prognosis and worse immune response and lower sensitivity to immune therapy. The novel PREs signature could help risk stratification, immunotherapy response prediction, individualized treatment strategy-making for glioma patients, and development of novel therapeutic approaches.
Wild-type SARS-CoV-2 neutralizing immunity decreases across variants and over time but correlates well with diagnostic testing
Authors: O’Shea Kelly M. , Schuler Charles F. , Chen Jesse , Troost Jonathan P. , Wong Pamela T. , Chen Kelsea , O’Shea Daniel R. , Peng Westley , Gherasim Carmen , Manthei David M. , Valdez Riccardo , Baldwin James L. , Baker James R. 
Published: February 2023

ImportanceThe degree of immune protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants provided by infection versus vaccination with wild-type virus remains unresolved, which could influence future vaccine strategies. The gold-standard for assessing immune protection is viral neutralization; however, few studies involve a large-scale analysis of viral neutralization against the Omicron variant by sera from individuals infected with wild-type virus.Objectives1) To define the degree to which infection versus vaccination with wild-type SARS-CoV-2 induced neutralizing antibodies against Delta and Omicron variants.2) To determine whether clinically available data, such as infection/vaccination timing or antibody status, can predict variant neutralization.MethodsWe examined a longitudinal cohort of 653 subjects with sera collected three times at 3-to-6-month intervals from April 2020 to June 2021. Individuals were categorized according to SARS-CoV-2 infection and vaccination status. Spike and nucleocapsid antibodies were detected via ADVIA Centaur® (Siemens) and Elecsys® (Roche) assays, respectively. The Healgen Scientific® lateral flow assay was used to detect IgG and IgM spike antibody responses. Pseudoviral neutralization assays were performed on all samples using human ACE2 receptor-expressing HEK-293T cells infected with SARS-CoV-2 spike protein pseudotyped lentiviral particles for wild-type (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants.ResultsVaccination after infection led to the highest neutralization titers at all timepoints for all variants. Neutralization was also more durable in the setting of prior infection versus vaccination alone. Spike antibody clinical testing effectively predicted neutralization for wild-type and Delta. However, nucleocapsid antibody presence was the best independent predictor of Omicron neutralization. Neutralization of Omicron was lower than neutralization of either wild-type or Delta virus across all groups and timepoints, with significant activity only present in patients that were first infected and later immunized.ConclusionsParticipants having both infection and vaccination with wild-type virus had the highest neutralizing antibody levels against all variants and had persistence of activity. Neutralization of WT and Delta virus correlated with spike antibody levels against wild-type and Delta variants, but Omicron neutralization was better correlated with evidence of prior infection. These data help explain why ‘breakthrough’ Omicron infections occurred in previously vaccinated individuals and suggest better protection is observed in those with both vaccination and previous infection. This study also supports the concept of future SARS-CoV-2 Omicron-specific vaccine boosters.
Exploration of teaching practice of analgesia and sedation in mainland China: CASER experience
Authors: Su Longxiang , Li Shu , Lou Ran , Liu Ying , Zhang Hua , Jiang Li 
Published: February 2023

ObjectiveAnalgesia and sedation assessments vary widely in clinical performance. This study investigated the cognition of intensivist and the importance of training for analgesia and sedation through the Chinese Analgesia and Sedation Education &amp; Research (CASER) group training program.MethodsA total of 107 participants studied the training courses on the “Sedation, Analgesia and Consciousness Assessment of Critically Ill Patients” held by CASER from June 2020 to June 2021. Ninety-eight valid questionnaires were recovered. The content of the questionnaire included the preface, general information of the trainees, students’ awareness of the importance of analgesia and sedation evaluation and related guidelines, and professional test questions.ResultsAll respondents were senior professionals engaged in the ICU. A total of 92.86% believed that analgesia and sedation treatment were very important parts of the ICU, and 76.5% believed that they had mastered relevant professional knowledge. However, when evaluating the relevant professional theory and practice of the respondents from an objective point of view, it can be seen that only 28.57% of the respondents could reach the passing line in the specific case analysis scenario. Before participating in the training, 42.86% of the medical staff believed that analgesia and sedation treatment should be evaluated in the daily work of the ICU; after participating in the training, 62.24% of the medical staff believed that the evaluation was necessary and believed that they had improved after the training. Moreover, 69.4% of the respondents affirmed the necessity and significance of jointly undertaking the task of analgesia and sedation in Chinese ICUs.ConclusionThis study revealed that the assessment of analgesia and sedation is not standardized in the ICU in mainland China. The importance and significance of standardized training for analgesia and sedation are presented. The CASER working group thus established has a long way to go in its future work.
Safety profile, antiviral capacity, and liver protection of a nasal therapeutic vaccine in patients with chronic hepatitis B: Five-year-follow-up outcomes after the end of treatment
Authors: Al Mahtab Mamun , Akbar Sheikh Mohammad Fazle , Aguilar Julio Cesar , Yoshida Osamu , Khan Sakirul , Gerardo Guillen Nieto , Hiasa Yoichi 
Published: February 2023

IntroductionThere is a pressing need to develop novel drugs for treating patients with chronic hepatitis B (CHB), as commercially available antiviral drugs are endowed with safety and efficacy concerns.MethodsA phase III clinical trial was conducted with a therapeutic vaccine containing two antigens of the hepatitis B virus (HBV; named NASVAC) in 78 patients with CHB expressing both HBV DNA and elevated levels of alanine aminotransferase (ALT) in the blood. Five years after the end of treatment (EOT), 60 NASVAC-recipient patients were enrolled in this long-term follow-up study to evaluate the safety, antiviral potential, and liver-protective capacity of NASVAC.ResultsNASVAC exhibited an excellent safety profile 5 years after EOT. The levels of HBV DNA in the sera were reduced in 55 of the 60 patients, and 45 of them were negative for HBV DNA in the sera. ALT levels were also normalized in 40 of the 60 patients 5 years after EOT. None of the patients receiving NASVAC developed liver cirrhosis or cancer.DiscussionThe present study is the first to exhibit long-term follow-up data of a finite immune therapy for CHB that is safe and endowed with potent antiviral and liver-protecting capacities.
Low-dose topiramate and hydrochlorothiazide-associated early acute myopia and angle narrowing: A case report
Authors: Wu Chao , Pan Hong , Feng Shijun , Wang Xiaokun , Liu Zhaoqiang , Zhao Bojun 
Published: February 2023

PurposeTo report a unique case of topiramate and hydrochlorothiazide associated with acute myopia and angle narrowing.Patients and methodsA 34-year-old Asian woman presented with prominent binocular visual acuity decrease 6 h after taking only one dose of 25 mg topiramate, 25 mg hydrochlorothiazide, and 22.4 mg fluoxetine to lose weight. She was subsequently diagnosed with acute bilateral myopia and angle narrowing and was started on topical therapy.ResultsInitial examination revealed a decreased visual acuity of 20/100 bilaterally, an elevated intraocular pressure of 23 mmHg in the right eye and 24 mmHg in the left eye, suprachoroidal effusions, and angle narrowing. After the discontinuation of these drugs and the use of IOP-lowering medication, the patient made full recovery.ConclusionWe speculate that there is a drug–drug interaction between topiramate and hydrochlorothiazide that may lead to the angle narrowing in a short time and at a low dose. Timely discontinuation of the drug usually leads to complete recovery within days to weeks.
A bibliometric analysis of 16,826 triple-negative breast cancer publications using multiple machine learning algorithms: Progress in the past 17 years
Authors: Wang Kangtao , Zheng Chanjuan , Xue Lian , Deng Dexin , Zeng Liang , Li Ming , Deng Xiyun 
Published: February 2023

BackgroundTriple-negative breast cancer (TNBC) is proposed at the beginning of this century, which is still the most challenging breast cancer subtype due to its aggressive behavior, including early relapse, metastatic spread, and poor survival. This study uses machine learning methods to explore the current research status and deficiencies from a macro perspective on TNBC publications.MethodsPubMed publications under “triple-negative breast cancer” were searched and downloaded between January 2005 and 2022. R and Python extracted MeSH terms, geographic information, and other abstracts from metadata. The Latent Dirichlet Allocation (LDA) algorithm was applied to identify specific research topics. The Louvain algorithm established a topic network, identifying the topic’s relationship.ResultsA total of 16,826 publications were identified, with an average annual growth rate of 74.7%. Ninety-eight countries and regions in the world participated in TNBC research. Molecular pathogenesis and medication are most studied in TNBC research. The publications mainly focused on three aspects: Therapeutic target research, Prognostic research, and Mechanism research. The algorithm and citation suggested that TNBC research is based on technology that advances TNBC subtyping, new drug development, and clinical trials.ConclusionThis study quantitatively analyzes the current status of TNBC research from a macro perspective and will aid in redirecting basic and clinical research toward a better outcome for TNBC. Therapeutic target research and Nanoparticle research are the present research focus. There may be a lack of research on TNBC from a patient perspective, health economics, and end-of-life care perspectives. The research direction of TNBC may require the intervention of new technologies.
Nomogram including indirect bilirubin for the prediction of post-stroke depression at 3 months after mild acute ischemic stroke onset
Authors: Wang Yanyan , Sun Wenzhe , Miao Jinfeng , Zhu Zhou , Liang Wenwen , Qiu Xiuli , Pan Chensheng , Li Guo , Lan Yan , Zhao Xin , Xu Yi 
Published: February 2023

