Our objective was to review the characteristics, current applications, and evaluation measures of conversational agents with unconstrained natural language input capabilities used for health-related ...purposes.
We searched PubMed, Embase, CINAHL, PsycInfo, and ACM Digital using a predefined search strategy. Studies were included if they focused on consumers or healthcare professionals; involved a conversational agent using any unconstrained natural language input; and reported evaluation measures resulting from user interaction with the system. Studies were screened by independent reviewers and Cohen's kappa measured inter-coder agreement.
The database search retrieved 1513 citations; 17 articles (14 different conversational agents) met the inclusion criteria. Dialogue management strategies were mostly finite-state and frame-based (6 and 7 conversational agents, respectively); agent-based strategies were present in one type of system. Two studies were randomized controlled trials (RCTs), 1 was cross-sectional, and the remaining were quasi-experimental. Half of the conversational agents supported consumers with health tasks such as self-care. The only RCT evaluating the efficacy of a conversational agent found a significant effect in reducing depression symptoms (effect size d = 0.44, p = .04). Patient safety was rarely evaluated in the included studies.
The use of conversational agents with unconstrained natural language input capabilities for health-related purposes is an emerging field of research, where the few published studies were mainly quasi-experimental, and rarely evaluated efficacy or safety. Future studies would benefit from more robust experimental designs and standardized reporting.
The protocol for this systematic review is registered at PROSPERO with the number CRD42017065917.
The design, synthesis, and fabrication of functional nanomaterials with specific properties remain a long-standing goal for many scientific fields. The self-assembly of sequence-defined biomimetic ...synthetic polymers presents a fundamental strategy to explore the chemical space beyond biological systems to create advanced nanomaterials. Moreover, subsequent chemical modification of existing nanostructures is a unique approach for accessing increasingly complex nanostructures and introducing functionalities. Of these modifications, covalent conjugation chemistries, such as the click reactions, have been the cornerstone for chemists and materials scientists. Herein, we highlight some recent advances that have successfully employed click chemistries for the postmodification of assembled one-dimensional (1D) and two-dimensional (2D) nanostructures to achieve applications in molecular recognition, mineralization, and optoelectronics. Specifically, biomimetic nanomaterials assembled from sequence-defined macromolecules such as peptides and peptoids are described.
The acquisition of resistance is a major obstacle to the clinical use of platinum drugs for ovarian cancer treatment. Increase of DNA damage response is one of major mechanisms contributing to ...platinum-resistance. However, how DNA damage response is regulated in platinum-resistant ovarian cancer cells remains unclear. Using quantitative high throughput combinational screen (qHTCS) and RNA-sequencing (RNA-seq), we show that dual oxidase maturation factor 1 (DUOXA1) is overexpressed in platinum-resistant ovarian cancer cells, resulting in over production of reactive oxygen species (ROS). Elevated ROS level sustains the activation of ATR-Chk1 pathway, leading to resistance to cisplatin in ovarian cancer cells. Moreover, using qHTCS we identified two Chk1 inhibitors (PF-477736 and AZD7762) that re-sensitize resistant cells to cisplatin. Blocking this novel pathway by inhibiting ROS, DUOXA1, ATR or Chk1 effectively overcomes cisplatin resistance in vitro and in vivo. Significantly, the clinical studies also confirm the activation of ATR and DOUXA1 in ovarian cancer patients, and elevated DOUXA1 or ATR-Chk1 pathway correlates with poor prognosis. Taken together, our findings not only reveal a novel mechanism regulating cisplatin resistance, but also provide multiple combinational strategies to overcome platinum-resistance in ovarian cancer.
•Providing multiple potential approaches for treatment of platinum resistant ovarian cancer.•Integrating qHTCS, RNA-seq and clinical studies to elucidate cisplatin resistant mechanism.•DUOXA1-mediated activation of ATR-Chk1 regulates cisplatin resistance in ovarian cancer.
Many critics raise concerns about the prevalence of 'echo chambers' on social media and their potential role in increasing political polarization. However, the lack of available data and the ...challenges of conducting large-scale field experiments have made it difficult to assess the scope of the problem
. Here we present data from 2020 for the entire population of active adult Facebook users in the USA showing that content from 'like-minded' sources constitutes the majority of what people see on the platform, although political information and news represent only a small fraction of these exposures. To evaluate a potential response to concerns about the effects of echo chambers, we conducted a multi-wave field experiment on Facebook among 23,377 users for whom we reduced exposure to content from like-minded sources during the 2020 US presidential election by about one-third. We found that the intervention increased their exposure to content from cross-cutting sources and decreased exposure to uncivil language, but had no measurable effects on eight preregistered attitudinal measures such as affective polarization, ideological extremity, candidate evaluations and belief in false claims. These precisely estimated results suggest that although exposure to content from like-minded sources on social media is common, reducing its prevalence during the 2020 US presidential election did not correspondingly reduce polarization in beliefs or attitudes.
Human colonic epithelial cell renewal, proliferation, and differentiation are stringently controlled by numerous regulatory pathways. To identify genetic programs of human colonic epithelial cell ...differentiation in vivo as well as candidate marker genes that define colonic epithelial stem/progenitor cells and the stem cell niche, we applied gene expression analysis of normal human colon tops and basal crypts by using expression microarrays with 30,000 genes. Nine hundred and sixty-nine cDNA clones were found to be differentially expressed between human colon crypts and tops. Pathway analysis revealed the differential expression of genes involved in cell cycle maintenance and apoptosis, as well as genes in bone morphogenetic protein (BMP), Notch, Wnt, EPH, and MYC signaling pathways. BMP antagonists gremlin 1, gremlin 2, and chordin-like 1 were found to be expressed by colon crypts. In situ hybridization and RT-PCR confirmed that these BMP antagonists are expressed by intestinal cryptal myofibroblasts and smooth muscle cells at the colon crypt. In vitro analysis demonstrated that gremlin 1 partially inhibits Caco-2 cell differentiation upon confluence and activates Wnt signaling in normal rat intestinal epithelial cells. Collectively, the expression data set provides a comprehensive picture of human colonic epithelial cell differentiation. Our study also suggests that BMP antagonists are candidate signaling components that make up the intestinal epithelial stem cell niche.
Continuity of care (COC) has been emphasized in research on terminal cancer patients to increase the quality of end-of-life care; however, limited research has been conducted on end-stage renal ...disease patients. We applied a retrospective cohort design on 29,095 elderly patients with end-stage renal disease who died between 2005 and 2013. These patients were identified from the National Health Insurance Research Database of Taiwan. The provider Continuity of Care Index (COCI) and site COCI were calculated on the basis of outpatient visits during the 6-12 months before death. We discovered that increases in the provider COCI were significantly associated with reductions in health expenditures after adjusting for confounders, especially in inpatient and emergency departments, where the treatment intensity is high. Higher provider and site COC were also associated with lower utilization of acute care and invasive treatments in the last month before death. Provider COC had a greater effect on end-of-life care expenditures than site COC did, which indicated significant care coordination gaps within the same facility. Our findings support the recommendation of prioritizing the continuity of end-of-life care, especially provider continuity, for patients with end-stage renal disease.
Abstract Sphingolipids are a ubiquitous membrane lipid present in every cell and found most abundantly in neural tissues. Disorders such as Tay-Sachs or Niemann-Pick disease are the most familiar ...examples of dysfunction in sphingolipid metabolism and are typically associated with neurodegeneration and ocular findings such as blindness. More recently, the role of bioactive sphingolipids has been established in a multitude of cellular events, including cell survival, growth, senescence and apoptosis, inflammation, and neovascularization. We discuss our current knowledge and understanding of sphingolipid metabolism and signaling in the pathogenesis of ocular diseases.
Accumulated evidence indicates that immune cells can support the replication of hepatitis C virus (HCV) in infected patients and in culture. However, there is a scarcity of data on the degree to ...which individual immune cell types support HCV propagation and on characteristics of virus assembly. We investigated the ability of authentic, patient-derived HCV to infect
two closely related but functionally distinct immune cell types, CD4
and CD8
T lymphocytes, and assessed the properties of the virus produced by these cells. The HCV replication system in intermittently mitogen-stimulated T cells was adapted to infect primary human CD4
or CD8
T lymphocytes. HCV replicated in both cell types although at significantly higher levels in CD4
than in CD8
T cells. Thus, the HCV RNA replicative (negative) strand was detected in CD4
and CD8
cells at estimated mean levels ± standard errors of the means of 6.7 × 10
± 3.8 × 10
and 1.2 × 10
± 0.8 × 10
copies/μg RNA, respectively (
< 0.0001). Intracellular HCV NS5a and/or core proteins were identified in 0.9% of CD4
and in 1.2% of CD8
T cells. Double staining for NS5a and T cell type-specific markers confirmed that transcriptionally competent virus replicated in both cell types. Furthermore, an HCV-specific protease inhibitor, telaprevir, inhibited infection in both CD4
and CD8
cells. The emergence of unique HCV variants and the release of HCV RNA-reactive particles with biophysical properties different from those of virions in plasma inocula suggested that distinct viral particles were assembled, and therefore, they may contribute to the pool of circulating virus in infected patients.
Although the liver is the main site of HCV replication, infection of the immune system is an intrinsic characteristic of this virus independent of whether infection is symptomatic or clinically silent. Many fundamental aspects of HCV lymphotropism remain uncertain, including the degree to which different immune cells support infection and contribute to virus diversity. We show that authentic, patient-derived HCV productively replicates
in two closely related but functionally distinct types of T lymphocytes, CD4
and CD8
cells. The display of viral proteins and unique variants, the production of virions with biophysical properties distinct from those in plasma serving as inocula, and inhibition of replication by an antiviral agent led us to ascertain that both T cell subtypes supported virus propagation. Infection of CD4
and CD8
T cells, which are central to adaptive antiviral immune responses, can directly affect HCV clearance, favor virus persistence, and decisively influence the development and progression of hepatitis C.
The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development and function of glutamatergic synapses. Disruption of the SHANK3-encoding gene ...has been strongly implicated as a monogenic cause of autism, and Shank3 mutant mice show repetitive grooming and social interaction deficits. Although basal ganglia dysfunction has been proposed to underlie repetitive behaviors, few studies have provided direct evidence to support this notion and the exact cellular mechanisms remain largely unknown. Here, we utilized the Shank3B mutant mouse model of autism to investigate how Shank3 mutation may differentially affect striatonigral (direct pathway) and striatopallidal (indirect pathway) medium spiny neurons (MSNs) and its relevance to repetitive grooming behavior in Shank3B mutant mice. We found that Shank3 deletion preferentially affects synapses onto striatopallidal MSNs. Striatopallidal MSNs showed profound defects, including alterations in synaptic transmission, synaptic plasticity, and spine density. Importantly, the repetitive grooming behavior was rescued by selectively enhancing the striatopallidal MSN activity via a Gq-coupled human M3 muscarinic receptor (hM3Dq), a type of designer receptors exclusively activated by designer drugs (DREADD). Our findings directly demonstrate the existence of distinct changes between 2 striatal pathways in a mouse model of autism and indicate that the indirect striatal pathway disruption might play a causative role in repetitive behavior of Shank3B mutant mice.
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