bluuebunny/crossref_metadata_2025_split huggingface dataset:
Videooculography “HINTS” in Acute Vestibular Syndrome: A Prospective Study
Authors: Korda Athanasia , Wimmer Wilhelm , Zamaro Ewa , Wagner Franca , Sauter Thomas C. , Caversaccio Marco D. , Mantokoudis Georgios 
Published: July 2022

ObjectiveA three-step bedside test (“HINTS”: Head Impulse-Nystagmus-Test of Skew), is a well-established way to differentiate peripheral from central causes in patients with acute vestibular syndrome (AVS). Nowadays, the use of videooculography gives physicians the possibility to quantify all eye movements. The goal of this study is to compare the accuracy of VOG “HINTS” (vHINTS) to an expert evaluation.MethodsWe performed a prospective study from July 2015 to April 2020 on all patients presenting at the emergency department with signs of AVS. All the patients underwent clinical HINTS (cHINTS) and vHINTS followed by delayed MRI, which served as a gold standard for stroke confirmation.ResultsWe assessed 46 patients with AVS, 35 patients with acute unilateral vestibulopathy, and 11 patients with stroke. The overall accuracy of vHINTS in detecting a central pathology was 94.2% with 100% sensitivity and 88.9% specificity. Experts, however, assessed cHINTS with a lower accuracy of 88.3%, 90.9% sensitivity, and 85.7% specificity. The agreement between clinical and video head impulse tests was good, whereas for nystagmus direction was fair.ConclusionsvHINTS proved to be very accurate in detecting strokes in patients AVS, with 9% points better sensitivity than the expert. The evaluation of nystagmus direction was the most difficult part of HINTS.
Healthy Eating Index-2015 and Predicted 10-Year Cardiovascular Disease Risk, as Well as Heart Age
Authors: Zhang Yinyin , Lu Cong , Li Xinyu , Fan Yameng , Li Jiaqiao , Liu Yamei , Yu Yan , Zhou Long 
Published: July 2022

Background and AimsDietary factor plays an important role in the prevention of cardiovascular disease (CVD). The healthy eating index-2015 (HEI-2015), an indicator of the overall dietary quality, has been introduced to reflect adherence to the 2015–2020 Dietary Guidelines for Americans (DGA). This study aims to explore the associations of the HEI-2015 with predicted 10-year CVD risk and heart age among United States adults aged 30–74 years old using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014.Methods and ResultsWe conducted a cross-sectional analysis among 6,614 participants aged 30–74 years old. The HEI-2015 scores were calculated from 2-days 24-h dietary recall interviews. The 10-year CVD risk and heart age were derived from the sex-specific Framingham general cardiovascular disease risk score. We defined high cardiovascular disease risk as a predicted 10-year cardiovascular disease risk of &gt; 20%. Multiple linear regression and binary logistic regression models were used to investigate the associations of the HEI-2015 with predicted 10-year CVD risk and heart age. Compared with participants in the lowest HEI-2015 quartile, those in the highest quartile had lower predicted 10-year CVD risk (β = −2.37, 95% CI: −3.09 to –1.65, P &lt; 0.0001), lower heart age (β = −2.63, 95% CI: −3.29 to –1.96, P &lt; 0.0001) and lower odds for high risk of CVD (OR = 0.62, 95% CI: 0.49 to 0.80, P-trend &lt; 0.0001) after adjusting for multiple covariates.ConclusionHigher adherence to the 2015–2020 Dietary Guidelines for Americans is associated with lower predicted 10-year cardiovascular disease risk and lower heart age among United States adults.
Resistin as a Systemic Inflammation-Related Biomarker for Sarcopenia in Patients With Chronic Obstructive Pulmonary Disease
Authors: Gao Jinghan , Deng Mingming , Li Yanxia , Yin Yan , Zhou Xiaoming , Zhang Qin , Hou Gang 
Published: July 2022

