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Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.

Trigeminal neuralgia (TN) is a disease characterized by recurring, short-lived, electric shock-like pain experienced on one side of the face. Microvascular decompression (MVD) is one of the most effective surgical interventions for resolving TN caused by neurovascular compression. This study aimed to determine the predictive and prognostic factors of surgical outcomes.This retrospective cohort study enrolled patients diagnosed with TN who underwent MVD at our hospital during 2013-2019. The demographic information, pain character, peri-operative Barrow Neurological Institute (BNI) scale, medication, operative finding were recorded. And the outcome was Outcomes were divided into drug-free and drug-dependent group. Predisposing factors for each outcome were analyzed by one-way analysis of variance, followed by a Mann-Whitney U test or Kruskal-Wallis test.A total of 104 consecutive patients received MVD to treat TN, and 88 patients were enrolled in this study. The overall postoperative drug-free outcome was 72.7%. A significant difference in drug-free outcomes was observed for patients with typical TN (80.8%) compared with patients with atypical TN (33.33%, p = 0001). When severe venous compression was encountered during MVD, the drug-free outcome fell to 50% (10/20, p = 0.009). The Mann-Whitney U test indicated typical TN as a positive predictive factor of a drug-free outcome, whereas severe venous compression was a negative predictive factor. The patients with preoperative BNI score of 4 had better improvement than others (p = 0.045). Age, onset duration, and arterial loop had no specific difference in this study.In our study, atypical TN and severe venous compression were associated with poor outcomes. Regrouping atypical TN into precise diagnosis represents an immediate priority according to our result. The preoperative BNI score could be used as an effective predictive tool for the outcome of MVD surgery.

Supplementary Figures 1-4, Tables 1-4, Methods from Coexpression of Oct4 and Nanog Enhances Malignancy in Lung Adenocarcinoma by Inducing Cancer Stem Cell–Like Properties and Epithelial–Mesenchymal Transdifferentiation

BACKGROUND Nanoparticles (NPs) have wide potential applications in biolabeling, bioimaging, and cell tracking. Development of dual functional nanoparticles increases the versatility. METHODS we combined the fluorescent property of nano-epoxy (N-Epo) and the magnetic characteristic of FePt to fabricate the FePt-decorated N-Epo (N-Epo-FePt). The size in diameter of N-Epo-FePt (177.38 ±39.25 nm) was bigger than N-Epo (2.28 ±1.01 nm), both could be absorbed into mesenchymal stem cells (MSCs) via clathrin-mediated endocytosis and have multiple fluorescent properties (blue, green, and red). RESULTS N-Epo-FePt prevented N-Epo-induced platelet activation, CD68+-macrophage differentiation in blood, and intracellular ROS generation in MSCs. The induction of apoptosis and the inhibitory effects of N-Epo-FePt on cell migration, MMP-9 activity, and secretion of SDF-1α were less than that of N-Epo in MSCs. CONCLUSION N-Epo-FePt was more biocompatible without altering biological performance than N-Epo in MSCs. These results suggest that N-Epo-FePt nanoparticle can be used for fluorescence labeling of MSCs and is potential to apply to bioimaging and cell tracking of MSCs in vivo by magnetic resonance imaging (MRI) or computed tomography (CT).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect countries worldwide. To inhibit the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), testing of patients, contact tracing, and quarantine of their close contacts have been used as major nonpharmaceutical interventions. The advantages of antigen tests, such as low cost and rapid turnaround, may allow for the rapid identification of larger numbers of infectious persons. This meta-analysis aimed to evaluate the diagnostic accuracy of antigen tests for SARS-CoV-2. METHODS: We searched PubMed, Embase, Cochrane Library, and Biomed Central databases from inception to January 2, 2021. Studies evaluating the diagnostic accuracy of antigen testing for SARS-CoV-2 with reference standards were included. We included studies that provided sufficient data to construct a 2 × 2 table on a per-patient basis. Only articles in English were reviewed. Summary sensitivity and specificity for antigen tests were generated using a random-effects model. RESULTS: Fourteen studies with 8624 participants were included. The meta-analysis for antigen testing generated a pooled sensitivity of 79% (95% CI, 66%-88%; 14 studies, 8624 patients) and a pooled specificity of 100% (95% CI, 99%-100%; 14 studies, 8624 patients). The subgroup analysis of studies that reported specimen collection within 7 days after symptom onset showed a pooled sensitivity of 95% (95% CI, 78%-99%; four studies, 1342 patients) and pooled specificity of 100% (95% CI, 97%-100%; four studies, 1342 patients). Regarding the applicability, the patient selection, index tests, and reference standards of studies in our meta-analysis matched the review title. CONCLUSION: Antigen tests have moderate sensitivity and high specificity for the detection of SARS-CoV-2. Antigen tests might have a higher sensitivity in detecting SARS-CoV-2 within 7 days after symptom onset. Based on our findings, antigen testing might be an effective method for identifying contagious individuals to block SARS-CoV-2 transmission.

