bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients’ Views On Using Human Embryonic Stem Cells To Treat Parkinson’s Disease - An Interview Study
Authors: Drevin Jennifer , Nyholm Dag , Widner Håkan , Vliet Trinette , Johansson Jennifer Viberg , Jiltsova Elena , Hansson Mats 
Published: February 2022

Abstract
Background: Human embryonic stem cells (hESC) as source for the development of advanced therapy medicinal products (ATMP) are considered for treatment of Parkinson’s disease (PD). Research has shown promising results and opened an avenue of great importance for patients who currently lack a disease modifying therapy. The use of hESC has given rise to moral concerns and been the focus of, sometimes heated, debates about the moral status of human embryos. Approval for marketing is still pending. Objective: To investigate the perspectives and concerns of patients with PD, patients being the directly concerned stake holders in the ethical discussion. Methods: Qualitative semi-structured interviews related to this new therapy in seventeen patients from two Swedish cities.Results: The participants expressed several interests related to the use of human embryos for development of medicinal therapies but were overall positive to the use of hESC for treatment of PD.Conclusion: It was important that the donating woman or couple are donating embryos voluntarily and there was a worry that the industry does not always prioritize the patient over profit and transparency is therefore seen as important.
Identification of Subtype-Specific Prognostic Biomarkers in Breast Cancer
Authors: Esfahani Farinaz Vafadar , Ghezlou Mansoureh , Moghaddam Marziyeh Mazaheri , Moghaddam Madiheh Mazaheri , Hozhabri Hossein 
Published: February 2022

Abstract
Breast cancer (BC) is a heterogeneous disease divided into four molecular subtypes that display different prognoses. Molecular alterations in breast cells contribute to breast carcinogenesis. However, the molecular characteristics involved in developing BC subtypes remain largely unknown. Further identification of molecular mechanisms involved in different BC subtypes might help improve treatment strategies and prognosis of patients. In the present study, two microarray datasets (GSE57297 and GSE65194) containing four BC subtypes were downloaded from the Gene Expression Omnibus (GEO) database. Comparative analyses were performed to identify specific differentially expressed genes (DEGs) for each BC subtype, as well as overlapped (core) between all subtypes. bc-GenExMiner and Kaplan-Meier plotter databases were respectively utilized to investigate the differential expression and prognostic value of DEGs. A total of 25 DEGs (12 specific and 13 core) were found to be significantly associated with prognosis. We found that a high level of C9orf116 predicted better OS in the Luminal A subtype. Also, increased transcription levels of FAM13A and RASIP1 were associated with shorter OS in the Luminal B subtype. High mRNA expression of PDE7A, and COTL1 conferred longer OS, while elevated expression of TM4SF1 and AREG predicted shorter OS in the TNBC subtype. Increased mRNA levels of GSR, and DAPK2 conferred better OS in the HER2 subtype; however, increased expression levels of HOTAIR, PLEKHG4, and POU6F1 predicted poor OS. For the core DEGs, increased expression of IFI6 and UBE2S predicted shorter OS. Meanwhile, increased mRNA levels of AK5, C2orf40, CNN1, HOXA5, NTRK2, PAMR1, PROS1, SCARA5, SDPR, TGFBR3, and TSHZ2 conferred better OS. In conclusion, this study strictly identified specific genes that may help to select precision prognostic biomarkers in different BC subtypes.
How Reliable Is the High-Volume Definition in Prostate Cancer Patients: The Potential Game-Changing Role of PSMA
Authors: Güven Osman , Karyağar Savaş , Arıcı Serdar , Ozulker Tamer , Can Orçun 
Published: February 2022

