Differential early diagnosis of benign versus malignant lung cancer using systematic pathway flux analysis of peripheral blood leukocytes

Early diagnosis of lung cancer is critically important to reduce disease severity and improve overall survival. Newer, minimally invasive biopsy procedures often fail to provide adequate specimens for accurate tumor subtyping or staging which is necessary to inform appropriate use of molecular targeted therapies and immune checkpoint inhibitors. Thus newer approaches to diagnosis and staging in early lung cancer are needed. This exploratory pilot study obtained peripheral blood samples from 139 individuals with clinically evident pulmonary nodules (benign and malignant), as well as ten healthy persons. They were divided into three cohorts: original cohort (n = 99), control cohort (n = 10), and validation cohort (n = 40). Average RNAseq sequencing of leukocytes in these samples were conducted. Subsequently, data was integrated into artificial intelligence (AI)-based computational approach with system-wide gene expression technology to develop a rapid, effective, non-invasive immune index for early diagnosis of lung cancer. An immune-related index system, IM-Index, was defined and validated for the diagnostic application. IM-Index was applied to assess the malignancies of pulmonary nodules of 109 participants (original + control cohorts) with high accuracy (AUC: 0.822 [95% CI: 0.75–0.91, p < 0.001]), and to differentiate between phases of cancer immunoediting concept (odds ratio: 1.17 [95% CI: 1.1–1.25, p < 0.001]). The predictive ability of IM-Index was validated in a validation cohort with a AUC: 0.883 (95% CI: 0.73–1.00, p < 0.001). The difference between molecular mechanisms of adenocarcinoma and squamous carcinoma histology was also determined via the IM-Index (OR: 1.2 [95% CI 1.14–1.35, p = 0.019]). In addition, a structural metabolic behavior pattern and signaling property in host immunity were found (bonferroni correction, p = 1.32e − 16). Taken together our findings indicate that this AI-based approach may be used for “Super Early” cancer diagnosis and amend the current immunotherpay for lung cancer

Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China

Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60~years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47~years, interquartile range IQR 38-55, range 18-60; 55.9{\%} female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5{\%}) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p {\textless} 0.001). The uni- and multivariable analysis suggested that several covariates such as elevated levels of serum amyloid A (SAA), C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased lymphocyte counts influence disease severity independently of age. Elevated levels of complement C3 (odds ratio OR 15.6, 95{\%} CI 2.41-122.3; p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients

Flexible Tactile Sensor Array Based on Aligned MWNTs-PU Composited Sub-Microfibers

This present paper describes a novel method to fabricate tactile sensor arrays by producing aligned multi-walled carbon nanotubes (MWNTs)-polyurethane (PU) composite sub-microfiber (SMF) arrays with the electrospinning technique. The proposed sensor was designed to be used as the artificial skin for a tactile sensation system. Although thin fibers in micro- and nanoscale have many good mechanical characteristics and could enhance the alignment of MWNTs inside, the high impedance as a consequence of a small section handicaps its application. In this paper, unidirectional composite SMFs were fabricated orthogonally to the parallel electrodes through a low-cost method to serve as sensitive elements (SEs), and the impedances of SEs were measured to investigate the changes with deformation caused by applied force. The particular piezoresistive mechanism of MWNTs disturbed in SMF was analyzed. The static and dynamic test results of the fabricated tactile sensor were also presented to validate the performance of the proposed design

Publics' communication on controversial sociopolitical issues: extending the situational theory of problem solving

Capturing a unique moment within a particularly volatile political climate where various issues such as climate change, immigration, and healthcare are increasingly polarized, this survey examines the factors driving publics' engagement in and disengagement from communication on controversial sociopolitical issues. It applies and expands the situational theory of problem solving (STOPS) by integrating the theoretical insights from the literature of information omission and avoidance. Results not only support the applicability of the STOPS model in explaining publics' communication on controversial sociopolitical problems but also the viability of integrating two new behavioral outcomes - information omission and avoidance - into the STOPS framework

