bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence Rates of Intraosseous Ameloblastoma Cases With Conservative or Aggressive Treatment: A Systematic Review and Meta-Analysis
Authors: Qiao Xue , Shi Junxiu , Liu Jiayi , Liu Jinwen , Guo Yan , Zhong Ming 
Published: May 2021

ObjectiveThis study aimed to systematically investigate and compare the post-treatment recurrence of intraosseous ameloblastoma in patients treated with conservative or aggressive approaches.MethodsSystemic searches of PubMed, Medline, Cochrane Library, and Embase databases from inception to October 28, 2020, were conducted. Studies that aimed to evaluate the recurrence of intraosseous ameloblastoma by conservative and aggressive treatment approaches were included.ResultsA total of 20 studies with 942 ameloblastoma cases were included. Fourteen studies included patients with ameloblastoma who received conservative treatment, and 16 studies reported the overall recurrence rate for patients undergoing aggressive treatment. The pooled results indicated that the recurrence rate for aggressive treatment [0.12, 95% confidence interval (CI) = 0.09–0.16] was significantly lower than that for conservative treatment, with a recurrence rate of 0.30 (95% CI = 0.23–0.39). Similar results were obtained when stratifying the participants by the histological classification. When trying stratification analysis following the original included studies, multicystic ameloblastoma presented a much higher recurrence rate than solid and unicystic ameloblastomas.ConclusionThese findings supported the hypothesis that aggressive treatment might lead to a lower recurrence rate than conservative treatment. More studies and meta-analyses following the new histological classification of ameloblastomas are needed to validate and support the findings.
LINC00467 Promotes Prostate Cancer Progression via M2 Macrophage Polarization and the miR-494-3p/STAT3 Axis
Authors: Jiang Hao , Deng Wen , Zhu Ke , Zeng Zhenhao , Hu Bing , Zhou Zhengtao , Xie An , Zhang Cheng , Fu Bin , Zhou Xiaochen , Wang Gongxian 
Published: May 2021

BackgroundThe long non-coding RNA LINC00467 plays a vital role in many malignancies. Nevertheless, the role of LINC00467 in prostate carcinoma (PC) is unknown. Herein, we aimed to explore the mechanism by which LINC00467 regulates PC progression.MethodsWe used bioinformatics analyses and RT-qPCR to investigate the expression of LINC00467 in PC tissues and cells. The function of LINC00467 in the progression of PC was confirmed by loss-of-function experiments. PC cell proliferation was assessed by CCK-8 and EdU assays. The cell cycle progression of PC cells was examined by flow cytometry. Moreover, Transwell assays were used to investigate the migration and invasion of PC cells. Western blot assays were used to detect the expression of factors associated with epithelial–mesenchymal transition. The interactions of LINC00467 with prostate cancer progression and M2 macrophage polarization were confirmed by RT-qPCR. The subcellular localization of LINC00467 was investigated via the fractionation of nuclear and cytoplasmic RNA. Bioinformatics data analysis was used to predict the correlation of LINC00467 expression with miR-494-3p expression. LINC00467/miR-494-3p/STAT3 interactions were identified by using a dual-luciferase reporter system. Finally, the influence of LINC00467 expression on PC progression was investigated with an in vivo nude mouse model of tumorigenesis.ResultsWe established that LINC00467 expression was upregulated in PC tissues and cells. Downregulated LINC00467 expression inhibited PC cell growth, cell cycle progression, migration, and invasion. Downregulated LINC00467 expression similarly inhibited PC cell migration via M2 macrophage polarization. Western blot analysis showed that LINC00467 could regulate the STAT3 pathway. We established that LINC00467 is mainly localized to the cytoplasm. Bioinformatics analysis and rescue experiments indicated that LINC00467 promotes PC progression via the miR-494-3p/STAT3 axis. Downregulated LINC00467 expression was also able to suppress PC tumor growth in vivo.ConclusionsOur study reveals that LINC00467 promotes prostate cancer progression via M2 macrophage polarization and the miR-494-3p/STAT3 axis.