BackgroundSarcopenia is common in patients with chronic obstructive pulmonary disease (COPD) and is mainly caused by systemic inflammation. Resistin acts as a proinflammatory cytokine and is involved in the activation of multiple inflammatory signaling pathways. The aim of this study was to determine the relationship between resistin levels and systemic inflammation and to assess the clinical value of circulating resistin for sarcopenia in patients with COPD.MethodsIn this prospective observational study, we enrolled 235 patients with COPD who were divided into development and validation sets. The definition of sarcopenia followed the guidelines from the Asian Working Group for Sarcopenia. Serum concentrations of resistin and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA).ResultsIn this study, higher serum resistin levels were significantly associated with lower skeletal muscle mass and muscular strength. The serum resistin levels in patients with sarcopenia were significantly higher than those in patients without sarcopenia. The serum resistin level had positive correlations with the serum TNF-α level (r = 0.250, p = 0.007). The predictive efficacy of the serum resistin level (AUC: 0.828) for sarcopenia was superior to that of the serum TNF-α level (AUC: 0.621). The cutoff point (7.138 ng/ml) for the serum resistin level was validated in the validation set (AUC: 0.818).ConclusionsSerum resistin levels were associated with systemic inflammation and can be used accurately and easily to predict sarcopenia in patients with COPD.
A Systematic Review and Meta-Analysis of Studies Comparing Concurrent Chemoradiotherapy With Radiotherapy Alone in the Treatment of Stage II Nasopharyngeal Carcinoma
Authors: Xu Yao-Can , Chen Kai-Hua , Liang Zhong-Guo , Zhu Xiao-Dong 
Published: July 2022

PurposeThe role of concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) is still controversial. Our objective is to evaluate the value of concurrent chemotherapy in stage II NPC receiving radiotherapy (RT).MethodsWe searched the PubMed, Embase, and Scopus databases for studies comparing CCRT versus RT alone in stage II NPC with survival outcomes and toxicities, including locoregional recurrence-free survival (LRFS), metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and grade 3–4 acute toxicities. The hazard ratios (HRs) of survival outcomes and risk ratios (RRs) of toxicities were extracted for meta-analysis. Subgroup analysis for stage N1 patients was performed to further explore whether these populations can earn benefits from concurrent chemotherapy.ResultsNine eligible studies with a total of 4,092 patients were included. CCRT was associated with a better OS (HR = 0.61, 95% CI 0.44–0.82), LRFS (HR = 0.62, 95% CI 0.50–0.78), and PFS (HR = 0.65, 95% CI 0.54–0.79), but with similar DMFS (HR = 0.81, 95% CI = 0.46–1.45) compared with two-dimensional RT (2DRT) alone. However, CCRT showed no survival benefit in terms of OS (HR = 0.84, 95% CI 0.62–1.15), LRFS (HR = 0.85, 95% CI 0.54–1.34), DMFS (HR = 0.96, 95% CI 0.60–1.54), and PFS (HR = 0.96, 95% CI 0.66–1.37) compared with intensity-modulated RT (IMRT) alone. Subgroup analyses indicated that CCRT had similar OS (HR = 1.04, 95% CI 0.37–2.96), LRFS (HR = 0.70, 95% CI 0.34–1.45), DMFS (HR = 1.03, 95% CI 0.53–2.00), and PFS (HR = 1.04, 95% CI 0.58–1.88) in the stage N1 populations. Meanwhile, compared to RT alone, CCRT significantly increased the incidence of grade 3–4 leukopenia (RR = 4.00, 95% CI 2.29–6.97), mucositis (RR = 1.43, 95% CI 1.16–1.77), and gastrointestinal reactions (RR = 8.76, 95% CI 2.63–29.12). No significant differences of grade 3–4 toxicity in thrombocytopenia (RR = 3.45, 95% CI 0.85–13.94) was found between the two groups.ConclusionFor unselected patients with stage II NPC, CCRT was superior to 2DRT alone with better LRFS, PFS, and OS, while adding concurrent chemotherapy to IMRT did not significantly improve survival but exacerbated acute toxicities.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022318253.
Association of Cell Death Markers With Tumor Immune Cell Infiltrates After Chemo-Radiation in Cervical Cancer
Authors: Oltean Teodora , Lippens Lien , Lemeire Kelly , De Tender Caroline , Vuylsteke Marnik , Denys Hannelore , Vandecasteele Katrien , Vandenabeele Peter , Adjemian Sandy 
Published: July 2022

