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Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1–10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi‐quantitative reverse transcription polymerase chain reaction (sqRT‐PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)‐induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa‐B ligand (RANKL). CP also enhanced osteoblast proliferation in MG‐63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL‐induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis. [ABSTRACT FROM AUTHOR]

Dengue fever is an acute febrile disease caused by dengue virus (DENV) infection. Over the past 60 years, DENV has spread throughout tropical regions and currently affects more than 50% of the world's population; however, there are as of yet no effective anti‐DENV drugs for clinical treatment. A number of research teams have investigated derivatives of glycolipids as possible agents for the inhibition of DENV. Our objective in this research was to study the antiviral effects of trehalose 6‐caprate (TMC), trehalose 6‐monolaurate (TML), and trehalose 6‐monooleate (TMO), based on reports that the corresponding glycosyl, trehalose, reduces the transmission of Zika virus (ZIKV). We also sought to elucidate the molecular mechanisms underlying inhibition using the RNA isolation and reverse transcription‐quantitative polymerase chain reaction, western blot analysis, median tissue culture infectious dose (TCID50) assay, and immunofluorescence assay and immunochemistry staining, in vitro. This is the first study to demonstrate the TML‐induced inhibition of DENV serotype 2 (DENV‐2) in a dose‐dependent manner. The inhibitory effects of TML in the pretreated, cotreated, and full‐treated groups were confirmed using time of addition assays. We determined that TML restricted viral binding, entry, replication, and release. We also confirmed the efficacy of TML against three clinical isolates of DENV serotypes 1, 3, and 4 (DENV‐1, DENV‐3, and DENV‐4). The findings obtained in this study identify TML as a promising candidate for the development of drugs to treat DENV infection. [ABSTRACT FROM AUTHOR]

The impact of the type, purpose, and timing of prior surgery on heart transplantation (HT) remains unclear. This study investigated the influence of conventional cardiac surgery (PCCS) on HT outcomes. This study analyzed HTs performed between 1999 and 2019 at a single institution. Patients were categorized into two groups: those with and without PCCS. Short-term outcomes, including post-transplant complications and mortality rates, were evaluated. Cox proportional and Kaplan-Meier survival analyses were used to identify risk factors for mortality and assess long-term survival, respectively. Of 368 patients, 29% had PCCS. Patients with PCCS had a higher incidence of post-transplant complications. The in-hospital and 1 year mortality rates were higher in the PCCS group. PCCS and cardiopulmonary bypass time were significant risk factors for 1 year mortality (hazard ratios = 2.485 and 1.005, respectively). The long-term survival rates were lower in the PCCS group, particularly in the first year. In sub-analysis, patients with ischemic cardiomyopathy and PCCS had the poorest outcomes. The era of surgery and timing of PCCS in relation to HT did not significantly impact outcomes. In conclusion, PCCS worsen the HT outcomes, especially in patients with ischemic etiology. However, the timing of PCCS and era of HT did not significantly affect this concern. [ABSTRACT FROM AUTHOR]

The impact of the type, purpose, and timing of prior surgery on heart transplantation (HT) remains unclear. This study investigated the influence of conventional cardiac surgery (PCCS) on HT outcomes. This study analyzed HTs performed between 1999 and 2019 at a single institution. Patients were categorized into two groups: those with and without PCCS. Short-term outcomes, including post-transplant complications and mortality rates, were evaluated. Cox proportional and Kaplan-Meier survival analyses were used to identify risk factors for mortality and assess long-term survival, respectively. Of 368 patients, 29% had PCCS. Patients with PCCS had a higher incidence of post-transplant complications. The in-hospital and 1 year mortality rates were higher in the PCCS group. PCCS and cardiopulmonary bypass time were significant risk factors for 1 year mortality (hazard ratios = 2.485 and 1.005, respectively). The long-term survival rates were lower in the PCCS group, particularly in the first year. In sub-analysis, patients with ischemic cardiomyopathy and PCCS had the poorest outcomes. The era of surgery and timing of PCCS in relation to HT did not significantly impact outcomes. In conclusion, PCCS worsen the HT outcomes, especially in patients with ischemic etiology. However, the timing of PCCS and era of HT did not significantly affect this concern. [ABSTRACT FROM AUTHOR]

To date, most studies in scientometric map and track the main topics in a knowledge domain by measuring publications in core journals or keyword searches in databases. The present study instead proposes a novel metrics in which a knowledge domain is mapped and tracked via articles that cite the same openly accessible dataset. We retrieved 1,537 journal articles citing the National Longitudinal Study of Adolescent to Adult Health (Add‐Health) as the basis for an investigation of the major research topics associated with this dataset and how they evolved over time. To identify the primary research interests associated with the dataset, co‐word network modularity analysis was used. Another novel aspect of this study is that it juxtaposes the research topics identified by the co‐word approach with those generated by topic modeling: an approach that complements network modularity analysis, and allows for cross‐referencing between the results of these two methods. Keyness analysis was also performed to identify significant keywords in different time periods, which enables tracing of research interests in Add‐Health as they evolve. The methodological implications of using data citation as the basis for delineating a knowledge domain and techniques for its mapping are also discussed. [ABSTRACT FROM AUTHOR]

