bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the inequality of medical resources allocation based on spatial and non-spatial accessibility: A case study of Wenzhou, China
Authors: Du Miao , Zhao Yuhua , Fang Tao , Fan Linyu , Zhang Minghua , Huang Hong , Mei Kun 
Published: April 2022

Abstract
Background: Environmental and social factors that impact resource allocation in rural, developing regions are key social determinants of health that require multi-sector collaboration to improve health opportunities. Thus, we sought to evaluate the spatial distribution and accessibility of medical resources to assess current disparities, determine best practices for resource allocation, and inform policies to improve regional health planning.Methods: We used the Gini coefficient and agglomeration degree to measure inequality among the frequency distribution of medical resources in Wenzhou, China. We applied the modified hierarchical two-step floating catchment area (H2SFCA) method to evaluate the spatial accessibility of medical institutions across the city. Finally, we explored the influencing factors of accessibility differences using the spearman correlation analysis. Results: The distribution of medical resources in Wenzhou is inequitable according to population and geographical distribution. The overall spatial accessibility of Wenzhou is poor, the accessibility of east region is higher than west region, and the accessibility of different levels of medical institutions varies greatly. Accessibility is positively correlated with the number of institutions (ρ=0.585), the number of doctors (ρ=0.670), population density (ρ=0.769), road density (ρ=0.792), and GDP (ρ=0.310).Conclusions: There are disparities in the spatial and unbalanced distribution of medical resources in Wenzhou. Policies and initiatives to improve the geographical distribution of resources, construct connected road networks, and enhance resident access to medical resources are needed.
Examination of risk factors influencing the time to in-the-bag intraocular lens dislocation
Authors: Tokunaga Yoshiro , Nishimura Eiichi , Soda Mitsutaka , Ochiai Hirotaka 
Published: April 2022

Abstract
Purpose: To verify the risk factors that influence the intraocular lens (IOL) dislocationMethods: The time to of in-the-bag IOL (242 eyes) dislocation after the initial surgery was examined using patient characteristics and risk factors. The examined risk factors included 11 factors associated with underlying diseases (trauma, pseudoexfoliation syndrome (PE), atopic dermatitis, retinitis pigmentosa, glaucoma attack, glaucoma, short axial length, long axial length, uveitis, scleral buckling, post-pars plana vitrectomy) and two factors associated with the initial surgical findings (zonular weakness [ZW], posterior capsule rupture).In addition, the 242 eyes were classified into four groups (group A, PE+ ZW+; group B, PE− ZW+; group C, PE+ ZW−; group D, PE− ZW−), and the dislocation period was examined.Results: The median patient age was 67 years, and the median time to dislocation after the first cataract surgery was 120 months. Among the risk factors, PE and ZW were significantly associated with the time to dislocation (both p < 0.05). In addition, the time to dislocation was significantly shorter in groups A (12.3 months) and B (83.6 months) than in group D (135.6 months; p < 0.001 and p = 0.007, respectively).Conclusions: The presence of PE and/or ZW increases the risk of IOL dislocation. However, positivity for PE alone may be associated with a lower risk of IOL dislocation, indicating the need to assess ZW in the initial surgery.
Nitidine chloride inhibits proliferation and induces apoptosis in colorectal cancer cells by activating the p53 signaling pathway
Authors: Zheng Qiao , Zhang Yan , Zhang Lanlan , Chen Nianzhi , Zhang Gang , Zhao Maoyuan , Liao Wenhao , Zeng Zhongzhen , Wei Yujie , Zhou Gang , Tang Jianyuan , Zhao Ziyi 
Published: April 2022

