bluuebunny/crossref_metadata_2025 huggingface dataset:
Older Patients’ Experience of Living With Cognitive Impairment Related to Hormone Therapy for Breast Cancer
Authors: Tenda Yasuko , Miyashita Mika , Yamada Akimitsu , Shimizu Chikako , Nakayama Kanako , Honma Naoko , Taira Naruto , Sawaki Masataka
Published: May 2021

Purpose

Patients with breast cancer may develop cognitive impairment as a result of hormone therapy and aging. This study aimed to describe older patients’ experience of cognitive impairment related to hormone therapy for breast cancer.
Methods

A qualitative and descriptive design was used. Semi-structured interviews were conducted for 11 patients to ask about their experience in daily life related to their cognitive impairment. Study participants were evaluated by cancer-specific geriatric assessment. Inductive content analysis was conducted using interview records.
Results

Three themes emerged from the patients’ narrative data: recognizing of cognitive impairments, impacts on mental health, and coping with cognitive impairments. Recognizing of cognitive function consisted of two categories: perception of cognitive changes and acknowledging their cognitive function status through interacting with others. Impacts on mental health consisted of six categories: decreased motivation for social activities, upset by perception of cognitive decline, concerns about impacts of cognitive impairment on treatment of breast cancer, concerns about care burden of their family, concerns about progressing of cognitive impairments, and feeling secure that their cognitive impairment is not unusual. Coping with cognitive impairments consisted of two categories: coping with problems related to cognitive impairment and trying to maintain and improve cognitive function.
Conclusion

Medical professionals should perform a comprehensive evaluation of older patients receiving hormone therapy for breast cancer.
Hotspots for rockfishes, structural corals, and large-bodied sponges along the central coast of Pacific Canada
Authors: Frid Alejandro , McGreer Madeleine , Du Preez Cherisse , Blaine Tristan , Norgard Tammy
Published: May 2021

Biological hotspots are places with outstanding biodiversity features, and their delineation is essential to the design of marine protected area networks (MPANs). For the Central Coast of Canada’s Northern Shelf Bioregion, where a MPAN is being developed, we identified hotspots for structural corals and large-bodied sponges, which are foundation species vulnerable to bottom contact fisheries, and for Sebastidae, a fish family that includes long-lived (> 100 years) and overexploited species with high trophic positions. Using 10 years of survey data that spanned from inland fjords to oceanic waters, we derived hotspot indices that accounted for species characteristics and abundances, and examined hotspot distributions across depths and oceanographic subregions. The results highlighted previously undocumented hotspot locations for each species group, thereby informing the placement of MPAs for which high levels of protection are warranted. Given the vulnerability of the species groups that we examined to cumulative fishery impacts, prospective MPAs derived from our data should be considered for interim protection measures during the protracted period between final network design and the enactment of MPA legislations. These recommendations reflect our scientific data, which are only one way of understanding the seascape. Our extensive surveys did not cover many locations known to Indigenous peoples as biologically important. Consequently, it is paramount that Indigenous knowledge also contributes substantially to the design of the MPAN.
Whole Transcriptome Analyses Identify Pairwise Gene Circuit Motif in Serous Ovarian Cancer
Authors: Cheng Lixin , Zheng Xubin , Ling Rennan , Gao Jing , Leung Kwong-Sak , Wong Man-Hon , Yang Shu , Liu Yakun , Dong Ming , Bai Huimin , Kang Lin , Li Haili
Published: May 2021

Background: Ovarian cancer is the most lethal gynaecological malignancy, resulting in approximately 14,000 deaths annually in the United States. Transcriptome data are emerging as an effective tool possibly leading to clinical applications for various cancers.Methods: We collected eight serous ovarian carcinomas (SOCs) and eight normal ovary samples, and generated a whole transcriptome profile of human ovarian cancer using microarrays, including mRNAs, lncRNAs, and circRNAs. We constructed a competing endogenous RNA (ceRNA) network involving these three types of RNAs and identified immune-related circRNAs from the network. Moreover, we proposed a gene-pair filtering method to identify significant expression reversals from integrated multi-cohorts, which mitigates the technical variation and improves the statistical power.Results: Three pairs of mRNAs (BIRC5:PRKCQ, PTK2B:OGN, and S100A14:NR2F1) were identified as promising biomarkers and were fused as an indicator (SOC index) for diagnostic prediction. Validation in three independent cohorts demonstrated that the SOC index carries a very high predictive capacity (average ROC, 0.99; sensitivity, 0.98; specificity, 1.00). Additionally, the SOC index exhibited its prognostic potential to discriminate SOC patients between early and late stage disease.Conclusions: Our findings elucidate the repertoire of RNA expressions in SOC and identified three gene pairs for the primary screening of SOC. Further biological experiments of the three gene pairs are warranted in order to investigate the underlying function mechanisms involved in ovarian cancer development.
The use of eHealth to promote physical activity in thoracic malignancies survivors: a systematic review and meta-analysis.
Authors: Rodríguez-Torres Janet , Calvache-Mateo Andrés , Ortíz-Rubio Araceli , Muñoz-Vigueras Natalia , López-López Laura , Martin-Núñez Javier , Valenza Marie Carmen
Published: May 2021

