cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase 2 clinical trial of sunitinib as adjunctive treatment in patients with advanced differentiated thyroid cancer

Objective Our objective was to evaluate the efficacy and safety of sunitinib following at least one course of radioactive iodine treatment in patients with advanced differentiated thyroid cancer (DTC). The study endpoints included best response rate (including best objective response rate) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, measurement of serum thyroglobulin (Tg), and toxicity evaluation. Design and methods This was a single center, nonrandomized, open-label, phase 2 clinical trial. In total, 23 patients were enrolled and were treated with a starting daily, oral dose of 37.5 mg sunitinib. Patients were evaluated with imaging, laboratory tests, and physical examination periodically per protocol. Results The mean best response was a decrease of 17.2% (S.D. 22.8) in tumor sum from baseline. Six (26%) patients achieved a partial response (PR), and 13 (57%) had stable disease (SD) for a clinical benefit rate (PR+SD) of 83%. The overall median PFS was 241 days (interquartile limits, 114-518). No statistically significant difference was observed between the medians of the baseline and post-treatment Tg values (P=0.24). The most common adverse events included grades 1 and 2 decreases in blood cell counts (especially leukocytes), diarrhea, fatigue, hand-foot skin reaction, nausea, musculoskeletal pain, and hypertension. Conclusions These data demonstrate that sunitinib exhibits significant anti-tumor activity in patients with advanced DTC. Since sunitinib was relatively well-tolerated, there is the potential for clinical benefit in these patients, and further investigation of this agent is warranted.
Cascade effects on the irradiation stability of amorphous SiOC

AbstractWe studied the heavy ion radiation tolerance of amorphous silicon oxycarbide (SiOC) alloys by in situ Kr ion irradiation within a transmission electron microscopy. The amorphous SiOC thin films were grown via co-sputtering from SiO2 and SiC targets on a surface-oxidized Si (100) substrate. These films were irradiated by 1 MeV Kr ions at both room temperature and 300 °C with damage levels up to 5 displacements per atom (dpa). TEM characterization shows no sign of crystallization, void formation or segregation in all irradiated samples. Our findings suggest that SiOC alloys are a class of promising radiation tolerant materials.
Management of Charcot–Marie–Tooth disease: improving long-term care with a multidisciplinary approach

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy and one of the most common inherited diseases in humans. The diagnosis of CMT is traditionally made by the neurologic specialist, yet the optimal management of CMT patients includes genetic counselors, physical and occupational therapists, physiatrists, orthotists, mental health providers, and community resources. Rapidly developing genetic discoveries and novel gene discovery techniques continue to add a growing number of genetic subtypes of CMT. The first large clinical natural history and therapeutic trials have added to our knowledge of each CMT subtype and revealed how CMT impacts patient quality of life. In this review, we discuss several important trends in CMT research factors that will require a collaborative multidisciplinary approach. These include the development of large multicenter patient registries, standardized clinical instruments to assess disease progression and disability, and increasing recognition and use of patient-reported outcome measures. These developments will continue to guide strategies in long-term multidisciplinary efforts to maintain quality of life and preserve functionality in CMT patients.
Effects of Intentionally Incorporated Metal Cations on the Oxygen Evolution Electrocatalytic Activity of Nickel (Oxy)hydroxide in Alkaline Media

Fe-doped Ni (oxy)hydroxide, Ni(Fe)OxHy, is one of the most-active oxygen-evolution-reaction (OER) catalysts in alkaline conditions, while Fe-free NiOxHy is a poor OER catalyst. One approach to better understand the role of Fe, and enable the design of catalysts with higher activities, is to find other cations that behave similarly and compare the common chemical features between them. Here we evaluate the effects of La, Mn, Ce, and Ti incorporation on the OER activity and redox behavior of NiOxHy in rigorously Fe-free alkaline solution using cyclic voltammetry and electrochemical quartz-crystal microgravimetry. We use X-ray photoelectron spectroscopy and time-of-flight secondary-ion-mass spectrometry to confirm that measurements are free from relevant levels of trace Fe contamination. We find that only Ce leads to increased activity in NiOxHy (about a factor of 10 enhancement), but this effect is transient, likely due to phase separation. We further find no clear correlation between activity and the nomin...
Enhancing Evapotranspiration Prediction to Improve Regional and Local Estimates of Agricultural Consumptive Water Use in Florida

