Butyrate acts as a positive allosteric modulator of the 5-HT transporter to decrease availability of 5-HT in the ileum.

BACKGROUND AND PURPOSE: Radiation therapy-induced gastrointestinal distress is partly associated with the elimination of gut microbiota. The effectiveness of 5-HT receptor antagonists to treat radiation therapy-induced emesis implies a pathophysiological role of 5-HT. Peripheral 5-HT is derived from intestinal epithelium. We have investigated the role of gut microbiota in regulating intestinal 5-HT availability. EXPERIMENTAL APPROACH: A radiation therapy murine model accompanied by faecal microbiota transplantation from donors fed different diets was investigated, and mouse ileal organoids were used for mechanistic studies. The clinical relevance was validated by a small-scale human study. KEY RESULTS: Short-term high-fat diet (HFD) induced gut bacteria to produce butyrate. Irradiated mice receiving HFD-induced microbiome had the lowest ileal levels of 5-HT, compared with other recipients. Treatment with butyrate increased 5-HT uptake in mouse ileal organoids, assayed by the real-time tracking of a fluorescent substrate for monoamine transporters. Silencing the 5-HT transporter (SERT) in the organoids abolished butyrate-stimulated 5-HT uptake. The competitive tests using different types of selective 5-HT reuptake inhibitors suggested that butyrate acted as a positive allosteric modulator of SERT. In human gut microbiota, butyrate production was associated with the interconversion between acetate and butyrate. Faecal contents of both acetate and butyrate were negatively associated with serum 5-HT, but only butyrate was positively correlated with body mass index in humans. CONCLUSION AND IMPLICATIONS: Short-term HFD may be beneficial for alleviating gastrointestinal reactions by increasing butyrate to suppress local 5-HT levels and providing energy to cancer patients given radiation therapy.

Using AI-ML to Augment the Capabilities of Social Media for Telehealth and Remote Patient Monitoring.

Artificial intelligence (AI) and machine learning (ML) have revolutionized the way health organizations approach social media. The sheer volume of data generated through social media can be overwhelming, but AI and ML can help organizations effectively manage this information to improve telehealth, remote patient monitoring, and the well-being of individuals and communities. Previous research has revealed several trends in AI-ML adoption: First, AI can be used to enhance social media marketing. Drawing on sentiment analysis and related tools, social media is an effective way to increase brand awareness and customer engagement. Second, social media can become a very useful data collection tool when integrated with new AI-ML technologies. Using this function well requires researchers and practitioners to protect users' privacy carefully, such as through the deployment of privacy-enhancing technologies (PETs). Third, AI-ML enables organizations to maintain a long-term relationship with stakeholders. Chatbots and related tools can increase users' ability to receive personalized content. The review in this paper identifies research gaps in the literature. In view of these gaps, the paper proposes a conceptual framework that highlights essential components for better utilizing AI and ML. Additionally, it enables researchers and practitioners to better design social media platforms that minimize the spread of misinformation and address ethical concerns more readily. It also provides insights into the adoption of AI and ML in the context of remote patient monitoring and telehealth within social media platforms.

DNA- and RNA-Binding Proteins Linked Transcriptional Control and Alternative Splicing Together in a Two-Layer Regulatory Network System of Chronic Myeloid Leukemia.

DNA- and RNA-binding proteins (DRBPs) typically possess multiple functions to bind both DNA and RNA and regulate gene expression from more than one level. They are controllers for post-transcriptional processes, such as splicing, polyadenylation, transportation, translation, and degradation of RNA transcripts in eukaryotic organisms, as well as regulators on the transcriptional level. Although DRBPs are reported to play critical roles in various developmental processes and diseases, it is still unclear how they work with DNAs and RNAs simultaneously and regulate genes at the transcriptional and post-transcriptional levels. To investigate the functional mechanism of DRBPs, we collected data from a variety of databases and literature and identified 118 DRBPs, which function as both transcription factors (TFs) and splicing factors (SFs), thus called DRBP-SF. Extensive investigations were conducted on four DRBP-SFs that were highly expressed in chronic myeloid leukemia (CML), heterogeneous nuclear ribonucleoprotein K (HNRNPK), heterogeneous nuclear ribonucleoprotein L (HNRNPL), non-POU domain-containing octamer-binding protein (NONO), and TAR DNA-binding protein 43 (TARDBP). By integrating and analyzing ChIP-seq, CLIP-seq, RNA-seq, and shRNA-seq data in K562 using binding and expression target analysis and Statistical Utility for RBP Functions, we discovered a two-layer regulatory network system centered on these four DRBP-SFs and proposed three possible regulatory models where DRBP-SFs can connect transcriptional and alternative splicing regulatory networks cooperatively in CML. The exploration of the identified DRBP-SFs provides new ideas for studying DRBP and regulatory networks, holding promise for further mechanistic discoveries of the two-layer gene regulatory system that may play critical roles in the occurrence and development of CML.