Abstract
Purpose
To evaluate whether metabolic and volumetric data from Ga-68 PSMA PET CT performed during staging of denovo high-volume mCSPC patients who received docetaxel could be used to predict survival.
Methods
Forty-two denovo high-volume metastatic castration-sensitive prostate cancer patients, who received ADT + Docetaxel and underwent Ga-68 PSMA PET CT for staging, were included in the study. The association between patients' pathological data, all PSA measurements, treatments they received, and the data obtained from Ga-68 PSMA PET CT and progression-free and overall survival were examined. In the univariant analysis performed with the log-rank test, it was evaluated whether the difference between subgroups of variables was statistically significant in terms of survival. Variables found statistically significant were included in the multivariate analysis with the Cox hazard ratio model.
Results
In the multivariate analysis, PSMA-TV (primary) and PSMA-TV (WB) variables were shown to be independent negative predictors of overall survival. For the threshold value of 19.91 cc obtained for PSMA-TV (primary), HR was calculated as 6.31, 95% CI: 1.01-39.18, p: 0.048. For the threshold value of 1226.5 cc obtained for PSMA-TV(WB) variable, HR was calculated as 58.62, 95% CI: 2.55-1344.43, p:0.011. In our study, SUVmax (WB) variable was found to be an independent and negative predictor of progression-free survival. For the determined threshold value of 17.74, HR was calculated as 16.24, 95% CI: 1.18-22.76, p: 0.037.
Conclusion
Metabolic and volumetric data obtained from Ga-68 PSMA PET CT can be used to predict survival in denovo high-volume mCSPC. Our results show that ADT + Docetaxel receiving patients with high PSMA-TV (WB) values have a significantly worse prognosis. This situation reveals that the high-volume disease definition in the literature is insufficient for this group and that Ga-68 PSMA PET CT can play an important role in demonstrating the heterogeneity within the group.
Pharmacological inhibition of TBK1/IKKε blunts COVID-19 immunopathology
Authors: Gantier Michael , Ullah Tomalika , Johansen Matt , Balka Katherine , Ambrose Rebecca , Gearing Linden , Wenholz Daniel , Zeng Jun , Miemczyk Stefan , Nguyen Duc , Venkatraman Rajan , Dennis Matthew , Alharbi Arwaf , Ellyard Julia , Wong Wilson , Kile Benjamin , Vinuesa Carola , Kelly Graham , Hansbro Philip , Laczka Olivier , De Nardo Dominic , Hansbro Nicole , Kumar Naresh 
Published: February 2022

Abstract
TANK-binding kinase 1 (TBK1) is a key signalling component that drives the production of type-I interferons (IFNs), which have essential antiviral activities including against SARS-CoV-2. TBK1 and its homolog IκB kinase-ε (IKKε) can also induce the production of pro-inflammatory factors that contribute to pathogen clearance. While initially protective, delayed engagement of type-I IFN is associated with lethal hyper-inflammation seen in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to this response is unknown. We have discovered that the small molecule idronoxil inhibits both IRF3 and NF-κB-driven inflammation by disrupting the formation of TBK1/IKKε signalling complexes following STING activation. Leveraging this unique activity, we show that therapeutic administration of idronoxil suppresses cellular and molecular lung inflammation in K18-hACE2 mice challenged with SARS-CoV-2, resulting in reduced pro-inflammatory cytokine production and decreased airway fibrosis in experimental COVID-19. Our results indicate a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation and identify a novel therapeutic intervention to limit disease severity in COVID-19 patients.
Tenascin-C Promotes Skin Inflammation and Wounds Healing after Scalding in Rats by Inducing Infiltration of Macrophages
Authors: Zhong Weiquan , Wang Jin , Liu Wenjun , Mao Yixin , Liu Hao , Qian Kai 
Published: February 2022

Abstract
We have known that Tenascin-C(TNC) has high expression in chronic inflammation. This research explores the proinflammatory mechanism and further discusses the relationship between the TNC and the macrophages in the inflammatory response. First, we successfully built the deep second-degree scald models of rats. Then we found that the level of TNC increased rapidly in the skin of young rats just after scalding, and its tendency also stays increased within a week in old rats. We also observed the infiltration of inflammatory cells in the scalded skin of rats by Immunohistochemistry (IHC) staining. In addition, we found that tenascin-c could confer a proangiogenic effect to macrophages. By monitoring the level of VEGF, CCL2, and CCR2, we can find out the relationship between TNC and macrophages. We concluded that TNC could promote skin inflammation and wound healing in rats after scalding by inducing infiltration of macrophages.
PepNet: A Fully Convolutional Neural Network for De novo Peptide Sequencing
Authors: Liu Kaiyuan , Ye Yuzhen , Tang Haixu 
Published: February 2022

Abstract
The de novo peptide sequencing, which does not rely on a comprehensive target sequence database, provided us a way to identify novel peptides from tandem mass (MS/MS) spectra. However, current de novo sequencing algorithms suffer from lower accuracy and coverage, which hinders their applications in proteomics. In this paper, we present PepNet, a fully convolutional neural network (CNN) for high accuracy de novo peptide sequencing. It takes an MS/MS spectrum (represented as a high dimensional vector) as input, and outputs the optimal peptide sequence along with its confidence score. Our model was trained using a total of 30 million high-energy collisional dissociation (HCD) MS/MS spectra from multiple human peptide spectral libraries. The evaluation results show that PepNet significantly outperformed currently best-performing de novo sequencing algorithms (e.g. PointNovo and DeepNovo) at both peptide level accuracy and positional level accuracy. In addition, PepNet can sequence a large fraction of spectra that were not identified by database search engines, and thus could be used as a complementary tool of database search engines for peptide identification in proteomics.
The impact of internet use on health outcomes in China: A longitudinal study using a three-wave nationwide survey
Authors: Oshio Takashi , Ma Xinxin , Komatsu Sho 
Published: February 2022

Abstract
Background: Previous studies have examined the impact of internet use on health in China but have not addressed the reverse causality problem nor analyzed the health status in detail. In this study, we conducted a longitudinal analysis to investigate the causal association between internet use and health status in China to address these problems.Methods: Using three-wave longitudinal data from the China Family Panel Studies conducted in 2014, 2016, and 2018, we adopted dynamic regression models with lagged internet use variables to examine the association between internet use and five types of health outcomes.Results: Internet use was positively associated with health outcomes (self-rated health, mental health, and outpatients), and these effects differed by gender, age, and urban/rural region groups. Conclusions: The results provided rich evidence of the positive effect of internet use on health outcomes in China. Thus, digital economic policies are expected to improve individuals’ health status.
Determination Of Reflection And Transmission Coefficient Of An Overlay Microstrip Antenna On Duroid Material Using Fem
Authors: Sahabi Suleiman , Yakubu Abubakar 
Published: February 2022

Abstract
Knowledge of materials behaviour placed in an electromagnetic field was found to be of immense significant especially as it is attributed to military hardware, electronics, communication and industrial applications. An overlay microstrip antenna was employed in this study to determine scattering parameters of an overlay microstrip antenna using finite element method (FEM). The substrate thickness used on the microstrip was 10 mm thick and 8 x 12 cm (width and length). All simulation was carried at X band frequency range (8-12 GHz) using FEM. The result amongst others showed that the transmission coefficient depends on the permittivity of the sample. The result also showed that lowest permittivity of material produced the greatest transmission coefficient. It is then concluded that the results obtained for the transmission and reflection coefficients can be used for the prediction of complex permittivity of materials used as overlay on a microstrip antenna.
Mesial temporal tau in amyloid-β negative cognitively normal older persons
Authors: Krishnadas Natasha , Doré Vincent , Groot Colin , Lamb Fiona , Bourgeat Pierrick , Burnham Samantha C , Huang Kun , Goh Anita MY , Masters Colin L , Villemagne Victor L , Rowe Christopher C 
Published: February 2022

