cssi/SciSciGPT-SciSciNet huggingface dataset:
The importance of carcinogen dose in chemoprevention studies: quantitative interrelationships between, dibenzo[a,l]pyrene dose, chlorophyllin dose, target organ DNA adduct biomarkers and final tumor outcome.

Chlorophyllin (CHL) is a potent antimutagen in vitro, an effective anti-carcinogen in several animal models, and significantly reduced urinary biomarkers of aflatoxin B 1 (AFB 1 ) exposure in a human population. Here we report an expanded analysis of CHL chemoprevention using the potent environmental hydrocarbon dibenzo[a,l]pyrene (DBP). A dose-dose matrix design employed over 12 000 rainbow trout to evaluate the interrelationships among dietary carcinogen dose, anti-carcinogen dose, carcinogen-DNA adduct levels at exposure and eventual tumor outcome in two target organs. Included was an evaluation of the pharmaceutical CHL preparation (Derifil), used previously in a study of individuals chronically exposed to AFB 1 . CHL was pre-, co- and post-fed at doses of 0-6000 p.p.m. and co-fed with DBP at doses of 0-371.5 p.p.m. for 4 weeks. This protocol generated a total of 21 dose-dose treatment groups, each evaluated with three or more replicates of 100 animals. The DBP-only treatment produced dose-responsive increases in liver and stomach DBP-DNA adducts, whereas increasing CHL co-treatment doses produced successive inhibition in liver (49-83%) and stomach (47-75%) adduct levels at each DBP dose examined. The remaining 8711 trout were necropsied, 10 months later. DBP treatment alone produced a logit incidence versus log [DBP] dose-response curve in stomach that was linear; CHL co-treatment provided dose-dependent tumor inhibition which ranged from 30 to 68% and was predictable from the adduct response. The Derifil CHL preparation was also found to effectively reduce DNA adduction and final tumor incidence in stomach (as well as liver), with a potency compatible with its total chlorin content. Liver tumor incidence in the DBP-only groups appeared to plateau near 60%. At DBP doses of ≤80 p.p.m., increasing CHL doses generally reduced tumor incidence and multiplicity consistent with early DNA adducts as biomarkers. At 225 p.p.m. DBP, however, very high CHL doses were required to reduce tumor incidence below the 60% plateau. Apparent tumor multiplicity in liver was neither linear nor monotonic with DBP dose, but peaked at 80 p.p.m. DBP and declined at 225 p.p.m., where it was increased by all but one CHL dose. Consequently, the effects of a given CHL dose and the predictivity of DNA adducts as biomarkers were highly dependent on carcinogen dose. These results underscore the critical importance of establishing carcinogen-end point dose-response relationships in chemoprevention studies, and the potential otherwise for misleading interpretations in chemoprevention studies carried out solely at high-carcinogen dose. (Supported by USPHS grants ES03850, ES00210, CA34732, ES07060, ES06052 and ES03819.)
Results of photon radiotherapy for unresectable salivary gland tumors: is neutron radiotherapy’s local control superior?

Background and Purpose: The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980’s reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution’s results of photon radiotherapy for unresectable salivary gland tumors. Methods and Materials: From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. LC, locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. Results: With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient’s experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. Conclusion: Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.
We've Got A Cure For You! Disease Awareness Campaigns

Over the last twenty years, the use of disease awareness campaigns has become predominant in our everyday lives. What started out as a technique to market lifestyle drugs for cosmetics and sexual enhancements in the 1980s and 1990s, has now increased in usage to include many other areas of medicine. Its not uncommon to see drug advertisements in consumer magazines and on television for everything from psychotropic drugs, to drugs that are intended to improve the quality of everyday life for more average Americans. Indeed, its hard to find a popular press magazine that doesnt have at least one such advertisement, while most magazine issues have many such advertisements.
High Specific Activity Iodination and Displacement Radioimmunoassay of Fructose-1,6-diphosphatase

SummaryDisplacement radioimmunoassay of fructose-1,6-diphosphatase is described, capable of measuring quantitatively 100 mμg of enzyme in biological fluids. The preparation of radioiodinated FDPase with high specific activity, a necessary prerequisite for the radioimmunoassay, was complicated by the lability of the enzyme and was, therefore, investigated in detail. Low specific activities of radioiodination in the range of 1-8 mCi/mg of protein were obtained by the IC1 method. Using chloramine-T as an oxidant resulted in radioiodinated FDPase with specific activities in the range of 20-80 mCi/mg of protein. However, the enzyme proved to be sensitive against exposure to chloramine-T; best yields were obtained at short reaction times of less than 10 sec.
Crystal and molecular structure of OC(CoC5H5)3(CF3CCCF3)

The structure of the title compound has been confirmed by an X-ray diffraction analysis, and refined by full-matrix least squares. The crystals are mono-clinic:a=9.171(3),b=25.176(15)c=9.192(3) A,β=117.08(3)°,Z=4,D x =1.976g cm−3,μ=2.66mm¯1, space groupP21/n (No. 14). The finalR value is 5.7%. Interatomic distances and bond angles are compared with those reported in related molecules.
Preventive conservation—more than ‘dusting objects’? An overview of the development of the preventive conservation profession