Irradiation induces distinct cellular responses such as apoptosis, necroptosis, iron-dependent cell death (a feature of ferroptosis), senescence, and mitotic catastrophe. Several of these outcomes are immunostimulatory and may represent a potential for immunogenic type of cell death (ICD) induced by radiotherapy triggering abscopal effects. The purpose of this study is to determine whether intra-tumoral ICD markers can serve as biomarkers for the prediction of patient’s outcomes defined as the metastasis status and survival over a 5-year period. Thirty-eight patients with locally advanced cervical cancer, treated with neoadjuvant chemoradiotherapy using cisplatin were included in this study. Pre-treatment tumor biopsy and post-treatment hysterectomy samples were stained for cell death markers and danger associated molecular patterns (DAMPs): cleaved caspase-3 (apoptosis), phosphorylated mixed lineage kinase domain like pseudokinase (pMLKL; necroptosis), glutathione peroxidase 4 (GPX4; ferroptosis) and 4-hydroxy-2-noneal (4-HNE; ferroptosis), high mobility group box 1 (HMGB1) and calreticulin. Although these markers could not predict the patient’s outcome in terms of relapse or survival, many significantly correlated with immune cell infiltration. For instance, inducing ferroptosis post-treatment seems to negatively impact immune cell recruitment. Measuring ICD markers could reflect the impact of treatment on the tumor microenvironment with regard to immune cell recruitment and infiltration.One Sentence SummaryCell death readouts during neoadjuvant chemoradiation in cervical cancer
A Practical Nomogram and Risk Stratification System Predicting the Cancer-Specific Survival for Patients With Advanced Hepatocellular Carcinoma
Authors: Yang Dashuai , Su Yang , Zhao Fangrui , Chen Chen , Zhao Kailiang , Xiong Xiangyun , Ding Youming 
Published: July 2022

BackgroundHepatocellular carcinoma (HCC) has the highest cancer-related mortality rate. This study aims to create a nomogram to predict the cancer-specific survival (CSS) in patients with advanced hepatocellular carcinoma.MethodsPatients diagnosed with advanced HCC (AJCC stage III and IV) during 1975 to 2018 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Qualified patents were randomized into training cohort and validation cohort at a ratio of 7:3. The results of univariate and multivariate Cox regression analyses were used to construct the nomogram. Consistency index (C-index), area under the time-dependent receiver operating characteristic (ROC) curve [time-dependent area under the curve (AUC)], and calibration plots were used to identify and calibrate the nomogram. The net reclassification index (NRI), integrated discrimination improvement (IDI), and C-index, and decision curve analysis DCA were adopted to compare the nomogram’s clinical utility with the AJCC criteria.ResultsThe 3,103 patients with advanced hepatocellular carcinoma were selected (the training cohort: 2,175 patients and the validation cohort: 928 patients). The C-index in both training cohort and validation cohort were greater than 0.7. The AUC for ROC in the training cohort was 0.781, 0.771, and 0.791 at 1, 2, and 3 years CSS, respectively. Calibration plots showed good consistency between actual observations and the 1-, 2-, and 3-year CSS predicted by the nomogram. The 1-, 2-, and 3-year NRI were 0.77, 0.46, and 0.48, respectively. The 1-, 2-, and 3-year IDI values were 0.16, 0.15, and 0.12 (P &lt; 0.001), respectively. DCA curves in both the training and validation cohorts demonstrated that the nomogram showed better predicted 1-, 2-, and 3-year CSS probabilities than AJCC criteria.ConclusionsThis study established a practical nomogram for predicting CSS in patients with advanced HCC and a risk stratification system that provided an applicable tool for clinical management.
Case Report: Malignant Brain Tumors in Siblings With MSH6 Mutations
Authors: Wu Di , Chen Qingshan , Chen Jian 
Published: July 2022

