bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity and Reliability of Event Related Potential in Subacute Stroke
Authors: Yun Dong Hyuk , Sohn Min Kyun , Jee Sungju 
Published: February 2022

Abstract
The aim of this study was assess the test-retest reliability of the ERP and resting EEG test in subacute stroke patients. Additionally, we compared the validity of the EEG, ERP test to MMSE (Mini-Mental State Exam) and MoCA (Montreal Cognitive Assessment) to use it as an objective tool to evaluate cognitive function. We recruited 20 patients with subacute ischemic stroke who were 19 years of age or older and had an MMSE score of 20 or higher. All participants were tested K-MMSE (Korean Mini Psychostatistics Test) and K-MoCA (Korea-Montreal Cognitive Assessment). The resting-state EEG and P300 wave using an auditory and visual oddball paradigm were measured at baseline and once again in 24 hours. We calculated the brain symmetry index (BSI) and directional BSI (BSIdir) over different frequency bands and delta/alpha ratio (DAR). The intra-rater reliability and validity of the P300 latency, amplitude, BSI, BSIdir and DAR were measured by intra-class correlation (ICC) analysis and by Pearson`s correlation coefficient analysis, respectively. P300 latency showed excellent ICC level (auditory P contralesional, ICC = 0.918, visual P contralesional, ICC = 0.972, visual Pz, ICC = 0.945). In the visual ERP (latency), there was a significant correlation between Cz, C ipsilesional and Mini-Mental State Exam (MMSE) and C ipsilesional and Montreal Cognitive Assessment (MoCA). The P contralesional and Pz latency of visual ERP showed significant reliability, and the Cz and C ipsilesional of visual latency showed effectiveness in reflecting the cognitive function. Thus, these montages could be used as a basis for future studies.
Histone demethylase UTX regulates glioblastoma progression through affecting periostin expression
Authors: Luan Yan , Liu Yingfei , Xue Jingwen , Wang Ke , Ma Kaige , Lu Haixia , Chen Xinlin , Liu Yong , Zhang Zhichao 
Published: February 2022

Abstract
The histone H3K27 demethylase UTX participates in regulating multiple cancer types. However, less is known about the function of UTX in glioblastoma (GBM), let alone in glioblastoma stem-like cells (GSCs). Our study aims to investigate the functional role and regulatory mechanism of UTX on GBM. By summarizing data from the TCGA database, we showed that UTX expression was significantly increased in GBM and inversely correlated with survival. And knockdown UTX inhibited LN-229 cell (a human GBM cell line) proliferation and promoted apoptosis in a mouse xenograft model. Gene expression profile of UTX knockdown LN-229 cells was analyzed by RNA-seq. The results indicated that the altered genes were strongly associated with tumor progression and the extracellular environment. Bioinformatics and STRING database were used to elucidate the mechanism of UTX and the target gene. Protein-protein interaction analysis periostin (POSTN) protein could interact with most of the other UTX-mediated proteins. More importantly, POSTN supplement abolished the effect of UTX knockdown in GBM cells. Furthermore, silencing UTX exhibited a similar antitumor effect in patient-derived GSCs, while UTX functions were partially restored after exposing POSTN. Our findings suggested that knockdown UTX inhibited GBM progression and tumorigenesis by enhancing the levels of H3K27 methylation in the POSTN gene, thereby suppressing the expression of POSTN and lots of extracellular matrix proteins, providing that UTX might be a vigorous therapeutic strategy for GBM treatment.
Clinical- and cost-effectiveness of a technology supported and solution-focused intervention (DIALOG+) in treatment of patients with chronic depression – study protocol for a multi-site, cluster randomised controlled trial [ TACK ]
Authors: McNamee Philip IJ , Matanov Aleksandra Matanov , Jerome Lauren , Walker Neil , Kerry Sally , Feng Yan , Molodynski Andrew , Scott Shonagh , Guruvaiah Latha , Collinson Sue , McCabe Rose , Geddes John , Priebe Stefan , Bird Victoria 
Published: February 2022

Abstract
Background: Many with an acute depressive disorder go on to develop chronic depression, despite ongoing care. There are few specifically designed interventions to treat chronic depression. DIALOG+, a technology-assisted intervention based on the principles of solution-focused therapy, may be beneficial. It has been shown to be effective as a treatment for patients with psychotic disorders, especially in regards to increasing quality of life. DIALOG+ was designed to be flexibly applied and not diagnosis-specific, aiming to structure communication and generate a personallytailored care plan. This cluster randomised controlled trial (RCT) is part of a programme of research to adapt and test DIALOG+ for patients with chronic depression. Methods: Patients will be eligible for the trial, if they have exhibited symptoms of depression or non-psychotic low mood for at least 2 years, have regular contact with a clinician and have a low subjective quality of life, and moderate depressive symptoms. Clinicians, who routinely see eligible patients, will be recruited from a number of sites across NHS England. Clusters will have between 1 and 6 patients per clinician and will be randomised in a 1:1 ratio to either the intervention (DIALOG+) or active control group (treatment as usual + DIALOG scale). Clinicians in the intervention group are trained and asked to deliver the intervention regularly for 12 months. Active control participants receive treatment as usual and are asked to rate their satisfaction with areas of life and treatment on the DIALOG scale at the end of the clinical session. Approximately 112 clinician clusters will be recruited to reach a total patient sample size of 376. Clinical and social outcomes including costs are assessed at baseline and 3-, 6- and 12-months post randomisation. The primary outcome will be subjective quality of life at 12 months. Discussion: This definitive multi-site, cluster RCT aims to evaluate the clinical- and cost-effectiveness of DIALOG+ for people with chronic depression. If shown to be effective for this patient population it could be used to improve outcomes of mental health care on a larger scale, ensuring that patients with complex and co-morbid diagnoses can benefit.
Dihydroartemisinin Inhibits Angiogenesis in Breast Cancer via Suppressing NF-κB/MMP-2/-9 Pathway
Authors: RAO QI , Yu He , Li Ruochan , He Bin , Wang Yuxue , Guo Xiaohong , Zhao Gang , Wu Fenghua 
Published: February 2022

Abstract
Purpose
Dihydroartemisinin (DHA), a derivative of artemisinin that is well-known as an antimalarial drug, has been reported to have anti-tumor and anti-angiogenesis effects. However, whether and how it inhibits angiogenesis in breast cancer is poorly understood. In this study, we detected the anti-angiogenesis effect of DHA on breast cancer.
Methods
Firstly, we detect the anti-angiogenesis effect of DHA on breast cancer in a chick chorioallantois membrane model. Then, we collected the conditioned medium of MDA-MB-231cells used in aortic ring angiogenesis assay, and HUVECs migration and tube formation assay. Finally, we used gelatin zymography, cellular immunofluorescence assay and western blot analysis to study signaling modulators regulated by DHA in MDA-MB-231 cells.
Results
The results showed that angiogenesis induced by MDA-MB-231 cells was attenuated by DHA. Vessel sprout and tube-formation of vascular endothelial cells were also depressed when cultured with CM from MDA-MB-231 pretreated with DHA. What’s more, the expression, and activities of matrix metalloproteinase 2 and 9 (MMP-2/-9) in MDA-MB-231 cells were downregulated by DHA. Further studies showed that DHA downregulated the expression of p-PI3K, p-AKT, p-ERK, and p-NF-κB proteins in tumor cells.
Conclusion
DHA was highly efficacious in inhibiting angiogenesis induced by breast cancer cells. The downregulating of MMP-2/9 through inhibiting phosphorylation of PI3K, AKT, and ERK in tumor cells may be the key factors in the inhibitory effect of DHA on angiogenesis.
Evaluating the Therapeutic Viability of Bacterially Expressed Human TLK1B-Kinase Domain for Cancer Drug Design
Authors: Johnson Delna , Hussain Javeena , Bhoir Siddhant , Sahsrawat Parul , Hans Tanya , Vaishali C , Thiruvenkatam Vijay , Kirubakaran Sivapriya 
Published: February 2022

Abstract
The role of protein kinases is vital in diverse cellular functions. The alterations in the expression patterns of protein kinases often implicate human cancer initiation and progression. Human Tousled-like kinases (TLKs) are evolutionary kinases found in the cell signalling pathway and are involved in DNA repair, replication and chromosomal integrity. The direct association of TLKs to cancer; amplification of both TLK1/1B and TLK2 has made them viable molecular targets for anticancer therapy. Several reports demonstrate numerous functions of TLKs in development of disease via different interacting partners. However, a detailed understanding of its substrates and regulation has yet remained elusive. In this report, through preliminary biophysical and biochemical characterization, we investigate and determine the usability of the recombinant Human Tousled-like Kinase 1B-Kinase Domain (hTLK1B-KD) purified from Escherichia coli for structural and functional studies. By illustrating hTLK1B-KD as an example, our attempts to generate a stable, homogenously dephosphorylated, and catalytically active hTLK1B-KD in high yields is utilizing a bacteriophage λ protein phosphatase (LPP) coexpression system represents a fundamental step towards the structure-based design of TLK-specific inhibitors.
Patterns Of Multimorbidity Of Patients In Geriatric Care – A Register-Based Cohort Study In Sweden
Authors: Carlsson Lennart , Lindqvist Rikard , Willers Carl , Fors Stefan , Rydwik Elisabeth , Nilsson Gunnar H 
Published: February 2022

Abstract
Background: Patients in geriatric care display a high degree of multimorbidity. We aimed to explore and visualise various patterns of multimorbidity in a person-oriented way. We used a register-based closed cohort (n=8104) of patients admitted to geriatric care in Region Stockholm, Sweden, from the year 2016.Methods: Patients were grouped by their degree of multimorbidity according to the Johns Hopkins Adjusted Clinical Groups® system. Exploration was made using the Expanded Diagnosis Groups, embedded in the system. Statistical analysis was conducted in “R” and results were visualised in Excel.Results: For half of all patients in the cohort, there were at least twelve diagnoses and at least thirteen active ingredients per patient. The quartile of patients with the highest level of multimorbidity were younger than the quartile of those with the lowest level. Patients with combinations of clusters of diagnoses showed various degrees of multimorbidity. Clusters of diagnoses with administrative character and cardiovascular diseases were present among nearly 80% each of all patients, followed by clusters of neurologic and musculoskeletal disorders with about 70% each. Comparisons between patients’ main diagnosis and all their diagnoses showed a shift to more of musculoskeletal disorders and less of cardiologic clusters when using main diagnoses. The morbidity status of patients measured by registered diagnoses was completed by including data on drugs, and revealed depression, persistent asthma and disorders of lipid metabolism.Conclusions: Grouping patients by their degree of multimorbidity, based on all their registered concurrent diagnoses and drugs, could illustrate various patterns of mixed multimorbidity, which in turn might lead to a better understanding of the essence of multimorbidity from a patient’s perspective.
Serum ferritin as an independent predictor of non-alcohol fatty liver disease in general adults: the TCLSIH cohort study
Authors: Gu Yeqing , Meng Ge , Chen Xiaowei , Wang Jinhan , Zhang Qing , Liu Li , Wu Hongmei , Zhang Shunming , Zhang Tingjing , Wang Xuena , Zhang Juanjuan , Sun Shaomei , Wang Xing , Jia Qiyu , Song Kun , Liu Qiang , Niu Kaijun 
Published: February 2022

Abstract
Background
Serum ferritin is an important iron storage protein in the human body, which indicates iron storage and the body’s nutritional status, and is associated with a variety of chronic diseases. Few prospective studies have assessed the association between serum ferritin levels and non-alcoholic fatty liver disease (NAFLD). This prospective cohort study aimed to explore whether serum ferritin levels were associated with the incidence of NAFLD in a large-scale adult population.
Methods
A total of 15,748 participants without baseline NAFLD were enrolled in the cohort study (1-9 years follow-up periods, median: 4.5 years). Serum ferritin levels were determined by protein chip-chemiluminescence method, and NAFLD was diagnosed by abdominal ultrasonography. Multivariable Cox proportional hazards regression models were used to assess the association between baseline serum ferritin levels and the risk of NAFLD.
Results
During the follow-up period, 3,374 new NAFLD cases were observed, and the incidence rate of NAFLD was 83.4 per 1000 person-years. In the fully adjusted model, the hazards ratios (95% confidence interval) for incident NAFLD across serum ferritin levels quartiles were 1.06 (0.94-1.19), 1.25 (1.11-1.41), and 1.52 (1.28-1.79) (P for trend <0.0001). Receiver operating characteristic (ROC) analysis showed that the optimal cut-off values were 55.9 mg/dl for serum ferritin levels (Area under the ROC curve (AUC)=0.61)
Conclusion
Increased serum ferritin level was independently associated with a higher risk of incident NAFLD in a large-scale general population. It is suggested that serum ferritin levels can be useful for the early detection of subjects at high risk of developing NAFLD.
Molecular detection and diversity of spotted fever group Rickettsia isolated from ticks in Iran
Authors: Afzalkhani Aliakbar , shayegh jalal , Jamali Vahab , Malekzadeh Parmida , Spotin Adel 
Published: February 2022

Abstract
Background: This study aimed to identify Rickettsia spp. and their circulation in ticks collected from sheep in the Khuzestan province, Southwest Iran. Methods: Four hundred and forty adult hard ticks were collected from the parasite-infected sheep from nine cities of Khuzestan province. DNA samples were extracted and subjected to the single-round polymerase chain reaction amplification of citrate synthase gene (gltA). Results: The tick species were identified as Hyalomma marginatum, Hyalomma anatolicum, Hyalomma dromedarii, Hyalomma schulzei, Rhipicephalus bursa, and Rhipicephalus turanicus. The presence of Rickettsia spp. was observed in half of the collected ticks (50%). For a definitive identification of Rickettsia spp., the amplicons (n: 10) were directly sequenced. Sequencing and phylogenetic analyses revealed the definitive presence of Rickettsia aeschlimannii (60%), Rickettsia massiliae (30%), and Rickettsia conorii (10%) in the infected ticks. Conclusions: The results indicated a significant incidence of tick-borne Rickettsia spp. and their unequivocal circulation in Southwest Iran. Hence, the prevalence of spotted fever group Rickettsia should be detected in suspected humans and domestic animals in wider areas of Iran.
Counterfactual Generation Through Multi-objective Constrained Optimisation
Authors: Monteiro Wellington Rodrigo , Reynoso-Meza Gilberto 
Published: February 2022

Abstract
Explainable artificial intelligence (XAI) techniques are often adopted to provide transparent feedback to decision-makers evaluating the results of trained machine learning (ML) models. One of these techniques covers the generation of counterfactuals -- slightly modified instances based on a given input that can change its predicted outcome. These counterfactuals enable decision-makers to know what actions they could do to modify an outcome and improve the trust and transparency of a trained ML model. This research aims to develop and apply a novel constrained multi-objective optimisation design (MOOD) to generate counterfactuals in classification and regression problems. The MOOD is composed of three steps: the definition of a constrained multi-objective problem (MOP); the multi-objective optimisation (MOO) using a multi-objective evolutionary algorithm (MOEA); and the multi-criteria decision making (MCDM) with a domination filter and the TOPSIS ranking technique. This MOOD generated large numbers of valid counterfactuals and selected and ranked only the most relevant to the decision-maker. Furthermore, the results show that the proposed MOOD outperformed other architectures available for production use in at least one of the objectives measured for all datasets analysed in both regression and classification problems.
Comparison of indicators for severe maternal morbidity among South Korean women who delivered from 2003 to 2018: a population-based cohort study
Authors: Nam Jin Young 
Published: February 2022

Abstract
Background: Previous studies of the relationship between severe maternal morbidity (SMM) and risk factors used only a single indicator for SMM and did not compare the various SMM indicators and the incidence differences with each. This study aimed to identify risk factors for SMM by reviewing four international SMM indicators and ascertaining the differences in SMM incidence in South Korea with each indicator.Methods: This study used the National Health Insurance delivery cohort in South Korea from 2003 to 2018. SMM was estimated using four indicators: the United States Centers for Disease Control and Prevention (US-CDC) SMM algorithm, the American College of Obstetricians and Gynecologists (ACOG) gold standard guidelines, Zwart et al.’s indicators for the Netherlands, and the European Network on Severe Acute Maternal Morbidity (EURONET-SAMM) index. Generalized estimating equations models were used to identify the relationships between SMM indicators and risk factors.Results: The SMM incidence rates in 6,421,091 deliveries, were 2.36%, 3.12%, 0.31%, and 1.36% using the US-CDC, ACOG, Zwart et al.’s, and EURONET SAMM indicators, respectively. In sub indicators, hemorrhage-related codes constituted the highest proportion of all SMM indicators. Advanced maternal age was related to high risk in all four SMM indicators (US-CDC: 40-44 years, RR 1.67, 95% CI 1.63-1.71; ACOG’s guidelines: 40-44 years, RR 1.52, 95% CI 1.49-1.56; Zwart’s indicators: RR 2.72, 95% CI 2.55-2.90; EURONET-SAMM: RR 2.04, 95% CI 1.97-2.11) compared to those aged 25-29 years. In residential area, women who lived in rural area had approximately 1.2- to 1.5-fold higher risk of SMM compared to those who lived in Seoul. Additionally, inadequate prenatal care was associated with a 1.1- to 1.4-fold higher risk of SMM compared to adequate prenatal care. Conclusions: SMM was associated with maternal age, socioeconomic status, and adverse obstetric factors using various international SMM indicators. Further studies are needed to further determine risk and preventable factors for SMM and to identify more specific causes associated with the frequent sub-indicators of SMM.
NSG-70, a new glioblastoma cell line with mixed proneural-mesenchymal features associates NOTCH1-WNT5A signaling with stem cell maintenance and angiogenesis
Authors: Singh Divya Kumari , Shivalingappa Pavan Kumar Mysuru , Sharma Aman , Mondal Abir , Muzumdar Dattatraya , Shiras Anjali , Bapat Sharmila A 
Published: February 2022