Irrigated agriculture is the primary consumer of water in the United States accounting for 80% of water use. In Florida alone, irrigated agriculture accounts for over 45% of the total freshwater withdrawals. As competition for freshwater rises, the demand for refined estimates of water requirements increases. In the Southeast U.S., regional scale water management has historically relied on relatively coarse approaches to estimate crop water requirements. In this study, we review the approach used to prioritize data and experimental needs, describe an experiment conducted to address these needs, and provide preliminary crop coefficient experimental results necessary to enhance estimates of agricultural consumptive water use. The results from a regional modeling study showed that crop water estimates are highly sensitive to crop coefficients. Based on this finding, we prioritized experimental data collection to determine crop coefficients for regionally significant crops. To develop crop coefficients, an eddy flux system was installed in a Bahia grass field. Here, we present preliminary results from the eddy flux system at the grass plot.
CORONARY CALCIUM SCORE VERSUS CHRONOLOGICAL AGE FOR CARDIOVASCULAR RISK PREDICTION IN THE ELDERLY: THE FRAMINGHAM OFFSPRING STUDY, THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS, AND THE CARDIOVASCULAR HEALTH STUDY

The 2013 ACC-AHA cardiovascular disease (CVD) prevention guidelines pose a challenge concerning how to select the high-risk elderly for statin drugs. An alternative marker besides chronological age to better discriminate between lower and higher CVD risk is needed for the elderly. Using meta-
Role of ADH in the loss of renal concentrating ability in primate hemorrhagic shock.

SummaryPositive free water clearance (CH2o), signifying production of hypotonic urine, is produced in the normally hydrated owl monkey after prolonged hypotension when hemorrhaged blood is transfused, and U/Posm less than unity is typically seen. Assay of plasma vasopressin showed marked increases after 2 hr of hypotension. After transfusion, concentrations still averaged twice the control value, demonstrating that the loss of concentrating ability of the collecting duct at this time was not due to inadequate ADH production and release. Moreover, when vasopressin was infused intra–ar–terially posttransfusion in amounts far in excess of those needed to inhibit water diuresis (6.5 mU/min/kg), no significant effects were observed on positive free water clearance, nor did experimentally reduced U/Posm improve significantly during infusion. Thus, prolonged hypotension had resulted in a type of vasopressin (ADH) resistant failure of the concentrating segment of the nephron.
Estrogen-dependent and independent activation of the P1 promoter of the p53 gene in transiently transfected breast cancer cells

Loss of p53 function by mutational inactivation is the most common marker of the cancerous phenotype. Previous studies from our laboratory have demonstrated 17 β estradiol (E2) induction of p53 protein expression in breast cancer cells. Although direct effects of E2 on the expression of p53 gene are not known, the steroid is a potent regulator of c-Myc transcription. In the present studies, we have examined the ability of E2 and antiestrogens to regulate the P1 promoter of the p53 gene which contains a c-Myc responsive element. Estrogen receptor (ER)-positive T47D and MCF-7 cells were transiently transfected with the P1CAT reporter plasmid and levels of CAT activity in response to serum, E2 and antiestrogens were monitored. Factors in serum were noted to be the dominant inducers of chloramphenicol acetyltransferase (CAT) expression in MCF-7 cells. The levels of CAT were drastically reduced when cells were maintained in serum free medium (SFM). However, a subtle ER-mediated induction of CAT expression was detectable when MCF-7 cells, cultured in SFM, were treated with E2. In serum-stimulated T47D cells, the CAT expression was minimal. The full ER antagonist, ICI 182 780 (ICI) had no effect. Treatment with E2 or 4-hydroxy tamoxifen (OHT) resulted in P1CAT induction; OHT was more effective than E2. Consistent with c-Myc regulation of the P1 promoter, E2 stimulated endogenous c-Myc in both cell lines. Two forms of c-Myc were expressed independent of E2 stimuli. The expression of a third more rapidly migrating form was E2-dependent and ER-mediated since it was blocked by the full ER antagonist, ICI, but not by the ER agonist/antagonist OHT. These data demonstrate both ER-mediated and ER-independent regulation of c-Myc and the P1 promoter of the p53 gene, and show differential effects of the two classes of antiestrogens in their ability to induce the P1 promoter of the p53 gene in breast cancer cells.
More than Native American narratives: Temporal shifting and authentic identities