BACKGROUND Medial displacement calcaneal osteotomy (MDCO) is frequently used for the surgical correction of flatfoot. This study aims to investigate the biomechanical effect of the different diagonal screw design on a novel-designed embedded calcaneal plate for MDCO using finite element analysis (FEA), mechanical test and digital image correlation (DIC) measurement. METHODS Four groups according to the varied implanted plate were set as control group (Group 1), non-diagonal screw (Group 2), one-diagonal screw (Group 3), and two-diagonal screws groups (Group 4). For FEA, A 450 N load was applied to on the anterior process of the calcaneus from top to bottom. Observational indices included the stress on the cortical and cancellous bone of the calcaneus surrounding the implant, the plate itself as well as screws, and the displacement of the overall structure. In addition, this study also used in vitro biomechanics test to investigate the stiffness of the structure after implantation, and used DIC to observe the displacement of the calcaneus structure after external force. RESULTS Under a simulated load in FEA, there are significant overall instability and high stress concentration on the calcaneal surrounding host bone and the plate/screws system, respectively, in group 2 compared with other groups. Regard to the mechanical testing with DIC system, significant increased rotation stability, maximum force and stiffness with the addition of diagonal screws. In comparison to Group 2, the increase of 112% and 157% in maximum force as well as 104% and 176% in stiffness were found in Group 3 and 4, respectively. CONCLUSION For reducing stress concentration and enhancing overall stability, more than one-diagonal screw design is recommended and two-diagonal screws design will be superior. This study provided biomechanical references for further calcaneal implants design to prevent clinical failure after MDCO.

Background Chitosan (Chi) is a natural material which has been widely used in neural applications due to possessing better biocompatibility. In this research study, a novel of nanocomposites film based on Chitosan (Chi) with Hyaluronic Acid (HA), combined with varying amounts of gold nanoparticles (AuNPs) was created resulting in pure Chi, Chi-HA, Chi-HA-AuNPs (25 ppm) and Chi-HA-AuNPs (50 ppm). Methods This study focused on evaluating their effects on Mesenchymal Stem Cell (MSC) viability, colony formation and biocompatibility. The surface morphology and chemical position was characterized through UV-Visible spectroscopy (UV-Vis), Fourier-transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and contact-angle assessment. Results When seeding MSCs on Chi-HA-AuNPs (50 ppm), the results showed high cell viability, biocompatibility, and the highest colony formation ability. Meanwhile, the evidence showed that Chi-HA-Au nano film was able to inhibit Nestin and β-Tubulin expression of MSCs, as well as inhibit the ability of neurogenic differentiation. Furthermore, the results of Matrix Metalloproteinase 2/9 (MMP2/9) expression in MSCs were also significantly higher in the Chi-HA-AuNP (50 ppm) group, guiding with angiogenesis and wound healing abilities. In addition, in our rat model, both capsule thickness and collagen deposition were the lowest in Chi-HA-AuNPs (50 ppm). Conclusion Thus, in view of the in vitro and in vivo results, Chi-HA-AuNPs (50 ppm) could not only maintain the greatest stemness properties and regulate the neurogenic differentiation ability of MSCs, but was able to also induce the least immune response. Herein, Chi-HA-Au 50 ppm nano film holds promise as a suitable material for nerve regeneration engineering.