Expression Analysis of Long Non-Coding RNAs Related With FOXM1, GATA3, FOXA1 and ESR1 in Breast Tissues
Authors: Hassani Bita , Taheri Mohammad , Asgari Yazdan , Zekri Ali , Sattari Ali , Ghafouri-Fard Soudeh , Pouresmaeili Farkhondeh 
Published: May 2021

Breast cancer is the most common neoplasm among females. Estrogen receptor (ESR) signaling has a prominent impact in the pathogenesis of breast cancer. Among the transcription factors associated with ESR signaling, FOXM1, GATA3, FOXA1 and ESR1 have been suggested as a candidate in the pathogenesis of this neoplasm. In the current project, we have designed an in silico approach to find long non-coding RNAs (lncRNAs) that regulate these transcription factors. Then, we used clinical samples to carry out validation of our in silico findings. Our systems biology method led to the identification of APTR, AC144450.1, linc00663, ZNF337.AS1, and RAMP2.AS1 lncRNAs. Subsequently, we assessed the expression of these genes in breast cancer tissues compared with the adjacent non-cancerous tissues (ANCTs). Expression of GATA3 was significantly higher in breast cancer tissues compared with ANCTs (Ratio of mean expressions (RME) = 4.99, P value = 3.12E−04). Moreover, expression levels of APTR, AC144450.1, and ZNF337.AS1 were elevated in breast cancer tissues compared with control tissues (RME = 2.27, P value = 5.40E−03; Ratio of mean expressions = 615.95, P value = 7.39E−19 and RME = 1.78, P value = 3.40E−02, respectively). On the other hand, the expression of RAMP2.AS1 was lower in breast cancer tissues than controls (RME = 0.31, P value = 1.87E−03). Expression levels of FOXA1, ESR1, and FOXM1 and linc00663 were not significantly different between the two sets of samples. Expression of GATA3 was significantly associated with stage (P value = 4.77E−02). Moreover, expressions of FOXA1 and RAMP2.AS1 were associated with the mitotic rate (P values = 2.18E−02 and 1.77E−02, respectively). Finally, expressions of FOXM1 and ZNF337.AS1 were associated with breastfeeding duration (P values = 3.88E−02 and 4.33E−02, respectively). Based on the area under receiver operating characteristics curves, AC144450.1 had the optimal diagnostic power in differentiating between cancerous and non-cancerous tissues (AUC = 0.95, Sensitivity = 0.90, Specificity = 0.96). The combination of expression levels of all genes slightly increased the diagnostic power (AUC = 0.96). While there were several significant pairwise correlations between expression levels of genes in non-tumoral tissues, the most robust correlation was identified between linc00663 and RAMP2.AS1 (r = 0.61, P value = 3.08E−8). In the breast cancer tissues, the strongest correlations were reported between FOXM1/ZNF337.AS1 and FOXM1/RAMP2.AS1 pairs (r = 0.51, P value = 4.79E−5 and r = 0.51, P value = 6.39E−5, respectively). The current investigation suggests future assessment of the functional role of APTR, AC144450.1 and ZNF337.AS1 in the development of breast neoplasms.
ALOX5AP Predicts Poor Prognosis by Enhancing M2 Macrophages Polarization and Immunosuppression in Serous Ovarian Cancer Microenvironment
Authors: Ye Xiang , An Limei , Wang Xiangxiang , Zhang Chenyi , Huang Wenqian , Sun Chenggong , Li Rongrong , Ma Hanlin , Wang Hongyan , Gao Min 
Published: May 2021

BackgroundSerous ovarian cancer (SOC) is a highly lethal gynecological malignancy with poor prognosis. Given the importance of the immune-related tumor microenvironment (TME) in ovarian cancer, investigating tumor-immune interactions and identifying novel prognostic and therapeutic targets in SOC is a promising avenue of research. ALOX5AP (Arachidonate 5-Lipoxygenase Activating Protein) is a key enzyme in converting arachidonic acid to leukotriene: a crucial immune-modulating lipid mediator. However, the role of ALOX5AP in SOC has yet to be studied.MethodsALOX5AP expression patterns across ovarian cancer and their normal tissue counterparts were cross-checked using public microarray and RNA-seq analyses and then validated in clinical samples by qRT-PCR. Kaplan-Meier survival analysis was performed in multiple independent SOC patient cohorts. Univariate and multivariate Cox regression analysis were then employed to identify clinical risk parameters associated with survival, and a genomic-clinicopathologic nomogram was built. Gene enrichment, immune infiltration, and immunosuppressor correlation analyses were then evaluated.ResultsALOX5AP mRNA levels in SOC tissues were significantly upregulated compared to normal tissues. Elevated ALOX5AP was markedly associated with poor overall survival and progression-free survival in multiple SOC patient cohorts as well as with adverse clinicopathological features, including lymphatic invasion, unsatisfactory cytoreductive surgery, rapid relapse after primary treatment, and platinum non-responsiveness. A predictive nomogram, which integrated ALOX5AP expression and two independent prognosis factors (primary therapy outcome and tumor residual), was conducted to predict the 3-year and 5-year survival rate of SOC patients. Mechanistically, functional and pathway enrichment analyses revealed that ALOX5AP was primarily involved in immune response and regulation. Further exploration demonstrated that ALOX5AP was highly expressed in the immunoreactive subtype of ovarian cancer and closely related to immunocyte infiltration, especially M2 macrophage polarization. Additionally, ALOX5AP was enriched in the C4 (lymphocyte depleted) immune subtype of SOC and associated with crucial immune-repressive receptors in the tumor microenvironment at the genomic level.ConclusionsALOX5AP expression indicates a worse survival outcome and has the potential to be utilized as a prognostic predictor for SOC patients. Given the availability of well-studied ALOX5AP inhibitors, this study has immediate clinical implications for the exploitation of ALOX5AP as an immunotherapeutic target in SOC.
Rapid Implementation and Evaluation of Virtual Health Training in a Subspecialty Hospital in British Columbia, in Response to the COVID-19 Pandemic
Authors: Hassani Kasra , McElroy Theresa , Coop Melissa , Pellegrin Joelle , Wu Wan Ling , Janke Rita D. , Johnson L. Kit 
Published: May 2021

Introduction: Adoption of virtual health (VH) solutions in healthcare has been challenging; this changed rapidly after implementation of physical distancing measures due to the COVID-19 pandemic. In response to the pandemic, British Columbia's Children's and Women's sub-specialty hospitals rapidly trained and scaled up support to equip staff and clinicians to use VH.Methods: Ninety-minute live online training workshops and frequently updated online support materials were offered for 6 weeks. Training was monitored via feedback collected at training sessions and a brief post-training survey. After training completion, a second survey was circulated to measure utilization outcomes and experiences with VH.Results: Eight hundred and ninety-five participants representing 82% of staff requiring support were trained through 101 sessions; 348 (38.9%) and 272 (30.4%) responses were collected for the monitoring and outcome surveys, respectively. Overall, 89% agreed that training was relevant to their needs; participants indicated average 58.1% (SD = 26.6) and 60.6% (SD = 25.2) increase in knowledge and confidence in VH after training; 90.1% had booked or conducted VH sessions. Increase in confidence was more pronounced in participants with lesser previous exposure to VH, but number of sessions conducted post-training and percentage of successful sessions were independent of previous exposure. For future training and support, participants suggested subject-tailored trainings, asynchronous trainings, and availability of experienced users.Discussion: Training is key to success of VH implementation. Moving forward, core competencies in VH should be developed to support standardization and allow for evaluation and quality improvement. Incorporation of VH training in continuous professional development and onboarding is also highly recommended.
