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The Caprini risk assessment model is widely used for venous thromboembolism (VTE) but has limited data in trauma. The study objective was to determine if the Caprini risk assessment model could effectively risk stratify trauma patients.We performed a retrospective review of trauma patients aged ≥18 years, admitted for greater than 24 h at a level one trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Multiple logistic regression assessed odds of inpatient VTE.A total of 1279 patients met study eligibility, with a total of 33 VTE (2.6%). When comparing those with VTE to those without, the mean age was lower (52.5 vs 59.5, p = 0.06, respectively), sex distribution was similar, but mean body mass index was higher (30.2 vs 27.4, p = 0.019, respectively). The mean Caprini score was 9.9, and 75.5% had a score4, the traditional Caprini high-risk cutoff. The VTE group had a higher mean Injury Severity Score (17.8 vs 12.6, p = 0.011), and mean Caprini score (16.4 vs 9.8, p 0.001). Multiple logistic regression found Caprini score, not Injury Severity Score, was associated with higher odds of VTE (adjusted odds ratio 1.06, 95% confidence interval 1.02-1.10), after adjusting for Injury Severity Score, any missed doses of VTE chemoprophylaxis, and VTE prophylaxis type.Higher Caprini scores are associated with elevated odds of inpatient VTE within hospitalized trauma patients. These data support using the Caprini risk assessment model in the trauma population, which may aid in risk stratification.

OBJECTIVE: To examine the association between caregiver-perceived neighborhood safety and pediatric asthma severity using a cross-sectional, nationally representative sample. STUDY DESIGN: Using data from the 2017–2018 National Survey of Children’s Health, children aged 6–17 years with primary caregiver report of a current asthma diagnosis were included (unweighted N = 3209; weighted N = 3,909,178). Perceived neighborhood safety, asthma severity (mild versus moderate/severe), demographic, household, and health/behavioral covariate data were collected from primary caregiver report. Poisson regression with robust error variance was used to estimate the association between perceived neighborhood safety and caregiver-reported pediatric asthma severity. RESULTS: Approximately one-third of children studied had moderate/severe asthma. Forty-two percent of children with mild asthma and 52% of children with moderate/severe asthma identified as Hispanic or non-Hispanic Black. Nearly 20% of children with mild asthma and 40% of children with moderate/severe asthma were from families living below the federal poverty level. Children living in neighborhoods perceived by their caregiver to be unsafe had higher prevalence of moderate/severe asthma compared to those in the safest neighborhoods (adjusted prevalence ratio: 1.34; 95% confidence interval: 1.04–1.74). This association was found to be independent of race/ethnicity, household federal poverty level, household smoking, and child’s physical activity level after adjusting for covariates. CONCLUSIONS: Children living in neighborhoods perceived by their caregiver to be unsafe have higher prevalence of moderate or severe asthma. Further investigation of geographic context and neighborhood characteristics that influence childhood asthma severity may inform public health strategies to reduce asthma burden and improve disease outcomes.

The Caprini risk assessment model (RAM) is widely used to assess risk of venous thromboembolism (VTE). However, it is cumbersome with 31 variables and poses challenges with inter-rater reliability. This study aimed to determine if an abbreviated model could perform similarly in VTE risk assessment. We performed a retrospective review of trauma patients ≥ 18 years old and admitted for over 24 h at a Level I trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Using a p-value cutoff of 2 h, transfusion, restricted mobility > 72 h, central venous catheter, current major surgery, age, history of VTE, hip or leg fracture, and serious trauma). Compared to the original, the abbreviated model had a similar odds ratio (1.17 vs 1.07, both p-values

BACKGROUND Venous thromboembolism (VTE) in injured children is rare, but its consequences are significant. Several risk stratification algorithms for VTE in pediatric trauma exist with little consensus, and all are hindered in development by relying on registry data with known inaccuracies. We performed a multicenter review to evaluate trauma registry fidelity and confirm the effectiveness of one established algorithm across diverse centers. METHODS Local trauma registries at 10 institutions were queried for all patients younger than 18 years admitted between 2009 and 2018. Additional chart review was performed on all "VTE" cases and random non-VTE controls to assess registry errors. Corrected data were then applied to our prediction algorithm using 10 real-time variables (Glasgow Coma Scale, age, sex, intensive care unit admission, transfusion, central line placement, lower extremity/pelvic fracture, major surgery) to calculate VTE risk scores. Contingency table classifiers and the area under a receiver operator characteristic curve were calculated. RESULTS Registries identified 52,524 pediatric trauma patients with 99 episodes of VTE; however, chart review found that 13 cases were misclassified for a corrected total of 86 cases (0.16%). After correction, the algorithm still displayed strong performance in discriminating VTE-fated encounters (sensitivity, 69%; area under the receiver operating characteristic curve, 0.96). Furthermore, despite wide institutional variability in VTE rates (0.04-1.7%), the algorithm maintained a specificity of >91% and a negative predictive value of >99.7% across centers. Chart review also revealed that 54% (n = 45) of VTEs were directly associated with a central line, usually femoral (n = 34, p < 0.001 compared with upper extremity), and that prophylaxis rates were underreported in the registries by about 50%; still, only 19% of the VTE cases had been on prophylaxis before diagnosis. CONCLUSION The VTE prediction algorithm performed well when applied retrospectively across 10 diverse pediatric centers using corrected registry data. These findings can advance initiatives for VTE screening/prophylaxis guidance following pediatric trauma and warrant prospective study. LEVEL OF EVIDENCE Clinical decision rule evaluated in a single population, level III.

Falls remain the leading cause of unintentional pediatric trauma in the United States. Identifying risk factors for pediatric building falls would influence public health policy. We hypothesized that building falls disproportionately affect low income communities.We performed a cross-sectional analysis of the Kids' Inpatient Database for years 2006, 2009, and 2012. We identified cases (age12 years) of falls from a building using external cause of injury codes. Patient characteristics and injuries were analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was performed to adjust for confounders.There were 2,294 hospitalizations nationally for pediatric falls from a building. The victims were predominately male, in early childhood, non-Hispanic White, in the lowest income quartile, resided in urban settings, and occurred during summer. The mean age was 3.76 years. Logistic regression revealed males were 33% more likely than females, and as compared to non-Hispanic White youth, Black (33%) and Asian or Pacific Islanders (65%) were more likely to experience a fall from a building. Toddlers and those in early childhood were at significantly increased odds than those younger than one year old. Children in the highest income quartile were 29% more likely to experience a building fall.Building falls are a common cause of injury in the U.S. for children under 12 years old. Injury prevention strategies focused on the parents of children aged 1-5 years has the potential to make a significant public health impact.

Background: A systematic review and meta-analysis of case-control animal model studies will help clarify the vascular effects of botulinum toxin (BTX). Methods: Preferred Reporting Items of Systematic reviews and Meta-Analyses guidelines were used to identify all animal case-control studies published before September 13, 2020, evaluating the vascular effects of BTX. Primary parameters included the following: perfusion, flap survival, arterial and venous dilation, and arterial and venous thrombosis. Results: Thirty-six studies with 1032 animals met the systematic review inclusion criteria. Twenty-nine studies had quantifiable data for statistical analysis. Statistically significant increases in perfusion with BTX over saline were detected within 1 day and sustained up to 8 weeks. The following represent weighted mean data from the meta-analysis. The administration of BTX has a 26% increase in both random pattern and pedicled flap survival area over controls. Botulinum toxin causes vasodilation. Botulinum toxin increases vessel diameter in arteries by 40% and in veins by 46% compared with saline controls. The administration of BTX reduces thrombosis by 85% in arteries and by 79% in veins compared with saline controls. Vascular effects were consistent across both BTX-A and BTX-B serotypes, multiple animal species, and various doses. No clear relationships between vascular effects and BTX pretreatment time were identified. Conclusions: Perivascular BTX administration intraoperatively or as a chemical delay pretreatment several days before surgery in multiple animal species and models shows multiple changes to the vascular system. Extrapolation of lessons learned from this systematic review and meta-analysis of animal models could expand research and clinical use of BTX in human vascular disease and surgery.

Using document review, we identified 963 publicly accessible NIH RePORT publications across the 16 funded U54 Partnerships to Advance Cancer Health Equity (PACHE) center programs. Using the 868 publications that met criteria, we determined the frequency of publications across the funded PACHE programs by longevity; reported the frequency of studies focused on cancer health disparities; determined the proportion of institutions serving underserved health disparity populations, underrepresented students (ISUPS), and co- and lead-authored works; and categorized the scope of studies by commonalities in their reported purposes. The study findings showed that (1) center longevity was not necessarily related to the number of publications; (2) less than 20% of studies focused on cancer health disparities (CHD); (3) ISUPU co-authors appeared in 72% of publications, while lead authors were 48%; (4) 6.07% publications focused on cancer diagnosis, screening, treatment, and risk factors; 57.5% studies were mechanistic; 21.53% focused on the impact of interventions on health promotion, prevention, and quality of life; 5.62% studies were related to educational outcomes; and 9.28% studies were classified as epidemiological/survey outcomes. One of the primary purposes of PACHE centers is CHD research. Thus, we advocate increasing the frequency of CHD-focused publications. We suggest increasing the number of ISUPU lead-authored papers. To align with the PACHE mission, we also recommend increasing the number of studies focused on cancer diagnosis, screening, treatment, and risk factors and the impact of interventions on health promotion, prevention, and quality of life. To demonstrate the effectiveness and impact of training, increasing the number of educational outcome studies is also proposed.

Practice patterns for the management of patent ductus arteriosus (PDA) in premature infants are changing with advances in medical management. We sought to determine the increased mortality for premature infants who had a PDA ligation with a co-existing diagnosis of intraventricular hemorrhage (IVH).Premature neonates (1 y old with known gestational week ≤36 wk) with a diagnosis of IVH were identified within the Kids' Inpatient Database (KID) for the years 2006, 2009, and 2012. Diagnoses and procedures were analyzed by ICD-9 codes and stratified by a diagnosis of PDA and procedure of ligation. Case weighting was used to make national estimations. Multivariable logistic regression was performed to adjust for confounders.We identified 7567 hospitalizations for premature neonates undergoing PDA ligation. The population was predominately male (51.6%), non-Hispanic white (41.1%), were from the lowest income quartile (33.1%), had a gestational week of 25-26 wk (34.0%), and a birthweight between 500 and 749 g (37.3%). There was an increased mortality (10.7% versus 6.3%, P 0.01) and an increased length of stay (88.2 d versus 74.4 d, P 0.01) in those with any diagnosis of IVH compared with those without. Adjusted multivariable logistic regression demonstrated that high-grade IVH (III or IV) was associated with a significantly increased risk of mortality in those undergoing PDA ligation (aOR 2.59, P 0.01). Specifically, grade III and IV were associated with an increased odds of in-hospital mortality (aOR 1.99 and 3.16, respectively, P 0.01).Attitudes regarding the need for surgical intervention for PDA have shifted in recent years. This study highlights that premature neonates with grade III or IV IVH are at significantly increased risk of mortality if undergoing PDA ligation during the same hospitalization.III.

Significance The photoreceptor outer segments are primary cilia, modified for phototransduction by incorporation of stacked opsin-loaded membrane disks that are continuously regenerated. This process is disrupted in several types of inherited retinal dystrophy, but the driving force remained unclear. We show that C2orf71/PCARE (photoreceptor cilium actin regulator), associated with inherited retinal dystrophy subtype RP54, efficiently recruits the Arp2/3 complex activator WASF3 to the cilium. This activates an actin dynamics-driven expansion of the ciliary tip, resembling membrane evagination in lamellipodia formation. Colocalization of this actin dynamics module to the base of the outer segments, and absence thereof in Pcare−/− mice, suggests PCARE-regulated actin dynamics as a critical process in outer segment disk formation., The outer segments (OS) of rod and cone photoreceptor cells are specialized sensory cilia that contain hundreds of opsin-loaded stacked membrane disks that enable phototransduction. The biogenesis of these disks is initiated at the OS base, but the driving force has been debated. Here, we studied the function of the protein encoded by the photoreceptor-specific gene C2orf71, which is mutated in inherited retinal dystrophy (RP54). We demonstrate that C2orf71/PCARE (photoreceptor cilium actin regulator) can interact with the Arp2/3 complex activator WASF3, and efficiently recruits it to the primary cilium. Ectopic coexpression of PCARE and WASF3 in ciliated cells results in the remarkable expansion of the ciliary tip. This process was disrupted by small interfering RNA (siRNA)-based down-regulation of an actin regulator, by pharmacological inhibition of actin polymerization, and by the expression of PCARE harboring a retinal dystrophy-associated missense mutation. Using human retinal organoids and mouse retina, we observed that a similar actin dynamics-driven process is operational at the base of the photoreceptor OS where the PCARE module and actin colocalize, but which is abrogated in Pcare−/− mice. The observation that several proteins involved in retinal ciliopathies are translocated to these expansions renders it a potential common denominator in the pathomechanisms of these hereditary disorders. Together, our work suggests that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane at the initiation of new outer segment disk formation.

The TNF superfamily ligands BAFF and APRIL interact with three receptors, BAFFR, BCMA, and TACI, to play discrete and crucial roles in regulating B cell selection and homeostasis in mammals. The interactions between these ligands and receptors are both specific and redundant: BAFFR binds BAFF, whereas BCMA and TACI bind to either BAFF or APRIL. In a previous phylogenetic inquiry, we identified and characterized a BAFF-like gene in lampreys, which, with hagfish, are the only extant jawless vertebrates, both of which have B-like and T-like lymphocytes. To gain insight into lymphocyte regulation in jawless vertebrates, in this study we identified two BCMA-like genes in lampreys, BCMAL1 and BCMAL2, which were found to be preferentially expressed by B-like lymphocytes. In vitro analyses indicated that the lamprey BAFF-like protein can bind to a BCMA-like receptor Ig fusion protein and to both BCMAL1- and BCMAL2-transfected cells. Discriminating regulatory roles for the two BCMA-like molecules are suggested by their differential expression before and after activation of the B-like lymphocytes in lampreys. Our composite results imply that BAFF-based mechanisms for B cell regulation evolved before the divergence of jawed and jawless vertebrates.

This reviews the history of gun buybacks and the literature to determine their impact and efficacy, as well as highlighting salient critiques. Finally, we discuss potential avenues that would enhance our understanding of buybacks and methods to address gun violence. Gun buybacks have become more prominent since their inception in the 1970s and often come in response to a tragic local event. The largest scale buyback was in the mid-1990s in Australia, which collected over 650,000 guns. Buybacks are a cost-effective method of reducing the number of weapons in the general public. Gun buybacks are a cost-effective means to reduce the number of unwanted firearms in the general public and also provide a means for education regarding injury prevention. Buybacks in conjunction with other methods have been shown to be successful in reducing the number of firearms that could lead to injury and death.

Percutaneous osseointegrated (OI) prostheses (POPs) are used to skeletally attach artificial limbs in amputees. While any permanent percutaneous interface is at risk of becoming infected by the resident microbiota colonizing the stoma, most of these patients remain infection-free. Avoidance of infection likely depends upon a mechanically and/or biologically stable skin-to-implant interface. The ultimate question remains, "why do some stomata become infected while others do not?" The answer might be found in the dynamic bacterial communities of the patient and within the stomal site itself. This study is an appendix to the first Food and Drug Administration approved prospective early feasibility study of OI prosthetic docking, in which, 10 transfemoral amputees were implanted with a unique POP device. In this analytical, longitudinal cohort study, each patient's skin and stomal microbiota were analyzed from the initial surgery to 1 year following the second-stage surgery. During each follow-up visit, three swab samples-stomal, device thigh skin and contralateral thigh skin-were obtained. DNA was extracted, and bacterial 16S ribosomal RNA (rRNA) genes were amplified and sequenced to profile microbial communities. The stomal microbiota were distinct from the microbiota on the adjacent thigh skin and the skin of the contralateral thigh, with a significantly increased abundance of Staphylococcus aureus within the stoma. Early on stomal microbiota were characterized by high diversity and high relative abundance of obligate anaerobes. Over time, the stomal microbiota shifted and stabilized in communities of lower diversity dominated by Streptococcus, Corynebacterium, and/or Staphylococcus spp. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2645-2654, 2019.

Cancer-associated systemic inflammation is strongly linked to poor disease outcome in patients with cancer1,2. For most human epithelial tumour types, high systemic neutrophil-to-lymphocyte ratios are associated with poor overall survival3, and experimental studies have demonstrated a causal relationship between neutrophils and metastasis4,5. However, the cancer-cell-intrinsic mechanisms that dictate the substantial heterogeneity in systemic neutrophilic inflammation between tumour-bearing hosts are largely unresolved. Here, using a panel of 16 distinct genetically engineered mouse models for breast cancer, we uncover a role for cancer-cell-intrinsic p53 as a key regulator of pro-metastatic neutrophils. Mechanistically, loss of p53 in cancer cells induced the secretion of WNT ligands that stimulate tumour-associated macrophages to produce IL-1β, thus driving systemic inflammation. Pharmacological and genetic blockade of WNT secretion in p53-null cancer cells reverses macrophage production of IL-1β and subsequent neutrophilic inflammation, resulting in reduced metastasis formation. Collectively, we demonstrate a mechanistic link between the loss of p53 in cancer cells, secretion of WNT ligands and systemic neutrophilia that potentiates metastatic progression. These insights illustrate the importance of the genetic makeup of breast tumours in dictating pro-metastatic systemic inflammation, and set the stage for personalized immune intervention strategies for patients with cancer.

Pediatric trauma centers are required to screen patients for alcohol or other drug use (AOD), Briefly Intervene, and Refer these patients to Treatment (SBIRT) to meet Level 1 and 2 trauma center requirements set by the American College of Surgeons. We evaluated if a mandatory electronic medical record tool increased SBIRT screening compliance for all trauma and non-trauma adolescent inpatients.A SBIRT electronic medical record tool was implemented for pediatric inpatient AOD screening. A positive screen prompted brief intervention and referral for treatment in coordination with social work and psychiatric consultants. We compared pre and post- implementation screening rates among inpatients age 12-18 years and performed sub-group analyses.There were 873 patients before and 1,091 after implementation. Questionnaire screening increased from 0% to 34.4% (p 0.001), without an increase in positivity rate, and lab screening decreased by 4.2% (p = 0.003). Females were more likely to receive a social work consultation than males (14.5 vs 7.5%, p 0.001), despite a greater number of positive questionnaires among males (9.5 vs 17.9%, p = 0.013). White patients were more likely to receive a social work consultation (12.9%) compared to Asian (2%), Black (6.3%), and Other (6.9%) (p = 0.007), despite comparable rates of positive screenings. When comparing English to non-English speakers, English speakers were more likely to have a social work consult (12.0% vs 2.4%, p 0.001) and psychiatry/psychology consult (13.6 vs 5.6%, p = 0.011).Multidisciplinary training along with an electronic medical record tool increased SBIRT protocol compliance. Demographic disparities in intervention rates may exist.

INTRODUCTION: Delivery of healthcare via video-chat (i.e. telemedicine) is growing in interest and applicability and has been shown to increase patient satisfaction. It minimizes travel costs and time expenditure for patients and families and more recently has been widely implemented to prevent the spread of communicable diseases. The aim of this study was to determine if pediatric surgeons could routinely offer telemedicine technologies to patients’ families for post-operative follow-up care. METHODS: We prospectively identified patients aged 5-18 years old who were scheduled to undergo one of …

Immune checkpoint inhibitor (ICI) treatment has thus far shown limited efficacy in triple-negative breast cancer (TNBC) patients, presumably due to sparse or unresponsive tumor-infiltrating lymphocytes. We reveal a strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of BRCA1-proficient and -deficient TNBC, MYC overexpression dramatically decreased lymphocyte infiltration in tumors, along with immune signature loss. Likewise, MYC overexpression suppressed inflammatory signaling induced by BRCA1/2 inactivation in human TNBC cell lines. Moreover, MYC overexpression prevented the recruitment and activation of lymphocytes in co-cultures with human and mouse TNBC models. Chromatin immunoprecipitation (ChIP)-sequencing revealed that MYC directly binds promoters of multiple interferon-signaling genes, which were downregulated upon MYC expression. Finally, MYC overexpression suppressed induction of interferon signaling and tumor growth inhibition by a Stimulator of Interferon Genes (STING) agonist. Together, our data reveal that MYC suppresses innate immunity and facilitates immune escape, explaining the poor immunogenicity of MYC-overexpressing TNBCs.Statement of SignificanceMYC suppresses recruitment and activation of immune cells in TNBC by repressing the transcription of interferon genes. These findings provide a mechanistic rationale for the association of high MYC expression levels with immune exclusion in human TNBCs, which might underlie the relatively poor response of many TNBCs to ICI.

Decussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish. Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain in part being the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis. Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g. the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.

Supplemental material, sj-pdf-1-han-10.1177_1558944721994250 for Botulinum Toxin A and B Improve Perfusion, Increase Flap Survival, Cause Vasodilation, and Prevent Thrombosis: A Systematic Review and Meta-analysis of Controlled Animal Studies by Steven H. Goldberg, Max D. Gehrman and Jove H. Graham in HAND

An Aloka SSD-500V real-time ultrasound unit, equipped with a 17.2cm carcass probe, was used to serially scan feedlot steers (n = 80; initial BW 271 ± 99) at 42-d intervals during a 378-d feeding period by a certified Ultrasound Guidelines Council (UGC) technician. This included 10 separate ultrasound scanning sessions following the initial weight and ultrasound data taken on day minus 7 (one week prior to initial start date). Steers were randomly assigned to implant treatment (REV) or not (CON) at day -7 with the implanted group being re-implanted on day 190. Cattle were weighed and scanned for 12th-rib fat thickness (FTU), 12th-rib longissimus muscle area (LMAU), percentage intramuscular fat (%FATU), and rump fat thickness (RFU) to determine the ability of ultrasound to predict carcass grading outcomes at harvest in implanted vs non-implanted steers. Eight steers were harvested each 42 days and evaluated 48h after harvest to determine final body weight (FBW), 12th-rib fat thickness (FTC), 12th-rib longissimus muscle area (LMAC), and marbling score (MARB). Data were analyzed to determine treatment (TRT) and days on feed (DOF) interactions using the GLIMMIX procedure. Least square (LS) means illustrated differences (P < 0.05) between TRT for FBW, FTU, REAU, and %FATU. No differences (P = 0.088) between TRT for RFU were observed. Differences (P < 0.05) between DOF were observed for FBW through all 10 weigh days. A difference (P < 0.05) across DOF for days 42, 84, 126, 168, 210, 252, and 294 was noted for FTU. These data suggest growth promoting implants cause differences (increases) in weight and traditional ultrasound measures of carcass endpoints.

Steers (n = 80; initial BW 271 ± 99) were serially scanned at 42-d intervals during a 378-d feeding period using an Aloka 500 device by a certified Ultrasound Guidelines Council (UGC) technician using real-time ultrasound. This included 10 separate ultrasound scanning sessions following the initial weight and ultrasound data taken on day minus 7 (one week prior to initial start date). Steers were randomly assigned to implant treatment (either implanted with Revalor XS or not) at day -7. Cattle were weighed and scanned for 12th-rib fat thickness (FTU), 12th-rib longissimus muscle area (LMAU), percentage intramuscular fat (%FATU), and rump fat thickness (RFU) to determine the ability of ultrasound to predict carcass grading outcomes at harvest. Scans were processed by CUP Lab technicians. Eight steers were harvested each 42 days. Carcasses were assessed 48h after harvest to determine 12th-rib fat thickness (FTC), 12th-rib longissimus muscle area (LMAC), and marbling score (MARB). Data were analyzed via Pearson correlation and linear regression to determine the relationship of ultrasound measures to carcass outcomes. Positive correlations (P < 0.01) between ultrasound measures taken the day before harvest and carcass measurements indicated strong relationships between FTU and FTC (r = 0.91), LMAU and LMAC (r = 0.93), and moderately strong relationships between %FATU and MARB (r = 0.76). Prediction equations were generated to estimate FTC = .0088 + (1.02585 x FTU), LMAC = 16.29720 + (0.77197 x LMAU) and MARB = 19.87510 + (5.19832 x %FATU). Results suggest real-time ultrasound data provides an effective tool to estimate carcass outcomes pre-harvest.

Background and aims Despite surgical and chemotherapeutic advances, the 5-year survival rate for stage IV hepatoblastoma (HB), the predominant pediatric liver tumor, remains at 27%. Yes-associated protein 1 (YAP1) and β-catenin co-activation occurs in 80% of children's HB; however, a lack of conditional genetic models precludes tumor maintenance exploration. Thus, the need for a targeted therapy remains unmet. Given the predominance of YAP1 and β-catenin activation in HB, we sought to evaluate YAP1 as a therapeutic target in HB. Approach and results We engineered the conditional HB murine model using hydrodynamic injection to deliver transposon plasmids encoding inducible YAP1S127A , constitutive β-cateninDelN90 , and a luciferase reporter to murine liver. Tumor regression was evaluated using bioluminescent imaging, tumor landscape characterized using RNA and ATAC sequencing, and DNA footprinting. Here we show that YAP1S127A withdrawal mediates more than 90% tumor regression with survival for 230+ days in mice. YAP1S127A withdrawal promotes apoptosis in a subset of tumor cells, and in remaining cells induces a cell fate switch that drives therapeutic differentiation of HB tumors into Ki-67-negative hepatocyte-like HB cells ("HbHeps") with hepatocyte-like morphology and mature hepatocyte gene expression. YAP1S127A withdrawal drives the formation of hbHeps by modulating liver differentiation transcription factor occupancy. Indeed, tumor-derived hbHeps, consistent with their reprogrammed transcriptional landscape, regain partial hepatocyte function and rescue liver damage in mice. Conclusions YAP1S127A withdrawal, without silencing oncogenic β-catenin, significantly regresses hepatoblastoma, providing in vivo data to support YAP1 as a therapeutic target for HB. YAP1S127A withdrawal alone sufficiently drives long-term regression in HB, as it promotes cell death in a subset of tumor cells and modulates transcription factor occupancy to reverse the fate of residual tumor cells to mimic functional hepatocytes.

Adaptive immunity in jawless fishes is based on antigen recognition by three types of variable lymphocyte receptors (VLRs) composed of variable leucine-rich repeats, which are differentially expressed by two T-like lymphocyte lineages and one B-like lymphocyte lineage. The T-like cells express either VLRAs or VLRCs of yet undefined antigen specificity, whereas the VLRB antibodies secreted by B-like cells bind proteinaceous and carbohydrate antigens. The incomplete VLR germline genes are assembled into functional units by a gene conversion–like mechanism that employs flanking variable leucine-rich repeat sequences as templates in association with lineage-specific expression of cytidine deaminases. B-like cells develop in the hematopoietic typhlosole and kidneys, whereas T-like cells develop in the thymoid, a thymus-equivalent region at the gill fold tips. Thus, the dichotomy between T-like and B-like cells and the presence of dedicated lymphopoietic tissues emerge as ancestral vertebrate features, whereas the somatic diversification of structurally distinct antigen receptor genes evolved independently in jawless and jawed vertebrates.

Understanding how tumors escape from immune attack may offer novel therapeutic opportunities. Veglia et al. (2019) demonstrate in Nature that fatty acid transport protein 2 (FATP2) endows neutrophils with immunosuppressive capabilities that promote cancer growth. This receptor can be targeted to unleash anti-tumor immunity and to potentiate immune checkpoint blockade.

Max Cooper recalls the discovery of variable lymphocyte receptors in lampreys and hagfish and explains the significance of this for understanding how adaptive immunity evolved in vertebrates.

Owing to their tremendous diversity and plasticity, immune cells exert multifaceted functions in tumor-bearing hosts, ranging from anti-tumor to pro-tumor activities. Tumor immune landscapes differ greatly between and within cancer types. Emerging evidence suggests that genetic aberrations in cancer cells dictate the immune contexture of tumors. Here, we review the current understanding of the mechanisms whereby common drivers of tumorigenesis modulate the tumor immune milieu. We discuss these findings in the context of clinical observations and examine how cancer-cell-intrinsic properties can be exploited to maximize the benefit of immunomodulatory therapies. Understanding the relationship between cancer cell-intrinsic genetic events and the immune response may enable personalized immune intervention strategies for cancer patients.

Foreword {#article-title-2} The ASHP Research and Education Foundation (“the Foundation”) is pleased to present the sixth edition of the annual Pharmacy Forecast . While the first 4 editions of the Pharmacy Forecast were published as standalone reports, the fifth edition of the Pharmacy

Introduction. Hepatitis B virus (HBV) infection leads to a chronic liver disease that is distributed worldwide. The characterization of HBV into genotypes/subgenotypes is not only a mere procedure for distinguishing different HBV strains around the world because determining their geographic distribution is crucial to understanding their spread across the world. Material and methods. We characterized different HBV genotypes and subgenotypes in five municipalities located in northeastern Maranhao, in the Brazilian north Atlantic coast. 92 HBsAg-positive individuals were submitted to PCR (polymerase chain reaction). Fifty samples were sequenced using automated Sanger sequencing and classified by phylogenetic methods. Results. Subgenotypes D4 and A1 were found in 42 (84%) and eight (16%) samples, respectively. To our knowledge, this is the first study to describe a high frequency of subgenotype D4 in any population. Subgenotype A1 is frequently found across Brazil, but D4 has been rarely detected and only in a few Brazilian states. This study shows the characterization of HBV subgenotypes from a population based study in the state of Maranhao, particularly in populations that do not have frequent contact with populations from other regions of the world. Conclusion. Our findings showed a HBV subgenotype profile that probably reflect the viruses that were brought with the slave trade from Africa to Maranhao. This study also reinforces the need to evaluate the status of HBV dispersion not only in large urban centers, but also in the hinterland, to enable the implementation of effective control and treatment measures.

The glucocorticoid receptor (GR) regulates gene expression, governing aspects of homeostasis, but is also involved in cancer. Pharmacological GR activation is frequently used to alleviate therapy-related side-effects. While prior studies have shown GR activation might also have anti-proliferative action on tumours, the underpinnings of glucocorticoid action and its direct effectors in non-lymphoid solid cancers remain elusive. Here, we study the mechanisms of glucocorticoid response, focusing on lung cancer. We show that GR activation induces reversible cancer cell dormancy characterised by anticancer drug tolerance, and activation of growth factor survival signalling accompanied by vulnerability to inhibitors. GR-induced dormancy is dependent on a single GR-target gene, CDKN1C, regulated through chromatin looping of a GR-occupied upstream distal enhancer in a SWI/SNF-dependent fashion. These insights illustrate the importance of GR signalling in non-lymphoid solid cancer biology, particularly in lung cancer, and warrant caution for use of glucocorticoids in treatment of anticancer therapy related side-effects., Glucocorticoids (GC) are reported to block cancer cell proliferation, but the mode of action is unclear. Here the authors show that glucocorticoid receptor activation induces cancer cell dormancy in lung cancer by regulating CDKN1C expression through a distal enhancer, and these dormant cells are addicted to IGF-1R signalling pathway.