BackgroundFamilial brain tumor incidences are low. Identifying the genetic alterations of familial brain tumors can help better understand the pathogenesis and make therapy regimens for these tumors.Case PresentationAn elder female and a younger male were diagnosed with brain tumors at the age of 10 and 5, respectively. Whole-genome sequencing analysis of the two patients’ blood, primary brain tumor tissues, and their parents’ blood samples was performed, which revealed that the two tumor samples harbored extremely high somatic mutation loads. Additionally, we observed pigmentation on the male patient’s skin.ConclusionGermline, biallelic mutation of MSH6—a gene related to DNA mismatch repair whose defect will result in constitutional mismatch repair deficiency (CMMRD)—is causal for the brain tumors of these two siblings.
Solamargine Inhibits the Development of Hypopharyngeal Squamous Cell Carcinoma by Decreasing LncRNA HOXA11-As Expression
Authors: Meng Ying , Jin Mengli , Yuan Dai , Zhao Yicheng , Kong Xiangri , Guo Xuerui , Wang Xingye , Hou Juan , Wang Bingmei , Song Wu , Tang Yong 
Published: July 2022

Hypopharyngeal squamous cell carcinoma (HSCC) is one of the high mortality cancers with a poor prognosis, which is driving the development of new chemotherapeutic agents. We identified the anticancer effects of a natural compound, solamargine (SM), on FaDU cells and explored its mechanism in terms of non-coding RNA. It was observed that SM inhibited the proliferation of FaDU cells with an IC50 of 5.17 μM. High-throughput sequencing data revealed that lncRNA HOXA11-AS was significantly downregulated in cells co-incubated with SM. Further assays demonstrated that SM-induced downregulation of lncRNA HOXA11-AS showed important implications for apoptosis. Given the properties of HOXA11-AS as a miR-155 sponge, we further confirmed that SM upregulated the expression of miR-155 in FaDU cells. C-Myc is a transcription factor that regulates cell differentiation and apoptosis, whose mRNA is considered to be targeted by miR-155. We showed that c-Myc expression was downregulated by SM and accompanied by increased apoptosis, which was consistent with the findings of transcriptome sequencing. Furthermore, SM administration suppressed xenograft tumor growth in a xenograft mouse model in vivo. In the light of the aforementioned findings, our results suggested that SM downregulated the expression of HOXA11-AS, which in turn induces apoptosis by downregulating c-Myc in FaDU, providing evidence for the anticancer effect of SM on HSCC and uncovering the effect of SM on non-coding RNAs as, at least partly, a mechanism of action.
Comprehensive Analysis of the Aberrance and Functional Significance of Ferroptosis in Gastric Cancer
Authors: Xiao Jun , Zheng Lingyan , Liu Jingfeng 
Published: July 2022

