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This article argues for a revisionist reading of The Goddess to redirect critical attention to its film form and narrative style. Yet, it also explores the social-economic and technological conditions of filmmaking in early Chinese cinema that circumvented the filmmaker’s aesthetic choices and devices. A political reading of the film within either the leftist-progressive or nationalist agenda is inadequate in explicating the film’s narrative capacity and affective power in engaging social commentary. Reading The Goddess as a Chinese manifestation of Hollywood’s maternal melodrama has equally dismissed the film’s contestation of the complex political and ideological discourses in which it was produced. Inspired by a neoformalist approach to studying film form and social reality, this article articulates the working of Wu Yonggang’s cinematic style as a crafted combination of artistic choices and interventions, which are made within the classical Hollywood paradigm and Soviet montage, to define an early Chinese cinematic language that is specific to 1930s Shanghai film industry and Chinese society, the filmmaker’s aesthetic pursuit, and Ruan Lingyu’s stardom.

Hypodiploid acute lymphoblastic leukemia (ALL) is an aggressive blood cancer with a poor prognosis despite intensive chemotherapy or stem cell transplant. Children and adolescents with positive end-of-induction minimal residual disease have an overall survival lower than 30%. However, data regarding therapeutic alternatives for this disease is nearly nonexistent, emphasizing the critical need for new or adjunctive therapies that can improve outcomes. We previously reported on the therapeutic efficacy of venetoclax (ABT-199) in hypodiploid B-lineage ALL but with limitations as monotherapy. In this study, we set out to identify drugs enhancing the anti-leukemic effect of venetoclax in hypodiploid ALL. Using a highthroughput drug screen, we identified dinaciclib, a cyclin-dependent kinase inhibitor that worked synergistically with venetoclax to induce cell death in hypodiploid cell lines. This combination eradicated leukemic blasts within hypodiploid ALL patient-derived xenografts mice with low off-target toxicity. Our findings suggest that dual inhibition of BCL-2 (venetoclax) and CDK9/MCL-1 (dinaciclib) is a promising therapeutic approach in hypodiploid ALL, warranting further investigation to inform clinical trials in this high-risk patient population.

In their general introduction to the present Special Issue the authors trace the origins of and motivation behind much of the independent documentary filmmaking produced in the city during a period of great sociopolitical turbulence, leading up to the tight censorship protocols put in place after the mainland government’s promulgation of the repressive National Security Law in 2020. With reference to the individual essays that comprise this volume, they chart the sudden and unprecedented rise of documentary filmmaking in Hong Kong following many decades of public indifference to the genre. Limited public and underground screenings that took place before absolute censorship measures were implemented in 2021 showed huge box-office demand for these topical films, reflecting images of ordinary Hong Kong people and their struggle for political representation. This opening essay introduces a range of essays and one interview, mostly in relation to specific films, dealing with the now-contentious coupling of documentary films or television broadcasts and democracy. As the essays indicate, some directors and producers of these observational and participatory documentaries are still active overseas and many of the films discussed can now only be screened outside Hong Kong. Nevertheless, they bear witness to a spirit of resilience and resistance as well as a deep-seated desire for a genuine democracy based on universal suffrage constantly reneged on by the city’s various rulers, from the colonial era until now.

DNA-based points accumulation for imaging in nanoscale topography (DNA-PAINT) is a powerful super-resolution microscopy method that can acquire high-fidelity images at nanometer resolution. It suffers, however, from high background and slow imaging speed, both of which can be attributed to the presence of unbound fluorophores in solution. Here we present two-color fluorogenic DNA-PAINT, which uses improved imager probe and docking strand designs to solve these problems. These self-quenching single-stranded DNA probes are conjugated with a fluorophore and quencher at the terminals, which permits an increase in fluorescence by up to 57-fold upon binding and unquenching. In addition, the engineering of base pair mismatches between the fluorogenic imager probes and docking strands allowed us to achieve both high fluorogenicity and the fast binding kinetics required for fast imaging. We demonstrate a 26-fold increase in imaging speed over regular DNA-PAINT and show that our new implementation enables three-dimensional super-resolution DNA-PAINT imaging without optical sectioning.