Automatic Facial Recognition of Williams-Beuren Syndrome Based on Deep Convolutional Neural Networks
Authors: Liu Hui , Mo Zi-Hua , Yang Hang , Zhang Zheng-Fu , Hong Dian , Wen Long , Lin Min-Yin , Zheng Ying-Yi , Zhang Zhi-Wei , Xu Xiao-Wei , Zhuang Jian , Wang Shu-Shui 
Published: May 2021

Background: Williams-Beuren syndrome (WBS) is a rare genetic syndrome with a characteristic “elfin” facial gestalt. The “elfin” facial characteristics include a broad forehead, periorbital puffiness, flat nasal bridge, short upturned nose, wide mouth, thick lips, and pointed chin. Recently, deep convolutional neural networks (CNNs) have been successfully applied to facial recognition for diagnosing genetic syndromes. However, there is little research on WBS facial recognition using deep CNNs.Objective: The purpose of this study was to construct an automatic facial recognition model for WBS diagnosis based on deep CNNs.Methods: The study enrolled 104 WBS children, 91 cases with other genetic syndromes, and 145 healthy children. The photo dataset used only one frontal facial photo from each participant. Five face recognition frameworks for WBS were constructed by adopting the VGG-16, VGG-19, ResNet-18, ResNet-34, and MobileNet-V2 architectures, respectively. ImageNet transfer learning was used to avoid over-fitting. The classification performance of the facial recognition models was assessed by five-fold cross validation, and comparison with human experts was performed.Results: The five face recognition frameworks for WBS were constructed. The VGG-19 model achieved the best performance. The accuracy, precision, recall, F1 score, and area under curve (AUC) of the VGG-19 model were 92.7 ± 1.3%, 94.0 ± 5.6%, 81.7 ± 3.6%, 87.2 ± 2.0%, and 89.6 ± 1.3%, respectively. The highest accuracy, precision, recall, F1 score, and AUC of human experts were 82.1, 65.9, 85.6, 74.5, and 83.0%, respectively. The AUCs of each human expert were inferior to the AUCs of the VGG-16 (88.6 ± 3.5%), VGG-19 (89.6 ± 1.3%), ResNet-18 (83.6 ± 8.2%), and ResNet-34 (86.3 ± 4.9%) models.Conclusions: This study highlighted the possibility of using deep CNNs for diagnosing WBS in clinical practice. The facial recognition framework based on VGG-19 could play a prominent role in WBS diagnosis. Transfer learning technology can help to construct facial recognition models of genetic syndromes with small-scale datasets.
Synthesis of Thiol-Modified Hemicellulose, Its Biocompatibility, Studies, and Appraisal as a Sustained Release Carrier of Ticagrelor
Authors: Zaman Muhammad , Bajwa Rabia Imtiaz , Qureshi Omer Salman , Rehman Atta Ur , Saeed Sadaf , Amjad Muhammad Wahab , Ghafoor Raja Maria Abdul , Hussain Muhammad Ajaz 
Published: May 2021

Background: Nature has always been considered as the primary source of pharmaceutical ingredients. A variety of hemicelluloses, as well as their modified forms, have been under investigation. Herein, a study was designed to explore the biocompatibility of hemicellulose and its modified form (thiolated hemicellulose) as well as its potential as a pharmaceutical excipient.Method: For thiol modification thiourea was used as the thiol donor, HCl as the catalytic reagent, and methanol was used for washing purposes. Modified polymers were characterized for physicochemical characteristics, including surface morphology, the amorphous or crystalline nature of the particles, modification of polymer by FTIR, and biocompatibilities. For acute oral toxicity study, a single dose of 2 g/kg was administered to albino rats of 200 g average weight (n = 3). Polymers were evaluated as pharmaceutical excipients by preparing compressed tablets of antiplatelet drug (Ticagrelor), followed by various quality control tests, such as swelling index, thickness and diameter, disintegration, and in-vitro drug release.Results: From the results, it was observed that thiol modification has been successfully accomplished as characteristic peaks belonging to –SH group appeared at 2667.7691 cm−1 in FTIR scan. The modified polymer was found safe in the use concentration range, confirming their safe use for in vivo analysis. No significant effect has been observed in the behavior, biological fluid (blood), or on vital organs. Thiolated hemicellulose was found to be an excellent drug retarding polymer as 8 h of dissolution studies showed that 67.08% of the drug has been released.Conclusion: Conclusively, incorporation of thiol moiety made the polymer more mucoadhesive with, and a worthy carrier of, the drug with good biocompatibilities.
Pharmacogenetic Associations Between Atazanavir/UGT1A1*28 and Efavirenz/rs3745274 (CYP2B6) Account for Specific Adverse Reactions in Chilean Patients Undergoing Antiretroviral Therapy
Authors: Poblete Daniela , Bernal Fernando , Llull Gabriel , Archiles Sebastian , Vasquez Patricia , Chanqueo Leonardo , Soto Nicole , Lavanderos María A. , Quiñones Luis A. , Varela Nelson M. 
Published: May 2021

Background: Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and atazanavir (ATV), a protease inhibitor, are drugs widely used in antiretroviral therapy (ART) for people living with HIV. These drugs have shown high interindividual variability in adverse drug reactions (ADRs). UGT1A1*28 and CYP2B6 c.516G&gt;T have been proposed to be related with higher toxicity by ATV and EFV, respectively.Objective: To study the association between genetic polymorphisms and ADRs related to EFV or ATV in patients living with HIV treated at a public hospital in Chile.Methods: Epidemiologic, case–control, retrospective, observational study in 67 adult patients under EFV or ATV treatment was conducted, in the San Juan de Dios Hospital. Data were obtained from patients’ medical records. Genotype analyses were performed using rtPCR for rs887829 (indirect identification of UGT1A1*28 allele) and rs3745274 (CYP2B6 c.516G&gt;T), with TaqMan® probes. The association analyses were performed with univariate logistic regression between genetic variants using three inheritance models (codominant, recessive, and dominant).Results: In ATV-treated patients, hyperbilirubinemia (total bilirubin &gt;1.2 mg/dl) had the main incidence (61.11%), and moderate and severe hyperbilirubinemia (total bilirubin &gt;1.9 mg/dl) were statistically associated with UGT1A1*28 in recessive and codominant inheritance models (OR = 16.33, p = 0.028 and OR = 10.82, p = 0.036, respectively). On the other hand, in EFV-treated patients adverse reactions associated with CNS toxicity reached 34.21%. In this respect, nightmares showed significant association with CYP2B6 c.516G&gt;T, in codominant and recessive inheritance models (OR = 12.00, p = 0.031 and OR = 7.14, p = 0.042, respectively). Grouped CNS ADRs (nightmares, insomnia, anxiety, and suicide attempt) also showed a statistically significant association with CYP2B6 c.516G &gt; T in the codominant and recessive models (OR = 30.00, p = 0.011 and OR = 14.99, p = 0.021, respectively).Conclusion: Our findings suggest that after treatment with ATV or EFV, UGT1A1*28 and CYP2B6 c.516G&gt;T influence the appearance of moderate-to-severe hyperbilirubinemia and CNS toxicity, respectively. However, larger prospective studies will be necessary to validate these associations in our population. Without a doubt, improving adherence in patients living with HIV is a critical issue to the success of therapy. Hence, validating and applying international pharmacogenetic recommendations in Latin American countries would improve the precision of ART: a fundamental aspect to achieve the 95–95–95 treatment target proposed by UNAIDS.