Objective: Ferroptosis is a type of iron-dependent necrosis related to cancer. Nevertheless, the features of ferroptosis in gastric cancer (GC) remain poorly understood. This study conducted a systematic analysis of ferroptosis regulators in GC.Methods: We gathered five GC cohorts, namely, TCGA-STAD, GSE84437, GSE62254, GSE26901, and GSE15459. Unsupervised clustering analysis was adopted to cluster GC patients into different ferroptosis subtypes based on ferroptosis regulators. Immune cell infiltration and hallmark pathway activity were estimated via ssGSEA. The ferroptosis index was developed with the PCA computational method. Response to chemotherapy agents and small molecular compounds was inferred via GDSC, CTRP, and PRISM projects. Two anti-PD-1 therapy cohorts were gathered and the potential of FPI in predicting immune response was assessed.Results: Expression profiles, genetic mutations, DNA methylation, prognostic implications, and drug sensitivity of ferroptosis regulators were characterized in GC. Three ferroptosis subtypes were clustered with distinct prognosis, hallmark pathway activity, and tumor-infiltrating immune cells. Ferroptosis levels were quantified based on the expression of prognostic ferroptosis-related signatures. The significant relationships between FPI and clinicopathological characteristics were observed. Furthermore, high FPI was in relation to poor prognosis, inflamed tumor microenvironment (TME) as well as high sensitivity to chemotherapy agents (docetaxel and cisplatin), and CTRP- and PRISM-derived compounds. Also, FPI acted as a promising predictor of immune response.Conclusion: Collectively, our findings identified a novel ferroptosis-based subtype classification of GC, and revealed the potential of ferroptosis in forming TME diversity and complexity, and guiding individualized treatment.
Nanostructured Lipid Carrier-Based Delivery of Pioglitazone for Treatment of Type 2 Diabetes
Authors: Ilyas Umair , Asif Muhammad , Wang Minglian , Altaf Reem , Zafar Hajra , Faran Ashraf Baig Mirza Muhammad , Paiva-Santos Ana Cláudia , Abbas Muhammad 
Published: July 2022

Pioglitazone (PGZ) is utilized as a therapeutic agent in the management of (type 2) diabetes to control blood glucose levels. The existing research work was intended to make and optimize PGZ-containing NLCs (nanostructured lipid carriers). The fabricated nanostructured lipid carrier preparation was optimized by using different concentrations of the surfactants (Tween 80 and Span 80) and solid lipid (Compritol® 888 ATO) and liquid lipid (Labrasol®) while keeping the concentration of drug (PGZ), and co-surfactants (poloxamer 188) the same. The optimized NLC formulation (PGZ-NLCs) was further assessed for physical and chemical characterization, in vitro PGZ release, and stability studies. The optimized PGZ-NLCs have shown an average diameter of 150.4 nm, EE of 92.53%, PDI value of 0.076, and zeta-potential of −29.1 mV, correspondingly. The DSC thermal analysis and XRD diffractograms had not presented the spectrum of PGZ, confirming the comprehensive encapsulation of PGZ in the lipid core. PGZ-NLCs showed significantly extended release (51% in 24 h) compared to the unformulated PGZ. Our study findings confirmed that PGZ-NLCs can be a promising drug delivery system for the treatment of type 2 diabetes.
Psychedelics, Mystical Experience, and Therapeutic Efficacy: A Systematic Review
Authors: Ko Kwonmok , Knight Gemma , Rucker James J. , Cleare Anthony J. 
Published: July 2022

The mystical experience is a potential psychological mechanism to influence outcome in psychedelic therapy. It includes features such as oceanic boundlessness, ego dissolution, and universal interconnectedness, which have been closely linked to both symptom reduction and improved quality of life. In this review, 12 studies of psychedelic therapy utilizing psilocybin, ayahuasca, or ketamine were analyzed for association between mystical experience and symptom reduction, in areas as diverse as cancer-related distress, substance use disorder, and depressive disorders to include treatment-resistant. Ten of the twelve established a significant association of correlation, mediation, and/or prediction. A majority of the studies are limited, however, by their small sample size and lack of diversity (gender, ethnic, racial, educational, and socioeconomic), common in this newly re-emerging field. Further, 6 out of 12 studies were open-label in design and therefore susceptible to bias. Future studies of this nature should consider a larger sample size with greater diversity and thus representation by use of randomized design. More in-depth exploration into the nature of mystical experience is needed, including predictors of intensity, in order to maximize its positive effects on treatment outcome benefits and minimize concomitant anxiety.Systematic Review Registration: PROSPERO, identifier CRD42021261752.
The Impact of the COVID-19 Pandemic on Smoking Consumption: A Systematic Review of Longitudinal Studies
Authors: Almeda Nerea , Gómez-Gómez Irene 
Published: July 2022