AbstractThis article revisits our concept of preventive conservation and how we define and practise it given the context of those present day challenges to both environmental and financial sustainability. In an attempt to get a better understanding of the role, scope and position of preventive conservation within the conservation profession, the author explores how the concept was first introduced within professional associations, and how it has subsequently found its way into conservation education. A snapshot of the development of preventive conservation in the job market in the English-speaking world (specifically in the UK and the US) over the last two decades was created. It is concluded that even though preventive conservation is now integrated into the profession, the opportunities for conservators to specialise in preventive conservation are limited. The current debate on sustainability demands conservators rise to the challenge and actively claim their role as a key stakeholder in decision making...
Comparing guideline-based care quality for inflammatory bowel disease and rheumatoid arthritis patients within a medical home.

ABSTRACTBackground: Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) patient populations face similar risks of chronic immunosuppression including corticosteroid use. We compared the receipt of preventive services between IBD and RA populations according to published quality metrics.Methods: We defined a single-center cohort of patients with IBD or RA receiving specialty and primary care. Electronic health record abstraction assessed quality metrics, sociodemographics, comorbidity, and utilization. Comparisons used multivariate odds ratios and Student’s t-tests.Results: 218 RA and 190 IBD patients were included. In multivariate analysis, IBD patients were less likely to receive pneumococcal vaccination (OR=0.29, 95% CI: 0.11-0.85), while RA patients underwent glucocorticoid-induced osteoporosis screening more often (100% vs. 82.5%, p = 0.023).Conclusions: Gastroenterologists can improve care quality for IBD patients by assuming greater responsibility for preventive care in IBD patients and/o...
Sources of Escherichia coli cultures that belonged to O antigen groups associated with infantile diarrheal disease.

human. Although a relatively large number of serotypes have been characterized within each of these O antigen groups, it was believed that certain serotypes occurred frequently in both epidemic and sporadic diarrheal disease, that others occurred infrequently in association with disease, and that many other serotypes were found in materials from diverse sources (0rskov, 1954a; Ewing, 1956; Ewing et al, 1957). Evidence in support of these views is presented.
Subject The Epidemiological Analysis of Motor Traffic of 2008 in Dalian Authors

Objective To analyze the distribution characters and epidemic rules of motor traffic injuries.Methods Descriptive epidemiological method was applied to analyze the injury cases in emergency departments of 3 top hospitals in Dalian from 2008.Results 3128 motor traffic injuries were reported, accounted for15.84%of total injury patients in these three hospitals.The ratio between male and female was 1.41:1.The highest risk age-group was 25~44. Business services were the most vulnerable population,and the percentage of servicer was 22.54%.Hurt scene where the accident happened was chiefly in the street,accounted for 92.65%.The nature of the cases from motor traffic injuries was mainly dampened,with the percentages of 61.57%.The part of injuries was mainly in head,with the percentages of 33.54%.Injury occurs mainly on activities by transportation accounting for 48.88%.Mostly accidents,accounting for 99.30.Conclusion Motor traffic injuries were the main types of injury cases of emergency.Young and middle-aged men were the highest risk age-group. The strategies and practice for motor traffic injuries should be focused on target population and meet targeting preventative requirements.
Surgical strategy for pulmonary atresia with ventricular septal defect associated with severely hypoplastic or absent central pulmonary artery

In patients of pulmonary atresia with ventricular septal defect associated with profound hypoplasia or complete absence of central pulmonary artery, surgical strategy depends on the morphology of native pulmonary artery and major aortopulmonary collateral arteries (MAPCAs). Type of surgery and timing of operation are determined by detailed analysis of angiography and 3-dimensional computed tomography (3D-CT) scan. When native central pulmonary artery exists, palliative procedure like systemicpulmonary shunt or palliative right ventricular outflow tract is recommended in order to promote growth of native pulmonary artery, followed by Rastelli-type definitive repair with/without uniforcalization of MAPCAs. In case of central pulmonary artery absence, staged reconstruction of bilateral pulmonary vascular bed by repeated uniforcalization or 1 stage uniforcalization and Rastelli operation is indicated. However, even after definitive repair, careful attention and scheduled cardiac catheterization with aggressive catheter intervention are required to maintain adequate pulmonary circulation.
137: Cytokine-induced tumor suppressors: A GRIM checkmates ST

The IFN family of cytokines act as potent tumor suppressors, whose growth inhibitory activity is further augmented by with other cell differentiating agents, such as vitamin A. Using a genome-wide knockdown screen, we have identified several IFN/RA-regulated novel tumor suppressive gene products called, the Gene(s)-associated with Retinoid-Interferon induced Mortality. One of the novel genes isolated in the screen, GRIM-19, binds to STAT3 and inhibits growth-promoting gene transcription. GRIM-19 inhibits oncogene induced cell motility, cytoskeletal remodeling, and tumor formation. We show that expression of GRIM-19 is lost and its gene is mutated in several primary human cancers. Tumor derived mutant GRIM-19 proteins have lost their ability suppress constitutively active STAT3 induced cellular transformation and tumor growth and metastasis. To understand the biological impact of GRIM-19 on tumorigenesis, we have developed a conditional knockout mouse. These mice are highly susceptible to carcinogenesis. Even a mono-allelic loss of GRIM-19 was sufficient promote carcinogenesis. Tumors from GRIM-19 null mice have disrupted mitochondrial functions. These tumors have a high STAT3 activity establishing the relevance of GRIM-19 as a potential negative regulator of STAT3.
Learners’ privilege and responsibility: A critical examination of the experiences and perspectives of learners from Chinese backgrounds in the United States

According to the Institute of International Education (2013), Chinese students from K-12 to higher education account for approximately 25% of all international students in the United States. As a result, it is imperative that educators show concern and support for them, as they are shaped by the culture of their home country and challenged by the culture of their adopted country. While researchers have explored how to help socialize English language learners into the American education system either for learning or teaching purposes (e.g., Harklau, 2003; Reinhardt & Zander, 2011), few have focused on Chinese students in the United States. Ma and Wang’s (2014) Learners’ Privilege and Responsibility, which includes contributions from several international scholars, fills this gap by presenting a wide scope of research topics on Chinese students from K-12 to higher education. This book aims to reveal “the complexity of this group of students and the challenges they face as a whole” (p. xiii), while at the same time suggesting how their academic and social challenges in the United States can be addressed by taking into account their prior educational and social experiences in China.
Trajectories for Europa Flyby Sample Return

Ballistic trajectories are computed which would enable a sample return mission to Europa without capturing, descending, or landing. The low-cost mission concept utilizes a free return trajectory that also involves a close flyby of Europa. Near Europa, a small impactor would kinetically impact the icy moon and generate a plume, subsequently sampled by the spacecraft. A broad search algorithm is developed to construct feasible itineraries, which considers Venus and Earth gravity assist sequences. High-quality solutions are then differentially corrected to be continuous using high-fidelity dynamics. The complete methodology is applicable to other outer-planet moons, notably Enceladus. The outbound VEEGA option is found to signifcantly reduce launch C3 compared to alternate options. The characteristics and quality of the solutions exhibit substantial variation over the 12-year period of Jupiter. Nevertheless, a variety of optimized results are computed with C3 as low as 16.0 sq.km/sq.sec, re-entry speed well below that of the Stardust capsule, and flight times of 9 to 15 years.
Linking Issue Management, Corporate Social Responsibility and Crisis Communication: Applying Balance Theory in Crisis and Issue Management

Through a 2 × 2 × 3 experiment design, this study examines effects of issue-related corporate social responsibility (CSR) programmes on stakeholder perceptions of an issue-related crisis (i.e., blame, scepticism and corporate credibility) through the lens of balance theory. Results indicate that issue-related CSR programmes work well in reducing scepticism when stakeholders have high issue involvement and positive attitudes. Scepticism is also found to be a mediator between issue-related CSR programmes and perceived corporate credibility.
Redeeming the Kāmasūtra, by Wendy Doniger, New York, Oxford University Press, 2016, 182 pp., $24.95 (hardback), ISBN 978 0 1904 9928 0

The present volume, penned by one of the most widely read of contemporary Indologists, explores a series of concerns presented in and by Vātsyāyana’s Kāmasūtra, and in doing so illustrates both the...
Intraoperative high-dose-rate brachytherapy: An American Brachytherapy Society consensus report.

Abstract Purpose This report presents recommendations from the American Brachytherapy Society for the use of intraoperative high-dose-rate (IOHDR) brachytherapy. Methods and Materials Members of the American Brachytherapy Society with expertise in IOHDR formulated this document based on their clinical experience and a review of the literature. This report covers the use of IOHDR in colorectal cancer, soft tissue sarcoma, gynecologic cancers, head and neck cancers, and pediatric cancers. This report does not cover intraoperative brachytherapy for breast cancer. Details about treatment planning and delivery are emphasized so this document can serve as a guide to practices implementing this technique. Results IOHDR brachytherapy is generally most beneficial for patients with either close or positive margins and/or recurrent disease in a previous resection bed or previously irradiated area. IOHDR brachytherapy requires a well-coordinated multidisciplinary team. IOHDR brachytherapy is recommended in the treatment of both recurrent and primary locally advanced disease for colorectal and gynecologic malignancies, soft tissue sarcoma, and selected head and neck and pediatric malignancies. Other techniques such as perioperative fractionated brachytherapy are also acceptable in many cases with some advantages and disadvantages compared to IOHDR. Conclusions IOHDR brachytherapy is a specialized technique in radiation therapy with unique properties and advantages in cancer control. Special considerations for treatment planning and delivery are outlined herein.
What are the associations between the quantity of faculty evaluations and residents' perception of quality feedback?

Objectives To determine if there is a correlation between the numbers of evaluations submitted by faculty and the perception of the quality of feedback reported by trainees on a yearly survey.
Lightweight Fault Attack Resistance in Software Using Intra-instruction Redundancy

Fault attack countermeasures can be implemented by storing or computing sensitive data in redundant form, such that the faulty data can be detected and restored. We present a class of lightweight, portable software countermeasures for block ciphers. Our technique is based on redundant bit-slicing, and it is able to detect faults in the execution of a single instruction. In comparison to earlier techniques, we are able to intercept data faults as well as instruction sequence faults using a uniform technique. Our countermeasure thwarts precise bit-fault injections through pseudo-random shifts in the allocation of data bit-slices. We demonstrate our solution on a full AES design and confirm the claimed security protection through a detailed fault simulation for a 32-bit embedded processor. We also quantify the overhead of the proposed fault countermeasure, and find a minimal increase in footprint (14%), and a moderate performance overhead between 125% to 317%, depending on the desired level of fault-attack resistance.
Role of Lewis and Brønsted Acidity in Metal Chloride Catalysis in Organic Media: Reductive Etherification of Furanics

Metal chlorides are demonstrated to behave as bifunctional acid catalysts in organic media in the one-pot reductive etherification of 5-hydroxymethylfurfural (HMF) in 2-propanol toward production of biodiesel. Two competing reaction pathways, direct etherification to 5-(isopropoxymethyl)furfural and reductive etherification to 2,5-bis(alkoxymethyl)furan, are proposed with the selectivity depending on the metal ion. Furfural and furfuryl alcohol are used as model compounds to investigate each pathway individually. The roles of Lewis/Bronsted acidity of metal chlorides solution are elucidated by kinetic studies in conjunction with salt speciation using electrospray soft ionization mass spectrometer. Bronsted acidic species, generated from alcoholysis of the metal chlorides, are the predominant catalytically active species in etherification. On the other hand, partially hydrolyzed metal cations produced by alcoholysis/hydrolysis are responsible Lewis acid centers for furfural reduction to furfuryl alcohol. I...
Yeasts in Insects and Other Invertebrates

Minute organisms, including yeasts with diverse physiological capabilities, make possible the existence of arthropods, especially insects, the most speciose group of organisms on Earth. The yeast growth form occurs throughout most of the fungal kingdom and is often associated with insects. Fungi and insects evolved together in the same habitats where casual associations certainly occurred early in their shared geological history and yeast attractants for insects developed over their lives together. Examples of their interactions range from accidental dispersal and the use of yeasts as food to obligate mutualisms described in this chapter. These include discussions of yeast-like symbionts, the use of the wasp gut for yeast outcrossing, extension of endophyte life cycles to include dispersal by insects, the advantage of yeasts in the diet of many insects such as blood-sucking dipterans, and the yeast-like germination of phoretic fungi in ephemeral habitats. Future studies of yeast–insect associations will continue to include species discovery but also approach theoretical questions of sexual and asexual reproduction, host specificity, host switching, advantages of horizontal and vertical dispersal, and studies that include entire interactive communities.
Cefoxitin vs. Piperacillin/Tazobactam for Acute Appendicitis in Pediatric Patients

Background Appendicitis is a medical emergency that usually necessitates surgery and antibiotics in pediatric patients. There is a lack of consensus regarding optimal antibiotics for pediatric appendicitis, with varying recommendations in guidelines and literature. Recent studies have shown that narrow-spectrum and broad-spectrum antibiotics produce similar outcomes in the treatment of pediatric appendicitis. At our institution, cefoxitin has replaced piperacillin/tazobactam for the management of pediatric appendicitis. We compared patient outcomes, including readmission rates, among patients treated with cefoxitin or piperacillin/tazobactam for surgically managed appendicitis.
Why the Two-Way Fixed Effects Model Is Difficult to Interpret, and What to Do About It

The two-way fixed effects (FE) model, an increasingly popular method for modeling time-series cross-section (TSCS) data, is substantively difficult to interpret because the model's estimates are a complex amalgamation of variation in the over-time and cross-sectional effects. We demonstrate this complexity in the two-way FE estimate through mathematical exposition. As an illustration, we develop a novel simulation that enables us to generate TSCS data with varying over-time and cross-sectional effects and examine the behavior of the two-way FE model as these effects change. We demonstrate that the two-way FE model makes specific assumptions about TSCS datasets, and if these assumptions are not met, the model may be unidentified even if substantial variation exists along both dimensions. Because of the difficulty in interpretation, we do not recommend that applied researchers rely on the two-way FE model except for situations in which the assumptions are well-understood, such as the canonical difference-in-difference design.
Placental implantation over prior cesarean scar causes activation of fetal regulatory T cells.

INTRODUCTION Maternal-fetal chimerism is miniscule, a testament to the integrity of the uteroplacental interface. The soundness of this border region is potentially altered through cesarean delivery of prior babies with uncertain consequences for the following pregnancies. METHODS Using multicolor flow cytometry and quantitative PCR of non-inherited maternal antigens we performed a retrospective case control pilot study and formulated the null hypothesis that placental implantation over a prior uterine scar does not result in the presence of memory Treg (CD45RO+) in the fetus. We then performed a power calculation and performed a blinded, appropriately powered prospective case control study to test the null hypothesis. RESULTS Fetuses born to mothers with prior uterine scar have a roughly five times higher maternal to fetal microchimerism when the placenta directly interacts with the uterine scar. Unlike exposure to antigens in adult life, in utero antigenic exposure induces tolerogenic (Treg) responses in fetuses and we here report the presence of fetal Treg with a memory phenotype (CD45RO+). However, we only find such CD45RO+ fetal Tregs when the placenta abuts the uterine scar (Risk Ratio = 5 [p < 0.05 CI:(1.448 to 17.27)]). These memory fetal Tregs are functionally highly suppressive compared to CD45RA-expressing fetal Tregs, and have specificity for non-inherited maternal antigens. CONCLUSIONS We found that uterine scars, in the case of our study these scars are from prior c-sections, fundamentally impair uterine integrity allowing for increased antigen exposure of the fetus; with our appropriately powered study we rejected the null hypothesis and accepted the alternative hypothesis that placental implantation over a prior uterine scar results in the presence of memory Treg (CD45RO+) in the fetus. Thus, our study demonstrates a previously unappreciated role for uterine integrity in limiting fetal antigenic exposure, a key element to avoid the formation of inappropriate tolerances by the fundamentally tolerogenic fetal immune system.
Utility of optical coherence tomography in the evaluation of sellar and parasellar mass lesions.

Purpose of review Anterior visual pathway compression is a common feature of sellar region masses. We review the visual pathway neuroanatomy pertaining to sellar and parasellar lesions and describe recent advances in optical coherence tomography (OCT) imaging that have provided a novel quantitative perspective in the evaluation and management of such patients. Recent findings Ultrastructural measurements of optic nerve integrity using OCT, namely peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCIPL) thicknesses, have been shown to correlate with visual acuity and visual field deficits on perimetry in patients with compressive sellar region masses. In some cases, OCT can visualize early signs of anterior visual pathway involvement in the absence of clinically evident visual field loss or optic disc pallor. OCT is particularly useful when assessing patients who demonstrate less reliable visual field testing. Furthermore, there is growing awareness that pRNFL and GCIPL thinning preoperatively correlate with worse visual recovery following chiasmal decompression, highlighting the prognostic utility of OCT in this patient population. Summary OCT provides a complimentary, yet critical, role in quantitatively assessing ultrastructural retinal injury in patients with sellar and parasellar lesions compressing the anterior visual pathway and should be incorporated into routine evaluation.
Postoperative Spindle Cell Nodule of the Prostate and Bladder

Postoperative spindle cell nodule of the prostate and bladder (a rare lesion often misinterpreted as sarcoma) is important to recognize. The nodule consists of a reactive proliferation of spindle cells occurring up to several months after a lower genitourinary tract procedure, such as transurethral resection or biopsy. We report on 5 patients with a spindle cell nodule after a prior operation on the prostate or bladder. Of these patients 2 initially were diagnosed as having leiomyosarcoma, including 1 who underwent radical cystoprostatectomy. Because of the potential for inappropriate treatment the clinician must be aware of this entity so that he might question the diagnosis and raise the possibility of a postoperative spindle cell nodule whenever sarcoma is diagnosed after recent surgical instrumentation for a nonmesenchymal lesion in the genitourinary tract.
A decision network based framework for multiagent coalition formation

Novel systems allocating teams of humans and unmanned heterogeneous vehicles are necessary for future applications. An intelligent framework is presented that reasons over a library of coalition formation algorithms to select the most appropriate algorithm(s) to apply to complex missions. The framework is based on decision networks to handle uncertainties in dynamic environments. A group of features is used to identify the most suitable algorithm(s). The proposed framework uses principal component analysis to extract the most significant features that are crucial for making decisions. A technique based on link analysis calculates the utility values for each feature-value pair and algorithm in the library. Experimental results demonstrate that the presented framework accurately chooses the most appropriate coalition formation algorithm(s) based on multiple specified mission criteria and requirements.
Healthcare Utilization and Expenditures in Working-Age Adults with Atrial Fibrillation: The Effect of Switching from Warfarin to Non-Vitamin K Oral Anticoagulants

Our objective was to evaluate the association between switching from warfarin to non-vitamin K oral anticoagulants (NOACs) and potential drug–drug interactions (DDIs), healthcare utilization, and expenditures in working-age adults with atrial fibrillation (AF). We conducted a retrospective cohort study using data from 2010 to 2015 for patients who switched from warfarin to NOACs (switchers) and those who continued to receive warfarin (non-switchers). We identified medications known or suspected to have clinically significant interactions with NOACs or warfarin. We used multivariate logistic regression, negative binomial, and generalized linear models to evaluate the influence of switching to NOACs and of potential DDIs on inpatient visits, outpatient visits, number of outpatient visits, and non-drug medical expenditures. Inverse probability of treatment weighting was also applied in analyses. A total of 4126 patients with AF were included in the study. Switching to NOACs was significantly and negatively related to the number of outpatient, inpatient, and emergency room (ER) visits and non-drug medical expenditures. When potential DDIs were included in the models, switching remained significantly associated only with reduced inpatient and outpatient visits. Notably, having at least one potential DDI was associated with an increased likelihood of ER visits and the number of outpatient visits; it was also significantly and positively associated with non-drug medical expenditures. Relative to persistent warfarin use, switching to NOACs was associated with fewer inpatient, ER, and outpatient visits and lower non-drug costs. Potential DDIs were also strongly and positively associated with healthcare utilization and expenditures. Both are critical to consider in the management of AF in working-age adults.
The Hairpin Form of r(G4C2)exp in c9ALS/FTD Is Repeat-Associated Non-ATG Translated and a Target for Bioactive Small Molecules.

Summary The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an expanded G4C2 repeat [(G4C2)exp] in C9ORF72. ALS/FTD-associated toxicity has been traced to the RNA transcribed from the repeat expansion [r(G4C2)exp], which sequesters RNA-binding proteins (RBPs) and undergoes repeat-associated non-ATG (RAN) translation to generate toxic dipeptide repeats. Using in vitro and cell-based assays, we identified a small molecule (4) that selectively bound r(G4C2)exp, prevented sequestration of an RBP, and inhibited RAN translation. Indeed, biophysical characterization showed that 4 selectively bound the hairpin form of r(G4C2)exp, and nuclear magnetic resonance spectroscopy studies and molecular dynamics simulations defined this molecular recognition event. Cellular imaging revealed that 4 localized to r(G4C2)exp cytoplasmic foci, the putative sites of RAN translation. Collectively, these studies highlight that the hairpin structure of r(G4C2)exp is a therapeutically relevant target and small molecules that bind it can ameliorate c9ALS/FTD-associated toxicity.
Feast not famine: Nitrogen pools recover rapidly in 25-yr-old postfire lodgepole pine.

The extent of young postfire conifer forests is growing throughout western North America as the frequency and size of high-severity fires increase, making it important to understand ecosystem structure and function in early seral forests. Understanding nitrogen (N) dynamics during postfire stand development is especially important because northern conifers are often N limited. We resampled lodgepole pine (Pinus contorta var. latifolia) stands that regenerated naturally after the 1988 fires in Yellowstone National Park (Wyoming, USA) to ask (1) How have N pools and fluxes changed over a decade (15 to 25 yr postfire) of very rapid forest growth? (2) At postfire year 25, how do N pools and fluxes vary with lodgepole pine density and productivity? Lodgepole pine foliage, litter (annual litterfall, forest-floor litter), and mineral soils were sampled in 14 plots (0.25 ha) that varied in postfire lodgepole pine density (1,500 to 344,000 stems/ha) and aboveground net primary production (ANPP; 1.4 to 16.1 Mg·ha-1 ·yr-1 ). Counter to expectation, foliar N concentrations in lodgepole pine current-year and composite needles (1.33 and 1.11% N, respectively) had not changed over time. Further, all measured ecosystem N pools increased substantially: foliar N increased to 89 kg N/ha (+93%), O-horizon N increased to 39 kg N/ha (+38%), and mineral soil percent total N (0-15 cm) increased to 0.08% (+33%). Inorganic N availability also increased to 0.69 μg N·[g resin]-1 ·d-1 (+165%). Thus, soil N did not decline as live biomass N pools increased. Among stands, biomass N pools at postfire year 25 remained strongly influenced by early postfire tree density: foliar and litterfall N concentrations declined with lodgepole pine density and ANPP, but the foliar N pool increased. Lodgepole pine ANPP correlated negatively with annual resin-sorbed N, and we found no indication of widespread N limitation. The large increases in N pools cannot be explained by atmospheric N deposition or presence of known N fixers. These results suggest an unmeasured N source and are consistent with recent reports of N fixation in young lodgepole pine.
Hyperactivity of factor IX Padua (R338L) depends on factor VIIIa cofactor activity

Adeno-associated-viral (AAV) vector liver-directed gene therapy (GT) for hemophilia B (HB) is limited by a vector-dose-dependent hepatotoxicity. Recently, this obstacle has been partially circumvented by the use of a hyperactive factor IX (FIX) variant, R338L (Padua), which has an eightfold increased specific activity compared to FIX-WT. FIX-R338L has emerged as the standard for HB GT. However, the underlying mechanism of its hyperactivity is undefined; as such, safety concerns of unregulated coagulation and the potential for thrombotic complications have not been fully addressed. To this end, we evaluated the enzymatic and clotting activity as well as the activation, inactivation, and cofactor-dependence of FIX-R338L relative to FIX-WT. We observed that the high-specific-activity of FIX-R338L requires factor VIIIa (FVIIIa) cofactor. In a novel system utilizing emicizumab, a FVIII-mimicking bispecific antibody, the hyperactivity of both recombinant FIX-R338L and AAV-mediated-transgene-expressed FIX-R338L from HB GT subjects is ablated without FVIIIa activity. We conclude that the molecular regulation of activation, inactivation, and cofactor-dependence of FIX-R338L is similar to FIX-WT, but that the FVIIIa-dependent hyperactivity of FIX-R338L is the result of a faster rate of factor X activation. This mechanism helps mitigate safety concerns of unregulated coagulation and supports the expanded use of FIX-R338L in HB therapy.
Prevalence of severe fever with thrombocytopenia syndrome virus in animals in Henan Province, China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). SFTSV has been found in humans, ticks and animals, and SFTS has high mortality and increasing prevalence in East Asia. In the study, the samples (heart, liver, lung, kidney, spleen, brain tissue and serum) were collected from 374 domestic animals and 241 wild animals in Pingqiao District and Xinxian County of Xinyang in Henan Province, China. 275 (44.72%, 275/615) animals were positive for anti-SFTSV antibodies, the anti-SFTSV antibodies positive ratios of domestic and wild animals were 43.58% (163/374) and 46.47% (112/241), respectively. There was no significant difference in domestic and wild animals, but significant differences were detected among different species of animals (χ2 = 112.59, P < 0.0001). Among 615 animals, 105 (17.07%, 105/615) animals were positive for SFTSV RNA, and only one SFTSV strain was isolated from heart tissue of a yellow weasel. The phylogenetic analysis shows that the sequence from animals belonged to the same group with viral sequences obtained from humans. The animals maybe play a reservoir host in maintaining the life cycle of SFTSV in nature.
Abstract 5285: The role of HIV-1 TAT interactive protein 2 in modulating tumor response to hypoxia

While there is ample evidence that HIV-1 TAT interactive protein 2 (HTATIP2) is a tumor suppressor exerting its pro-apoptotic and anti-metastatic activities by regulating the expression of a subset of pro-apoptotic and anti-apoptotic genes and metastasis suppressor genes, it remains unclear if HTATIP2 has a role in tumor response to hypoxia. The objective of this study was to define the role of HTATIP2 in mediating certain molecular and cellular changes in response to hypoxia in tumors. We employed a series of isogenic A549 human lung adenocarcinoma sublines that were genetically deficient for HTATIP2 and/or HIF-1α to examine the potential modulatory effect of HTATIP2 on oncogenic signaling pathways mediated by HIF-1α and HIF-2α, and established the HTATIP2-deficient A549 xenograft model to explore the impact of deletion of HTATIP2 on tumor response to hypoxia. Results from the human HIF-regulated cDNA plate array study revealed that under hypoxic condition (0.5% O2), several genes promoting tumor metastasis and resistance to apoptosis and anticancer treatment, including HIF1α, CYSD, MMP1, MXI1, NDRG2, PAI1 and NDRG1, were upregulated to a greater extent in HTATIP2 knockdown A549 cells than in the control A549 cells. In contrast, genes involved in angiogenesis, glucose metabolism and protection of apoptosis under hypoxia, such as PDGF, PDK1, CA9, and SAG, were upregulated to a greater extent in control A549 cells than in HTATIP2-knockdown A549 cells. Results from the in vivo study demonstrated that the mean growth rate of HTATIP2-deficient A549 xenograft tumors was significantly increased as compared with that of parental A549 xenograft tumors irrespective of the presence or absence of sorafenib treatment. Moreover, the data of photoacoustic imaging (PAI) of tumor hypoxia revealed that the parental A549 tumors were better oxygenated than the counterpart HTATIP2-deficient A549 tumors. After the 10-day sorafenib treatment, the oxygenated regions in sorafenib-treated parental A549 tumors were significantly reduced as compared with the vehicle-treated parental A549 tumors, whereas no significant change in the oxygenated regions was found between vehicle- and sorafenib-treated HTATIP2-deficient A549 tumors. The overall finding of our study suggests that downregulation of HTATIP2 affords growth advantage to tumor cells by fine-tuning tumor adaptation to hypoxia, leading to tumor progression and aggression. Citation Format: Qingyu Stephanie Zhou, Xiaofang Guo, Minghua Li, Hua Pan. The role of HIV-1 TAT interactive protein 2 in modulating tumor response to hypoxia [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 5285.
Was Ezra Pound the “midwife” of The Waste Land? Surgeons, midwives, and “sage homme”

ABSTRACTThis essay reveals a flaw in the critical consensus that regards Ezra Pound as the intellectual “midwife” of The Waste Land, a metaphor used so frequently over the last century it has becom...
A growth model of neuroendocrine tumor surrogates and the efficacy of a novel somatostatin-receptor–guided antibody-drug conjugate: Perspectives on clinical response?

Abstract Background As patient-derived xenografts and other preclinical models of neuroendocrine tumors for testing personalized therapeutics are lacking, we have developed a perfused, 3D bioreactor model to culture tumor surrogates from patient-derived neuroendocrine tumors. This work evaluates the duration of surrogate culture and surrogate response to a novel antibody-drug conjugate. Methods Twenty-seven patient-derived neuroendocrine tumors were cultured. Histologic sections of a pancreatic neuroendocrine tumor xenograft (BON-1) tumor were assessed for SSTR2 expression before tumor implantation into 2 bioreactors. One surrogate was treated with an antibody-drug conjugate composed of an anti-mitotic Monomethyl auristatin-E linked to a somatostatin receptor 2 antibody. Viability and therapeutic response were assessed by pre-imaging incubation with IR-783 and the RealTime-Glo AnnexinV Apoptosis and Necrosis Assay (Promega Corporation, Madison, WI) over 6 days. A primary human pancreatic neuroendocrine tumor was evaluated similarly. Results Mean surrogate growth duration was 34.8 days. Treated BON-1 surrogates exhibited less proliferation (1.2 vs 1.9-fold) and greater apoptosis (1.5 vs 1.1-fold) than controls, whereas treated patient-derived neuroendocrine tumor bioreactors exhibited greater degrees of apoptosis (13- vs 9-fold) and necrosis (2.5- vs 1.6-fold). Conclusion Patient-derived neuroendocrine tumor surrogates can be cultured reliably within the bioreactor. This model can be used to evaluate the efficacy of antibody-guided chemotherapy ex vivo and may be useful for predicting clinical responses.
Laser microdissection coupled with RNA-seq reveal cell-type and disease-specific markers in the salivary gland of Sjögren's syndrome patients.

Objectives Little is known about the molecular details regarding the contribution of different cell types of the salivary gland to the altered gene expression profile seen in Sjogren's syndrome (SS). Methods Using laser microdissection, tissue samples enriched in acini, ducts and inflammatory foci in subjects with and without SS were isolated for RNA-seq analysis. Gene expression profiles were analysed and selected enriched genes were further examined using real time PCR and by immunofluorescence. Results RNA-seq analysis of salivary biopsies from subjects with and without SS revealed marked differences in gene expression occurring in the ductal and infiltrating cells compared to acinar cells. Up-regulated genes in the SS ductal cells included C4A complement and the SLC26A9 ion channel. The inflammatory infiltrate showed the most dramatic differences in gene expression and contained up-regulated genes associated with T-cells, natural killer, dendritic and basophils/mast cells. qPCR with total salivary gland mRNA confirmed the differential mRNA expression of several genes (MMP9, FOL1HB, CCL21, CCR7), thereby validating the approach. Additional immunofluorescence studies demonstrated high expression and co-localisation of CCL21 chemokine and CCR7 chemokine receptor within the SS infiltrates. Conclusions Major gene expression changes in the salivary gland of SS were detected in the ductal and inflammatory cells and not in the acinar cells. Two chemokines involved in immune cell trafficking to secondary lymphoid tissue, CCR7 and CCL21, showed markedly increased expression and may contribute to the recruitment of diverse immune cells to the salivary glands, causing inflammation and loss of secretory function.
The Ideologue as Genocidaire: Alfred Rosenberg and the Murder of the Jews in the Soviet Union

‘There was no silence’ writes David Cesarani in the introduction to his 2012 book on postwar Jewish Holocaust responses. This chapter addresses a related myth; that of Jews failing during World War Two to comprehend the deadly dynamics of German Judenpolitik. It does so by focusing on wartime reports from the office of Richard Lichtheim, the Jewish Agency representative in Geneva during World War II. The assumption of a centrally devised and systematically executed annihilation project taking shape in the summer of 1942 became a compelling and enduring conceptual frame of reference to explain Nazi genocide, leaving little room for interpretations that—like Lichtheim’s pre-1942 reports and later accounts by functionalist historians—highlight the radicalizing force of improvisation and local initiative. This chapter examines the collecting, mental processing, and transfer of information on the unfolding ‘final solution’ in order to reassess prevailing patterns of understanding Holocaust violence.
Streaming video acquisitions: factors to consider

In a world where streaming video services like Netflix, Hulu, Amazon Prime Video, and Disney + are overwhelmingly popular, libraries are embracing streaming video collections rather than DVD collec...
Social Institutions and the Differential Development of Northern Iroquoian Confederacies

Political units labeled as confederacies have received significantly less theoretical attention than other complex societies organized into chiefdoms and states. An analytical approach that focuses on the development, transformation, and articulation of the social institutions that comprise confederacies is suggested as one way to overcome this deficiency. The author reviews ethnographic and archaeological evidence for the development of the Wendat (Huron) and Haudenosaunee (Iroquois), two historically documented Northern confederacies and uses an institutional approach to analyze each. The results reveal key differences in the character of these Indigenous institutions and their constituent parts. This includes the legacies of agglomerative versus rapid politogenesis, the role of geography in forging strong versus weak ties between institutions, and the multidimensional nature of power in middle-range societies.