The goal of this research is to understand how Native American storytellers challenge stereotypes and reclaim ‘authentic identities’ for themselves and their listeners with the stories that they tell. Employing qualitative methodology — thematic analysis, grounded theory, and narrative analysis — I examine one hundred and three stories featured on two affiliated websites that have recorded stories told by Native American elders, historians, storytellers, and song carriers. I find that the storytellers construct subversive narratives that challenge “the Native American” stereotypes, mythologies, and formula stories that circulate through the dominant culture. Temporal shifting, a new concept I develop in this paper, facilitates in the construction of what the storytellers believe to be an “authentic” identity. Temporal shifting, as I define it, is the past/present division in the double-consciousness of a marginalized person — it is a tool used to construct subversive stories. This research expands sociological understanding of Native Americans in general and Native American storytellers, in particular. I also introduce a new concept, temporal shifting, to the fields of critical race theory, cognitive sociology, and symbolic interactionism as an analytical device to use when looking at marginalized peoples’ narrative identities.
Cultural Control of the Boll Weevil: Influence of Bed Shape

Since 85% of the cotton is planted in the furrow in the Texas Rolling Plains, a rolling cultivator can be used to modify bed shape after plant emergence. Damage caused by Anthonomus grandis grandis Boheman to squares ≥ 6 mm in diameter can be reduced with tall-sloped beds, as compared with that in flat beds, in east-west row orientations. Bed shape had no influence on boll weevil damage in north-south row directions.
The value of noninvasive testing before and after hemodialysis access in the prevention and management of complications

The relative value of and selective indications for specific applications of noninvasive testing and imaging in hemodialysis access patients are reviewed. Preoperatively, clinical arterial assessment, including an Allen's test, should be done routinely. This should be augmented by interrogating the ulnar and radial arteries with a Doppler probe, using collateral compression testing, in complex cases, particularly in patients with a history of previous failed fistulas or radial artery cannulations for blood pressure or blood gas monitoring. Vein mapping, using a duplex scan, is valuable in any patient in whom the superficial veins are not easily visible and distend nicely with tourniquet application. Patients who have previously had chronic cannulation of the subclavian or jugular veins, for hemodialysis or other reasons, should have proximal venous outflow obstruction ruled out by a duplex study. Postoperatively, baseline and serial noninvasive monitoring of the arteriovenous fistula (AVF) or shunt cannot be justified as a routine, but study is indicated if a thrill over the venous outflow cannot be detected postoperatively, veins do not become progressively distended after creation of a fistula, or good flows cannot be achieved during hemodialysis. However, in current practice, a dysfunctional, failing, or failed fistula or shunt is usually identified by the observations of the dialysis technician, and the patient is directly referred to the angiography suite, not the vascular diagnostic laboratory. The true identity and extent of such local complications as hematoma, seroma, abscess, cellulitis with phlegmon, or pseudoaneurysm may be difficult to define without the help of ultrasound imaging, which also can direct diagnostic aspiration. Finally, noninvasive testing, consisting of monitoring digital pressures and plethysmography, and their response to compression of the fistula, its venous outflow, the feeding artery proximally and distally, and the companion artery, is a key initial step in evaluating patients with disabling hand symptoms, distinguishing distal steal from focal ischemia, or, by elimination, pointing to venous congestion or secondary carpal tunnel syndrome.
Ethics and Experimental Economics

