cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract LB-425: Design of ß-cyclodextrin-curcumin self-assembly: A new approach for enhanced curcumin delivery and therapeutic efficacy in prostate cancer cells

Curcumin (CUR), a hydrophobic polyphenolic compound derived from the rhizome of the herb Curcuma longa, has shown a wide range of biological applications including cancer prevention and treatment. However, low water solubility, poor pharmacokinetics and suboptimal tumor uptake, greatly hamper its anti-cancer efficacy. This study was designed to develop a novel s-cyclodextrin-curcumin (CD-CUR) self-assembly approach for sustained release and improved curcumin delivery in prostate cancer cells. Cyclodextrin-curcumin self-assemblies were prepared by solvent evaporation technique. The formation of self-assemblies was evaluated by Fourier Transform Infra-red (FTIR), Differential Scanning Calorimetry (DSC), Thermo-gravimetric Analysis (TGA), Scanning and Transmission Electron Microscopic (SEM/TEM) analyses. Intracellular uptake of these self-assemblies was evaluated by Flow cytometry and immunofluorescence microscopy analyses. Therapeutic efficacy of these self-assemblies was determined by cell proliferation and colony formation assays using C4-2, DU145, LNCaP and PC3 prostate cancer cells. The effect of CD-CUR formulation on apoptosis related proteins was determined by immunoblotting. Physico-chemical characterization analyses confirm the formation of CD-CUR self-assemblies, which demonstrated excellent stability and solubility in physiological solutions and showed enhanced intracellular uptake in cells. Additionally, CD-CUR formulation has exhibited an improved therapeutic efficacy and enhanced PARP cleavage in prostate cancer cells compared to free curcumin. In conclusion, CD-CUR self-assemblies enhance intracellular delivery of active curcumin in prostate cancer cells and improved its therapeutic efficacy. This study suggests that CD-CUR self-assembly may be a useful nanoscale formulation for improved curcumin delivery in prostate cancer cells. Tumor specific antibody targeted CD-CUR formulation can further improve the in vivo delivery of curcumin in prostate tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-425.
Implementation and Discussion on Standard Guide for Condition Evaluation of Lightning Protection and Grounding Devices for Substation

Lightning protection and grounding devices for substation plays an important role in the power system, which is an important factor to constraint the safe of the equipment and person when shorted to ground, the evaluation results is the key basis to guide the development of the annual technical and overhaul plan. Currently, the evaluation of the lightning protection and grounding devices based on the Q/GDW611-2011 Guide for condition evaluation of lightning protection and grounding devices for substation. With the ongoing work of the evaluation, there are some confusions about several scoring projects in this guide, and these are explained and analyzed and meanwhile some suggestions are proposed for promoting a more objective and efficiently evaluating the true state. It is also proposed some suggestions for the evaluation of lightning protection and grounding devices.
Strength the discipline of pediatric allergy,immunology and rheumatology in China

The discipline of pediatric allergy,immunology and rheumatology is a new and rapidly developing subspecialty in China.It includes pediatric immunodeficiency diseases,allergic diseases,rheumatic autoimmune diseases,inflammation and inflammatory diseases.It is a frontier discipline involving multi-subspecialty of pediatrics.This review commented on the history,domestic and international situation and the future development of this discipline.
Spinal stenosis. When arthritis is more than arthritis

Spinal stenosis is the result of disc degeneration and narrowing accompanied by facet joint changes culminating in nerve root entrapment. Symptoms of back and leg pain appear gradually usually over a period of years and slowly worsen. Patients are usually in their 50s or older. Most patients are treated initially with nonoperative measures concentrating on pain relief and maintenance of activity. If the symptoms worsen, surgical intervention to relieve pain by decompressing the affected nerve roots is appropriate. Some patients with instability require a fusion. Most patients are satisfied with the results of surgery in relieving preoperative leg pain. Pain relief is often dramatic, allowing most patients to return to normal activity. Elderly patients tolerate this procedure surprisingly well. Old age alone should not be a contra-indication for this surgery. Therefore, the elderly should not be denied the benefits of surgical decompression. Nursing interventions can help these patients learn about spinal stenosis and assist them in pursuing appropriate treatment resulting in improved quality of living.
A Collaborative Engineering Design Research Model—An Aerospace Manufacturer’s View

Bringing new technologies into products and out to a market require continuously improved methods, tools, and skills in engineering design. Following, a brief introduction into challenges for an engine component manufacturer and how engineering design research play an integral role, the aim of this chapter is to discuss experiences from university and industry collaborative research. The university and industry collaborative research is a necessary means to improve practice in industry, and the experience narrated through the cases presented will give some basis as to why this has been, and continues to be the case. Four collaborative research modes are introduced where after three cases from GKN Aerospace Engine Systems as are presented where design research have made impact in several ways. Common to all cases is the long term and deep relation between the academic research team and the company’s key stakeholders, who have been decisive to efficiently transit research results into practice. A common understanding of the challenges while ensuring mutual benefit in research initiatives is considered a key pre-requisite for successful introduction of Engineering Design research results. A main argument is that for adoption of research results that impacts the mindset of people—which is often the case of engineering design research—the research must be seen from a change management perspective. The success factors and learning’s are summarized into key factors for enabling an effective and efficient collaborative design research.
MRI in Congenital Myotonic Dystrophy

