bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insomnia subtypes characterised by objective sleep duration and NREM spectral power and the effect of acute sleep restriction: an exploratory analysis
Authors: Kao Chien-Hui , D'Rozario Angela L. , Lovato Nicole , Wassing Rick , Bartlett Delwyn , Memarian Negar , Espinel Paola , Kim Jong-Won , Grunstein Ronald R. , Gordon Christopher J. 
Published: September 2021

Abstract
Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD (p = 0.03), with a trend observed for NSDD (p = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.
Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
Authors: Pavlenkova Zuzana , Varga Lukas , Borecka Silvia , Karhanek Miloslav , Huckova Miroslava , Skopkova Martina , Profant Milan , Gasperikova Daniela 
Published: September 2021

Abstract
The genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome sequencing (WES). Thirty families segregating mid-frequency SNHL, in whom biallelic GJB2 mutations had been previously excluded, were selected from among 851 families in our DNA repository of SNHL. DNA samples from the probands were subjected to WES analysis and searched for candidate variants associated with SNHL. We were able to identify the genetic aetiology in six probands (20%). In total, we found three pathogenic and three likely pathogenic variants in four genes COL4A5, OTOGL, TECTA, TMPRSS3). One proband was a compound heterozygote for a pathogenic variant and a variant of uncertain significance (VUS) in MYO15A gene. To date, MYO15A and TMPRSS3 have not yet been described in association with mid-frequency SNHL. In eight additional probands, eight candidate VUS variants were detected in five genes (DIAPH1, MYO7A, TECTA, TMC1, TSPEAR). Seven of these 16 variants have not yet been published or mentioned in the available databases. The most prevalent gene was TECTA, identified in 23% of all tested families. Furthermore, we confirmed the hypothesis that a substantive portion of cases with this conspicuous audiogram shape is a consequence of a genetic disorder.
Endothelial cells induce proliferation and bone morphogenic protein mediated differentiation of PDGFRα+ human oligodendrocyte precursor cells to astrocytes in trans-well co-culture
Authors: Dasgupta Asmita 
Published: September 2021

Abstract
Background
CD140a /PDGFRα + human oligodendrocyte precursor cells (OPCs) are a lineage of OPCs with proven potential for use in cell therapy against demyelinating diseases. However, little is known about the contribution of human endothelial cells in the biology of PDGFRα + human OPCs in the stem cell niche.
Methods
Transwell co-culture technique with human umbilical vein endothelial cells (HUVECs) was adopted under proliferative or differentiating conditions to understand the role of endothelial cells in these processes within OPCs. Proliferation was followed by measuring OPC sphere size, count, sphere dissociation followed by cell count and 3H-methyl thymidine incorporation. Differentiation was followed by immunocytochemistry. Taqman gene expression assay for selective soluble factors was performed for the two co-culture partner cells to determine the expression of these factors on the biology of the OPCs in presence of the endothelial cells.
Results
In co-culture with HUVECs, under proliferative conditions, OPCs show increased proliferation and sphere formation. In contrast, under differentiating conditions, OPCs show increased differentiation to astrocytes, with a concomitant decrease in differentiation to oligodendrocytes, compared to no co-culture controls. Transcript assay for selected humoral factors in the OPCs and HUVECs revealed bone morphogenic proteins (BMPs), endothelin1, growth arrest specific 6 (GAS6), and interleukin 6 (IL6) to be in higher abundance in HUVECs than OPCs. Whereas the OPCs show higher expression for pleiotrophin (PTN), fibroblast growth factor 9 (FGF9), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF) compared to the endothelial cells. Among the transcripts analyzed, BMP4 transcripts were the highest in relative abundance in the endothelial cells indicating possibilities of BMPs being the critical mediator of endothelial cell-mediated effects. In agreement to this, Noggin effectively attenuated HUVEC mediated astrocytic differentiation of CD140a /PDGFRα + fetal human OPCs.
Conclusion
Based on the above results, the study concludes that human endothelial cells can significantly alter the biology of PDGFαR + fetal human OPCs mediated by humoral factors to induce increased proliferation and BMP mediated astrocytic differentiation. It can be secondarily inferred from these conclusions that using pharmacological inhibitors of BMP signaling along with the PDGFRα + fetal OPC transplantation may make these cells more effective in remyelination therapy.
Wnt Pathway Activation by Placental Mesenchymal Stem Cells Promotes Hepatic Regeneration in a Cirrhotic Rat Model
Authors: Choi Jong Ho , Jun Ji Hye , Kim Gi Dae , Jho Eek-hoon , Baik Soon Koo , Bae Si Hyun , Kim Gi Jin 
Published: September 2021