Variable lymphocyte receptors (VLRs), the leucine-rich repeat (LRR)-based antigen receptors of jawless fish, have great utility in a wide variety of biochemical and biological applications, similar to classical Ig-based antibodies. VLR-based reagents may be particularly useful when traditional antibodies are not available. An anti-idiotype lamprey VLR, VLR39, has previously been identified that recognizes the heavy-chain CDR3 of the B-cell receptor (BCR) of a leukemic clone from a patient with chronic lymphocytic leukemia (CLL). VLR39 was used successfully to track the re-emergence of this clone in the patient following chemotherapy. Here, the crystal structure of VLR39 is presented at 1.5 Å resolution and compared with those of other protein-specific VLRs. VLR39 adopts a curved solenoid fold and exhibits substantial structural similarity to other protein-binding VLRs. VLR39 has a short LRRCT loop that protrudes outwards away from the concave face and is similar to those of its protein-specific VLR counterparts. Analysis of the VLR39–BCR interaction by size-exclusion chromatography and biolayer interferometry using the scFv version of the BCR confirms that VLR39 recognizes the BCR Fv region. Such VLR-based reagents may be useful for identifying and monitoring leukemia in CLL patients and in other clinical diagnostic assays.

Kinetics and thermodynamics in supramolecular systems are intimately linked, yet both are independently important for application in sensing assays and stimuli-responsive switching/self-healing of materials. Host-guest interactions are of particular interest in many water-based materials, sensing and drug delivery applications. Herein we investigate the binding dynamics of a variety of electron-rich aromatic moieties forming hetero-ternary complexes with the macrocycle cucurbit[8]uril (CB[8]) and an auxiliary guest, dimethyl viologen, with high selectivity and equilibrium binding constants (Keq up to 1014M−2). Using stopped-flow spectrofluorimetry, association rate constants were observed to approach the diffusion limit, and were found to be insensitive to the structure of the guest. Conversely, the dissociation rate constants of the ternary complexes varied dramatically with the guest structure and were correlated with the thermodynamic binding selectivity. Hence differing molecular features were found to contribute to the associative and dissociative processes, mimicking naturally occurring reactions and giving rise to a decoupling of these kinetic parameters. Moreover, we demonstrate the ability to exploit the phenomena and selectively perturb the associative process with external stimuli (e.g.viscosity and pressure). Significantly, these complexes exhibit increased binding equilibria with increasing pressure, carrying important implications in the application of theCB[8] ternary complex for the formation of hydrogels, as these gels exhibit unprecedented pressure-insensitive rheological properties. A high degree of flexibility therefore exists in the design of host-guest systems with tunable kinetic and thermodynamic parameters for tailor-made applications across a broad range of fields.

Background Unintentional injury is the leading cause of death among pediatric patients. There were 13,436 injuries related to snow sports in those younger than 15 in 2015, with 4.8% requiring admission. These sports are high-risk given the potential for injury even when using protective equipment. We hypothesized that snow sport injury patterns would differ based on patient age. Methods A cross-sectional analysis of the 2009 and 2012 Kids' Inpatient Database was performed. Cases of injuries were identified and analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was used to assess for confounders. Results Within 745 admissions, there was a statistically significant decrease in skull/facial fractures with increasing age and a statistically significant increase in abdominal injuries with increasing age. Children in early and middle childhood were at increased odds of being hospitalized with skull/facial fractures, while older children were more likely hospitalized with abdominal injuries. Conclusions Within the pediatric snow sport population, younger children are more likely to experience head injuries, while older children are more likely to experience abdominal injuries. Further research is needed to determine the origin of this difference, and continued legislation on helmets is also necessary in reducing intracranial injuries. Level of Evidence III

More than a million times every year, an ambulance is deployed in the Netherlands. Of these instances, 87% of the patients will be administered intravenous (IV) fluids. In the current situation, the IV bag always needs to be held above the patient to function properly. This action requires an extra pair of hands, which is very inefficient and can result in the loss of precious time that could otherwise be directed at the patient. Besides needing an extra pair of hands, there is also a chance of air bubbles entering the patient through the drip feed. The novel drip chamber design proposed in this paper aims to solve these problems, as it enables the IV bag to be placed in any orientation and in any manner relative to the patient with a negligible number of air bubbles entering the drip feed. This novel drip chamber was tested in an experimental setting in different orientations and at different flowrates. From the test results, it can be concluded that at a clinical relevant flowrate, a negligible number of air bubbles were present within the IV system. Because of the ease of use of the novel drip chamber and the fact that it is fool-proof, cost-efficient, and shows promising test results, future research on several aspects could make this product a promising addition to health care.

Purpose To compare surgeon and patient assessment of upper extremity functional status at the time of initial consultation. We hypothesized that surgeons and patients demonstrate low levels of agreement with respect to assessing pain scores, functional status, and self-efficacy. Methods One hundred forty-three consecutive new patients were evaluated by 1 of 5 fellowship-trained upper extremity surgeons. Patients completed a Numeric Pain Rating Scale as well as the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity (UE), Pain Interference (PI), and Self-Efficacy (SE) instruments. Surgeons provided their own estimates of patient function on each questionnaire at the conclusion of the visit and were blinded to the results of the patient-reported outcome measures (PROMs) for the duration of the study. Estimation errors, which represent the absolute value of the difference between the patient’s actual score and the surgeon’s estimated score on each questionnaire, were calculated for each questionnaire. Results As a group, surgeons assumed that the PROMIS UE and SE scores were higher than the patients’ actual scores and assumed that patients had lower PROMIS PI scores than were actually reported. Mean estimation errors for all PROMIS instruments were greater than 10 points and larger than the SD for these instruments in the general population. Conclusions Upper extremity surgeons demonstrate difficulty assessing their patient’s self-reported functional status, pain interference, and level of self-efficacy during initial consultations. Clinical relevance Although formalized PROMs are infrequently administered in orthopedic clinics, increased utilization of these questionnaires would allow for a more accurate baseline functional assessment. When evaluating new patients in the outpatient clinic, surgeons should recognize the potential limitations of their assessments of patient-reported function.

Bamboo achieves its mechanical efficiency in bending and compression, meaning mechanical performance per unit mass, due to its hierarchical structure. As an orthotropic tube with a higher strength and stiffness parallel to the tube axis and with a density and property gradient across the tube wall, in which fiber bundles are embedded in a porous matrix, the bamboo culm is both stiffer and stronger in bending and less prone to ovalization and catastrophic failure than an orthotropic tube without property gradients would be. Few engineered materials exist that emulate bamboo's mechanical efficiency. The results of the study presented here demonstrate that freeze casting (ice templating) is a manufacturing process with which bamboo-inspired tubular scaffolds with property gradients across the tube wall can be custom-made. A highly aligned, honeycomb-like porosity is generated by ice crystal growth opposite to the direction of heat flow. Using a core-shell mold, the microstructure of the tube wall material, such as the pore size, geometry, and alignment, is defined by the mold materials' properties and applied cooling conditions. These also allow to custom-design the desired property gradient across the section. Further customization of the tube gradient structure and properties is possible through the deposition of additional layers on the freeze-cast scaffolds. Characterizing the pore structures of the tubes using X-ray microtomography, pore morphology and property gradients can be analyzed and correlated to both the processing conditions and the resulting mechanical properties determined in three-point bending, longitudinal and radial compression. The resulting fundamental structure-property-processing correlations support the custom design of tubular scaffolds that are ideally suited for applications that range from conduits for peripheral nerve repair to ureteral stents.

The glucocorticoid receptor directly regulates thousands of genes across the human genome in a cell-type specific manner, governing various aspects of homeostasis. The influence of the glucocorticoid receptor is also seen in various pathologies, including cancer, where it has been linked to tumorigenesis, metastasis, apoptosis resistance, and therapy bypass. Nonetheless, the direct genetic and molecular underpinnings of glucocorticoid action in cancer remain elusive. Here, we dissected the glucocorticoid receptor signalling axis and uncovered the mechanism of glucocorticoid-mediated cancer cell dormancy. Upon glucocorticoid receptor activation cancer cells undergo quiescence, subserved by cell cycle arrest through CDKN1C and reprogramming of signalling orchestrated via FOXO1/IRS2. Strikingly, co-expression of these three genes, directly regulated by glucocorticoid-induced chromatin looping, correlates with a benign molecular phenotype across human cancers, whereas triple loss is associated with increased expression of proliferation/aggressiveness markers. Finally, we show that the glucocorticoid receptor signalling axis is inactivated by alterations of either the chromatin remodelling complex or TP53 in vitro and in vivo. Our results indicate that the activation of the glucocorticoid receptor leads to cancer cell dormancy, which has several implications in terms of glucocorticoid use in cancer therapy.

Case A 23-year-old female athlete presented with postoperative hip pain and laxity following 3 arthroscopic hip procedures. Conclusions Open reconstruction of the anterior hip capsule with Achilles allograft can correct arthroscopy-induced hip laxity.

Neuroscience has been transformed by the ability to genetically modify inbred mice, including the ability to express fluorescent markers specific to cell types or activation states. This approach has been put to particularly good effect in the study of the innate immune cells of the brain, microglia. These specialized macrophages are exceedingly small and complex, but also highly motile and mobile. To date, there have been no tools similar to those in mice available for studying these fundamental cells in the rat brain, and we seek to fill that gap with the generation of the genetically modified Sprague Dawley rat line:SD-Tg(Iba1-EGFP)Mmmc. Using CRISPR-Cas/9 technology, we knocked inEGFPto the promoter of the geneIba1. With four male and three female founders confirmed by quantitative PCR analysis to have appropriate and specific insertion, we established a breeding colony with at least three generations of backcrosses to obtain stable and reliable Iba1-EGFP expression. The specificity of EGFP expression to microglia was established by flow cytometry for CD45low/CD11b+cells and by immunohistochemistry. Microglial EGFP expression was detected in neonates and persisted into adulthood. Blood macrophages and monocytes were found to express low levels of EGFP, as expected. Last, we show that EGFP expression is suitable for live imaging of microglia processes in acute brain slices and via intravital two-photon microscopy.

Molecularly targeted therapies benefit approximately 15–20% of non-small cell lung cancer (NSCLC) patients carrying specific drug-sensitive mutations. Thus, there is a clinically unmet need for the identification of novel targets for drug development. Here, we performed RNA-deep sequencing to identify altered gene expression between malignant and non-malignant lung tissue. Matrix Metalloproteinase 14 (MMP14), a membrane-bound proteinase, was significantly up-regulated in the tumor epithelial cells and intratumoral myeloid compartments in both mouse and human NSCLC. Overexpression of a soluble dominant negative MMP14 (DN-MMP14) or pharmacological inhibition of MMP14 blocked invasion of lung cancer cells through a collagen I matrix in vitro and reduced tumor incidence in an orthotopic K-Ras G12D/+ p53 −/− mouse model of lung cancer. Additionally, MMP14 activity mediated proteolytic processing and activation of Heparin-Binding EGF-like Growth Factor (HB-EGF), stimulating the EGFR signaling pathway to increase proliferation and tumor growth. This study highlights the potential for development of therapeutic strategies that target MMP14 in NSCLC with particular focus on MMP14-HB-EGF axis.

Identify associated clinical factors and characterize the various forms of hearing loss in the context of blast-related traumatic tympanic membrane (TM) perforation sustained in the combat setting.A prospective study of 41 patients who sustained a TM perforation secondary to blast injury between 2010 and 2012 while serving in combat. Clinical examinations and audiograms were obtained for all patients by a single-institution Otolaryngology service with comparative data generated from review of pre and post-trauma hearing screens. Follow-up clinical and audiogram data were obtained on all available subjects.59 TM perforations were documented with audiograms. A conductive hearing loss of 14.8, 22.4, 20.3, and 18.9 dB and sensorineural hearing loss (SNHL) of 18.0, 13.5, 19.9, and 22.0 dB at 500, 1,000, 3,000, and 4,000 Hz, respectively, were observed. 49% of all hearing loss was SNHL. Clinical factors did not correlate statically to hearing loss (p0.05). On average, patients demonstrated a 51% improvement in SNHL at time of follow-up.In the subacute setting, patients with traumatic TM perforations secondary to combat blast injury demonstrate both a conductive hearing loss and SNHL, with 49% of all loss being sensorineural. An average SNHL improvement of 51% was seen at follow-up.

SummaryStudy Objectives Sleep disruption is increasingly recognized in hospitalized patients. Impaired sleep is associated with measureable alterations in neurodevelopment. The neonatal intensive care unit (NICU) environment has the potential to affect sleep quality and quantity. We aimed: (i) to determine the frequency and duration of hands-on care, and its impact on sleep, for NICU patients; and (ii) to assess the incidence of respiratory events associated with handling for a cohort of sick neonates. Methods Term and near-term neonates admitted to the NICU and at risk for cerebral dysfunction due to severity of illness or clinical suspicion for seizures underwent attended, bedside polysomnography. Continuous polysomnogram segments were analyzed and data on handling, infant behavioral state, and associated respiratory events were recorded. Results Video and polysomnography data were evaluated for 25 infants (gestational age 39.4 ± 1.6 weeks). The maximum duration between handling episodes for each infant was 50.9 ± 26.2 min, with a median of 2.3 min between contacts. Handling occurred across all behavioral states (active sleep 29.5%; quiet sleep 23.1%; awake 29.9%; indeterminate 17.4%; P = 0.99). Arousals or awakenings occurred in 57% of contacts with a sleeping infant. Hypopnea, apnea, and oxygen desaturation occurred with 16%, 8%, and 19.5% of contacts, respectively. Hypopnea was most likely to occur following contact with infants in active sleep (28%; P

Tumor heterogeneity - resulting from genetic and epigenetic alterations acquired during tumor progression - is a critical driver of phenotypic diversity in most cancers. A lethal consequence of tumor heterogeneity is the acquisition of metastatic traits by tumor cells, leading to poor clinical outcomes. This remains a major problem in pancreatic ductal adenocarcinoma (PDAC), which continues to have the worst prognosis of any major cancer type. While most cases of PDAC present with metastatic disease at the time of diagnosis, the patterns and burden of metastasis can vary widely, with some patients exhibiting a limited metastatic burden while others have more extensive spread, which impacts clinical outcomes. However, the biological and functional differences that drive metastatic heterogeneity are poorly understood. One barrier to understanding metastatic heterogeneity has been a paucity of model systems that capture this natural variation and allow for direct assessment of paired primary tumors and metastases. We previously developed an autochthonous model of PDAC – the KPCX model – that employs multiplexed fluorescence-based labeling to track the contribution of multiple distinct tumor populations to metastasis. Importantly, this technique allows for ascertainment of primary-metastatic lineage relationships in vivo, so that primary tumor clones with substantial metastatic potential can be distinguished with those having poor metastatic potential. To understand the factors underlying differences in metastatic potential, we analyzed paired primary tumors and metastases in the KPCX model and from a cohort of 398 PDAC patients. Genomic and transcriptomic analysis of murine and human metastatic PDAC revealed an association between the highly metastatic state and gene amplification or transcriptional upregulation of MYC and its transcriptional targets. Functional assessments showed that MYC promotes metastasis by recruiting tumor associated macrophages (TAMs), leading to greater bloodstream intravasation. Consistent with these findings, metastatic progression in human PDAC was also associated of MYC signaling pathways and enrichment for MYC amplification in metastasis. Collectively, these results implicate MYC activity as a major determinant of metastatic burden and heterogeneity in advanced PDA. Citation Format: Ravikanth Maddipati, Robert J. Norgard, Timour Baslan, Komal S. Rathi, Amy Zhang, Pichai Raman, Max D. Wengyn, Taiji Yamazoe, Jinyang Li, David Balli, Michael J. LaRiviere, Ian W. Folkert, Ian D. Millstein, Jonathan Bermeo, Erica L. Carpenter, Scott Lowe, Christine Iacobuzio-Donahue, Faiyaz Notta, Ben Z. Stanger. MYC Influences metastatic heterogeneity in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-053.

Tumor heterogeneity - resulting from genetic and epigenetic alterations acquired during tumor progression - is a critical driver of phenotypic diversity in most cancers. A lethal consequence of tumor heterogeneity is the acquisition of metastatic traits by tumor cells, leading to poor clinical outcomes. This remains a major problem in pancreatic ductal adenocarcinoma (PDAC), which continues to have the worst prognosis of any major cancer type. While most cases of PDAC present with metastatic disease at the time of diagnosis, the patterns and burden of metastasis can vary widely, with some patients exhibiting a limited metastatic burden while others have more extensive spread, which impacts clinical outcomes. However, the biological and functional differences that drive metastatic heterogeneity are poorly understood. Citation Format: Ravikanth Maddipati, Robert J. Norgard, Timour Baslan, Komal S. Rathi, Amy Zhang, Pichai Raman, Max D. Wengyn, Taiji Yamazoe, Jinyang Li, David Balli, Michael LaRiviere, Ian W. Folkert, Ian D. Millstein, Jonathan Bermeo, Erica L. Carpenter, Scott Lowe, Christine Iacobuzio-Donahue, Faiyaz Notta, Ben Z. Stanger. MYC influences metastatic heterogeneity in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-071.

BACKGROUND To describe the demographic characteristics and burden of pediatric suicides by firearm in the United States using a large all-payer pediatric inpatient care database. METHODS Children and young adults (

Skin is colonized by microbial communities (“microbiota”) that participate in immune homeostasis, development and maintenance of barrier function, and protection from pathogens. The past decade has been marked by an increased interest in the skin microbiota and its role in cutaneous health and disease, in part due to advances in next-generation sequencing platforms that enable high-throughput culture-independent detection of bacteria, fungi, and viruses. Various approaches, including bacterial 16S ribosomal RNA gene sequencing and metagenomic shotgun sequencing, have been applied to profile microbial communities colonizing healthy skin and diseased skin including atopic dermatitis, psoriasis, and acne, among others. Here, we provide an overview of culture-dependent and -independent approaches to profile the skin microbiota and the types of questions that may be answered by each approach. We additionally highlight important study design considerations, selection of controls, interpretation of the results, and limitations and challenges.