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Youth interpersonal firearm violence disproportionately affects Black youth, with residential racial segregation as a key determinant. Racially segregated neighborhoods, which are economically isolated (e.g., neighborhood disadvantage), are linked to increased exposure to violence. This exposure, in turn, is a determinant of youth firearm aggression (i.e., using a gun on someone else). Mechanisms from residential racial segregation to firearm aggression, however, have not been evaluated. Therefore, we tested neighborhood disadvantage and exposure to violence as mediators in the association between residential racial segregation and youth firearm aggression. Participants were 338 Black youth who had used drugs in the past 6 months and sought care in an urban emergency department. Using serial mediation analysis, residential racial segregation was indirectly associated with youth firearm aggression via neighborhood disadvantage and then exposure to violence. While researchers have documented the association between structural racism and firearm violence injury and incidents, our study assessed multiple socioecological mechanisms simultaneously. Identifying the downstream socioecological consequences of residential segregation can guide the development of firearm aggression prevention programs addressing the consequences of racism.

Mixed-reality simulation is a technology-based tool used to augment preservice teacher education in special education; as such, researchers have conducted several studies to assess mixed-reality simulation for its effectiveness and efficacy. Though these researchers have concluded that mixed-reality simulation can be an effective tool, there is limited information regarding a synthesis of the study characteristics (e.g., participants' demographic information, amount of time, skills taught using simulation, and participants' perceptions). Understanding these components is critical to the continued success and growth of using mixed-reality simulation in special education coursework. We identified and synthesized eight mixed-reality simulation studies with a total of 256 participants from 2005 to 2021. Together, the eight studies suggest that mixed-reality simulation is a valuable practice-based experience for preservice special educators. Implications for practice and future research are discussed.

Abstract Background Firearm injuries are the leading cause of death for U.S. adolescents. Given the prevalence of firearm ownership in the U.S., particularly among parental figures in homes with children and teens, and the relationship between firearm access and injury outcomes, it is vital to shed light on potential parental motivations for keeping firearms in their homes. The purpose of this analysis was to examine whether exposure to community violence is associated with parental firearm ownership. Methods Data from the Firearm Safety Among Children and Teens Consortium’s National Survey (6/24/2020-7/24/2020) was examined. The survey sample comprised parents/caregivers of high-school-age teens (age 14–18). The survey examined various measures, including firearm ownership, storage, community violence exposure, and sociodemographic characteristics. Stepwise logistic regression was used to examine the association between community violence exposure and parental firearm ownership. Results The study included 2,924 participants, with 45.1% identifying as male, 12.9% identifying as Hispanic, and 25.3% identifying as non-White. Among these participants, 43.1% reported firearm ownership, and 49.9% reported exposure to community violence. Regression models demonstrate that community violence exposure is associated with an increased likelihood of firearm ownership among parents/caregivers of high-school age teens (OR = 1.08, p

The complex, trichlorido(1,4,11-triaza-8-azoniatetracyclo[6.6.2.04,16.011,15]hexadecane 1-oxide-κO)zinc(II) monohydrate, [ZnCl3(C12H23N4O)]·H2O, (I), has monoclinic symmetry (space group P21/n) at 120 K. The zinc(II) center adopts a slightly distorted tetrahedral coordination geometry and is coordinated by three chlorine atoms and the oxygen atom of the oxidized tertiary amine of the tetracycle. The amine nitrogen atom, inside the ligand cleft, is protonated and forms a hydrogen bond to the oxygen of the amine oxide. Additional hydrogen-bonding interactions involve the protonated amine, the water solvate oxygen atom, and one of the chloro ligands.

Abstract Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10−8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

The ability to work with data to extract valuable information is a useful skill set, especially in STEM disciplines that produce large amounts of scientific data. This paper reports on the pedagogy and experience of incorporating fundamental database concepts into a STEM Success course, which included a hands-on project. Students worked in groups to design a database for existing tabular data available on the Web and then derived the data to populate the database using SQL queries. This paper reflects on the experience both from a pedagogical perspective as well as a student perspective, including qualitative code analysis of student feedback and survey results regarding attitudes of confidence using, interest in, and usefulness of databases.

Summary: Here, we show that a NOT gated cell therapy (Tmod) can exploit antigens such as epidermal growth factor receptor (EGFR) and human leukocyte antigen-E (HLA-E) which are widely expressed on cancer cells. Noncancerous cells—despite high expression of these antigens—are protected from cytotoxicity by the action of an inhibitory receptor (“blocker”) via a mechanism that involves blocker modulation of CAR surface expression. The blocker is triggered by the product of a polymorphic HLA allele (e.g., HLA-A∗02) deleted in a significant subset of solid tumors via loss of heterozygosity. Moreover, Tmod constructs that target mouse homologs of EGFR or HLA-E for activation, and a mouse-equivalent of HLA-A∗02 for inhibition, protect mice from toxicity caused by the CAR alone. The blocker also controls graft vs. host response in allogeneic T cells in vitro, consistent with the use of Tmod cells for off-the-shelf therapy without additional gene-editing.