The results of CT and MRI of the brain were analyzed and neurological development was assessed from the neonatal period in 7 children with congenital myotonic dystrophy aged 2-8 years at the Division of Neurology, Chiba Children’s Hospital and Department of Pediatrics, Chiba University School of Medicine, Chiba, Japan.
Surface breakdown of dielectrics in vacuum with microsecond pulses

When dielectrics are used for electrical insulation in vacuum the maximum pulsed field is frequently limited by flashover in the region on or near the surface of the dielectric.1–4 The pulsed field at which surface flashover occurs may be a factor of ten or more below the potential at which volume breakdown occurs. 5 The vacuum at which this phenomenon begins is about an order of magnitude below that required for the Paschen minimum and hence cannot be fully explained in terms of the Paschen relation. 1,2,6 This paper presents results obtained on surface flashover for several insulating materials in a vacuum of 10−5 Torr using pulsed dc voltage.
The Impact of Epilepsy on Quality of Life

Epilepsy is one of the most common chronic neurological conditions. The impact of epilepsy extends well beyond the direct effects of seizures and includes a number of challenges, which may lead to disability and severely reduced quality of life. People with epilepsy can face diminished social support and family function, cognitive challenges, medical and psychiatric comorbidities, and stigmatization. In addition, those with epilepsy also report more difficulty in employment, lower annual incomes, and physical limitations. It is important to understand and to work to improve quality of life for people with epilepsy. This chapter reviews epilepsy as a syndrome (causes, incidence), specific effects of epilepsy on quality of life, methods for assessing quality of life, and treatment to improve the lives of people diagnosed with epilepsy.
"Ultimate Skepsis": Nietzsche on Truth as a Regime of Interpretation

Presentation This article is the first English translation of French scholar Patrick Wotling’s extensive research on Nietzsche. In order to understand Nietzsche’s work, Patrick Wotling follows closely Nietzsche’s well-known injunction to his readers: “ learn to read me well!” Hence, he seeks to do a close reading of Nietzsche’s texts, which often resemble a seemingly random juxtaposition of ideas, looking for signs that allow the reader to follow Nietzsche’s thought and weave together a correct interpretation. In so doing it is imperative to reject any reading based on an interpretive framework that is not found in the text itself. This approach is tied to the specificity of Nietzsche’s work in that unlike philosophers before him, he does not hold the pursuit of truth to be the genuine goal of philosophy, and therefore does not write traditional systematic treatises. It is thus necessary to use this close reading approach to reveal the new patterns of thought that Nietzsche uses in place of traditional logical frameworks. Using this method, P. Wotling contends that Nietzsche’s thinking is organized along two tightly bound lines: on the one hand there is a genealogical inquiry, which consists of identifying and evaluating the value of values, and on the other hand there is a concern for the cultivation, or breeding ( Zuchtung ) of human life, which aims at putting in place certain values with the goal of elevating humanity and creating human flourishing. The second goal implies the first, meaning that before knowing what values should be instituted, it is necessary to establish the hierarchy of values, in order to identify which ones are the most useful for the cultivation and enrichment of humanity. Abstract What are Nietzsche’s reasons for criticizing truth? How far does such criticism extend, and how does Nietzsche understand the consequences of his position as regards the philosophical praxis? The discovery of a radical opposition between truth and thought shows that being irrefutable cannot be assimilated to being true, and, at the same time, that truth is interpretation. On closer scrutiny, it appears to be not an essence, but a value, that is to say a type of error that has become essential for the continuation of our life, linked to a long process of physical-psychological absorption, and now productive of a deceptive feeling of necessity. As a consequence, philosophy cannot be equated with the pursuit of truth any longer: first, because, as a free spirit, the genuine philosopher is to be thought of as a lover of riddles, shaped on Epicurus’ pattern rather than on Plato’s; and more importantly, because the philosopher’s real aim is to investigate the value of all particular values (including “truth”) for the development of human life, and, in accordance, to create and impose new “truths.”
On the shape memory of red blood cells