Health behaviors related to COVID-19 prevention measures, especially vaccination, are used to exemplify mechanisms whereby misinformation and disinformation can spark an "infodemic": a situation in which false information can spread more rapidly and widely than its truthful, science-based counterpart. We define key terminologies and identify potential sources that led to the pandemic infodemic, and highlight the harmful implications of such events. Issues related to scientific communication, how the public perceives information, and factors influencing individuals' decision-making are also discussed. This is the first in a series of two perspective articles on this topic. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: This study develops a conceptual framework and a series of instruments for capturing researchers' data-sharing practices in the social sciences, by synergizing the theory of knowledge infrastructure and the theory of remote scientific collaboration. Design/methodology/approach: This paper triangulates the results of three studies of data sharing across the social sciences, with 144 participants in total, and classifies the confusion, "frictions" and opportunities arising from such sharing into four overarching dimensions: data characteristics, technological infrastructure, research culture and individual drivers. Findings: Based on the sample, the findings suggest that the majority of faculty and students in social science research do not share their data because many of them are unaware of the benefits and methods of doing so. Additional findings regarding social scientists' data-sharing behaviors include: (1) those who do share qualitative data in data repositories are more likely to share their research tools than their raw data; and (2) perceived technical support and extrinsic motivation are both strong predictors of qualitative data sharing (a previously underresearched subtype of social science data sharing). Originality/value: The study confirms the previously hypothesized nature of "friction" in qualitative data sharing in the social sciences, arising chiefly from the time and labor intensiveness of ensuring data privacy. Peer review: The peer review history for this article is available at: https://publons.com/publon/10.1108/OIR-03-2020-0079. [ABSTRACT FROM AUTHOR]

Background: Active bloodstream infection (BSI) is a contraindication for heart transplantation (HT). However, some critical patients with BSI may undergo HT as a life‐saving procedure. We aimed to investigate the impact of pre‐transplant BSI on the clinical outcomes after HT. Methods: We enrolled 511 consecutive patients who underwent HT between 1999 and 2019. Patients were divided into two groups based on the presence of BSI within 30 days preoperatively. Forty‐three patients (8.4%) with BSI who were clinically stable and had no metastatic infection were considered for HT on an individual basis. In‐hospital mortality, incidence of early postoperative BSI, length of postoperative hospital stays, and long‐term survival were compared between the groups. Logistic and Cox regression analyses were performed to identify risk factors for in‐hospital and 1‐year mortality. Results: Patients with pre‐transplant BSI had a high incidence of previous cardiopulmonary resuscitation, pre‐transplant ventilator use, mechanical circulatory support use, renal replacement therapy, United Network for Organ Sharing status 1A, and a prolonged preoperative hospital waiting period. The in‐hospital mortality rate was higher in patients with pre‐transplant BSI (21% vs. 12%, p =.081), and the mortality rate was very high (33.3%) for those with BSI 0–15 days before HT. In addition, patients with pre‐transplant BSI had a significantly longer postoperative hospital stay than patients in the control group. However, long‐term survival was similar in both groups. Conclusions: Although pre‐transplant BSI was associated with higher in‐hospital mortality and prolonged postoperative hospital stay, patients who survived the early period had a similar long‐term prognosis. [ABSTRACT FROM AUTHOR]

Background: Emergency surgery for acute type A aortic dissection (AAAD) was usually avoided or denied in octogenarians because of high surgical mortality. Refined surgical techniques and improved postoperative care have led to an improved in‐hospital outcome. However, a significant number of operative survivors suffered from postoperative complications and had compromised quality of life. We sought to assess the clinical outcome of emergency surgery using a standard conservative approach in octogenarians with AAAD. Methods: From 2004 to 2021, 123 patients underwent emergency surgery for AAAD by one surgeon using a standard conservative approach with right subclavian artery cannulation, no aortic cross‐clamp, selective antegrade cerebral perfusion, moderate systemic hypothermia, reinforced sandwich technique, and a strategy of limited aortic resection. Hospital and late outcomes were assessed in patients with age >80 years. Results: Eighteen patients (15%) were octogenarians with seven males (39%) and median age of 82 years (range, 80–89). Hypertension was present in six patients (33%). None had diabetes mellitus, Marfan, or bicuspid aortic valve. Dissection was intramural hematoma in six (33%) and DeBakey type I in 15 patients (83%). Cardiac tamponade with shock was present in seven patients (39%). Ascending aortic grafting was performed in 17 patients, and additional hemiarch replacement in one patient. The hospital mortality rate was 17% (3/18). Fourteen patients (82%) were alive and well at discharge. Conclusions: Emergency surgery for AAAD using a standard conservative approach showed an improved outcome in octogenarians. The majority of patients could return home with an acceptable living. [ABSTRACT FROM AUTHOR]