BACKGROUND Most reproductive system studies suggest the protective effects of vitamin D, but vitamin D deficiency and insufficiency are growing global health issues. The present study investigates the association between vitamin D deficiency/insufficiency and gynecologic diseases to identify illness risks at different serum vitamin D levels in Taiwan. METHODS A total of 7699 female adults aged ≥20 years with results for both serum vitamin D and gynecologic-associated diseases were drawn from the Taiwan MJ cohort. We analyzed the correlation between serum vitamin D levels and results from reproductive system evaluations, including history of dysmenorrhea, results of Pap smear, high-risk human papillomavirus (HPV) infection of the cervix, mammography, and ultrasound of breast and pelvis. RESULTS Over 80% of participants showed vitamin D deficiency/insufficiency. Participants with abnormal Pap smear results, high-risk HPV infection, and history of dysmenorrhea showed significantly lower levels of serum vitamin D (p < 0.001-0.05). Serum vitamin D deficiency was significantly associated with positive high-risk HPV infection of the cervix (p < 0.05) and dysmenorrhea (p < 0.001). After controlling for age as a confounding variable for each gynecologic disease, level of serum vitamin D was significantly associated with abnormal breast ultrasound (odds ratio = 0.724) and uterus ultrasound (odds ratio = 0.673 - 0.8), and dysmenorrhea (odds ratio = 0.829). CONCLUSION Associations were found between vitamin D deficiency and endometriosis, uterine myoma, dysmenorrhea, abnormal Pap smear results, and high-risk HPV infection of the cervix. Therefore, vitamin D supplements may present a cost-effective benefit for the prevention and treatment of gynecologic diseases, and thus reduction of healthcare expenditures.

The Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented disruption to the normal operation of the healthcare system. On a worldwide scale, hospitals suspended non-urgent surgeries and outpatient visits to downsized clinical loadings to redistribute manpower to counteract the pandemic's impact. So far, there is no evidence-based guideline defining a clear line between urgent and non-urgent indications of intravitreal injections (IVI). Herein, we aimed to summarize IVI algorithm modifications and discuss the patient prioritization according to medical needs in the hostile environment in the COVID crisis. Assessing current literature, we found that neovascular age-related macular degeneration is considered the utmost priority among conditions that require IVI. Other conditions assigned with a high priority include monocular or quasi-monocular patients (only one eye > 20/40), neovascular glaucoma, and new patients with significant vision loss. Although patients with central retinal vein occlusion and proliferative diabetic retinopathy are not advised to delay treatments, we found no consistent evidence that correlated with a worse outcome. Diabetic macular edema and branched retinal vein occlusion patients undertaking treatment delay should be regularly followed up every 2-3 months. Serving as the principle of management behind the algorithm modifications, the reduction of both patient visit and IVI therapy counts should be reckoned together with the risk of permanent visual loss and COVID infection.

The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.

A systematic analysis of the source duration (τ) and seismic moment (M0) for seismogenic earthquakes (MW 5.5–7.1) in the Taiwan region was completed by using a teleseismic P-wave inversion method. Irrespective of the source self-similarity, the M0–τ relationship derived in this study had a power-law form, namely M0 ∝ τ3, under the assumption that ΔσVr3 is constant following a circular fault model (Δσ: static stress drop; Vr: rupture velocity). For Taiwan’s earthquakes, the derived M0–τ relationship not only provides information to predict the source duration of large earthquakes, but also probes the rupture features of seismogenic earthquakes. That is, there are different rupture patterns for earthquakes, but the product ΔσVr3 remains nearly constant.

Electronic healthcare (e-health) has gained more and more research attention in recent years, due to its flexibility and convenience. E-health is efficiently enabled by telecare medicine information system (TMIS). TMIS provides seamless transfer and timely sharing of medical information for specific healthcare services. Since communications in TMIS are carried out through unreliable channels, data security and user privacy concerns become prominent. With traditional single-server architecture, users must store massive credentials, which causes inefficient communication and significant overhead. Moreover, user credentials in previously proposed schemes are stored at server side, suffering potential risks. Our work proposes a three-factor user-controlled single sign-on (UCSSO) with fast authentication and privacy protection for TMIS. The contributions of this paper are as follows. Our work integrates three factors including password, smart card and biometrics in authentication procedure, for providing a high-security and privacy-preserved communication. We introduce single sign-on solution that allows users to log in to multiple servers using a single password. User-controlled mechanism is proposed to address insider attacks and the risk that registration center may be compromised. The proposed scheme is designed with fast authentication mechanism that helps to efficiently establishes new session key. Our work is proved secure using BAN logic, ROR model, and AVISPA toolset. The results of performance comparison show that our scheme provides more security properties and bears the least overhead, compared with competitive schemes.

