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"Chang, Kevin"
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autopsych: An R Shiny tool for the reproducible Rasch analysis, differential item functioning, equating, and examination of group effects
In this paper, we present autopsych , a novel online tool that allows school assessment experts, test developers, and researchers to perform routine psychometric analyses and equating of student test data and to examine the effect of student demographic and group conditions on student test performance. The app extends current open-source software by providing (1) extensive embedded result narration and summaries for written reports, (2) improved handling of partial credit data via customizable item-person Wright maps, (3) customizable item- and person-flagging systems, (4) item-response theory model constraints and controls, (5) many-facets Rasch analysis to examine item bias, (6) Rasch fixed item equating for mapping student ability across test forms, (7) tabbed spreadsheet outputs and immediate options for secondary data analysis, (8) customizable graphical color schemes, (9) extended ANOVA analysis for examining group differences, and (10) inter-rater reliability analyses for the verifying the consistency of rater scoring systems. We present the app’s architecture and functionalities and test its performance with simulated and real-world small-, medium-, and large-scale assessment data. Implications and planned future developments are also discussed.
Journal Article
AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery
Ionizable lipid nanoparticles (LNPs) are seeing widespread use in mRNA delivery, notably in SARS-CoV-2 mRNA vaccines. However, the expansion of mRNA therapies beyond COVID-19 is impeded by the absence of LNPs tailored for diverse cell types. In this study, we present the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry. AGILE streamlines ionizable lipid development with efficient library design, in silico lipid screening via deep neural networks, and adaptability to diverse cell lines. Using AGILE, we rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery, selecting from a vast library. Intriguingly, AGILE reveals cell-specific preferences for ionizable lipids, indicating tailoring for optimal delivery to varying cell types. These highlight AGILE’s potential in expediting the development of customized LNPs, addressing the complex needs of mRNA delivery in clinical practice, thereby broadening the scope and efficacy of mRNA therapies.
In this work, the authors develop a platform called AGILE or AI Guided Ionizable Lipid Engineering, which streamlines ionizable lipid development. Using AGILE, they rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery.
Journal Article
Means restriction for suicide prevention
Limitation of access to lethal methods used for suicide—so-called means restriction—is an important population strategy for suicide prevention. Many empirical studies have shown that such means restriction is effective. Although some individuals might seek other methods, many do not; when they do, the means chosen are less lethal and are associated with fewer deaths than when more dangerous ones are available. We examine how the spread of information about suicide methods through formal and informal media potentially affects the choices that people make when attempting to kill themselves. We also discuss the challenges associated with implementation of means restriction and whether numbers of deaths by suicide are reduced.
Journal Article
Impact of COVID-19 pandemic on mobility in ten countries and associated perceived risk for all transport modes
The restrictive measures implemented in response to the COVID-19 pandemic have triggered sudden massive changes to travel behaviors of people all around the world. This study examines the individual mobility patterns for all transport modes (walk, bicycle, motorcycle, car driven alone, car driven in company, bus, subway, tram, train, airplane) before and during the restrictions adopted in ten countries on six continents: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. This cross-country study also aims at understanding the predictors of protective behaviors related to the transport sector and COVID-19. Findings hinge upon an online survey conducted in May 2020 (N = 9,394). The empirical results quantify tremendous disruptions for both commuting and non-commuting travels, highlighting substantial reductions in the frequency of all types of trips and use of all modes. In terms of potential virus spread, airplanes and buses are perceived to be the riskiest transport modes, while avoidance of public transport is consistently found across the countries. According to the Protection Motivation Theory, the study sheds new light on the fact that two indicators, namely income inequality, expressed as Gini index, and the reported number of deaths due to COVID-19 per 100,000 inhabitants, aggravate respondents’ perceptions. This research indicates that socio-economic inequality and morbidity are not only related to actual health risks, as well documented in the relevant literature, but also to the perceived risks. These findings document the global impact of the COVID-19 crisis as well as provide guidance for transportation practitioners in developing future strategies.
Journal Article
Rectal cancer lexicon 2023 revised and updated consensus statement from the Society of Abdominal Radiology Colorectal and Anal Cancer Disease-Focused Panel
The Society of Abdominal Radiology’s Colorectal and Anal Cancer Disease-Focused Panel (DFP) first published a rectal cancer lexicon paper in 2019. Since that time, the DFP has published revised initial staging and restaging reporting templates, and a new SAR user guide to accompany the rectal MRI synoptic report (primary staging). This lexicon update summarizes interval developments, while conforming to the original lexicon 2019 format. Emphasis is placed on primary staging, treatment response, anatomic terminology, nodal staging, and the utility of specific sequences in the MRI protocol. A discussion of primary tumor staging reviews updates on tumor morphology and its clinical significance, T1 and T3 subclassifications and their clinical implications, T4a and T4b imaging findings/definitions, terminology updates on the use of MRF over CRM, and the conundrum of the external sphincter. A parallel section on treatment response reviews the clinical significance of near-complete response and introduces the lexicon of “regrowth” versus “recurrence”. A review of relevant anatomy incorporates updated definitions and expert consensus of anatomic landmarks, including the NCCN’s new definition of rectal upper margin and sigmoid take-off. A detailed review of nodal staging is also included, with attention to tumor location relative to the dentate line and locoregional lymph node designation, a new suggested size threshold for lateral lymph nodes and their indications for use, and imaging criteria used to differentiate tumor deposits from lymph nodes. Finally, new treatment terminologies such as organ preservation, TNT, TAMIS and watch-and-wait management are introduced. This 2023 version aims to serve as a concise set of up-to-date recommendations for radiologists, and discusses terminology, classification systems, MRI and clinical staging, and the evolving concepts in diagnosis and treatment of rectal cancer.