End stage renal disease (ESRD) is a contraindication to isolated heart transplantation (HT). However, heart candidates with cardiogenic shock may experience acute kidney injury and require renal replacement therapy (RRT) and isolated HT as a life-saving operation. The outcomes, including survival and renal function, are rarely reported. We enrolled 569 patients undergoing isolated HT from1989 to 2018. Among them, 66 patients required RRT before HT (34 transient and 32 persistent). The survival was worse in patients with RRT than those without (65.2% vs 84.7%; 27.3% vs 51.1% at 1- and 10-year, p < 0.001 and p = 0.012, respectively). Multivariate Cox analysis identified pre-transplant hyperbilirubinemia (Hazard ratio (HR) 2.534, 95% confidence interval (CI) 1.098-5.853, p = 0.029), post-transplant RRT (HR 5.551, 95%CI 1.280-24.068, p = 0.022) and post-transplant early bloodstream infection (HR 3.014, 95%CI 1.270-7.152, p = 0.012) as independent risk factors of 1-year mortality. The majority of operative survivors (98%) displayed renal recovery after HT. Although patients with persistent or transient RRT before HT had a similar long-term survival, patients with persistent RRT developed a high incidence (49.2%) of dialysis-dependent ESRD at 10 years. In transplant candidates with pretransplant RRT, hyperbilirubinemia should be carefully reevaluated for the eligibility of HT whereas prevention and management of bloodstream infection after HT improve survival. [ABSTRACT FROM AUTHOR]

In this commentary, the authors, an international group data curation researchers and educators, reflect on some of the challenges and opportunities for data curation in the wake of the COVID‐19 pandemic. We focus on some topics of particular interest to the information science community: data infrastructures for scholarly communication and research, the politicization of data curation and visualization for public‐facing "dashboards," and human subjects research and policies. We conclude with some areas of opportunity and need, including broader and richer data curation education in the information schools, the establishment of better data management policy implementations by research funders, the award of formal academic credit for data curation activities and data sharing, and engagement in cooperative action around data ethics and security. [ABSTRACT FROM AUTHOR]

Shot peening is a widely used technique in aerospace to enhance the fatigue life of a part. However, it leads to an increased surface roughness, which necessitates an additional Vibropolishing technique to improve the fatigue life and aerodynamic efficiency. Alternatively vibratory peening, a relatively new technology, can replace both Shot peening and Vibropolishing and achieve similar fatigue life and aerodynamic efficiency. This paper reports the development of a novel smart vibratory peening system, using which several experimental investigations are conducted to characterize the part and validate them using the conventional Almen strips. Data from the experimental investigations are used to train a machine learning model and predict the characteristics of the given part and hence eliminating the use of Almen strips. With the help of the feature redundancy removal technique, 79% of the redundant features were removed to retain 94% of the process information. The results show that out of various established machine learning models, the Kernel Ridge model demonstrated the best performance with an RMSE of 0.0443. With the introduction of the smart vibratory peening system, the overall process time has been significantly reduced by 76%. • Introduced a novel smart vibratory peening system with 11 digital features, ensuring accurate predictions of Almen intensity while retaining 94% of process information. • Provided scientific insights into the mechanisms of smart vibratory peening process signature, including the high-frequency and low-amplitude media impacts. • Demonstrated the effectiveness of Kernel Ridge model with an RMSE of 0.0443, resulting in 79% reduction in process time by eliminating Almen peening. • Proposed a framework for integrating vibratory peening into smart factories, representing a step change in special process control. [ABSTRACT FROM AUTHOR]

Research transparency has been advocated as a key means of addressing the current crisis of reproducibility. This article proposes an enhanced form of research transparency, termed lifecycle transparency. Over the entire lifecycle of a research effort, this approach captures the syntactical contexts of artifacts and stakeholders, such as timestamps, agreements, and/or dependency requirements for completing each research phase. For example, such contexts might include when, where, and from whom patients' consent and institutional review board approvals were received before a clinical trial was carried out. However, as existing open-science tools are often dedicated to certain research phases or disciplines, and thus insufficient to support lifecycle transparency, we propose a novel decentralized framework to serve as a common medium for interaction among open-science tools, and produces irrefutable and immutable proofs of progress that can be verified automatically. [ABSTRACT FROM AUTHOR]

Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti‐inflammatory and antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal‐induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose‐dependent incubation by MTT assays, and expression levels of iNOS and COX‐2 proteins as well as secretion of IL‐1β were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co‐stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX‐2 and IL‐6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra‐articular injection rat model for gouty arthritis was utilized in which treatment groups received 5‐daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra‐articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal‐induced inflammation by suppressing the production of pro‐inflammatory cytokines and inflammatory mediators. Our findings that the anti‐inflammatory activities of AXT may be beneficial in the treatment of MSU crystal‐induced arthritis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive deterioration of articular cartilage. There have been reports that small molecule inhibitors have anti-osteoarthritis effects; however, the effects of 3-(4-chloro-2-fluorophenyl)-6-(2,4-difluorophenyl)-2 H -benzo[ e ] [1,3]oxazine-2,4(3 H)-dione (Cm -02) and 6-(2,4-difluorophenyl)-3-(3,4-difluorophenyl)-2 H -benzo[ e ] [1,3]oxazine-2,4(3 H)-dione (Ck -02), small molecule inhibitors which share many structural similarities with quercetin (a potent anti-inflammatory flavonoid), remain unclear. In this study, TNF-α-stimulated porcine and human chondrocyte models were used to investigate the inhibitory effects of Cm -02 and Ck -02 on the molecular mechanisms underlying the anti-OA effects. TNF-α was used to stimulate porcine and human chondrocytes to mimic immunomodulatory potency in-vitro. Anti-osteoarthritic effects were characterized in terms of protein and mRNA levels associated with the pathogenesis of OA. We also examined (1) the inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system in cultured chondrocytes, (2) matrix metalloproteinases (MMPs) in cultured chondrocytes, and (3) aggrecan degradation in cartilage explants. Finally, we tested the activation of nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), and activate the protein-1 (AP-1), and we tested the signal transduction and activation of transcription-3 (STAT-3). Our results indicate that, in chondrocytes, Cm -02 and Ck -02 inhibit TNF-α induced NO production, iNOS, MMP, the expression of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the enzyme activity of MMP-13. Furthermore, both Cm -02 and Ck -02 were found to stimulate TNF-α, which has been shown to suppress the activation of several transcription factors, including NF-κB, STAT-3, and IRF-1 in porcine and human chondrocytes. Cm -02 and Ck -02 were also found to help prevent the release of proteoglycans from cartilage explants. Our findings demonstrate that both Cm -02 and Ck -02 have potent anti-inflammatory activities and the ability to protect cartilage in an OA cell model. These findings indicate that Cm -02 and Ck -02 have the potential to be further developed for the therapeutic treatment of OA. • Cm -02 and Ck-02 inhibits the TNF-α induced NO production, iNOS, MMPs, and ADAMTS expression in chondrocytes. • Cm -02 and Ck-02 inhibit inflammatory mediators, including the activation of NF-κB, STAT-3, IRF-1. • Cm -02 and Ck-02 prevent proteoglycan release from cartilage explants. • Our observations suggest that Cm -02 and Ck-02 may be candidate small molecule inhibitors for the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

• There is a sex disparity of liver tumor progression and regression in Myc/xmrk transgenic zebrafish. • Male transgenic fish have faster liver tumor progression and slower tumor regression than females. • Androgen accelerates tumor progression in females and estrogen attenuates liver tumors in males. Hepatocellular carcinoma (HCC) shows clear sex disparity with men being more prone to developing HCC and having higher mortality than women. Previous studies have indicated that sex hormones play important roles in HCC initiation and development, but the effects of sex hormones on HCC in clinical trials remain inconsistent. Using zebrafish liver tumor model co-induced by oncogenes Myc and xmrk , we observed similar sex disparity between male and female zebrafish in liver tumor progression and regression; i.e. male Myc/xmrk transgenic zebrafish developed HCC significantly faster and regressed HCC significantly slower than female Myc/xmrk transgenic zebrtafish. To investigate the effects of sex hormones on liver tumor progression and regression, Myc/xmrk fish were treated with either androgen or estrogen, we observed that androgen promoted HCC progression and retarded HCC regression in females, while estrogen attenuated HCC progression and accelerated HCC regression in males. Furthermore, androgen promoted cell proliferation while estrogen inhibited it. Overall, the present study suggested that sex hormones affected liver tumor progression and regression in the Myc/xmrk transgenic zebrafish. [ABSTRACT FROM AUTHOR]

Abstract KRAS mutations are a major risk factor in colorectal cancers. In particular, a point mutation of KRAS of amino acid 12, such as KRAS V12 , renders it stable activity in oncogenesis. We found that kras V12 promotes intestinal carcinogenesis by generating a transgenic zebrafish line with inducible kras V12 expression in the intestine, Tg (ifabp:EGFP-kras V12 ). The transgenic fish generated exhibited significant increases in the rates of intestinal epithelial outgrowth, proliferation, and cross talk in the active Ras signaling pathway involving in epithelial-mesenchymal transition (EMT). These results provide in vivo evidence of Ras pathway activation via kras V12 overexpression. Long-term transgenic expression of kras V12 resulted in enteritis, epithelial hyperplasia, and tubular adenoma in adult fish. This was accompanied by increased levels of the signaling proteins p-Erk and p-Akt and by downregulation of the EMT marker E-cadherin. Furthermore, we also observed a synergistic effect of kras V12 expression and dextran sodium sulfate treatment to enhance intestinal tumor in zebrafish. Our results demonstrate that kras V12 overexpression induces intestinal tumorigenesis in zebrafish, which mimics intestinal tumor formation in humans. Thus, our transgenic zebrafish may provide a valuable in vivo platform that can be used to investigate tumor initiation and anticancer drugs for gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Chikungunya is a severe disease that results from infection with the chikungunya virus (CHIKV), an arbovirus. Thus, we (1) explored a new approach to combining previously researched drugs that have shown the potential to inhibit CHIKV infection; and (2) demonstrated the antiviral effects of (−)-Epigallocatechin-3-gallate (EGCG) and the underlying mechanisms. Specifically, we used U2OS cells infected with CHIVK to assess the synergistic antiviral activities of EGCG and suramin. EGCG presented the ability to inhibit the viral RNA, progeny yield, and cytopathic effect (CPE) of CHIKV and also demonstrated the ability to protect against virus entry, replication, and release. Moreover, the results confirmed that EGCG and suramin can have synergistic effects against CHIKV strain S27 infection and two other clinical isolates of CHIKV. Our findings suggest that treatment with a combination of EGCG and suramin could provide a basis for the development of novel stretages against CHIKV infection. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common autoimmune disease. Janus kinase inhibitors (JAKi) have been approved for the treatment of RA; however, the impact of JAKi on immune cells remains inconclusive. This study investigated the response of immune cells to JAKi treatment to identify biomarkers by which to evaluate and predict clinical outcomes. Blood samples were collected from RA patients before and after JAKi treatment for the analysis of immunophenotypes. Our results revealed that JAKi mainly inhibited Fas+ T cell subsets. The percentage changes of Th Fas+ and Naive Th Fas+ cells were positively correlated with the 28‐joint Disease Activity Score with erythrocyte sedimentation rate (DAS28‐ESR) values. Following treatment, moderate response (MR) RA patients presented a decrease in the number of Naive Th Fas+ cells (p = 0.0001). Initial percentages of 14 T cell and 20 B cell subsets were correlated with percentage changes in DAS28‐ESR. Overall, 16 cell subsets presented significant differences between the non‐response (NR) and MR groups. Excluding the multicollinearity of the immune cells, we constructed a JAKi treatment response prediction index (JRPI) using 5 subsets of T/B cells, the results of which were strongly correlated with percentage changes in DAS28‐ESR (receiver operating characteristic curve of 1). Note that the NR group was clearly distinguished from the MR group (p = 0.0167). In conclusion, the efficacy of JAKi can be attributed mainly to the suppression of Fas+ T cell subsets. A positive correlation was shown between the therapeutic efficacy of JAKi and the percentage changes in both Th Fas+ cells and Naive Th Fas+ cells. Furthermore, the proposed JRPI could potentially be used as an indicator to predict the efficacy of JAKi prior to treatment in RA patients. These findings may contribute to the development of personalized treatment strategies for RA patients using JAKi. [ABSTRACT FROM AUTHOR]