Red blood cells (RBCs) undergo remarkably large deformations when subjected to external forces but return to their biconcave discoid resting shape as the forces are withdrawn. In many experiments, such as when RBCs are subjected to a shear flow and undergo the tank-treading motion, the membrane elements are also displaced from their original (resting) locations along the cell surface with respect to the cell axis, in addition to the cell being deformed. A shape memory is said to exist if after the flow is stopped the RBC regains its biconcave shape and the membrane elements also return to their original locations. The shape memory of RBCs was demonstrated by Fischer [“Shape memory of human red blood cells,” Biophys. J. 86, 3304–3313 (2004)] using shear flow go-and-stop experiments. Optical tweezer and micropipette based stretch-relaxation experiments do not reveal the complete shape memory because while the RBC may be deformed, the membrane elements are not significantly displaced from their original loca...
Advocate Safety Planning Training, Feedback, and Personal Challenges

Of all the advocacy services provided to partner violence and sexual assault victims, safety planning may be most central. However, unlike many community behavioral health or case management services, there is virtually no literature on standards of care in safety planning, ways to measure its effectiveness, or discussion of the challenges advocates face in their day-to-day practice of planning for victim safety. The purpose of this paper is to describe advocate perceptions of training and supervision, how they obtain feedback about their work with victims, and their personal challenges in safety planning with victims. Study results highlight the need for more guidance, training, and support as well as more coping strategies for the numerous personal challenges advocates face in their day-to-day safety planning work. Implications for research and practice are discussed.
Assessing Risk and Related Complications after Reversal of Combat-Associated Ostomies.

Background During the past decade of conflict, numerous patients with combat-associated injuries required the formation of an ostomy. However, outcomes in those patients undergoing ostomy reversal have yet to be analyzed. We review the experience and identify risk factors for complications after ostomy reversal in a series of patients with combat injuries at our military treatment facility. Study Design A retrospective review of patients with combat-associated injuries managed with a diverting ostomy who underwent ostomy reversal at our military treatment facility during a 13-year period. Demographic and clinical data were collected for all patients and postoperative complications were identified. Multivariate analysis was performed to identify independent risk factors for complications after reversal. Complication rates were calculated for 90-day periods of time after ostomy creation and best-fit curve analysis was conducted. Results Ninety-nine patients were identified who underwent ostomy reversal. Forty patients (40.4%) suffered a post-reversal complication. On multivariate analysis, older age (odds ratio 1.11/y; p = 0.038), severe perineal injury indication for diversion (odds ratio 4.37; p = 0.028), and increased time interval between ostomy creation and reversal (odds ratio 1.005/d; p = 0.037), were independently associated with postoperative complications. A cubic regression best fit quarterly complication rate data (R2 0.526; p Conclusions Ostomy reversal in patients wounded in combat is a major undertaking with a high complication rate. The finding of a shorter interval from ostomy creation to reversal independently associated with a reduction in complications provides a modifiable risk factor to guide future practice and potentially reduce complications. Our modeling suggests reversal in the 3- to 6-month time frame can have the lowest rate of complications. Future research to reduce complications is indicated, especially in older patients with perineal wounds.
Labor supply of engineers and scientists for nuclear electric utilities, 1987-1992

An assessment of the adequacy of the supply of health physicists, nuclear engineers, and other engineers for the nuclear electric utility industry is based on job openings for scientists and engineers in broader nuclear-power-related fields, which include engineering and design, manufacturing, fabrication, supporting services, and government. In assessing the likely adequacy of labor supplies for commercial nuclear power job openings over the next 5 yr, consideration has been given to competing sources of labor demands, including nuclear energy research and development activities, nuclear defense, and the total US economy, and to the likely supply of new graduates. In particular, over the last 3 yr, the number of degrees awarded and enrollments in nuclear engineering programs have declined 12 and 14%, respectively, and in health physics programs, 5 and 14%, respectively. For health physics and nuclear engineers, tight labor market conditions (i.e. labor supplies and demand balanced at relatively high salaries) are expected over the next 5 yr because of declining enrollments and slowly growing employment levels plus job replacement needs. The commercial nuclear power field is expected to face tight labor markets for electrical and materials engineers because of strong competing demands in the economy. Other engineering occupations are likelymore » to have adequate supplies for the nuclear power field but at salaries that continue to be relatively higher than salaries for other professional occupations.« less
Studies of the Prefrontal Cortex of Normal Human Subjects: Contributions from Modern Imaging Techniques

Over the past decade modern brain imaging techniques, especially positron emission tomography (PET), have been used with increasing frequency to study the functional anatomy of the normal human brain. In the course of these studies a number of interesting features of the prefrontal cortex have emerged. Novelty and the direction of conscious attention to task execution seem to be important in engaging the prefrontal cortex. Thus, brief rehearsal of tasks initially engaging the prefrontal cortex not only lead to marked changes in performance but also to a disengagement of prefrontal participation, emphasizing its role in certain forms of learning and memory. As a general rule responses are quite lateralized, a feature that depends upon the task requirements. Finally, the responses of prefrontal cortex are not seen in isolation but rather in conjunction with widely distributed responses in other areas of the brain, suggesting that the prefrontal cortex operates as a component of various distributed networks.
Abstract 2241: Tricuspid E/e’ Identifies Elevated Mean Right Atrial Pressures

