bluuebunny/crossref_metadata_2025 huggingface dataset:
FNDC5 Attenuates Oxidative Stress and NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells via Activating the AMPK-SIRT1 Signal Pathway
Authors: Zhou Bing , Qiu Yun , Wu Nan , Chen Ai-Dong , Zhou Hong , Chen Qi , Kang Yu-Ming , Li Yue-Hua , Zhu Guo-Qing
Published: May 2020

Vascular oxidative stress and inflammation play a major role in vascular diseases. This study was aimed at determining the protective roles of fibronectin type III domain-containing 5 (FNDC5) in angiotensin II- (Ang II-) induced vascular oxidative stress and inflammation and underlying mechanisms. Wild-type (WT) and FNDC5-/- mice, primary mouse vascular smooth muscle cells (VSMCs), and the rat aortic smooth muscle cell line (A7R5) were used in the present study. Subcutaneous infusion of Ang II caused more serious hypertension, vascular remodeling, oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in the aorta of FNDC5-/- mice than those of WT mice. Exogenous FNDC5 attenuated Ang II-induced superoxide generation, NADPH oxidase 2 (NOX2) and NLRP3 upregulation, mature caspase-1, and interleukin-1β (IL-1β) production in A7R5 cells. The protective roles of FNDC5 were prevented by SIRT-1 inhibitor EX527, AMPK inhibitor compound C, or integrin receptor inhibitor GLPG0187. FNDC5 attenuated the Ang II-induced inhibition in SIRT1 activity, SIRT1 protein expression, and AMPKα phosphorylation in A7R5 cells, which were prevented by compound C, EX527, and GLPG0187. FNDC5 deficiency deteriorated Ang II-induced oxidative stress, NLRP3 inflammasome activation, AMPK phosphorylation inhibition, and SIRT1 downregulation in primary aortic VSMCs of mice, which were prevented by exogenous FNDC5. These results indicate that FNDC5 deficiency aggravates while exogenous FNDC5 alleviates the Ang II-induced vascular oxidative stress and NLRP3 inflammasome activation via the AMPK-SIRT1 signal pathway in VSMCs.
Proapoptotic and Antiangiogenic Activities of Arctium Lappa L. on Breast Cancer Cell Lines
Authors: Taleb Agha Mohamad , Baharetha Hussein M. , Al-Mansoub Majed Ahmed , Tabana Yasser M. , Kaz Abdul Aziz Nur Hidayah , Yam Mun Fei , Abdul Majid Amin Malik Shah
Published: May 2020

In this study, the bioactivity-guided fractionation was conducted on the aerial parts of Arctium lappa L. and then the extracts were tested in vitro on breast cancer (MCF-7), colorectal cancer (HCT-116), and normal cells (EA.hy926). The n-hexane fraction (EHX) of the ethanolic extract showed strong activity against both MCF-7 and EA.hy926 cell lines (IC50 values: 14.08 ± 3.64 and 27.25 ± 3.45 μg/mL, respectively). The proapoptotic activity of EHX was assessed using MCF-7. Morphological alterations were visualized using Hoechst staining and a transmission electron microscope. Cancer cell signal transduction pathways were investigated, and EHX significantly upregulated p53, TGF-β, and NF-κB. Furthermore, EHX was found to disrupt the metastatic cascade of breast cancer cells by the inhibition of cell proliferation, migration, invasion, and colonization. The antiangiogenic activity of EHX fraction showed potent inhibition of rat aorta microvessels with IC50 value: 4.34 ± 1.64 μg/mL. This result was supported by the downregulation of VEGF-A expression up to 54%. Over 20 compounds were identified in EHX using GC-MS, of which stigmasterol, ß-sitosterol, and 3-O-acetyllupeol are the major active compounds. Phytochemical analysis of EHX showed higher phenolic and flavonoid contents with a substantial antioxidant activity. In conclusion, this work demonstrated that A. lappa has valuable anticancer activity and antiangiogenic properties that might be useful in breast cancer therapy.
The Stability of Magnetic Levitation Milling System Based on Modal Decoupling Control
Authors: Qiao Xiaoli , Tang Xiaoping
Published: May 2020

Milling stability not only reduces the surface quality of the workpiece but also seriously restricts the high-speed development of CNC machine tools. The electric spindle rotor system with the active magnetic bearing has a strong gyro coupling effect, and with the increasing rotor speed, it will become a major unfavorable factor for the stability of the system during high-speed milling. The strong gyro coupling effect makes the stability region narrow at the time of high-speed milling. So, a modal decoupling control method that can reduce the effects of the gyro effect on the magnetic levitation milling system under high-speed milling is proposed. The effects of the gyro coupling of the magnetic bearing rotor on the milling stability region before and after the decoupling control are studied, which show that the modal decoupling control technology can reduce the effects of the gyro effect on the magnetic levitation milling system.
An Adaptive Shrinking Grid Search Chaotic Wolf Optimization Algorithm Using Standard Deviation Updating Amount
Authors: Wang Dongxing , Ban Xiaojuan , Ji Linhong , Guan Xinyu , Liu Kang , Qian Xu
Published: May 2020