Despite numerous attempts to mitigate their spread, misinformation and disinformation are rampant on social media and other public networks, posing a substantial risk to public health and individual well-being. A concerted, multi-channel approach is required to effectively tackle this evolving problem. This paper outlines potential strategies and actionable plans to improve the response to misinformation and disinformation by stakeholders from various healthcare ecosystems. [ABSTRACT FROM AUTHOR]

In this paper, we present an epilepsy analysis system, referred to as EAS, for long-term electroencephalography (EEG) monitoring of patients with epilepsy. In our previous works, a high accuracy seizure detection algorithm had been devised. Six support vector machines (SVMs) had been trained to collaboratively classify EEG data into four types, i.e., normal, spike, sharp wave, and seizure. The EAS had initially extracted a total of 980 features from raw EEG data of patients, and then, for each SVM, it used a naïve genetic algorithm (GA) to determine a feature subset of the 980 features. However, the feature subsets still included some low-impact features for the EEG classification, and the training process of the seizure detector was time consuming. In this study, the GA is enhanced to further exclude low-impact features from the feature subsets and MapReduce parallel processing is adopted to speed up the training process. In the experiment, a 363-h clinical EEG records were acquired from 28 participants, 3 of which were normal, and 25 were patients with epilepsy. The experiment results show that average size of the feature subsets is reduced from 133.5 to 92.5 and the overall classification accuracy increases from 88.8 to 90.1 %. The new seizure detector processes a 10-s EEG record within 0.6 s, meaning that it meets the real-time requirement for online EEG monitoring gracefully. When the number of servers increases from 1 to 15, the training time of the detector is reduced from 38.3 to 4.9 h. Our new approach improves the EAS significantly. [ABSTRACT FROM AUTHOR]

The increasing popularity of academic social networking sites (ASNSs) requires studies on the usage of ASNSs among scholars and evaluations of the effectiveness of these ASNSs. However, it is unclear whether current ASNSs have fulfilled their design goal, as scholars' actual online interactions on these platforms remain unexplored. To fill the gap, this article presents a study based on data collected from ResearchGate. Adopting a mixed-method design by conducting qualitative content analysis and statistical analysis on 1,128 posts collected from ResearchGate Q&A, we examine how scholars exchange information and resources, and how their practices vary across three distinct disciplines: library and information services, history of art, and astrophysics. Our results show that the effect of a questioner's intention (i.e., seeking information or discussion) is greater than disciplinary factors in some circumstances. Across the three disciplines, responses to questions provide various resources, including experts' contact details, citations, links to Wikipedia, images, and so on. We further discuss several implications of the understanding of scholarly information exchange and the design of better academic social networking interfaces, which should stimulate scholarly interactions by minimizing confusion, improving the clarity of questions, and promoting scholarly content management. [ABSTRACT FROM AUTHOR]

Chikungunya disease results from an infection with the arbovirus, chikungunya virus (CHIKV). Symptoms of CHIKV include fever and persistent, severe arthritis. In recent years, several antiviral drugs have been evaluated in clinical trials; however, no registered antivirals have been approved for clinical therapy. In this study, we established a high-throughput screening (HTS) system based on CHIKV 26S mediated insect cell fusion inhibition assay. Our screening system was able to search potential anti-CHIKV drugs in vitro. Using this system, four compounds (niclosamide, nitazoxanide, niflumic acid, tolfenamic acid) were identified. These compounds were then further analyzed using a microneutralization assay. We determined that niclosamide and nitazoxanide exhibit ability to against CHIKV-induced CPE. The anti-CHIKV abilities of these compounds were further confirmed by RT-qPCR and IFA. Moreover, niclosamide and nitazoxanide were found to (1) limit virus entry, (2) inhibit both viral release and cell-to-cell transmission, and (3) possess broad anti-alphavius activities, including against two clinical CHIKV isolates and two alphaviruses: Sindbis virus (SINV) and Semliki forest virus (SFV). In conclusion, our findings suggested that niclosamide and nitazoxanide were able to inhibit CHIKV entry and transmission, which might provide a basis for the development of novel human drug therapies against CHIKV and other alphavirus infections. [ABSTRACT FROM AUTHOR]