PurposeSurvival rates for many forms of thoracic malignancies have improved over the past few decades, however, many survivors are coping with the side effects of cancer treatment for longer. Physical activity has been proposed as a therapeutic strategy to act across multiple organ systems and improve clinical outcomes and eHealth could be a good way to encourage patients. The aim of this systematic review was to explore the effects of eHealth in the promotion of PA among thoracic malignancies.MethodsSuitable articles were searched using PubMed, Web of Science and Scopus databases using a combination of medical subject headings. Articles were screened by two independent reviewers and were included if they presented an eHealth intervention to improve PA in thoracic malignancies.ResultsIn total, 4781 articles were identified, of which ten met eligibility criteria. Different eHealth interventions were described in these studies: mobile application (app) (n=3), website (n=2), email (n=2), web and mobile application (n=1), telephone counseling (n=1) and online sheet (n=1). All studies reported improvements in PA, with 8/10 studies reporting statistically significant changes. ConclusionMeta-analysis revealed eHealth is a good way to improve PA in thoracic malignancies survivors, compared to no intervention, conventional treatment or a diet approach. Future studies are needed to clarify the specific intervention to improve these patients’ recovery.
Enhanced Sensitivity of Non-Small-Cell Lung Cancer with Acquired Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors to Phenformin: The Roles of a Metabolic Shift to Oxidative Phosphorylation and Redox Balance
Authors: Kim Suntae , Im Ji Hye , Kim Wan Kyu , Choi Young Jae , Lee Ji-Yoon , Kim Sang Kyum , Kim Sun Jo , Kwon Sung Won , Kang Keon Wook
Published: May 2021

Background Although the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR- TKI) therapy has been proven in non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs presents a serious clinical problem. Hence, the identification of new therapeutic strategy is needed to treat EGFR-TKI-resistant NSCLC. MethodsAcquired EGFR-TKI resistant lung cancer cell lines (HCC827, H1993 and H292 cells with acquired resistance to gefitinib or erlotinib) were used for cell-based studies. IncuCyte live cell analysis system and XFp analyzer were used for the determination of cell proliferation and energy metabolism, respectively. In vivo anti-cancer effect of phenformin was assessed in xenografts implanting HCC827 and gefitinib-resistant HCC827 (HCC827 GR) cells. ResultsHCC827 GR and erlotinib-resistant H1993 (H1993 ER) cells exhibited different metabolic properties compared with their respective parental cells, HCC827 and H1993. In EGFR-TKI-resistant NSCLC cells, glycolysis markers including the glucose consumption rate, intracellular lactate level, and extracellular acidification rate were decreased; however, mitochondrial oxidative phosphorylation (OXPHOS) markers including mitochondria-driven ATP production, mitochondrial membrane potential, and maximal OXPHOS capacity were increased. Cell proliferation and tumor growth were strongly inhibited by biguanide phenformin via targeting of mitochondrial OXPHOS complex 1 in EGFR-TKI-resistant NSCLC cells. Inhibition of OXPHOS resulted in a reduced NAD+/NADH ratio and intracellular aspartate levels. Recovery of glycolysis by hexokinase 2 overexpression in erlotinib-resistant H292 (H292 ER) cells significantly reduced the anti-cancer effects of phenformin.Conclusion Long-term treatment with EGFR-TKIs causes reactivation of mitochondrial metabolism, resulting in vulnerability to OXPHOS inhibitor such as phenformin. We propose a new therapeutic option for NSCLC with acquired EGFR-TKI resistance that focuses on cancer metabolism.
About Magnets and Superconductors of Mr Scanners
Authors: Vujović Željko Đ.
Published: May 2021

The topic of this paper are parts of modern MR devices, in which the magnet windings are located. MR scanner magnets are made of four types of electromagnetic windings: 1) The main magnet, made of superconducting material, creates a variable magnetic field; 2) X coil, made of a resistive material, creates a variable magnetic field, horizontally, from left to right, across scanning tube; 3) Y coil creates varaing magnetic field, vertically, from botom to top; 4) Z coil creates varaing magnetic field, longitudinally, from head to toe, within scanning tube.Superconductors, which create the main magnetic field, should be cooled by liquid helium and liquid nitrogen. Main magnets made of superconductors should use cryostat, with cooling vessels with liquid helium and liquid nitrogen, thermal insulation and other protective elements of magnet system. The types of magnets that exist in the basic configurations of MR scanners are analyzed. Scanners in the form of a closed cylindrical cavity create their own, magnetic, fields by passing current through the solenoid, which is held at the temperature of the superconductor. The superconductors used exclusively are: niobium-titanium (NbTi), niobium-tin (Nb3Sn), vanadium-gallium (V3Ga) and magnesium-diboride (MgB2). Only magnesium diboride is a high temperature superconductor, with a critical temperature Tc = 390K. The three remaining superconductors are low temperature. New high-temperature superconductors have been discovered, as well as room-temperature superconductors. Newly discovered superconducting materials are not used in MR scanners. The magnet structure of the MR scanner is complex. The resonant frequency changes at each point of the field in a controlled manner. The windings of the main magnet made of superconducting material in the form of microsial fibers are built into the copper core. The nonlinear gradient field is created by windings of conductive material. It is added to the main magnetic field. Thus, the resulting magnetic field is obtained.
Giant Ovarian Cysts Treated by Single-Port Laparoscopic Surgery: A Case Series
Authors: Jiang Lili , Liu Kuiran
Published: May 2021