To improve the optimization quality, stability, and speed of convergence of wolf pack algorithm, an adaptive shrinking grid search chaotic wolf optimization algorithm using standard deviation updating amount (ASGS-CWOA) was proposed. First of all, a strategy of adaptive shrinking grid search (ASGS) was designed for wolf pack algorithm to enhance its searching capability through which all wolves in the pack are allowed to compete as the leader wolf in order to improve the probability of finding the global optimization. Furthermore, opposite-middle raid method (OMR) is used in the wolf pack algorithm to accelerate its convergence rate. Finally, “Standard Deviation Updating Amount” (SDUA) is adopted for the process of population regeneration, aimed at enhancing biodiversity of the population. The experimental results indicate that compared with traditional genetic algorithm (GA), particle swarm optimization (PSO), leading wolf pack algorithm (LWPS), and chaos wolf optimization algorithm (CWOA), ASGS-CWOA has a faster convergence speed, better global search accuracy, and high robustness under the same conditions.
Striae Gravidarum, Acne, Facial Spots, and Hair Disorders: Risk Factors in a Study with 1284 Puerperal Patients
Authors: Hoefel Isadora da Rosa , Weber Magda Blessmann , Manzoni Ana Paula Dornelles , Lovato Bárbara Hartung , Bonamigo Renan Rangel
Published: May 2020

Objective. To determine the prevalence of skin changes during pregnancy and to relate their occurrence to specific factors in a population of south Brazil. Methods. A cross-sectional analytical study was carried out with 1284 puerperal patients. A questionnaire about skin changes during pregnancy was developed and applied by the authors to all puerperal women admitted in a tertiary hospital in south Brazil. Results. The appearance of striae during pregnancy was reported by 633 women (49.5%) and had a statistically significant association with primiparity, presence of stretch marks before pregnancy, and gestational weight gain above 21 kg. Facial blemishes were reported by 33.9% (n=434) and were associated with a positive family history, multiparity, and the use of facial sunscreen (p<0.0001). The onset or worsening of acne was identified in 35.7% (n=456) and was statistically associated with primiparity and Fitzpatrick phototypes IV and V. Hair alterations were reported by 44.5% (n=569) and were associated with primiparity (p=0.029). Conclusion. Although most of the skin changes during pregnancy are considered “physiologic,” they can cause significant discomfort. Thus, it is important to know them and to understand which risk factors may be associated with such changes.
An Efficient Design of Systematic Rateless Codes
Authors: Dai Jingke , Zhang Fenggan , Yang Wenke , Kang Kai
Published: May 2020

The asymptotic performance of systematic rateless codes is first analysed using Gaussian approximation (GA) based on mutual information, which provides more accurate decoding thresholds than the method based on message mean. A modified linear program (LP) algorithm is proposed, where two key parameters are precomputed to efficiently search degree distributions with low overhead and appropriate average degree. The asymptotic analysis and simulation results show that the optimized code outperforms the codes obtained by conventional LP. Furthermore, the effects of outer code on overall code rate and decoding complexity are discussed.
α‐Glucosidase Inhibitor Can Effectively Inhibit the Risk of Tuberculosis in Patients with Diabetes: A Nested Case‐Control Study
Authors: Lin Kai-Huang , Luo Ci-Wen , Chen Shih-Pin , Tu Dom-Gene , Lin Ming-Shian , Kuan Yu-Hsiang
Published: May 2020

Diabetes mellitus (DM) and tuberculosis (TB) are major public health and economic burdens. DM increases Mycobacterium tuberculosis (M.tb) infection rates and treatment durations. This study evaluated the relationship between five classes of oral DM medications and TB infection risk in DM patients. We used longitudinal records from the Taiwan Longitudinal Health Insurance Research Database. DM patients were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) code 250 and A code A181. TB patients were identified using ICD‐9‐CM code 010.x‐017.x. Oral DM medications were divided into five classes: sulfonylureas, biguanides, meglitinides, α‐glucosidase inhibitors (AGIs), and thiazolidinediones. Users were classified as nonusers, low‐concentration users, and high‐concentration users. The incidence rate ratio (IRR) was derived using multivariate Poisson regression to calculate the relative risk of TB infection. DM patients using low‐ and high‐concentration AGIs had significantly lower TB infection risks compared with nonusers. The IRRs of the sulfonylureas and AGI users were [CI] 0.693–0.948) and (95% CI 0.651–0.995), respectively. The other four classes of medications exhibited no significant effect on TB infection risk in DM patients. Furthermore, DM patients using high‐concentration AGIs had a significantly lower TB infection risk compared with those using low‐concentration AGIs (IRR 0.918, 95% CI: 0.854–0.987). We noted a dose‐response relationship in the effects of DM medications on TB risk. Accordingly, we suggest that DM patients use AGIs to benefit from their protective effect on TB infection risk.
Clinical Review of Microbial Corneal Ulcers Resulting in Enucleation and Evisceration in a Tertiary Eye Care Center in Hungary
Authors: Tóth Gábor , Pluzsik Milán Tamás , Sándor Gábor László , Németh Orsolya , Lukáts Olga , Nagy Zoltán Zsolt , Szentmáry Nóra
Published: May 2020