Socially engaged engineering provides for student learning of the design, analysis, and practices of engineering as well as the ways that engineering is situated in sociocultural contexts. This paper provides a conceptual framework regarding socially engaged engineering for K-8 educators, researchers, and curriculum designers. The framework identifies ways to support youth learning of engineering and considerations of technical, social, environmental, and ethical dimensions of engineering. As engineering enters K-8 educational settings, it is important to introduce the discipline in equity-oriented ways. We draw from the field of engineering for social justice to build this framework for examining engineering at the macro-, meso-, and microscales. Situating engineering in sociocultural contexts can be motivating to learners and provide perspectives on the nature of engineering. Our framework was concurrently designed with Youth Engineering Solutions (YES; https://YouthEngineeringSolutions.org) curricular units. To test the applicability of our principles, we applied them to K-8 YES curricula for school and out-of-school environments. Through the coevolution of principles and curricular materials, we developed age-appropriate learning objectives for three levels--lower elementary, upper elementary, and middle school. This paper shares the principles and progression, showing worked examples from curricula to demonstrate how the principles translate into curricular resources. We discuss constraints to the implementation of socially engaged engineering curricula, including those imposed in educational settings and the ideological assumptions about science, engineering, and STEM disciplines. [Paper presented at 2023 American Society for Engineering Education Annual Conference & Exposition, Baltimore, MD.]

Abstract Brown seaweeds are a rich source of carotenoids, particularly fucoxanthin, which has a wide range of potential health applications. Fucoxanthin fluctuates within and among seaweeds over time, frustrating efforts to utilise this resource. Thus, we require comprehensive analyses of long- and short-term concentrations across species in field conditions. Here, we used High Performance Liquid Chromatography to compare fucoxanthin content in four brown macroalgae, Ascophyllum nodosum, Fucus serratus, Fucus vesiculosus and Saccharina latissima, monthly for 1 year. F. serratus and F. vesiculosus had significantly higher fucoxanthin content (mg/g), which was highest in Spring (0.39 ± 0.04) and Autumn (0.45 ± 0.04) [mean (± SE)]. Two species, A. nodosum and F. serratus, were collected monthly at the same location for a further two non-consecutive years. For both A. nodosum and F. serratus, a significant interaction effect of seasons and years was identified, highlighting that there is variation in fucoxanthin content among and within species over time. We also show that fucoxanthin content differs significantly among months even within seasons. Therefore, it is not sufficient to assess fucoxanthin in single months to represent seasonality. We discuss how weather, nutrients and reproduction may have driven the seasonal variation, and reveal patterns of fucoxanthin concentration that can provide information concerning its availability for many important medical functions.

Adolescent and young adult (AYA) cancer patients receive palliative medicine consultation at a late stage and face diagnostic delays. Failure to address social determinants of health (SDOH) and AYA-specific needs can adversely impact patient experience. This retrospective observational cohort study used data from chart review to assess the frequency of SDOH impacting AYA patients and setting of initial diagnosis at a US urban safety-net hospital. The association of SDOH variables with delays in treatment, loss of follow-up, and no-shows was tested using Chi-square and t -tests. One hundred seventy five patient charts were reviewed. Sixty-two percent were diagnosed in acute care settings. Substance use disorders, financial, employment, and insurance issues were associated with delayed treatment, with weak to moderate effect sizes. Mental health diagnoses, substance use disorder, homelessness, and financial burdens were associated with patient no-shows, with moderate to large effect sizes. Twenty-five percent of patients received palliative medicine consultation; 70% of these occurred at end of life. This study demonstrates the impact of SDOH on AYA cancer care and the need for policy allowing for intervention on SDOH.

PurposeThe total time of radiation treatment delivery for pancreatic cancer patients with daily online adaptive radiation therapy (ART) on an MR-Linac can range from 50 to 90 min. During this period, the target and normal tissues undergo changes due to respiration and physiologic organ motion. We evaluated the dosimetric impact of the intrafraction physiological organ changes.MethodsTen locally advanced pancreatic cancer patients were treated with 50 Gy in five fractions with intensity-modulated respiratory-gated radiation therapy on a 0.35-T MR-Linac. Patients received both pre- and post-treatment volumetric MRIs for each fraction. Gastrointestinal organs at risk (GI-OARs) were delineated on the pre-treatment MRI during the online ART process and retrospectively on the post-treatment MRI. The treated dose distribution for each adaptive plan was assessed on the post-treatment anatomy. Prescribed dose volume histogram metrics for the scheduled plan on the pre-treatment anatomy, the adapted plan on the pre-treatment anatomy, and the adapted plan on post-treatment anatomy were compared to the OAR-defined criteria for adaptation: the volume of the GI-OAR receiving greater than 33 Gy (V33Gy) should be ≤1 cubic centimeter.ResultsAcross the 50 adapted plans for the 10 patients studied, 70% were adapted to meet the duodenum constraint, 74% for the stomach, 12% for the colon, and 48% for the small bowel. Owing to intrafraction organ motion, at the time of post-treatment imaging, the adaptive criteria were exceeded for the duodenum in 62% of fractions, the stomach in 36%, the colon in 10%, and the small bowel in 48%. Compared to the scheduled plan, the post-treatment plans showed a decrease in the V33Gy, demonstrating the benefit of plan adaptation for 66% of the fractions for the duodenum, 95% for the stomach, 100% for the colon, and 79% for the small bowel.ConclusionPost-treatment images demonstrated that over the course of the adaptive plan generation and delivery, the GI-OARs moved from their isotoxic low-dose region and nearer to the dose-escalated high-dose region, exceeding dose-volume constraints. Intrafraction motion can have a significant dosimetric impact; therefore, measures to mitigate this motion are needed. Despite consistent intrafraction motion, plan adaptation still provides a dosimetric benefit.