Lung cancer is the leading cause of death from cancer in Taiwan and throughout the world. Immunotherapy has revealed promising and significant efficacy in NSCLC, through immune checkpoint inhibition by blocking programmed cell death protein (PD)-1/PD-1 ligand (PD-L1) signaling pathway to restore patients’ T-cell immunity. One novel type of long, non-coding RNAs, circular RNAs (circRNAs), are endogenous, stable, and widely expressed in tissues, saliva, blood, urine, and exosomes. Our previous results revealed that the plasma level of hsa_circ_0000190 can be monitored by liquid-biopsy-based droplet digital PCR and may serve as a valuable blood-based biomarker to monitor the disease progression and the efficacy of immunotherapy. In this study, hsa_circ_0000190 was shown to increase the PD-L1 mRNA-mediated soluble PD-L1 (sPD-L1) expression, consequently interfering with the efficacy of anti-PD-L1 antibody and T-cell activation, which may result in immunotherapy resistance and poor outcome. Our results unraveled that hsa_circ_0000190 facilitated the tumorigenesis and immune evasion of NSCLC by upregulating sPD-L1 expression, potentially developing a different aspect in elucidating the molecular immunopathogenesis of NSCLC. Hsa_circ_0000190 upregulation can be an effective indicator for the progression of NSCLC, and hsa_circ_0000190 downregulation may possess a potential therapeutic value for the treatment of NSCLC in combination with immunotherapy.

Acute myocardial infarction (AMI) and atrial fibrillation (AF) are risk factors for stroke. The risk of stroke after AMI may differ between patients with and without AF. The aim of this study was to evaluate the impact of AF on stroke in patients after the first AMI.This was a retrospective, nationwide cohort study. Patients with a primary diagnosis of a first AMI between 2000 and 2012 were included. All patients were followed up until ischemic stroke or transient ischemic attack (TIA), or December 31, 2012, whichever occurred first. Kaplan-Meier cumulative survival curves were constructed to compare ischemic stroke or TIA between AMI patients with and without AF.A total of 170 472 patients were enrolled in this study. Among them, 8530 patients with AF were identified. The propensity score matching technique was used to match 8530 patients without AF of similar ages and sexes. Overall, the 12-year stroke rate was significantly higher in patients with AF than in those without AF (log-rank p0.001), including different sexes, ages, and interventional therapy subgroups. Patients with pre-existing AF had higher stroke rates than those with newly diagnosed AF in male sex, age below 65 years, and those receiving interventional therapy subgroups. In Cox proportional-hazard regression analysis, AF was an independent risk factor for stroke after the first AMI (hazard ratio, 1.67; 95% CI: 1.5-1.87).AF significantly increases stroke risk after the first AMI. In patients with AF, those with pre-existing AF have higher stroke risks in male sex, age below 65 years, and those with interventional therapy than those with newly diagnosed AF.

Terrible triad of the elbow injury is difficult to manage, and the role of the coronoid process in instability is very important. We describe a simple, modified suture technique to fix a coronoid process fragment using suture anchor fixation.Eight patients (three female and five male) with coronoid process injuries with the fragment involving50% of the total height (Regan-Morrey type I/II) in terrible triad of elbow injury were included. Patients were treated operatively via a lateral Kocher's approach, and coronoid process fractures were repaired with a single pulley double-strand suture technique. Structures were addressed in a sequential fashion-the coronoid process, radial head, lateral ulnar collateral ligament.All patients were treated with the single pulley double-strand anchor suture technique and the coronoid process fragment was found to be in good contact with the original avulsion site using the method. The final Mayo Elbow Performance Score was excellent (90) in six patients and good (between 85 and 89) in two patients after operation 6 months.The single pulley double-strand suture tie method using a suture anchor is a less invasive and simpler fixation method for the repair of coronoid process fractures in patients with terrible triad of the elbow injuries and results in good outcomes.

Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of death around the world. Bystander cardiopulmonary resuscitation (CPR) is an independent factor to improve OHCA survival. However, the prevalence of bystander CPR remains low worldwide. Community interventions such as mandatory school CPR training or targeting CPR training to family members of high-risk cardiac patients are possible strategies to improve bystander CPR rate. Real time feedback, hands-on practice with a manikin, and metronome assistance may increase the quality of CPR. Dispatcher-assistance and compression only CPR for untrained bystanders have shown to increase bystander CPR rate and increase survival to hospital discharge. After return of spontaneous circulation, targeted temperature management should be performed to improve neurological function. This review focuses on the impact of bystander CPR on clinical outcomes and strategies to optimize the prevalence and quality of bystander CPR.