Purpose. To analyse the clinical and microbiological characteristics and preexisting ophthalmic and systemic conditions of infectious keratitis resulting in enucleation/evisceration in a large tertiary referral center in a developed country (Hungary) over a period of 12 years.Patients and Methods. A retrospective review of enucleated/eviscerated eyes undergoing surgery between 2007 and 2018 at the Department of Ophthalmology of Semmelweis University, Budapest, Hungary, with infectious keratitis as the primary indication for enucleation or evisceration. For each subject, clinical history, B-scan ultrasound report, and microbiological analyses were reviewed.Results. There were 48 enucleated/eviscerated eyes from 47 patients (29 females (61.7%), age at the time of surgery 66.4 ± 18.5 years). Indication for surgery was hopeless, unmanageable keratitis (62.5%), and keratitis with endophthalmitis (37.5%). The most common preexisting ophthalmic conditions were previous cataract surgery (60.4%), previous therapeutic penetrating keratoplasty (PKP) (56.3%), corneal perforation (52.1%), glaucoma (41.7%), and long-term topical steroid usage (31.3%). In order to treat keratitis, before enucleation or evisceration, 20 eyes (41.7%) underwent PKP, 12 eyes (25.0%) amniotic membrane transplantation, 8 eyes (16.7%) conjunctival autograft transplantation, 6 eyes (12.5%) tarsorrhaphy, and 4 eyes (8.3%) vitrectomy to salvage the eye prior to the final treatment of enucleation or evisceration. The most frequent preexisting systemic diseases were hypertension (62.5%), cardiac disease (20.8%), diabetes mellitus (20.8%), and rheumatoid arthritis (14.6%).Staphylococcus aureus(17.0%) andPropionibacterium acnes(12.8%) were the most commonly isolated gram-positive bacteria, andPseudomonas aeruginosawas the most frequently isolated gram-negative pathogen bacterium (10.6%). Six globes (12.5%) had positive fungal cultures (1 case ofCandida albicans,Candida parapsilosis,Trichosporon inkin,Acremoniumsp.,Fusariumsp., andPenicilliumsp.).Conclusions.Staphylococcus aureus, Propionibacterium acnes, andPseudomonas aeruginosakeratitis with or without endophthalmitis represent the most common indication for ocular enucleation/evisceration in patients with microbial keratitis in a tertiary referral center in Hungary. The incidence of enucleation and evisceration related to mycotic keratitis does not seem to have increased within the last decade. Most frequent preexisting systemic diseases in cases of enucleation and evisceration are hypertension, cardiac disease, diabetes mellitus, and rheumatoid arthritis.
Lutein plus Water Chestnut (Trapa bispinosa Roxb.) Extract Inhibits the Development of Cataracts and Induces Antioxidant Gene Expression in Lens Epithelial Cells
Authors: Ishida Hidetoshi , Shibata Teppei , Shibata Shinsuke , Tanaka Yuki , Sasaki Hiroshi , Kubo Eri
Published: May 2020

Age‐related cataract (ARC) is the major cause of blindness worldwide. The most significant factors are the maximal exposure of the eye lens to environmental stressors, including oxidative and glycative load. The administration of antioxidant and antiglycative supplements may reduce the risk of cataract progression. In this study, the effects of lutein (LU) and water chestnut (Trapa bispinosa Roxb.) extract (TBE) on cataracts and the expression of antioxidant‐related genes were assessed in Shumiya cataract rats (SCRs). LU+TBE or castor oil (COil) as a control was administered to 6‐ or 9‐week‐old cataractous SCRs and noncataractous SCRs via a feeding needle for 3 or 4 weeks. Five‐week‐old SCRs were provided ad libitum access to solid regular chow containing LU, TBE, LU+TBE, or the same chow without LU and/or TBE for 3 weeks. Lenses from all rats were then extracted and photographed. The right eyes of the rats were processed for histological observation, and the left eyes were used for total RNA extraction from lens epithelial cells (LEC). The mRNA levels of antioxidant proteins, peroxiredoxin 6, and catalase were examined using real‐time quantitative polymerase chain reaction. Lens opacity appeared in all cataractous SCRs that began receiving LU+TBE at 9 weeks of age. However, compared to the COil group, lens opacity was decreased in the cataractous LU+TBE SCRs in all experiments. The mRNA expression levels of peroxiredoxin 6 and catalase in LECs of cataractous SCRs and cultured human LECs increased after the administration of LU+TBE. Collectively, our results highlight the anticataract and antioxidative effects of LT+TBE in SCRs. LT+TBE supplementation may, thus, be useful in delaying cataract progression.
Influence of Polypropylene Fibre (PF) Reinforcement on Mechanical Properties of Clay Soil
Authors: Taha Mazahir M. M. , Feng Cheng Pei , Ahmed Sara H. S.
Published: May 2020

This study investigated the effects of polypropylene fibre (PF) reinforcement on the mechanical behaviour of clay soil. Using clay soil and polypropylene fibres from China’s Inner Mongolia and Hebei Provinces, respectively, a series of soil samples with 0%, 1.5%, 2.25%, and 3% PF content by soil weight were subjected to compaction, shear strength, consolidation, California bearing ratio, and microstructure analyses. The study results indicate improved compaction, shear strength, consolidation, and the bearing ratio of the PF-stabilised clay soil. As the PF content increased, its maximum dry density increased and its optimum moisture content decreased; its angle of internal friction increased and its cohesion coefficient decreased; and its void ratio, consolidation coefficient, and hydraulic conductivity all decreased. Comparing the unstabilised (0% PF) and stabilised (3% PF) clay soil, the void ratio, consolidation coefficient, and hydraulic conductivity decreased from 0.96 to 0.93, from 2.52 to 2.34 cm2/s, and from 1.12 to 1.02 cm/s, respectively. The optimum PF content was determined to be 3% by the weight of the soil, as this quantity resulted in the best improvement in soil properties.
The Use of RNAi Technology to Interfere with Zfx Gene Increases the Male Rates of Red Deer (Cervus elaphus) Offspring
Authors: Wei Limin , Xi Jifeng , Zhang Yongsheng , Zeng Bo , Li Feng , Wang Kaisheng , Zhang Siyuan , Zhao Xitang , Li Ying , Shen Hong , Jiang Song , Jia Bin
Published: May 2020