Abstract
Background: Colorectal cancer, as a general malignancy of the digestive system, has long constituted a threat to the health of the population and the development of the social economy. It has been widely recognized that exploiting a drug with weaken toxic side effects and excellent antitumor activity can be a viable and promising strategy. Nitidine chloride is a typical bioactive base extracted from the dried roots of the Zanthoxylum nitidum (Roxb.) DC, has been clinically evidenced to exhibit robust immune efficacy against several types of tumor cells. However, the underlying function mechanism of the anti-colorectal-cancer effectiveness is still in its exploratory stage and thereby deserves further in-depth investigations.Objective: To examine the anti-cancer activity of Nitidine chloride against colorectal cancer in vitro and in vivo and its mechanism of effect.Methods: In this work, we combined a series of cellular characterization techniques to examine the inhibitory effect of Nitidine chloride (NC) on colorectal cancer cells, including RKO, HCT116 and HT29 cells. In addition, the potential signaling pathways were clarified via transcriptome sequencing technique. Moreover, we proposed a reliable biomedical mechanism towards the inhibition effects of the NC against colorectal cancer on the basis of qRT-PCR and western blot.Results: At first, we examined the toxic effect of NC on several colorectal cancer cells (RKO, HCT116 and HT29), within which the value of IC30 and IC50 were determined to be 2 µM and 3 µM for RKO; 3.5 µM and 5 µM for HCT116; and 6 µM and 10 µM for HT29, respectively. Through transcriptome sequencing, it is acquired that the p53 pathway and downstream signaling was prominently activated, indicating that NC is strongly correlated with cell proliferation and apoptosis. We also reveal that NC was able to suppress malignant behaviors, including proliferation, migration, invasion and tumor formation in RKO, HCT116 and HT29 cells. Besides, NC treatment significantly modified EMT-related hall marker proteins, including E-cadherin, N-cadherin and MMP9, which is indicative of the inhibition of EMT. Furthermore, the IC50 of NC significantly upregulated the pro-apoptosis-related factors, including Bax, Noxa, and caspase-3 and down-regulated the apoptosis-inhibiting factor Bcl2. Conclusion: In conclusion, the above experimental results and data analysis pointed out that colorectal cancer can be considerably suppressed by NC treatment, which effectively activates p53 signaling. Our approach should hold substantial promise for therapeutic applications in the therapy of colorectal cancer.
Isolated partial anomalous pulmonary veins: ten-year experience in a single center
Authors: Jin Can , Wu Yongtao , Wang Zhiyi , Liu Xiaoran , Yang Jing , Fan Xiangming 
Published: April 2022

Abstract
Background: Isolated partial anomalous pulmonary venous connection (PAPVC) is difficult to diagnose. Surgical indications remain controversial. This study aimed to review cases of isolated PAPVC treated from 2010 to 2019 and share our 10-year experiences in managing these cases.Methods: Patients with isolated PAPVC admitted to the Anzhen Congenital Heart Disease Department from 2010 to 2019 were reviewed.Results: A total of 30 patients between 4 months and 32 years of age were included. Correlations of right ventricular (RV) end-diastolic dimension z-score (RVED-z) with age (P=0.003) and estimated pulmonary pressure with age (P=0.03) were significant. There were no significant correlations between RVED-z and the number of anomalous PVs (P=0.121), between estimated pulmonary pressure and RVED-z (P=0.094), and between estimated pulmonary pressure with the number of anomalous veins (P=0.110). Transthoracic echocardiography confirmed 90% of the cases of isolated PAPVC. Surgical repair was performed in 29 patients with RV enlargement, persistent low weight, two or more anomalous veins, pulmonary hypertension, or respiratory symptoms. No mortality or re-intervention was observed in the surgical patients. The mean duration of echocardiographic follow-up was 1.9 years, during which 25 patients (86%) had a reduction in RV size. Nine patients had elevated pulmonary pressure before surgery, and the pressure decreased after surgery.Conclusions: Transthoracic echocardiography is recommended for routine assessment; PAPVC should be considered as a possibility when unexplained right chamber enlargement appears. Patients with symptoms, pathologic changes, or more than one anomalous pulmonary vein may require surgical treatment to reduce morbidity and mortality.
The Combination of BRAFV600E mutation and Chinese Thyroid Imaging Reporting and Data System is Helpful in the Management of AUS/FLUS Thyroid Nodules
Authors: Li Qiang 
Published: April 2022

Abstract
Purpose To explore the utility of the BRAFV600E mutation in combination with Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) in the management of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) thyroid nodule (TN).Methods 138 AUS/FLUS TNs in 129 patients were included. Each TN underwent preoperative BRAFV600E mutation analysis and was classified using the C-TIRADS. Histopathologic diagnosis served as reference standard.Results 46 benign TNs and 92 malignant TNs were identified. Malignant TNs were more commonly observed in TNs with a size less than 10mm (P = 0.033). There were significant differences in malignancy rate among the different C-TIRADS TNs (P = 0.000), and these TNs with higher C-TIRADS were associated with increased malignancy rate (P for trend = 0.000). The rate of nodule with BRAFV600E mutation increased with the increase of C-TIRADS (P for trend = 0.001). For AUS/FLUS TNs without BRAFV600E mutation, the malignancy rates of the C-TIRADS 3, 4A, 4B, 4C, and 5 were 0%, 21.4%, 20.8%, 70.8%, and 100%, respectively (P = 0.000), and the malignancy rate increased from C-TIRADS 3 to C-TIRADS 5 (P for trend = 0.000). The diagnostic performance of C-TIRADS was similar to the BRAFV600E mutation (P > 0.05), and the sensitivity, negative predictive value, and accuracy of the combination were significantly higher than BRAFV600E gene or C-TIRADS alone (P < 0.05).Conclusions C-TIRADS can effectively provide risk stratification for AUS/FLUS TNs. The combination can be helpful in selecting appropriate management for AUS/FLUS patients.
New Tobacco Products Variety and Regulation Avoidance: Findings from Points of Sale Survey in Indonesia
Authors: Bigwanto Mouhamad , Muhammad Fathi , Widad Sarah Muthia , Yudha Laksmana 
Published: April 2022

Abstract
Background: Since the imposition of excise tax in 2018, the new tobacco products are considered legal and it has been growing rapidly in Indonesia. This study aims to determine the variety of new tobacco products available in the market and evaluate the points of sale environment.Methods: Data collection was carried out by 12 trained surveyors from 7-13 March 2022 in three provinces that had the most e-cigarette users; Yogyakarta, East Kalimantan, and Jakarta. All vape stores that have >4.5 rating on Google with a minimum of 100 reviews were included. In addition to vape stores, the nearest retail stores were also included. The data collected includes available products, product displays, and how the point of sale follows tobacco control measures such as health warnings and smoke-free regulations.Results: A total of 27 vape stores and 35 retail stores were observed. The available sizes of liquids range from 15 - 100 ml with nicotine levels from 3 - 50 mg. No stores sell flavorless products and all products were sold without pictorial health warnings. Most of the vape stores (92.6%) reported selling products that used cartoon images or public figures and allow (96.3%) their customers to use the products inside the store. There were 5 vape stores and 4 retail stores that reported no identity verification process to buy products. More than half (55.6%) of vape stores and 46.6% of retail stores were reported to be located <500 meters from the school. Conclusions: The products' availability is widely varied and it was easy to access through online and offline stores. The new tobacco products have successfully avoided several tobacco control measures such as smoke-free regulation and pictorial health warnings on the products. The government needs to provide adequate regulation to prevent youth from consuming the products.
Systematic Pan-Cancer Analysis Identifies REST as an Oncogenic and Immunological Biomarker in Brain Low Grade Glioma
Authors: Wang Guan , Li Meng , Dong Meng , Xu Rui , Zhang Chen 
Published: April 2022

Abstract
Background
The repressor element 1 silencing transcription factor (REST) has been proposed to function as a transcription factor to silence gene transcription by binding to repressor element 1 (RE1), a highly conserved DNA motif. The functions of REST in various tumors have been studied, but its role and correlation with immune cell infiltration remains uncertain in low grade gliomas (LGGs).
Methods
REST expression was analyzed in datasets of The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx). The clinical prognosis of REST was evaluated by clinical survival data of TCGA. MicroRNAs (miRNAs) contributing to REST overexpression in LGG were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. The correlations between immune cell infiltration level and REST expression were analyzed by TIMER2 and GEPIA2 tools. Enrichment analysis of REST was performed using STRING and Metascape tools.
Results
REST was highly expressed and associated with poorer overall survival and disease-specific survival in LGG and some other tumors. MiR-105-5p and miR-9-5p were identified as the most potential upstream miRNAs of REST in LGG. REST expression was positively correlated with infiltration of immune cells and the expressions of immune checkpoints such as PD1/PD-L1 and CTLA-4 in LGG. Furthermore, the histone deacetylase 1 (HDAC1) was the potential REST-related gene in LGG. Enrichment analysis of REST found chromatin organization and histone modification were the most significant enriched terms, and Hedgehog-Gli pathway might be involved in the effect of REST on the pathogenesis of LGG.
Conclusions
Our study suggests REST to be the oncogenic gene and the biomarker of poor prognosis in LGG. High REST expression might affect the tumor microenvironment of LGG. More basic experiments and large clinical trials aimed at the carcinogenetic study of REST in LGG will be needed in the future.
Autonomic nerve activity in dry eye with decreased tear stability
Authors: Kaido Minako , Arita Reiko , Mitsukura Yasue , Ishida Reiko , Tsubota Kazuo 
Published: April 2022