Flexible Piezoelectric Tactile Sensor Array for Dynamic Three-Axis Force Measurement

A new flexible piezoelectric tactile sensor array based on polyvinylidene fluoride (PVDF) film is proposed for measuring three-axis dynamic contact force distribution. The array consists of six tactile units arranged as a 3 × 2 matrix with spacing 8 mm between neighbor units. In each unit, a PVDF film is sandwiched between four square-shaped upper electrodes and one square-shaped lower electrode, forming four piezoelectric capacitors. A truncated pyramid bump is located above the four piezoelectric capacitors to improve force transmission. A three-axis contact force transmitted from the top of the bump will lead to the four piezoelectric capacitors underneath undergoing different charge changes, from which the normal and shear components of the force can be calculated. A series of dynamic tests have been carried out by exerting sinusoidal forces with amplitudes ranging from 0 to 0.5 N in the x-axis, 0 to 0.5 N in the y-axis, and 0 to 1.5 N in the z-axis, separately. The tactile units show good sensitivities with 14.93, 14.92, and 6.62 pC/N in the x-, y-, and z-axes, respectively. They can work with good linearity, relatively low coupling effect, high repeatability, and acceptable frequency response in the range of 5–400 Hz to both normal and shear load. In addition, dynamic three-axis force measurement has been conducted for all of the tactile units. The average errors between the applied and calculated forces are 10.68% ± 6.84%. Furthermore, the sensor array can be easily integrated onto a curved surface, such as robotic and prosthetic hands, due to its excellent flexibility

Echo chambers and social mediators in public advocacy issue networks

•Explored how politically motivated consumer advocacy was communicated on Twitter.•Employed a mixed method combining content analysis and social network analysis.•Showed political homophily varied across retweet, mention, and reply networks.•Illustrated the dominance of the echo chamber phenomenon.•Identified two social mediators, bridgers and echoers, in advocacy communication. The growing trend of politically motivated consumer boycotts and buycotts on social media not only impacts a company’s financial bottom line, but more fundamentally disrupts relationships between the firm and its publics, the cornerstone of public relations (Ferguson, 1984; Sommerfeldt, & Kent, 2015). On a broader level, such politically motivated advocacy is a critical facet of civil society with important implications on the societal role of public relations (Taylor, 2010). In light of the significance of politically motivated consumer advocacy to public relations, a multi-phase, exploratory study was conducted. Study 1 applies content analysis and social network analysis to examine how different interactive mechanisms on social media—retweet, mention, and reply—may affect communication within and between communities of different ideological views surrounding the boycott and buycott issues. Study 2 further explores the challenges and opportunities of fostering exchange of diverse viewpoints by identifying new social mediators—the “echoers” who propel information flow among in-group members, and the “bridgers” who initiate communication with political out-group members—and assess the key network characteristics of these social mediators. The findings of these two studies advance public relations theories on networks, intergroup communication, and civil society by illustrating how social media structure and social mediators shape the networked public discourse to facilitate or inhibit conversations between publics of different ideological orientations

Meaning transfer in celebrity endorsement and co-branding: meaning valence, association type, and brand awareness

Building upon the theory of meaning transfer, this study examines how non-evaluative associations, negative (e.g. crazy) and positive (e.g. brave), are transferred from celebrities to brands to influence brand attitudes, when celebrities and brands are associated in different ways (co-branding vs. endorsement) and when brand awareness varies (lesser-known vs. well-known brand). Additionally, to reveal the underlying mechanism of the meaning transfer effect on brand attitudes, this study tests a moderated mediation model, highlighting transferred brand belief and original brand belief as two serial mediators. Results of an online experiment confirmed the transfer of celebrity traits to brands: Changes in brand belief and attitude were consistent with the valence of the celebrity's traits. More importantly, such a meaning transfer effect became stronger when lesser-known brands were associated with celebrities via co-branding. This effect pattern, however, did not hold for well-known brands. Lastly, regarding the meaning transfer mechanism, the results showed that celebrity meaning transfer first promoted the formation of brand meanings that correspond to celebrity traits, which then impacted original brand beliefs held by consumers, resulting in a change in brand attitudes. This study presents one of the earliest empirical investigations that compare the effects of celebrity endorsement and co-branding based on the meaning transfer theory. It not only provides much-needed causal evidence that directly supports the theory but also illustrates the strategic advantages of celebrity co-branding to capitalize on celebrities' influence. Supplemental data for this article is available online at https://doi.org/10.1080/02650487.2021.1940059