Background: Tissue Doppler (TDI) and Doppler echocardiography (Echo) has been successfully used to estimate filling pressures (FP) of the left ventricle (LV) and LV diastolic function. However, there is a paucity of data regarding Doppler and TDI parameters in estimation of right ventricular (RV) FP. Objectives: To assess the value of tricuspid (TV) inflow Doppler, TDI of the lateral TV annulus, and M-mode diastolic slope of the lateral tricuspid annular motion (TAM) in estimating mean right atrial pressure (mRAP) compared to invasive mRAP. Methods: One hundred patients who underwent cardiac surgery were prospectively enrolled. Intraoperative transesophageal Echo were performed simultaneously with measurement of mRAP obtained with Swan Ganz catheters. Results: Mean age was 63 ± 14. Mean RAP was significantly correlated with the ratio of TV E wave (E) velocity to TV annulus early diastolic velocity (e’) (TV E/e’), and inversely correlated with TV E wave deceleration time (TV E DT) and lateral TV e’ velocity. TV E and A velocities, Diastolic slope of TAM, late diastolic tissue velocity of TV annulus (TV a’), and TV e’/a’ did not predict elevated mRAP. Receiver operating characteristic (ROC) curve for TV DT, TV e’, and TV E/e’ were determined (Table), and the best area under the curve for predicting mRAP > 10 mmHg was TV E/e’. All patients with TV E/e’>12 had mRAP >10 mmHg, and 100% of those with TV E/e’ 10 mmHg. Wide variability presented in those with TV E/e’ of 2 to 12. The most predictive bivariate model included TV E/e’ (p Conclusion: Mean RA pressure can reliably estimated by the use of Tricuspid annulus e’ velocity as well as Tricuspid E/e’ ratio.
Management of a Traumatic Penetrating Abdominal Wound and Associated Complications in a Horse

Abstract An 8-year-old American Quarter Horse mare presented for acute, traumatic lacerations sustained along the ventral abdomen and hind limbs after an accident involving a manure spreader. A penetrating abdominal wound, extended through the peritoneum, was explored surgically. Peritoneal fluid drained from the abdominal wound for approximately 14 days, which was managed with absorbent bandages and a hernia belt. Wound debridement was augmented with medical maggot therapy initiated on day 11 of hospitalization. On day 37 of hospitalization, febrile episodes and a draining tract along the right lateral abdominal wall prompted ultrasonic examination, leading to the identification and retrieval of 12 sequestered costochondral fragments. The mare was discharged 69 days after presentation with a well granulated, contracting wound bed. This case report describes the management of an open, penetrating, ventral abdominal wound in a horse with a functional outcome.
Parent perspectives on multidisciplinary pediatric hearing healthcare.

Abstract Introduction Family-centered healthcare demands that families provide input regarding the care of their children. Very little is known, however, about how families perceive their experience in different types of multidisciplinary team models, and specifically, in the multidisciplinary setting currently utilized in many pediatric hearing clinics. Methods Quantitative and qualitative parent survey responses were collected and analyzed in a tertiary care pediatric medical center after a one-day multidisciplinary assessment clinical appointment. Questions pertained to information across five domains, including overall experience, diagnosis, treatment plan formulation, additional testing, and resources. Quantitative responses were analyzed descriptively while qualitative responses were evaluated using content analysis to derive themes. Quantitative and qualitative data were evaluated separately and then compared to delineate themes for strengths and weaknesses. Results Overall, high satisfaction was evident in both quantitative and qualitative responses. Results suggested that a one-day multidisciplinary assessment appointment may contribute to parents feeling overwhelmed by information shared and not fully understanding which disciplines are providing care. Analysis revealed a specific area of weakness in our particular setting was inadequate provision of information about functional hearing (e.g., listening socially and academically). Results contributed to a change from a multidisciplinary team model to an interdisciplinary care coordination approach to pediatric hearing healthcare. Conclusions Understanding parent perspectives and expectations is the corner stone of family-centered care and may ultimately influence a child's developmental outcome. A systematic way of evaluating parent perspectives on the clinical process can influence service delivery and help children with hearing loss meet their potential.
Full-scale anaerobic bioremediation of trinitrotoluene (TNT) contaminated soil

An anaerobic bioremediation process for the degradation of nitroaromatic compounds in soil was demonstrated. Thisex situ process was demonstrated full-scale at a 2,4,6-trinitrotoluene (TNT)-contaminated site near Weldon Spring, MO. A bioreactor was loaded with approx 23 m3 of TNT-contaminated soil in the form of a 50∶50 soil: water slurry. This slurry was augmented with a starchy carbon source (1–2% w/v) and buffered with phosphate to near-neutral pH. Indigenous soil bacteria utilized the oxygen, making the slurry anaerobic within 1–2 d. Anaerobes then degraded the TNT (3000 mg/kg) in approx 11 wk. A relatively long treatment time for the bioremediation of the TNT-contaminated soil was necessary, possibly because of the cool ambient temperatures, high clay content of the soil, high level of contamination, and high level of recalcitrance of TNT in soils.
From negation to shared knowledge: The evolution of utterance-final -canha in spoken Korean