Zinc finger protein X‐linked (Zfx) was regarded to be a sex determination factor and plays a critical role in spermatogenesis. RNAi is an effective method of silencing Zfx mRNA expression. However, there has been little research on the use of RNAi technology to control the sex of the offspring of red deer (Cervus elaphus). The objective of this study was first to explore an efficient method to alter the red deer offspring sex‐ratio by silencing the gene Zfx during spermatogenesis. Three recombinant expression vectors pLL3.7/A, pLL3.7/B, and pLL3.7/C were constructed to interrupt the Zfx gene. The results showed that the expression of Zfx mRNA was significantly silenced by pLL3.7/A (P < 0.01), compared with the control group. The group injected with pLL3.7/A produced 94 red deer, including 68 males and 26 females. The male rates (72.34%) were significantly higher than the control groups (P < 0.01). Our result suggests that Zfx siRNA is a useful approach to control offspring sex in red deer. This study further confirms that the Zfx gene plays a significant role in the process of X spermatogenesis.
Electroacupuncture Pretreatment as a Novel Avenue to Protect Heart against Ischemia and Reperfusion Injury
Authors: Zhang Jiyao , Zhu Luwen , Li Hongyu , Tang Qiang
Published: May 2020

In recent years, the efficacy of electroacupuncture (EA) pretreatment generating ischemic tolerance mimicking ischemic pretreatment (IP) has been continuously confirmed, which was first found in the brain and then in the heart. Furthermore, researchers have observed the intensive cardioprotection impact of EA pretreatment on patients undergoing percutaneous coronary intervention (PCI) and heart valve replacement, indicating that EA pretreatment tends to be a valuable and advantageous avenue for preventing acute myocardial ischemia/reperfusion (I/R) injury or treatment of ischemic heart disease (IHD). In reality, the heart protection mechanism of EA pretreatment is robust and pleiotropic, of which the regulatory molecular pathways are involved in multichannel, multilevel, and multitarget, including energy metabolism, inflammatory response, calcium overload, oxidative stress, autophagy, and apoptosis. Through a growing number of clinical tests and basic experiments with animal models, researchers progressively explored the optimal acupoints and parameters, where EA pretreatment induced acute and delayed ischemic tolerance for myocardial protection. Thereby, this article aims to collect the relevant evidence on EA pretreatment against myocardial ischemia/reperfusion injury (MIRI) and summarize the mechanism of cardioprotection of EA pretreatment to provide ideas and methods for further clinical applications.
CD8+ T-cell–Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas
Authors: Kane Joshua R. , Zhao Junfei , Tsujiuchi Takashi , Laffleur Brice , Arrieta Víctor A. , Mahajan Aayushi , Rao Ganesh , Mela Angeliki , Dmello Crismita , Chen Li , Zhang Daniel Y. , González-Buendia Edgar , Lee-Chang Catalina , Xiao Ting , Rothschild Gerson , Basu Uttiya , Horbinski Craig , Lesniak Maciej S. , Heimberger Amy B. , Rabadan Raul , Canoll Peter , Sonabend Adam M.
Published: May 2020

Purpose:

Cancer immunoediting shapes tumor progression by the selection of tumor cell variants that can evade immune recognition. Given the immune evasion and intratumor heterogeneity characteristic of gliomas, we hypothesized that CD8+ T cells mediate immunoediting in these tumors.

Experimental Design:

We developed retrovirus-induced PDGF+Pten−/− murine gliomas and evaluated glioma progression and tumor immunogenicity in the absence of CD8+ T cells by depleting this immune cell population. Furthermore, we characterized the genomic alterations present in gliomas that developed in the presence and absence of CD8+ T cells.

Results:

Upon transplantation, gliomas that developed in the absence of CD8+ T cells engrafted poorly in recipients with intact immunity but engrafted well in those with CD8+ T-cell depletion. In contrast, gliomas that developed under pressure from CD8+ T cells were able to fully engraft in both CD8+ T-cell–depleted mice and immunocompetent mice. Remarkably, gliomas developed in the absence of CD8+ T cells exhibited increased aneuploidy, MAPK pathway signaling, gene fusions, and macrophage/microglial infiltration, and showed a proinflammatory phenotype. MAPK activation correlated with macrophage/microglia recruitment in this model and in the human disease.

Conclusions:

Our studies indicate that, in these tumor models, CD8+ T cells influence glioma oncogenic pathways, tumor genotype, and immunogenicity. This suggests immunoediting of immunogenic tumor clones through their negative selection by CD8+ T cells during glioma formation.
Targeting Casein Kinase 1 Delta Sensitizes Pancreatic and Bladder Cancer Cells to Gemcitabine Treatment by Upregulating Deoxycytidine Kinase
Authors: Vena Francesca , Bayle Simon , Nieto Ainhoa , Quereda Victor , Aceti Massimiliano , Frydman Sylvia M. , Sansil Samer S. , Grant Wayne , Monastyrskyi Andrii , McDonald Patricia , Roush William R. , Teng Mingxiang , Duckett Derek
Published: May 2020