Lung cancer is the leading cause of cancer-related mortality worldwide, and its tumorigenesis involves the accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic modifications, such as DNA methylation, RNA modification, and histone modifications, have been widely reported to play an important role in lung cancer development and in other pulmonary diseases. Whereas the functionality of DNA and chromatin modifications referred to as epigenetics is widely characterized, various modifications of RNA nucleotides have recently come into prominence as functionally important. N6-methyladosine (m6A) is the most prevalent internal modification in mRNAs, and its machinery of writers, erasers, and readers is well-characterized. However, several other nucleotide modifications of mRNAs and various noncoding RNAs have also been shown to play an important role in the regulation of biological processes and pathology. Such epitranscriptomic modifications play an important role in regulating various aspects of RNA metabolism, including transcription, translation, splicing, and stability. The dysregulation of epitranscriptomic machinery has been implicated in the pathological processes associated with carcinogenesis including uncontrolled cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In recent years, with the advancement of RNA sequencing technology, high-resolution maps of different modifications in various tissues, organs, or disease models are being constantly reported at a dramatic speed. This facilitates further understanding of the relationship between disease development and epitranscriptomics, shedding light on new therapeutic possibilities. In this review, we summarize the basic information on RNA modifications, including m6A, m1A, m5C, m7G, pseudouridine, and A-to-I editing. We then demonstrate their relation to different kinds of lung diseases, especially lung cancer. By comparing the different roles RNA modifications play in the development processes of different diseases, this review may provide some new insights and offer a better understanding of RNA epigenetics and its involvement in pulmonary diseases.

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.

Through forward multiple-event analysis of teleseismic P-waves using source time functions (STFs), derived by non-negative time-domain deconvolution, we inferred the rupture features of the 2018 Hualien earthquake. At least six sub-events composed the Hualien earthquake, with the largest one (corresponding to Mw = 6.3) occurring 4.8 s later than the initiation of rupture. The total seismic moment (M0) of 6.48 × 1018 Nm (Mw = 6.5) and radiated seismic energy (ES) of 1.76 × 1014 Nm led to the ES/M0 ratio ~2.72 × 10-5. A static stress drop (ΔσS) of 5.03 MPa was also derived for the earthquake. On average, the rupture parameters of the 2018 Hualien earthquake from this study were similar to globally average values. From M0 and source duration (10.9 s), this implied an average rupture velocity (Vr) less than 2.0 km s-1. The forward multiple-event modeling showed that ΔσS varied with the sub-events and increased with ES/M0 to imply the frictional strength being heterogeneous along the fault. From the highest STF peak (6.9 s after the initiation) near the land-sea interface, we suggested that the Hualien earthquake be divided into two rupture processes. One with low ΔσS, low ES/M0, and high Vr occurred at sea; the other with high ΔσS, high ES/M0, and low Vr occurred on land. Both seawater and local velocity structures probably played crucial factors behind these rupture discrepancies during the 2018 Hualien earthquake.

The pathogenesis and molecular mechanisms of ovarian low malignant potential (LMP) tumors or borderline ovarian tumors (BOTs) have not been fully elucidated to date. Surgery remains the cornerstone of treatment for this disease, and diagnosis is mainly made by histopathology to date. However, there is no integrated analysis investigating the tumorigenesis of BOTs with open experimental data. Therefore, we first utilized a functionome-based speculative model from the aggregated obtainable datasets to explore the expression profiling data among all BOTs and two major subtypes of BOTs, serous BOTs (SBOTs) and mucinous BOTs (MBOTs), by analyzing the functional regularity patterns and clustering the separate gene sets. We next prospected and assembled the association between these targeted biomolecular functions and their related genes. Our research found that BOTs can be accurately recognized by gene expression profiles by means of integrative polygenic analytics among all BOTs, SBOTs, and MBOTs, the results exhibited the top 41 common dysregulated biomolecular functions, which were sorted into four major categories: immune and inflammatory response-related functions, cell membrane- and transporter-related functions, cell cycle- and signaling-related functions, and cell metabolism-related functions, which were the key elements involved in its pathogenesis. In contrast to previous research, we identified 19 representative genes from the above classified categories (IL6, CCR2 for immune and inflammatory response-related functions, IFNG, ATP1B1, GAS6, and PSEN1 for cell membrane- and transporter-related functions, CTNNB1, GATA3, and IL1B for cell cycle- and signaling-related functions, and AKT1, SIRT1, IL4, PDGFB, MAPK3, SRC, TWIST1, TGFB1, ADIPOQ, and PPARGC1A for cell metabolism-related functions) that were relevant in the cause and development of BOTs. We also noticed that a dysfunctional pathway of galactose catabolism had taken place among all BOTs, SBOTs, and MBOTs from the analyzed gene set databases of canonical pathways. With the help of immunostaining, we verified significantly higher performance of interleukin 6 (IL6) and galactose-1-phosphate uridylyltransferase (GALT) among BOTs than the controls. In conclusion, a bioinformatic platform of gene-set integrative molecular functionomes and biophysiological pathways was constructed in this study to interpret the complicated pathogenic pathways of BOTs, and these important findings demonstrated the dysregulated immunological functionome and dysfunctional metabolic pathway as potential roles during the tumorigenesis of BOTs and may be helpful for the diagnosis and therapy of BOTs in the future.