Journal Article
Aminode: Identification of Evolutionary Constraints in the Human Proteome
Evolutionarily constrained regions (ECRs) are a hallmark for sites of critical importance for a protein’s structure or function. ECRs can be inferred by comparing the amino acid sequences from multiple protein homologs in the context of the evolutionary relationships that link the analyzed proteins. The compilation and analysis of the datasets required to infer ECRs, however, are time consuming and require skills in coding and bioinformatics, which can limit the use of ECR analysis in the biomedical community. Here, we developed Aminode, a user-friendly webtool for the routine and rapid inference of ECRs. Aminode is pre-loaded with the results of the analysis of the whole human proteome compared with proteomes from 62 additional vertebrate species. Profiles of the relative rates of amino acid substitution and ECR maps of human proteins are available for immediate search and download on the Aminode website. Aminode can also be used for custom analyses of protein families of interest. Interestingly, mapping of known missense variants shows great enrichment of pathogenic variants and depletion of non-pathogenic variants in Aminode-generated ECRs, suggesting that ECR analysis may help evaluate the potential pathogenicity of variants of unknown significance. Aminode is freely available at
http://www.aminode.org
.
Journal Article
Criminalisation of suicide and suicide rates: an ecological study of 171 countries in the world
ObjectiveIn the last half of the 20th century, many countries have already abolished antisuicide laws; however, more than 20 countries still adopt them. This paper is the first to systematically explore the association between criminalisation of suicide and national suicide rates in 171 countries/regions to examine the deterring effects of the antisuicide laws.DesignA cross-sectional ecological study.Setting171 countries in the world.ParticipantsIn 2012, 25 countries were identified to carry antisuicide laws. A linear regression analysis was adopted to explore the association between national suicide rates (log transformed) and criminalisation of suicide in the world in 2012, having controlled for the Human Development Index (HDI), majority religious affiliations and the national unemployment rate.Main outcome measureSex-specific age standardised suicide mortality rates.ResultsCriminalisation of suicide was associated with slightly increased national suicide rates (β estimate=0.29, 95% CI −0.04 to 0.61). Stronger association was found in women (β estimate=0.40, 95% CI 0.06 to 0.74), connecting criminalisation of suicide and higher suicide rates. The harmful effect of antisuicide laws on women was particularly prominent in non-Muslim countries and countries with lower HDI.ConclusionsLaws penalising suicide were associated with higher national suicide rates and even more so in the female population in the low HDI, non-Muslim countries. The non-supportive patriarchal culture with laws penalising suicide may render women vulnerable to suicidality. Instead of criminalising suicide, alternative approaches such as providing good mental healthcare and adjusting the socioeconomic, legal and cultural factors that contribute to suicide should be considered.
Journal Article
A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer
Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and transferred to the Golgi complex by interaction with the Batten disease protein CLN8 (ceroid lipofuscinosis, neuronal, 8). Here we investigated the relationship of this pathway with CLN6, an ER-associated protein of unknown function that is defective in a different Batten disease subtype. Experiments focused on protein interaction and trafficking identified CLN6 as an obligate component of a CLN6-CLN8 complex (herein referred to as EGRESS: ER-to-Golgi relaying of enzymes of the lysosomal system), which recruits lysosomal enzymes at the ER to promote their Golgi transfer. Mutagenesis experiments showed that the second luminal loop of CLN6 is required for the interaction of CLN6 with the enzymes but dispensable for interaction with CLN8. In vitro and in vivo studies showed that CLN6 deficiency results in inefficient ER export of lysosomal enzymes and diminished levels of the enzymes at the lysosome. Mice lacking both CLN6 and CLN8 did not display aggravated pathology compared with the single deficiencies, indicating that the EGRESS complex works as a functional unit. These results identify CLN6 and the EGRESS complex as key players in lysosome biogenesis and shed light on the molecular etiology of Batten disease caused by defects in CLN6.
Journal Article
Suicide in Asia: Opportunities and Challenges
Asian countries account for approximately 60% of the world’s suicides, but there is a great mismatch in the region between the scale of the problem and the resources available to tackle it. Despite certain commonalities, the continent itself is culturally, economically, and socially diverse. This paper reviews current epidemiologic patterns of suicide, including suicide trends, sociodemographic factors, urban/rural living, suicide methods, sociocultural religious influences, and risk and protective factors in Asia, as well as their implications. The observed epidemiologic distributions of suicides reflect complex interplays among the traditional value/culture system, rapid economic transitions under market globalization, availability/desirability of suicide methods, and sociocultural permission/prohibitions regarding suicides. In general, compared with Western countries, Asian countries still have a higher average suicide rate, lower male-to-female suicide gender ratio, and higher elderly-to-general-population suicide ratios. The role of mental illness in suicide is not as important as that in Western countries. In contrast, aggravated by access to lethal means in Asia (e.g., pesticide poisoning and jumping), acute life stress (e.g., family conflicts, job and financial security issues) plays a more important role than it does in Western countries. Some promising suicide prevention programs in Asia are illustrated. Considering the specific socioeconomic and cultural aspects of the region, community-based suicide intervention programs integrating multiple layers of intervention targets may be the most feasible and cost-effective strategy in Asia, with its populous areas and limited resources.
Journal Article