Abstract This paper explores the functional and formal shift from the negative construction in Korean -ci anh- to -canha, which currently functions as an utterance-final particle that manages the information structure in discourse, by explicitly marking what the speaker believes to be shared with the other interlocutor. Although linguistic changes that have taken place over time usually requires a thorough examination of diachronic data, this paper shows that it is sometimes possible to trace a linguistic change by examining its synchronic uses, particularly when the change is quite recent and hence ‘historical’ data are not particularly relevant. Because the former form -ci anh- and its reduced form -canha co-exist in Modern Spoken Korean with very distinct functions, a comparative study of these forms will provide insight into how the utterance-final particle -canha has evolved. A usage-based analysis is used to show how a negative construction evolved into a marker of shared knowledge. Furthermore, this study argues that the recurrent (inter)subjectification in the evolution of -canha not only shows the constant, dynamic negotiation of common ground between the speakers in spoken language, but is an important motivation for the shifts of a construction from one function to another.
Evaluating machine learning performance in predicting injury severity in agribusiness industries

Abstract Although machine learning methods have been used as an outcome prediction tool in many fields, their utilization in predicting incident outcome in occupational safety is relatively new. This study tests the performance of machine learning techniques in modeling and predicting occupational incidents severity with respect to accessible information of injured workers in agribusiness industries using workers’ compensation claims. More than 33,000 incidents within agribusiness industries in the Midwest of the United States for 2008–2016 were analyzed. The total cost of incidents was extracted and classified from workers’ compensation claims. Supervised machine learning algorithms for classification (support vector machines with linear, quadratic, and RBF kernels, Boosted Trees, and Naive Bayes) were applied. The models can predict injury severity classification based on injured body part, body group, nature of injury, nature group, cause of injury, cause group, and age and tenure of injured workers with the accuracy rate of 92–98%. The results emphasize the significance of quantitative analysis of empirical injury data in safety science, and contribute to enhanced understanding of injury patterns using predictive modeling along with safety experts’ perspectives with regulatory or managerial viewpoints. The predictive models obtained from this study can be used to augment the experience of safety professionals in agribusiness industries to improve safety intervention efforts.
Formal Total Synthesis of (+)-Salicylihalamides A and B: A Combined Chiral Pool and RCM Strategy

The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral pool approach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for the formation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, the formal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It was found that substitution at the remote phenolic group significantly influenced the ratio of the E- and Z-double bond products in the RCM step. The introduction of phenol protecting groups provided E-isomers preferentially and also enhanced the rates of the RCM reactions.
Challenging human driver taxis with shared autonomous vehicles: a case study of Chicago

When autonomous vehicles (AVs) are fully functional, they will compete with existing mainstays in the transportation system. Sharing AVs can mitigate the inefficient use of privately-owned AVs (e.g...
Impact of in ovo administered pioneer colonizers on intestinal proteome on day of hatch.

Pioneer colonization of the gastrointestinal tract (GIT) by bacteria is thought to have major influence on neonatal tissue development. Previous studies have shown in ovo inoculation of embryos with saline (S), species of Citrobacter (C, C2), or lactic acid bacteria (L) resulted in an altered microbiome on day of the hatch (DOH). The present study investigated GIT proteomic changes at DOH in relation to different inoculations. Embryos were inoculated in ovo with S or ∼102 cfu of C, C2, or L at 18 embryonic days. On DOH, the GIT was collected, and tissue proteins were extracted for analysis via tandem mass spectrometry. A total of 493 proteins were identified for differential comparison with S at P ≤ 0.10. Different levels were noted in 107, 39, and 78 proteins in C, C2, and L groups, respectively, which were uploaded to Ingenuity Pathway Analysis to determine canonical pathways and biological functions related to these changes. Three members of the cytokine family (interleukin [IL]-1β, IL6, and Oncostatin M) were predicted to be activated in C2, indicated with Z-score ≥ 1.50, which suggested an overall proinflammatory GIT condition. This was consistent with the activation of the acute-phase response signaling pathway seen exclusively in C2 (Z-score = 2.00, P < 0.01). However, activation (Z-score = 2.00) of IL-13, upregulation of peroxiredoxin-1 and superoxide dismutase 1, in addition to activation of nitric oxide signaling in the cardiovascular system of the L treatment may predict a state of increased antioxidant capacity and decreased inflammatory status. The nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress response (Z-score = 2.00, P < 0.01) was predicted to be upregulated in C which suggested that chicks were in an inflammatory state and associated oxidative stress, but the impact of these pathways differed from that of C2. These changes in the proteome suggest that pioneer colonizing microbiota may have a strong impact on pathways associated with GIT immune and cellular development.
Parenting and child-caretaking among black men who have sex with men and associated sexual and reproductive health factors: a brief report

The purpose of this exploratory study was to examine the prevalence of parenting and child-caretaking among a sample of black men who have sex with men (MSM), as well as associations between parent...
A Retrospective Chart Review Evaluating Efficacy, Tolerability, and Cost of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i) in Older Adults.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are proven to have profound lowering of low-density lipoprotein cholesterol (LDL-C) in patients with clinical atherosclerotic cardiovascular disease or familial hypercholesterolemia. The primary purpose of this study was to evaluate PCSK9i utilization in older adults, with a focus on efficacy outcomes within 6 months of initiation. Secondary outcomes included tolerability, out-of-pocket expenses (OPE), and barriers to initiation of therapy. We conducted a retrospective chart review of patients ≥ 65 years prescribed PCSK9i therapy by a pharmacist-run lipid clinic within a cardiology practice. A total of 136 older adults were prescribed PCSK9i therapy for a Food and Drug Administration-approved indication between September 2015 and March 2019 with 98 patients included in the analyses. In terms of efficacy, 51 patients who took ≥ 3 doses of PCSK9i with baseline and follow-up lipid panels were assessed. On average, LDL-C reduced by 60% (169–67 mg/dL, p < 0.001). For tolerability, 15 patients reported treatment-emergent side effects, resulting in 10 therapy discontinuations. For the cost analysis, 72 patients reported anticipated OPE for 1 month of therapy. Ultimately 17 patients were approved for manufacturer patient assistance with $0 OPE and 31 patients utilized insurance coverage to obtain therapy reporting a median OPE of $9 United States Dollars ($0–$450). The main barrier to initiation was high OPE. PCSK9i are effective at lowering LDL-C in older adults. Tolerability was high among patients without a history of statin intolerance. PCSK9i remain high-cost medications to both insurance companies and patients in terms of cost-sharing responsibilities.
Species-Dependent Heterophilic and Homophilic Cadherin Interactions in Intestinal Intermicrovillar Links

ABSTRACT Enterocytes are specialized epithelial cells lining the luminal surface of the small intestine that build densely packed arrays of microvilli known as brush borders. These microvilli drive nutrient absorption and are arranged in a hexagonal pattern maintained by intermicrovillar links formed by two non-classical members of the cadherin superfamily of calcium-dependent cell adhesion proteins: protocadherin-24 (PCDH24, also known as CDHR2) and the mucin-like protocadherin (CDHR5). The extracellular domains of these proteins are involved in heterophilic and homophilic interactions important for intermicrovillar function, yet the structural determinants of these interactions remain unresolved. Here we present X-ray crystal structures of the PCDH24 and CDHR5 extracellular tips and analyze their species-specific features relevant for adhesive interactions. In parallel, we use binding assays to identify the PCDH24 and CDHR5 domains involved in both heterophilic and homophilic adhesion for human and mouse proteins. Our results suggest that homophilic and heterophilic interactions involving PCDH24 and CDHR5 are species dependent with unique and distinct minimal adhesive units.
Inpatient admissions and costs for adolescents and young adults with congenital heart defects in New York, 2009-2013.

OBJECTIVES Most individuals born with congenital heart defects (CHDs) survive to adulthood, but healthcare utilization patterns for adolescents and adults with CHDs have not been well described. We sought to characterize the healthcare utilization patterns and associated costs for adolescents and young adults with CHDs. METHODS We examined 2009-2013 New York State inpatient admissions of individuals ages 11-30 years with ≥1 CHD diagnosis codes recorded during any admission. We conducted multivariate linear regression using generalized estimating equations to examine associations between inpatient costs and sociodemographic and clinical variables. RESULTS We identified 5,100 unique individuals with 9,593 corresponding hospitalizations over the study period. Median inpatient cost and length of stay (LOS) were $10,720 and 3.0 days per admission, respectively; 55.1% were emergency admissions. Admission volume increased 48.7% from 2009 (1,538 admissions) to 2013 (2,287 admissions), while total inpatient costs increased 91.8% from 2009 ($27.2 million) to 2013 ($52.2 million). Inpatient admissions and costs rose more sharply over the study period for those with nonsevere CHDs compared to severe CHDs. Characteristics associated with higher costs were longer LOS, severe CHD, cardiac/vascular hospitalization classification, surgical procedures, greater severity of illness, and admission in New York City. CONCLUSION This study provides an informative baseline of health care utilization patterns and associated costs among adolescents and young adults with CHDs in New York State. Structured transition programs may aid in keeping this population in appropriate cardiac care as they move to adulthood.
Perceptions of electronic cigarettes among ethno-culturally diverse Latino adults in four US urban centers.

The aim of this study was to examine perceptions including knowledge, attitudes, and beliefs about e-cigarettes among ethno-culturally diverse Latino adults living in the US, a rapidly growing mino...
Wind Tunnel-Based Aerodynamic Model Identification for a Tilt-Wing, Distributed Electric Propulsion Aircraft

This paper describes the methodology used to develop a high-fidelity aerodynamic model for the Langley Aerodrome No. 8 (LA-8) tandem tilt-wing, distributed electric propulsion, vertical takeoff and landing aircraft. Electric vertical takeoff and landing (eVTOL) vehicle configurations exhibit aerodynamic characteristics of both fixed-wing and rotary-wing aircraft as well as complex vehicle-specific phenomena, such as propeller-wing interactions and high incidence angle propeller aerodynamics. Consequently, conventional aircraft aerodynamic modeling strategies require modification when applied to eVTOL aircraft. Two novel system identification-based approaches are used to develop an aerodynamic model for the LA-8 aircraft configuration using wind tunnel data collected with design of experiments techniques. The modeling strategies are compared by assessing their predictive performance for validation data acquired separately from the data used to identify the model and are shown to have sufficient predictive capability. Research findings are presented with a discussion of unique eVTOL aerodynamic modeling characteristics and practical strategies to inform future aerodynamic modeling efforts for eVTOL aircraft.
Randomized Trial of Show Me FIRST: A Brief School-Based Intervention for Internalizing Concerns

Better integration of evidence-based practices (EBPs) in schools can improve access to effective youth mental health care. However, EBPs typically developed and tested within clinics may not be fea...
Solving the problem of overdetermination of quasisymmetric equilibrium solutions by near-axis expansions. I. Generalized force balance

It is well known that the process of construction of quasisymmetric magnetic fields in magnetostatic equilibrium with isotropic pressure suffers from the problem of overdetermination. This has led to the widespread belief that global quasisymmetric solutions are likely not to exist. We develop a general near-axis expansion procedure that does not rely on the assumption of magnetostatic equilibria with isotropic pressure. We then demonstrate that in equilibria with anisotropic pressure, it is possible to circumvent the problem of overdetermination and carry out the power-series solutions to higher order. This suggests, contrary to current belief, that the existence of globally quasisymmetric fields is likely if one relaxes the assumption of magnetostatic equilibria with isotropic pressure.
Disability and Designer Babies

If deaf parents purposely use new genetic technologies to give their child the genes for deafness, have the parents harmed the child? This and similar questions regarding parents who make genetic choices in favor of disability have preoccupied much of the scholarship regarding new artificial reproductive technologies. Some have argued that we should determine whether a child has been harmed by pondering whether the child’s “right to an open future” has been violated by the parents’ genetic intervention. If that right is violated, some say, the parents should be subject to tort liability for inflicting harm upon the child. This Article considers the consequences of attempting to hold parents liable in tort for making genetic decisions in favor of socially disfavored physical attributes, such as disabilities. A legal scheme that asks judges and juries to separate “good” physical attributes from “bad” ones is problematic, especially when dealing with disabilities. Parents, who have personal experience with the physical traits in question, are better equipped to decide what is best for their offspring than jurors who have less experience and less at stake. Using the “open future” framework to second-guess parental decisions about socially disfavored physical traits only disrupts the parent-child relationship and suggests that discriminatory attitudes are natural and acceptable. Moreover, the concern over genetic interventions in favor of disability is largely misplaced. Disabled parents who want disabled children are few in number and diverse in purpose. The recent focus on these parents in the debate over genetic intervention improperly assumes that such parents are incapable of making good choices and that the physical traits they prefer are inherently damning.
Abstract PS16-07: Blocking H3K27me3 methyltransferase or demethylase activity impacts epithelial-mesenchymal plasticity, suppressing tumor growth and metastasis

Background: Epithelial-mesenchymal plasticity (EMP) is key feature driving breast cancer metastasis. Induction of epithelial-mesenchymal transition (EMT) increases the migratory and invasive capabilities associated with metastatic competence and endows tumors with stem cell properties necessary for initiating tumor growth in the metastatic site. Mesenchymal-epithelial transition (MET) has been increasingly recognized as an integral part of the latter stages of the metastatic cascade as it is required for re-epithelialization, proliferation, and expansion of micro-metastases into macro-metastases with a histopathology similar to that of the primary tumor. Interconversion between epithelial and mesenchymal states requires remodeling of the epigenome–including addition and erasure of H3K27me3, especially near gene promoter and enhancers. Deposited by EZH1 or EZH2, members of the PRC2 complex, H3K27me3 is associated with gene silencing. However, gene activation occurs upon H3K27me3 demethylation to H3K27me1, mediated by KDM6A or KDM6B, members of the Compass-like complex. Results: Based upon our prior work, which showed EMT-driven re-distribution of H3K27me3 onto and off of genes that are critical regulators of cell fate and differentiation, we asked whether inhibition of H3K27me3-directed methyltransferases and demethylases could impact breast cancer. We found that the EZH2 inhibitor, EPZ011989, reduced EMP by preventing recovery of epithelial trails in cells exposed to TGFβ, but did not, on its own, induce EMT. However, we found that either inhibition of the H3K27me3-directed demethylases, KDM6A and KDM6B, using GSK-J4 or shRNA knockdown, induced EMT and promoted cellular migration. Thus, manipulation of either EZH2 or KDM6A/B affected the capacity of cells to repress or activate expression of genes known to exhibit dynamic gain or loss of H3K27me3 during EMT. Given the effects of inhibitors of H3K27-targeted enzymes on EMP, we sought to ascertain their impact on tumor growth and metastasis. Using a GFP-expressing patient-derived xenograft (PDX) model of ER-positive breast cancer, we observed a dose-dependent suppression of primary tumor growth and fewer disseminated tumor cells (DTCs) in response to small molecules targeting H3K27me3 regulators. Conclusions: These results indicate that addition and removal of H3K27me3 is critical for maintenance of cell fate and plasticity. Furthermore, targeting this pathway suppresses breast cancer growth and metastasis in a mouse model of ER-positive breast cancer. Citation Format: Joseph Taube, Provas Das, Kelsey Johnson, John Landua, Lacey Dobrolecki, Michael Lewis. Blocking H3K27me3 methyltransferase or demethylase activity impacts epithelial-mesenchymal plasticity, suppressing tumor growth and metastasis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-07.
Domain adaptive neural networks improve cross-species prediction of transcription factor binding

The intrinsic DNA sequence preferences and cell-type specific cooperative partners of transcription factors (TFs) are typically highly conserved. Hence, despite the rapid evolutionary turnover of individual TF binding sites, predictive sequence models of cell-type specific genomic occupancy of a TF in one species should generalize to closely matched cell types in a related species. To assess the viability of cross-species TF binding prediction, we train neural networks to discriminate ChIP-seq peak locations from genomic background and evaluate their performance within and across species. Cross-species predictive performance is consistently worse than within-species performance, which we show is caused in part by species-specific repeats. To account for this domain shift, we use an augmented network architecture to automatically discourage learning of training species-specific sequence features. This domain adaptation approach corrects for prediction errors on species-specific repeats and improves overall cross-species model performance. Our results demonstrate that cross-species TF binding prediction is feasible when models account for domain shifts driven by species-specific repeats.
Multi-resolution characterization of the COVID-19 pandemic: A unified framework and open-source tool

Amidst the continuing spread of COVID-19, real-time data analysis and visualization remain critical to track the pandemic’s impact and inform policy making. Multiple metrics have been considered to evaluate the spread, infection, and mortality of infectious diseases. For example, numbers of new cases and deaths provide measures of absolute impact within a given population and time frame, while the effective reproduction rate provides a measure of the rate of spread. It is critical to evaluate multiple metrics concurrently, as they provide complementary insights into the impact and current state of the pandemic. We describe a unified framework for estimating and quantifying the uncertainty in the smoothed daily effective reproduction number, case rate, and death rate in a region using log-linear models. We apply this framework to characterize COVID-19 impact at multiple geographic resolutions, including by US county and state as well as by country, demonstrating the variation across resolutions and the need for harmonized efforts to control the pandemic. We provide an open-source online dashboard for real-time analysis and visualization of multiple key metrics, which are critical to evaluate the impact of COVID-19 and make informed policy decisions.
Perceived prototypicality of Asian subgroups in the United States and the United Kingdom

Abstract Asians are monolithically categorized under one broad racial label despite their diverse compositions (e.g., with national origins from South, East, Southeast, or West Asia). Some Asian subgroups are perceived to be more prototypically Asian than others and cultural contexts may further shape such perception. With historically longstanding presence of East Asians in the United States and South Asians in the United Kingdom, we theorized that the perceived prototypicality of different Asian subgroups in the two countries would reflect these respective historical saliencies. Three studies (N = 849) examined how (non-Asian) Americans and Britons perceived different Asian subgroups in terms of how prototypically Asian and how foreign they seem. Studies 1 and 2 found that compared to British participants, Americans perceived East and Southeast Asians as more prototypically Asian; Britons considered South Asians as more prototypically Asian than American participants. Study 3 showed that Americans perceived East and Southeast Asians to be less foreign and more prototypically American than South and West Asians; in contrast, Britons perceived South Asians to be less foreign and more prototypically British than all other Asian subgroups. This research demonstrates the importance of disaggregating Asian subgroups and contextualizing prototype theories within sociohistorical frameworks.