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Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to lack of effective endocrine or targeted therapies, aggressive nature and high rate of chemoresistance. Cancer stem cells (CSCs) are considered to play critical roles in cancer recurrence and chemoresistance. THEMIS2 was identified as the sole common elevated gene in three triple negative breast cancer (TNBC) and two ovarian CSC lines. We discovered an intrinsic signaling scaffold function of THEMIS2, which acts as a novel regulator of cancer stemness in promoting multiple cancer stemness properties including sphere formation, stemness markers expression, chemoresistance and tumorigenicity with low numbers of cancer cells implantation. For the first time, we demonstrated that THEMIS2 specifically enhanced MET activating phosphorylation by suppressing the association of protein-tyrosine phosphatases 1B (PTP1B) with p-MET and MET, which accounted mainly for THEMIS2-mediated effect on cancer stemness and chemoresistance. Increased THEMIS2 expression was associated with poor survival in TNBC patients and in patients from our breast cancer cohort. We found that non-cytotoxic dosages of cryptotanshinone (CPT) could potently inhibit cancer stemness, chemoresistance and tumorigenicity by suppressing expression of THEMIS2. Notably, stable overexpression of THEMIS2 is associated with enhanced sensitivity toward Capmatinib and CPT treatment. Expression levels of THEMIS2 and p-MET protein were positively correlated in the 465 breast cancer specimens. Our study revealed the novel oncogenic role of THEMIS2 and its underlying mechanism via suppressing PTP1B association with MET and thus leading to its activation. Our findings suggest that THEMIS2 could be a biomarker for MET targeted therapy and also provide a potential clinical application using low dosages of CPT for treatment of THEMIS2 positive TNBC.

Designing future IoT ecosystems requires new approaches and perspectives to understand everyday practices. While researchers recognize the importance of understanding social aspects of everyday objects, limited studies have explored the possibilities of combining data-driven patterns with human interpretations to investigate emergent relationships among objects. This work presents Thing Constellation Visualizer (thingCV), a novel interactive tool for visualizing the social network of objects based on their co-occurrence as computed from a large collection of photos. ThingCV enables perspective-changing design explorations over the network of objects with scalable links. Two exploratory workshops were conducted to investigate how designers navigate and make sense of a network of objects through thingCV. The results of eight participants showed that designers were actively engaged in identifying interesting objects and their associated clusters of related objects. The designers projected social qualities onto the identified objects and their communities. Furthermore, the designers changed their perspectives to revisit familiar contexts and to generate new insights through the exploration process. This work contributes a novel approach to combining data-driven models with designerly interpretations of thing constellation towards More-Than Human-Centred Design of IoT ecosystems., Accepted at CSCW 2021

Hepatocellular carcinoma (HCC) accounts for almost 80% of all liver cancers and is the sixth most common cancer and the second most common cause of cancer-related death worldwide. The survival rate of sorafenib-treated advanced HCC patients is still unsatisfactory. Unfortunately, no useful biomarkers have been verified to predict sorafenib efficacy in HCC. We assessed a sorafenib resistance-related microarray dataset and found that anterior gradient 2 (AGR2) is highly associated with overall and recurrence-free survival and several clinical parameters in HCC. However, the mechanisms underlying the role of AGR2 in sorafenib resistance and HCC progression remain unknown. We found that sorafenib induces AGR2 secretion via posttranslational modification, and AGR2 plays a critical role in sorafenib-regulated cell viability and endoplasmic reticulum (ER) stress and induces apoptosis in sorafenib-sensitive cells. Sorafenib downregulated intracellular AGR2 and conversely induces AGR2 secretion, which suppresses its regulation of ER stress and cell survival in sorafenib-sensitive cells. In addition, AGR2 is highly intracellularly expressed in sorafenib-resistant cells, which supports ER homeostasis and cell survival. We suggest that AGR2 regulates ER stress to influence HCC progression and sorafenib resistance. This is the first report that AGR2 can modulate ER homeostasis via the IRE1α-XBP1 cascade to regulate HCC progression and sorafenib resistance. Elucidation of the predictive value of AGR2 and its molecular and cellular mechanisms in sorafenib resistance could provide additional opportunities for HCC treatment.