Although gemcitabine is the cornerstone of care for pancreatic ductal adenocarcinoma (PDA), patients lack durable responses and relapse is inevitable. While the underlying mechanisms leading to gemcitabine resistance are likely to be multifactorial, there is a strong association between activating gemcitabine metabolism pathways and clinical outcome. This study evaluated casein kinase 1 delta (CK1δ) as a potential therapeutic target for PDA and bladder cancer, in which CK1δ is frequently overexpressed. We assessed the antitumor effects of genetically silencing or pharmacologically inhibiting CK1δ using our in-house CK1δ small-molecule inhibitor SR-3029, either alone or in combination with gemcitabine, on the proliferation and survival of pancreatic and bladder cancer cell lines and orthotopic mouse models. Genetic studies confirmed that silencing CK1δ or treatment with SR-3029 induced a significant upregulation of deoxycytidine kinase (dCK), a rate-limiting enzyme in gemcitabine metabolite activation. The combination of SR-3029 with gemcitabine induced synergistic antiproliferative activity and enhanced apoptosis in both pancreatic and bladder cancer cells. Furthermore, in an orthotopic pancreatic tumor model, we observed improved efficacy with combination treatment concomitant with increased dCK expression. This study demonstrates that CK1δ plays a role in gemcitabine metabolism, and that the combination of CK1δ inhibition with gemcitabine holds promise as a future therapeutic option for metastatic PDA as well as other cancers with upregulated CK1δ expression.
Pathway-Specific Genome Editing of PI3K/mTOR Tumor Suppressor Genes Reveals that PTEN Loss Contributes to Cetuximab Resistance in Head and Neck Cancer
Authors: Izumi Hiroki , Wang Zhiyong , Goto Yusuke , Ando Toshinori , Wu Xingyu , Zhang Xuefeng , Li Hua , Johnson Daniel E. , Grandis Jennifer R. , Gutkind J. Silvio
Published: May 2020

Cetuximab, an mAb targeting EGFR, is a standard of care for the treatment for locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC). However, despite overexpression of EGFR in more than 90% of HNSCC lesions, most patients with HNSCC fail to respond to cetuximab treatment. In addition, there are no available biomarkers to predict sensitivity or resistance to cetuximab in the clinic. Here, we sought to advance precision medicine approaches for HNSCC by identifying PI3K/mTOR signaling network–specific cetuximab resistance mechanisms. We first analyzed the frequency of genomic alterations in genes involved in the PI3K/mTOR signaling circuitry in the HNSCC TCGA dataset. Experimentally, we took advantage of CRISPR/Cas9 genome editing approaches to systematically explore the contribution of genomic alterations in each tumor suppressor gene (TSG) controlling the PI3K–mTOR pathway to cetuximab resistance in HNSCC cases that do not exhibit PIK3CA mutations. Remarkably, we found that many HNSCC cases exhibit pathway-specific gene copy number loss of multiple TSGs that normally restrain PI3K/mTOR signaling. Among them, we found that both engineered and endogenous PTEN gene deletions can mediate resistance to cetuximab. Our findings suggest that PTEN gene copy number loss, which is highly prevalent in HNSCC, may result in sustained PI3K/mTOR signaling independent of EGFR, thereby representing a promising mechanistic biomarker predictive of cetuximab resistance in this cancer type. Further prospective studies are needed to investigate the impact of PTEN loss on cetuximab efficacy in the clinic.
The p.R206C Mutation in MYO7A Leads to Autosomal Dominant Nonsyndromic Hearing Loss
Authors: Lu Jiawen , Chen Penghui , Chen Tuanjie , Li Lin , Fu Xiaoli , Yang Tao , Wu Hao
Published: May 2020

Background: Dominant mutations in MYO7A may lead to nonsyndromic deafness DFNA11. A p.R206C variant in MYO7A has previously been reported in a small deaf family from Taiwan but with ambiguous pathogenicity and inheritance pattern. Aims/Objectives: Our study aims to clarify the pathogenicity of this variant by clinical characterization and genetic analysis of a separate autosomal dominant deaf family harboring this variant in mainland China. Materials and Methods: Auditory features of hearing loss were characterized in representative affected family members. Mutation screening was performed by targeted next-generation sequencing of 138 known deafness genes in the proband. Candidate pathogenic mutations were confirmed by Sanger sequencing in family members and ethnically matched controls. Results: Consistent with typical DFNA11 phenotype, the affected family members in this study showed delayed-onset, progressive hearing loss affecting mostly high frequencies. Targeted next-generation sequencing identified a p.R206C mutation in MYO7A as the only candidate pathogenic mutation cosegregating with the hearing phenotype. This mutation is not seen in 200 Chinese Han normal-hearing controls. Conclusions and Significance: The recurrent p.R206C variant in MYO7A is pathogenic and is likely in a mutation hot spot or due to a founder effect. Reports of such rare variants in multiple patients or families may facilitate exploitation of its pathogenicity.
Associated Myocarditis: A Predictive Factor for Response?
Authors: Shalata Walid , Peled Nir , Gabizon Itzhak , Abu Saleh Omar , Kian Waleed , Yakobson Alexander
Published: May 2020

In the present case report, we aimed to describe 2 cases of myocarditis occurring as serious adverse effects of immune checkpoint inhibitors (ICIs) administered as treatment for metastatic melanoma. We describe 2 female patients: an 81-year-old treated with pembrolizumab and a 55-year-old treated with a combination of nivolumab and ipilimumab. Both patients underwent resection of metastases; while under treatment, both developed myocarditis, most probably as a toxicity from pembrolizumab and nivolumab plus Ipilimumab, respectively. While they achieved complete response, the occurrence of myocarditis as a toxicity of ICIs may have been a predictive sign that the immune system was sufficiently activated by the checkpoint inhibitor therapy to induce complete remission.
Ceiling Fan-Related Head Injuries in Children: A Queensland Neurosurgical Experience
Authors: Stephens Sean , Ma Norman
Published: May 2020