Cabozantinib is an oral multikinase inhibitor that exhibits anti-tumor activity in several cancers. We found that cabozantinib was significantly cytotoxic to MV4-11 and Molm-13 cells that harbored FLT3-ITD, resulting in IC50 values of 2.4 nM and 2.0 nM, respectively. However, K562, OCI-AML3 and THP-1 (leukemia cell lines lacking FLT3-ITD) were resistant to cabozantinib, showing IC50 values in the micromolar range. Cabozantinib arrested MV4-11 cell growth at the G0/G1 phase within 24 h, which was associated with decreased phosphorylation of FLT3, STAT5, AKT and ERK. Additionally, cabozantinib induced MV4-11 cell apoptosis in a dose-dependent manner (as indicated by annexin V staining and high levels of cleaved caspase 3 and PARP-1), down-regulated the anti-apoptotic protein survivin and up-regulated the pro-apoptotic protein Bak. Thus, cabozantinib is selectively cytotoxic to leukemia cells with FLT3-ITD, causing cell-cycle arrest and apoptosis. In mouse xenograft model, cabozantinib significantly inhibited MV4-11 and Molm-13 tumor growth at a dosage of 10 mg/kg and showed longer survival rate. Clinical trials evaluating the efficacy of cabozantinib in acute myeloid leukemia (AML) with FLT3-ITD are warranted. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to report on an information gathering study on users’ research data-related challenges and proposals for library research data services (RDS). This study probes how early career researchers visually conceptualize the research process in their disciplines, their self-reported research data challenges, and their recommendations for library RDS. Design/methodology/approach – Two focus group sessions were undertaken with a total of eight early career researchers. Adopting the visual narrative inquiry method, the participants were asked to sketch the general research process in their domain. The individuals’ illustrations of the research process were then used as the basis for reflecting on their data-related needs and potential RDS that would assist them during the research process. Findings – Participants presented a research process that was more personal and, in most cases, more imperfect than the research lifecycle models that academic libraries are increasingly using for RDS development and communication. The authors present their data-related challenges, which included data access barriers, low knowledge of best practices for research data management, the need for a deeper understanding of post-publication impact, and inconsistent awareness of existing library and institution RDS. The authors outline RDS recommendations that participants proposed, which included a web-based tools, customized training sessions, and “distilled” guides to research data best practices. Practical implications – The study flagged users’ gaps in understandings of existing library and institutional RDS, suggesting that there may be an opportunity to engage users in the design of communications plans for services. The findings from this user study will inform the development of RDS at the institution. Originality/value – This paper puts forth a methodological approach that academic libraries can adapt for understanding users’ needs and user-generated design solutions. [ABSTRACT FROM AUTHOR]

Synchronized spontaneous neuronal activity is a characteristic feature of the developing brain. Rhythmic network discharges in the neonatal medial entorhinal cortex (mEC) in vitro depend on activation of ionotropic glutamate receptors, but spontaneously active neurons are required for their initiation. Field potential recordings revealed synchronized neuronal activity in the mEC in vivo developmentally earlier than in vitro. We suggested that not only ionotropic receptors, but also other components of the glutamatergic system modulate neuronal activity in the mEC. Ca imaging was used to record neuronal activity in neonatal murine brain slices. Two types of spontaneous events were distinguished: global synchronous discharges (synchronous activity) and asynchronously (not synchronized with global discharges) active cells (asynchronous activity). AMPA receptor blockade strongly reduced the frequency of synchronous discharges, while NMDA receptor inhibition was less effective. AMPA and NMDA receptor blockade or activation of group 2/3 metabotropic glutamate receptors (mGluR2/3) completely suppressed synchronous discharges and increased the number of active cells. Blockade of glutamate transporters with dl-TBOA led to NMDA receptor-mediated hyper-synchronization of neuronal activity. Inhibition of NMDA receptors in the presence of dl-TBOA failed to restore synchronous discharges. The latter were partially reestablished only after blockade of mGluR2/3. We conclude that the glutamatergic system can influence neuronal activity via different receptors/mechanisms. As both NMDA and mGluR2/3 receptors have a high affinity for glutamate, changes in extracellular glutamate levels resulting for instance from glutamate transporter malfunction can balance neuronal activity in the mEC, affecting in turn synapse and network formation. [ABSTRACT FROM AUTHOR]

Branchial Na ＋ -K ＋ -ATPase (NKA) activity has been suggested as a promising biomarker for assessing metal stress in aquatic organisms. However, studies that systematically show the effectiveness of using NKA activity to detect metal exposure and toxicity at the individual level are limited. In this study, we aimed to determine whether branchial NKA activity mechanistically responds to the accumulation of waterborne copper (Cu) and accounts for observed toxicity over time under environmentally-relevant and aquafarming Cu exposure levels (0.2, 1 and 2 mg L −1 ). Temporal trends in Cu accumulation and the corresponding responses of branchial NKA activity resulting from Cu exposure were investigated in laboratory experiments conducted on juvenile tilapia ( Oreochromis mossambicus ), a freshwater teleost that shows potential as a bioindicator of real-time and historical metal pollution. We used the process-based damage assessment model (DAM) to inspect the time course of Cu toxicity by integrating the compensation process between Cu-induced inhibition and repair of branchial NKA activity. NKA activity acted as a sensitive biomarker for Cu exposure and accumulation in tilapia, which showed induced impairment of osmoregulation and lethality when they were exposed to environmentally relevant levels (0.2 mg L −1 ), but not to higher exposure levels (1 and 2 mg L −1 ) in aquaculture farms or contaminated aquatic ecosystems. This study highlights the benefits and limitations of using branchial NKA activity as a sensitive biomarker to assess the health status of a fish population and its ecosystem. [ABSTRACT FROM AUTHOR]

Myeloid malignancies are heterogeneous disorders characterized by uncontrolled proliferation or/and blockage of differentiation of myeloid progenitor cells. Although a substantial number of gene alterations have been identified, the mechanism by which these abnormalities interact has yet to be elucidated. Over the past decades, zebrafish have become an important model organism, especially in biomedical research. Several zebrafish models have been developed to recapitulate the characteristics of specific myeloid malignancies that provide novel insight into the pathogenesis of these diseases and allow the evaluation of novel small molecule drugs. This report will focus on illustrative examples of applications of zebrafish models, including transgenesis, zebrafish xenograft models, and cell transplantation approaches, to the study of human myeloid malignancies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine JMJD2B expression in human hepatocellular carcinoma (HCC) and elucidate relationships between various expression patterns and clinicopathological parameters of HCC patients. Immunohistochemical techniques were performed to detect JMJD2B expression in a tissue microarray from patients with breast, cerebrum, colon, esophagus, kidney, liver, lung, prostate, stomach, and uterus cancers. We performed immunohistochemical staining of a multiple tissue array to examine the expression profile of JMJD2B. Our results demonstrate that JMJD2B protein levels were upregulated in malignant human tumors, including breast, colon, liver, and lung. Immunohistochemistry staining examination of liver tumor tissue microarray revealed that the expression of JMJD2B is significant according to the histological grade and TNM stage of liver tumor. Moreover, JMJD2B was also correlated with Ki-67 expression in HCC samples. These results reveal that JMJD2B is dramatically upregulated in HCC, making it a potential diagnostic marker for the further development of HCC treatment therapies. [ABSTRACT FROM AUTHOR]

Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/ SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis. [ABSTRACT FROM AUTHOR]

Background and Aim Suture line dehiscence and pseudoaneurysm formation is one of the leading causes of late reoperation after surgical repair of acute type A aortic dissection (AAD). A sandwich technique can affect the need of reoperation. We sought to assess the late outcomes (mortality and reoperation) of a modified reinforced sandwich technique in conventional AAD repair. Methods Retrospective review of 63 consecutive patients undergoing AAD repair between 2003 and 2013. Aortic anastomosis was performed with a modified reinforced sandwich technique using Hemashield strips and two-layer polypropylene continuous and interrupted mattress sutures. Results Marfan syndrome was diagnosed in five (8%) and bicuspid aortic valve in three patients (5%). Twenty-one patients (33%) had preoperative cardiogenic shock necessitating inotropic support. Replacement of the ascending aorta with aortic valve preservation was performed in 58 (92%) and hemiarch replacement in five patients (8%). Four patients died during initial hospitalization, yielding a hospital mortality of 6%. Median follow-up duration was 73 months (range, 1-124). Kaplan-Meier survival rates were 94 ± 3%, 84 ± 5%, and 59 ± 11% at 1, 5, and 10 years. One patient (1.7%) required proximal reoperation 44 months after AAD repair because of progressive dilatation of the aortic root. No patient had severe aortic regurgitation or pseudoaneurysm after AAD repair. Actuarial freedom from reoperation at 1, 5, and 10 years was 100%, 97%, and 97%. Conclusions A reinforced sandwich technique was a good technique resulting in a low incidence of late reoperation and pseudoaneurysm formation. doi: 10.1111/jocs.12359 (J Card Surg 2014;29:641-646) [ABSTRACT FROM AUTHOR]

Hepatocarcinogenesis commonly involves the gradual progression from hepatitis to fibrosis and cirrhosis, and ultimately to hepatocellular carcinoma (HCC). Endothelin 1 (Edn1) has been identified as a gene that is significantly up-regulated in HBx-induced HCC in mice. In this study, we further investigated the role of edn1 in hepatocarcinogenesis using a transgenic zebrafish model and a cell culture system. Liver-specific edn1 expression caused steatosis, fibrosis, glycogen accumulation, bile duct dilation, hyperplasia, and HCC in zebrafish. Overexpression of EDN1 in 293T cells enhanced cell proliferation and cell migration in in vitro and xenotransplantation assays and was accompanied with up-regulation of several cell cycle/proliferation- and migration-specific genes. Furthermore, expression of the unfolded protein response (UPR) pathway-related mediators, such as spliced XBP1, ATF6, IRE1, and PERK, was also up-regulated at both the RNA and protein levels. In the presence of an EDN1 inhibitor or an AKT inhibitor, these increases were diminished and the EDN1-induced migration ability also was disappeared, suggesting that the EDN1 effects act through activation of the AKT pathway to enhance the UPR and subsequently activate the expression of downstream genes. Additionally, p-AKT is enhanced in the edn1 transgenic fish compared to the GFP-mCherry control. The micro RNA miR-1 was found to inhibit the expression of EDN1. We also observed an inverse correlation between EDN1 and miR-1 expression in HCC patients. In conclusion, our data suggest that EDN1 plays an important role in HCC progression by activating the PI3K/AKT pathway and is regulated by miR-1. [ABSTRACT FROM AUTHOR]