Objective This national cohort study investigated the incidence, site-specific mortality and prognostic factors of native septic arthritis (SA). Methods Tapping Taiwan’s National Health Insurance Research Database, we identified inpatients with newly diagnosed SA between 1998 and 2012. They were categorized by site of infection and followed to calculate 30-day, 90-day and 1-year mortality. Predictors of mortality were calculated using Cox models. Results A total of 31 491 patients were identified as having SA, the most common site of infection being the knee (50.1%), followed by the hip (14.4%), other sites (26.8%), the shoulder (5.5%) and multiple sites (1.2%). Knee joint involvement was the most common site for all subgroups. Incidence increased from 9.8/105 in 1998 to 13.3/105 in 2012. The 30-day, 90-day and 1-year mortality rates were 4.3, 8.6 and 16.4% respectively. Predictors for mortality were hip infection, shoulder infection, multiple-site infection, being male, age ≥65 years old and comorbidities. We derived a mortality scoring model over age/SA site/comorbidity, and age ≥65 years old had the greatest risk contribution to mortality. No matter whether 1-month, 3-month or 1-year mortality was being considered, patients with the higher risk scores had the higher mortality rates (P Conclusion SA is an emerging infectious disease with a rising incidence, long duration of hospital stay and high mortality rate. The most common affected joint was knee for all subgroups. Patients aged ≥65 years old had a high SA incidence and the greatest risk contribution.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma worldwide, accounting for about 40% of cases. The role of cytokines in the pathogenesis of lymphomas has been rarely addressed, although cytokines have a close immunological relationship with lymphocytes. We observed overexpression of interleukin (IL)-20 in reactive germinal centres (GCs) leading us to hypothesise that IL-20 may play a role in lymphomagenesis. In this study, we surveyed for IL-20 expression in various types of lymphoma and found that IL-20 was expressed most frequently in follicular lymphoma (94%), but also in Burkitt lymphoma (81%), mantle cell lymphoma (57%), nodal marginal zone lymphoma (56%), Hodgkin lymphomas (50%), small lymphocytic lymphoma (50%) and diffuse large B-cell lymphoma (DLBCL, 48%). IL-20 was not expressed in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), lymphoplasmacytic lymphoma, and plasmacytoma. T-cell lymphomas were largely negative for IL-20 expression, except for anaplastic large cell lymphoma (ALCL, 61%), which frequently expressed IL-20, especially in cutaneous ALCL, and showed an inverse association with ALK expression (p=0.024). We further tested IL-20 expression in another large cohort of DLBCL and found IL-20 expression more frequently in germinal centre B-cell (GCB) than in non-GCB subtype [16/26 (62%) versus 24/64 (38%), p=0.038]. In this cohort, IL-20 was associated with a lower rate of extranodal involvement (p=0.009), bone marrow involvement (p=0.040), and better overall survival (p=0.020). Mechanistically, IL-20 overexpression promoted G1 cell cycle arrest and subsequent apoptosis of DLBCL cells and vice versa in vitro. We conclude that IL-20 may be involved in lymphomagenesis and may be useful as a prognostic marker in patients with DLBCL. In addition, IL-20 plays an inhibitory role in DLBCL growth, probably through cell cycle regulation.