Introduction: Ceiling fans are a widespread energy-efficient appliance required for managing the sweltering weather extremes encountered in northern Australian states including Queensland. Ceiling fans are also a rare cause of serious head injury in children requiring neurosurgical intervention. There is limited available evidence on the presentation, mechanism, and management of these injuries. Methods: A retrospective analysis of children who suffered ceiling fan injuries admitted to the Queensland Children’s Hospital, a level-1 paediatric trauma hospital in Brisbane, Queensland, under the neurosurgery unit from November 2014 to July 2018 was performed. Results: Seventeen children (64.7% male) with a mean age of 4.24 years (range 0.66–7.25) sustained ceiling fan injuries requiring neurosurgical management during this period. Children were injured following being accidentally lifted or thrown into the ceiling fan path; jumping, playing, climbing, or being pushed from a bunk bed; or climbing on other furniture. All patients suffered skull fractures (88.2% depressed), and 65% suffered extra-axial or intracerebral haemorrhage. Operative management was required in 76.5% of the patients. No patients suffered adverse outcomes, and no complications, including infections, were recorded. Conclusions: Despite their rarity, paediatric ceiling fan injuries requiring neurosurgical management are a cause of significant morbidity. Surgical management targeted elevation of depressed fractures and washout of open fractures rather than evacuation of intracranial collections. Almost all included patients required transfer with associated social and economic implications. Such injuries are largely preventable with improved supervision and safety awareness. Hazard modification may be extended to regulatory changes or improved ceiling fan design.
Post-Transplant Cyclophosphamide Combined with Anti-Thymocyte Globulin as Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Alanazi Wael , Chen Shiyi , Lipton Jeffrey H. , Kim Dennis D. , Viswabandya Auro , Kumar Rajat , Lam Wilson , Law Arjun D. , Al-Shaibani Zeyad , Mattsson Jonas , Michelis Fotios V.
Published: May 2020

Background: Allogeneic hematopoietic cell transplantation (HCT) is curative for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) but with significant non-relapse mortality (NRM) and relapse. We compared the combination of anti-thymocyte globulin (ATG; 4.5 mg/kg) and post-transplant cyclophosphamide (PTCy; 50 mg/kg on day +3 and +4) with other graft-versus-host disease (GvHD) prophylaxis regimens used for these patients. Methods: We retrospectively analyzed 159 patients, aged 22–73 (median 56) years, having undergone transplantation for high-risk AML (n = 120) or MDS (n = 39). The donors were matched related (33%), unrelated (55%) and haploidentical (12%). Almost all patients used peripheral blood stem cells. Conditioning was myeloablative (34%) or reduced intensity (66%). ATG + PTCy was used in 69 patients (43%), and other GvHD prophylaxis regimens in 90 patients (57%). Results: Grade III–IV acute GvHD occurred in 4% of the ATG + PTCy patients versus 20% of those using other regimens (p = 0.004), and chronic GvHD in 19% of the ATG + PTCy patients versus 41% of those using other regimens (p = 0.003). Two-year GvHD-free relapse-free survival (GRFS) was 30% with ATG + PTCy versus 18% with other regimens (p = 0.04). Multivariable analysis demonstrated that while ATG + PTCy had no significant influence on overall survival, cumulative incidence of relapse or NRM, there was a significant influence on GRFS in favor of ATG + PTCy (HR = 0.69, 95% CI 0.45–0.99, p = 0.04). Conclusions: We conclude that the ATG + PTCy combination significantly improved GRFS in allogeneic HCT for high-risk AML and MDS without influencing other outcomes.
Lack of Association between IFNL3 Polymorphism and Human Papillomavirus Infection and Their Progression in HIV-Infected Women Receiving Antiretroviral Treatment
Authors: Ouladlahsen Ahd , Bensghir Rajaa , Baba Hanâ , Haddaji Asmaa , Abbadi Islam , Zaidane Imane , Badi Hanan , Sodqi Mustapha , Marih Latifa , Wakrim Lahcen , Marhoum El Filali Kamal , Benjelloun Soumaya , Ezzikouri Sayeh
Published: May 2020

Background: It has been reported that interferon-λ3 (IFNL3)might influence the pathogenesis and clearance of human papillomavirus (HPV) infection. The impact of IFNL3 single-nucleotide polymorphism (SNP) on HPV infection is currently unknown. The aim of this study was to investigate the association between variants in the IFNL3 region and HPV infection in women with human immunodeficiency virus (HIV) infection. Methods: A total of 236 HIV patients, including 65 HPV-negative and 171 HPV DNA-positive women, were enrolled into this study. The IFNL3 rs12979860 polymorphism was genotyped using a predesigned TaqMan SNP genotyping assay. Results: Data showed no significant differences in genotypes or allele frequencies between the HPV DNA-positive and the HPV-negative women (p > 0.05). After dividing the HPV-positive women according to cytology results into patients with abnormal and normal lesions, the genotype and allele distribution of the SNP did not significantly differ between the 2 groups (p > 0.05). Conclusions: Our results showed that the IFNL3 rs12979860 polymorphism is not a major determinant of the susceptibility to HPV infection and their progression to abnormal cervical lesions in women living with HIV.
Localization of Cell Receptor-Related Genes of SARS-CoV-2 in the Kidney through Single-Cell Transcriptome Analysis
Authors: Chen Qi-Lin , Li Jia-Qi , Xiang Zhi-Dan , Lang Yue , Guo Guo-Ji , Liu Zhi-Hong
Published: May 2020

Background: The new coronavirus (SARS-CoV-2), which has been responsible for the recent coronavirus disease 2019 (COVID-19) pandemic, uses the cell receptor angiotensin converting enzyme-2 (ACE2) for entry and the serine protease TMPRSS2 for spike (S) protein priming. Meanwhile, the presence of B0AT1 (SLC6A19) may prevent TMPRSS2 from accessing the cutting position on ACE2. Identifying the expression of these cell receptor-related genes of SARS-CoV-2 is critical for understanding the pathogenesis of SARS-CoV-2 in various tissues, especially in the kidney. Methods: The single-cell transcription datasets of the human cell landscape (HCL) and other relevant single-cell transcription databases were used to analyze the expression of ACE2, TMPRSS2, and SLC6A19 in various organs and tissues, but mainly in the kidney. Results: ACE2 was significantly expressed in the S1, S2, and S3 segments of proximal tubule (PT) cells. TMPRSS2 was widely expressed in several renal tubule populations extending from the PT cells to the collection system cell type, of which intercalated cells and the distal convoluted tubule cells showed more significant expression than PT cells. Unexpectedly, although expressed on various renal tubule populations, SLC6A19 was mainly enriched in PT cells, in line with ACE2 expression. Although alveolar-type (AT) 2 cells of the lung and intestinal epithelial cells expressed ACE2 as well as PT cells, AT 2 cells significantly expressed TMPRSS2 but not SLC6A19, while all 3 genes were significantly expressed in intestinal epithelial cells. Conclusions: ACE2 was widely expressed in specific cell subgroups of various human tissues, especially in intestinal epithelial cells, kidney PT cells, and also AT 2 cells of the lung. These 3 types of cells demonstrated significant differences in the distribution of the cell receptor-related genes of SARS-CoV-2, which may indicate the diversity of cell surface structures and differences in the affinity between SARS-CoV-2 and cells.
Meta-Analysis of the Pharmacogenetics of ARMS2 A69S Polymorphism and the Response to Advanced Age-Related Macular Degeneration
Authors: Zhang Jun , Liu Zhaohui , Hu Shuqiong , Qi Jian
Published: May 2020

Age-related macular degeneration (AMD) causes irreversible vision loss, and targeted anti-vascular endothelial growth factor (VEGF) therapy is now the most common and effective treatment. The aim of this meta-analysis is to discuss whether genetic polymorphism of ARMS2 A69S could confer susceptibility to advanced AMD with the response to anti-VEGF treatment. We performed a meta-analysis of relevant published studies selected through electronic databases. A total of 21 preferred studies regarding the association between ARMS2 gene and anti-VEGF treatment response in advanced AMD were generally included in the meta-analysis. The pooled results demonstrated that the carriage of G allele for ARMS2 A69S presented a better clinical prognosis for advanced AMD treated with anti-VEGF drugs (OR = 1.38, 95% CI = 1.13–1.69, p = 0.002). In addition, in the subgroup analysis based on ethnicity, ARMS2 polymorphisms were more likely to be a positive responder for East Asian patients (OR = 1.67, 95% CI = 1.29–2.16, p < 0.001). This meta-analysis through a series of rigorous methodology data demonstrated a significant association between ARMS2 A69S polymorphism and the anti-VEGF treatment response in advanced AMD, especially among East Asian population. Numerous well-designed, randomized, multicenter clinical trials with large sample size are required to validate the association.
Features detection based blind handover using kullback leibler distance for 5G HetNets systems
Authors: Hanjri Adnane El , Hayar Aawatif , Haqiq Abdelkrim
Published: May 2020

The Fifth Generation of Mobile Networks (5G) is changing the cellular network infrastructure paradigm, and Small Cells are a key piece of this shift. But the high number of Small Cells and their low coverage involve more Handovers to provide continuous connectivity, and the selection, quickly and at low energy cost, of the appropriate one in the vicinity of thousands is also a key problem. In this paper, we propose a new method, to have an efficient, blind and rapid handover just by analysing Received Signal probability density function instead of demodulating and analysing Received Signal itself as in classical handover. The proposed method exploits KL Distance, Akaike Information Criterion (AIC) and Akaike weights, in order to decide blindly the best handover and the best Base Station (BS) for each user
A deep learning AlexNet model for classification of red blood cells in sickle cell anemia
Authors: Abdulkarim Hajara Aliyu , Abdul Razak Mohd Azhar , Sudirman Rubita , Ramli Norhafizah
Published: May 2020

Sickle cell anemia (SCA) is a serious hematological disorder, where affected patients are frequently hospitalized throughout a lifetime and even can cause death. The manual method of detecting and classifying abnormal cells of SCA patient blood film through a microscope is time-consuming, tedious, prone to error, and require a trained hematologist. The affected patient has many cell shapes that show important biomechanical characteristics. Hence, having an effective way of classifying the abnormalities present in the SCA disease will give a better insight into managing the concerned patient's life. This work proposed algorithm in two-phase firstly, automation of red blood cells (RBCs) extraction to identify the RBC region of interest (ROI) from the patient’s blood smear image. Secondly, deep learning AlexNet model is employed to classify and predict the abnormalities presence in SCA patients. The study was performed with (over 9,000 single RBC images) taken from 130 SCA patient each class having 750 cells. To develop a shape factor quantification and general multiscale shape analysis. We reveal that the proposed framework can classify 15 types of RBC shapes including normal in an automated manner with a deep AlexNet transfer learning model. The cell's name classification prediction accuracy, sensitivity, specificity, and precision of 95.92%, 77%, 98.82%, and 90% were achieved, respectively.
Nutrient deficiency detection in Maize (Zea mays L.) leaves using image processing
Authors: Sabri Nurbaity , Shafekah Kassim Nurul , Ibrahim Shafaf , Roslan Rosniza , Mangshor Nur Nabilah Abu , Ibrahim Zaidah
Published: May 2020