Annexin A1 can inhibit the in vitro invasive ability of nasopharyngeal carcinoma cells possibly through Annexin A1/S100A9/Vimentin interaction.

Annexin A1 is a member of a large superfamily of glucocorticoid-regulated, calcium- and phospholipid-binding proteins. Our previous studies have shown that the abnormal expression of Annexin A1 is related to the occurrence and development of nasopharyngeal carcinoma (NPC). To understand the roles of Annexin A1 in the tumorigenesis of NPC, targeted proteomic analysis was performed on Annexin A1-associated proteins from NPC cells. We identified 436 proteins associated with Annexin A1, as well as two Annexin A1-interacted key proteins, S100A9 and Vimentin, which were confirmed by co-immunoprecipitation. Gene function classification revealed that the Annexin A1-associated proteins can be grouped into 21 clusters based on their molecular functions. Protein-protein interaction analysis indicated that Annexin A1 /S100A9/Vimentin interactions may be involved in the invasion and metastasis of NPC because they can form complexes in NPC cells. The down-regulation of Annexin A1 in NPC may lead to the overexpression of S100A9/Vimentin, which may increase the possibility of the invasion ability of NPC cells by adjusting the function of cytoskeleton proteins. Results suggested that the biological functions of Annexin A1 in NPC were diverse, and that Annexin A1 can inhibit the in vitro invasive ability of NPC cells through Annexin A1 /S100A9/Vimentin interaction

Membrane structure-dependent limiting flux behavior and membrane selectivity loss during gypsum scaling : implications for pressure-retarded osmosis operation and membrane design

Herein, we systematically investigated the influence of membrane structural properties on limiting flux behavior and selectivity loss during gypsum scaling in osmotically driven membrane processes. We selected two typical osmotic membranes, thin-film composite (TFC) polyamide (PA) membrane and integrally asymmetric cellulose triacetate (CTA) membrane with different structures, for gypsum scaling tests in active-layer-facing-draw-solution orientation (an operating mode preferred for pressure-retarded osmosis). Compared to the CTA membrane, the TFC membrane suffered severer internal scaling and achieved a lower limiting flux primarily due to its greater structural parameter that induced severer internal concentration polarization (ICP)-enhanced scaling. The limiting flux is inversely proportional to the membrane structural parameter. For the first time we observed that the TFC membrane suffered a drastic loss of integrity and selectivity after gypsum scaling in PRO. We confirmed that the thin PA layer of TFC membrane is more prone to being damaged by the growth of gypsum crystals inside the confined and unstirred support layer, whereas the integrally asymmetric membrane with a thicker active layer could better maintain its integrity. While TFC membrane is the mainstream for PRO in osmotic power harvesting, our study suggests that the integrally asymmetric membrane may be more suitable under severe scaling conditions.Nanyang Technological UniversityThis research was supported by the Faculty of Engineering and Information Technologies Early Career Researcher Funding Scheme at The University of Sydney, Australia. Q.S. is also grateful to the support of the Start-up Grant (SUG) from Nanyang Technological University, Singapore

Evaluating the Role of PTH in Promotion of Chondrosarcoma Cell Proliferation and Invasion by Inhibiting Primary Cilia Expression

Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP) has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84), and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma