Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collect single nuclei RNA-seq data from 84,700 nuclei of 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues and characterize tumor heterogeneity and transcriptomic alterations. We distinguish cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observe pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identify transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. Here we address current gaps in understanding single nuclei gene expression profiles of previously under-investigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.

Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors.

Although intratumoral heterogeneity has been established in pediatric central nervous system tumors, epigenomic alterations at the cell type level have largely remained unresolved. To identify cell type-specific alterations to cytosine modifications in pediatric central nervous system tumors, we utilize a multi-omic approach that integrated bulk DNA cytosine modification data (methylation and hydroxymethylation) with both bulk and single-cell RNA-sequencing data. We demonstrate a large reduction in the scope of significantly differentially modified cytosines in tumors when accounting for tumor cell type composition. In the progenitor-like cell types of tumors, we identify a preponderance differential Cytosine-phosphate-Guanine site hydroxymethylation rather than methylation. Genes with differential hydroxymethylation, like histone deacetylase 4 and insulin-like growth factor 1 receptor, are associated with cell type-specific changes in gene expression in tumors. Our results highlight the importance of epigenomic alterations in the progenitor-like cell types and its role in cell type-specific transcriptional regulation in pediatric central nervous system tumors.

Impact of Apolipoprotein E4 on the Locus Coeruleus Functional Connectivity in Preclinical Alzheimer's Disease.

Background: Recent interest has surged in the locus coeruleus (LC) for its early involvement in Alzheimer's disease (AD), notably concerning the apolipoprotein ɛ4 allele (APOE4). Objective: This study aimed to discern LC functional connectivity (FC) variations in preclinical AD subjects, dissecting the roles of APOE4 carrier status and amyloid-ß (Aß) deposition. Methods: A cohort of 112 cognitively intact individuals, all Aß-positive, split into 70 APOE4 noncarriers and 42 carriers, underwent functional MRI scans, neuropsychological assessments, and APOE genotyping. The research utilized seed to voxel analysis for illustrating LC rsFC discrepancies between APOE4 statuses and employed a general linear model to examine the interactive influence of APOE4 carrier status and Aß deposition on LC FC values. Results: The investigation revealed no significant differences in sex, age, or SUVR between APOE4 carriers and noncarriers. It found diminished LC FC with the occipital cortex in APOE4 carriers and identified a significant interaction between APOE4 carrier status and temporal lobe SUVR in LC FC with the occipital cortex. This interaction suggested a proportional increase in LC FC for APOE4 carriers. Additional notable interactions were observed affecting LC FC with various brain regions, indicating a proportional decrease in LC FC for APOE4 carriers. Conclusions: These findings confirm that APOE4 carrier status significantly influences LC FC in preclinical AD, showcasing an intricate relationship with regional Aß deposition. This underscores the critical role of genetic and pathological factors in early AD pathophysiology, offering insights into potential biomarkers for early detection and intervention strategies.

Alteration of DNA methyltransferases by eribulin elicits broad DNA methylation changes with potential therapeutic implications for triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options. Eribulin, a chemotherapeutic drug, induces epigenetic changes in cancer cells, suggesting a unique mechanism of action. Materials & methods: MDA-MB 231 cells were treated with eribulin and paclitaxel, and the samples from 53 patients treated with neoadjuvant eribulin were compared with those from 14 patients who received the standard-of-care treatment using immunohistochemistry. Results: Eribulin treatment caused significant DNA methylation changes in drug-tolerant persister TNBC cells, and it also elicited changes in the expression levels of epigenetic modifiers (DNMT1, TET1, DNMT3A/B) in vitro and in primary TNBC tumors. Conclusion: These findings provide new insights into eribulin's mechanism of action and potential biomarkers for predicting TNBC treatment response.

Risk of non-thyroidal autoimmune diseases in patients with Graves' disease: a nationwide retrospective cohort study.