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020 and 2022 and used Bayesian phylodynamics to describe county and regional spread in Minnesota. The earliest calculated introduction into Minnesota was to Hennepin County from a domestic source around 22 January 2020; 6 weeks before the first confirmed case in the state. This led to the virus spreading to Northern Minnesota and, eventually, the rest of the state. International introductions were most abundant in Hennepin (home to the Minneapolis/St. Paul International Airport) totaling 45 (out of 107) over the 2-year period. Southern Minnesota counties were most common for domestic introductions, with 19 (out of 64), potentially driven by bordering states such as Iowa and Wisconsin as well as Illinois, which is nearby. Hennepin also was, by far, the most dominant source of in-state transmissions to other Minnesota locations (n = 772) over the 2-year period. We also analyzed the diversity of the location source of SARS-CoV-2 viruses in each county and noted the timing of state-wide policies as well as trends in clinical cases. Neither the number of clinical cases nor the major policy decisions, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, appeared to have an impact on virus diversity across each individual county.IMPORTANCEWe analyzed over 22,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes of patient samples tested at Mayo Clinic Laboratories during a 2-year period in the COVID-19 pandemic, which included Alpha, Delta, and Omicron variants of concern to examine the roles and relationships of Minnesota virus transmission. We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after an initial predicted introduction with the virus in early 2020 from an international source, while other counties acted as transmission “sinks.” In addition, major policies, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, did not appear to have an impact on virus diversity across individual counties.

An offset T-intersection splits a conventional four leg intersection into two three-leg T-intersections to reduce the number of conflicts. While the safety benefits of offset T-intersections have been widely documented, the effects on operations are not well understood. To fix that, this paper employed microsimulation modeling to investigate the differences in operational performance between offset T-intersections and four-leg standard intersections under various traffic demands, intersection spacings, and signal timing schemes for three development types: superstore, hybrid gas station, and residential area. Queue length and delay were employed as measurements of effectiveness. Based on microsimulation modeling, we found that under most of the tested scenarios, offset T-intersections were superior to four-leg intersections in terms of reducing delay for the main street traffic. In addition, we found that the left–right (L-R) offset T-intersection configuration outperformed the right-left (R-L) offset configuration in terms of preventing main-street left turn queue spillback. Based on the simulation results, the paper provided practice-ready guidelines on selecting an optimum intersection configuration for each specific development type given the volume demands and known geometric constraints for a given site.

Abstract Background Formalin-fixed, paraffin-embedded (FFPE) tissues have many advantages for identification of risk biomarkers, including wide availability and potential for extended follow-up endpoints. However, RNA derived from archival FFPE samples has limited quality. Here we identified parameters that determine which FFPE samples have the potential for successful RNA extraction, library preparation, and generation of usable RNAseq data. Methods We optimized library preparation protocols designed for use with FFPE samples using seven FFPE and Fresh Frozen replicate pairs, and tested optimized protocols using a study set of 130 FFPE biopsies from women with benign breast disease. Metrics from RNA extraction and preparation procedures were collected and compared with bioinformatics sequencing summary statistics. Finally, a decision tree model was built to learn the relationship between pre-sequencing lab metrics and qc pass/fail status as determined by bioinformatics metrics. Results Samples that failed bioinformatics qc tended to have low median sample-wise correlation within the cohort (Spearman correlation 4). The median RNA concentration and pre-capture library Qubit values for qc failed samples were 18.9 ng/ul and 2.08 ng/ul respectively, which were significantly lower than those of qc pass samples (40.8 ng/ul and 5.82 ng/ul). We built a decision tree model based on input RNA concentration, input library qubit values, and achieved an F score of 0.848 in predicting QC status (pass/fail) of FFPE samples. Conclusions We provide a bioinformatics quality control recommendation for FFPE samples from breast tissue by evaluating bioinformatic and sample metrics. Our results suggest a minimum concentration of 25 ng/ul FFPE-extracted RNA for library preparation and 1.7 ng/ul pre-capture library output to achieve adequate RNA-seq data for downstream bioinformatics analysis.

Abstract Induced pluripotent stem cells (iPSCs) are a valuable resource for neurological disease-modeling and drug discovery due to their ability to differentiate into neurons reflecting the genetics of the patient from which they are derived. iPSC-derived cultures, however, are highly variable due to heterogeneity in culture conditions. We investigated the effect of passage number on iPSC differentiation to optimize the generation of sensory neurons (iPSC-dSNs). Three iPSC lines reprogrammed from the peripheral blood of three donors were differentiated into iPSC-dSNs at passage numbers within each of the following ranges: low (5–10), intermediate (20–26), and high (30–38). Morphology and pluripotency of the parent iPSCs were assessed prior to differentiation. iPSC-dSNs were evaluated based on electrophysiological properties and expression of key neuronal markers. All iPSC lines displayed similar morphology and were similarly pluripotent across passage numbers. However, the expression levels of neuronal markers and sodium channel function analyses indicated that iPSC-dSNs differentiated from low passage numbers better recapitulated the sensory neuron phenotype than those differentiated from intermediate or high passage numbers. Our results demonstrate that lower passage numbers may be better suited for differentiation into peripheral sensory neurons.

Summary: Mechanisms underlying distinct specification, commitment, and differentiation phases of cell fate determination remain undefined due to difficulties capturing these processes. Here, we interrogate the activity of ETV2, a transcription factor necessary and sufficient for hematoendothelial differentiation, within isolated fate intermediates. We observe transcriptional upregulation of Etv2 and opening of ETV2-binding sites, indicating new ETV2 binding, in a common cardiac-hematoendothelial progenitor population. Accessible ETV2-binding sites are active at the Etv2 locus but not at other hematoendothelial regulator genes. Hematoendothelial commitment coincides with the activation of a small repertoire of previously accessible ETV2-binding sites at hematoendothelial regulators. Hematoendothelial differentiation accompanies activation of a large repertoire of new ETV2-binding sites and upregulation of hematopoietic and endothelial gene regulatory networks. This work distinguishes specification, commitment, and sublineage differentiation phases of ETV2-dependent transcription and suggests that the shift from ETV2 binding to ETV2-bound enhancer activation, not ETV2 binding to target enhancers, drives hematoendothelial fate commitment.

