bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Plantar Tissue Hardness and Plantar Pressure Distributions in People With Diabetic Peripheral Neuropathy
Authors: Duan Yijie , Ren Weiyan , Liu Wei , Li Jianchao , Pu Fang , Jan Yih-Kuen 
Published: April 2022

Objective: People with diabetic peripheral neuropathy (DPN) are usually accompanied with increased plantar pressure. Such high plantar loading during daily activities may cause changes in the biomechanical properties of plantar soft tissue, whose viability is critical to the development of foot ulcers. This study aimed to investigate the relationship between plantar tissue hardness and plantar pressure in people with and without DPN, and preliminarily explore the influence of plantar loading patterns on the plantar pressure and tissue hardness.Methods: The study was conducted on 14 people with DPN and 14 diabetic people without DPN. The Shore durometer and MatScan System were used to measure the plantar tissue hardness and plantar pressure, respectively. The plantar loading level was evaluated by the duration of daily weight-bearing activity and was used to group diabetic participants with and without DPN into two subgroups (lower loading group and higher loading group).Results: The plantar tissue hardness was significantly correlated with static peak plantar pressure (PPP, p &lt; 0.05) and dynamic pressure-time integral (PTI, p &lt; 0.05) in the forefoot region in people with DPN. Results of variance analysis showed a significant interaction effect between peripheral neuropathy and plantar loading on tissue hardness (p &lt; 0.05), but not plantar pressure. For people with DPN, significant differences in tissue hardness between the higher loading group and lower loading group were observed in the forefoot, midfoot and hindfoot regions. In the higher loading group, people with DPN had significantly greater tissue hardness than that in people without DPN in the toes, forefoot, midfoot and hindfoot regions (p &lt; 0.05).Conclusions: There is a significant correlation between tissue hardness and PPP, and between tissue hardness and PTI in people with DPN. Plantar loading associated with daily activities plays a significant role on the plantar tissue hardness in people with DPN. The findings of this study contribute to further understand the relationship between increased plantar tissue hardness and high plantar pressure in people with diabetic peripheral neuropathy.
Breast Cancer Patients With Positive Apical or Infraclavicular/Ipsilateral Supraclavicular Lymph Nodes Should Be Excluded in the Application of the Lymph Node Ratio System
Authors: Wang Zhe , Chong Wei , Zhang Huikun , Liu Xiaoli , Zhao Yawen , Guo Zhifang , Fu Li , Ma Yongjie , Gu Feng 
Published: April 2022

Aim: Increasing studies have demonstrated lymph node ratio (LNR) to be an accurate prognostic indicator in breast cancer and an alternative to pN staging; however, the AJCC-TNM staging system classified apical or infraclavicular/ipsilateral supraclavicular lymph node-positive (APN(+)) patients with a worse prognosis as the pN3 stage. Until now, different reports on LNR in breast cancer have ignored this possibility. Consequently, it is necessary to discuss the role of APN(+) patients in the LNR system to obtain a precise LNR that predicts the prognosis accurately.Materials and Methods: We collected data on 10,120 breast cancer patients, including 3,936 lymph node-positive patients (3,283 APN(−) and 653 APN(+) patients), who visited our hospital from 2007 to 2012. Then we applied X-tile analysis to calculate cut-off values and conduct survival analysis and multivariate analysis to evaluate patients’ prognosis.Results: We confirmed that some APN(+) patients were mis-subgrouped according to previously reported LNR, indicating that APN(+) patients should be excluded in the application of LNR to predict prognosis. Then we applied X-tile analysis to calculate two cut-off values (0.15 and 0.34) for LNR-APN(−) patients and conducted survival analysis and found that LNR-APN(−) staging was superior to pN staging in predicting the prognosis of APN(−) breast cancer patients.Conclusion: From this study, we conclude that excluding APN(+) patients is the most necessary condition for effective implementation of the LNR system. LNR-APN(−) staging could be a more comprehensive approach in predicting prognosis and guiding clinicians to provide accurate and appropriate treatment.
Development and Validation of a GC-EI-MS/MS Method for Ethyl Glucuronide Quantification in Human Hair
Authors: Mattia Alessandro , Moschella Clementina , David Maria Chiara , Fiore Marco , Gariglio Sara , Salomone Alberto , Vincenti Marco 
Published: April 2022

Ethyl glucuronide (EtG) is a minor, non-oxidative ethanol metabolite detectable in several matrices for specific periods of time. In recent years, quantification of EtG in hair has been established as the most reliable biomarker for long-term alcohol consumption, with the Society of Hair Testing offering cut-off values for assessment of both abstinence and heavy drinking. Instrumental constrains and wide inter- and intra-laboratory variability represent the ultimate barriers to widespread acceptance of hair EtG determination in the forensic context. In this study, a new analytical method for hair EtG based on gas chromatographic (GC) separation, electron impact (EI) ionization, and tandem mass spectrometry (MS/MS) detection was developed and validated. At the same time, several parameters for sample pretreatment and instrumental analysis were optimized using real hair samples obtained from different drinking subjects. A full-factorial design-of-experiment approach included procedures for hair washing, pulverization, and extraction. Rigorous multi-step washing proved not to reduce the EtG content extracted in the subsequent sample incubation. Hair pulverization with a ball mill significantly improved the EtG extraction from the keratin matrix and allowed us to reduce the time needed for the subsequent extraction step, without affecting the extraction recovery. The hair extract was derivatized with N-methyl-N-(trimethylsilyl)-trifluoroacetamide. Upon electron impact ionization of the EtG-TMS derivative, triple quadrupole mass analyzers were operated in the selected reaction monitoring (SRM) mode using the fragment m/z 405 as the precursor ion (m/z 410 for the EtG-D5 internal standard), the transitions m/z 405 → 359 and m/z 410 → 359 for quantitation, and m/z 405 → 331 and m/z 405 → 287 for qualification/confirmation, all at 10 V collision energy. The final method was fully validated and then applied to 25 real hair samples. The calibration curve proved linear between 6 and 60 pg/mg. The limit of detection (LOD) was 4 pg/mg. Intra- and inter-assay precision and accuracy tests showed a variability and bias close to 15% or lower over the entire calibration range. The new method is routinely applied in the Italian State Police’s toxicology laboratory for hair analyses addressed to exclude excessive alcohol drinking and verify the psycho-physical requirements of the personnel.
Epidemiology of Atrial Fibrillation and Related Myocardial Ischemia or Arrhythmia Events in Chinese Community Population in 2019
Authors: Li Cheng , Wang Haicheng , Li Mohan , Qiu Xiangjun , Wang Qunshan , Sun Jian , Yang Mei , Feng Xiangfei , Meng Shu , Zhang Pengpai , Liu Bo , Li Wei , Chen Mu , Zhao Yan , Zhang Rui , Mo Binfeng , Zhu Yuling , Zhou Baohong , Chen Min , Liu Xia , Zhao Yuelin , Shen Mingzhen , Huang Jinkang , Luo Li , Wu Hong , Li Yi-Gang 
Published: April 2022

BackgroundAtrial fibrillation (AF) is the most common arrhythmia, and the incidence increases rapidly all over the world. The global prevalence of AF (age-adjusted) is 0.60% for men and 0.37% for women and the prevalence of AF in China is 0.65%. It is expected that the number of patients with AF will continue to rise in the future worldwide due to population aging.ObjectiveTo explore the prevalence of AF in Chinese community population in 2019 and clarify the prevalence of AF complicated with other arrhythmias and myocardial ischemia (MI) events.MethodsThe remote electrocardiogram (ECG) diagnosis system of Xinhua Hospital was assessed to the screen participants with ECG evidence of AF between January 1 and December 31, 2019. The prevalence rates of AF and its association with other arrhythmias and MI events were analyzed and subgroup analysis was performed between different sexes and age groups.ResultsA total of 22,016 AF cases were identified out of all ECGs derived from the remote ECG diagnosis system in 2019. It is estimated that AF was presented in nearly 10.15 million people in China (age-adjusted standardized rate 0.72%, 95% CI 0.20–1.25%) in 2019 and 62% of the AF cases (6.27 million) affected people aged 65 years and above (age-adjusted standardized rate 3.56%, 95% CI 3.28–3.85%). The prevalence rate of AF in males was higher than that in females (p &lt; 0.001), and the ventricular rate of AF patients was faster in females (p &lt; 0.001) and younger patients (p &lt; 0.001). AF patients with lower ventricular rate (under 60 beats per min) were associated with increased prevalence of ventricular escape/escape rhythm [p &lt; 0.001, odds ratio (OR) 5.14] and third-degree atrioventricular block (p &lt; 0.001, OR 32.05).ConclusionThe prevalence of AF is higher in the Chinese community population than that was previously reported. AF patients complicated with ECG patterns suggesting myocardial infarction is common in men, and stricter measures should be taken to control the common risk factors of AF and coronary heart disease. It is also important that more attention should be paid to recognize fatal arrhythmias, especially in elderly male patients with AF.
Clinical Implications of Atrial Fibrillation Detection Using Wearable Devices in Patients With Cryptogenic Stroke (CANDLE-AF) Trial: Design and Rationale
Authors: Jung Sodam , Lee Hye Ah , Kang In Sook , Shin Sang Hoon , Chang Yoonkyung , Woo Shin Dong , Park Moo-Seok , Kim Young Dae , Nam Hyo Suk , Heo Ji Hoe , Kim Tae-Hoon , Yu Hee Tae , Lee Jung Myung , Heo Sung Hyuk , Woo Ho Geol , Park Jin-Kyu , Roh Seung-Young , Kim Chi Kyung , Lee Young-Soo , Do Jin Kuk , Kim Dong-Hyeok , Song Tae-Jin , Park Junbeom ,   CANDLE-AF Trial Investigators
Published: April 2022

BackgroundAlthough many electrocardiography wearable devices have been released recently for the detection of atrial fibrillation (AF), there are few studies reporting prospective data for wearable devices compared to the strategy of the existing guidelines in the detection of atrial fibrillation (AF) after cryptogenic stroke. A tiny single-patch monitor is more convenient than a conventional Holter monitor recording device and, therefore, longer duration of monitoring may be acceptable.Methods and DesignThe CANDLE-AF study is a multicenter, prospective, randomized controlled trial. Patients with transient ischemic attack or ischemic stroke without any history of AF will be enrolled. The superiority of the 72-h single-patch monitor to standard strategy and non-inferiority of the 72-h single-patch monitor to an event-recorder-type device will be investigated. Single-patch monitor arm will repeat monitoring at 1, 3, 6, and 12 months, event-recorder-type arm will repeat monitoring twice daily for 12 months. The enrollment goal is a total of 600 patients, and the primary outcome is the detection of AF which continues at least 30 s during study period. The secondary outcome is the rate of changes from antiplatelet to anticoagulant and major adverse cardiac and cerebrovascular events within 1 year.ConclusionsThe results of CANDLE-AF will clarify the role of a single-lead patch ECG for the early detection of AF in patients with acute ischemic stroke. In addition, the secondary outcome will be analyzed to determine whether more sensitive AF detection can affect the prognosis and if further device development is meaningful. (cris.nih.go.kr KCT0005592).
The Role of Urinary Extracellular Vesicles Sodium Chloride Cotransporter in Subtyping Primary Aldosteronism
Authors: Kong Linghui , Tang Xiaofeng , Kang Yuanyuan , Dong Lei , Tong Jianhua , Xu Jianzhong , Gao Ping-jin , Wang Ji-guang , Shen Weili , Zhu Limin 
Published: April 2022

BackgroundAdrenal venous sampling (AVS) is recognized as the gold standard for subtyping primary aldosteronism (PA), but its invasive nature and technical challenges limit its availability. A recent study reported that sodium chloride cotransporter (NCC) in urinary extracellular vesicles (uEVs) is a promising marker for assessing the biological activity of aldosterone and can be treated as a potential biomarker of PA. The current study was conducted to verify the hypothesis that the expression of NCC and its phosphorylated form (pNCC) in uEVs are different in various subtypes and genotypes of PA and can be used to select AVS candidates.MethodsA total of 50 patients with PA were enrolled in the study. Urinary extracellular vesicles (uEVs) were isolated from spot urine samples using ultracentrifugation. NCC and pNCC expressions were tested in patients diagnosed with PA who underwent AVS. Sanger sequencing of KCNJ5 was performed on DNA extracted from adrenal adenoma.ResultspNCC (1.89 folds, P&lt;.0001) and NCC (1.82 folds, P=0.0002) was more abundant in the uEVs in the high lateralization index (h-LI, ≥ 4) group than in the low LI (l-LI, &lt; 4) group. Carriers of the somatic KCNJ5 mutations, compared with non-carriers, had more abundant pNCC expression (2.16 folds, P=0.0039). Positive correlation between pNCC abundance and plasma aldosterone level was found in this study (R = 0.1220, P = 0.0129).ConclusionsThe expression of pNCC in uEVs in patients with PA with various subtypes and genotypes was different. It can be used as biomarker of AVS for PA subtyping.
Nexuses Between Energy Efficiency, Renewable Energy Consumption, Foreign Direct Investment, Energy Consumption, Global Trade, Logistics and Manufacturing Industries of Emerging Economies: In the Era of COVID-19 Pandemic
Authors: Rehman Khan Syed Abdul , Hassan Shafiqul , Khan Mubashir Ali , Khan M. R. , Godil Danish Iqbal , Tanveer Muhammad 
Published: April 2022

This study aims to find the nexuses among energy efficiency, renewable energy consumption, foreign direct investment, logistics industry, manufacturing industry and global trade during the COVID-19 pandemic and their impact on global supply chains in exporting nations of the world. The data for this study has been extracted from the World Development Indicators and Statista 2021 for 13 years ranging from 2007-to 2020 for nine top exporting countries. The fixed effect panel estimation technique was implied to examine and analyze the data. The results of our study revealed that highly risky diseases significantly impact supply chain operations globally. Global supply chains, logistics and manufacturing industries significantly influence global trade operations. Our results implicate that the overall international trade and logistics can be enhanced by improving the manufacturing and logistics industries by coping with the risk of pandemic diseases. Moreover, by utilizing cost-effective, renewable and efficient energy resources companies address sustainability issues of global trade and operations. By exerting further attention to the proficiency of the levies approval process, competence and quality of logistics services, and ease of assembling competitively priced shipments, the governments can significantly enhance the export from the logistics industry. Also, increasing manufacturing and agricultural value-added healthier consequences might be acquired in global supply chain operations from the manufacturing industry.
Clinical and Genetic Analysis in Neurological Wilson’s Disease Patients With Neurological Worsening Following Chelator Therapy
Authors: Hou Haiman , Chen Dingbang , Liu Junxiu , Feng Li , Zhang Jiwei , Liang Xiuling , Xu Yuming , Li Xunhua 
Published: April 2022

Objectives: None of the previous studies have focused on the genetic effect on neurological worsening in neurological Wilson’s disease (WD) patients following chelator therapy. We aimed to evaluate the clinical and genetic role in the occurrence of neurological worsening.Methods: We retrospectively reviewed the medical records of neurological WD patients who received initial chelator therapy and genetic test. Clinical, laboratory, and genetic data were collected. The genotype was classified into two types: 1) severe mutation genotype: patients who carried at least one of the following three types of mutations: frameshift mutation, splicing mutation, or nonsense mutation; 2) non-severe mutation genotype: patients who only carried missense mutations. Then, the clinical features and genotype of the patients with and without neurological worsening were investigated.Results: Forty-seven neurological WD patients were identified with a median age at onset of 16.17 years (range 7.75–47 years) and 35 (74.5%) males. The mean interval from onset to diagnosis was 0.6 years (range: 0.5 months-6.25 years). Neurological deterioration was observed in 29 patients (61.7%) and the other 18 patients (38.3%) were stable or improved during anti-copper treatment. The neurological worsening was completely irreversible in 6 cases (20.7%) and partially irreversible in 16 cases (55.2%). The common deteriorated symptoms were as follows: rigidity in 20 cases (69%), speech difficulties in 20 cases (69%)), walking difficulties in 13 cases (44.8%), dysphagia in 9 cases (31%), and salivation in 9 cases (31%). The patients with neurological worsening had significantly younger age (p = 0.028), shorter delayed diagnosis time (p = 0.011), higher rate of dystonia (p = 0.003), and severe mutation genotype (p = 0.036), compared to those without neurological worsening.Conclusion: We found that younger age of onset, the presence of dystonia, and genotype with severe mutations may be predictive of neurological worsening in the neurological WD patients that received chelator therapy. For those patients, chelator therapy should be given with caution and needs closer observation during follow-up.
Pan-Cancer Analysis Shows That ALKBH5 Is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Gliomas
Authors: Wei Cheng , Wang Bo , Peng Dazhao , Zhang Xiaoyang , Li Zesheng , Luo Lin , He Yingjie , Liang Hao , Du Xuezhi , Li Shenghui , Zhang Shu , Zhang Zhenyu , Han Lei , Zhang Jianning 
Published: April 2022

BackgroundAlkB homolog 5 (ALKBH5) is a N6-methyladenosine (m6A) demethylase associated with the development, growth, and progression of multiple cancer types. However, the biological role of ALKBH5 has not been investigated in pan-cancer datasets. Therefore, in this study, comprehensive bioinformatics analysis of pan-cancer datasets was performed to determine the mechanisms through which ALKBH5 regulates tumorigenesis.MethodsOnline websites and databases such as NCBI, UCSC, CCLE, HPA, TIMER2, GEPIA2, cBioPortal, UALCAN, STRING, SangerBox, ImmuCellAl, xCell, and GenePattern were used to extract data of ALKBH5 in multiple cancers. The pan-cancer patient datasets were analyzed to determine the relationship between ALKBH5 expression, genetic alterations, methylation status, and tumor immunity. Targetscan, miRWalk, miRDB, miRabel, LncBase databases and Cytoscape tool were used to identify microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate expression of ALKBH5 and construct the lncRNA-miRNA-ALKBH5 network. In vitro CCK-8, wound healing, Transwell and M2 macrophage infiltration assays as well as in vivo xenograft animal experiments were performed to determine the biological functions of ALKBH5 in glioma cells.ResultsThe pan-cancer analysis showed that ALKBH5 was upregulated in several solid tumors. ALKBH5 expression significantly correlated with the prognosis of cancer patients. Genetic alterations including duplications and deep mutations of the ALKBH5 gene were identified in several cancer types. Alterations in the ALKBH5 gene correlated with tumor prognosis. GO and KEGG enrichment analyses showed that ALKBH5-related genes were enriched in the inflammatory, metabolic, and immune signaling pathways in glioma. ALKBH5 expression correlated with the expression of immune checkpoint (ICP) genes, and influenced sensitivity to immunotherapy. We constructed a lncRNA-miRNA network that regulates ALKBH5 expression in tumor development and progression. In vitro and in vivo experiments showed that ALKBH5 promoted proliferation, migration, and invasion of glioma cells and recruited the M2 macrophage to glioma cells.ConclusionsALKBH5 was overexpressed in multiple cancer types and promoted the development and progression of cancers through several mechanisms including regulation of the tumor-infiltration of immune cells. Our study shows that ALKBH5 is a promising prognostic and immunotherapeutic biomarker in some malignant tumors.
YTHDF1 Negatively Regulates Treponema pallidum-Induced Inflammation in THP-1 Macrophages by Promoting SOCS3 Translation in an m6A-Dependent Manner
Authors: Li Zhijia , Teng Muzhou , Jiang Yinbo , Zhang Litian , Luo Xi , Liao Yuhui , Yang Bin 
Published: April 2022

BackgroundPrevious studies have confirmed that the bacterium Treponema pallidum (TP) or its proteins provide signals to macrophages that induce an inflammatory response; however, little is known about the negative regulation of this macrophage-mediated inflammatory response during syphilis infection or the underlying mechanism. Recent evidence suggests the role of the RNA modification, N6-adenosine methylation (m6A), in regulating the inflammatory response and pathogen-host cell interactions. Therefore, we hypothesized that m6A plays a role in the regulation of the inflammatory response in macrophages exposed to TP.MethodsWe first assessed m6A levels in TP-infected macrophages differentiated from the human monocyte cell line THP-1. The binding and interaction between the m6A “writer” methyltransferase-like 3 (METTL3) or the m6A “reader” YT521-B homology (YTH) domain-containing protein YTHDF1 and the suppressor of cytokine signaling 3 (SOCS3), as a major regulator of the inflammatory response, were explored in differentiated TP-infected THP-1 cells as well as in secondary syphilitic lesions from patients. The mechanisms by which YTHDF1 and SOCS3 regulate the inflammatory response in macrophages were assessed.Results and ConclusionAfter macrophages were stimulated by TP, YTHDF1 was upregulated in the cells. YTHDF1 was also upregulated in the syphilitic lesions compared to adjacent tissue in patients. YTHDF1 recognizes and binds to the m6A methylation site of SOCS3 mRNA, consequently promoting its translation, thereby inhibiting the JAK2/STAT3 pathway, and reducing the secretion of inflammatory factors, which results in anti-inflammatory regulation. This study provides the first demonstration of the role of m6A methylation in the pathological process of syphilis and further offers new insight into the pathogenesis of TP infection.