A variety of ethical considerations in designing, conducting, and reporting both laboratory and field experiments in economics are reviewed. An important area of ethical concern in experimental economics stems from its use of human subjects. The standards used by Institutional Review Boards to sanction research using human subjects are expounded upon, with an emphasis on application to economics experiments. The authors draw from other experimental researchers and from their own experience to discuss issues related to the interaction of experimenter and subject—e.g., deception, informed consent, blindness, and monetary incentives—and issues related to the interaction of experimenter and consumer of research—e.g., the reporting of negative results, pilot data, or details of the experiment that may offer alternative interpretations of results.
Yoga research review

This paper is a review of empirical studies, review and meta-analysis publications on yoga from the last few years. The review includes demographics/prevalence of yoga as a practice, bibliometric analyses of the yoga publications and the use of yoga for physical fitness and cognitive function. Most of the studies reviewed here involve yoga effects on psychiatric and medical conditions. These include pregnancy, prenatal and postpartum depression; stress, PTSD, anxiety, and obesity; cardiovascular conditions including hypertension; pain syndromes including arthritis, headaches and low back pain; autoimmune conditions including asthma, type II diabetes and multiple sclerosis; immune conditions including HIV and breast cancer; and aging problems including balance, osteoporosis and Parkinson's. The methods and results of those studies are briefly summarized along with their limitations and suggestions for future research. Basically yoga has been more effective than control and waitlist control conditions, although not always more effective than treatment comparison groups such as other forms of exercise. More randomized controlled studies are needed in which yoga is compared to active exercise groups. Having established the physical and mental health benefits of yoga makes it ethically questionable to assign participants to inactive control groups. Shorter sessions should be investigated for cost-effectiveness and for daily practice. Multiple physical and physiological measures need to be added to the self-report research protocols and potential underlying mechanisms need to be further explored. In the interim, the studies reviewed here highlight the therapeutic effects of yoga, a practice that could come to be called yoga therapy.
Intrasubject variation of warfarin binding to protein in serum of patients with cardiovascular disease

A study of 31 patients with cardiovascular disease who were taking warfarin regularly had shown pronounced intersubject differences in serum protein binding of warfarin and a highly significant correlation between the body clearance of warfarin and the free fraction of the drug in serum. Similar observations have been made in experimental animals and are consistent with predictions based on theoretical considerations. The purpose of this investigation was to determine the intrasubject variation in the free fraction of warfarin in serum. Samples of serum were obtained from 23 of the 31 patients previously studied. The time interval between the two studies was 3.4 to 5.7 mo. The daily dose of warfarin had been changed by 10.6% on the average. With two exceptions, there was no change in concurrent medications. The ratio of free fraction values of warfarin in serum, second/first study, was 0.948 +/- 0.297 (mean +/- S.D.), and there was a highly significant correlation (P less than 0.001) between the individual free fraction values in the first and second studies.
Absolutely Contingent: Slavoj Žižek and the Hegelian Contingency of Necessity

One of the red threads of Slavoj Žižek’s entire intellectual career up through the present is the enactment of a ‘return to Hegel’ partly modeled on Jacques Lacan’s ‘return to Freud.’ In diametrical opposition to received exegetical wisdom about Hegelian philosophy, Žižek maintains that Hegel’s is the philosophy of contingency par excellence. Furthermore, in his defenses of Hegel against commonplace objections and caricatures, Žižek turns the very features of Hegelian thought provoking these objections and caricatures into the precise means of debunking them. Herein, I focus on Žižek’s handling of the interrelated issues of the end-of-history closure and apparently fatalistic-teleological character of Hegel’s System. In so doing, I develop an immanent critique of these Žižekian efforts, presenting Hegelian criticisms of Žižek’s Hegelianism, ways that point to how Hegel remains relevant for contemporary Marxism.
The Western Politics of East-West Trade Negotiations: East European Countries and the Gatt

One of the major changes occurring in the global political economy relates to the reintegration of the socialist countries. The importance of this topic has increased dramatically in the 1980s. Rapid changes in Soviet foreign economic policy confront the Western countries with a significantly altered situation that can be neither ignored nor wished away. These developments clearly call for an attempt to come to grips with the question of how East-West economic integration will proceed. As a contribution towards addressing this issue, this chapter focuses on the subject of participation by East European countries in the post-war international trade institution, the General Agreement on Tariffs and Trade (GATT).
Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors.
Multiple hazard incidents lifecycle cost assessment of structural systems considering state-dependent repair times and fragility curves

Summary The performance and serviceability of structural systems during their lifetime can be significantly affected by the occurrence of extreme events. Despite their low probability, there is a potential for multiple occurrences of such hazards during the relatively long service life of systems. This paper introduces a comprehensive framework for the assessment of lifecycle cost of infrastructures subject to multiple hazard events throughout their decision-making time horizon. The framework entails the lifecycle costs of maintenance and repair, as well as the salvage value of the structure at the end of the decision-making time horizon. The primary features of the proposed framework include accounting for the possibility of multiple hazard occurrences, incorporating effects of incomplete repair actions on the accumulated damage through damage state-dependent repair times, and requiring limited resources in terms of input data and computational costs. A dynamic programming procedure is proposed to calculate the expected damage condition of the structure for each possibility of the number of hazard incidents based on state-dependent fragility curves. The proposed framework is applied to a moment-frame building located in a region with high seismicity, and lifecycle costs are evaluated for six retrofit plans. The results displayed variation in the ranking of the retrofit actions with respect to decision-making time horizon. Furthermore, the sensitivity analyses demonstrated that disregarding repair time in the lifecycle cost analysis can result in false identification of unsafe retrofit actions as optimal and reliable strategies. Copyright © 2016 John Wiley & Sons, Ltd.
Bodleian Library, MS. Laud Misc. 479. The Paradisus anime intelligentis as a Paradise for Editors?

The starting point for this article is Nigel Palmer’s contribution to research on Meister Eckhart. It focuses on Dominican adaptations in the manuscript MS. Laud Misc. 479 in the Bodleian Library, one of two manuscripts of the collection “Paradisus anime intelligentis” (before 1340) which unites at least 31 sermons by Meister Eckhart together with sermons by Dominican Lektors. The modifications and abbreviations alter the text in line with Dominican doctrine. The Table of Contents presents a treasure trove to be used both for assessing the content as for questions of editorial practice. This is demonstrated by analysing the newly edited (Lectura Eckhardi IV) sermon 87 of the critical Eckhart edition.Der Beitrag knupft an der Bedeutung Nigel Palmers fur die Forschung uber Meister Eckhart an. Er stellt die Handschrift MS. Laud Misc. 479 der Bodleian Library in den Mittelpunkt, eine von zwei Handschriften der Sammlung “Paradisus anime intelligentis”: Vor 1340 entstanden, versammelt sie mindestens 31 Predigte...
Core Existential Treatment Approaches with Adolescents

This chapter is dedicated to reviewing helpful techniques, tools, and areas of focus for therapists working with adolescents from an existential-integrative (EI) framework. The discussion is split into “core” and “specific” techniques, with the “core” techniques consisting of key intervention strategies that might assist a wider array of adolescents, while the “specific” techniques might be useful in more isolated cases. The author primarily reviews techniques introduced by Schneider, while also including research and techniques from van Deurzen, Frankl, and Spinelli, among other researchers. The chapter aims to provide the reader with helpful tools as well as the benefits of incorporating an existential approach into adolescent treatment plans.
Control of autonomous ground vehicles: a brief technical review

This paper presents a brief review of the developments achieved in autonomous vehicle systems technology. A concise history of autonomous driver assistance systems is presented, followed by a review of current state of the art sensor technology used in autonomous vehicles. Standard sensor fusion method that has been recently explored is discussed. Finally, advances in embedded software methodologies that define the logic between sensory information and actuation decisions are reviewed.
Análisis del sistema de gestión ambiental basado en la norma técnica colombiana ISO 14001:2015 para las empresas que realicen la fracturación hidráulica para la explotación de gas de lutitas

El articulo analiza la NTC ISO 14001: 2015 para las empresas que realizan fracturacion hidraulica en yacimientos de lutitas en Colombia. Se utilizaron los requisitos de la norma NTC ISO 14001: 2015 aplicados a este tipo de empresas como fundamento metodologico. Se encontro que si bien la fracturacion hidraulica puede traer beneficios para el sector petrolero, tecnica que aumenta los impactos ambientales; de manera que la implementacion de un sistema de gestion ambiental no es suficiente para controlar los impactos ambientales generados por la practica, factor que cuestiona el papel de las organizaciones frente a la gestion de sus actividades.
Glutamate Dehydrogenase to the Rescue.

Tumor cell metabolism can be altered to support specific pathological functions or to adapt to environmental stresses. In this issue of Molecular Cell, Jin et al. (2018) identify induction of glutamate dehydrogenase as a critical metabolic adaptation in matrix-detached cancer cells that is required for metastasis of LKB1-deficient lung tumors.
Postnatal lung function and protein permeability after fetal or maternal corticosteroids in preterm lambs

Rebello, Celso M., Machiko Ikegami, M. Gore Ervin, Daniel H. Polk, and Alan H. Jobe. Postnatal lung function and protein permeability after fetal or maternal corticosteroids in preterm lambs.J. App...
Effective Quark Propagator and QQ̄ States in QCD

He discuss in this contribution the role of the quark propagator in an approximation scheme [1] to calculate masses and wavefunctions of the states in quantum chromodynamics. The scheme is based on the Bethe-Salpeter equation for the QQ amplitude solved together with the Schwinger-Dyson equation for the quark propagator.
Rarity and Exponentiality

If a system is modeled by a finite Markov chain which is ergodic, the passage time from some specified initial distribution over the state space to a subset B of the state space visited infrequently is often exponentially distributed to good approximation. The chapter is devoted to the limit theorems surrounding such behavior for processes and the characterization of the circumstances under which exponentiality is present. In the absence of certain “jitter,” i.e., clustering of the entry epochs into the good set G, the time to failure from the perfect state, the quasi-stationary exit time, the ergodic exit time and the sojourn time on the good set then have a common asymptotic exponential distribution and common expectations. For engineering purposes, it is essential to quantify departure from exponentiality via error bounds. When one is dealing with time-reversible chains e.g., systems with independent Markov components, the complete monotonicity present permits such quantification and the error bounds needed.
Berkeley’s Metaphysical Instrumentalism

Berkeley is widely held to be a scientific instrumentalist, but the scope of his ­instrumentalism has been repeatedly brought into question. Some have asserted that Berkeley capitulated wholesale to a form of external realism at the end of his life, others have supposed principled reasons for thinking that Berkeley is an instrumen­talist about some things and not about others. Lisa Downing, for instance, has argued that Berkeley is an instrumentalist about forces but not about corpuscles, and Douglas Jesseph contends that Berkeley rejects mathematical instrumentalism despite being a stronger instrumentalist in the sciences.
The Breadth of Monoterpene Synthesis by Marine Red Algae: Potential Difficulties in their Application as Taxonomic Markers

Our interest in the organic chemistry of toxic marine organisms has led us to study a number of species of marine red algae. Several years ago our attention was drawn to the family Plocamiaceae, and this has resulted in our discovery of an interesting series of polyhalogenated monoterpenesl–3.
Development of the human female reproductive tract.

Development of the human female reproductive tract is reviewed from the ambisexual stage to advanced development of the uterine tube, uterine corpus, uterine cervix and vagina at 22 weeks. Historically this topic has been under-represented in the literature, and for the most part is based upon hematoxylin and eosin stained sections. Recent immunohistochemical studies for PAX2 (reactive with Mullerian epithelium) and FOXA1 (reactive with urogenital sinus epithelium and its known pelvic derivatives) shed light on an age-old debate on the derivation of vaginal epithelium supporting the idea that human vaginal epithelium derives solely from urogenital sinus epithelium. Aside for the vagina, most of the female reproductive tract is derived from the Mullerian ducts, which fuse in the midline to form the uterovaginal canal, the precursor of uterine corpus and uterine cervix an important player in vaginal development as well. Epithelial and mesenchymal differentiation markers are described during human female reproductive tract development (keratins, homeobox proteins (HOXA11 and ISL1), steroid receptors (estrogen receptor alpha and progesterone receptor), transcription factors and signaling molecules (TP63 and RUNX1), which are expressed in a temporally and spatially dynamic fashion. The utility of xenografts and epithelial-mesenchymal tissue recombination studies are reviewed.
Modeling and simulation of nonlinear electro-thermo-mechanical continua with application to shape memory polymeric medical devices