OBJECTIVE: Graves' disease (GD) is a major autoimmune thyroid disorder and associated with non-thyroidal autoimmune disease (NTAD). We aimed to investigate the risk of NTAD in patients with GD compared with age- and sex-matched controls and to evaluate whether the risk differs between individuals with or without Graves' ophthalmopathy (GO). METHODS: This was a retrospective cohort study using data from the Korean National Health Claims database. We included 77 401 patients with GD (2,310 with GO) and 77 401 age- and sex-matched controls. Risk of NTAD were compared between the entire cohort and within the GD cohort. RESULTS: During a mean follow-up period of 9 years, NTAD developed in 12 341 (16.1%) patients in the GD cohort. Risk for systemic lupus erythematosus (SLE) [adjusted hazard ratio (aHR):1.15, 95% confidence interval (CI): 1.02-1.29], vitiligo (aHR: 1.24, 95% CI: 1.10-1.40), and alopecia areata (aHR: 1.11, 95% CI: 1.10-1.40) were higher in the GD cohort than in the control cohort. In the GD cohort, risk for SLE (aHR: 1.60, 95% CI: 1.11-2.33), Sjogren's syndrome (aHR: 1.89, 95% CI: 1.30-2.74), and ankylosing spondylitis (aHR: 1.53, 95% CI: 1.08-2.17) were higher in the GO group than in the non-GO group. CONCLUSION: This study demonstrated an increased risk of SLE, vitiligo and alopecia areata in patient with GD. In the GD cohort, patients with GO had an increased risk of SLE, Sjogren's syndrome and ankylosing spondylitis. These findings suggest that importance of implementing a strategy for early detection of NTAD based on the presence of GO.

Cumulative exposure to hypertriglyceridemia and risk of type 2 diabetes in young adults.

AIM: This study aimed to examine whether cumulative exposure to hypertriglyceridemia is associated with an increased risk of developing type 2 diabetes in young adults. METHODS: The study included 1,840,251 participants aged 20-39 years who had undergonefourconsecutiveannualhealth checkups and had no history of type 2 diabetes. Participants werecategorized into five groups (exposure score 0-4) based on the frequencies of hypertriglyceridemia diagnosis over a four-year period. The primary outcome was newly diagnosed type 2 diabetes. Exploratory analyses were performed for the different subgroups. RESULTS: During a follow-up period of 6.53 years, 40,286 participants developed type 2 diabetes. The cumulative incidence of type 2 diabetes significantly increased with higher exposure scores for hypertriglyceridemia (log-rank test, P < 0.001). The multivariable-adjusted hazard ratios for incident diabetes were 1.674 (95 % CI, 1.619, 1.732), 2.192 (95 % CI, 2.117, 2.269), 2.637 (95 % CI, 2.548, 2.73), and 3.715 (95 % CI, 3.6, 3.834) for participants with scores of 1-4, respectively, compared with those with an exposure score of 0. CONCLUSIONS: In this large-scale prospective cohort study of young adults, cumulative exposure to hypertriglyceridemia was significantly associated with an increased risk of type 2 diabetes, independent of lifestyle-related factors.

The Impact of Gender Affirming Medical Care During Adolescence on Adult Health Outcomes Among Transgender and Gender Diverse Individuals in the United States: The Role of State-Level Policy Stigma.

