Paired Box 5 (PAX5) Gene Has Diagnostic and Prognostic Potential in Nasopharyngeal Carcinoma.

Purpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC. Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis. Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice. Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.

Investigation of personal data protection mechanism based on blockchain technology.

Blockchain technology is increasingly being used in personal data protection. Inspired by the importance of data security, this paper proposes a personal data protection mechanism based on blockchain, combined with distributed hash tables and cryptography, to enhance users' control over the data generated using web applications. This paper designs this mechanism's system model and describes the three aspects in detail: data storage mechanism, data encryption mechanism, and data trading mechanism. Among them, the data storage mechanism restricts user data to be stored only in the local storage space of the user terminal, the decentralized blockchain network, and the distributed hash table network to ensure that enterprises providing network applications cannot privately store user interaction data, the encryption mechanism is responsible for encrypting all user data recorded in the network and allows users to control the key of the data to ensure the security of the user data in the blockchain and distributed hash tables, the data transaction mechanism allows users to trade their data, and to incentivize enterprises to assist users in collecting personal data, data transaction contracts are built into the data transaction mechanism, allowing enterprises to receive a share of the revenue from user data transactions. Then, for data transactions, use the Stackelberg game to simulate the revenue sharing between users and service providers in data trading to incentivize enterprises providing web services to assist users in collecting their data. The simulation results show that when the number of users is 1000, the revenues of this scheme for service providers are 31%, 561%, and 19% higher than the existing scheme. Finally, the personal data protection platform is implemented by code to verify the feasibility of the theory proposed in this paper in personal data protection.

The single pregnancy predicting model of 1 minute Apgar score less than 7 after preterm birth: A retrospective study.

Preterm delivery is greatly associated with perinatal mortality and morbidity, while there is no objective way to identify high-risk newborns currently. This study aimed at discovering the risk factor for Apgar score less than 7 at 1 minute of preterm neonates born with vaginal delivery. A retrospective study was performed in single pregnancy women with a vaginal delivery before 37 weeks of gestation. All the preterm infants were categorized into three types: very preterm birth (28 to 32 weeks), moderate preterm birth (32 to 34 weeks) and late preterm birth (34 to 37 weeks). Risk factors were identified through logistic regression analysis in every category of newborns mentioned above. And the receiver operating characteristic analysis was used in continuous variables to determine the best threshold of the outcome. On the basis of the selected factors, the predicting models are created and its prognosticating ability is compared by the area under the curve. A nomogram was established for the proved best model. A total of 981 cases were investigated, of whom 55 were found with 1 min Apgar scores less than 7. The nomogram was set for the predicting model with larger area under the receiver operating characteristic curve, of which is 0.742(95% confidence interval = 0.670-0.805) in very preterm birth, with the variables of first and second labor stage(> = 1.6 hours), birthweight and MgSO4(magnesium sulfate), and is 0.807(95% confidence interval = 0.776-0.837) in late preterm birth, with the variables of second labor stage(> = 1.23 hours), birthweight, a history of previous cesarean delivery, fetal distress and placental abruption. The combination of first and second labor stage, newborn weight and MgSO4 use can predict 74.2% of 1 minute Apgar score < 7 in very preterm neonates. And 80.7% high-risk infants can be identified when second labor stage, newborn weight, VBAC (vaginal birth after cesarean) and the occur of placental abruption and fetal distress were combined in the predicting model for late preterm birth. These predicting models would bring out great assistance towards obstetricians and reduce unnecessary adverse fetal outcomes.

Risk Factors for Dental Caries Experience in Children and Adolescents with Cerebral Palsy-A Scoping Review.

Cerebral palsy is a developmental motor disorder which has far-reaching impacts on oral health. This scoping review examined the extent of research undertaken regarding the risk factors affecting dental caries experience in children and adolescents with cerebral palsy. Data were obtained from the electronic databases Web of Science and PubMed, using 10 search strings, for studies published between 1983 and 2018. Eligible studies were required to have investigated caries in children under 18 with cerebral palsy, as well as be written in English. 30 papers published were identified for inclusion in the review. These included 23 cross-sectional, 6 case-control, and 1 longitudinal study. Studies were categorized into six domains of risk factors: socioeconomic status (SE); cerebral palsy subtype (CPS); demographics (D); condition of oral cavity (OC); dental habits (DH); nutrition and diet (ND). This review was conducted and reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. The most significant risk factors were caregiver-related education levels, oral health literacy, and sugar intake; this underlines the important role of special education and dental awareness in reducing dental caries incidence in CP children. Other factors showed divergent findings, highlighting the need for standardization and culturally specific studies in future literature.