Abstract
Background: Sinusoidal endothelial cells (SECs) in liver play important roles in hepatocyte regeneration. We recently reported placenta-derived mesenchymal stem cells (PD-MSCs) can promote hepatic regeneration in a damaged liver model via dynamic events. However, the effects of PD-MSCs on vascular structure in liver tissues remain unknown. We therefore investigated alteration of vascular structure and function in carbon tetrachloride (CCl4)-injured rat model following transplantation (Tx) with PD-MSCs. Methods: PD-MSCs were engrafted into CCl4-injured rat model via intravenous Tx. Expression markers related to angiogenic factors and Wnt signaling pathway were analyzed by quantitative real time-PCR, Western blot, and immunofluorescence in vitro and in vivo. Furthermore, endothelial permeability assay was performed to confirm the effect of PD-MSCs on the functional regeneration of injured endothelial cells in vitro co-culture system.Results: PD-MSCs were found to significantly reduce the expanded hepatic vein diameter and increased tube formation of the aorta in both in vitro and ex vivo co-culture systems. PD-MSCs also increased the expression of angiogenic factors and activated the Wnt signaling pathway. Furthermore, PD-MSCs reduced endothelial permeability via activation of β-catenin in the in vitro co-culture system. Conclusions: Taken together, PD-MSCs transplantation (PD-MSC Tx) improves the structure and function of SECs by activating Wnt signaling, which triggers hepatic regeneration, in a CCl4-injured rat model. Therefore, these findings suggest that vascular restoration induced by PD-MSCs supports liver regeneration in a hepatic failure model and can be applied as a cell-based therapy.
Effectiveness of kinesio taping on functional outcomes in patellofemoral pain syndrome patients with abnormal patellar tracking
Authors: Lee Jin Hyuck , Shin Ki Hun , Jang Ki-Mo 
Published: September 2021

Abstract
This study aimed to compare quadriceps strength, muscle reaction time, and patient-reported outcomes in PFPS patients with abnormal patellar tracking with and without kinesio taping. Twenty patients with PFPS who applied kinesio taping and 19 who did not were included. Muscle strength and reaction time (acceleration time; AT) were evaluated using an isokinetic device. Patient-reported outcomes were measured using the visual analog scale (VAS) and Kujala anterior knee pain scale (AKPS). Conservative therapeutic exercises were performed in both groups. In each group, all parameters (quadriceps strength: p < 0.001, quadriceps AT: p < 0.001, patient-reported outcomes, including VAS: p < 0.001, AKPS: p < 0.001 for taping group; quadriceps strength: p < 0.001, quadriceps AT: p < 0.001, patient-reported outcomes, including VAS: p < 0.001, AKPS: p < 0.001 for non-taping group), improved after intervention in the symptomatic knees. However, there were no significant differences in quadriceps strength and AT, and patient-reported outcomes in the symptomatic knees between the groups with and without kinesio taping (all p > 0.05). In patients with PFPS with abnormal patellar tracking, the present study shows that kinesio taping seems to be ineffective for quadriceps strength and muscle reaction time, and patient-reported outcomes. Further studies are needed to clarify the effects of kinesio taping without conservative therapeutic exercise in PFPS patients with abnormal patellar tracking.
Downregulation of KIF21B by miR-132-3p suppresses cellular functions in gastric cancer via regulating Wnt/β-catenin signaling pathway
Authors: Liu Bingtian , Qiang Ling , Guan Bingxin , Ji Zhipeng 
Published: September 2021

Abstract
Recently, kinesin family member 21B (KIF21B) has been reported to be an oncogene in non-small cell lung cancer and hepatocellular carcinoma. However, the functional role and related mechanisms underlying gastric cancer (GC) pathogenesis remain largely uncovered. Here, we first found that the expression of KIF21B was upregulated in GC tissues compared with adjunct normal tissues by analysis of Oncomine microarray gene expression datasets and clinical specimens. Knockdown of KIF21B significantly suppressed the proliferation, migration and invasion in GC cell lines using CCK-8 assay and transwell assay. By luciferase reporter assay, KIF21B was confirmed as the target of miR-132-3p in GC cells and suppressed after miR-132-3p overexpression. Moreover, miR-132-3p was down-regulated and inversely correlated with KIF21B expression in GC tissues. Further functional experiments demonstrated that overexpression of KIF21B remarkedly reversed the suppressive effects of miR-132-3p overexpression on GC cell proliferation, migration and invasion. Furthermore, western blot analysis manifested that miR-132-3p overexpression downregulated the protein levels of Wnt1, c-Myc, β-catenin, PCNA and N-cadherin, and upregulated E-cadherin expression in GC cells, which were all alleviated after KIF21B overexpression. In summary, our findings provide the first evidence that down-regulation of KIF21B by miR-132-3p suppresses cellular functions in gastric cancer via regulating Wnt/β-catenin signaling.
An Ignored Pitfall in Selecting Reference Genes and the Solution with Emphasis on Subtypes and Sex of Thyroid Cancer Patients
Authors: Esfandiarpour Ghazal , Mokhtari Mohammad , Javadirad seyed-Morteza , Kolahdouzan Mohsen , Almuslimawi Ahmed 
Published: September 2021

Abstract
Routine tissue specific reference genes are widely used in transcriptomics studies without concerning their target genes, sex of patients, and diseases subtype. We proposed the concept of specific reference genes for each target gene after considering sex of patients and thyroid cancer subtypes. RT-qPCR technique was coupled with expression meta-analysis of samples with different races and ethnicities, in both sexes, and in different thyroid cancer subtypes. Eight common reference genes were evaluated and some of them undoubtedly ruled out. We found that mean and SD values of the genes must be considered carefully before the selection of reference genes. A formula was also developed accordingly and we equipped it with statistical analysis of more than 25000 genes. In conclusion, the reckless selection of reference genes can distort the output and must be prohibited.
Association Between Surrogate Index of Insulin Resistance and Coronary Collateral Circulation in Patients with Coronary Chronic Total Occlusion Lesions
Authors: Liu Jinxing , Hu Chengping , Liu Yan , Zhu Yong , Han Hongya , Zhou Yujie , Zhao Yingxin 
Published: September 2021

Abstract
Background: Recent studies have substantiated the role of triglyceride glucose index (TyG index) in the prognosis of coronary artery disease (CAD) patients while no relevant studies revealed the association between TyG index and coronary collateral circulation (CCC) in the event of coronary chronic total occlusion (CTO). Our study intends to explore whether or to what extent TyG index is associated with less developed CCC in CAD patients with CTO lesions.Methods: The study enrolled 1093 ACS patients undergoing percutaneous coronary intervention (PCI) for at least one CTO lesion. Relevant data was collected from Beijing Anzhen Hospital record system. The degree of collaterals was determined according to Rentrop classification system. The correlation between TyG index and coronary collateralization was assessed.Results: Overall, 318 patients were divided into poor CCC group. TyG index was significantly higher in patients with poor CCC (9.3±0.65 vs. 8.8±0.53, P＜0.001). After adjusting for various confounding factors, TyG index remained to be correlated with the occurrence of poor CCC, with an ORs (95% CIs) of 1.59 (1.07-2.36) in T2 group and 5.72 (3.83-8.54) in T3 group compared with the first tertile. Besides, subgroup analysis showed that higher TyG index values remained to be strongly associated with increased risks of poor CCC. Lastly, to compare the risk assessment efficacy for the formation of CCC between TyG index and glycosylated hemoglobin A1c (HbA1c) and another insulin resistance (IR) surrogate marker triglyceride-to-high-density lipoprotein cholesterol ratio, area under the receiver-operating characteristic (ROC) curve (AUC) was obtained, a significant improvement on the risk assessment performance for the poor CCC emerged when adding TyG index into a baseline model [AUC, 0.629 for baseline model vs. 0.724 for baseline model + TyG index vs. 0.638 for baseline model +HbA1c vs. 0.721 for baseline model +TG/HDL-C, P<0.001; net reclassification improvement (NRI) for TyG index, 0.238, P＜0.001; integrated discrimination improvement (IDI) for TyG index, 0.103, P＜0.001].Conclusions: The TyG index is strongly associated with the occurrence of poor CCC in CAD patients with CTO lesions and its risk assessment performance is better than HbA1c and TG-to-HDL-C ratio.
The Impact of COVID-19 Pandemic on Oncological Disease Extent at Staging FDG PET/CT: the ONCOVIPET Study.
Authors: Caldarella Carmelo , Cocciolillo Fabrizio , Taralli Silvia , Lorusso Margherita , Scolozzi Valentina , Pizzuto Daniele Antonio , Calcagni Maria Lucia , Rufini Vittoria , Guido Davide , Palluzzi Fernando , Giacò Luciano , Giordano Alessandro , Leccisotti Lucia 
Published: September 2021

Abstract
Purpose: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at staging using FDG PET/CT as surrogate marker.Methods: Retrospective observational study including cancer patients submitted to FDG PET/CT for staging purposes from June 1 to October 31, 2020, and June 1 to October 31, 2021, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. Results: 611 patients were included in the study (240 in 2019 vs. 371 in 2020, respectively). A significant increase in the rate of advanced disease patients in 2020 compared to 2019 was found (rate 1.56, p<0.001) as well as in the rate of N+ or M+ patients (rate 1.84 and 2.09 respectively, p<0.001) and in the rate of patients with a greater number of involved N stations or M (rate 2.01 and 2.06 respectively, p<0.001). Analysis by tumour type showed a significant increase of advanced disease, N+ or M+ status and number of involved N stations or M in lung cancer and lymphoma in 2020 compared with 2019 (p<0.003). Advanced disease rate resulted also significantly increased in gynaecologic cancer and N rate was significantly increased in gastro-intestinal cancer (p<0.05). Conclusion: The rate of cancer patients with advanced disease at staging FDG PET/CT increased by 1.5-fold in 2020, following the national lockdown due to the COVID-19 pandemic, compared to 2019 with a significant increase of patients with N involvement or M. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.
Trophic And Immunomodulatory Effects of Adipose Tissue-Derived Stem Cells In A Preclinical Murine Model of Endometriosis
Authors: Hirakawa Toyofumi , Yotsumoto Fusanori , Shirasu Naoto , Kiyoshima Chihiro , Urushiyama Daichi , Yoshikawa Kenichi , Miyata Kohei , Kurakazu Masamitsu , Koga Kaori Azuma , Aoki Mikiko , Nabeshima Kazuki , Osuga Yutaka , Komatsu Hiroaki , Taniguchi Fuminori , Harada Tasuku , Yasunaga Shin’ichiro , Miyamoto Shingo , Koga Kaori S 
Published: September 2021

Abstract
Endometriosis, which exhibits enigmatic pathological features such as stromal fibrosis and proliferation of ectopic epithelial cells, is known as a refractory disease. Mesenchymal stem cells modulate the fibrosis in stromal tissues through their trophic and immunomodulatory properties. To investigate the potential of stem cells in treating endometriosis, we examined the secondary morphology and molecular alterations in endometriosis-like lesions after the administration of adipose tissue-derived stem cells (ASCs) to an experimental murine model of endometriosis. The infused ASCs were found integrated in the endometriosis-like lesions. Accompanied by the suppression of stromal fibrosis and proliferation of endometriotic epithelial cells, the infusion of ASCs with stemness potential suppressed the growth of endometriosis-like lesions and inhibited the expression of pro-inflammatory and pro-fibrotic cytokines, whereas no significant attenuation of endometriosis-like lesions occurred after the infusion of ASCs without stemness potential. Accordingly, it is plausible that the trophic and immunomodulatory properties of ASCs may regulate fibrosis in endometriosis-like lesions, suggesting that regenerative medicine has strong potential as an innovative treatment for patients with endometriosis.
Methionine Aminopeptidase 2 as a Potential Target in Pancreatic Ductal Adenocarcinoma
Authors: Steinberg Eliana , Esa Rawnaq , Schwob Ouri , Stern Tali , Orehov Natalie , Zamir Gideon , Hubert Ayala , Panigrahy Dipak , Benny Ofra 
Published: September 2021

Abstract
Pancreatic ductal adenocarcinoma (PDA) is an aggressive metastatic cancer with a very low survival rate. This tumor is hypovascularized and characterized by hypoxic regions, yet they are not impeded by the oxidative stress in their microenvironment. PDA’s high resilience raises the need to find new effective therapeutic targets. This study investigated methionine aminopeptidase 2 (MetAp2) — a metallopeptidase known to play an important role in tumor progression — as a potential target for treating PDA by blocking its activity. Immunohistology of patient-derived PDA tissue sections revealed high expression of MetAp2 in metastatic regions compared with primary sites. Pancreatic cancer cells (cell lines and patient derived) exhibited high expression levels of MetAp2 and significant inhibition of proliferation upon exposure to a selective MetAp2 inhibitor. The growth of Orthoptic pancreatic PancOH7 tumors in mice was significantly suppressed when MetAp2 inhibitor was administered orally. Our finding revealed that the inhibition of MetAp2 in cells was associated with a significant reduction in glutathione (GSH) levels, a substance known for its role in alleviating oxidative stress, which suggests a possible rationale for the anti-cancer activity in highly hypoxic tumors such as PDA. Taken together, our results indicate that MetAp2 can be a studied as a target in PDA and possibly in other tumors with high expression levels of MetAp2 which are not necessarily highly angiogenic tumors.
Systemic COVID-19 vaccination also enhances the humoral immune response after SARS CoV-2 infection. An approach to criteria for COVID-19 re-immunization is needed. Do we need a third dose?
Authors: Kosiorek Piotr , Kazberuk Dorota , Hryniewicz Anna , Milewski Robert , Stróż Samuel , Stasiak-Barmuta Anna 
Published: September 2021

Abstract
Systemic vaccination of the BNT162b2 mRNA stimulates humoral response. The aim of our study was to compare the intensity of humoral immune response, measured by SARS CoV-2 IgG, SARS CoV-2 IgM, and neutralization S-RBD IgG antibodies level, post COVID-19 vaccination versus post SARS COV-2 infection. We analysed 1060 people in the following groups: convalescents, healthy vaccinated, vaccinated with COMIRNATY, AstraZeneca, Moderna, Johnson&Johnson and vaccinated SARS CoV-2 convalescents. A concentration of SARS CoV-2 IgG, SARS CoV-2 IgM, and neutralizing S-RBD IgG was estimated in Bialystok Oncology Center laboratory by chemiluminescent immunoassay- CLIA, MAGLUMI. Results: 1. We observed a raise of antibodies response in both, convalescent SARS CoV-2 and COVID-19 vaccinated groups 2. The level of all antibodies’ concentrations in vaccinated COVID-19 convalescents was significantly higher. 3. We differentiated an asymptomatic SARS CoV-2 convalescents from control group. Based on our analysis we suggest that it is important to monitor SARS CoV-2 antibodies concentrations as an indicator of asymptomatic COVID-19 infection, and as an equivalent of effectiveness of humoral response in convalescents and vaccinated people. Taking into consideration the time-limited nature of the effects of post infection SARS CoV-2 recovery or vaccination, among others physiological half-life, we suggested monitoring IgG antibodies level as a criterium for next vaccination.