Purpose: Gender affirming medical care (GAMC) aims to alleviate gender dysphoria by helping people align their physical body more closely with their gender identity. Bills seeking to limit or prohibit GAMC for trans children and adolescents have become a controversial topic. This study aimed to examine whether exposures to GAMC during adolescence are associated with adult psychological and general health outcomes, and to demonstrate the mechanism through which state-level legislation may work to moderate the association. Methods: We conducted analyses using data from the 2015 U.S. Transgender Survey, which surveyed 27,715 transgender and gender diverse (TGD) adults between August and September of 2015. The study compared the health outcomes of those who had GAMC exposures during adolescence with those who did not. Moderation analysis with propensity score matching was used to adjust for potential confounding factors. The general and psychological health outcomes measured were past-month severe psychological distress, past-year suicidal ideation, participant's general health, and past-year health care avoidance due to possible mistreatment. Results: GAMC during adolescence was negatively associated with severe psychological distress in adulthood. When examining past-year health care avoidance due to possible mistreatment, the effect sizes differed significantly between those in a trans-supportive state and those in a trans-unsupportive state. Conclusion: Our work highlights the importance of state-level policy stigma in understanding the association between GAMC and health outcomes. Findings point to the importance of enacting long-term legislative safeguards against TGD discrimination and removing barriers to access the full spectrum of care for adolescents who identify as TGD.

Differential Regulation of Intracisternally Injected Angiotensin II-Induced Mechanical Allodynia and Thermal Hyperalgesia in Rats.

The present study examined the underlying mechanisms of mechanical allodynia and thermal hyperalgesia induced by the intracisternal injection of angiotensin (Ang) II. Intracisternal Ang II injection decreased the air puff threshold and head withdrawal latency. To determine the operative receptors for each distinct type of pain behavior, we intracisternally injected Ang II receptor antagonists 2 h after Ang II injection. Losartan, an Ang II type 1 receptor (AT1R) antagonist, alleviated mechanical allodynia. Conversely, PD123319, an Ang II type 1 receptor (AT2R) antagonist, blocked only thermal hyperalgesia. Immunofluorescence analyses revealed the co-localization of AT1R with the astrocyte marker GFAP in the trigeminal subnucleus caudalis and co-localization of AT2R with CGRP-positive neurons in the trigeminal ganglion. Intracisternal pretreatment with minocycline, a microglial inhibitor, did not affect Ang II-induced mechanical allodynia, whereas L-α-aminoadipate, an astrocyte inhibitor, significantly inhibited Ang II-induced mechanical allodynia. Furthermore, subcutaneous pretreatment with botulinum toxin type A significantly alleviated Ang II-induced thermal hyperalgesia, but not Ang II-induced mechanical allodynia. These results indicate that central Ang II-induced nociception is differentially regulated by AT1R and AT2R. Thus, distinct therapeutic targets must be regulated to overcome pain symptoms caused by multiple underlying mechanisms.

Older Adults' Trust and Distrust in COVID-19 Public Health Information: Qualitative Critical Incident Study.

BACKGROUND: The COVID-19 infodemic has imposed a disproportionate burden on older adults who face increased challenges in accessing and assessing public health information, but little is known about factors influencing older adults' trust in public health information during COVID-19. OBJECTIVE: This study aims to identify sources that older adults turn to for trusted COVID-19 public health information and factors that influence their trust. In addition, we explore the relationship between public health information sources and trust factors. METHODS: Adults aged 65 years or older (N=30; mean age 71.6, SD 5.57; range 65-84 years) were recruited using Prime Panels. Semistructured phone interviews, guided by critical incident technique, were conducted in October and November 2020. Participants were asked about their sources of COVID-19 public health information, the trustworthiness of that information, and factors influencing their trust. Interview data were examined with thematic analysis. RESULTS: Mass media, known individuals, and the internet were the older adults' main sources for COVID-19 public health information. Although they used social media for entertainment and personal communication, the older adults actively avoided accessing or sharing COVID-19 information on social media. Factors influencing their trust in COVID-19 public health information included confirmation bias, personal research, resigned acceptance, and personal relevance. CONCLUSIONS: These findings shed light on older adults' use of information sources and their criteria for evaluating the trustworthiness of public health information during a pandemic. They have implications for the future development of effective public health communication, policies, and interventions for older adults during health crises.

Alteration of DNMT1/DNMT3A by eribulin elicits global DNA methylation changes with potential therapeutic implications for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive disease subtype with limited treatment options. Eribulin is a chemotherapeutic approved for the treatment of advanced breast cancer that has been shown to elicit epigenetic changes. We investigated the effect of eribulin treatment on genome-scale DNA methylation patterns in TNBC cells. Following repeated treatment, The results showed that eribulin-induced changes in DNA methylation patterns evident in persister cells. Eribulin also affected the binding of transcription factors to genomic ZEB1 binding sites and regulated several cellular pathways, including ERBB and VEGF signaling and cell adhesion. Eribulin also altered the expression of epigenetic modifiers including DNMT1, TET1, and DNMT3A/B in persister cells. Data from primary human TNBC tumors supported these findings: DNMT1 and DNMT3A levels were altered by eribulin treatment in human primary TNBC tumors. Our results suggest that eribulin modulates DNA methylation patterns in TNBC cells by altering the expression of epigenetic modifiers. These findings have clinical implications for using eribulin as a therapeutic agent.

Type 2 Diabetes and Its Association With Psychiatric Disorders in Young Adults in South Korea.

Importance: Because type 2 diabetes (T2D) has become increasingly prevalent among young adults, the study of the association of T2D with psychiatric disorders in young adults is important for early detection and timely intervention. Objective: To determine whether a diagnosis of a psychiatric disorder is associated with increased risk of developing T2D in young adults. Design, Setting, and Participants: This large-scale prospective cohort study used data collected by the South Korean National Health Insurance Service between 2009 and 2012, representing 97% of the South Korean population. Young adults aged 20 to 39 years with and without diagnoses of psychiatric disorders were included in the study. Young adults with missing data and those with a history of T2D were excluded from the study. The cohort was followed up to monitor development of T2D until December 2018. Data were analyzed from March 2021 to February 2022. Exposure: Diagnosis of 1 of 5 psychiatric disorders, including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. Main Outcomes and Measures: The primary outcome was newly diagnosed T2D during a follow-up period of 7.59 years. The incidence rate of T2D was calculated as the number of new cases per 1000 person-years during the follow-up period. The Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% CIs for T2D incidence. Exploratory analyses were performed for subgroups stratified by age and sex. Results: In total, 6 457 991 young adults (mean [SD] age, 30.74 [4.98] years; 3 821 858 men [59.18%]) were followed up, including 658 430 individuals with psychiatric disorders. The cumulative incidence of T2D differed significantly between individuals with and without psychiatric disorders (log-rank test, P < .001). Incidence rates of T2D for individuals with and without psychiatric disorders were 2.89 and 2.56 per 1000 person-years, respectively. Individuals with a diagnosis of any psychiatric disorder showed a higher risk of developing T2D than those without a diagnosis (adjusted HR, 1.20; 95% CI, 1.17-1.22). The adjusted HRs for T2D were 2.04 (95% CI, 1.83-2.28) for individuals with schizophrenia, 1.91 (95% CI, 1.73-2.12) for individuals with bipolar disorder, 1.24 (95% CI, 1.20-1.28) for individuals with depressive disorder, 1.13 (95% CI, 1.11-1.16) for individuals with anxiety disorder, and 1.31 (95% CI, 1.27-1.35) for individuals with sleep disorder. Conclusions and Relevance: In this large-scale prospective cohort study of young adults, 5 psychiatric disorders were significantly associated with an increased risk of developing T2D. Young adults with schizophrenia and bipolar disorder in particular were at a higher risk of T2D. These results have important implications for early detection of and timely intervention in T2D for young adults with psychiatric disorders.

BMP-2 Genome-Edited Human MSCs Protect against Cartilage Degeneration via Suppression of IL-34 in Collagen-Induced Arthritis.

Even though the regenerative potential of mesenchymal stem cells (MSCs) has been extensively studied, there is a debate regarding their minimal therapeutic properties. Bone morphogenetic proteins (BMP) are involved in cartilage metabolism, chondrogenesis, and bone healing. In this study, we aimed to analyze the role of genome-edited BMP-2 overexpressing amniotic mesenchymal stem cells (AMMs) in a mouse model of collagen-induced arthritis (CIA). The BMP-2 gene was synthesized and inserted into AMMs using transcription activator-like effector nucleases (TALENs), and BMP-2-overexpressing AMMs (AMM/B) were sorted and characterized using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The co-culture of AMM/B with tumor necrosis factor (TNF)-α-treated synovial fibroblasts significantly decreased the levels of interleukin (IL)-34. The therapeutic properties of AMM/B were evaluated using the CIA mouse model. The injection of AMM/B attenuated CIA progression and inhibited T helper (Th)17 cell activation in CIA mice. In addition, the AMM/B injection increased proteoglycan expression in cartilage and decreased the infiltration of inflammatory cells and factors, including IL-1ß, TNF-α, cyclooxygenase (COX)-2, and Nuclear factor kappa B (NF-kB) in the joint tissues. Therefore, editing the BMP-2 genome in MSCs might be an alternative strategy to enhance their therapeutic potential for treating cartilage degeneration in arthritic joints.

IF-City: Intelligible Fair City Planning to Measure, Explain and Mitigate Inequality.

With the increasing pervasiveness of Artificial Intelligence (AI), many visual analytics tools have been proposed to examine fairness, but they mostly focus on data scientist users. Instead, tackling fairness must be inclusive and involve domain experts with specialized tools and workflows. Thus, domain-specific visualizations are needed for algorithmic fairness. Furthermore, while much work on AI fairness has focused on predictive decisions, less has been done for fair allocation and planning, which require human expertise and iterative design to integrate myriad constraints. We propose the Intelligible Fair Allocation (IF-Alloc) Framework that leverages explanations of causal attribution (Why), contrastive (Why Not) and counterfactual reasoning (What If, How To) to aid domain experts to assess and alleviate unfairness in allocation problems. We apply the framework to fair urban planning for designing cities that provide equal access to amenities and benefits for diverse resident types. Specifically, we propose an interactive visual tool, Intelligible Fair City Planner (IF-City), to help urban planners to perceive inequality across groups, identify and attribute sources of inequality, and mitigate inequality with automatic allocation simulations and constraint-satisfying recommendations (IF-Plan). We demonstrate and evaluate the usage and usefulness of IF-City on a real neighborhood in New York City, US, with practicing urban planners from multiple countries, and discuss generalizing our findings, application, and framework to other use cases and applications of fair allocation.

Cumulative exposure to metabolic syndrome in a national population-based cohort of young adults and sex-specific risk for type 2 diabetes.

BACKGROUND: Metabolic syndrome is associated with type 2 diabetes and its prevalence is increasing worldwide in young adults. We aimed to determine whether cumulative exposure to metabolic syndrome is associated with type 2 diabetes risk in young adults. METHODS: Data of 1,376,540 participants aged 20-39 years without a history of type 2 diabetes and who underwent four annual health check-ups were collected. In this large-scale prospective cohort study, we evaluated the incidence rates and hazard ratios (HRs) of diabetes according to cumulative frequencies of metabolic syndrome over 4 years of consecutive annual health check-ups (burden score 0-4). Subgroup analyses were performed by sex and age. RESULTS: During 5.18 years of follow-up, 18,155 young adults developed type 2 diabetes. The incidence of type 2 diabetes increased with burden score (P < 0.0001). The multivariable-adjusted HRs for type 2 diabetes were 4.757, 10.511, 18.288, and 31.749 in participants with a burden score of 1 to 4, respectively, compared to those with 0. In subgroup analyses, the risk of incident diabetes was greater in women than men and in the 20-29 years age group than the 30-39 years age group. The HRs were 47.473 in women and 27.852 in men with four burden scores. CONCLUSION: The risk of type 2 diabetes significantly increased with an increase in the cumulative burden of metabolic syndrome in young adults. Additionally, the association between cumulative burden and diabetes risk was stronger in women and the 20s age group.

Tumor type and cell type-specific gene expression alterations in diverse pediatric central nervous system tumors identified using single nuclei RNA-seq.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collected single nuclei RNA-seq data from 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues (84,700 nuclei) and characterized tumor heterogeneity and transcriptomic alterations. We distinguished cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observed pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identified transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. In this study, we address current gaps in understanding single nuclei gene expression profiles of previously uninvestigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.

Lineage plasticity enables low-ER luminal tumors to evolve and gain basal-like traits.

Stratifying breast cancer into specific molecular or histologic subtypes aids in therapeutic decision-making and predicting outcomes; however, these subtypes may not be as distinct as previously thought. Patients with luminal-like, estrogen receptor (ER)-expressing tumors have better prognosis than patients with more aggressive, triple-negative or basal-like tumors. There is, however, a subset of luminal-like tumors that express lower levels of ER, which exhibit more basal-like features. We have found that breast tumors expressing lower levels of ER, traditionally considered to be luminal-like, represent a distinct subset of breast cancer characterized by the emergence of basal-like features. Lineage tracing of low-ER tumors in the MMTV-PyMT mouse mammary tumor model revealed that basal marker-expressing cells arose from normal luminal epithelial cells, suggesting that luminal-to-basal plasticity is responsible for the evolution and emergence of basal-like characteristics. This plasticity allows tumor cells to gain a new lumino-basal phenotype, thus leading to intratumoral lumino-basal heterogeneity. Single-cell RNA sequencing revealed SOX10 as a potential driver for this plasticity, which is known among breast tumors to be almost exclusively expressed in triple-negative breast cancer (TNBC) and was also found to be highly expressed in low-ER tumors. These findings suggest that basal-like tumors may result from the evolutionary progression of luminal tumors with low ER expression.

Hydroxymethylation alterations in progenitor-like cell types of pediatric central nervous system tumors are associated with cell type-specific transcriptional changes.

Although intratumoral heterogeneity has been established in pediatric central nervous system tumors, epigenomic alterations at the cell type level have largely remained unresolved. To identify cell type-specific alterations to cytosine modifications in pediatric central nervous system tumors we utilized a multi-omic approach that integrated bulk DNA cytosine modification data (methylation and hydroxymethylation) with both bulk and single-cell RNA-sequencing data. We demonstrate a large reduction in the scope of significantly differentially modified cytosines in tumors when accounting for tumor cell type composition. In the progenitor-like cell types of tumors, we identified a preponderance differential CpG hydroxymethylation rather than methylation. Genes with differential hydroxymethylation, like HDAC4 and IGF1R, were associated with cell type-specific changes in gene expression in tumors. Our results highlight the importance of epigenomic alterations in the progenitor-like cell types and its role in cell type-specific transcriptional regulation in pediatric CNS tumors.

Implementation of pharmacists' monitoring for intravenous drug compatibility.

BACKGROUND: Injectable medication errors primarily occur during preparation and administration. Currently, South Korea is experiencing chronic pharmacist shortages. Moreover, pharmacists have not routinely conducted prescription monitoring for intravenous compatibility. In the present study, we analysed the implementation of a pre-issue monitoring program using recently released cloud-based software to provide information on intravenous compatibility in the pharmacy at a general hospital in South Korea. OBJECTIVES: The aims of this study were to determine whether adding an intravenous drug prescription review to pharmacists' actual work scope could promote patient safety, and to assess the impact of this new task on pharmacists' workload. METHODS: Data on intravenous drugs prescribed in the intensive care unit and haematology-oncology ward were prospectively collected during January 2020. Four quantitative items were evaluated: the run-time, intervention ratio, acceptance ratio, and the information completeness ratio with regard to the compatibility of intravenous drugs. RESULTS: The mean run-time of two pharmacists was 18.1 min in the intensive care unit and 8.7 min in the haematology-oncology ward (p<0.001). Significant differences were also found between the intensive care unit and the haematology-oncology wards in terms of the mean intervention ratio (25.3% vs 5.3%, respectively; p<0.001) and the information completeness ratio (38.3% vs 34.0%, respectively; p=0.007). However, the mean acceptance ratio was comparable (90.4% in the intensive care unit and 100% in the haematology-oncology ward; p=0.239). The intravenous pairs that most frequently triggered interventions were tazobactam/piperacillin and famotidine in the intensive care unit, and vincristine and sodium bicarbonate in the haematology-oncology ward. CONCLUSION: This study suggests that despite a shortage of pharmacists, intravenous compatibility can be monitored before issuing injectable products in all wards. Because the prescribing pattern of injections varies across wards, pharmacists' tasks should be established accordingly. To improve the completeness of information, efforts to generate more evidence should continue.

Pedestrian crash frequency: Unpacking the effects of contributing factors and racial disparities.

In this paper, we unpack the magnitude effects of the determinants of pedestrian crashes using a multivariate analysis approach. We consider four sets of exogenous factors that characterize residential neighborhoods as well as potentially affect pedestrian crashes and the racial composition of such crashes: (1) crash risk exposure (CE) attributes, (2) cultural variables, (3) built environment (BE) features, and (4) sociodemographic (SD) factors. Our investigation uses pedestrian crash and related data from the City of Houston, Texas, which we analyze at the spatial Census Block Group (CBG) level. Our results indicate that social resistance considerations (that is, minorities resisting norms as they are perceived as being set by the majority group), density of transit stops, and road design considerations (in particular in and around areas with high land-use diversity) are the three strongest determinants of pedestrian crashes, particularly in CBGs with a majority of the resident population being Black. The findings of this study can enable policymakers and planners to develop more effective countermeasures and interventions to contain the growing number of pedestrian crashes in recent years, as well as racial disparities in pedestrian crashes. Importantly, transportation safety engineers need to work with social scientists and engage with community leaders to build trust before leaping into implementing planning countermeasures and interventions. Issues of social resistance, in particular, need to be kept in mind.

Misinformation and COVID-19 vaccine hesitancy.

BACKGROUND: COVID-19 vaccine hesitancy has emerged as a major public health challenge. Although medical and scientific misinformation has been known to fuel vaccine hesitancy in the past, misinformation surrounding COVID-19 seems to be rampant, and increasing evidence suggests that it is contributing to COVID-19 vaccine hesitancy today. The relationship between misinformation and COVID-19 vaccine hesitancy is complex, however, and it is relatively understudied. METHODS: In this article, we report qualitative data from two related but distinct studies from a larger project. Study 1 included semi-structured, open-ended interviews conducted in October-November 2020 via phone with 30 participants to investigate the relationship between misinformation and COVID-19 vaccine hesitancy. Study 1's results then informed the design of open-ended questions for Study 2, an online survey conducted in May-June 2021 to consider the relationship between misinformation and vaccine hesitancy further. The data were examined with thematic analysis. RESULTS: Study 1 led to the identification of positive and negative themes related to attitudes toward COVID-19 vaccines. In Study 2, responses from vaccine-hesitant participants included six categories of misinformation: medical, scientific, political, media, religious, and technological. Across both Study 1 and Study 2, six vaccine hesitancy themes were identified from the data: concerns about the vaccines' future effects, doubts about the vaccines' effectiveness, commercial profiteering, preference for natural immunity, personal freedom, and COVID-19 denial. CONCLUSIONS: The relationship between misinformation and vaccine hesitancy is complicated. Various types of misinformation exist, with each related to a specific type of vaccine hesitancy-related attitude. Personal freedom and COVID-19 denial are vaccine attitudes of particular interest, representing important yet understudied phenomena. Medical and scientific approaches may not be sufficient to combat misinformation based in religion, media, or politics; and public health officials may benefit from partnering with experts from those fields to address harmful misinformation that is driving COVID-19 vaccine hesitancy.