To evaluate whether adjusted computed tomography (CT) scan image-based radiomics combined with immune genomic expression can achieve accurate stratification of cancer recurrence and identify potential therapeutic targets in stage III colorectal cancer (CRC), this cohort study enrolled 71 patients with postoperative stage III CRC. Based on preoperative CT scans, radiomic features were extracted and selected to build pixel image data using covariate-adjusted tensor classification in the high-dimension (CATCH) model. The differentially expressed RNA genes, as radiomic covariates, were identified by cancer recurrence. Predictive models were built using the pixel image and immune genomic expression factors, and the area under the curve (AUC) and F1 score were used to evaluate their performance. Significantly adjusted radiomic features were selected to predict recurrence. The association between the significantly adjusted radiomic features and immune gene expression was also investigated. Overall, 1037 radiomic features were converted into 33 × 32-pixel image data. Thirty differentially expressed genes were identified. We performed 100 iterations of 3-fold cross-validation to evaluate the performance of the CATCH model, which showed a high sensitivity of 0.66 and an F1 score of 0.69. The area under the curve (AUC) was 0.56. Overall, ten adjusted radiomic features were significantly associated with cancer recurrence in the CATCH model. All of these methods are texture-associated radiomics. Compared with non-adjusted radiomics, 7 out of 10 adjusted radiomic features influenced recurrence-free survival. The adjusted radiomic features were positively associated with PECAM1, PRDM1, AIF1, IL10, ISG20, and TLR8 expression. We provide individualized cancer therapeutic strategies based on adjusted radiomic features in recurrent stage III CRC. Adjusted CT scan image-based radiomics with immune genomic expression covariates using the CATCH model can efficiently predict cancer recurrence. The correlation between adjusted radiomic features and immune genomic expression can provide biological relevance and individualized therapeutic targets.

Designers have used everyday photos as stimuli to speculate alternative scenarios about the future. Many studies have developed diverse ways of re-designing roles of an actor to stimulate scenario speculation; however, a lack of understandings of how the presence of an actor influences the scenario speculation process. Therefore, this work conducted a study that investigates how everyday photos with and without human actors affect people to speculate possible scenarios. We recruited 29 crowd workers from Amazon Mechanical Turk to generate 80 scenarios for two groups of photos (i.e., with-actor and non-actor photos). We analysed these scenarios and found that with-actor photos led people to speculate consistent scenarios around human actors and their activities. By contrast, non-actor photos allowed people to speculate the scenarios flexibly and diversely. These insights suggest a new design opportunity of using non-actor photos as potential materials to encourage people to generate diverse scenarios.

Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to development of chemoresistance and lack of effective endocrine or targeted therapies. MiR-491-5p has been found to play a tumor suppressor role in many cancers including breast cancer. However, the precise role of miR-491-5p in TNBC has never been elucidated. In this study, we reported the novel tumor suppressor function of FOCAD/miR-491-5p in TNBC. High expression of miR-491-5p was found to be associated with better overall survival in breast cancer patients. We found that miR-491-5p could be an intronic microRNA processed form FOCAD gene. We are the first to demonstrate that both miR-491-5p and FOCAD function as tumor suppressors to inhibit cancer stemness, epithelial-mesenchymal transition, drug resistance, cell migration/invasion, and pulmonary metastasis etc. in TNBC. MiR-491-5p was first reported to directly target Rab interacting factor (RABIF) to downregulate RABIF-mediated TNBC cancer stemness, drug resistance, cell invasion, and pulmonary metastasis via matrix metalloproteinase (MMP) signaling. High expression of RABIF was found to be correlated with poor clinical outcomes of breast cancer and TNBC patients. Our data indicated that miR-491-5p and RABIF are potential prognostic biomarkers and targeting the novel FOCAD/miR-491-5p/RABIF/MMP signaling pathway could serve as a promising strategy in TNBC treatment.