Dapsone Ameliorates Isoproterenol-Induced Myocardial Infarction via Nrf2/ HO-1; TLR4/ TNF-α Signaling Pathways and the Suppression of Oxidative Stress, Inflammation, and Apoptosis in Rats
Authors: Abdelzaher Walaa Yehia , Ahmed Sabreen Mahmoud , Welson Nermeen N. , Alsharif Khalaf F. , Batiha Gaber El-Saber , Labib Dina A. Aly 
Published: May 2021

Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rodents were assigned to four groups (n = 7) and the treatments were given for 12 days as follows; Group 1 (control): were administrated normal saline, Group 2 (DAP control): were administrated DAP (10 mg/kg/day IP), Group 3 (ISO group): were administrated ISO (100 mg/kg, IP on the 11th and 12th days of the experiment), and Group 4 (DAP + ISO): co-treated with DAP plus ISO. The measured parameters were cardiac malondialdehyde (MDA), reduced glutathione (GSH), total nitrite/nitrate (NOx), catalase (CAT), serum cardiac biomarkers; CK-MB, ALT, LDH, and ALK-PH. Also, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), caspase-3 activity, and hepatic BAX and Bcl-2 were also assessed. Also, histological examination and vimentin immuno-expressions were studied. ISO group exhibited MI as evidenced by the elevation in serum cardiac biomarkers, MDA, NOx, IL-1β, TNF-α, and caspase-3 together with the reduction in GSH, Nrf2, HO-1 levels, and a faint vimentin immuno-reaction. Histological alterations revealing distorted cardiomyocytes; vacuolation, edema, pyknosis, and fragmentation were also noticed. DAP significantly ameliorated all the examined toxicity indicators. DAP revealed efficient ameliorative actions against ISO-caused MI by marked reduction in myocardial infarct size and suppressed oxidative stress, inflammation, and apoptosis via the up-regulation of the Nrf2/HO-1; TLR4/TNF-α signaling pathways.
Alteration of Autonomic Nervous System Is Associated With Severity and Outcomes in Patients With COVID-19
Authors: Pan Yuchen , Yu Zhiyao , Yuan Yuan , Han Jiapeng , Wang Zhuo , Chen Hui , Wang Songyun , Wang Zhen , Hu Huihui , Zhou Liping , Lai Yanqiu , Zhou Zhen , Wang Yuhong , Meng Guannan , Yu Lilei , Jiang Hong 
Published: May 2021

BackgroundPrevious studies suggest that coronavirus disease 2019 (COVID-19) is a systemic infection involving multiple systems, and may cause autonomic dysfunction.ObjectiveTo assess autonomic function and relate the findings to the severity and outcomes in COVID-19 patients.MethodsWe included consecutive patients with COVID-19 admitted to the 21st COVID-19 Department of the east campus of Renmin Hospital of Wuhan University from February 6 to March 7, 2020. Clinical data were collected. Heart rate variability (HRV), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer, and lymphocytes and subsets counts were analysed at two time points: nucleic-acid test positive and negative. Psychological symptoms were assessed after discharge.ResultsAll patients were divided into a mild group (13) and a severe group (21). The latter was further divided into two categories according to the trend of HRV. Severe patients had a significantly lower standard deviation of the RR intervals (SDNN) (P &lt; 0.001), standard deviation of the averages of NN intervals (SDANN) (P &lt; 0.001), and a higher ratio of low- to high-frequency power (LF/HF) (P = 0.016). Linear correlations were shown among SDNN, SDANN, LF/HF, and laboratory indices (P &lt; 0.05). Immune function, D-dimer, and NT-proBNP showed a consistent trend with HRV in severe patients (P &lt; 0.05), and severe patients without improved HRV parameters needed a longer time to clear the virus and recover (P &lt; 0.05).ConclusionHRV was associated with the severity of COVID-19. The changing trend of HRV was related to the prognosis, indicating that HRV measurements can be used as a non-invasive predictor for clinical outcome.