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S1. Confirmation of AP-2α expression. S2. Comparative growth of parental and KO clones. S3. FACS Analysis of Apoptotic Cells with TFAP2AKO. S4. AP-2α binding site. S5. Colon cancer tissue microarray analysis (TMA). S6. TFAP2Aand TGM2 Expression in Response to BKM120.

Supplemental Video KO Cells

Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2–M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and a panel of colon cancer cell lines; however, loss of AP-2α induced resistance to buparlisib. Similarly, buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition. Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors.Implications:AP-2α regulated cell cycle through the PI3K cascade and activation of AKT mediated through TGM2. AP-2α induced sensitivity to Buparlisib/BKM120, indicating that AP-2α is a biomarker predictive of response to PI3K inhibitors.

Supplemental Video 1 Parental Cells

Humanity has created machines throughout history as extensions of people’s bodies and minds. Cyber-utopians believed these creations can solve problems and drive change. Nowadays, society exists in a world of machines where its products – the Internet, ubiquitous computing and artificial intelligence – empower mankind to have godlike qualities. However, the cycle of robotisation and transformation has become an inevitable loop, a race,where some are winning while the rest are losing. Through arguments of various media, political and digital experts, this paper will critically review the notable victories and the undeniable tragedies brought upon mankind by living with technology. Do the consequences outweigh the benefits? Where must society draw the line between convenience and the dependence on machines? In more ways than one, morality must be encoded in machines and creators should reflect on their roles in the master plan. It is time to question the present and reimagine the future

Humanity has created machines throughout history as extensions of people’s bodies and minds. Cyber-utopians believed these creations can solve problems and drive change. Nowadays, society exists in a world of machines where its products – the Internet, ubiquitous computing and artificial intelligence – empower mankind to have godlike qualities. However, the cycle of robotisation and transformation has become an inevitable loop, a race,where some are winning while the rest are losing. Through arguments of various media, political and digital experts, this paper will critically review the notable victories and the undeniable tragedies brought upon mankind by living with technology. Do the consequences outweigh the benefits? Where must society draw the line between convenience and the dependence on machines? In more ways than one, morality must be encoded in machines and creators should reflect on their roles in the master plan. It is time to question the present and reimagine the future

Dermal fillers such as hyaluronic acid, poly-l-lactic acid, and polymethyl-methacrylate are often used to treat cutaneous defects such as lipoatrophy. However, concern exists regarding their use in patients with a connective tissue disease (CTD) because of a theoretical risk of disease reactivation or exacerbation. Evidence regarding their use in patients with CTD also remains limited.This review intends to summarize and evaluate the available literature regarding the use of dermal fillers in patients with CTD.A literature search until May 2020 was conducted through PubMed, Ovid MEDLINE, and Ovid Embase to identify articles discussing the treatment of cutaneous defects secondary to CTD. Articles discussing the use of autologous fat transfer alone were excluded.Twenty-three articles were reviewed. The amount of available evidence varies between the type of CTD and type of filler with morphea having the most published evidence out of the CTDs discussed and hyaluronic acid having the most published evidence out of the fillers discussed. Most studies demonstrated positive results with no report of disease reactivation or exacerbation.Despite limited available evidence, dermal fillers seem to be safe as an adjunctive treatment for cutaneous defects in patients with CTD.

BACKGROUND Most patients with scleroderma suffer from microstomia, which can have debilitating consequences on their quality of life. Unfortunately, treatment options remain limited. No specific guidelines exist; hence, microstomia remains a challenge to treat in this patient population. OBJECTIVE This review aims to evaluate the different medical and surgical treatment modalities currently available for microstomia in patients with scleroderma and make recommendations for future research. MATERIALS AND METHODS A search of PubMed, Ovid MEDLINE, and Ovid Embase was conducted to identify articles discussing the treatment of microstomia in scleroderma. Twenty articles discussing surgical therapy and one article discussing medical therapy were reviewed. RESULTS Mostly because of a scarcity of high-level evidence, no individual therapy has documented long-term efficacy. Some treatments demonstrate positive results and warrant further research. CONCLUSION Given the variability of results, specific recommendations for the treatment of microstomia in patients with scleroderma are difficult to establish. A multifaceted approach that includes surgical and medical therapy is likely the best option to improve oral aperture in this patient population. Surgical treatments such as neurotoxins, autologous fat grafting, and ultraviolet A1 phototherapy may hold the most potential for improvement.