Background:
Ovarian cysts are very common diseases of female reproductive system. Giant ovarian cysts refer to the tumors with diameters greater than 10 cm. In recent years, due to the development of clinical diagnosis, imaging modalities and the improvement of patients' cognition of the diseases, the occurrence of giant ovarian cysts become rare. The purpose of this study was to show a new operation method of single-port laparoscopy to treat giant ovarian cysts.
Methods:
We report a case series of 5 patients with giant ovarian cysts who underwent single-port laparoscopic surgery in gynecology department, Shengjing Hospital of China Medical University between June 2020 and March 2021. The inclusion criteria were ovarian cysts at least 20 cm in diameters, and cases which the tumor might be malignant were excluded.
Results:
The patients' mean age was 26.2years. The most common clinical presentation was progressive abdominal distension. Median size of the cysts at imaging was 39.2 cm (range 21–63 cm). All patients underwent single-port laparoscopic surgery, and none of them converted to laparotomy. On final pathological reports, two cysts were serous cystadenomas, and three were mucinous cystadenomas. All patients recovered well and discharged on time.
Conclusion:
Giant ovarian cysts can be treated by single-port laparoscopic surgery. In addition to the well-known advantages of laparoscopic surgery (e.g., small pelvic interference, fast postoperative recovery), it can also play the role of perfect cosmetic results, which has more advantages for young women.
The effect of using instrumental music on the pain and anxiety levels of patients with impacted third molar surgery
Authors: Moadabi Amirhossein , Kazemi Mahsa , Moosazadeh Mahmood , Zamanzadeh Maryam , Ghasemi Shohreh , Akbari Sara
Published: May 2021

Background :Anxiety and fear about dentistry are a global problem that affects a large number of people around the world. Music, as a soothing method, can be used as a relaxing treatment to relieve anxiety and discomfort pain of the patient.Purpose: This analysis aimed to check the instrumental music therapy effect on anxiety and pain levels in patients undergoing surgical treatment of an impacted third molar.Materials and Methods: In this investigation, 88 patients who were contender for third molar extraction were isolated into the mediation and control groups. In the mediation bunch, delicate instrumental music was played from the time the patients went into the working room until the finish of the medical procedure when the patient left the room. Patients' pain and nervousness levels were estimated by the Visual Analog Scale (VAS).Results: The consequences of this investigation showed that there were no measurably critical difference in depression, pain, preoperative anxiety, and postoperative uneasiness in the control and intervention group (P>0.05); however, preoperative anxiety was basically more noteworthy than postoperative anxiety in the two group (p=0.001).Conclusion: As per the outcomes, it sems to be that utilizing music doesn't lead to measurably significant difference in the nervousness level in patients going through third molar medical procedure. However, it is suggested that different analysts direct further examinations with larger sample sizes just as choosing the music dependent on the people's preferences.
The Relationship of Individual, Occupational and Psychological Factors With Low Back Pain Among Steel Industry Workers
Authors: Ahmadi Fatemeh , Esmaily Habibollah , Pakdaman Seyedeh Paria , Rafeemanesh Ehsan
Published: May 2021

Objectives: Low back pain (LBP) is one of the most common and most costly work-related musculoskeletal disorders. There are numerous factors that may affect the development of this disease. The aim of this study was to determine the prevalence of low back pain (LBP) and its association with individual, occupational and psychosocial factors among steel industry workers.Methods: For this cross-sectional study, 273 workers in a steel plant were selected by random sampling method. The participants were divided into production (n=168) and administrative (n=105) Workers. Data was collected through in-person interview, physical examination, modified Nordic questionnaire and Osipow questionnaire. Data was analyzed by descriptive statistical methods, chi-square test, t-student،test and logistic regression model using SPSS-20 software. In all statistical analysis P value≤ 0.05 was considered as statistically significant.Results: Despite the young age of participants (39.63±6.32 years) and their short employment duration, the prevalence of LBP was high (38.5%) in this industry. Gender, body mass index, smoking status and total stress score were similar in two groups. No significant relationship was found between LBP and current job status. However, LBP prevalence was significantly associated with age and duration of employment (P<0.05).Conclusion: In our study no association was observed between LBP and the participants' current job status and work- related stress. It appears that life style modifications along with education can decrease the rate of low back pain and its risk factors in employees of this industry.
COVID 19 disease independently predicted endothelial dysfunction measured by flow-mediated dilatation
Authors: Ergül Elif , YILMAZ AHMET Seyda , Öğütveren Muhammed Mürsel , Emlek Nadir , Kostakoğlu Uğur , Çetin Mustafa
Published: May 2021

Background: The systemic effects of COVID-19 disease are still largely uncertain and needs to be scrutinized with further trials. Endothelial dysfunction (ED) is responsible of the majority of adverse cardiovascular events. Flow-mediated dilation (FMD) is easily obtainable method to assess ED accurately. It is aimed to evaluate ED by measuring FMD following COVID-19 disease.Methods: Patients diagnosed with COVID-19 disease were recruited to the hospital two month after the discharge. Sex and age-matched healthy subjects were determined as the control group. Blood samples and FMD measurements were obtained from each participant. All subjects were divided into two groups according to the presence of ED determined by FMD measurements. These two groups were compared in terms of demographic features and the presence of recovered COVID-19 disease.Results: A total of 92 subjects were included in the study. ED (+) group was older (p=0.015) and more likely to have hypertension (p=0.044) and COVID-19 rate was higher in ED (+) group (p=0.009). While neutrophil count (p=0.047) and CRP (p=0.036) were higher, eGFR (p=0.044) was lower in ED (+) group. In the backward multivariable regression analysis, COVID-19 disease [OR=3.611, 95% CI: 1.069-12.198, p=0.039] and BMI [OR=1.122, 95% CI: 1.023-1.231, p=0.015] were independent predictors of ED.Conclusion: COVID-19 disease may cause ED which is the major underlying factor of cardiovascular diseases. Furthermore, COVID-19 disease may deteriorate the existing cardiovascular disease course. Detecting ED in the early phase or preventing by new treatment modalities may improve short and long-term outcome.
TCF7L2 Gene Polymorphism as a Risk for Type 2 Diabetes Mellitus and Diabetic Microvascular Complications
Authors: Aboelkhair Noran Talaat , Kasem Heba Elsayed , Abdelmoaty Amera Anwar , Eledel Rawhia Hassan
Published: May 2021

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition with various genetics and environmental influences that affects the capacity of the body to produce or use insulin resulting in hyperglycemia, which may lead to variable complications. It is one of the world’s rising health problems. There is emerging evidence that some genetic polymorphisms can impact the risk of evolving T2DM. We try to determine the relationship of (rs7903146) variant of the Transcription factor 7-like 2 (TCF7L2) gene with T2DM and its microvascular complications.Methods and Results: This case-control study included 180 subjects: 60 diabetic patients without complications, 60 diabetic patients with microvascular complications and 60 matched healthy controls. Genotypes of rs7903146 (C/T) SNP in the TCF7L2 gene were evaluated by real-time polymerase chain reaction via TaqMan allelic discrimination. Logistic regression was used to detect the most independent factor for development of diabetes and diabetic microvascular complications. Variant homozygous TT and heterozygous TC genotypes were significantly increased in diabetic without complications and diabetic with complications groups than controls (p=0.003, 0.001) respectively. The T allele was more represented in both patient groups than controls with no significant difference between patient groups. TT genotype as well as T allele was significantly associated with increased T2DM risk.Conclusion: The T allele of rs7903146 polymorphism of TCF7L2 confers susceptibility to development of T2DM. However, no significant association was found for diabetic complications.
Research Status, Key Technology and Its Application Prospect of Complex Products Assembly Quality Control and Prediction Based on Digital Twin
Authors: Guo Xuepeng , Liu Linyan , Wang Huifeng , Yuan Tangxiao
Published: May 2021

In order to solve the problem of unmeasurable assembly performance of complex product, the digital twin-driven assembly quality control and prediction of complex product is studied by means of cyber-physical fusion in the assembly workshop. The connotation of digital twin intelligent assembly is introduced, the current research status of complex product assembly quality is compared and analyzed, and three main key technologies for the assembly quality control of complex product are proposed: (1) multidimensional, multi-scale, multidisciplinary modeling and simulating of digital twin-driven assembly; (2) multi-source heterogeneous data collection, sensing and fusion for assembly processes; (3) data-driven decision making, feedback and optimization technology. Finally, the application of digital twin technology in the field of assembly quality control of complex product is prospected.
Prediction of Approximate Multiplier for 16-Bit DICOM Image Contrast Scaling Using Classical Machine Learning Approach
Authors: dominic maria , T DEEPA
Published: May 2021

The role of approximate arithmetic are involved when the processors are used for multimedia signal processing application. The impact of multiplier is very important in many processes done by these processors. The compressors are the core architecture for reduction stage if the multiplier width is increased. Later approximations are done in the compressor to limited error without affecting the signal standard. The design of scalable-split compressor is designed in this work and a counter matching method has been developed for approximation. The design of 32x32 and 16x16 multiplier with these new compressors are synthesised in 45nm Synopsis Design Compiler and shows an improvement of 25 % of Chip area and 27% power. The split-scalable architecture attempts to reduce the delay with trade-off in area and power. Mean Error Distance (MED) and Normalized Error Distance (NED) are the parameters that ensure the quality of any approximate arithmetic based design. 16-bit medical images are processed with both existing and proposed multipliers then the Peak Signal to Noise Ratio (PSNR) is compared. Finally with several input nature and targeted PSNR the best system is identified using classical machine learning model.
An Efficient Integrated Framework of Reliability-Based Robust Design Optimization for Computation-Intensive Structures
Authors: lai xiongming , Huang Ju , Wang Cheng , Zhang Yong
Published: May 2021

When carrying out robust design optimization for complex engineering structures, they are computed by finite element software and are always computation-intensive. Aim at this problem, the paper proposes an efficient integrated framework of Reliability-based Robust Design Optimization (RBRDO). Firstly, the conventional RBRDO problem is changed as percentile form, that is, the improved percentile formulation of computing the objective robustness and probabilistic constraints is presented by resorting to the employment of Performance Measure Approach (PMA). Secondly, the above improved RBRDO problem is simplified by a series of new approximation methods due to the need of reducing computation. An efficient approximation method is proposed to estimate PMA functions of the RBRDO formulation. Based on it, the above improved RBRDO problem can be transformed into a sequence of approximate deterministic sub-optimization problems, whose objective function and constraints are expressed as the approximate explicit form only in relation to the design variables. Furthermore, use the trust region method to solve the above sequence of sub-optimization. Lastly, several examples are used to demonstrate the effectiveness and efficiency of the proposed method.
Serum Dopamine Level in Acute Murine Toxoplasmosis
Authors: Omidian Mostafa , Asgari Qasem , Bahreini Mohammad Saleh , Moshki Shokoufeh , Sedaghat Bahareh , Sadati Seyed Jafar Adnani
Published: May 2021

Toxoplasmosis is a globally parasitic zoonotic disease transmitted by Toxoplasma gondii protozoa. This infection in its chronic form can cause a change in its host's specific behavior and is also associated with developing neuropsychological symptoms in humans. Changes in neurotransmitters' levels, especially dopamine, have been identified as a behavior change factor in the infected host. This study aimed to evaluate serum dopamine levels in acute murine toxoplasmosis. In this study, 50 mice infected with Toxoplasma were studied in 5 separate groups, and ten healthy mice were considered a control group. For five consecutive days after parasite injection, blood sampling and serum isolation were performed daily from one of the groups. Serum dopamine levels were measured by HPLC method. Statistical studies showed that serum dopamine on the first to the fourth day after parasite inoculation was the same as the control group, but the fifth day began to increase. The present study results indicate that dopamine production in mice infected with Toxoplasma gondii increases from day five after infection. This result suggests that in acute toxoplasmosis, dopamine production is low, and the trend of chronic disease increases dopamine production.
Phillygenin Alleviates Lipopolysaccharide-Induced Acute Pneumonia by Modulating the Tumor Necrosis Factor α Signaling Pathway
Authors: Wang Cong-jie , Tan Yu-jun , Lv Chang-jun , Liu Zhong , Zhang Gui-min , Li Bing-bing , Cheng Guo-liang
Published: May 2021

Purpose: There is an urgent need to develop effective anti-pneumonia drugs. Phillygenin (PHI) is derived from Forsythia suspense and possesses anti-inflammation, anti-oxidant bioactivities. In the present study, we aimed to evaluate the therapeutic potential of phillygenin (PHI) on lipopolysaccharide (LPS)-induced acute pneumonia.Methods: The molecular target of PHI was predicted by bioinformatic analysis. Hollow fiber-based ligand fishing (HFLF) strategy and luciferase reporter assay were further used to identify the target of PHI. LPS-induced acute pneumonia rat model and A549 cells model were used to evaluate PHI function. TNF-α pathway and apoptosis associated proteins were detected by Western Blot, immunofluorescence and immunohistochemistry. Cell cycle and cytokines were determined by flow cytometry.Results: The bioinformatic analysis and luciferase reporter assay identified that the target protein of PHI was pregnane X receptor (PXR) PHI could directly bind to PXR protein and inhibit NF-κB P65 activity. PHI significantly decreased the expression of phosphorylated JNK, P38, Erk, P65 in acute pneumonia rat model. PHI also declined the expression of Bax, Caspase-3 and Caspase-9 and repressed lung epithelial cell apoptosis induced by LPS in vivo and in vitro. In addition, PHI inhibited inflammation cytokines production including TNF-α, IFN-γ, IL-6, IL-1β and IL-18.Conclusions: PHI significantly alleviated LPS-induced lung injury in vivo by exerting anti-inflammatory effects. This is the first study to demonstrate that PHI, a small molecule natural product, significantly alleviates LPS-induced acute pneumonia by binding to PXR. Thus, PHI can be a novel therapeutic agent for pneumonia.
BeCaked: An Explainable Artificial Intelligence Model For COVID-19 Forecasting
Authors: Nguyen Duc , Vo Nghia , Nguyen Thinh , Nguyen Khuong , Nguyen Quang , Tran Dang , Quan Tho
Published: May 2021

From the end of 2019, one of the most serious and largest spread pandemics occurred in Wuhan (China) named Coronavirus (COVID-19). As reported by the World Health Organization, there are currently more than 100 million infectious cases with an average mortality rate of about five percent all over the world. To avoid serious consequences on people’s lives and the economy, policies and actions need to be suitably made in time. To do that, the authorities need to know the future trend in the development process of this pandemic. This is the reason why forecasting models play an important role in controlling the pandemic situation. However, the behavior of this pandemic is extremely complicated and difficult to be analyzed, so that an effective model is not only considered on accurate forecasting results but also the explainable capability for human experts to take action pro-actively.
With the recent advancement of Artificial Intelligence (AI) techniques, the emerging Deep Learning (DL) models have been proving highly effective when forecasting this pandemic future from the huge historical data. However, the main weakness of DL models is lacking the explanation capabilities. To overcome this limitation, we introduce a novel combination of the Susceptible-Infectious-Recovered-Deceased (SIRD) compartmental model and Variational Autoencoder (VAE) neural network known as BeCaked. With pandemic data provided by the Johns Hopkins University Center for Systems Science and Engineering, our model achieves 0.98 R2 and 0.012 MAPE at world level with 31-step forecast and up to 0.99 R2 and 0.0026 MAPE at country level with 15-step forecast on predicting daily infectious cases. Not only enjoying high accuracy, but BeCaked also offers useful justifications for its results based on the parameters of the SIRD model. Therefore, BeCaked can be used as a reference for authorities or medical experts to make on-time right decisions.
Identification of The Key miRNAs And Target Genes In Basal Cell Carcinoma By Bioinformatics Analysis
Authors: Liu Hao , Chen Ling
Published: May 2021