Extended-spectrum β-lactamases (ESBLs) and/or AmpC enzymes combined with deficiency of porins OmpK35 and OmpK36 are important for the development of carbapenem-resistant Klebsiella pneumoniae. We characterized the clinical K. pneumoniae human isolates and investigated the effect of meropenem induction on the ompK35 and ompK36 mutation to develop carbapenem resistance from six carbapenem-susceptible ESBL-producing K. pneumoniae strains. 163 clinical K. pneumoniae isolates were grouped mostly into the ESBL + AmpC (44.2%) and ESBL (42.9%) phenotypes. The resistance rate differed between cephalosporins (52.1% for cefepime - 97.5% for cefotaxime) and carbapenems (16% for meropenem - 28.2% for imipenem) (P blaTEM, blaSHV, blaCTX-M-3-like, and blaCTX-M-14-like of AmpA β-lactamase genes and blaDHA and blaCMY of AmpC β-lactamase genes. Compared to all 163 clinical isolates, the 56 carbapenem-resistant isolates carried less frequently of blaTEM, blaCTXM-14-like, and blaCTXM-3-like and more frequently of blaDHA-1 and blaCMY-2. The carbapenem-resistant isolates differed in prevalence against imipenem, ertapenem, and meropenem and lacked OmpK35 more frequently than OmpK36, but abnormal PCR amplicons were detected fewer in the Omp K35-deficient group than in the OmpK36-deficient group (32.5% vs. 68.4%, respectively). The carbapenem-resistant isolate mostly carried blaDHA (91.1%) and three isolates carried blaKPC-2. Following induction with meropenem insertion sequences in ompK36, not ompK36, were identified as IS5 for KP08, IS1 for KP15, and IS903 for KP16 isolates. OmpK36 deficiency increased resistance to ertapenem, but not imipenem and meropenem. Clinical isolates belonged mainly to ESBL + AmpC group and ESBL group with difference in resistance to cephalosporins and carbapenems, the bla genes. Carbapenem resistant isolates lacked OmpK35 expression, than the OmpK36 expression, Meropenem induction developed the carbapenem resistant isolates with insertion of different insertion sequences in ompK36, not ompK35.

TiO2 nanotube-based heterostructures grafted with ZnO nanorods, Ag nanoparticles, or Pd nanodendrites were synthesized for photocatalytic H2O/CH3OH splitting and H2 generation. Compared with P25 TiO2 nanoparticles and bare TiO2 nanotubes, these heterostructures, in particular, the one grafted with Pd nanodendrites, were found to present a markedly enhanced photocatalytic H2 generation efficiency (net H2 generation rate ∼143 μmol/h). Rather than the surface area of the photocatalysts, the lifetime (separation) of photogenerated carriers and, in particular, the surface plasmon resonance-stimulated carrier excitation dominated the number of total effective carriers. A power relationship with an exponent of 0.2 between the H2 generation rate and the number of total photogenerated carriers was determined, which suggests that the number of effective carriers or the efficiency in H2O/CH3OH splitting might decay in an exponential way.

This study was aimed to compare the effectiveness of aromatherapy and acupressure massage intervention strategies on the sleep quality and quality of life (QOL) in career women.The randomized controlled trial experimental design was used in the present study. One hundred and thirty-two career women (24-55 years) voluntarily participated in this study and they were randomly assigned to (1) placebo (distilled water), (2) lavender essential oil (Lavandula angustifolia), (3) blended essential oil (1:1:1 ratio of L. angustifolia, Salvia sclarea, and Origanum majorana), and (4) acupressure massage groups for a 4-week treatment. The Pittsburgh Sleep Quality Index and Short Form 36 Health Survey were used to evaluate the intervention effects at pre- and postintervention.After a 4-week treatment, all experimental groups (blended essential oil, lavender essential oil, and acupressure massage) showed significant improvements in sleep quality and QOL (p 0.05). Significantly greater improvement in QOL was observed in the participants with blended essential oil treatment compared with those with lavender essential oil (p 0.05), and a significantly greater improvement in sleep quality was observed in the acupressure massage and blended essential oil groups compared with the lavender essential oil group (p 0.05).The blended essential oil exhibited greater dual benefits on improving both QOL and sleep quality compared with the interventions of lavender essential oil and acupressure massage in career women. These results suggest that aromatherapy and acupressure massage improve the sleep and QOL and may serve as the optimal means for career women to improve their sleep and QOL.

Background Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood. Objective This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging. Methods Dermal papilla cells were challenged with H 2 O 2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo . Result Dermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo . Conclusion Stress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.