The COVID-19 pandemic has generated a global health crisis that has negatively impacted the mental health and wellbeing of the population. A large amount of scientific literature has emerged since 2019, but none of these studies have focused on assessing the impact of COVID-19 on smoking consumption. We aimed to analyse the changes in smoking consumption during the COVID-19 pandemic through longitudinal studies. This systematic review follows the PRISMA Statement. This study was registered on PROSPERO (CRD42021282235). MEDLINE, ERIC, PsycARTICLES, Scopus, Web of Science and PsycINFO databases were searched from inception to 24 October 2021. We completed an extensive assessment of all prospective cohort studies that aimed to explore the effect of the COVID-19 pandemic on tobacco consumption habits. According to the PICOS's acronym, we included all population (P) types and studies developed before and during the COVID-19 pandemic (I) with a change in nicotine consumption as the outcome (O), as well as prospective cohort studies. The risk of bias was assessed using the Newcastle–Ottawa Scale for observational studies. The results showed that 14 cohorts reported in 11 articles fulfilled the inclusion criteria. A total of 58,052 participants were included in the review. Most of the studies pointed out a reduction in the number of cigarettes and e-cigarettes consumed from baseline (before the pandemic) to follow-up (during the pandemic). Only two studies reported an increase in cigarette or e-cigarette consumption from baseline to follow-up. The majority of studies presented a low risk of bias. In conclusion, the impact of the COVID-19 pandemic on smoking behavior is complex and uncertain. The decrease in smoking consumption during the pandemic could be related to the fear of becoming infected by COVID-19, the advancement of COVID-19, and the reduction in social gatherings. In several cases, the increases in nicotine consumption can be explained by psychological distress. These findings can be used to create strategies to prevent relapses during the post-vaccination phases of the pandemic.Systematic Review Registration: PROSPERO, identifier: CRD42021282235.
Age-Related Sex Disparities in Esophageal Cancer Survival: A Population-Based Study in the United States
Authors: Xiang Zhen-Fei , Xiong Hua-Cai , Hu Dan-Fei , Li Ming-Yao , Zhang Zhan-Chun , Mao Zheng-Chun , Shen Er-Dong 
Published: July 2022

BackgroundThe association between sex and the survival of patients with esophageal cancer (EC) remains controversial. We sought to systematically investigate sex-based disparities in EC survival using the Surveillance, Epidemiology, and End Results (SEER) registry data from the United States.MethodsPatients with EC diagnosed from 2004 to 2015 registered in the SEER database were selected. The association between sex and cancer-specific survival (CSS) was evaluated using survival analysis. The Inverse Probability Weighting (IPW) approach was applied to reduce the observed bias between males and females. Subgroup analyses were used to investigate the robustness of the sex-based disparity and to explore potential interaction effects with other variables.ResultsOverall, 29,312 eligible EC patients were analyzed, of whom 5,781 were females, and 23,531 were males. Females had higher crude CSS compared to males (10-year CSS: 24.5 vs. 21.3%; P &lt; 0.001). Similar results were obtained after adjusting for selection bias using the IPW approach and multivariate regression. Subgroup analyses confirmed the relative robustness of sex as a prognostic factor. However, significant interactions were observed between sex and other variables, such as age, race, tumor grade, histology, and treatment modality. In particular, there was no survival advantage for premenopausal females compared to their male counterparts, but the association between sex and EC survival was prominent in 46–55-year-old patients.ConclusionsFemale EC patients had better long-term survival than males. The association between sex and EC survival vary according to age, race, tumor grade, histology, and treatment modality. Sex-based disparity in EC-specific survival was age-related in the United States population.