The purpose of this study was to demonstrate the use of social network analysis to understand public discourse on Twitter around the novel coronavirus disease 2019 (COVID-19) pandemic. We examined ...different network properties that might affect the successful dissemination by and adoption of public health messages from public health officials and health agencies.
We focused on conversations on Twitter during 3 key communication events from late January to early June of 2020. We used Netlytic, a Web-based software that collects publicly available data from social media sites such as Twitter.
We found that the network of conversations around COVID-19 is highly decentralized, fragmented, and loosely connected; these characteristics can hinder the successful dissemination of public health messages in a network. Competing conversations and misinformation can hamper risk communication efforts in a way that imperil public health.
Looking at basic metrics might create a misleading picture of the effectiveness of risk communication efforts on social media if not analyzed within the context of the larger network. Social network analysis of conversations on social media should be an integral part of how public health officials and agencies plan, monitor, and evaluate risk communication efforts.
Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from ...retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.
Businesses and organizations involved in growing, distributing, and supplying food may face severe disruptions from natural and human-generated hazards, ranging from extreme weather to political ...unrest. Baltimore, Maryland, is developing policies to improve local food system organizations’ ability to prepare for, respond to, and recover from disruptive events and ultimately to contribute to food system resilience.
To identify factors that may be associated with organization-level food system resilience, how these factors may play out in disaster response, and how they may relate to organizations’ confidence in their ability to withstand disruptive events.
Semi-structured in-depth interviews with representatives of key food system businesses and organizations identified by means of stratified purposive sampling and snowball sampling.
Representatives of 26 food system businesses and organizations in Baltimore stratified by two informant categories: organizations focused on promoting food access, such as governmental offices and nonprofits, and businesses and organizations involved in supplying and distributing food in Baltimore City, such as retailers, wholesalers, and producers.
Interviews were analyzed using a phronetic iterative approach.
The following 10 factors that may contribute to organization-level resilience were identified: formal emergency planning; staff training; staff attendance; redundancy of food supply, food suppliers, infrastructure, location, and service providers; insurance; and post-event learning. Organizations that were larger, better resourced, and affiliated with national or government partners typically demonstrated more resilience factors compared with smaller, independent, and nonprofit organizations.
To ensure reliable access to safe food for all people, food system organizations must strengthen their operations to safeguard against a variety of potential threats. This study’s examination of factors that contribute to resilience can help food system organizations, researchers, and government officials identify priorities for investigating vulnerabilities in diverse operations and potential strategies to improve resilience in the face of ongoing and growing threats.
Applications of machine learning in the biomedical sciences are growing rapidly. This growth has been spurred by diverse cross-institutional and interdisciplinary collaborations, public availability ...of large datasets, an increase in the accessibility of analytic routines, and the availability of powerful computing resources. With this increased access and exposure to machine learning comes a responsibility for education and a deeper understanding of its bases and bounds, borne equally by data scientists seeking to ply their analytic wares in medical research and by biomedical scientists seeking to harness such methods to glean knowledge from data. This article provides an accessible and critical review of machine learning for a biomedically informed audience, as well as its applications in psychiatry. The review covers definitions and expositions of commonly used machine learning methods, and historical trends of their use in psychiatry. We also provide a set of standards, namely Guidelines for REporting Machine Learning Investigations in Neuropsychiatry (GREMLIN), for designing and reporting studies that use machine learning as a primary data-analysis approach. Lastly, we propose the establishment of the Machine Learning in Psychiatry (MLPsych) Consortium, enumerate its objectives, and identify areas of opportunity for future applications of machine learning in biological psychiatry. This review serves as a cautiously optimistic primer on machine learning for those on the precipice as they prepare to dive into the field, either as methodological practitioners or well-informed consumers.
DNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability
. At present, it is unknown how the locations of replication origins are ...determined in the human genome. Here we dissect the role of topologically associating domains (TADs)
, subTADs
and loops
in the positioning of replication initiation zones (IZs). We stratify TADs and subTADs by the presence of corner-dots indicative of loops and the orientation of CTCF motifs. We find that high-efficiency, early replicating IZs localize to boundaries between adjacent corner-dot TADs anchored by high-density arrays of divergently and convergently oriented CTCF motifs. By contrast, low-efficiency IZs localize to weaker dotless boundaries. Following ablation of cohesin-mediated loop extrusion during G1, high-efficiency IZs become diffuse and delocalized at boundaries with complex CTCF motif orientations. Moreover, G1 knockdown of the cohesin unloading factor WAPL results in gained long-range loops and narrowed localization of IZs at the same boundaries. Finally, targeted deletion or insertion of specific boundaries causes local replication timing shifts consistent with IZ loss or gain, respectively. Our data support a model in which cohesin-mediated loop extrusion and stalling at a subset of genetically encoded TAD and subTAD boundaries is an essential determinant of the locations of replication origins in human S phase.
Non-coding genetic variants that influence gene transcription in pancreatic islets play a major role in the susceptibility to type 2 diabetes (T2D), and likely also contribute to type 1 diabetes ...(T1D) risk. For many loci, however, the mechanisms through which non-coding variants influence diabetes susceptibility are unknown.
We examine splicing QTLs (sQTLs) in pancreatic islets from 399 human donors and observe that common genetic variation has a widespread influence on the splicing of genes with established roles in islet biology and diabetes. In parallel, we profile expression QTLs (eQTLs) and use transcriptome-wide association as well as genetic co-localization studies to assign islet sQTLs or eQTLs to T2D and T1D susceptibility signals, many of which lack candidate effector genes. This analysis reveals biologically plausible mechanisms, including the association of T2D with an sQTL that creates a nonsense isoform in ERO1B, a regulator of ER-stress and proinsulin biosynthesis. The expanded list of T2D risk effector genes reveals overrepresented pathways, including regulators of G-protein-mediated cAMP production. The analysis of sQTLs also reveals candidate effector genes for T1D susceptibility such as DCLRE1B, a senescence regulator, and lncRNA MEG3.
These data expose widespread effects of common genetic variants on RNA splicing in pancreatic islets. The results support a role for splicing variation in diabetes susceptibility, and offer a new set of genetic targets with potential therapeutic benefit.
The Wnt signalling pathway, one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL), is activated in only a subset of patients through somatic mutations. Here we describe ...alternative, microenvironment-dependent mechanisms of Wnt activation in malignant B cells. We show that tumour cells specifically induce Notch2 activity in mesenchymal stromal cells (MSCs) required for the transcription of the complement factor C1q. MSC-derived C1q in turn inhibits Gsk3-β mediated degradation of β-catenin in CLL cells. Additionally, stromal Notch2 activity regulates N-cadherin expression in CLL cells, which interacts with and further stabilises β-catenin. Together, these stroma Notch2-dependent mechanisms induce strong activation of canonical Wnt signalling in CLL cells. Pharmacological inhibition of the Wnt pathway impairs microenvironment-mediated survival of tumour cells. Similarly, inhibition of Notch signalling diminishes survival of stroma-protected CLL cells in vitro and disease engraftment in vivo. Notch2 activation in the microenvironment is a pre-requisite for the activation of canonical Wnt signalling in tumour cells.
As cases of coronavirus disease 2019 (COVID-19) mount worldwide, attention is needed on potential long-term neurologic impacts for the majority of patients who experience mild to moderate illness ...managed as outpatients. To date, there has not been discussion of persistent neurocognitive deficits in patients with milder COVID-19. We present two cases of non-hospitalized patients recovering from COVID-19 with persistent neurocognitive symptoms. Commonly used cognitive screens were normal, while more detailed testing revealed working memory and executive functioning deficits. An observational cohort study of individuals recovering from COVID-19 (14 or more days following symptom onset) identified that among the first 100 individuals enrolled, 14 were non-hospitalized patients reporting persistent cognitive issues. These 14 participants had a median age of 39 years (interquartile range: 35–56), and cognitive symptoms were present for at least a median of 98 days (interquartile range: 71–120 following acute COVID-19 symptoms); no participants with follow-up evaluation reported symptom resolution. We discuss potential mechanisms to be explored in future studies, including direct viral effects, indirect consequences of immune activation, and immune dysregulation causing auto-antibody production.
Medical and public health professionals recommend wearing face masks to combat the spread of the coronavirus disease of 2019 (COVID-19). While the majority of people in the United States support ...wearing face masks as an effective tool to combat COVID-19, a smaller percentage declared the recommendation by public health agencies as a government imposition and an infringement on personal liberty. Social media play a significant role in amplifying public health issues, whereby a minority against the imposition can speak loudly, perhaps using tactics of verbal aggression taking the form of toxic language. We investigated the role that toxicity plays in the online discourse around wearing face masks. Overall, we found tweets including anti-mask hashtags were significantly more likely to use toxic language, while tweets with pro-mask hashtags were somewhat less toxic with the exception of #WearADamnMask. We conclude that the tensions between these two positions raise doubt and uncertainty around the issue, which make it difficult for health communicators to break through the clutter in order to combat the infodemic. Public health agencies and other governmental institutions should monitor toxicity trends on social media in order to better ascertain prevailing sentiment toward their recommendations and then apply these data-driven insights to refine and adapt their risk communication messaging toward mask wearing, vaccine uptake, and other interventions.
Current national preparedness plans require local health departments to play an integral role in responding to an influenza pandemic, a major public health threat that the World Health Organization ...has described as "inevitable and possibly imminent". To understand local public health workers' perceptions toward pandemic influenza response, we surveyed 308 employees at three health departments in Maryland from March-July 2005, on factors that may influence their ability and willingness to report to duty in such an event.
The data suggest that nearly half of the local health department workers are likely not to report to duty during a pandemic. The stated likelihood of reporting to duty was significantly greater for clinical (Multivariate OR: 2.5; CI 1.3-4.7) than technical and support staff, and perception of the importance of one's role in the agency's overall response was the single most influential factor associated with willingness to report (Multivariate OR: 9.5; CI 4.6-19.9).
The perceived risk among public health workers was shown to be associated with several factors peripheral to the actual hazard of this event. These risk perception modifiers and the knowledge gaps identified serve as barriers to pandemic influenza response and must be specifically addressed to enable effective local public health response to this significant threat.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK