cssi/SciSciGPT-SciSciNet huggingface dataset:
A requirement for filopodia extension toward Slit during Robo-mediated axon repulsion

Axons navigate long distances through complex 3D environments to interconnect the nervous system during development. Although the precise spatiotemporal effects of most axon guidance cues remain poorly characterized, a prevailing model posits that attractive guidance cues stimulate actin polymerization in neuronal growth cones whereas repulsive cues induce actin disassembly. Contrary to this model, we find that the repulsive guidance cue Slit stimulates the formation and elongation of actin-based filopodia from mouse dorsal root ganglion growth cones. Surprisingly, filopodia form and elongate toward sources of Slit, a response that we find is required for subsequent axonal repulsion away from Slit. Mechanistically, Slit evokes changes in filopodium dynamics by increasing direct binding of its receptor, Robo, to members of the actin-regulatory Ena/VASP family. Perturbing filopodium dynamics pharmacologically or genetically disrupts Slit-mediated repulsion and produces severe axon guidance defects in vivo. Thus, Slit locally stimulates directional filopodial extension, a process that is required for subsequent axonal repulsion downstream of the Robo receptor.
Public health response to an avian influenza A (H5N1) poultry outbreak in Suffolk, United Kingdom, in November 2007.

An outbreak of highly pathogenic avian influenza (HPAI) H5N1 in a poultry farm in Suffolk, United Kingdom, in November 2007 prompted a comprehensive public health response to stop the transmission of avian influenza to humans. A total of 176 of 178 potentially exposed (99%) received oseltamivir prophylaxis. The majority of them, 169 people (96%), received the influenza vaccine during the outbreak. Thirty people who had been given post-exposure prophylaxis were actively followed up for one week. None of them developed symptoms suggestive of influenza-like illness. Serological investigation (28-day testing) of those who reported symptoms is ongoing.
Isolation of Cdnas Encoding Thymidylate Synthase from Soybean Seedlings and Expression of the Protein in E. Coli

Thymidylate synthase (5,10-methyltetrahydrofolate: dUMP C-methyl-transferase, EC 2.1.1.45) (TS) catalyzes the conversion of deoxyuridylate to thymidylate. Because of its important role in the synthesis of DNA precursors, this enzyme has been extensively studied. The primary structure of thymidylate synthase is highly conserved as revealed by comparison of amino acid sequences of the avian1, mammalian2, and bacterial3 enzymes. Most of these enzymes are homodimers made up of about 35 kDa subunits. However, the enzyme from protozoal parasite, Leishmania major is contained in a bifunctional polypeptide with both thymidylate synthase and dihydrofolate reductase (DHFR) activity. Little is known about TS from plants, although there has been a report of the isolation of a protein complex containing both TS and DHFR activities4. Whether plant TS is a bifunctional enzyme with DHFR or the two enzymes are non-covalently associated can be addressed by cDNA cloning and sequencing. Isolation and expression of the plant TS gene will facilitate characterization of the enzyme at the molecular level, providing biochemical evidence for the study of macromolecule evolution.
Structures of the Mg2+ Channel Cora in the Open State by Cryo Electron Microscopy

Magnesium ions are essential for life and play key roles in signaling and metabolism. The ∼200 kDa pentameric membrane channel CorA opens when the intracellular Mg2+ levels are low, to allow diffusion of Mg2+ into the cell, and closes again when the Mg2+ concentration is sufficiently high. X-ray crystallographic studies have reported similar conformations in both Mg2+-bound (closed) and Mg2+-free states, but EPR spectroscopic studies in lipid-reconstituted CorA show large Mg2+-driven quaternary conformational changes. Using single-particle cryo-EM, we have determined structures of CorA in the Mg2+-bound “closed” conformation plus two “open” Mg2+-free states at resolutions of 3.8 A, 7.1 A and 7.1 A respectively. Comparison of the different conformations reveals dramatic differences in channel symmetry triggered by the unbinding of Mg2+ at the inter-subunit interfaces. Highly asymmetric gating rearrangements were observed from large hinge-bending movements of the long “stalk” helix (as much as ∼35°) in two of the five subunits, leading to large reorientations (∼10 to ∼25 A) of the cytoplasmic domains, which propagate to the transmembrane segments. Our findings suggest an unprecedented gating mechanism where the reversible loss of five-fold symmetry represents the key structural signature of the transition between a single closed state and an ensemble of low-Mg2+, open conformational states.
Using the predictive distribution to determine control limits for the Bayesian MEWMA chart

ABSTRACTBayesian control charts have been proposed for monitoring multivariate processes with the multivariate exponentially weighted moving average (MEWMA) statistic. It has been suggested that we use limits based on the predictive distribution of the MEWMA statistic. This analysis, however is based on the erroneous result that the average run length (ARL) is a function of the exceedance probability, that is, the probability that the first point exceeds the control limit. We show how this result can be corrected and we discuss how the Bayesian MEWMA chart with limits based on the predictive distribution compares with other multivariate control chart procedures.
Transplantation without Hemolysis in a Kell Antigen Positive Patient Undergoing Peripheral Hematopoietic Stem Cell Transplant from a Donor with Anti-Kell Antibodies.

Abstract Red blood cell (RBC) antibody formation, with or without hemolysis, is a well known post-transplant complication of ABO and non-ABO mismatched patients and is seen in both solid organ and hematopoietic stem cell transplants (HSCT). Hemolysis secondary to donor lymphocytes transfused during transplant, which produce antibodies directed toward the patient's remaining red blood cells, is most commonly reported among HSCT donor-recipients with minor ABO blood group mismatching. Passenger Lymphocyte Syndrome (PLS) has been noted to occur in non-ABO group mismatched HSCTs involving the following blood group systems: Rh, Kidd, Lewis, MNS and Duffy. We present a case of a patient with acute myeloid leukemia (AML) in first complete remission who was Kell antigen positive and underwent a non-myeloablative peripheral blood HSCT from a 10/10 HLA matched, related donor who had anti-Kell antibodies. The patient was a 69-year-old male with AML in first remission who consented for transplant with non-myeloablative conditioning on CALGB 100103. At the time of transplantation, the patient was ABO type A positive, had a negative antibody screen, and was positive for the Kell (K1) antigen. The patient had not been transfused RBC or platelets for 4 months prior to HSCT. The related donor was found to be A positive and had anti-Kell that was reactive 1+ at antihuman globulin phase (GEL) prior to filgrastim mobilized peripheral blood HSC collection. The patient received a conditioning regimen of fludarabine 30mg/m2 daily (days -7 to -3) and bulsulfan 0.8mg/kg IV every 6 hours for 8 doses (days -4 to -3). GVHD prophylaxis consisted of methotrexate (5mg/m2) on day +1, +3, and +6 and tacrolimus starting on day -2. After HSCT, no RBC or platelet transfusions were required throughout the patient's course. Neutrophil and platelet engraftment occurred by day +20. Chimerism studies on peripheral blood[c1] at day +30 revealed 61% donor CD3 T cells, 99% CD14 and CD15, myeloid cells, 90% CD19, B cells, and 96% donor whole blood. Weekly direct antiglobulin tests were performed (day +7 through day +21) with monitoring of hemoglobin, hematocrit, LDH, total and direct bilirbuin, BUN, and creatinine to evaluate for hemolysis. No evidence of hemolysis was seen in the immediate post-transplant period, and the patient's antibody screen has remained negative to date through day +100. In conclusion, this case demonstrates that peripheral blood HSCT may be done safely in the setting of non-ABO incompatibility due to Kell in the donor-recipient direction. Given the increasing use of non-myeloablative conditioning regimens and peripheral blood HSCT, both of which increase the risk of PLS, the case highlights that the risks of hemolysis for HSCT are evolving and demonstrates the successful implementation of one strategy for monitoring at risk patients.
Sexually Transmitted Infections

High prevalence of sexually transmitted infections (STI) among adolescents is a significant public health concern. New and repeat STI acquisition in teens and young adults remains disproportionate to other age groups. Conversations with adolescent patients should include education about abstinence, use of barrier protection, reducing number of sexual partners, STI screening recommendations, how to access services for testing and treatment, partner treatment, and availability of effective vaccines against STIs such as human papillomavirus and hepatitis B virus. As early detection and prompt intervention is critical to decreasing disease complications, transmission, and overall community prevalence, it is essential to provide greater access to testing and treatment.
Species-environment relationships among filter-feeding caddisflies (Trichoptera: Hydropsychidae) in Rocky Mountain streams

Species-environment relationships were determined for filter-feeding macroinvertebrates from 55 Rocky Mountain stream sites to establish species distribution patterns. Species abundance and 20 environmental variables were measured at each site with species-environment relationship determined using canonical correspondence analysis and stepwise multiple regression. Results suggest that the distribution of several taxa was strongly related to upstream-downstream environmental gradients. Arctopsyche grandis abundance increased with stream size (width and depth) and decreased with increasing turbulence (Reynolds number). Brachycentrus abundance also increased with stream size (depth). Hydropsyche abundance increased with increasing baseflow. Parapsyche elsis abundance also increased with stream size (depth). Hydropsyche abundance increased with increasing baseflow. Parapsyche elsis abundance demonstrated negative correlation with depth, Froude number, and conductivity. Taxa followed previously reported patterns, partitioning habitat according to stream size. Arctopsyche grandis , Brachycentrus , and Hydropsyche were found in larger (3rd- to 6th order) streams, while Parapsyche elsis was observed in small headwater (1st- and 2nd- order) streams. Other filter-feeding taxa such as Simulium, Pisidium and ostracods exhibited little or no apparent habitat partitioning among stream sites.
Learner-Driven Synthesis of Assessment Data: Engaging and Motivating Residents in Their Milestone-Based Assessments

Competency-based medical education empowers learners to use self-assessment to monitor progress and to improve function. Given the difficulties inherent in self-assessment, we propose an externally calibrated, but resident-owned system to facilitate resident involvement in assessment while minimizing the unreliability of self-assessment. Resident-driven synthesis of assessment data applies self-determination theory to foster residents’ intrinsic motivation to improve by involving them in all the steps in the assessment process. Residents would review data, assign milestone levels, complete a program-specific assessment template, and discuss their findings with the clinical competency committee. Inclusion and empowerment of residents could benefit learners and programs alike.
The Role of Explanations in Casual Observational Learning about Nutrition

The ubiquity of internet-based nutrition information sharing indicates an opportunity to use social computing platforms to promote nutrition literacy and healthy nutritional choices. We conducted a series of experiments with unpaid volunteers using an online Nutrition Knowledge Test. The test asked participants to examine pairs of photographed meals and identify meals higher in a specific macronutrient (e.g., carbohydrate). After each answer, participants received no feedback on the accuracy of their answers, viewed proportions of peers choosing each response, received correctness feedback from an expert dietitian with or without expert-generated explanations, or received correctness feedback with crowd-generated explanations. The results showed that neither viewing peer responses nor correctness feedback alone improved learning. However, correctness feedback with explanations (i.e., modeling) led to significant learning gains, with no significant difference between explanations generated by experts or peers. This suggests the importance of explanations in social computing-based casual learning about nutrition and the potential for scaling this approach via crowdsourcing.
Piperidine-Based Spiro-Fused Biheterocycles

This chapter describes methods of synthesis, pharmacological properties and the use of derivatives of piperidine-based spiro-fused biheterocycles that are represented on the pharmaceutical market with six drugs: typical antipsychotics spiperone, fluspirilene and mosapramine, and three other drugs with diverse spiro-cyclic structure: bronchodilator fenspiride, a neuroleptic agent clospirazine, and an investigational sedative and anxiolytic drug, pazinaclone.
Phosphorylation-Dependent Effects on the Structural Flexibility of Phosphoglucosamine Mutase from Bacillus anthracis.

Phosphoglucosamine mutase (PNGM) is an evolutionarily conserved bacterial enzyme in the peptidoglycan biosynthetic pathway, catalyzing the reversible conversion between glucosamine 1- and 6-phosphate. Previous structural studies of PNGM from the pathogen Bacillus anthracis revealed its dimeric assembly and highlighted the rotational mobility of its C-terminal domain. Recent studies of two other enzymes in the same superfamily have demonstrated the long-range effects on the conformational flexibility associated with phosphorylation of the conserved, active site phosphoserine involved in phosphoryl transfer. Building on this work, we use a combination of experimental and computational studies to show that the active, phosphorylated version of B. anthracis PNGM has decreased flexibility relative to its inactive, dephosphorylated state. Limited proteolysis reveals an enhanced and accelerated cleavage of the dephosphorylated enzyme. 15N transverse relaxation-optimized NMR spectra corroborate a conformational a...
Molecular Level Models for CO2 Sorption in Nanopores

Adsorption of carbon dioxide in slit-shaped carbon micropores at 273 K has been studied by means of the grand canonical Monte Carlo (GCMC) simulations and the nonlocal density functional theory (NLDFT). Three molecular models of CO2 have been used. Long-run GCMC simulations were performed with the three-center model of Harris and Yung (J. Phys. Chem. 1995, 99, 12021). For NLDFT calculations, we developed an effective Lennard-Jones (LJ) model. GCMC simulations of the effective LJ model of CO2 have been performed for comparison. For each model used, parameters of intermolecular potentials have been determined and validated against two-phase bulk equilibrium data and experimental adsorption isotherms on graphite at 273 and 195 K. In the range of pore widths from 3 to 15 A, the NLDFT isotherms of CO2 adsorption are overall in a satisfactory agreement with the GCMC isotherms generated using the three-center model. Some deviations have been observed between 6.5 and 8.5 A, where the adsorbate undergoes a transit...
Abstract 17524: Predictors of Mortality in Patients With Persistent Pulmonary Hypertension Following Transcatheter Aortic Valve Replacement

Introduction: Pulmonary hypertension (PH) is highly prevalent in patients with severe aortic stenosis referred for transcatheter aortic valve replacement (TAVR) evaluation. We sought to assess the ...
A dynamic model-based approach to motion and deformation tracking of prosthetic valves from biplane x-ray images.

Purpose Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure in which a prosthetic heart valve is placed and expanded within a defective aortic valve. The device placement is commonly performed using two-dimensional (2D) fluoroscopic imaging. Within this work, we propose a novel technique to track the motion and deformation of the prosthetic valve in three dimensions based on biplane fluoroscopic image sequences. Methods The tracking approach uses a parameterized point cloud model of the valve stent which can undergo rigid three-dimensional (3D) transformation and different modes of expansion. Rigid elements of the model are individually rotated and translated in three dimensions to approximate the motions of the stent. Tracking is performed using an iterative 2D-3D registration procedure which estimates the model parameters by minimizing the mean-squared image values at the positions of the forward-projected model points. Additionally, an initialization technique is proposed, which locates clusters of salient features to determine the initial position and orientation of the model. Results The proposed algorithms were evaluated based on simulations using a digital 4D CT phantom as well as experimentally acquired images of a prosthetic valve inside a chest phantom with anatomical background features. The target registration error was 0.12 ± 0.04 mm in the simulations and 0.64 ± 0.09 mm in the experimental data. Conclusions The proposed algorithm could be used to generate 3D visualization of the prosthetic valve from two projections. In combination with soft-tissue sensitive-imaging techniques like transesophageal echocardiography, this technique could enable 3D image guidance during TAVR procedures.
Ultra-Thin Films with Eu 3+ Ions for Probing Effects of Local Environment

Ultra-thin films of Eu(TTA) 3 (L1a) have been fabricated by Langmuir-Blodgett technique on plasmonic and dielectric substrates and used to probe the effect of local environment on magnetic dipole emission and charge transfer processes.
Fashion Brands' Use of Emojis on Twitter: An Exploratory Study

The purpose of this study is to explore the use of emojis by fashion brands on their Twitter accounts. This study attempts to contribute knowledge that is helpful in the development and implementation of effective Twitter strategies for fashion brands. Consumers are increasing their use of emojis to communicate with fashion brands on Twitter; however, the use of emojis by fashion brands is minimal and tends to be limited to simple objects as opposed to conveying emotion or brand personality. The findings of this study show that the tweets of fashion brands using emojis were positively related to the number of replies, retweets, and likes. Therefore, fashion brands should explore a wide array of emojis and develop creative ways to implement them into their Twitter messages.
Curricular standpoints and native feminist theories: Why native feminist theories should matter to curriculum studies

In this article I provide a brief overview of feminist standpoint theories, as well as how Native feminist theories complicate and enrich this political and epistemic tradition. Following this over...
Reflection Electron Microscopy Studies of Crystal Lattice Termination at Surfaces

Reflection Electron Microscopy (REM) is applied to the imaging of stacking faults immediately beneath the surface of bulk crystals. Strong contrast is obtained on stacking fault ribbons in graphite. The contrast on Pt(lll) surfaces is also attributed to the stacking sequence change of the topmost layer of atoms.
Social Adjustment and Academic Achievement: A Predictive Model for Students with Diverse Academic and Behavior Competencies

This study examined the hypothesized relationship between social adjustment, as measured by perceived social support, self-concept, and social skills, and performance on academic achievement tests....
Turkish Water Exports: A Model for Regional Cooperation in the Development of Water Resources

This chapter analyzes the status of Turkish plans to export water to Israel, Palestine, Cyprus, and other countries in the Middle East. The most ambitious of these was President Turgut Ozal’s 1986 ‘Peace Water Pipeline’, a $ 21 billion project to bring water from the Seyhan and Ceyhan rivers via pipelines to cities in Syria, Jordan, and the Arab Gulf States. This chapter examines why this was not implemented. A shorter pipeline from the Seyhan or Ceyhan rivers to Syria and Jordan, estimated to cost $ 5 billion, may become feasible following the recent rapprochement between Turkey and Syria, but extension of the pipeline to Israel and the Palestinian territories requires a breakthrough in Syrian-Israeli relations, including resolution of disputes over Jordan River headwaters and the Syrian access to the Sea of Galilee (Kinneret). This chapter will assess the progress of a Turkish export scheme that has been approved in principle: Manavgat water to Israel. Israel has agreed to purchase 50 MCM annually for 20 years from the Manavgat River near Antalya, but as of November 2006 the agreement had been shelved because the parties had neither finalized the price nor selected the company to implement the water transfer. Israeli advocates of desalination object to the price of Turkish water and question the wisdom of relying on Ankara, whose government has lately been critical of Israeli policies. Palestinian water officials express interest in Turkish water if the cost is subsidized by international aid agencies. Ankara views the Manavgat ‘Peace Water Project’ as its contribution to the Arab-Israel peace process. A 100 MCM capacity desalination plant was opened in Israel’s coastal city of Ashkelon in October 2005, while the idea of importing Turkish water was revived in April 2006 as part of a multi-million-dollar energy and water project that will utilize four underwater pipelines to transport water, electricity and high-speed data, natural gas and oil to Israel. Some of the water would be earmarked for Palestinian and Jordanian use, while most of the oil would be transferred by tankers to the Far East. The European Investment Bank is undertaking a $ 50 million feasibility study.
Kyne–Donner Model of Authority’s Recommendation and Hurricane Evacuation Decisions: A Study of Hypothetical Hurricane Event in the Rio Grande Valley, Texas

Many previous studies identified factors influencing hurricane evacuation decisions by testing the protective action decision model (PADM). This study further examines factors that affect the trust in authority’s recommendation and evacuation decision-making in a proposed Kyne–Donner Model. The model provides an understanding of the predictive factors influencing evacuation decision-making through the mediating factor of trust in authority’s recommendation. This study takes advantage of the structural equation modeling method to simultaneously test multi-stages of the model. There are factors, namely, age, gender, education, household size, decision maker, risk area, house materials, hurricane evacuation experience, information seeking frequency, information seeking behavior, and information sources which influence trust in authority’s recommendation which, together with hurricane evacuation impediments, influence the hurricane evacuation decision. The study’s findings are consistent with the PADM and demonstrate the importance of trust in authority’s recommendation and hurricane evacuation decision-making.
Factors influencing the measurement of assimilation and stomatal conductance with the LI-COR 6400XT gas exchange system.

Abstract Although CO2 and H2O exchange rates are often measured in experiments as indicators of physiological plant responses these “gas exchange” measurements are prone to large experimental error. Gas exchange equipment and technology have improved greatly over the past two decades which supports scrutinizing current issues of experimental error in measuring plant photosynthesis and stomatal conductance. This report shows results of a greenhouse experiment with the goal of identifying lessor understood sources of experimental error and variation in measurements with the LI-COR 6400XT gas exchange system. A variety of plant types were used to encompass differing species variation. We found significant sources of experimental error in 1) the time for initial adjustment when placing a leaf in the leaf chamber 2) the time-of-day when measuring 3) leaf age 4) having the chamber window full vs. partially full with leaf tissue 5) using a leaf chamber environment that greatly diverges from the whole plant environment 6) differing degree of experimental error depending upon plant species. A situation with multiple contributors to error would result in useless gas-exchange data. Recommendations for minimizing these experimental errors are given.
The Nationwide Children's Hospital BMT Index (BMTI): A Novel Quality Improvement Metric to Assess the Overall Performance of a Pediatric Blood and Marrow Transplant Program

Objective Hematopoietic cell transplant metrics are often focused on survival at day 100 and 1-year and transplant-related morbidity and mortality due to infection, graft-versus-host disease, and disease relapse. Our objectives were to design and test a metric that reflected overall quality and safety performance of a blood and marrow transplant program and use the metric to drive improvement of the quality of care provided to patients. Method The Blood and Marrow Transplant Index (BMTI) aggregates safety events and missed opportunities for best practices into a composite score that reflects overall clinical performance of the BMT program irrespective of type of transplant or patient outcome. Thirteen domains (Table 1) were selected to include (1) treatment-related quality and safety, (2) provision of harm-free environment, and (3) psychosocial support. The BMTI is an aggregate number of adverse events or missed opportunities to provide quality care in a given period within these domains. In this regard, lower aggregate BMTI scores reflect better care and improved overall systems performance. Results The BMTI was easy to calculate and well accepted across the team. The annual BMTI aggregate score progressively decreased from 133 in 2014 to 35 in 2016 (73% reduction) (Figure 1), leading to the development of a second version of the BMTI in 2017 that addressed some new domain measures. Improvements were noted in all domains. Conclusion The BMTI is a valuable metric to monitor overall clinical efficiency and effectiveness of the BMT service. Specifically, the index documented both the ability to avoid preventable harm and to provide consistent, evidence-based care and psychosocial support. It also improved staff awareness for some overlooked domains of care.
Population Identifiability from Forensic Genetic Markers: Ancestry Variation in Latin America

The Combined DNA Index System (CODIS) loci comprise a standard microsatellite marker set widely used for distinguishing among individuals in forensic DNA identity testing for medicolegal casework in the United States and in other countries. In anthropological genetic research, CODIS markers have become an important tool for uses extending beyond case investigations to quantify ancestry proportions, reveals patterns of admixture, and trace population histories. These investigations are especially prevalent in studies of Latin American population structure. Nevertheless, the accuracy of the ancestry estimates computed from the CODIS loci for highly admixed Latino populations has not been formally tested. Longstanding arguments have been made that small ancestry panels, including the CODIS loci specifically, are not suitable for ancestry inference in admixed populations, due to high heterozygosity and limited number of loci used. Recent studies on ancestry inference using the CODIS loci suggest that these do confer more information of population-level identifiability than recognized in forensic genetic scholarship and by the medicolegal community. Here, we formally test the ability of CODIS and CODIS-proxy (e.g., high-heterozygosity and individual-identifiability loci) marker panels to accurately estimate admixture proportions of individuals, including a sample of Latinos with a wide range of ancestry proportions. Using the same individuals to make direct comparisons of the outcomes, the authors produced ancestry estimates from (a) a small CODIS/CODIS-proxy locus panel and (b) a robust and validated microsatellite ancestry-informative panel. They found evidence (e.g., ρ = 0.80-0.88) that supports the use of CODIS/ CODIS-proxy loci to capture the general ancestry estimation trends of a sample. This finding is in line with results of studies using CODIS on Latin American populations: the ancestry estimations generated by CODIS present trends supported by documented population histories (e.g., colonialism and population movements) and microevolutionary events (e.g., gene flow) in Latin America. However, this study also highlights the limitations of CODIS for making individual-level inferences of ancestry: the associated estimates for an acceptable level of statistical confidence (95%) are too broad to make any nuanced inferences regarding an individual's actual ancestry composition.
Abstract 2494: Emodin inhibits colon cancer by altering BCL-2 family proteins and cell survival pathways

The therapeutic outcome of colon cancer (CoCa) is often compromised due to the development of chemoresistance and toxicities associated with current therapeutics. Hence, identification of less toxic and efficacious agent is needed to treat CoCa. In this study, we tested the effect of natural agent, Emodin (6-methyl-1,3,8-trihydroxyanthraquinone) isolated from Asian plant rhubarb, on CoCa cell death and survival. Effects of Emodin on CoCa (DLD-1 and COLO-201) cell viability and death was determined by MTT and Annexin-V assays, respectively. Apoptosis-specific protein antibody array was used to define the Emodin induced molecular mechanisms involved in cell death vs. survival and results were confirmed by western blot analysis. Mitochondrial membrane potential and the expression/localization of Bcl-2 family protein were assessed via flow cytometry and WB, respectively. Our data show Emodin decreased the viability of CoCa cells and induced apoptotic cell death in a time and dose-dependent manner. Emodin-induced apoptosis resulted in increased death receptor expression, modulated caspase activation, and an imbalance in the Bax/Bcl-2 ratio. Changes in Bcl-2 family protein expression and localization correlated with loss in mitochondrial membrane potential. Emodin also negatively impacted MAPK/JNK, PI3K/AKT, NF-kB and STAT signaling pathways, which are associated with cell growth, differentiation, and Bcl-2 family expression or function. Modulation of cell survival and apoptotic pathways by Emodin and specifically the impact on Bcl-2 projects Emodin significance as promising therapeutic agent for CoCa treatment. Citation Format: Ian T. Saunders, Neeraj Kapur, Hina Mir, Shailesh Singh. Emodin inhibits colon cancer by altering BCL-2 family proteins and cell survival pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2494.
Thyroid Disease and Pregnancy

The thyroid gland undergoes several specific changes during pregnancy, including an increase in the size of the gland depending on the status of iodine nutrition. Iodine deficiency and Hashimoto's disease are the most common causes of hypothyroidism globally and in the U.S., respectively. Hypothyroidism in pregnancy can be associated with several adverse obstetric and infant outcomes and thyroid hormone requirements increase in gestation. Graves' disease in pregnancy is usually managed with antithyroid medications. The diagnosis of Graves' disease may be challenging in pregnancy and should be distinguished from other causes of thyrotoxicosis to optimize outcomes to the mother and fetus.
Genomic stratification beyond Ras/B-Raf in colorectal liver metastasis patients treated with hepatic arterial infusion.

Background Resection of colorectal liver metastases (CLM) can cure disease, but many patients with extensive disease cannot be fully resected and others recur following surgery. Hepatic arterial infusion (HAI) chemotherapy can convert extensive liver disease to a resectable state or decrease recurrence risk, but response varies and no biomarkers currently exist to identify patients most likely to benefit. Methods We performed a retrospective cohort study of CLM patients receiving HAI chemotherapy whose tumors underwent MSK-IMPACT sequencing. The frequency of oncogenic alterations and their association with overall survival (OS) and objective response rate were analyzed at the individual gene and signaling pathway levels. Results Three hundred and seventy patients met inclusion criteria: 189 (51.1%) who underwent colorectal liver metastasectomy followed by HAI + systemic therapy (Adjuvant cohort), and 181 (48.9%) with unresectable CLM (Metastatic cohort) who received HAI + systemic therapy, consisting of 63 (34.8%) with extrahepatic disease and 118 (65.2%) with liver-restricted disease. Genomic alterations were similar in each cohort, and no individual gene or pathway was significantly associated with objective response. Patients in the adjuvant cohort with concurrent Ras/B-Raf alteration and SMAD4 inactivation had worse prognosis while in the metastatic cohort patients with co-alteration of Ras/B-Raf and TP53 had worse OS. Similar findings were observed in a validation cohort. Conclusions Concurrently altered Ras/B-Raf and SMAD4 mutations were associated with worse survival in resectable patients, while concurrent Ras/B-Raf and TP53 alterations were associated with worse survival in unresectable patients. The mutual exclusivity of Ras/B-Raf, SMAD4, and TP53 may have prognostic value for CLM patients receiving HAI.
Noncanonical autophagy in dermal dendritic cells mediates immunosuppressive effects of UV exposure

Background Control of the inflammatory response is critical to maintaining homeostasis, and failure to do so contributes to the burden of chronic inflammation associated with several disease states. The mechanisms that underlie immunosuppression, however, remain largely unknown. Although defects in autophagy machinery have been associated with inflammatory pathologic conditions, we now appreciate that autophagic components participate in noncanonical pathways distinct from classical autophagy. We have previously demonstrated that LC3-associated phagocytosis (LAP), a noncanonical autophagic process dependent on Rubicon (rubicon autophagy regulator [RUBCN]), contributes to immunosuppression. Objective We used Rubcn-/- mice to examine the role of the LAP pathway in mediating the UV-induced immunotolerant program in a model of contact hypersensitivity (CHS). Methods Flow cytometry and transcriptional analysis were used to measure immune cell infiltration and activation in the skin of Rubcn+/+ and Rubcn-/- mice during the CHS response. Results Here, we demonstrate that LAP is required for UV-induced immunosuppression and that UV exposure induces a broadly anti-inflammatory transcriptional program dependent on Rubicon. Rubcn-/- mice are resistant to UV-induced immunosuppression and instead display exaggerated inflammation in a model of CHS. Specifically, RUBCN deficiency in CD301b+ dermal dendritic cells results in their increased antigen presentation capacity and subsequent hyperactivation of the CD8+ T-cell response. Conclusions LAP functions to limit the immune response and is critical in maintaining the balance between homeostasis and inflammation.
Behavioral and neural processes in counterconditioning: Past and future directions

Counterconditioning refers both to the technique and putative process by which behavior is modified through a new association with a stimulus of an opposite valence. Similar to extinction, counterconditioning is considered a form of inhibition that interferes with the expression of the originally learned response without erasing it. But whereas interest in extinction continues to rise, counterconditioning has received far less attention. Here, we provide an in-depth review of counterconditioning research and detail whether counterconditioning is any more effective than extinction at preventing relapse of the originally learned behavior. We consider the clinical implications of counterconditioning, describe recent neurobiological and neuroimaging research in this area, and consider future avenues in need of further investigation.
Critical Care Services: Scope of Practice

Critical care services provide care, monitoring, and therapeutic interventions to patients with life-threatening conditions or injuries and complex multi-organ dysfunction in and beyond the intensive care unit (ICU) settings. The ICU is a complex organizational system. Improvement in performance and outcomes depends on the structure and processes of such systems. High-intensity staffing and closed ICU organizational models are associated with improved outcomes. A dedicated ICU physician-led multidisciplinary team that provides collaborative high-quality critical care, the use of evidence-based care and protocols, and multidisciplinary patient and family-centered ICU rounds are key elements for the provision of critical care to seriously ill patients.
Translation, Subtitling, and Tokyo Placemaking

This chapter examines Tokyo placemaking as a function of the processes of literary translation and cinematic subtitling. Cross-border readers/viewers increasingly seek texts that enable a direct, authentic, and intense relationship between themselves and the authors/directors whose work they consume. It is a relationship made possible by those who translate literature and subtitle film in transnational circulation and those who publish and distribute those works. The first part of the chapter looks at some of the challenges related to literary translation and cinematic subtitling—as well as the struggle for recognition on the part of professionals engaged in those fields. If Tokyo fiction and film literally and figuratively map the city, cultural references—the subject of the remainder of the chapter—are the data points that define the contours and fill in the details of those maps.
The Resilience of Religion in American Higher Education: by John Schmalzbauer and Kathleen A. Mahoney, Waco, TX: Baylor University Press, 2018, 283 pp., $49.95 (hardcover), ISBN 978-1-4813-0871-7

Scholarship on the history of higher education has generally assumed a broad and uninterrupted narrative of secularization. As the story goes, religion dominated America’s colleges and universities...
Diagnosis and treatment of Currarino syndrome in neonates

Objective To explore the diagnosis and treatment of Currarino syndrome in neonates.Methods A retrospective study was conducted on the basis of clinical and imaging features,treatments and prognoses of 6 neonatal cases with Currarino syndrome.Results The diagnoses of sacral mass were missed for 4 patients on initial computed tomography.Definite diagnoses were not made prior to stage Ⅰ operation for 2 cases.Four patients were cured without incision infection by one time or staged operations.Short-term urinary retention developed in 1 case.All 4 surgical patients had normal defecation during a follow-up period of 6-10 months.Conclusions Correct preoperative imaging is important for the diagnosis of Currarino syndrome.Great attention should be paid to the clinical significance of sacral malformations and widened sacrorectal gap. Key words: Neonate; Syndrome; Anus abnormalities; Rectum abnormalities
Three-dimensional guided selective right ventricular septal pacing preserves ventricular systolic function and synchrony in pediatric patients.

Background Nonfluoroscopic 3-dimensional (3D) electroanatomic mapping systems (EAMs) have been developed to guide cardiac catheter navigation and reduce fluoroscopy. Selective right ventricular (RV) septal pacing could prevent pacing-induced left ventricular (LV) dysfunction. Objective The purpose of this study was to determine whether EAM-guided selective RV septal pacing preserves LV contractility/synchrony in pediatric patients with complete atrioventricular block (CAVB) and no other congenital heart defects. Methods Prospective analysis of children/adolescents who underwent EAM-guided selective RV pacing was performed. A 3D pacing map guided ventricular lead implantation at septal sites with narrow paced QRS. Serial echocardiograms were obtained after pacemaker implantation to monitor for function (volumes, ejection fraction [EF], global longitudinal/circumferential strain) and synchrony (interventricular mechanical delay, septal to posterior wall motion delay, systolic dyssynchrony index). Data are reported as median (25th–75th percentile). Results Thirty-two CAVB patients (age 9.8 [7.0–14.0] years; 11 with a previous pacing system) underwent selective RV septal pacing (13 DDD, 19 VVIR pacemaker; midseptum 22, parahisian 7, RV outflow tract 3) with narrow paced QRS (110 [100–120] ms) and low radiation exposure. Follow-up over 24 (5–33) months showed preserved LV function and synchrony, without significant differences between pacing sites (midseptum–parahisian) and mode (VVIR-DDD). EF decreased after implantation in patients without previous pacing, although values were mainly within normal limits. Three parahisian patients underwent early lead repositioning. Conclusion EAM-guided selective RV septal pacing is a feasible technique associated with preserved LV systolic function and synchrony and low radiation exposure in pediatric patients with CAVB.
Magnetic resonance imaging and neurological findings in dogs with disc-associated cervical spondylomyelopathy: a case series.

Canine cervical spondylomyelopathy can be separated into osseous and disc-associated (DA-CSM) forms. Our aim was to describe the magnetic resonance imaging (using a high-field scanner) and neurological findings in dogs with DA-CSM and investigate a relationship between these findings. Sixty-three dogs were included: 60/63 (95 %) were large breeds, with Doberman Pinschers and males over-represented (70 %). Mean and median age at the time of diagnosis was 7.25 and 7.2 years (range 0.41–12 years). Chronic signs were noted in 52/63 (83 %) dogs, with proprioceptive ataxia the most common. Main site of spinal cord compression was commonly C6-7 or C5-6. Thirty-six (57 %) dogs had various sites of spinal cord compression. Most dogs younger than 6 years of age had a single affected site. Foraminal stenosis was present in 51/63 dogs (81 %). T2-weighted hyperintensity was present in 40/63 dogs (63 %). 88 % of the articular processes showed degenerative changes, which correlated strongly with intervertebral disc degeneration. Ligamentum flavum hypertrophy was seen in 38 % of dogs. No correlation was observed between neurologic signs and number of affected sites. A moderate positive correlation was observed between severity of spinal cord compression and neurologic grade (r 0.48; p < 0.001). DA-CSM was predominantly observed in older, male Dobermans, with lesions located in the caudal cervical vertebral region. It was also seen in dogs 3 years of age or even younger (8 %). Single compressive lesions were more common in dogs younger than 6 years of age. Many dogs had concomitant changes (e.g.: ligamentum flavum hypertrophy and foraminal stenosis). Most dogs with ligamentum flavum hypertrophy were 6 years or older. A positive correlation was observed between severity of spinal cord compression and neurologic grade, but multilevel compression was not associated with more severe neurologic signs. A very high percentage of dogs had articular process degenerative changes. Possible biomechanical or genetic relationships between degenerative changes in articular processes, ligamentum flavum, and intervertebral discs warrants further investigation.
Secure Communication in a Multi-antenna Wiretap Channel with a Reconfigurable Intelligent Surface

Reconfigurable Intelligent Surfaces (RIS) are being considered as a candidate technology for next generation of wireless systems (6G), for improving reliability and range extension owing to their low cost and complexity, and suitability for high-frequency schemes. RIS terminals can effectively operate as relaying nodes for transmitted signals, while saving the energy needed for Radio Frequency (RF) transmission. This is implemented by deploying controllable reflecting arrays of meta-surface elements, whose phase can be adjusted by applying fast switching voltage. RIS thus creates a valuable resource in wireless communication: the control over the channel realizations from the RIS relays to the receiver. In this work, we investigate the impact of this resource on improving secure communication rates between a transmitter (base station) and a receiver (end user), in the presence of an external eavesdropper. We consider a multi-antenna wiretap channel aided with a RIS array, and derive the achievable secure degrees of freedom for various number of antennas at different terminals. Our achievability scheme relies on designing the RIS beamforming such that the signals received at the eavesdropper experience destructive interference. Compared to our previous work on multi-antenna wiretap channel with a multi-antenna helper, where active user cooperation enables/improves secure communication rates, here secure communication is enabled/improved by utilizing passive terminals (deployed at low cost).