Cosmopolitanism promises to go beyond national thinking and tradition-bound parochialism by reemphasizing the interconnectedness of individuals, communities, and cultures. This article probes the politics of adaptation of the left-leaning Cantonese Union Film Enterprise (Zhonglian 中聯, 1952–1967) in colonial Hong Kong, and scrutinizes how it embraced world literary classics to enhance the prestige of Cantonese films. It focuses on three 1955 adaptations: An Orphan's Tragedy (Guxing xuelei 孤星血淚; from Great Expectations), Anna (Chuncan mengduan 春殘夢斷; from Anna Karenina), and Eternal Love (Tianchang dijiu 天長地久; from Sister Carrie). The founding of Union was a conscientious response of Cantonese film workers to the call of the Cantonese Film Clean-up Campaign (Yueyu dianying qingjie yundong 粵語電影清潔) in the 1940s, launched by leftist filmmakers from Shanghai (Cai Chusheng 蔡楚生, Situ Huimin司徒慧敏) and supported by Cantonese film leaders Ng Cho-fan 吳楚帆 and Lo Duen 盧敦. The study interrogates the predicaments and vicissitudes of Union's cosmopolitan stances as it wrestled with the cultural politics of Chinese cinema during the Cold War. It elucidates the ethnically rooted and culturally cosmopolitan Cantonese progressive cinema. The social realism represented by Union is not local or passé. The Union artists envisioned from below a humane and cosmopolitan community inhabited by workers and intellectuals, locals and diasporic Chinese subjects, which connects people beyond their parochialism and nationhood.

Background Z scores are the method of choice to report dimensions in pediatric echocardiography. Z scores based on body surface area (BSA) have been shown to cause systematic biases in overweight and obese children. Using aortic valve (AoV) diameters as a paradigm, the aims of this study were to assess the magnitude of z score underestimation in children with increased body mass index z score (BMI-z) and to determine if a predicting model with height and weight as independent predictors would minimise this bias. Methods In this multicentre, retrospective, cross-sectional study, 15,006 normal echocardiograms in healthy children 1-18 years old were analyzed. Residual associations with body size were assessed for previously published z score. BSA-based and alternate prediction models based on height and weight were developed and validated in separate training and validation samples. Results Existing BSA-based z scores incompletely adjusted for weight, BSA, and BMI-z and led to an underestimation of > 0.8 z score units in subjects with higher BMI-z compared with lean subjects. BSA-based models led to overestimation of predicted AoV diameters with increasing weight or BMI-z. Models using height and weight as independent predictors improved adjustment with body size, including in children with higher BMI-z. Conclusions BSA-based models result in underestimation of z scores in patients with high BMI-z. Prediction models using height and weight as independent predictors minimise residual associations with body size and generate well fitted predicted values that could apply to all children, including those with low or high BMI-z.

Mini-tablets (MTs) have been utilized as an alternative to monolithic tablets due to their ease of use for pediatric populations, dose flexibility and tailoring of drug release profiles. Similar to monolithic tablets, MTs can develop film coat and internal core defects during manufacturing processes that may adversely affect their dissolution performance. The use of x-ray computed microtomography (XRCT) is well documented for monolithic tablets as a means of identifying internal defects, but applications to MTs have not been well studied. In this study, we have developed a workflow that analyzes reconstructed XRCT images of enteric-coated mini-tablets using deep learning convolutional neural networks. This algorithm was utilized to extract key physical features of individual MTs, such as micro-crack volume and enteric coat thickness. By performing dissolution studies on individual MTs, correlations were established based on the physical parameters obtained by XRCT and the dissolution performance, enabling prediction of dissolution performance utilizing non-destructive imaging data. This workflow provides insight into the physical variability of MT populations that are generated during manufacturing, enabling optimization of critical tableting and coating parameters to achieve the target dissolution criteria. Through this mechanistic understanding, quality is built into the final drug product through rational development of formulation and process parameters.

PURPOSE: To explore facilitators and barriers for male partner follow through carrier screening (CS) after their female partners were identified as carriers, from both male and female perspectives. METHODS: Participants were either females identified as a carrier through CS (512 participants) or males who had CS (125 participants). Participants were recruited via e-mails with survey links. The survey explored factors surrounding decisions to pursue CS or not. RESULTS: Males who attended the females’ CS appointment were more likely to have CS (OR: 2.07). More male partners of females identified as carriers of severe or profound conditions pursued CS (82.0%) than male partners of females who were carriers for moderate conditions (50.0%). Logistic factors were more impactful for males who pursued CS. Females whose male partners did not test endorsed personal belief factors as most impactful, reporting the perceived low risk (75.0%) and his low concern for the specific condition (65.5%) were the top reasons their partners did not test. CONCLUSION: Many factors impact how male partners appraise reproductive risk from CS and make decisions regarding their own screening. Advising that male partners attend CS appointments may increase the likelihood of follow through CS. Thorough and repeated risk counseling is indicated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-02029-5.

Latest work regarding personal informatics, gamification, and feedback has suggested that visualizing behavioural data for daily reflection should consider dynamic representations in metaphors and ...