Learning Agility of Learning and Development Professionals in the Life Sciences Field During the COVID-19 Pandemic: Empirical Study.

BACKGROUND: The COVID-19 pandemic has impacted the life sciences field worldwide. Life sciences organizations (eg, pharmaceutical and med-tech companies) faced a rapidly increasing need for vital medical products, patient support, and vaccine development. Learning and development (L&D) departments play a crucial role in life sciences organizations as they apply learning initiatives to organizational strategy within a constantly evolving sector. During the COVID-19 pandemic, the work of L&D professionals in life sciences organizations changed profoundly during the abrupt shift to remote work, since learning and training normally occur in a face-to-face environment. Given the complex and dynamic situation of the pandemic, both individuals and organizations needed to learn quickly and apply what they learned to solve new, unprecedented problems. This situation presents an opportunity to study how characteristics of learning agility were evidenced by life sciences organizations and individual employees in the remote working mode. OBJECTIVE: In collaboration with Life Sciences Trainers & Educators Networks (LTEN), this study investigated the responses and learning agility of L&D professionals and their organizational leadership within the life sciences sector to the work changes due to the pandemic. The study answered the following questions: (1) How did L&D professionals in the life sciences sector respond to the changes in their work environment during the COVID-19 pandemic? (2) How did L&D professionals in the life sciences sector demonstrate learning agility during remote working? METHODS: We adopted a mixed methods approach that included a semistructured interview and a survey. Participants who were life sciences or health care L&D practitioners and in relevant positions were recruited via email through the LTEN and its partner pharmaceutical, biotech, or medical devices organizations. Interviews with 12 L&D professionals were conducted between June and August 2020 through phone or online conferencing, covering 22 open-ended questions to stimulate ideas that could be explored further in the survey. The semistructured interview questions were grounded in theory on learning agility. In total, 4 themes were developed from the interviews, which formed the basis for developing the survey items. The subsequent survey regarding 4 specific themes was conducted from August to October 2020 using Qualtrics. Both interview and survey data were analyzed based on a learning agility framework. RESULTS: Findings revealed generally positive organizational and individual responses toward the changes brought about by the pandemic. Results also indicated that a disruptive crisis, such as the shift from working in the office to working from home (WFH), required professionals' learning agility to both self-initiate their own learning and to support the learning agility of others in the organization. CONCLUSIONS: This study was designed to better understand education and training in the life sciences field, particularly during the unique circumstances of the global COVID-19 pandemic. We put forward several directions for future research on the learning agility of L&D professionals in life sciences organizations.

Mapping and application of enhancer-trap flippase expression in larval and adult Drosophila CNS.

The Gal4/ UAS binary method is powerful for gene and neural circuitry manipulation in Drosophila. For most neurobiological studies, however, Gal4 expression is rarely tissue-specific enough to allow for precise correlation of the circuit with behavioral readouts. To overcome this major hurdle, we recently developed the FINGR method to achieve a more restrictive Gal4 expression in the tissue of interest. The FINGR method has three components: 1) the traditional Gal4/UAS system; 2) a set of FLP/FRT-mediated Gal80 converting tools; and 3) enhancer-trap FLP (ET-FLP). Gal4 is used to define the primary neural circuitry of interest. Paring the Gal4 with a UAS-effector, such as UAS-MJD78Q or UAS-Shi(ts), regulates the neuronal activity, which is in turn manifested by alterations in the fly behavior. With an additional UAS-reporter such as UAS-GFP, the neural circuit involved in the specific behavior can be simultaneously mapped for morphological analysis. For Gal4 lines with broad expression, Gal4 expression can be restricted by using two complementary Gal80-converting tools: tub(P)>Gal80> ('flip out') and tub(P)>stop>Gal80 ('flip in'). Finally, investigators can turn Gal80 on or off, respectively, with the help of tissue-specific ET-FLP. In the flip-in mode, Gal80 will repress Gal4 expression wherever Gal4 and ET-FLP intersect. In the flip-out mode, Gal80 will relieve Gal4 repression in cells in which Gal4 and FLP overlap. Both approaches enable the restriction of the number of cells in the Gal4-defined circuitry, but in an inverse pattern. The FINGR method is compatible with the vast collection of Gal4 lines in the fly community and highly versatile for traditional clonal analysis and for neural circuit mapping. In this protocol, we demonstrate the mapping of FLP expression patterns in select ET-FLPx2 lines and the effectiveness of the FINGR method in photoreceptor cells. The principle of the FINGR method should also be applicable to other genetic model organisms in which Gal4/UAS, Gal80, and FLP/FRT are used.