Background: Overweight and obese older people face a high risk of muscle loss and impaired physical function, which may contribute to sarcopenic obesity. Resistance exercise training (RET) has a beneficial effect on muscle protein synthesis and can be augmented by protein supplementation (PS). However, whether body weight affects the augmentation of muscular and functional performance in response to PS in older people undergoing RET remains unclear.Objective: This study was conducted to identify the effects of PS on the body composition and physical function of older people undergoing RET.Design: We performed a comprehensive search of online databases to identify randomized controlled trials (RCTs) reporting the efficacy of PS for lean mass gain, strength gain, and physical mobility improvements in older people undergoing RET.Results: We included 17 RCTs; the overall mean ± SD age and body mass index (BMI; in kg/m2) in these RCTs were 73.4 ± 8.1 y and 29.7 ± 5.5, respectively. The participants had substantially greater lean mass and leg strength gains when PS and RET were used than with RET alone, with the standard mean differences (SMDs) being 0.58 (95% CI: 0.32, 0.84) and 0.69 (95% CI: 0.39, 0.98), respectively. The subgroup of studies with a mean BMI ≥30 exhibited substantially greater lean mass (SMD: 0.53; 95% CI: 0.19, 0.87) and leg strength (SMD: 0.88; 95% CI: 0.42, 1.34) gains in response to PS. The subgroup of studies with a mean BMI

Background There are numerous biologics for treating patients with severe asthma. A cost-effective method for selecting the most appropriate biologic therapy for a patient is thus important. Bronchoscopy-guided bronchial epithelium sampling may provide information for determining the type of inflammation in the airways of severe asthma patients through immunochemical analysis and thus help clinicians select the correct biologics. Case presentation We report the case of a female with severe asthma and eosinophilia who initially responded to omalizumab treatment. She developed an allergic reaction after four injections of omalizumab. Omalizumab desensitization was successfully conducted. To select an appropriate biologic agent after this hypersensitivity episode, we performed bronchoscopy-guided bronchial epithelium sampling. Omalizumab treatment was resumed based on the findings of immunohistochemical staining after a successful desensitization procedure, leading to long-term control of her severe asthma. Conclusions Selecting an adequate biologic agent for severe, uncontrolled asthma is a challenge in clinical medical practice. Although phenotypes, blood eosinophils, and serum IgE levels have been proposed for use as a reference, there is a dissociation between the blood immune-cell level and the airway epithelium immune reaction, as confirmed in previous studies. Airway epithelium immunohistochemistry staining for targeted immune cells has been used to determine various types of airway inflammation; however, this technique is rarely used in a clinical setting. Previous studies have revealed the relative safety of performing bronchoscopy biopsies for patients with severe asthma. Among the sampling techniques used for tissue diagnosis, including nasal biopsies, nasal or bronchial brushing, and bronchoalveolar lavage, bronchoscopy-guided bronchial epithelium sampling provides more accurate information about the epithelial and inflammatory cells in the tissue context. It is thus a powerful tool for selecting the most suitable biologics in difficult clinical conditions.

Voice Conversational Agents (VCAs) are increasingly becoming part of our daily life. Calling them by their names can solve more than just a problem of efficiency in interaction between users and VCAs, but also can cast them as actors capable of playing a role in a relationship. However, due to the immature state of the technology and its related services, such relationships between users and VCAs can be limited in practice. To broaden the scope in designing different relationships, this study explores VCAs depicted in sci-fi movies. Sci-fi is not purely based on fantasy, but also is a social reflection on technology, which in turn can inspire design researchers to understand and speculate the complexity of VCAs. Through community sourcing with sci-fi enthusiasts, 43 Sci-fi VCAs were deduced. A movie event was also organized to discuss the role of VCAs. Finally, this paper presents several possible design insights for designing the role of VCAs.

In this paper, we investigate a fault estimation and decentralized control problem for an integrated networked control system whose configuration between subsystems is with variable structures. Taking advantage of the variable structures, the NCS could be formulated as a distributed type or a decentralized one, or as a time-varying switching kind between these two types. In these cases, these subsystems subject to network induced phenomena, such as networked induced time-varying delay, packets losses, and some faults caused by faulty actuators. To deal with these considerations, we introduce a fault dynamics and derive a set of LMI-based delay-dependent conditions for stability analysis problems of the corresponding augmented fault estimation system. Based on the resultant stability conditions, we also derive a set of LMI-based synthesis conditions for designing estimators and decentralized controllers to cope with faults. At the end of this paper, a numerical example is presented to show the feasibility and efficiency of the proposed method.