Abstract
BackgroundGlioblastoma initiation and progression is believed to be driven by Glioma stem cells (GSCs). Activation of NOTCH1 and WNT, and more recently, non-canonical WNT5A signaling, has been demonstrated to regulate self-renewal and differentiation of the GSCs crucially. High expression levels of NOTCH1 and WNT in GBM tumors contribute to the sustenance of GSCs and mediate characteristic phenotypic plasticity, which is reflected by the different subtypes and tremendous intra-tumor heterogeneity. However, the coregulation of NOTCH1 and WNT5A is not well understood. Here, we studied the role of these molecules in regulating the characteristics of different GSC subtypes. MethodsWe established a novel GSC-enriched cell model, referred to as NSG-70, from a patient with recurrent GBM. NSG-70 cells harbor a unique cytogenetic feature, viz. isochromosome 9q. At the same time, its expression profiles indicate it to represent a mixed lineage comprising of proneural and mesenchymal subtypes. We examined the relevance of NOTCH1 and WNT5A signaling and their coordinated action in GBM using these cells and other patient-derived models representing different GSC subtypes. ResultsOur data revealed that the downregulation of NOTCH1 resulted in the suppression of stem cell and mesenchymal markers and significantly reduced the levels of WNT5A. NOTCH1 knockdown also led to a notable reduction in the vasculogenic mimicry of GSCs. Interestingly, knockdown of WNT5A exhibited similar effects and drove quiescent GSC towards proliferation. In a complementary manner, ectopic expression of WNT5A or rhWNT5A treatment rescued the effects of NOTCH1 knockdown. ConclusionsGiven the resistance of GSCs towards conventional therapies in part due to subtype, interconversion demands therapies targeting specific GSC subtype. Our study suggests the need for a combinatorial approach that could effectively target the NOTCH1-WNT5A signaling axis towards eliminating GSCs.
Lung Ultrasound Score has Better Diagnostic Ability Than NT-PROBNP to Predict Moderate–Severe Bronchopulmonary Dysplasia
Authors: Alonso-Ojembarrena Almudena , Mendez-Abad Paula , Alonso-Quintela Paula , Zafra-Rodriguez Pamela , Oulego-Erroz Ignacio , Lubián-López Simón Pedro 
Published: February 2022

Abstract
Purpose: N-terminal end of B-type natriuretic peptide (NT-proBNP) and lung ultrasound (LUS) score have been proven to be adequate early biomarkers of bronchopulmonary dysplasia (BPD) in preterm infants. Our aim was to study if the predictive capacity of each one is increased by analyzing them together.Methods: We included infants born before 32 weeks, with NT-proBNP and LUS score on the first day of life (DOL), 3rd, 7th and 14th DOL, and compare the diagnostic ability for moderate-severe BPD (msBPD) of each biomarker and in combination. We also compared them with a multivariate model of msBPD using only clinical variables.Results: The sample size was 133 patients, and twenty seven (20%) developed msBPD. LUS score on 7th DOL had better performance, compared to NT-proBNP at the same moment: area under the receiver operating characteristic curve (AUC) 0.83 (0.75-0.89) versus 0.66 (0.56-0.75), p=0.003, without differences in the rest of times studied. This values did not increase using the combination of both. A multivariate regression model that included birth weight and invasive mechanical ventilation (IMV) at 7th DOL predicted msBPD with the same AUC-ROC than NT-proBNP, LUS score or both. Neither the addition of any of these biomarkers, nor together, increase the diagnostic accuracy of the clinical model.Conclusion: LUS score is better predictor of msBPD on 7th DOL than NT-proBNP in preterm infants born before 32 weeks, although they have similar diagnostic accuracy on 14th DOL. Neither of them, nor together, have better AUC for msBPD than a clinical model with birthweight and the need of IMV at 7th DOL.