Abstract
Stress might activate sympathetic nerve activity, causing dry eye (DE). We investigated biological parameters reflecting autonomic nerve activity in DEs with decreased tear stability. This prospective, cross-sectional, comparative study enrolled 34 eyes of 34 participants (mean age: 52.5 ± 13.4 years; range: 20–81 years) without keratoconjunctival damage. The 19 eyes in the DE group showed DE symptoms and tear break-up time (BUT) ≤ 5 seconds (short BUT DE); the 15 eyes in the non-DE group showed no DE symptoms. Autonomic nerve activity was measured for 10 minutes—starting and ending 5 minutes before and after instilling ophthalmic solution—and evaluated using the low-frequency component (LF) to the high-frequency component (HF) ratio of heart rate variability (autonomic balance). The pre-instillation LF/HF ratio was not significantly different (P = 0.86). The pre-instillation standard deviation of the LF/HF ratio (LF/HF-SD) was higher in the DE group than in the non-DE group (P = 0.05). DE symptoms intensity was significantly related to LF/HF-SD (P = 0.005). The LF/HF-SD significantly decreased post-instillation in the DE group (P = 0.03). The large fluctuations observed in the autonomic balance were related to DE symptom intensity in short BUT DE and may improve understanding of the DE-symptom mechanism.
The effects of breastfeeding and formula feeding on the metabolic factors and the expression level of obesity and diabetes-predisposing genes in healthy infants
Authors: Cheshmeh Sahar , Nachvak Seyed Mostafa , Hojati Niloofar , Elahi Negin , Heidarzadeh Neda , Saber Amir 
Published: April 2022

Abstract
Background
Diabetes mellitus (DM) and obesity are common illnesses characterized by glucose metabolism issues and excessive weight gain. Breastfeeding is the best way to feed a newborn up to six months old and it has been shown to reduce the risk of diabetes and obesity later in life due to its nutritional properties. The aim of this study was to investigate the effects of breastfeeding, formula feeding, and formula-plus breastfeeding (mix-feeding) on the anthropometric indices, metabolic variables, and the expression level of obesity and diabetes-predisposing genes of healthy infants.
Methods
A total of 150 healthy infants were enrolled in this cross-sectional study. All infants (aged 24 months) were divided into three groups based on the type of feeding, breastfeeding, formula feeding, and mix-feeding. The anthropometric indices, glycemic indexes, lipid profile, and the expression levels of acetyl-coenzyme A carboxylase beta (ACACB), brain-derived neurotrophic factor (BDNF), liver X receptor α (LXR-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and phosphatase and tensin homolog (PTEN) genes were measured in all infants using reverse transcription-polymerase chain reaction (RT-PCR) method.
Results
The anthropometric indices including weight, height, head circumference, insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were lower in the breastfeeding infants in comparison to other groups. As well, the expression level of the ACACB gene was significantly downregulated in breastfeeding infants, while the PPAR-γ gene was significantly upregulated, but the expression levels of LXR- α, PTEN and BDNF didn’t change significantly across groups.
Conclusions
Breastfeeding compared to formula feeding had positive effects on anthropometric indices, metabolic variables, and diabetes-predisposing genes.
Activation of intra-nodose ganglion P2X7 receptors elicit increases in neuronal activity
Authors: Alcayaga Julio , Vera Jorge , Rio Rodrigo , Retamal Mauricio A. 
Published: April 2022