Background Patients with connective tissue disease (CTD) often suffer from facial cutaneous defects and resultant facial asymmetry. Unfortunately, these issues have been known to be difficult-to-treat, and concern exists regarding the use of cosmetic procedures in this patient population due to the theoretical risk of disease flare-up or reactivation. Injectable poly-L-lactic acid (PLLA) is one type of filler that has been used to treat skin atrophy in patients with morphea and lupus erythematous panniculitis. However, overall, there is a dearth in literature regarding the safety and efficacy of PLLA filler in patients with CTDs. Aims This case series intends to evaluate the safety and efficacy of PLLA filler in treating facial atrophy in patients with CTDs. Patients/methods Three patients underwent various treatment courses involving the use of PLLA filler to treat facial atrophy. Results Two patients demonstrated significant improvement in facial atrophy following their treatment course. No patient experienced reactivation or exacerbation of their CTD following PLLA injection. Conclusion PLLA filler appears to have good viability as a safe and potentially effective treatment for facial atrophy in patients with CTDs.

BACKGROUND Dermal fillers such as hyaluronic acid, poly-l-lactic acid, and polymethyl-methacrylate are often used to treat cutaneous defects such as lipoatrophy. However, concern exists regarding their use in patients with a connective tissue disease (CTD) because of a theoretical risk of disease reactivation or exacerbation. Evidence regarding their use in patients with CTD also remains limited. OBJECTIVE This review intends to summarize and evaluate the available literature regarding the use of dermal fillers in patients with CTD. MATERIALS AND METHODS A literature search until May 2020 was conducted through PubMed, Ovid MEDLINE, and Ovid Embase to identify articles discussing the treatment of cutaneous defects secondary to CTD. Articles discussing the use of autologous fat transfer alone were excluded. RESULTS Twenty-three articles were reviewed. The amount of available evidence varies between the type of CTD and type of filler with morphea having the most published evidence out of the CTDs discussed and hyaluronic acid having the most published evidence out of the fillers discussed. Most studies demonstrated positive results with no report of disease reactivation or exacerbation. CONCLUSION Despite limited available evidence, dermal fillers seem to be safe as an adjunctive treatment for cutaneous defects in patients with CTD.

Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2–M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and a panel of colon cancer cell lines; however, loss of AP-2α induced resistance to buparlisib. Similarly, buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition. Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors. Implications: AP-2α regulated cell cycle through the PI3K cascade and activation of AKT mediated through TGM2. AP-2α induced sensitivity to Buparlisib/BKM120, indicating that AP-2α is a biomarker predictive of response to PI3K inhibitors.

Endovascular thrombectomy revolutionized the treatment of acute ischemic stroke. Nevertheless, access to endovascular thrombectomy is limited in many parts of the world. Asia holds 60% of the world’s population and its countries carry some of the highest stroke disease burden. To understand the availability of endovascular thrombectomy and intravenous thrombolysis in this region, we interviewed stroke neurologists and neuro-interventionists of 19 Asian countries, and found a large disparity in access to endovascular thrombectomy and intravenous thrombolysis between high- and low-income countries. Lack of neuro-interventionists, comprehensive stroke units, stroke triage systems and high treatment cost are the major obstacles to wider accessibility of endovascular thrombectomy, especially among developing countries. The potential solutions to provide equitable access to stroke revascularization therapy are discussed.

Supplemental material, WSO881345 Supplemental Material for Overview of endovascular thrombectomy accessibility gap for acute ischemic stroke in Asia: A multi-national survey by Anderson Chun On Tsang, I-Hsiao Yang, Emanuele Orru, Quang-Anh Nguyen, Roselyn V Pamatmat, Gorky Medhi, Yue Wan and Song Huang in International Journal of Stroke

In the business world, service quality is a prized commodity as it directly impacts the profitability performance of any establishment. On the other hand, Higher Education Institutions (HEIs), while may not be considered business institutions, also depend on service quality which is believed to be an equally important factor in providing services to stakeholders. While it is noted that State colleges and universities are experiencing financial downturn due to the struggling economy and decreasing subsidy from the government, HEIs are dealing with reduced budget and searching for ways to do more with less. One way for universities to accomplish this objective is to place a renewed focus on meeting or exceeding the expectations and needs of their students. In all universities around the globe student satisfaction has been considered an important factor in measuring the quality of services provided by the institution. Being the most important beneficiary of the educational institution?s services, students are in the right position to determine the quality of services offered by their university. This research examined the relationship between service quality dimensions and the level of students? satisfaction with the quality of services provided by the university. A questionnaire was used to collect the related data hence establish the relationship between the two types of variables - service quality dimension variables and students? satisfaction level of identified services. Recommendations were identified to strengthen the delivery of services within the university system to bridge the gaps towards excellence. The study also examined how efficient and effective the services are provided to LSPU customers, particularly the students through assessment on their expectations and their perception or observation. After the investigation, the study revealed that students? level of satisfaction is correlated with their observations related to the five service quality dimensions such as reliability, assurance, tangibles, empathy, and responsiveness. The effort of LSPU to continuously improve the services (academic and administrative) provided to its clients and stakeholders spell how competitive it is and how far it will reach towards achieving excellence.