Background The highly tissue-destructive and localized accumulation of basal cell carcinoma(BCC) makes it one of the most important cancers affecting people's lives. Existing therapeutic approaches, including surgical treatment, chemotherapy, and Hedgehog pathway inhibitors, have failed to achieve broad therapeutic effects for various reasons. This study aims to explore additional potential therapeutic targets and possible diagnostic and prognostic biomarkers using bioinformatics analysis.Material/Methods The Gene Expression Omnibus (GEO) database identified the microarray dataset GSE34535. The GEO2R tool was used to screen out differentially expressed genes (DEGs) between BCC and non-lesional skin. Potential target genes of DE-miRNA were screened using the miRWalk, mirDIP and miRTarBase databases. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for target genes were established using the DAVID database. Protein–protein interaction network and miRNA-hub gene network were analyzed based on the STRING database and visualized by Cytoscape software. Results 51 up-regulated DE-miRNAs and 38 down-regulated DE-miRNAs were identified from the BCC samples. miR-455-5p was mainly up-regulated and miR-139-5p was mainly down-regulated. Two key bub genes MAPK1 and EGFR were identified in the PPI network. Four out of the ten hub genes were regulated by up-regulated miR-18a and four by down-regulated miR-133b. Viral infections were also identified in the study.Conclusions Bioinformatics identified four miRNAs and two important hub genes that may be associated with BCC, and it was suggested that viruses may play a role in BCC.
Hidden Blood Loss in Percutaneous Endoscopic Lumbar Discectomy (PELD): a Prospective Study
Authors: Chen Chong , Xiao Dan , Gu Honglin , Liang Guoyan , Zhang Ruiying , Zheng Xiaoqing , Liang Changxiang , Chang Yunbing
Published: May 2021

Background: Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive technique for treatment of lumbar disc herniation (LDH) that requires only an eight-mm skin incision and promotes faster recovery. It is widely believed that the procedure is associated with minimal blood loss. However, significant perioperative hidden blood loss (HBL) is frequently unaccounted for. This study aimed to investigate HBL and peri-operative factors contributing to HBL in a series of individuals undergoing PELD.Methods: As a prospective observational study, 156 patients, mean age 41.6 years (ranged from 17 to 71), undergoing PELD were finally enrolled between May 2019 and November 2020. The analyzed factors included gender, age, body mass index (BMI), symptom duration, operation approach/technique, operation duration, the presence of associated chronic diseases (e.g., hypertension, rheumatoid arthritis, and diabetes mellitus), and improvements in Visual Analog Scale (VAS), Japanese Orthopedic Association (JOA), and Oswestry Disability Index (ODI) scores. Gross’s formula was applied to calculate blood loss from recorded values for patient height, weight, and hematocrit levels before and after surgery. Multivariate linear regression analysis and t test were performed to identify factors that contributed significantly to HBL.Results: The mean HBL during PELD was 201 ± 126 mL, and the Hb reduction observed post-operatively was 7.4 ± 4.5 g/L. A lateral surgical approach was associated with greater HBL compared with an interlaminar approach. However, no significant differences in VAS, JOA, and ODI score improvements were noted between the two surgical approaches. Increased surgical times and foraminal decompression were identified by multivariate linear regression analysis as linked to increased HBL. As expected, the occurrence of post-operative anemia was significantly associated with HBL. Age, gender, BMI, symptom duration, and associated chronic diseases showed no association with increased HBL during PELD. Conclusions: HBL is increased in PELD patients with long surgical times and lumbar foraminal decompression.
Statin therapy inhibits fatty acid synthase via dynamic protein modifications
Authors: Trub Alec , Wagner Greggory , Crown Scott , Zhang Guo-Fang , Thompson J. Will , Ilkayeva Olga , Stevens Robert , Grimsrud Paul , Backos Donald , Hirschey Matthew
Published: May 2021

Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the reactive HMG-CoA into mevalonate. Recent discoveries revealed HMG-CoA is a highly reactive metabolite that can non-enzymatically modify proteins and impact their activity. Therefore, we predicted that inhibition of HMGCR by statins would increase HMG-CoA levels and subsequent protein modifications. We found a strong increase in HMG-CoA levels, but only a single protein being modified. Fatty acid synthase (FAS) was modified on active site residues and, importantly, the modification is located on non-lysine residues. The dynamic modifications occur only on a subpool of FAS that is located near HMGCR and alters cellular signaling around the ER and Golgi. These results uncover communication between cholesterol and lipid biosynthesis by the substrate of one pathway inhibiting another in a rapid and reversible manner.
The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes
Authors: Gao Yinjie , Ma Xiaosen , Wang Huiping , Cui Yunying , Zhang Yushi , Nie Min , Tong Anli
Published: May 2021