CORN-Condition Orientated Regulatory Networks: bridging conditions to gene networks.

A transcriptional regulatory network (TRN) is a collection of transcription regulators with their associated downstream genes, which is highly condition-specific. Understanding how cell states can be programmed through small molecules/drugs or conditions by modulating the whole gene expression system granted us the potential to amend abnormal cells and cure diseases. Condition Orientated Regulatory Networks (CORN, https://qinlab.sysu.edu.cn/home) is a library of condition (small molecule/drug treatments and gene knockdowns)-based transcriptional regulatory sub-networks (TRSNs) that come with an online TRSN matching tool. It allows users to browse condition-associated TRSNs or match those TRSNs by inputting transcriptomic changes of interest. CORN utilizes transcriptomic changes data after specific conditional treatment in cells, and in vivo transcription factor (TF) binding data in cells, by combining TF binding information and calculations of significant expression alterations of TFs and genes after the conditional treatments, TRNs under the effect of different conditions were constructed. In short, CORN associated 1805 different types of specific conditions (small molecule/drug treatments and gene knockdowns) to 9553 TRSNs in 25 human cell lines, involving 204TFs. By linking and curating specific conditions to responsive TRNs, the scientific community can now perceive how TRNs are altered and controlled by conditions alone in an organized manner for the first time. This study demonstrated with examples that CORN can aid the understanding of molecular pathology, pharmacology and drug repositioning, and screened drugs with high potential for cancer and coronavirus disease 2019 (COVID-19) treatments.

Cell fate conversion prediction by group sparse optimization method utilizing single-cell and bulk OMICs data.

Cell fate conversion by overexpressing defined factors is a powerful tool in regenerative medicine. However, identifying key factors for cell fate conversion requires laborious experimental efforts; thus, many of such conversions have not been achieved yet. Nevertheless, cell fate conversions found in many published studies were incomplete as the expression of important gene sets could not be manipulated thoroughly. Therefore, the identification of master transcription factors for complete and efficient conversion is crucial to render this technology more applicable clinically. In the past decade, systematic analyses on various single-cell and bulk OMICs data have uncovered numerous gene regulatory mechanisms, and made it possible to predict master gene regulators during cell fate conversion. By virtue of the sparse structure of master transcription factors and the group structure of their simultaneous regulatory effects on the cell fate conversion process, this study introduces a novel computational method predicting master transcription factors based on group sparse optimization technique integrating data from multi-OMICs levels, which can be applicable to both single-cell and bulk OMICs data with a high tolerance of data sparsity. When it is compared with current prediction methods by cross-referencing published and validated master transcription factors, it possesses superior performance. In short, this method facilitates fast identification of key regulators, give raise to the possibility of higher successful conversion rate and in the hope of reducing experimental cost.

Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth.

Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine belonging to the IL-7 family and a key initiator of allergic inflammation. Two main isoforms of TSLP, classified as long- (lfTSLP) and short-form (sfTSLP), have been reported in human, but their expression patterns and role(s) in cancers are not yet clear. mRNA expression was examined by isoform-specific RT-PCR and RNA in situ hybridisation. Epigenetic regulation was investigated by chromatin immunoprecipitation-PCR and bisulfite sequencing. Tumour progression was investigated by gene overexpression, cell viability assay, cancer organoid culture and transwell invasion. Signals were investigated by proteome profiler protein array and RNA-sequencing. With the use of isoform-specific primers and probes, we uncovered that only sfTSLP was expressed in the cell lines and tumour tissues of human ovarian and endometrial cancers. We also showed the epigenetic regulation of sfTSLP: sfTSLP transcription was regulated by histone acetylation at promoters in ovarian cancer cells, whereas silencing of the sfTSLP transcripts was regulated by promoter DNA methylation in endometrial cancer cells. In vitro study showed that ectopically overexpressing sfTSLP promoted tumour growth but not invasion. Human phosphokinase array application demonstrated that the sfTSLP overexpression activated phosphorylation of multiple intracellular kinases (including GSK3α/ß, AMPKα1, p53, AKT1/2, ERK1/2 and Src) in ovarian cancer cells in a context-dependent manner. We further investigated the impact of sfTSLP overexpression on transcriptome by RNA-sequencing and found that EFNB2 and PBX1 were downregulated in ovarian and endometrial cancer cells, suggesting their role in sfTSLP-mediated tumour growth. In conclusion, sfTSLP is predominantly expressed in ovarian and endometrial cancers and promotes tumour growth.