BackgroundPost-stroke depression (PSD) has been proven to be associated with stroke severity. Thus, we hypothesized that the prevalence of PSD would be lower in patients with mild stroke. We aim to explore predictors of depression at 3 months after mild acute ischemic stroke (MAIS) onset and to develop a practical and convenient prediction model for the early identification of patients at high risk.MethodsA total of 519 patients with MAIS were consecutively recruited from three hospitals in Wuhan city, Hubei province. MAIS was defined as a National Institute of Health Stroke Scale (NIHSS) score of ≤5 at admission. Meeting the DSM-V diagnostic criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) score of &gt;7 at their 3-month follow-up were considered the primary outcomes. A multivariable logistic regression model was used to determine the factors adjusted for potential confounders, and all independent predictors were brought into the construction of a nomogram to predict PSD.ResultsThe prevalence of PSD is up to 32% at 3 months after MAIS onset. After adjusting for potential confounders, indirect bilirubin (p = 0.029), physical activity (p = 0.001), smoking (p = 0.025), hospitalization days (p = 0.014), neuroticism (p &lt; 0.001), and MMSE (p &lt; 0.001) remained independently and significantly related with PSD. The concordance index (C-index) of the nomogram jointly constructed by the aforementioned six factors was 0.723 (95% CI: 0.678–0.768).ConclusionThe prevalence of PSD seems equally high even if the ischemic stroke is mild, which calls for great concern from clinicians. In addition, our study found that a higher level of indirect bilirubin can lower the risk of PSD. This finding may provide a potential new approach to PSD treatment. Furthermore, the nomogram including bilirubin is convenient and practical to predict PSD after MAIS onset.
Nano-pulse stimulation™ therapy (NPS™) is superior to cryoablation in clearing murine melanoma tumors
Authors: McDaniel Amanda , Freimark Bruce , Navarro Cebrina , Von Rothstein Kristin , Gonzalez Dacia , Linder Keith , Nuccitelli Richard 
Published: February 2023

BackgroundNano-Pulse Stimulation™ Therapy (NPS™) is a new, bioelectric modality that applies ultrashort pulses of electric energy to trigger regulated cell death in treated tissues. Instead of initiating necrosis by heating or freezing, NPS therapy permeabilizes intracellular organelles to activate the cell’s own self-destruct pathway of programmed or regulated cell death. Unlike cryotherapies that can both damage structural tissues and diffuse into the periphery beyond the margins of the lesion, NPS only affects cells within the treated zone leaving surrounding tissue and acellular components unaffected.MethodsWe generated melanoma tumors in mice by injecting B16-F10 cells intradermally and compared the efficacy and resulting skin damage from Nano-Pulse Stimulation Therapy with that of cryoablation in clearing these tumors.ResultsThe results of the study demonstrate that NPS is superior at clearing B16-F10 melanoma lesions. NPS permanently eliminated up to 91% of all tumor lesions with a single treatment compared to cryoablation that only eliminated up to 66%. Importantly, NPS permanently eliminated these lesions with no recurrence and with minimal dermal fibrosis, underlying muscle atrophy, permanent hair follicle loss or other markers of permanent skin damage.ConclusionsThese findings suggest that NPS is a promising new modality for the clearance of melanoma tumors and is a more efficacious, less damaging approach than cryoablative methods for the treatment of aggressive malignant tumors.
The feasibility of decreasing the thresholds for biopsy in Kwak and C TIRADSs
Authors: Fu Chao , Cui Yiyang , Li Jing , Wang Yan , Si Caifeng , Cui Kefei 
Published: February 2023

ObjectivesTo estimate the feasibility of decreasing the original thresholds for biopsy in the Kwak Thyroid Imaging Reporting and Data System (Kwak TIRADS) and Chinese Thyroid Imaging Reporting and Data System (C TIRADS).MethodsThis retrospective study included 3,201 thyroid nodules from 2,146 patients with a pathological diagnosis. We lowered the original fine-needle aspiration (FNA) thresholds with the TR4a-TR5 in Kwak and C TIRADSs and calculated the ratio of additional benign-to-malignant nodules being biopsied (RABM). If the RABM is less than 1, the decreased FNA thresholds could be accepted and used to the modified TIRADSs (modified C and Kwak TIRADSs). Then, we estimated and compared the diagnostic performance between the modified TIRADS and the original TIRADS to determine if the decreased thresholds could be an effective strategy.ResultsA total of 1,474 (46.0%) thyroid nodules were diagnosed as malignant after thyroidectomy. The TR4c-TR5 in Kwak TIRADS and TR4b-TR5 in C TIRADS had a rational RABM (RABM &lt; 1). The modified Kwak TIRADS had higher sensitivity, a positive predictive value, a negative predictive value, lower specificity, an unnecessary biopsy rate, and a missed malignancy rate compared with the original Kwak TIRADS (94.1% vs. 42.6%, 59.4% vs. 44.6%, 89.9% vs. 52.8%, 45.0% vs. 54.9%, 40.6% vs. 55.4%, and 10.1% vs. 47.1%, respectively, P &lt; 0.05 for all). Similar trends were seen in the modified C TIRADS versus the original C TIRADS (95.1% vs. 38.7%, 61.7% vs. 47.8%, 92.3% vs. 55.0%, 49.7% vs. 64.0%, 38.3% vs. 52.2%, and 7.7% vs. 44.9%, respectively, P &lt; 0.05 for all).ConclusionsThe biopsy of all nodules with TR4C-TR5 in the Kwak TIRADS and TR4B-TR5 in the C TIRADS might be an effective strategy. This paper contributes to the contradiction concerning whether to perform FNA for the nodules smaller than 10 mm.
CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in uterine corpus endometrial carcinoma
Authors: Xue Shen , Su Xiao-min , Ke Li-na , Huang Yu-gang 
Published: February 2023

BackgroundThe C-X-C motif chemokine ligand-9 (CXCL9) is related to the progression of multiple neoplasms. Yet, its biological functions in uterine corpus endometrioid carcinoma (UCEC) remain shrouded in confusion. Here, we assessed the prognostic significance and potential mechanism of CXCL9 in UCEC.MethodsFirstly, bioinformatics analysis of the public cancer database, including the Cancer Genome Atlas / the Genotype-Tissue Expression project (TCGA+ GTEx, n=552) and Gene Expression Omnibus (GEO): GSE63678 (n=7), were utilized for the CXCL9 expression-related analysis in UCEC. Then, the survival analysis of TCGA-UCEC was performed. Futher, the gene set enrichment analysis (GSEA) was carried out to reveal the potential molecular signaling pathway in UCEC associated with CXCL9 expression. Moreover, the immunohistochemistry (IHC) assay of our validation cohort (n=124) from human specimens were used to demonstrate the latent significance of CXCL9 in UCEC.ResultsThe bioinformatics analysis suggested that CXCL9 expression was significantly upregulated in UCEC patients; and hyper-expression of CXCL9 was related to prolonged survival. the GSEA enrichment analysis showed various immune response-related pathways, including T/NK cell, lymphocyte activation, cytokine-cytokine receptor interaction network, and chemokine signaling pathway, mediated by CXCL9. In addition, the cytotoxic molecules (IFNG, SLAMF7, JCHAIN, NKG7, GBP5, LYZ, GZMA, GZMB, and TNF3F9) and the immunosuppressive genes (including PD-L1) were positively related to the expression of CXCL9. Further, the IHC assay indicated that the CXCL9 protein expression was mainly located in intertumoral and significantly upregulated in the UCEC patients; UCEC with high intertumoral CXCL9 cell abundance harbored an improved prognosis; a higher ratio of anti-tumor immune cells (CD4+, CD8+, and CD56+ cell) and PD-L1 was found in UCEC with CXCL9 high expression.ConclusionOverexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC. It hinted that CXCL9 may serve as an independent prognostic biomarker or therapeutic target in UCEC patients, which augmented anti-tumor immune effects to furnish survival benefits.