Abstract
The vagus nerve innervates several organs including the heart, stomach and pancreas among others. Somas of sensory neurons that project through the vagal nerve are located into the nodose ganglion. The presence of purinergic receptors has been reported in neurons and satellite glial cells in several sensory ganglia. In the nodose ganglion, calcium depletion-induced increases in neuron activity can be partly reversed by P2X₇ blockers applied directly into the ganglion. The later suggest a possible role of P2X₇ receptors in the modulation of neuronal activity within this sensory ganglion. We aimed to characterize the neuronal response to the P2X₇ activation in neurons located in the nodose ganglion under physiological conditions. Using an ex-vivo preparation for electrophysiological recordings of the neural discharges of nodose ganglion neurons, we found that applications of both ATP and Bz-ATP (a selective P2X7 receptor agonist) induce a transient increase of the neuronal activity. Also, we found a concentration dependent increase in neural activity in response to Bz-ATP (ED₅₀ = 0.55 mM) with a clear desensitization when applied every ~30 sec. Isolated nodose ganglion neuron electrophysiological recordings reveal no differences in the response to Bz-ATP and ATP. Finally, we showed that the P2X₇ receptor was constitutively express in the nodose ganglion in both neurons and satellite glial cells. Our results showed the presence of functional P2X7 receptors under physiological conditions within the nodose ganglion of the rat and suggest that ATP modulation of nodose ganglion activity may be in part mediated by activation of P2X7 receptors.
Population-dependent stress response of bivalve mollusc Unio tumidus to ibuprofen, microplastic and their mixture
Authors: Stoliar Oksana , Martinyuk Viktoria , Gylytė Brigita , Matskiv Tetiana , Khoma Vira , Tulaidan Halyna , Gnatyshyna Lesya , Orlova-Hudim Kateryna , Manusadžianas Levonas 
Published: April 2022

Abstract
Even though bivalve molluscs are recognized as bioindicators of freshwater quality, their responses to multiple stressors are unpredictable. This study aims to elucidate the inter-population peculiarities of the effect in the sub-chronic environmentally relevant exposure to novel contaminants. The specimens of Unio tumidus from pristine (Pr) and contaminated (Ct) areas were treated with ibuprofen (IBU, 0.8 µg L− 1), microplastic (MP, 1.0 mg L− 1, size 0.1–0.5 mm), or their combination (Mix) for 14 days. Untreated mussels (PrC- and CtC-groups) served as controls. The PrC-group had higher levels of antioxidants Mn-SOD, Cu,Zn-SOD, catalase, and cholinesterase (AChE) as well as lesser levels of oxidative lesions (TBARS and protein carbonyls) in digestive gland than the CtC-group, confirming different quality of life in two populations. However, lysosomal stability was similar in all studied groups. IBU induced antioxidant and AChE responses and lysosomal integrity in the Ct-group, only. MP caused the up-regulation of Mn-SOD and TBARS, and the suppression of Cu,Zn-SOD solely in the Pr-group. Discriminant analyses indicated lesser differences between Pr-groups, demonstrating their resistance across all treatments compared to Ct-groups. Most remarkable response was revealed in the CtIBU-group, and the alleviation of individual effects was established in combined exposures. The qualification of stress-neutral and stress-positive populations were proposed for Pr- and Ct-populations correspondingly. Inter-population peculiarities must be taken into consideration when environmental impact of MP and pharmaceuticals is evaluated.
Expression Pattern and Prognostic Potential of Histamine Receptors in Epithelial Ovarian Cancer
Authors: Kraus FBT , Topalov NE , Deuster E , Hysenaj I , Mayr D , Chelariu-Raicu A , Beyer S , Kolben T , Burges A , Mahner S , Trillsch F , Jeschke U , Czogalla Bastian 
Published: April 2022

Abstract
Purpose: Despite recent advances in the treatment of ovarian cancer (OC), long-term remissions remain scarce. For a targeted approach, prognostic markers are indispensable for predicting survival and treatment response. Given their association with multiple hallmarks of cancer, histamine receptors (HR) are emerging as promising candidates. Here, we investigate their expression pattern and prognostic value in OC.Methods: Specimens of 156 epithelial OC patients were collected during cytoreductive surgery at the Department of Obstetrics and Gynecology, LMU, between 1990 and 2002 and combined in a tissue microarray. Immunohistochemical staining of the HR H1, H2, H3 and H4 was quantified by an immunoreactive score and linked with clinico-pathological data by Spearman’s correlation. Via ROC curve analysis, optimal cut-off values for potential prognostic markers were defined. Overall survival (OS) was visualized in Kaplan-Maier curves and significances determined by log-rank testing. A Cox regression model was applied for multivariate analysis.Results: HR H3 and H4 expression was restricted to the cytosol of OC cells, whilst H1 was also present in the nucleus. A significant association between HR H1, H3 and H4 expression with several clinico-pathological parameters was revealed. In addition, HR H1 and H3 expression correlated positively, HR H4 expression negatively with OS. Additionally, HR H3 was identified as independent prognostic marker for OS. HR H2 expression had no prognostic value.Conclusion: HR H1, H3 and H4 could serve as potential predictors for OS of OC patients. Further research is warranted to elucidate their pathophysiologic role and their predictive and therapeutic potential in OC.