Maize is one of the world's leading food supplies. Therefore, the crop's production must continue to reproduce to fulfill the market demand. Maize is an active feeder, therefore, it need to be adequately supplied with nutrients. The healthy plants will be in deep green color to indicate it consist of adequate nutrient. Current practice to identify the nutrient deficiency on maize leaf is throught a laboratory test. It is time consuming and required agriculture knowledge. Therefore, an image processing approach has been done to improve the laboratory test and eliminate a human error in identification process. The purpose of this research is to help agriculturist, farmers and researchers to identify the type of maize nutrient deficiency to determine an action to be taken. This research using image processing techniques to determine the type of nutrient deficiency that occurs on the plant leaf. A combination of Gray-Level Co-Occurrence Matrix (GLCM), hu-histogram and color histogram has been used as a parameter for further classification process. Random forest technique was used as classifiers manage to achive 78.35% of accuracy. It shows random forest is a suitable classifier for nutrient deficiency detection in maize leaves. More machine learning algorithm will be tested to increase current accuracy.
Conflicting opinions in connection with digital superintelligence
Authors: Al-Imam Ahmed , Motyka Marek A. , Jędrzejko Mariusz Z.
Published: May 2020

In 1964, Nikolai Kardashev proposed the Kardashev scale, a system for measuring the extent of technological advancement of a civilization based on the magnitude of energy consumption. We are approaching an inevitable type-1 civilization, and artificial superintelligence superior to that of humans can concur with a higher-hierarchy Kardashev civilization. We aim to survey public opinions, specifically video gamers, worldwide compared to those in Poland, concerning artificial general intelligence and superintelligence. We implemented an amalgam of cross-sectional and longitudinal analyses of the database of literature and Google search engine. The geographic mapping of surface web users who are interested in artificial superintelligence revealed the top ten contributing countries: Iran, Mexico, Colombia, Brazil, India, Peru, South Africa, Romania, Switzerland, and Chile. Developing countries accounted for 54.84% of the total map. Polish people were less enthusiastic about artificial general intelligence and superintelligence compared with the rest of the world. Futuristic technological innovations imply an acceleration in artificial intelligence and superintelligence. This scenario can be pessimistic, as superintelligence can render human-based activities obsolete. However, integrating artificial intelligence with humans, via brain-computer interface technologies, can be protective. Nonetheless, legislation in connection with information technologies is mandatory to regulate upcoming digital knowledge and superintelligence.
Evaluation of particle swarm optimization for strength determination of tropical wood polymer composite
Authors: Yusoff Marina , Basir Alya Nurizzati Mohd , A Kadir Norhidayah , Anuar Bahari Shahril
Published: May 2020

A wood-polymer composite (WPCs) refers to wood-based components that are coupled with polymers to produce a composite material. Obtaining the best strength for the tropical WPCs is still a lack of research mainly for the tropical timber species and require a large consumption of time and cost. This paper highlighted the evaluation of particle swarm optimization (PSO) to assist in finding the optimal value of the composition of tropical WPCs to obtain the best strength that would offer a betterment in a quality product of WPCs. The findings demonstrate that PSO has been shown as a viable and efficient method for WPCs strength. The composition of Sentang, wood sawdust of 50%, HDPE of 49% and 1% coupling agent is demonstrated the best strength for the WPC. The employment of PSO as an assisted tool would give significant benefit to the manufacturer and researcher to determine the composition of material with less cost and time.
Catheter Ablation Improves Mortality and Other Outcomes in Real‐World Patients With Atrial Fibrillation
Authors: Yang Pil‐Sung , Sung Jung‐Hoon , Jang Eunsun , Yu Hee Tae , Kim Tae‐Hoon , Uhm Jae‐Sun , Kim Jong‐Youn , Pak Hui‐Nam , Lee Moon‐Hyoung , Joung Boyoung
Published: May 2020

Background

It is still controversial whether catheter ablation for atrial fibrillation (
AF
) improves survival and other outcomes in patients with AF. This study evaluated whether ablation reduces death and other events in nationwide real‐world Asian patients with
AF
.

Methods and Results

From the Korean National Health Insurance Service database, 194 928 adult patients (aged ≥18 years) with newly diagnosed
AF
were treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between January 1, 2005, and December 1, 2015. Among these patients, this study included 9185 with ablation and 18 770 with medical therapy. The time at risk was counted from the first medical therapy, and ablation was analyzed as a time‐varying covariate. Inverse probability of treatment weighting was used to correct for differences between the groups. After weighting, the 2 cohorts had similar background characteristics. During a median (25th, 75th percentiles) follow‐up of 43 (19, 81) months, ablation of
AF
was associated with lower incidence and risk of composite outcome, including death, heart failure admission, and stroke/systemic embolism (2.5 and 6.4 per 100 person‐years, respectively; hazard ratio [HR], 0.47; 95%
CI
, 0.43–0.52;
P
<0.001), all‐cause death (1.0 and 3.6 per 100 person‐years; HR, 0.41; 95%
CI,
0.36–0.47;
P
<0.001), heart failure admission (0.7 and 1.9 per 100 person‐years; HR, 0.43; 95%
CI,
0.37–0.50), and ischemic stroke/systemic embolism (1.1 and 2.8 per 100 person‐years; HR, 0.39; 95%
CI,
0.34–0.44) than medical therapy.

Conclusions

Ablation may be associated with lower risk of death, heart failure admission, and ischemic stroke/systemic embolism in real‐world Asian patients with
AF
.