This article examines the promises and predicaments of May Fourth writers in their experimental writing of the “long novel” (changpian xiaoshuo 長篇小說) as a Chinese brand of the modern epic. May Fourth intellectuals showed a conscious effort to institute a new brand of fictional genre to enlighten the reading public. Yet their “education of the novel” was far from complete, as New Literature writers found fictional expressions primarily in the form of the short story, with strong undertones of individualism, subjective lyricism, and elitism. By focusing on Mao Dun's 茅盾 (1896–1981) Ziye 子夜 (Midnight; 1933), the article examines his call for the establishment of the long novel and his strenuous efforts to “take over” the modern novel as an ideological form to narrate a teleological progression of history. How do Mao Dun's fictional narratives illuminate the representational problems between fiction, locality, and modernity? For Mao Dun and his May Fourth contemporaries, modernity at large was expressed in a teleological mode of time and progress, both in the rhetoric of modernity and in fiction writing. The article reflects on Mao Dun's creative and ideological impasse by teasing out the narrative loopholes of traditional voices and popular fictional registers in the modern epic.

PurposexDECIDE is a clinical decision support system, accessed through a web portal and powered by a “Human-AI Team”, that offers oncology healthcare providers a set of treatment options personalized for their cancer patients, and provides outcomes tracking through an observational research protocol. This article describes the xDECIDE process and the AI-assisted technologies that ingest semi-structured electronic medical records to identify and then standardize clinico-genomic features, generate a structured personal health record (PHR), and produce ranked treatment options based on clinical evidence, expert insights, and the real world evidence generated within the system itself.MethodPatients may directly enroll in the IRB-approved pan-cancer XCELSIOR registry (NCT03793088). Patient consent permits data aggregation, continuous learning from clinical outcomes, and sharing of limited datasets within the research team. Assisted by numerous AI-based technologies, the xDECIDE team aggregates and processes patients’ electronic medical records, and applies multiple levels of natural language processing (NLP) and machine learning to generate a structured case summary and a standardized list of patient features. Next a ranked list of treatment options is created by an ensemble of AI-based models, called xCORE. The output of xCORE is reviewed by molecular pharmacologists and expert oncologists in a virtual tumor board (VTB). Finally a report is produced that includes a ranked list of treatment options and supporting scientific and medical rationales. Treating physicians can use an interactive portal to view all aspects of these data and associated reports, and to continuously monitor their patients’ information. The xDECIDE system, including xCORE, is self-improving; feedback improves aspects of the process through machine learning, knowledge ingestion, and outcomes-directed process improvement.ResultsAt the time of writing, over 2,000 patients have enrolled in XCELSIOR, including over 650 with CNS cancers, over 300 with pancreatic cancer, and over 100 each with ovarian, colorectal, and breast cancers. Over 150 VTBs of CNS cancer patients and ∼100 VTBs of pancreatic cancer patients have been performed. In the course of these discussions, ∼450 therapeutic options have been discussed and over 2,000 consensus rationales have been delivered. Further, over 500 treatment rationale statements (“rules”) have been encoded to improve algorithm decision making between similar therapeutics or regimens in the context of individual patient features. We have recently deployed the xCORE AI-based treatment ranking algorithm for validation in real-world patient populations.ConclusionClinical decision support through xDECIDE is available for oncologists to utilize in their standard practice of medicine by enrolling a patient in the XCELSIOR trial and accessing xDECIDE through its web portal. This system can help to identify potentially effective treatment options individualized for each patient, based on sophisticated integration of real world evidence, human expert knowledge and opinion, and scientific and clinical publications and databases.

Personal technology plays an integral role in shaping people’s quality of life which includes leisure and tourism experiences. A number of personal informatics tools can support people in performing their activities by collecting biometric and environmental data; however, little is known regarding the use of psychological data to enrich leisure and tourism experiences. To address this research gap, this study aims to propose a conceptual framework that fosters memorable and meaningful leisure experiences (MMEs) based on theories from serious leisure and positive psychology. In particular, this study probes into the MMEs of serious leisure practitioners who put their efforts and resources into pursuing intrinsically rewarding leisure activities. Excelling at these activities, which may draw upon participants’ character strengths, yields sustained fulfillment which fosters personal transformation. The idiosyncratic nature of MMEs demands a phenomenological inquiry that involves in-depth interviews concerning the character strengths used and their development trajectories. Using theory triangulation from both positive psychology and serious leisure allows researchers to gain a holistic view of participants’ well-being. Character strengths were found to be the integral factors that contribute to MMEs at different stages of leisure activities. The result identified three aspects of strengths used: strengths well spent, reflection and introspection, and anticipation of the future self, which informs the development of a strengths-based personal informatics framework for leisure and tourism.

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Localization-based super-resolution microscopy techniques such as PALM, STORM, and PAINT are increasingly critical tools for biological discovery. These methods generate lists of single fluorophore positions that capture nanoscale structural details of subcellular organisation, but to develop biological insight, we must post-process and visualize this data in a meaningful way. A large number of algorithms have been developed for localization post-processing, transforming point data into representations which approximate traditional microscopy images, and performing specific quantitative analysis directly on points. Implementations of these algorithms typically stand in isolation, necessitating complex workflows involving multiple different software packages. Here we present PYMEVisualize, an open-source tool for the interactive exploration and analysis of 3D, multicolor, single-molecule localization data. PYMEVisualize brings together a broad range of the most commonly used post-processing, density mapping, and direct quantification tools in an easy-to-use and extensible package. This software is one component of the PYthon Microscopy Environment (python-microscopy.org), an integrated application suite for light microscopy acquisition, data storage, visualization, and analysis built on top of the scientific Python environment.

Somatic embryogenesis in Arabidopsis encompasses an induction phase requiring auxin as the inductive signal to promote cellular dedifferentiation and formation of the embryogenic tissue, and a developmental phase favoring the maturation of the embryos. Strigolactones (SLs) have been categorized as a novel group of plant hormones based on their ability to affect physiological phenomena in plants. The study analyzed the effects of synthetic strigolactone GR24, applied during the induction phase, on auxin response and formation of somatic embryos. The expression level of two SL biosynthetic genes, MORE AXILLARY GROWTH 3 and 4 (MAX3 and MAX4), which are responsible for the conversion of carotene to carotenal, increased during the induction phase of embryogenesis. Arabidopsis mutant studies indicated that the somatic embryo number was inhibited in max3 and max4 mutants, and this effect was reversed by applications of GR24, a synthetic strigolactone, and exacerbated by TIS108, a SL biosynthetic inhibitor. The transcriptional studies revealed that the regulation of GR24 and TIS108 on somatic embryogenesis correlated with changes in expression of AUXIN RESPONSIVE FACTORs 5, 8, 10, and 16, known to be required for the production of the embryogenic tissue, as well as the expression of WUSCHEL (WUS) and Somatic Embryogenesis Receptor-like Kinase 1 (SERK1), which are markers of cell dedifferentiation and embryogenic tissue formation. Collectively, this work demonstrated the novel role of SL in enhancing the embryogenic process in Arabidopsis and its requirement for inducing the expression of genes related to auxin signaling and production of embryogenic tissue.

Personal technologies are widely used to capture the memorable and meaningful experiences travellers have during their journeys. These digital footprints serve as memorabilia for travellers to share and reminiscence about these special experiences. This study showcases an exploratory study of the creation of a travel diary from the traveller’s digital footprints to facilitate the expression of and reminiscences about memorable and meaningful moments. In this study, 15 participants were asked to share their memorable and meaningful travel experiences and were then instructed to use their photos and a set of prototyping tools to create a paper-based visual diary of their experiences. The goal of this study was to examine the process of creating a visual diary to understand the differences in how these experiences are recounted and the ways they are expressed. We used a Labovian approach to compare and contrast the participants’ oral narratives and visual diaries. As in comics studies, the visual diaries are analysed with respect to their spatio–temporal dimensions and the recurring patterns in these two narrative forms are discussed. Based on the results, recommendations are made regarding the future design of travel diary platforms.

Background The Royal College of Physicians and Surgeons of Canada officially launched ‘Competence by Design’ in July 2017, moving from time-based to outcomes-based training. Transitioning to competency-based medical education (CBME) necessitates change in resident assessment. A greater frequency of resident observation will likely be required to adequately assess whether entrustable professional activities have been achieved. Purpose Characterize faculty and resident experiences of direct observation in a single paediatric residency program, pre-CBME implementation. Qualitatively describe participants’ perceived barriers and incentives to participating in direct observation. Methods Surveys were sent to paediatric residents and faculty asking for demographics, the frequency of resident observation during an average 4-week rotation, perceived ideal frequency of observation, and factors influencing observation frequency. Descriptive data were analyzed. Institutional research ethics board approval was received. Results The response rate was 54% (34/68 faculty and 16/25 residents). When asked the MAXIMUM frequency FACULTY observed a resident take a history, perform a physical examination, or deliver a plan, the median faculty reply was 1, 2, and 3, for outpatient settings and 0, 1, and 2, for inpatient settings. The median RESIDENT reply was 2, 4, and 10 for outpatient settings and 1, 2, and 20 for inpatient settings. When asked the MINIMUM frequency for each domain, the median FACULTY and RESIDENT reply was 0, except for delivering a plan in the inpatient setting. Faculty reported observing seniors delivering the plan more frequently than junior residents. Faculty and resident median replies for how frequently residents should be observed for each domain were the same, three to four, three to four, and five to six times. Four per cent of faculty reported regularly scheduling observations, and 77% of residents regularly ask to be observed. The most common barriers to observation were too many patients to see and both faculty and residents were seeing patients at the same time. Most faculty and resident responders felt that observation frequency could be improved if scheduled at the start of the rotation; faculty were provided a better tool for assessment; and if residents asked to be observed. Conclusions This study provides baseline data on how infrequent faculty observation is occurring and at a frequency lower than what faculty and residents feel is necessary. The time needed for observation competes with clinical service demands, but better scheduling strategies and assessment tools may help.

Interest in canola (Brassica napus L.). In response to this interest, scientists have been tasked with altering and optimizing the protein production chain to ensure canola proteins are safe for consumption and economical to produce. Specifically, the role of plant breeders in developing suitable varieties with the necessary protein profiles is crucial to this interdisciplinary endeavour. In this article, we aim to provide an overarching review of the canola protein chain from the perspective of a plant breeder, spanning from the genetic regulation of seed storage proteins in the crop to advancements of novel breeding technologies and their application in improving protein quality in canola. A review on the current uses of canola meal in animal husbandry is presented to underscore potential limitations for the consumption of canola meal in mammals. General discussions on the allergenic potential of canola proteins and the regulation of novel food products are provided to highlight some of the challenges that will be encountered on the road to commercialization and general acceptance of canola protein as a dietary protein source.

Ionic polymer-metal composites are electro-active soft actuators that, when stimulated by an electric field, convert electrical energy into mechanical energy. This study focuses on an ionic polymer-metal composite soft actuator that has been realized with Nafion-117 and platinum electrodes. Three black-box models, i.e., curve fitting, multi-layer perceptron, and long short-term memory recurrent neural network, are designed based on the forces exerted by the soft actuator at fixed displacements when stimulated by different voltages. The capability of the three black-box models to predict unseen forces is evaluated and compared. This study shows that the multi-layer perceptron has the best predictive capability in capturing the dynamics of unseen force data, with a root mean square error of 0.109 mN and computation time of $13 \mu \mathrm{s}$

We previously showed how triterpene saponin bacopaside (bac) II, purified from the medicinal herb Bacopa monnieri, induced cell death in colorectal cancer cell lines and reduced endothelial cell migration and tube formation, and further demonstrated a synergistic effect of a combination of bac I and bac II on the inhibition of breast cancer cell line growth. Here, we assessed the effects of bac I and II on the colorectal cancer HT-29 cell line, and mouse (2H-11) and human umbilical vein endothelial cell (HUVEC) lines, measuring outcomes including cell viability, proliferation, migration, tube formation, apoptosis, cytosolic Ca2+ levels and plasma membrane integrity. Combined bac I and II, each applied at concentrations below IC50 values, caused a synergistic reduction of the viability and proliferation of HT-29 and endothelial cells, and impaired the migration of HT-29 and tube formation of endothelial cells. A significant enhancement of apoptosis was induced only in HUVEC, although an increase in cytosolic Ca2+ was detected in all three cell lines. Plasma membrane integrity was compromised in 2H-11 and HUVEC, as determined by an increase in propidium iodide staining, which was preceded by Ca2+ flux. These in vitro findings support further research into the mechanisms of action of the combined compounds for potential clinical use.

The number of emotional illnesses rises every year . The efforts of using HCI and VR technology to create prevention tools require to extend the design learning knowledge to provide appropriate emotional cognitive experiences. Research has shown that VR provides better engagement and improvement on basic emotional and social dimensions of learning, however, the literature shows that it is necessary for the continuous study to develop effective emotional learning experience addressed to the next generations on immersive virtual learning environment. This study aims to identify how VR experiences impact the learning of a specific emotional dimension on adolescents (responsible decision-making RDM) and identify which cognitive and experience elements have incidence in the design of the learning experience. Based on literature and theories of VR and learning sciences, we experimented using VR on learning sessions with a control group based in ethical and emotional situations using the SODAS method to learn responsible decision making. Results show that the VR group gets a higher score after the sessions, and qualitative and quantitative data reveals that learning timing, cognitive articulation, learning attribution, cognitive load, and specific emotional dimensions might be impacted by the emotional learning experience. The analyses provide helpful information for the future design of cognitive experiences on VR technology.