BackgroundVeterinarians hold distinct breed-specific pain sensitivity beliefs that differ from the general public but are highly consistent with one another. This is remarkable as there is no current scientific evidence for biological differences in pain sensitivity across dog breeds. Therefore, the present study evaluated whether pain sensitivity thresholds differ across a set of dog breeds and, if so, whether veterinarians’ pain sensitivity ratings explain these differences or whether these ratings are attributed to behavioral characteristics.MethodsPain sensitivity thresholds [using quantitative sensory testing (QST) methods] and canine behaviors (using owner questionnaires and emotional reactivity tests) were prospectively measured across selected dog breeds. Adult, healthy dogs from 10 dog breeds/breed types were recruited, representing breeds subjectively rated by veterinarians as high (chihuahua, German shepherd, Maltese, Siberian husky), average (border collie, Boston terrier, Jack Russell terrier), or low (golden retriever, pitbull, Labrador retriever) pain sensitivity. A final sample of 149 dogs was included in statistical analyses.ResultsVeterinarians’ pain sensitivity ratings provided a minimal explanation for pain sensitivity thresholds measured using QST in dogs; however, dog breeds did differ in their pain sensitivity thresholds across the QST methods evaluated. Breed differences were observed for some aspects of emotional reactivity tests; however, these behavioral differences did not explain the differences in pain sensitivity thresholds found. Veterinarians’ pain sensitivity ratings were positively associated with dog approach scores for the disgruntled stranger test suggesting that the way dogs greet strangers may be a factor influencing veterinarians’ ratings of pain sensitivity across dog breeds.Conclusions and clinical relevanceOverall, these findings highlight a need to investigate biological mechanisms that may explain breed differences in pain sensitivity because this may inform pain management recommendations. Further, future research should focus on when and how these breed-specific pain sensitivity beliefs developed in veterinarians, as veterinarians’ beliefs could impact the recognition and treatment of pain for canine patients.

Abstract The Irish Sea is an important area for Norway Lobster Nephrops norvegicus fisheries, which are the most valuable fishing resource in the UK. Norway lobster are known to ingest microplastic pollution present in the sediment and have displayed reduced body mass when exposed to microplastic pollution. Here, we identified microplastic pollution in the Irish Sea fishing grounds through analysis of 24 sediment samples from four sites of differing proximity to the Western Irish Sea Gyre in both 2016 and 2019. We used µFTIR spectroscopy to identify seven polymer types, and a total of 77 microplastics consisting of fibres and fragments. The mean microplastics per gram of sediment ranged from 0.13 to 0.49 and 0 to 1.17 MP/g in 2016 and 2019, respectively. There were no differences in the microplastic counts across years, and there was no correlation of microplastic counts with proximity to the Western Irish Sea Gyre. Considering the consistently high microplastic abundance found in the Irish Sea, and the propensity of N. norvegicus to ingest and be negatively impacted by them, we suggest microplastic pollution levels in the Irish Sea may have adverse impacts on N. norvegicus and negative implications for fishery sustainability in the future.

Previous research regarding behaviors of zoo visitors near exhibits has shown that they can influence animals’ well-being. What is unclear is whether people’s views concerning the purpose of zoos or their beliefs might influence their perception of what is acceptable behavior when visiting the zoo. In this study, we used naturalistic observation to examine zoo visitor behavior near specific exhibits. We also surveyed visitors regarding the purpose of zoos, their perception of animals and the zoo, and if they have seen inappropriate behavior in other zoo visitors. We observed visitors engaging in various inappropriate behaviors such as hitting the glass and trying to provoke the animals. These same inappropriate behaviors were also reported by visitors in our survey, indicating an awareness of what behaviors might be disruptive to animals. Visitors who reported similarities between humans and animals reported more inappropriate behaviors in others partially due to having more empathy for animals. When asked to consider the purpose of the zoo, education and conservation were ranked as being the most important, entertainment and research the least important priorities. However, of those who identified entertainment as most important, this group also reported humans to have less similarity with animals and reported less inappropriate behaviors in other visitors. Our findings suggest that zoo visitors’ views regarding the purpose of zoos and perceived human similarities to animals influence what they considered inappropriate behavior around captive zoo animals. This study provides the first exploration concerning the perception of visitors regarding other visitor behaviors directed towards zoo animals.

Understanding the transport and accumulation of microplastics is useful to determine the relative risk they pose to global biodiversity. The exact contribution of microplastic sources is hard to elucidate; therefore, investigating the Antarctic Weddell Sea, an area known for its remoteness and little human presence (i.e. limited pollution sources), will help us to better understand microplastic transportation. Here, we investigate the presence of microplastics in a range of Antarctic sample media including air, seawater, and sediment. We hypothesised that multiple transportation processes including atmospheric and oceanic vectors determine the presence of microplastics in the Antarctic. Using techniques including Polarised Light Microscopy and Raman Spectrometry, we identified mostly fibres and categorised them based on their optical and chemical properties. A total of 47 individual microplastic categories (45 of which were fibres) were identified in the air, seawater, and sediment samples. The majority of categories did not overlap multiple media (42/47); however, four fibre categories were present in both air and water samples, and another fibre category was found in all three media (category 27). We suggest that the large variety of fibres identified and the overlap of fibre categories among media indicates that the pollution may result from multiple diffuse sources and transportation pathways. Additionally, our Air Mass Back Trajectory analyses demonstrates that microplastic fibres are being transported by air masses or wind, and strongly suggests that they are transported to the Antarctic from southern South America. We also propose that fibres may be transported into the Antarctic in subsurface waters, and as pollution was identified in our sediment and additional sea ice samples, we suggest that the coastal and Antarctic deep sea may be a sink for microplastic fibres. The results shown here from a remote, near-pristine system, further highlight the need for a global response to the plastic pollution crisis.

The objective of this study was to investigate the effect of high-tunnel production on preharvest losses and harvest quality of two tomato (Solanum lycopersicum) cultivars. Our results indicate that using high tunnels for tomato production can reduce the preharvest food losses for this crop compared with open-field production, as indicated by increased productivity and percent marketability during the span of three production seasons. The tomato harvest quality did not differ in terms of physical attributes. However, open-field–grown tomatoes demonstrated a significantly greater antioxidant capacity when compared with the high-tunnel–grown tomatoes.

Abstract Background Benign breast disease (BBD) is a risk factor for breast cancer (BC); however, little is known about the genetic alterations present at the time of BBD diagnosis and how these relate to risk of incident BC. Methods A subset of a long-term BBD cohort was selected to examine DNA variation across three BBD groups (42 future estrogen receptor-positive (ER+) BC, 36 future estrogen receptor-negative (ER−) BC, and 42 controls cancer-free for at least 16 years post-BBD). DNA extracted from archival formalin fixed, paraffin-embedded (FFPE) tissue blocks was analyzed for presence of DNA alterations using a targeted panel of 93 BC-associated genes. To address artifacts frequently observed in FFPE tissues (e.g., C>T changes), we applied three filtering strategies based on alternative allele frequencies and nucleotide substitution context. Gene-level associations were performed using two types of burden tests and adjusted for clinical and technical covariates. Results After filtering, the variant frequency of SNPs in our sample was highly consistent with population allele frequencies reported in 1 KG/ExAC (0.986, p

Vaccine hesitancy remains a global health threat. Addressing parental vaccine hesitancy is essential to maintaining high vaccine coverage levels and preventing disease outbreaks; however, it is unknown if administering a vaccine hesitancy screening tool negatively impacts parental vaccine beliefs. We conducted a stratified randomized controlled trial in pediatric primary care practices. English-speaking parents ≥18 years of age seeking routine care for infants

Magnetic interference source identification is a critical preparation step for magnetometer-mounted unmanned aircraft systems (UAS) used for high-sensitivity geomagnetic surveying. A magnetic field scanner was built for mapping the low-frequency interference that is produced by a UAS. It was used to compare four types of electric-powered UAS capable of carrying an alkali-vapour magnetometer: (1) a single-motor fixed-wing, (2) a single-rotor helicopter, (3) a quad-rotor helicopter, and (4) a hexa-rotor helicopter. The scanner's error was estimated by calculating the root-mean-square deviation of the background total magnetic intensity over the mapping duration; averaged values ranged between 3.1 and 7.4 nT. Each mapping was performed above the UAS with the motor(s) engaged and with the UAS facing in two orthogonal directions; peak interference intensities ranged between 21.4 and 574.2 nT. For each system, the interference is a combination of both ferromagnetic and electrical current sources. Major sources of interference were identified such as servo(s) and the cables carrying direct current between the motor battery and the electronic speed controller. Magnetic intensity profiles were measured at various motor current draws for each UAS, and a change in intensity was observed for currents as low as 1 A.

Abstract To better understand the full-length transcriptome of the nucleus accumbens (NAc)—a key brain reward region—in chronic cocaine treatment, we perform the first single molecule, long-read sequencing analysis using the Iso-seq method to detect 42,114 unique transcripts from mouse NAc polyadenylated RNA. Using GENCODE annotation as a reference, we find that over half of the Iso-seq derived transcripts are annotated, while 46% of them harbor novel splicing events in known genes; around 1% of them correspond to other types of novel transcripts, such as fusion, antisense and intergenic. Approximately 34% of the novel transcripts are matched with a compiled transcriptome assembled from published short-read data from various tissues, with the remaining 69% being unique to NAc. These data provide a more complete picture of the NAc transcriptome than existing annotations and can serve as a comprehensive reference for future transcriptomic analyses of this important brain reward region.

Purpose: The superior soft-tissue contrast of MRI-guided radiotherapy offers enhanced localization accuracy of the spinal cord in spine Stereotactic Body Radiotherapy (SBRT). This work includes a planning study for spine-SBRT on an MR-Linac. Additionally, a patient with spine metastasis was treated using an adaptive radiation therapy workflow. We report our initial experience of targeting accuracy, image-guided localization, on-line adaptive planning, and treatment with real-time intrafraction imaging with automatic beam gating.Methods: Six spine-SBRT patients were retrospectively re-planned to 18 Gy in 1-fraction on a commercial, Monte Carlo-based MR-Linac treatment planning system. Plans were generated using 9–13 step-and-shoot intensity-modulated radiation therapy 6 MV-flattening filter free beams and optimized to achieve plan quality criteria recommended by RTOG-0631. One thoracic vertebral body clinical case was treated to 27 Gy in 3-fractions utilizing ART, where daily anatomical changes were accounted for via re-planning and treatment in an on-line manner to account for limited ability to correct rotational setup uncertainties.Results: Plans met all critical-tissue constraints outlined in RTOG-0631 and AAPM Task Group-101, while covering 90% of the target with the prescription dose. Clinically, visibility of the spinal cord allowed for patient setup focusing on spinal cord-alignment. Utilization of the online ART workflow, while re-contouring the target and spinal cord, enabled an increase in prescription dose coverage from 89 to 95% in two of three fractions while maintaining acceptable doses to organs-at-risk. Real-time MR-cine imaging demonstrated sufficient quality for the automatic beam gating algorithm to provide intrafraction motion management of the spinal canal utilizing a 3.0 mm gating boundary and 1–2% region of excursion allowance, in the sagittal plane. A decrease in coverage, below the 95% threshold was noted in post-treatment volumetric imaging due to lateral movement not observed during real-time gating.Conclusion: Achieved plan quality and deliverability was within accepted standards. MR-guidance with an on-line ART workflow offered increased accuracy in the localization of the spinal cord at the time of treatment to enhance both tissue sparing and target volume coverage. Increased spatial resolution of cine-images, and tracking in three-dimensions would be beneficial for future spine-SBRT treatments on the MR-Linac.

Abstract Background The United States Food and Drug Administration is investigating possible diet‐associated dilated cardiomyopathy (DCM) in dogs and cats. Objectives To retrospectively review DCM cases for signalment, diet information, echocardiographic changes, and survival. Animals Client‐owned dogs (n = 71). Methods Medical records of dogs diagnosed with DCM between January 1, 2014 and September 30, 2018 were reviewed. Dogs were grouped into “traditional” or “nontraditional” diet categories and whether or not diet was changed after diagnosis. Results For dogs eating nontraditional diets, those that had their diets changed had a larger percentage decrease in normalized systolic left ventricular internal dimension (P = .03) and left atrial:aorta ratio (P

Abstract Background Varicella zoster virus central nervous system infections can present as aseptic meningitis, encephalitis, myelitis, and vasculopathy. Diagnosis is based on identification of varicella zoster virus deoxyribonucleic acid (DNA) in the cerebrospinal fluid by polymerase chain reaction. Therapy for these infections is acyclovir or valacyclovir. However, acyclovir can have neurotoxic effects that can mimic the presentation of varicella zoster virus central nervous system disease. We present a rare presentation of a patient who had acyclovir-induced neurotoxicity who also had a false-positive cerebrospinal fluid varicella zoster virus polymerase chain reaction result, creating a management dilemma. We review the clinical characteristics of acyclovir-induced neurotoxicity. In addition, we present the diagnostic characteristics of the cerebrospinal fluid viral polymerase chain reaction and alternative methods to diagnose central nervous system varicella zoster virus disease. Case presentation A 68-year-old Hispanic man with end-stage renal disease was diagnosed with cutaneous zoster at an outside facility and was started on acyclovir 4 days prior to admission. His family noted worsening confusion, agitation, speech difficulty, and hallucinations, leading them to bring him to the emergency department. His cerebrospinal fluid varicella zoster virus polymerase chain reaction result was positive, indicating the presence of varicella zoster virus deoxyribonucleic acid in the cerebrospinal fluid; however, he did not have cerebrospinal fluid pleocytosis typical of varicella zoster virus meningoencephalitis. Pharmacy records from the outside hospital revealed supratherapeutic acyclovir dosing. This led to a diagnostic dilemma over whether this patient had varicella zoster virus encephalitis or acyclovir-induced neurotoxicity. Acyclovir was discontinued, and the patient underwent two sessions of hemodialysis to remove acyclovir, which led to a full neurologic recovery. Conclusions Varicella zoster virus encephalitis and acyclovir-induced neurotoxicity can have similar presentations. Varicella zoster virus deoxyribonucleic acid can be present in the cerebrospinal fluid during active cutaneous zoster in the absence of central nervous system disease. If concern for central nervous system varicella zoster virus disease remains high, additional testing with cerebrospinal fluid serology can be performed. Compared with central nervous system varicella zoster virus disease, acyclovir-induced neurotoxicity has a more predictable clinical resolution once drug therapy is discontinued or the patient undergoes hemodialysis, which can aid in making the diagnosis. Clinicians should be aware of this rare and dangerous complication of acyclovir. In addition, clinicians should have an understanding of the diagnostic limitations of cerebrospinal fluid viral polymerase chain reaction and have alternative approaches available to diagnose central nervous system varicella zoster virus disease when it is suspected.

Abstract Background Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by IgM autoantibodies that trigger hemolysis via classical complement pathway. Increased incidence of thrombotic events (TEs) has been reported in patients with other forms of hemolysis. The incidence of TEs in patients with CAD is unknown. Objective Evaluate TE risk in patients with CAD. Patients/Methods This is a matched cohort comparison study evaluating the risk of TEs in patients with CAD and without CAD over a 10‐year period. A total of 608 patients with CAD were identified in the Optum Claims–Clinical data set by reviewing clinical notes for CAD terms and matched with up to 10 patients without CAD (N = 5873). TEs were defined as the first medical claim for a TE using International Classification of Diseases, Ninth and Tenth Revision codes. Cox regression models were used to estimate time to first TE. Sensitivity analyses were conducted to estimate TE risk among patients with primary CAD. Results At least 1 TE occurred in 29.6% of patients with CAD and 17.6% of patients without CAD. The proportion of patients experiencing venous, arterial, and cerebral TEs were each higher among CAD patients. The overall risk of having TEs was higher in patients with CAD (adjusted hazard ratio [aHR], 1.94; 95% confidence interval [CI], 1.64‐2.30). Patients with presumed primary CAD also demonstrated an increased risk of TEs (aHR, 1.80; 95% CI, 1.46‐2.22). Patients with CAD with the fewest comorbidities had 2.44‐fold higher risk of having a TE (95% CI, 1.70‐3.52). Conclusions Patients with CAD have an increased risk of TEs when compared with a matched non‐CAD population.

We tested whether acute microplastic exposure impacts information gathering and processing (cognition) in hermit crabs (Pagurus bernhardus). For five days, we kept 51 hermit crabs in tanks containing either polyethylene microspheres (n = 27) or no plastic (n = 24). We then transferred individuals into an intermediate-quality shell and presented them with two vials containing either a better or worse shell. Because touching both shell vials required an equivalent behavioural response, this design controlled for general activity. Plastic-exposed hermit crabs were less likely and slower than controls to touch the better shell vial, instead preferring the worse shell vial. Microplastics, therefore, impaired assessments and decision-making, providing direct evidence of acute microplastic exposure disrupting hermit crab cognition.

Background: We aimed to assess the extent to which the buffy coat DNA methylome is representative of methylation patterns in constitutive white blood cell (WBC) types in normal pregnancy.Methods: A comparison of differential methylation of buffy coat DNA vs DNA isolated from polymorphonuclear (PMN) and lymphocytic fractions was performed for each blood sample obtained within 24 h prior to delivery from 29 normotensive pregnant women. Methylation profiles were obtained using an Illumina Human Methylation 450 BeadChip and CHaMP bioinformatics pipeline. A subset of differentially methylated probes (DMPs) showing discordant methylation were further investigated using statistical modeling and enrichment analysis.Results: The smallest number of DMPs was found between the buffy coat and the PMN fraction (2.96%). Pathway enrichment analysis of the DMPs identified biological pathways involved in the particular leukocyte lineage, consistent with perturbations during isolation. The comparisons between the buffy coat and the isolated fractions as a group using linear modeling yielded a small number of probes (∼29,000) with discordant methylation. Demethylation of probes in the buffy coat compared to derived cell lines was more common and was prevalent in shelf and open sea regions.Conclusion: Buffy coat is representative of methylation patterns in WBC types in normal pregnancy. The differential methylations are consistent with perturbations during isolation of constituent cells and likely originate in vitro due to the physical stress during cell separation and are of no physiological relevance. These findings help the interpretation of DNA methylation profiling in pregnancy and numerous other conditions.

Monitoring the environment for pollution, pesticides, and pathogens is crucial for protecting human, agriculture, and overall ecosystem health. Diverse strategies ranging from physical sensors to sentinel species have been used for environmental monitoring. The European honey bee, Apis mellifera, is a globally managed pollinator that can serve as a continuous biomonitoring species. During foraging, honey bees are exposed to contaminants and pathogens and carry them to their hives where they can be detected and quantified. Although individual bees are vulnerable to environmental stressors, the honey bee colony as a whole is more resilient and can accumulate contaminants or respond to them without collapsing. This allows for long-term monitoring of the colony to map contaminants in a geographical area and study ecotoxicology gradients over space and time. In this paper, we review demonstrated and proposed uses of honey bees for environmental monitoring. We focus our discussion on heavy metals, air pollutants, pesticides, and plant pathogens that can be detected in bees and their hive materials including honey, wax, and stored pollen. We present the use of gene expression, microbiome profiling, and other high-throughput methodologies to study dose-dependent exposure and increase detection sensitivity; for example, stored pollen analysis with next generation sequencing can reveal the presence of plant viruses, fungi, and invasive species earlier than traditional detection methods. Finally, we discuss opportunities for using honey bees to monitor emerging threats such as climate change and antimicrobial resistance. This narrative review highlights the versatility and potential utility of the European honey bee as a biomonitoring species for ecosystem health.

Taxane-induced peripheral neuropathy (TIPN) is a devastating survivorship issue for many cancer patients. In addition to its impact on quality of life, this toxicity may lead to dose reductions or treatment discontinuation, adversely impacting survival outcomes and leading to health disparities in African Americans (AA). Our lab has previously identified deleterious mutations in SET-Binding Factor 2 (SBF2) that significantly associated with severe TIPN in AA patients. Here, we demonstrate the impact of SBF2 on taxane-induced neuronal damage using an ex vivo model of SBF2 knockdown of induced pluripotent stem cell-derived sensory neurons. Knockdown of SBF2 exacerbated paclitaxel changes to cell viability and neurite outgrowth while attenuating paclitaxel-induced sodium current inhibition. Our studies identified paclitaxel-induced expression changes specific to mature sensory neurons and revealed candidate genes involved in the exacerbation of paclitaxel-induced phenotypes accompanying SBF2 knockdown. Overall, these findings provide ex vivo support for the impact of SBF2 on the development of TIPN and shed light on the potential pathways involved.

Plasmapheresis for the treatment of hypertriglyceridemia is relatively uncommon and mostly reported either in patients experiencing hypertriglyceridemia-induced acute pancreatitis or patients with therapy-resistant familial hypercholesterolemia. Standard therapies for hypertriglyceridemia include dietary modification and lipid-lowering medication. For severe hypertriglyceridemia, the risk of pancreatitis increases significantly as triglyceride levels increase above 1000 mg/dL, and current therapies are unable to reduce triglyceride levels rapidly enough. Here, we report a case of a 48-year-old male patient who presented to the emergency department due to an amitriptyline overdose. In addition to being started on IV sodium bicarbonate therapy, an intravenous 20% fat emulsion bolus at 1.5 mL/kg was administered followed by 0.25 mL/kg/min infusion for 4 hours as a strategy to absorb lipophilic amitriptyline. Two days posttreatment, he was noted to have substantial hypertriglyceridemia (serum triglycerides: 6,475 mg/dL). His amylase was within the normal range at 37 U/L (reference range: 20-100 U/L), his lipase was low at 40 U/L (reference range: 75-390 U/L), and he was without evidence of any clinical sequelae secondary to hypertriglyceridemia (e.g., pancreatitis). Due to the severity of his hypertriglyceridemia, plasmapheresis was initiated urgently for rapid reduction in serum triglyceride levels to prevent pancreatitis and end-organ damage. He underwent a 1-plasma volume exchange with 5% albumin as the replacement fluid. This reduced his triglyceride levels to 185 mg/dL (reference range: 3-149 mg/dL). His symptoms secondary to his amitriptyline overdose were also resolved. Here, we report a 2-step process of intravenous lipid emulsion followed by plasmapheresis for amitriptyline overdose.

We report a patient with hereditary erythrocytosis who underwent a therapeutic phlebotomy and had a post-phlebotomy hematocrit that was higher than the pre-phlebotomy hematocrit. We could not discern a reason for this hematocrit increase after phlebotomy. Instead of performing another phlebotomy, we performed an automated red cell depletion via an apheresis instrument. This procedure is essentially a red cell exchange, but 5% albumin is used as the replacement fluid instead of red blood cells. The patient’s hematocrit decreased from 80% to 39% after three consecutive daily red cell depletion procedures. We share our experience to report the unusual finding of a patient’s hematocrit that increased with phlebotomy and to raise awareness of the red cell depletion procedure.

Microplastics are ubiquitous in global marine systems and may have negative impacts on a vast range of species. Recently, microplastics were shown to impair shell selection assessments in hermit crabs, an essential behaviour for their survival. Hermit crabs also engage in ‘rapping’ contests over shells, based on cognitive assessments of shell quality and opponent fighting ability and, hence, are a useful model species for examining the effects of microplastics on fitness-relevant behaviour in marine systems. Here, we investigated how a 5-day microplastic exposure (25 microplastics/litre) affected the dynamics and outcome of 120 staged hermit crab contests. Using a 2 × 2 factorial design, we examined how microplastics (i.e. presence or absence) and contestant role (i.e. attacker or defender) affected various behavioural variables. Significantly higher raps per bout were needed to evict microplastic-treated defenders when attackers were pre-exposed to control conditions (i.e. no plastic). Also, significantly longer durations of rapping bouts were needed to evict control-treated defenders when attackers were pre-exposed to microplastics. We suggest that microplastics impaired defenders' ability to identify resource holding potential and also affected attackers’ rapping strength and intensity during contests. These impacts on animal contests indicate that microplastics have broader deleterious effects on marine biota than currently recognized.

Rapidly assaying cell viability for diverse bacteria species is not always straightforward. In eukaryotes, cell viability is often determined using colorimetric dyes; however, such dyes have not been identified for bacteria. We screened different dyes and found that erythrosin B (EB), a visibly red dye with fluorescent properties, functions as a vital dye for many Gram-positive and -negative bacteria. EB worked at a similar concentration for all bacteria studied and incubations were as short as 5 min. Given EB's spectral properties, diverse experimental approaches are possible to rapidly visualize and/or quantitate dead bacterial cells in a population. As the first broadly applicable colorimetric viability dye for bacteria, EB provides a cost-effective alternative for researchers in academia and industry.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Video games are often seen as a medium for entertainment. However, there is an emerging genre of video games that are designed to raise awareness about important social issues like poverty, immigration, and war. These games use persuasive strategies for engaging communities in conversations about human rights issues. This paper provides analyses of the educational strategies of twenty-one human rights video games on the Games For Change website. Our analysis reveals that the ways these games increase cognition, increase empathy and teach affective responses, as well as teach players how to participate in social change processes, serve to educate for behavioral change. Through this medium, players are immersed in simulations which give them a language to not only understand the dynamics at play in issues such as deportation, but also offers players insight into how to change these dynamics and why it is important.

Abstract Background Archived formalin fixed paraffin embedded (FFPE) samples are valuable clinical resources to examine clinically relevant morphology features and also to study genetic changes. However, DNA quality and quantity of FFPE samples are often sub-optimal, and resulting NGS-based genetics variant detections are prone to false positives. Evaluations of wet-lab and bioinformatics approaches are needed to optimize variant detection from FFPE samples. Results As a pilot study, we designed within-subject triplicate samples of DNA derived from paired FFPE and fresh frozen breast tissues to highlight FFPE-specific artifacts. For FFPE samples, we tested two FFPE DNA extraction methods to determine impact of wet-lab procedures on variant calling: QIAGEN QIAamp DNA Mini Kit (“QA”), and QIAGEN GeneRead DNA FFPE Kit (“QGR”). We also used negative-control (NA12891) and positive control samples (Horizon Discovery Reference Standard FFPE). All DNA sample libraries were prepared for NGS according to the QIAseq Human Breast Cancer Targeted DNA Panel protocol and sequenced on the HiSeq 4000. Variant calling and filtering were performed using QIAGEN Gene Globe Data Portal. Detailed variant concordance comparisons and mutational signature analysis were performed to investigate effects of FFPE samples compared to paired fresh frozen samples, along with different DNA extraction methods. In this study, we found that five times or more variants were called with FFPE samples, compared to their paired fresh-frozen tissue samples even after applying molecular barcoding error-correction and default bioinformatics filtering recommended by the vendor. We also found that QGR as an optimized FFPE-DNA extraction approach leads to much fewer discordant variants between paired fresh frozen and FFPE samples. Approximately 92% of the uniquely called FFPE variants were of low allelic frequency range ( T|G > A” mutational signature known to be representative of FFPE artifacts resulting from cytosine deamination. Based on control samples and FFPE-frozen replicates, we derived an effective filtering strategy with associated empirical false-discovery estimates. Conclusions Through this study, we demonstrated feasibility of calling and filtering genetic variants from FFPE tissue samples using a combined strategy with molecular barcodes, optimized DNA extraction, and bioinformatics methods incorporating genomics context such as mutational signature and variant allelic frequency.