Abstract: Aflatoxin B1 (AFB1) and the hepatitis B virus X antigen (HBx) are linked to the formation of liver diseases and hepatocellular carcinoma (HCC). The aim of this study was to investigate the synergistic effects between HBx and AFB1 in causing liver disorders using a transgenic zebrafish animal model. Histopathology, Periodic acid-Schiff (PAS) staining, Sirius red staining, TdT-mediated dUTP Nick End Labeling (TUNEL) assay, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) were used to examine the livers of the HBx transgenic fish injected with AFB1. We found that HBx and AFB1 synergistically promoted steatosis as indicated by histopathological examinations and the increased expression of lipogenic factors, enzymes, and genes related to lipid metabolism. Moreover, treatment of AFB1 in HBx transgenic fish accelerated the development of liver hyperplasia and enhanced the expression of cell cycle related genes. PCNA was co-localized with active caspase 3 protein expression in HBx zebrafish liver samples and human HBV positive HCC samples by double fluorescence immunostaining. Finally, we found that in human patients with liver disease, significant glycogen accumulated in the inflammation, cirrhosis stage, and all cases of hepatocellular and cholangiocellular carcinoma showed a moderate cytoplasmic accumulation of glycogen. Our data demonstrated a synergistic effect of AFB1 and HBx on the regulation of lipid metabolism related genes and cell cycle/division-related genes which might contribute to enhanced steatosis and hyperplasia at 5.75months. [Copyright &y& Elsevier]

Zika virus (ZIKV) has been the cause of some epidemics since 2007. The correlations of microcephaly and Guillain–Barré syndrome with ZIKV have been noticed. Unfortunately, researchers have yet to develop an effective vaccine or drug approved for ZIKV infection. Anidulafungin is a member of echinocandins that is used to treat candida infections. This study assessed the antiviral capability of anidulafungin against ZIKV. Anidulafungin was shown to significantly decrease viral RNA levels, protein expression levels, viral yields, and the rate of infection. In time of addition assays, anidulafungin exhibited inhibitory activities in the early stages of ZIKV infection. In binding and entry assays, administering anidulafungin did not lead to a corresponding decrease in quantity of viral RNA, but a significant decrease in ZIKV infectivity was observed in virucidal assays. This indicated that anidulafungin interferes directly with virions. T-1105 is a viral polymerase inhibitor, which functions in the late stage of ZIKV infection. When anidulafungin was administered in combination with T-1105, an obvious synergistic effect was observed, resulting in a combination index (CI) value of 0.85 ± 0.13. Finally, we evaluated the effects of echinocandins in terms of half-maximal inhibitory concentration (IC 50), calculation of cytotoxicity concentration 50% (CC 50), selectivity index (SI), and Patchdock score. Among the tests, anidulafungin bears the lowest IC 50 and highest Patchdock score. Although anidulafungin is classified as a pregnancy category C agent; however, combination therapy of anidulafungin with a viral RNA replication inhibitor could expand treatment options for ZIKV infection. • Anidulafungin is a new anti-ZIKV agent via direct virucidal effect. • Anidulafungin and T-1105 possess synergistic anti-ZIKV activity. • Echinocandins all reduced ZIKV infection and were predicted to bind with envelope binding. [ABSTRACT FROM AUTHOR]

Proteolytic fragments of fibronectin can have catabolic effects on cartilage, menisci, and synovium. Previous studies have reported that Toll-like receptor (TLR) signaling pathways might be associated with joint inflammation and joint destruction. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions; however, it has yet to be determined whether PRP influences fibronectin fragment (FN-f) procatabolic activity and TLRs. In this study, human primary culture cells were treated with 30 kDa FN-f with/without PRP co-incubation, and then analyzed using real-time PCR to determine gene expression levels in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts. Protein levels were evaluated by Western immunoblotting. This study observed an increase in the protein expression of matrix metalloproteinases (MMPs), Toll-like receptor 2 (TLR2), nitric oxide synthase 2 (NOS2), prostaglandin-endoperoxide synthase (PTGS2), and cyclooxygenase 2 (COX2) in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts following insult with 30 kDa FN-f. Upregulation of these genes was significantly attenuated by PRP treatment. TLR2 and matrix metalloproteinase 13 (MMP-13) were also significantly attenuated by cotreatment with 30 kDa FN-f + PRP + TLR2 inhibitor. PRP treatment was shown to attenuate the 30 kDa FN-f-induced MMP-13 expression associated with the decreased expression of TLR2 in osteoarthritic chondrocytes and synovial fibroblasts. PRP treatment was also shown to attenuate procatabolic activity associated with MMP-13 expression via the TLR2 signaling pathway. [ABSTRACT FROM AUTHOR]

Highlights: [•] Undesired properties of NH4NO3 were minimized by co-crystal formation. [•] Spherical crystallization was employed to enhance the flowability of co-crystals. [•] Co-crystals were smokeless upon heating and exhibited a slower burning rate. [ABSTRACT FROM AUTHOR]