This paper presents findings from a design research project that looks into the phenomenon of communication and expression in the diasporic family relationship, particularly between Filipino domestic workers and their kin. The research also looks into material culture and the meaning of the “balikbayan box” metaphor as a design prompt, leading to the creation of design guidelines and a concept development for Bukas, a tangible product linked with a mobile interface that facilitates meaningful daily communication for migrant Filipina workers and their families through a material artifact. The design inquiry consists of immersive human-centered qualitative methods including semi-structured field interviews, cultural probes, and participatory workshops to deepen the understanding of the stakeholders’ mindsets, behaviors, and expressive needs. These methods reveal migrant workers’ latent needs for self-identity expression and communication. The research endeavors to explore migrant workers’ self-identity and results in a coexisting spectrum of values consisting of positive achievements and negative feelings of sadness, from which we posit a set of criteria and develop a design concept that tests these guidelines .

This study explores how technology-mediated journaling can support memorable and meaningful tourism experiences (MMEs). The digital photo is the most common medium for travelers to keep a record of memorable and meaningful moments and share them via social media. We explore the potential of using these footprints for travelers to connect the implicit dimensions of their well-being. In particular, we draw reference from positive psychology, which emphasizes that human well-being is rooted in people’s implicit personal factors and psychological needs such as character strengths, motives, and values. Making the implicit explicit may help people to make a wiser choice that matches their own aspirations. To support people in (re)creating meaningful narratives, we created a proof-of-concept prototype by incorporating character strengths into the design of a digital journaling platform. This study involved ten participants and each of them created at least five MME narratives from their past journeys. In this article, we discuss the design concerns for such a platform and examine the effectiveness of the platform in producing meaningful narrative by collecting participant feedback, and looking into the character strengths that the participants draw upon in their MMEs. The result suggests that not only the platform supports the reminiscing of MMEs, but the narration also deepened their self-awareness and allowed the participants to connect their behaviors with their personality traits and implicit values. Some participants were able to identify meanings that were hitherto obscured to them. Implications for quantified travelers and smart tourism are discussed.

Drug-induced liver injury is an important cause of non-approval in drug development and the withdrawal of already approved drugs from the market. Screening human hepatic cell lines for toxicity has been used extensively to predict drug-induced liver injury in preclinical drug development. Assessing hepatic-cell health with more diverse markers will increase the value of in vitro assays and help predict the mechanism of toxicity. We describe three live cell-based assays using HepG2 cells to measure cell health parameters indicative of hepatotoxicity. The first assay measures cellular ATP levels using luciferase. The second and third assays are multiparametric high-content screens covering a panel of cell health markers including cell count, mitochondrial membrane potential and structure, nuclear morphology, vacuolar density, and reactive oxygen species and glutathione levels. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Measurement of cellular ATP content Basic Protocol 2: High-content analysis assay to assess cell count, mitochondrial membrane potential and structure, and reactive oxygen species Basic Protocol 3: High-content analysis assay to assess nuclear morphology, vacuoles, and glutathione content Support Protocol 1: Subculturing and maintaining HepG2 cells Support Protocol 2: Plating HepG2 cell line Support Protocol 3: Transferring compounds by pin tool Support Protocol 4: Generating dose-response curves.

Hospitals and ambulatory facilities significantly reduced cardiac care delivery in response to the first wave of the COVID-19 pandemic. The deferral of elective cardiovascular procedures led to a marked reduction in healthcare delivery with a significant impact on optimal cardiovascular care. International and Canadian data have reported dramatically increased wait-times for diagnostic tests and cardiovascular procedures, as well as associated increased cardiovascular morbidity and mortality. In the wake of the demonstrated ability to rapidly create critical care and hospital ward capacity, we advocate a different approach during the second and possible subsequent COVID-19 pandemic waves. We suggest an approach, informed by local data and experience, which balances the need for an expected rise in demand for healthcare resources to ensure appropriate COVID-19 surge capacity, with continued delivery of essential cardiovascular care. Incorporating cardiovascular care leaders into pandemic planning and operations will help healthcare systems minimize cardiac care delivery disruptions, while maintaining critical care and hospital ward surge capacity and continuing measures to reduce transmission risk in healthcare settings. Specific recommendations targeting the main pillars of cardiovascular care are presented: ambulatory, inpatient, procedural, diagnostic, surgical and rehabilitation., Cardiovascular care delivery was significantly reduced during the first wave of the COVID-19 pandemic, leading to reports of increased wait-times, with associated cardiovascular morbidity and mortality. Recommendations are presented advocating for a different approach in the second and subsequent waves of COVID-19 to balance surge capacity while preserving delivery of essential cardiovascular care.