BackgroundPrevious studies have investigated the transcriptional modulations of aldosterone overproduction of aldosterone-producing adenomas (APAs), and several potential genes were found with high expressions. PurposeWe aimed to systematically study the genes and pathways associated with molecular mechanism underlying APA by bioinformatics analysis and experimental validation for the expression profile. MethodsThis study was performed based on three gene expression profiles (GSE64957, GSE8514, and GSE60042). Differentially expressed gene (DEG) investigation, function and pathway enrichment, as well as protein-protein interaction (PPI) network, were performed by the bioinformatics analysis. For the validation with quantitative PCR, tissues from 11 patients with non-functioning adrenal adenoma (NFA) and 13 with APA were included in our cohort. ResultsIn this study, the bioinformatics analysis was performed and 182 upregulated and 88 downregulated DEGs were identified. As expected, the upregulated DEGs were primarily involved in calcium ion homeostasis (GO: 0055074, n = 3, p = 2.00X10-4). In the KEGG pathway analysis, calcium signaling pathway (hsa04020, n = 8, p= 4.38X10-6) and the aldosterone synthesis and secretion (hsa04925, n = 6, p = 8.73X10-6) were enriched. Moreover, quantitative PCR was performed to detect the expression of 7 upregulated genes (PCP4, ATP2A3, CYP11B2, CLCN5, HTR4, VDR and AQP2) among the intersection of DEGs. The mRNA levels of CYP11B2, HTR4 and AQP2 were significantly increased in APA samples compared to NFA (24.420 folds of NFA, p<0.001, 3.753 folds of NFA, p=0.002 and 11.487 folds of NFA, p=0.018).ConclusionIn summary, the present study showed several candidate genes with high expression from bioinformatics analysis and our cohort. And the DEGs were enriched in aldosterone synthesis and secretion and calcium signaling pathway as expected.
A New Risk Model Predicting Overall Survival Using Preoperative Nutritional and Inflammation Status (NIS) in Patients After Curative Resection of Colorectal Cancer
Authors: Hayama Tamuro , Ozawa Tsuyoshi , Tsukamoto Mitsuo , Fukushima Yoshihisa , Shimada Ryu , Nozawa Keijiro , Matsuda Keiji , Fujii Shoichi , Fukagawa Takeo , Hashiguchi Yojiro
Published: May 2021

It has been shown that nutritional status correlates with survival in patients with various kinds of cancers. Besides, cancer causes inflammation which has been suggested to stimulate cancer progression. Therefore, inflammation status also has shown to reflect prognosis of cancers. In this study, we evaluated several kinds of nutritional and inflammation parameters in preoperative blood samples and constructed new risk model predicting a survival in patients with CRC (colorectal cancers). We retrospectively examined 286 patients with stage I-III CRC who had undergone curative resection in Teikyo University Hospital between 2013 to 2017. The association between overall survival (OS) and preoperative body mass index, albumin (Alb), cholesterol (Chol), and lymphocyte count, white blood cell count (WBC), neutrophil count (Neu), platelet count (Plt), C-reactive protein (CRP) were examined using Kaplan-Meier curve and log rank test. and eventually Alb, Chol, Neu, Plt, and CRP were shown to correlate with OS. Alb, Chol, Neu, Plt, and CRP were shown to correlate with OS. We constructed a new risk model (NIS: nutrition inflammation status) using these factors, and compared its usefulness with known models such as CRP-albumin ratio (CAR), Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and neutrophil lymphocyte ratio (NLR). NIS prepared using nutritional indicators and inflammatory findings was useful as a new model for predicting overall survival in patients undergoing curative resection for CRC, compared with known models.
An Observational Study Investigating the CRY1Δ11 Variant Associated with Delayed Sleep-wake Patterns and Circadian Metabolic Output
Authors: Smieszek Sandra P. , Brzezynski Jennifer L. , Kaden Alyssa R. , Shinn Jordan A. , Wang Jingyuan , Xiao Changfu , Polymeropoulos Christos , Özçelik Tayfun , Polymeropoulos Mihael
Published: May 2021

We conducted an observational research study to collect information on sleep-wake patterns from participants with a confirmed status of the cryptochrome circadian clock 1 (CRY1) splicing variant, CRY1Δ11 c.1657+3A>C, and their controls, defined as wild-type (WT) family members. Altogether, 67 participants were enrolled and completed this study in Turkey, recruited from a list of families with at least one CRY1-confirmed member. We measured sleep-wake patterns and metabolic output, specifically time and frequency of bowel movements, for all participants by daily post-sleep diaries over 28 days. The sleep diary measured self-reported bed time, wake time, midpoint of sleep, and latency to persistent sleep (LPS), and accounted for naps and awakenings for religious purposes. Wake time and midpoint of sleep were significantly later in the CRY1Δ11 variant group versus WT, and LPS was significantly greater in participants in the CRY1Δ11 variant group. The mean bed time on all nights of sleep was later in participants with a CRY1Δ11 variant versus WT. Additionally, participants with a CRY1Δ11 variant had significantly affected metabolic outputs, measured by later bowel movements than WT participants. These results demonstrate that, on average, individuals with the studied splicing variant experience pronounced delays in sleep period and circadian-related metabolic processes.
TRIM59 is Suppressed by Androgen Receptor and Acts to Promote Lineage Plasticity and Neuroendocrine Differentiation in Prostate Cancer
Authors: Fan Liancheng , Gong Yiming , He Yuman , Gao Wei-Qiang , Dong Baijun , Zhu Helen He , Xue Wei
Published: May 2021

Background: The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of second-generation androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood. Methods: TRIM59 expression was evaluated in PCa samples from patients at first diagnosis or at relapse stage post ARPI treatment by immunohistochemistry; in vitro effects of TRIM59 were determined by cell proliferation, sphere formation and cell migration assays; while in vivo analysis was performed using subcutaneous tumor model. Western blot, qPCR assay, dual luciferase assessment, chromatin immunoprecipitation and RNA sequencing were applied for mechanistic exploration.Results: Here we report that upregulation of TRIM59, a TRIM family protein, is strongly correlated with ARPI treatment mediated NED and shorter patient survival in PCas. AR binds to TRIM59 promoter and represses its transcription. ARPI treatment leads to a reversal of repressive epigenetic modifications on TRIM59 gene and the transcriptional restraint on TRIM59 by AR. Upregulated TRIM59 then drives the NED of PCa by enhancing the degradation of RB1 and P53 and upregulating downstream lineage plasticity-promoting transcription factor SOX2. Conclusion: Altogether, TRIM59 is negatively regulated by AR and acts as a key driver for NED in PCas. Our study provides a novel prognostic marker for PCas and shed new light on the molecular pathogenesis of t-NEPC, a deadly variant of PCa.
Scutellarin acts on the AR-NOX Axis to Remediate Oxidative Stress Injury in a Mouse Model of Cerebral Ischemia/Reperfusion Injury
Authors: Peng Llin , Deng Minzhen , Huang Yan , Wu Shuang , Cao Yucheng , Gao Zhijie , Wu Xiaoli , Zhou Lihua , Chung Sookja Kim , Sun Jingbo , Cheng Xiao
Published: May 2021

BackbroundOxidative stress plays an important role in the ischemic stroke induced brain damage. Our previous study showed that Scutellarin protects against ischemic injury in vitro and in vivo induced oxidative damage in rats, and we also reported that the involvement of Aldose reductase (AR) in oxidative stress and cerebral ischemic injury, in this study we furtherly explicit whether the antioxidant effect of Scutellarin on cerebral ischemia injury is related to AR gene regulation and its specific mechanism.MethodsC57BL/6N mice (Wild-type, WT) and AR knockout (AR-/-) mice were subjected to transient middle cerebral artery occlusion (tMCAO) model with 1h occlusion followed by 3d reperfusion, and Scutellarin was administered from 2h before surgery to 3 days after surgery. Subsequently, Neurological function were assessed by the modified Longa score method, the histopathological morphology observed with 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was used to detect the levels of ROS, 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHDG), Neurotrophin-3 (NT-3), poly ADP-ribose polymerase-1 (PARP1) and 3-nitrotyrosine (3-NT) in the ischemic penumbra regions. Quantitative proteomics profiling using quantitative nano-HPLC-MS/MS were performed to compare the protein expression difference between AR-/- and WT mice with or without tMCAO injury. The expression of AR, NOX1, NOX2 and NOX4 in the ipsilateral side of ischemic brain were detected by Real time-PCR, Western blot and immunofluorescence co-staining with NeuN.ResultsScutellarin treatment alleviated brain damage suffered from tMCAO injury such as improved neurological function deficit, brain infarct area and neuronal injury and reduced the expression of oxidation-related products, moreover, also down-regulated tMCAO induced AR mRNA and protein expression.ConclusionsScutellarin would be a potential drug for the treatment of ischemic stroke through regulating AR-NOX Axis modulate oxidative stress injury to play the protective role of cerebral ischemia injury.
Surgical and Percutaneous Revascularization Outcomes based on SYNTAX I, II, and Residual Scores. A Long-Term follow-up Study.
Authors: Martins Eduardo Bello , Hueb Whady , Brown David L , Scudeler Thiago Luis , Lima Eduardo Gomes , Rezende Paulo Cury , Soares Paulo Rogério , Garzillo Cibele Larrosa , Filho Jaime Paula Pessoa Linhares , Batista Daniel Valente , Ramires Jose Antonio Franchini , Filho Roberto Kalil
Published: May 2021

BackgroundThe objective of this study was to evaluate the association of SYNTAX scores I, II, and residual with cardiovascular outcomes of patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) and compare both procedures in a long-term follow-up.MethodsThis is a retrospective single-center study from the MASS registry at the Heart Institute of the University of São Paulo, Brazil in which 969 patients with stable coronary artery disease undergoing CABG (559) or PCI (410) were included. Clinical endpoints were the first occurrence of a composite of overall death, myocardial infarction (MI), stroke, or repeat revascularization (MACCE) and the total occurrence of each component of MACCE.ResultsIn the CABG sample, SSI had a median of 23 (IQR:17-29.5), median SSII of 25.4 (IQR:19.2-32.8), and median rSS of 2 (IQR:0-6.5); in PCI SSI had a median of 14 (IQR:10-19.1), median SSII of 28.7 (IQR:23-34.2), and median rSS of 4.7 (IQR:0-9). Total of 174 events were documented and CABG patients had a lower rate of MACCE (15.6% versus 21.2%; adjusted HR: 1.98; 95% CI, 1.13-3.47; P=.016) and repeat revascularization (3.8% versus 11.5%; adjusted HR: 4.35; CI 95%: 1.74-10.85; P=.002) compared with PCI. No SYNTAX score tertile found a difference in death rate between procedures. In a multivariate analysis, the rSS was an independent predictor for MACCE (HR=1.04; 95% CI, 1.01-1.06; P=.001). Regarding death, the only independent predictors were ejection fraction and renal function.Conclusion﻿Surgical revascularization resulted in a more complete revascularization and lower rates of major cardiac or cerebrovascular events in a long-term follow-up. Also, grading the incompleteness of revascularization through the residual SYNTAX score identified a higher event rate, suggesting that complete revascularization is associated with a better prognosis.