5G networks have an efficient effect in energy consumption and provide a quality experience to many communication devices. Device-to-device communication is one of the key technologies of 5G networks. Internet of Things (IoT) applying 5G infrastructure changes the application scenario in many fields especially real-time communication between machines, data, and people. The 5G network has expanded rapidly around the world including in healthcare. Telemedicine provides long-distance medical communication and services. Patient can get help with ambulatory care or other medical services in remote areas. 5G and IoT will become important parts of next generation smart medical healthcare. Telemedicine is a technology of electronic message and telecommunication related to healthcare, which is implemented in public networks. Privacy issue of transmitted information in telemedicine is important because the information is sensitive and private. In this paper, 5G-based federated anonymous identity management for medical privacy protection is proposed, and it can provide a secure way to protect medical privacy. There are some properties below. (i) The proposed scheme provides federated identity management which can manage identity of devices in a hierarchical structure efficiently. (ii) Identity authentication will be achieved by mutual authentication. (iii) The proposed scheme provides session key to secure transmitted data which is related to privacy of patients. (iv) The proposed scheme provides anonymous identities for devices in order to reduce the possibility of leaking transmitted medical data and real information of device and its owner. (v) If one of devices transmit abnormal data, proposed scheme provides traceability for servers of medical institute. (vi) Proposed scheme provides signature for non-repudiation.

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought an unprecedented impact upon the global economy and public health. Although the SARS-CoV-2 virology has been gradually investigated, measures to combat this new threat in public health are still absent. To date, no certificated drug or vaccine has been developed for the treatment or prevention of coronavirus disease Extensive researches and international coordination has been conducted to rapidly develop novel vaccines against SARS-CoV-2 pandemic. Several major breakthroughs have been made through the identification of the genetic sequence and structural/non-structural proteins of SARS-CoV-2, which enabled the development of RNA-, DNA-based vaccines, subunit vaccines, and attenuated viral vaccines. In this review article, we present an overview of the recent advances of SARS-CoV-2 vaccines and the challenges that may be encountered in the development process, highlighting the advantages and disadvantages of these approaches that may help in effectively countering COVID-19.

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought an unprecedented impact upon the global economy and public health. Although the SARS-CoV-2 virology has been gradually investigated, measures to combat this new threat in public health are still absent. To date, no certificated drug or vaccine has been developed for the treatment or prevention of coronavirus disease Extensive researches and international coordination has been conducted to rapidly develop novel vaccines against SARS-CoV-2 pandemic. Several major breakthroughs have been made through the identification of the genetic sequence and structural/non-structural proteins of SARS-CoV-2, which enabled the development of RNA-, DNA-based vaccines, subunit vaccines, and attenuated viral vaccines. In this review article, we present an overview of the recent advances of SARS-CoV-2 vaccines and the challenges that may be encountered in the development process, highlighting the advantages and disadvantages of these approaches that may help in effectively countering COVID-19.

Lung cancer (LC) causes the majority of cancer-related deaths. Circular RNAs (circRNAs) were reported to play roles in cancers by targeting pro- and anti-oncogenic miRNAs. However, the mechanisms of circRNAs in LC progression and their prognostic value of treatment response remain unclear. By using next generation sequencing (NGS) of LC cell lines&rsquo, transcriptomes, we identified highly overexpressed hsa_circ_0000190 and hsa_circ_000164 as potential biomarkers. By using the highly sensitive RT-ddPCR method, these circRNAs were shown to be secreted by cell lines and were detected in human blood. Clinical validation by RT-ddPCR was carried out on 272 (231 LC patients and 41 controls) blood samples. Higher hsa_circ_0000190 levels were associated with larger tumor size (p &lt, 0.0001), worse histological type of adenocarcinoma (p = 0.0028), later stage (p &lt, 0.0001), more distant metastatic organs (p = 0.0039), extrathoracic metastasis (p = 0.0004), and poor survival (p = 0.047) and prognosis. Using liquid biopsy-based RT-ddPCR, we discovered the correlation between increased hsa_circ_0000190 plasma level (p &lt, 0.0001) and higher programmed death-ligand 1 (PD-L1) level in tumor (p = 0.0283). Notably, long-term follow-up of the immunotherapy treated cases showed that upregulated plasma hsa_circ_0000190 level correlated with poor response to systemic therapy and immunotherapy (p = 0.0002, 0.0058, respectively). Secretory circRNAs are detectable in blood by LB-based RT-ddPCR and may serve as blood-based biomarkers to monitor disease progression and treatment efficacy.

The fifth generation (5G) mobile network delivers high peak data rates with ultra-low latency and massive network capacity. Wireless sensor network (WSN) in Internet of Thing (IoT) architecture is of prominent use in 5G-enabled applications. The electronic healthcare (e-health) system has gained a lot of research attention since it allows e-health users to store and share data in a convenient way. By the support of 5G technology, healthcare data produced by sensor nodes are transited in the e-health system with high efficiency and reliability. It helps in reducing the treatment cost, providing efficient services, better analysis reports, and faster access to treatment. However, security and privacy issues become big concerns when the number of sensors and mobile devices is increasing. Moreover, existing single-server architecture requires to store a massive number of identities and passwords, which causes a significant database cost. In this paper, we propose a three-factor fast authentication scheme with time bound and user anonymity for multi-server e-health systems in 5G-based wireless sensor networks. In our work, the three-factor authentication scheme integrating biometrics, password, and smart card ensures a high-security sensor-enabled environment for communicating parties. User anonymity is preserved during communication process. Besides, time bound authentication can be applied to various healthcare scenarios to enhance security. The proposed protocol includes fast authentication, which can provide a fast communication for participating parties. Our protocol is also designed with multi-server architecture to simplify network load and significantly save database cost. Furthermore, security proof and performance analysis results show that our proposed protocol can resist various attacks and bear a rational communication cost.

Ovarian clear cell carcinoma (OCCC) is the second most common epithelial ovarian carcinoma (EOC). It is refractory to chemotherapy with a worse prognosis after the preliminary optimal debulking operation, such that the treatment of OCCC remains a challenge. OCCC is believed to evolve from endometriosis, a chronic immune/inflammation-related disease, so that immunotherapy may be a potential alternative treatment. Here, gene set-based analysis was used to investigate the immunofunctionomes of OCCC in early and advanced stages. Quantified biological functions defined by 5917 Gene Ontology (GO) terms downloaded from the Gene Expression Omnibus (GEO) database were used. DNA microarray gene expression profiles were used to convert 85 OCCCs and 136 normal controls into to the functionome. Relevant offspring were as extracted and the immunofunctionomes were rebuilt at different stages by machine learning. Several dysregulated pathogenic functions were found to coexist in the immunopathogenesis of early and advanced OCCC, wherein the complement-activation-alternative-pathway may be the headmost dysfunctional immunological pathway in duality for carcinogenesis at all OCCC stages. Several immunological genes involved in the complement system had dual influences on patients&rsquo, survival, and immunohistochemistrical analysis implied the higher expression of C3a receptor (C3aR) and C5a receptor (C5aR) levels in OCCC than in controls.

Hydrogels are widely used in tissue engineering owing to their high water retention and soft characteristics. It remains a challenge to develop hydrogels with tunable degradation rates, proper environmental responsiveness, and injectability. In this study, biodegradable difunctional polyurethane (DFPU) nanoparticle dispersions are synthesized from an eco‐friendly waterborne process involving the use of glyoxal. Such DFPU is used to crosslink chitosan (CS). Schiff base linkages between DFPU and CS successfully produce self‐healing hydrogels at room temperature. Moreover, cryogels are generated after being frozen at −20 °C. These gels are found to be sensitive to low pH and amine‐containing molecules owing to the property of Schiff bases. Furthermore, the degradation rates can be adjusted by the type of the component oligodiols in DFPU. Rheological evaluation verifies the excellent self‐healing properties (≈100% recovery after damage). Both the self‐healing gels and cryogels are injectable (through 26‐gauge and 18‐gauge needles, respectively) and biocompatible. Rat implantation at 14 d shows the low immune responses of cryogels. The functionalized biodegradable polyurethane nanoparticles represent a new platform of crosslinkers for biomacromolecules such as chitosan through the dynamic Schiff reaction that may give rise to a wide variety of self‐healing gels and cryogels for biomedical applications., A new biodegradable waterborne difunctional polyurethane (DFPU) crosslinker is obtained by modifying waterborne polyurethane (PU) with glyoxal. Adding the crosslinker to glycol chitosan (CS) produces CS‐PU self‐healing hydrogel at room temperature and generates CS‐PU cryogel after being temporally frozen at −20 °C. Both gels are featured with injectability (26‐gauge and 18‐gauge needles, respectively), multiresponsiveness, tunable degradation rates, good cell proliferation, and biocompatibility.

Accumulating evidence indicates that exercise can improve learning and memory as well as attenuate neurodegeneration, including Alzheimer’s disease (AD). In addition to improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates systems like angiogenesis and glial activation that are known to support neuroplasticity. Moreover, exercise helps to maintain a cerebral microenvironment that facilitates synaptic plasticity by enhancing the clearance of Aβ, one of the main culprits of AD pathogenesis. The purpose of this review is to highlight the positive impacts of exercise on promoting neuroplasticity. Possible mechanisms involved in exercise-modulated neuroplasticity are also discussed. Undoubtedly, more studies are needed to design an optimal personalized exercise protocol for enhancing brain function.

The present work develops an atomic layer reduction (ALR) method to accurately tune oxidation level, electrical conductance, band-gap structure, and photoluminescence (PL) response of graphene oxide (GO) sheets. The ALR route is carried out at 200 °C within ALR cycle number of 10–100. The ALR treatment is capable of striping surface functionalities (e.g., hydroxyl, carbonyl, and carboxylic groups), producing thermally-reduced GO sheets. The ALR cycle number serves as a controlling factor in adjusting the crystalline, surface chemistry, electrical, optical properties of GO sheets. With increasing the ALR cycle number, ALR-GO sheets display a high crystallinity, a low oxidation level, an improved electrical conductivity, a narrow band gap, and a tunable PL response. On the basis of the results, the ALR technique offers a great potential for accurately tune electrical and optical properties of carbon materials through the cyclic removal of oxygen functionalities, without any complicated thermal and chemical desorption processes.

Graphene sheets that can exhibit electrical conducting and semiconducting properties are highly desirable and have potential applications in fiber communications, photodetectors, solar cells, semiconductors, and broadband modulators. However, there is currently no efficient method that is able to tune the band gap of graphene sheets. This work adopts an efficient atomic layer oxidation (ALO) technique to cyclically increase the oxidation level of graphene sheets, thus, tuning their electrical conductance, band-gap structure, and photoluminescence (PL) response. The O/C atomic ratio as an increasing function of the ALO cycle number reflects two linear regions: 0.23% per cm2 per cycle (0-15 cycles) and 0.054% per cm2 per cycle (15-100 cycles). The excellent correlation coefficients reveal that the ALO process follows a self-limiting route to step-by-step oxidize graphene layers. The interlayer distance of ALO-graphene sheets shows an obvious increase after the ALO treatment, proved by X-ray diffraction. As analyzed by X-ray photon spectroscopy, the hydroxyl or epoxy group acts as a major contributor to the interlayer spacing distance and oxidation extent in the initial ALO stage, as compared to carbonyl and carboxyl groups. The ALO mechanism, based on Langmuir-Hinshelwood and Eley-Rideal models, is proposed to clarify the formation of oxygen functionalities and structural transformation from pristine graphene sheets to oxidized ones during the ALO cycle. With a tunable oxidation level, the electrical resistivity, semiconductor character, and PL response of ALO-graphene samples can be systematically controlled for desired applications. The ALO approach is capable of offering a straightforward route to tune the oxidation level of graphene sheets or other carbons.

In this study, amorphous MoO x films and Ag metal films were deposited on soda-lime glass via a sputtering system at room temperature. The experimental results indicate that MoO x films prepared with a 6% O 2 /Ar flow rate exhibit an amorphous phase with high transparency and an optical band gap of 2.7 eV. In-situ O 2 /Ar plasma was adopted to further modify the surface of the Ag mid-layer after deposition. This approach can enhance the visible transmittance of MoO x and Ag-based multilayers with the same sheet resistance. The polygrains oriented along the (111) and (200) directions in the inserted Ag thin films were adopted to supply carriers into the MoO x film and decrease the sheet resistance of the MoO x and Ag-based multilayer. The multilayer structure exhibited a sufficiently large Ag thickness (>10 nm), low resistance, and visible transmittance to serve as a transparent conductive electrode. The dependence of the Ag thickness, MoO x thickness, and plasma treatment time on the optical and electrical properties of Ag/MoO x and symmetric MoO x /Ag/MoO x were also explored. A figure of merit (FOM) of 5.3×10 −2 (Ω −1 ) was achieved at the visible wavelength of 550 nm for a MoO x /Ag/MoO x stacked layer with a 10-nm-thick Ag layer and a 30-nm-thick MoO 3 layer. Such a MoO x /Ag/MoO x stacked structure might be a promising electrode in potential applications of transparent conductive oxides.