Oxidative stress is a central part of innate-immune induced neurodegeneration. However, the transcriptomic landscape of the central nervous system (CNS) innate immune cells contributing to oxidative stress is unknown, and therapies to target their neurotoxic functions are not widely available. Here, we provide the oxidative stress innate immune cell atlas in neuroinflammatory disease, and report the discovery of new druggable pathways. Transcriptional profiling of oxidative stress-producing CNS innate immune cells (Tox-seq) identified a core oxidative stress gene signature coupled to coagulation and glutathione pathway genes shared between a microglia cluster and infiltrating macrophages. Tox-seq followed by a microglia high-throughput screen (HTS) and oxidative stress gene network analysis, identified the glutathione regulating compound acivicin with potent therapeutic effects decreasing oxidative stress and axonal damage in chronic and relapsing multiple sclerosis (MS) models. Thus, oxidative stress transcriptomics identified neurotoxic CNS innate immune populations and may enable the discovery of selective neuroprotective strategies.

Excessive use of smartphones or other electronic screen products and the associated symptoms of addiction among youngsters have sparked concerns. This study explores possibilities of preventing adolescents or young adults from excessive smartphone use via a character-based mobile application stimulating their imagination and reflection. The character responds contingently to a user’s act of switching on or off the screen, causing one to associate the effects on the character with excessive use. This approach, grounded in the embodied cognition thesis, combines behavior with imaginative consequences for one to experience, which combat the rewarding neural pathways activated in addictive behaviors. The application was deployed in a field trial. Each participant’s usage was tracked via automated logging, and cognitive responses were probed through in-depth interviews. Interview data were analyzed, followed by comparison with logged data. Overall, about half of the participants attributed imaginative consequences to their ways of using phones. One third of the participants showed evidence of positive change in using phones. These two groups substantially overlapped. The results suggest that experientially grounded association of virtual consequences with physical acts could correlate with behavior change. Using figurative representation as feedback could be promising in supporting individuals for healthy habits.

This study investigated Millennials’ source selection while searching for financial information to improve financial well-being. Results from an online survey of 488 business students at a Western U.S. university showed that Millennials used multiple sources when looking for financial information, but only sources whose perceived attributes fit the seekers’ preferences were considered; respondents favored family, employer/university, and government sources. Associations between personal characteristics (personal financial well-being, financial issue involvement, financial health self-efficacy, gender, and perception of source attributes) and financial information source selection were examined. Findings suggest financial practitioners, universities, and employers can improve their “fit” as financial information sources for Millennials by cocreating financial information with them, tailoring the communication channels, and enhancing the accessibility of information.

The rapid growth in the usage of mobile and screen-based products and the corresponding addiction of adolescents to such devices continue to cause great concerns among different stakeholders. Family, as a potential psychosocial support for reducing the likelihood of addiction development, can be weakened as a result of the deterioration of parent-adolescent relationships associated with mobile devices overuse. Based on the family functioning and gamification-enhanced concepts, positive and fun interactions between family members can be a vital component in fostering a supportive relationship. An innovative and alternative family-focused intervention strategy, the interactive play platform named “Lamb Lamp,” has been developed to facilitate fun and pleasurable parent-adolescent interactivities. The design aims to divert family members’ attention away from their phones, while facilitating joyful and cheerful engagements for the whole family, with the ultimate aim of fostering the development of a supportive relationship. This paper reports the initial results of a pilot study on 5 families recruited at a community-based treatment center, with at least one child aged between 12 and 19 who exhibited excessive Internet or mobile phone use problems. Daily patterns related to the adolescents’ Internet and mobile use and personal reflections on the perceptions of family interrelationships were recorded through lifestyle probes—a set of self-reporting home assignments—before the placement of the Lamb Lamp. Semi-structured interviews were conducted after the intervention to further solicit feedback from the families. The findings were then summarized and verified by parents and the counselors of the families engaged. Although the feedback collected from the families did not indicate an obvious reduction in mobile use behavior, they confirmed the benefits of this gamification-enhanced intervention in a family context. Collective play not only stimulated emotional connectivity between parents and adolescents, but also encouraged them to relive joyful memories of family activities while dealing with the problem of excessive mobile use.

Insulin production by the pancreatic β cell is critical for the glucose homeostasis of the whole organism. Although the transcription factors required for insulin production are known, the upstream pathways that control insulin production are less clear. To further elucidate this regulatory network, we created a genetic interaction map of insulin production by performing ∼20,000 pairwise RNA interference knockdowns of insulin promoter regulators. Our map correctly predicted known physical complexes in the electron transport chain and a role for Spry2 in the unfolded protein response. To further validate our map, we used it to predict the function of an unannotated gene encoding a 37-kDa protein with no identifiable domains we have termed mitochondrial fission factor interactor (Mfi). We have shown that Mfi is a binding partner of the mitochondrial fission factor and that Mfi inhibits dynamin-like protein 1 recruitment to mitochondria. Our data provide a resource to understand the regulatory network of insulin promoter activity.