Comparison of the protective effects of truncated bFGF and native bFGF against murine lung carcinoma.

Basic fibroblast growth factor (bFGF), an angiogenic factor, exhibits pro-angiogenic abilities by interacting with tyrosine kinase receptors and heparin-sulfated proteoglycan receptors. Here, we designed an N-, C-terminally truncated basic fibroblast growth factor (tbFGF) for immuno-therapy of murine lung carcinoma with PCEC hydrogel as adjuvant, comparing it with the wild-type bFGF. In vitro, tbFGF did not stimulate NIH-3T3 fibroblast proliferation. In vivo, after immunization, both tbFGF and bFGF were able to induce a robust bFGF-specific immune response. The protective anti-tumor investigation showed a significant inhibition of tumor growth and reduction of tumor vascularization detected by immunohistochemical staining and the alginate-encapsulated tumor cell assay in the tbFGF or the bFGF group. These data suggested that tbFGF can be used in the immunotherapy of tumors, without the risks associated with bFGF, which induces neovascularization in normal tissues.

Biodegradable thermosensitive injectable PEG-PCL-PEG hydrogel for bFGF antigen delivery to improve humoral immunity.

In this contribution, a biodegradable and injectable thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel system was successfully prepared for basic fibroblastic growth factor (bFGF) antigen delivery. bFGF encapsulated PECE hydrogel system (bFGF-hydrogel) is an injectable free-flowing sol at ambient temperature, and forms a non-flowing gel at physiological temperature acting as antigen depot. Furthermore, the cytotoxicity results showed that the PECE hydrogel could be regarded as a safe carrier, and bFGF could be released from the hydrogel system in an extended period in vitro. Otherwise, the immunogenicity of bFGF was improved significantly after encapsulated into the hydrogel. Strong humoral immunity created by bFGF-hydrogel was maintained for more than 14 weeks. Therefore, the prepared bFGF loaded PECE hydrogel might have great potential as a novel vaccine adjuvant for protein antigen.

Poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) nanoparticles for honokiol delivery in vitro.

In this article, poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles were successfully prepared for honokiol delivery in vitro. Blank or honokiol loaded PCL-PEG-PCL nanoparticles were prepared in moderate condition by solvent diffusion method without using any surfactants. The prepared blank PCL-PEG-PCL nanoparticles are mono-dispersed and smaller than 200 nm. The particle size increased with increase in polymer concentration and oil-water (O/W) ratio. The prepared PCL-PEG-PCL nanoparticles (40 mg/mL, ca. 106 nm) did not induce hemolysis in vitro. And the 50% inhibiting concentration (IC50) of it (48 h) on HEK293 cells was higher than 5 mg/mL. Honokiol could be efficiently loaded into PCL-PEG-PCL nanoparticles and released from these nanoparticles in an extended period in vitro. After honokiol (HK) was entrapped into PCL-PEG-PCL nanoparticles, the particle size increased with the increase in HK/PCEC mass ratio in feed, and the encapsulated honokiol retained potent anticancer activity in vitro. The PCL-PEG-PCL nanoparticle was suitable for honokiol delivery, and such honokiol loaded PCL-PEG-PCL nanoparticle was a novel honokiol formulation.