Integration of single-cell multi-omics for gene regulatory network inference.

The advancement of single-cell sequencing technology in recent years has provided an opportunity to reconstruct gene regulatory networks (GRNs) with the data from thousands of single cells in one sample. This uncovers regulatory interactions in cells and speeds up the discoveries of regulatory mechanisms in diseases and biological processes. Therefore, more methods have been proposed to reconstruct GRNs using single-cell sequencing data. In this review, we introduce technologies for sequencing single-cell genome, transcriptome, and epigenome. At the same time, we present an overview of current GRN reconstruction strategies utilizing different single-cell sequencing data. Bioinformatics tools were grouped by their input data type and mathematical principles for reader's convenience, and the fundamental mathematics inherent in each group will be discussed. Furthermore, the adaptabilities and limitations of these different methods will also be summarized and compared, with the hope to facilitate researchers recognizing the most suitable tools for them.

Increasing the Impact of JMIR Journals in the Attention Economy.

The Journal of Medical Internet Research (JMIR) has attained remarkable achievements in the past twenty years. By depth, JMIR has published the most impactful research in medical informatics and is top ranked in the field. By width, JMIR has spun off to about thirty sister journals to cover topics such as serious games, mobile health, public health, surveillance, and other medical areas. With ever-increasing data and research findings, academic publishers need to be competitive to win readers' attention. While JMIR is well-positioned in the field, the journal will need more creative strategies to increase its attention base and maintain its leading position. Viable strategies include the creation of online collaborative spaces, the engagement of more diverse audience from less traditional channels, and partnerships with other publishers and academic institutes. Doing so could also enable JMIR researchers to turn research insights into practical strategies to improve personal health and medical services.

ENPD - A Database of Eukaryotic Nucleic Acid Binding Proteins: Linking Gene Regulations to Proteins.

Eukaryotic nucleic acid binding protein database (ENPD, http://qinlab.sls.cuhk.edu.hk/ENPD/) is a library of nucleic acid binding proteins (NBPs) and their functional information. NBPs such as DNA binding proteins (DBPs), RNA binding proteins (RBPs), and DNA and RNA binding proteins (DRBPs) are involved in every stage of gene regulation through their interactions with DNA and RNA. Due to the importance of NBPs, the database was constructed based on manual curation and a newly developed pipeline utilizing both sequenced transcriptomes and genomes. In total the database has recorded 2.8 million of NBPs and their binding motifs from 662 NBP families and 2423 species, constituting the largest NBP database. ENPD covers evolutionarily important lineages which have never been included in the previous NBP databases, while lineage-specific NBP family expansions were also found. ENPD also focuses on the involvements of DBPs, RBPs and DRBPs in non-coding RNA (ncRNA) mediated gene regulation. The predicted and experimentally validated targets of NBPs have both been recorded and manually curated in ENPD, linking the interactions between ncRNAs, DNA regulatory elements and NBPs in gene regulation. This database provides key resources for the scientific community, laying a solid foundation for future gene regulatory studies from both functional and evolutionary perspectives.

Social Media Users' Perception of Telemedicine and mHealth in China: Exploratory Study.

BACKGROUND: The use of telemedicine and mHealth has increased rapidly in the People's Republic of China. While telemedicine and mHealth have great potential, wide adoption of this technology depends on how patients, health care providers, and other stakeholders in the Chinese health sector perceive and accept the technology. OBJECTIVE: To explore this issue, we aimed to examine a social media platform with a dedicated focus on health information technology and informatics in China. Our goal is to utilize the findings to support further research. METHODS: In this exploratory study, we selected a social media platform-HC3i.cn-to examine the perception of telemedicine and mHealth in China. We performed keyword analysis and analyzed the prevalence and term frequency-inverse document frequency of keywords in the selected social media platform; furthermore, we performed qualitative analysis. RESULTS: We organized the most prominent 16 keywords from 571 threads into 8 themes: (1) Question versus Answer; (2) Hospital versus Clinic; (3) Market versus Company; (4) Doctor versus Nurse; (5) Family versus Patient; (6) iPad versus Tablet; (7) System versus App; and (8) Security versus Caregiving. Social media participants perceived not only significant opportunities associated with telemedicine and mHealth but also barriers to overcome to realize these opportunities. CONCLUSIONS: We identified interesting issues in this paper by studying a social media platform in China. Among other things, participants in the selected platform raised concerns about quality and costs associated with the provision of telemedicine and mHealth, despite the new technology's great potential to address different issues in the Chinese health sector. The methods applied in this paper have some limitations, and the findings may not be generalizable. We have discussed directions for further research.

Are the current thresholds, indicators, and time window for cold warning effective enough to protect cardiovascular health?

More extreme cold weather and larger weather variations have raised concerns regarding their effects on public health. Although prior studies assessed the effects of cold air temperature on health, especially mortality, limited studies evaluated wind chill temperatures on morbidity, and health effects under the current cold warning threshold. This study identified the thresholds, lag periods, and best indicators of extreme cold on cardiovascular disease (CVD) by comparing effects of wind chill temperatures and cold air temperatures on CVD emergency department (ED) visits in winter and winter transition months. Information was collected on 662,625 CVD ED visits from statewide hospital discharge dataset in New York State. Meteorological factors, including air temperature, wind speed, and barometric pressure were collected from National Oceanic and Atmospheric Administration. A case-crossover approach was used to assess the extreme cold-CVD relationship in winter (December-February) and transition months (November and March) after controlling for PM2.5. Conditional logistic regression models were employed to analyze the association between cold weather factors and CVD ED visits. We observed CVD effects occurred when wind chill temperatures were as high as -3.8 °C (25 °F), warmer than current wind chill warning standard (≤-28.8 °C or ≤-20 °F). Wind chill temperature was a more sensitive indicator of CVD ED visits during winter with temperatures ≤ -3.8 °C (25 °F) with delay effect (lag 6); however, air temperature was better during transition months for temperatures ≤ 7.2 °C (45 °F) at earlier lag days (1-3). Among all CVD subtypes, hypertension ED visit had the strongest negative association with both wind chill temperature and air temperature. This study recommends modifying the current cold warning temperature threshold given larger proportions of CVD cases are occurring at considerably higher temperatures than the current criteria. We also recommend issuing cold warnings in winter transitional months.

CrusTF: a comprehensive resource of transcriptomes for evolutionary and functional studies of crustacean transcription factors.

BACKGROUND: Crustacea, the second largest subphylum of Arthropoda, includes species of major ecological and economic importance, such as crabs, lobsters, crayfishes, shrimps, and barnacles. With the rapid development of crustacean aquaculture and biodiversity loss, understanding the gene regulatory mechanisms of growth, reproduction, and development of crustaceans is crucial to both aquaculture development and biodiversity conservation of this group of organisms. In these biological processes, transcription factors (TFs) play a vital role in regulating gene expression. However, crustacean transcription factors are still largely unknown, because the lack of complete genome sequences of most crustacean species hampers the studies on their transcriptional regulation on a system-wide scale. Thus, the current TF databases derived from genome sequences contain TF information for only a few crustacean species and are insufficient to elucidate the transcriptional diversity of such a large animal group. RESULTS: Our database CrusTF ( http://qinlab.sls.cuhk.edu.hk/CrusTF ) provides comprehensive information for evolutionary and functional studies on the crustacean transcriptional regulatory system. CrusTF fills the knowledge gap of transcriptional regulation in crustaceans by exploring publicly available and newly sequenced transcriptomes of 170 crustacean species and identifying 131,941 TFs within 63 TF families. CrusTF features three categories of information: sequence, function, and evolution of crustacean TFs. The database enables searching, browsing and downloading of crustacean TF sequences. CrusTF infers DNA binding motifs of crustacean TFs, thus facilitating the users to predict potential downstream TF targets. The database also presents evolutionary analyses of crustacean TFs, which improve our understanding of the evolution of transcriptional regulatory systems in crustaceans. CONCLUSIONS: Given the importance of TF information in evolutionary and functional studies on transcriptional regulatory systems of crustaceans, this database will constitute a key resource for the research community of crustacean biology and evolutionary biology. Moreover, CrusTF serves as a model for the construction of TF database derived from transcriptome data. A similar approach could be applied to other groups of organisms, for which transcriptomes are more readily available than genomes.

Capturing Parent-Child Interactions With Social Media: Comment on Zhang et al. (2015).

Zhang et al. conducted a qualitative study of children presented with 19 parental structuring behaviors of parental control and were asked to attribute the parent's intent behind the behaviors. The authors developed several conceptual categories, "parent-centered," "child-centered," or "social" interests. Here, we describe how their 12 propositions could be empirically tested in further studies using social media.

Attitudes towards suicide in urban and rural China: a population based, cross-sectional study.

BACKGROUND: Suicide intervention programs have been guided by findings that attitude towards suicide and suicidal behavior may be causally linked. These findings also make it imperative to identify the factors that influence attitudes towards suicide. However, there has been little research on attitudes towards suicide among the general population, especially in low-income and middle-income countries. This population-based, cross-sectional study investigated the associated factors of attitudes towards suicide among a representative sample of urban and rural adult residents in China. METHODS: A multi-stage, stratified random sampling approach was implemented to select participants. Data were collected by a survey using the Scale of Public Attitudes about Suicide (SPAS). The survey also collected some socio-demographic factors and suicidal history of participants. Statistical tests were conducted to identify associated factors that account for variations in attitudes towards suicide. RESULTS: The residents in China generally hold a neutral attitude towards suicide. Attitudes towards suicide among Chinese residents were associated with age, duration of formal education, marital status, job and suicidal ideation. Different attitudinal subscales seemed not to share the same risk factors. However, gender, ethnicity, religious belief, housing style and economic status might not influence residents' attitudes towards suicide. Attitudes towards suicide among Chinese urban and rural residents generally had no statistical difference with one notable exception: opinions on whether or not suicides and suicide attempts are different phenomena. CONCLUSIONS: Age, duration of formal education, marital status, job and suicidal ideation seem to have an impact on attitudes towards suicide among residents. Urban and rural residents have similar attitudes towards suicide with the only statistically significance difference being their opinions on whether or not suicides and suicide attempts are different phenomena.

The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013.

BACKGROUND: The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. METHODS: Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. RESULTS: In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. CONCLUSIONS: Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Building Mobile Apps for Underrepresented Mental Health care Consumers: A Grounded Theory Approach.

Cell phone mobile application ("app") use has risen dramatically within the past several years. Many individuals access apps to address mental health issues. Unlike individuals from privileged backgrounds, individuals from oppressed backgrounds may rely on apps rather than costly mental health treatment. To date, very little research has been published evaluating mental health apps' effectiveness. This paper focuses on three methods through which grounded theory can facilitate app development and evaluation for people underrepresented in mental health care. Recommendations are made to advance mobile app technology that will help clinicians provide effective treatment, and consumers to realize positive treatment outcomes.

Identification of putative ecdysteroid and juvenile hormone pathway genes in the shrimp Neocaridina denticulata.

Although the sesquiterpenoid juvenile hormone (JH) and the steroidal ecdysteroids are of vital importance to the development and reproduction of insects, our understanding of the evolution of these crucial hormonal regulators in other arthropods is limited. To better understand arthropod hormone evolution and regulation, here we describe the hormonal pathway genes (e.g. those involved in hormone biosynthesis, degradation, regulation and signal transduction) of a new decapod model, the shrimp Neocaridina denticulata. The majority of known insect sesquiterpenoid and ecdysteroid pathway genes and their regulators are contained in the N. denticulata genome. In the sesquiterpenoid pathway, these include biosynthetic pathway components: juvenile hormone acid methyltransferase (JHAMT); hormone binding protein: juvenile hormone binding protein (JHBP); and degradation pathway components: juvenile hormone esterase (JHE), juvenile hormone esterase binding protein (JHEBP) and juvenile hormone epoxide hydrolase (JHEH), with the JHBP, JHEBP and JHEH genes being discovered in a crustacean for the first time here. Ecdysteroid biosynthetic pathway genes identified include spook, phantom, disembodied, shadow and CYP18. Potential hormonal regulators and signal transducers such as allatostatins (ASTs), Methoprene-tolerant (Met), Retinoid X receptor (RXR), Ecdysone receptor (EcR), calponin-like protein Chd64, FK509-binding protein (FKBP39), Broad-complex (Br-c), and crustacean hyperglycemic hormone/molt-inhibiting hormone/gonad-inhibiting hormone (CHH/MIH/GIH) genes are all present in the shrimp N. denticulata. To our knowledge, this is the first report of these hormonal pathways and their regulatory genes together in a single decapod, providing a vital resource for further research into development, reproduction, endocrinology and evolution of crustaceans, and arthropods in general.

Evaluating the benefits of collaboration in simulation games: the case of health care.

BACKGROUND: Organizations have used simulation games for health promotion and communication. To evaluate how simulation games can foster collaboration among stakeholders, this paper develops two social network measures. OBJECTIVE: The paper aims to initiate two specific measures that facilitate organizations and researchers to evaluate the effectiveness of Web-based simulation games in fostering collaboration. METHODS: The two measures are: (1) network density and (2) network diversity. They measure the level of connectedness and communication evenness within social networks. To illustrate how these measures may be used, a hypothetical game about health policy is outlined. RESULTS: Web-based games can serve as an effective platform to engage stakeholders because interaction among them is quite convenient. Yet, systematic evaluation and planning are necessary to realize the benefits of these games. The paper suggests directions for testing how the social network dimension of Web-based games can augment individual-level benefits that stakeholders can obtain from playing simulation games. CONCLUSIONS: While this paper focuses on measuring the structural properties of social networks in Web-based games, further research should focus more attention on the appropriateness of game contents. In addition, empirical research should cover different geographical areas, such as East Asian countries where video games are very popular.

Health information technology and dynamic capabilities.

BACKGROUND: Health information technology (HIT) purports to increase quality and efficiency in health care organizations. However, health care organizations are situated in constantly changing environments. They need dynamic capabilities to implement HIT effectively. PURPOSES: This article builds on the dynamic capabilities perspective and generates propositions about implementing HIT in dynamic environments. Specifically, I identify the (1) the necessary resources and capabilities for organizations to implement HIT; (2) the organizational capabilities and benefits that can be enhanced by HIT; and (3) the similarities and differences between three distinct forms of HIT. APPROACH: I synthesized the literature on dynamic capabilities and HIT to identify dynamic capabilities that are associated with (1) electronic medical records, (2) telemedicine, and (3) social media. In addition, I discuss the benefits of these HITs for improving the dynamic capabilities of health care organizations. PROPOSITIONS/FINDINGS: This article generates three sets of propositions that can be tested empirically. First, I am concerned with how organizational size and human resources affect successful implementation of HIT. In addition, I argue that three technology-specific factors--hospital type, medical specialty, and socially desirable technical features--may affect the implementation of HIT. PRACTICAL IMPLICATIONS: To cope with constantly changing environmental pressures, health administrators need to deploy, modify, and/or acquire organizational resources skillfully. Practitioners need to identify dynamic capabilities to support specific forms of HIT and understand how HIT enables health care organizations in turn. The concept of evolutionary fitness in the dynamic capabilities perspective may be developed to measure HIT implementation.

Atrophin 2 recruits histone deacetylase and is required for the function of multiple signaling centers during mouse embryogenesis.

Atrophins are evolutionarily conserved proteins that are thought to act as transcriptional co-repressors. Mammalian genomes contain two atrophin genes. Dominant polyglutamine-expanded alleles of atrophin 1 have been identified as the cause of dentatorubralpallidoluysian atrophy, an adult-onset human neurodegenerative disease with similarity to Huntington's. In a screen for recessive mutations that disrupt patterning of the early mouse embryo, we identified a line named openmind carrying a mutation in atrophin 2. openmind homozygous embryos exhibit a variety of patterning defects that first appear at E8.0. Defects include a specific failure in ventralization of the anterior neural plate, loss of heart looping and irregular partitioning of somites. In mutant embryos, Shh expression fails to initiate along the anterior midline at E8.0, and Fgf8 is delocalized from the anterior neural ridge at E8.5, revealing a crucial role for atrophin 2 in the formation and function of these two signaling centers. Atrophin 2 is also required for normal organization of the apical ectodermal ridge, a signaling center that directs limb pattern. Elevated expression of atrophin 2 in neurons suggests it may interact with atrophin 1 in neuronal development or function. We further show that atrophin 2 associates with histone deacetylase 1 in mouse embryos, providing a biochemical link between Atr2 and a chromatin-modifying enzyme. Based on our results, and on those of others, we propose that atrophin proteins act as transcriptional co-repressors during embryonic development.