Objective To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). Study design Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. Results We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in 20% of patients. Nonsteroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their patients with large/giant CAAs. Conclusions In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

La saturométrie est un moyen simple, sécuritaire, non invasif et démontré d’améliorer le dépistage de la cardiopathie congénitale grave chez les nouveau-nés. Pourtant, ce test n’est pas encore utilisé systématiquement au Canada. Le présent point de pratique fait ressortir l’information essentielle et les recommandations en matière de dépistage. Selon les recherches, la saturométrie de dépistage est hautement spécifique et comporte un faible taux de résultats faussement positifs. Le dépistage optimal de la cardiopathie congénitale grave devrait inclure une échographie prénatale, un examen physique et une saturométrie. Celle-ci devrait être effectuée de 24 à 36 heures après la naissance, à la main droite et l’un des deux pieds du nouveau-né, afin de réduire au minimum le nombre de résultats faussement positifs. Si les résultats sont anormaux, le dispensateur de soins qui a la plus grande responsabilité du nouveau-né doit le soumettre à une évaluation approfondie. Dans l’impossibilité d’exclure un diagnostic de trouble cardiaque, il est recommandé d’orienter le nouveau-né vers un cardiologue pédiatre et de lui faire subir une échocardiographie.

Pulse oximetry screening is safe, noninvasive, easy to perform and proven to enhance detection of critical congenital heart disease in newborns. However, this test has yet to be adopted as routine practice in Canada. The present practice point highlights essential details and recommendations for screening, which research has shown to be highly specific, with low false-positive rates. Optimal screening for critical congenital heart disease should include prenatal ultrasound, physical examination and pulse oximetry screening. Screening should be performed between 24 hours and 36 hours postbirth, using the infant's right hand and either foot to minimize false-positive results. Newborns with abnormal results should undergo a thorough evaluation by the most responsible health care provider. When a cardiac diagnosis cannot be excluded, referral to a paediatric cardiologist for consultation and echocardiogram is advised.

Previous work in HCI about personal informatics and behavior change suggests that representing data in intuitive metaphors and meaningful stories on glace-able displays should be considered to complement typical data visualization for daily user reflection and understanding. Informed by insights from social psychology, providing information regarding one's behavior (i.e., feedback) should (1) link behavioral data to positively or negatively valued outcomes; (2) show changes in the outcomes over time; and (3) include measures for pursuing different outcomes. Grounded in metaphor and blending theories from embodied cognition, we suggest metaphorically mapping less intuitive behavior-outcome links with more direct cause-effect relations from seemingly unrelated yet familiar domains. A behavior and a comparable scenario are cognitively compressed into an "animated parable". This paper describes the theoretical framework and design guidelines, and reports the development of a blended concept, "incingarette" (cigarette and incinerator), and its prototype. The work-in-progress informs updates on design recommendations.

The Academy of Administrators in Academic Emergency Medicine Benchmark Survey of academic emergency departments (EDs) was conducted in 2017. We compared operational measures between pediatric and adult (defined as fewer than 5% pediatric visits) EDs based on survey data. Emergency departments in dedicated pediatric hospitals were not represented.Measures included: (1) patient volumes, length of stay, and acuity; and 2) faculty staffing, productivity, and percent effort in academics. t Tests were used to compare continuous measures and inferences for categorical variables were made using Pearson χ2 test.The analysis included 17 pediatric and 52 adult EDs. We found a difference in the number of annual visits between adult (median, 66,275; interquartile range [IQR], 56,184-77,702) and pediatric EDs (median, 25,416; IQR, 19,840-29,349) (P0.0001). Mean "arrivals per faculty clinical hour" and "total arrivals per treatment space" showed no differences. The proportion of visits (1) arriving by emergency medical services and (2) for behavioral health were significantly higher in adult EDs (both P0.0001). The mean length of stay in hours for "all" patients was significantly longer in adult (5.4; IQR, 5.0-6.6) than in pediatric EDs (3.5; IQR, 2.9-4.3; P = 0.017). A similar difference was found for "discharged" patients (P = 0.004). Emergency severity indices, professional evaluation and management codes, and hospitalization rates all suggest higher acuity in adult EDs (all P0.0001). There were no differences in mean work relative value units per patient or in the distribution of full time equivalent effort dedicated to academics.In this cohort, significant differences in operational measures exist between academic adult and pediatric EDs. No differences were found when considering per unit measures, such as arrivals per faculty clinical hour or per treatment space.