Abstract
BackgroundTau deposition in the mesial temporal lobe (MTL) in the absence of amyloid-β (Aβ-) occurs with ageing. The tau PET tracer 18F-MK6240 has low non-specific background binding so is well suited to exploration of early-stage tau deposition. The aim of this study was to investigate the associations between MTL tau, age, hippocampal volume (HV), cognition and neocortical tau in Aβ- cognitively unimpaired (CU) individuals.MethodsOne hundred and ninety-nine Aβ- participants (Centiloid <25) who were CU underwent 18F-MK6240 PET at age 75±5.2 years. Tau standardized uptake value ratio (SUVR) was estimated in mesial temporal (Me), temporoparietal (Te) and rest of neocortex (R) regions and four Me sub-regions. Tau SUVR were analysed as continuous variables and compared between high and low MTL SUVR groups.ResultsIn this cohort with a stable clinical classification of CU for a mean of 5.3 years prior to, and at the time of tau PET, MTL tau was visually observed in 9% of the participants and was limited to Braak stages I-II. MTL tau was correlated with age (r=0.24, p<0.001). Age contributed to the variance in cognitive scores but MTL tau did not. MTL tau was not greater with subjective memory complaint, nor was there a correlation between MTL tau and Aβ Centiloid value, but high tau was associated with smaller HV. Participants with MTL tau had higher tau SUVR in neocortex but this was driven by the cerebellar reference region and was not present when using white matter normalization.ConclusionsIn an Aβ- CU cohort, tau tracer binding in the mesial temporal lobe was age-related and associated with smaller hippocampi, but not with subjective or objective cognitive impairment. Trial registrationNot applicable.
Multilevel Lumbar Fusion and Sacral Fusion Affect Joint Space Narrowing of the Hip: A Retrospective Study
Authors: Ukai Taku , Katoh Hiroyuki , Yokoyama Katsuya , Omura Haruka , Watanabe Masahiko 
Published: February 2022

Abstract
Background: This study aimed to elucidate the effect of lumbosacral fusion on joint space narrowing of the hip. Methods: We retrospectively studied 511 hips of 261 patients who had undergone lumbar fusion. Whole-spine X-ray was performed for all the patients before surgery and at final follow-up. Center edge angle, joint space of the hip, sagittal vertical axis, thoracic kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope were measured. The number of lumbar fusion levels, inclusion of sacral fusion, follow-up duration, and wear of the hip joint (mm/year) were also recorded. Multi regression analysis was performed to identify the risk factors for joint space narrowing.Results: Female sex (P=0.04), number of fixed lumbar levels (P=0.002), sacral fusions (P=0.039), and follow-up period (P<0.001) were independent risk factors for joint space narrowing of the hip. The patients who underwent four or more levels of lumbar fusion experienced more rapid wearing of the hip joint space than that experienced by patients with less than three levels of lumbar fusion (P=0.044). Conclusion: Surgeons should pay attention to joint space narrowing of the hip after performing multiple lumbar fusions or sacral fusion in women.
Analysis of Low-Density Lipoprotein Receptor Gene Mutations in A Family with Familial Hypercholesterolemia
Authors: Hu Ya-nan , Wu Min , Ji Yuan-yuan , Zhang Jian-Hui , Zhang Yan-ping , Wu Qiu-yan , Lin Xin-fu , Wu Jia-bin , Liao Li-sheng , Luo Jie-Wei , Chen Xin 
Published: February 2022

Abstract
Background: Familial hypercholesterolemia (FH) is a common monogenic autosomal dominant hereditary disease, mainly caused by pathogenic mutations in the low-density lipoprotein receptor (LDLR) gene. It is characterized by severely elevated LDL cholesterol (LDL-C) levels, cutaneous xanthomatosis, and premature coronary heart disease.Materials and Methods: Whole exome sequencing of the proband with familial hypercholesterolemia was performed to identify the target gene and screen for suspicious pathogenic mutations. Sanger sequencing of family members was conducted to analyze family genetic-phenotypic associations. In addition, the changes in the structure and function of mutant LDLR were predicted using biological information analysis.Results: Next Generation Sequencing revealed that the proband carried two heterozygous missense point mutations c.G1027A (p.G343S) and c.G1879A (p.A627T) in LDLR (NM_000527), which could lead to FH syndrome. In this pedigree, the proband and her brother with hypercholesterolemia and xanthelasma carried the compound heterozygous mutations p.G343S and p.A627T. Her father, children, and nephew carried the p.G343S mutation, and her mother and niece carried the p.A627T mutation. The total cholesterol (TC) of a compound heterozygote was 20.50–21.35 mmol/L, the cholesterol of a heterozygote was 6.52–8.81 mmol/L, and the TC of other family members without a mutation was 2.94–3.61 mmol/L. G343S and A627T had a slight effect on the protein structure of LDLR, as simulated by Chimera. In addition, Rredictprotein software predicted that G343S and A627T affected the disordered region, protein interaction binding region, and RNA binding region of the LDLR. Gly343 and Ala627 are highly conserved in mammals and play a vital role in maintaining the function of the LDLR. YinOYang 1.2 predicted that these two sites had great potential for O-GlcNac modification, and GPS 5.0 predicted that the variants modified phosphorylation. Mutations may affect protein post-translational modification, thus changing the structure, function, location, and fate of the protein.Conclusions：The mutations c.G1027A in LDLR exon 7 and c.G1879A in exon 13 may be the molecular genetic basis of FH in this family. Compared to patients with a heterozygous variant, patients with compound heterozygous variants had much higher levels of cholesterol and had xanthoma
Niclosamide induces growth inhibition and apoptosis through down-regulation of PDGFRβ and STAT3 in human chondrosarcoma cells
Authors: Zhang Xueping , Yan Jing , Shao Xiaoning , Che Yingyu , Cheng Jingliang , Lu Xinchang 
Published: February 2022

Abstract
Background and objectives Chondrosarcoma is a destructive neoplasm of chondrocytes. Surgery is the principal procedure for this condition. The efficacy of traditional chemotherapy drugs is controversial. Niclosamide is an antihelminthic drug used to treat parasitic infections for nearly 50 years. However recent studies suggested that niclosamide might have the inhibitory effects of cancer. Methods We investigated the efficaciousness of niclosamide on a chondrosarcoma cell line SW1353.To determine the efficacy of niclosamide on chondrosarcoma, MTT, Flow cytometry, and DAPI assays were used to determine the effects of niclosamide. We determine the activity of niclosamide on the expression of the Raf/MEK/ERK pathway, and the phosphorylation of PDGFRβ and STAT3. Results Niclosamide dramatically inhibited cell growth and triggered apoptosis. And niclosamide down-regulated the expression of p- PDGFRβ and p-STAT3. Furthermore, niclosamide significantly reduced cyclin D1, Rb expressing, which were concurrent with the cell cycle block. We also found a decrease in p-MEK, p-ERK, Bcl-xl, and Bcl-2. Conclusion These results suggested that niclosamide effectively induced growth inhibition in vitro. And niclosamide could a new therapeutic method for chondrosarcoma.
A high triglyceride to high-density lipoprotein cholesterol ratio is associated with poor renal outcome in IgA nephropathy patients
Authors: Qin Wei , Pei Gaiqin , Qin Aiya , Dong Lingqiu , Wang Siqing , Liu Xiang , Yang Dandan , Tan Jiaxing , Zhou Xiaoyuan , Tang Yi 
Published: February 2022

Abstract
Background: Dyslipidemia is common in patients with chronic kidney disease. However, whether markers of atherogenic dyslipidaemia correlate with outcomes in IgA nephropathy (IgAN) patients as in the general population is uncertain. The aim of this study was to explore the prognostic value of the serum triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio to predict ESRD in IgAN patients.Methods: A total of 1149 patients from West China Hospital of Sichuan University were retrospectively analysed between 2008 and 2018, with a median follow-up of 54.0 months. The demographic, clinical and pathological data of all patients at the time of biopsy were collected. Receiver operating curve (ROC) was used to determine the optimal threshold for the TG/HDL ratio at baseline to predict ESRD during follow-up. Prognostic values were assessed by univariate and multivariate Cox regression analyses and Kaplan–Meier curves.Results: The optimal cut-off value for the TG/HDL-C ratio was 1.495. The correlation analysis showed that the TG/HDL-C ratio was negatively correlated with the eGFR (r = 0.248, P < 0.001) but positively correlated with proteinuria (r = 0.229, P< 0.001) and serum uric (r =0.306, P< 0.001). Patients with a higher TG/HDL-C ratio tended to have hypertension [odds ratio (OR), 1.702; 95% CI, 1.298-2.233; P<0.001] and more severe pathologic lesions with tubular atrophy/interstitial fibrosis (OR, 3.593; 95% CI, 2.528-5.107; P<0.001). A high TG/HDL ratio was strongly correlated with worse renal survival in IgAN patients (log-rank: P <0.001). Multivariate Cox analysis demonstrated that an elevated TG/HDL-C ratio (HR 2.118, 95% CI 1.333-3.367, P=0.002) was an independent risk marker to predict ESRD.Conclusion: The TG/HDL-C ratio may serve as potential prognostic biomarkers in IgAN patients.