Abstract Shape memory materials have gained considerable attention thanks to their ability to change physical properties when subjected to external stimuli such as temperature, pH, humidity, electromagnetic fields, etc. These materials are increasingly used for a large number of biomedical applications. For applications inside the human body, contactless control can be achieved by the addition of electric and/or magnetic particles that can react to electromagnetic fields, thus leading to a composite biomaterial. The difficulty of developing accurate numerical models for smart materials results from their multiscale nature and from the multiphysics coupling of involved phenomena. This coupling involves electromagnetic, thermal and mechanical problems. This paper contributes to the multiphysics modeling of a shape memory polymer material used as a medical stent. The stent is excited by electromagnetic fields produced by a coil which can be wrapped around a failing organ. In this paper we develop large deformation formulations for the coupled electro-thermo-mechanical problem using the electric potential to solve the electric problem. The formulations are then discretized and solved using the finite element method. Results are validated by comparison with results in the literature.
Structural health monitoring and field validation of civil engineering structures

Abstract: With the increasing age of infrastructure and the use of new technologies, there is a need to derive, on a continuous basis, knowledge about the actual condition of a structure, or system, with the aim of not just knowing that its performance may have deteriorated, but rather to be able to pinpoint the area of degradation and more importantly to assess remaining performance levels and life. This has led to the development of the field of structural health monitoring (SHM) as a means of validating current and assessing potential future performance characteristics of structures and systems.
Regulation of melanocyte development by ligand-dependent BMP signaling underlies oncogenic BMP signaling in melanoma

Abstract Preventing terminal differentiation is important in the development and progression of many cancers including melanoma. Recent identification of the BMP ligand GDF6 as a novel melanoma oncogene showed GDF6-activated BMP signaling suppresses differentiation of melanoma cells. Previous studies have identified roles for GDF6 orthologs during early embryonic and neural crest development, but have not identified direct regulation of melanocyte development by GDF6. Here, we investigate the BMP ligand gdf6a, a zebrafish ortholog of human GDF6, during the development of melanocytes from the neural crest. We establish that the loss of gdf6a or inhibition of BMP signaling during neural crest development disrupts normal pigment cell development, leading to an increase in the number of melanocytes and a corresponding decrease in iridophores, another neural crest-derived pigment cell type in zebrafish. This shift occurs as pigment cells arise from the neural crest and depends on mitfa, an ortholog of MITF, a key regulator of melanocyte development that is also targeted by oncogenic BMP signaling. Together, these results indicate that the oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.
Acute Neuromuscular Disorders in the Pediatric Intensive Care Unit.

Background:The neuromuscular disorders encountered in the pediatric intensive care unit (PICU) encompass a broad spectrum of pathologies. These include acute disorders (eg, Guillain-Barre syndrome)...
Extended imaging depth of en-face optical coherence tomography based on fast measurement of a reflection matrix by wide-field heterodyne detection

Multiple light scattering in biomedical tissue limits the penetration depth of optical imaging systems such as optical coherence tomography. To increase the imaging depth in scattering media, a computational method based on coherent reflection matrix measurement has been developed using low coherence interferometry. The complex reflection matrix is obtained via point-by-point scanning followed by a phase-shifting method; then singular value decomposition is used to retrieve the singly back-scattered light. However, the in vivo application of the current reported method is limited due to the slow acquisition speed of the matrix. In this Letter, a wide-field heterodyne-detection method is adopted to speed up the complex matrix measurement at a deep tissue layer. Compared to the phase-shifting method, the heterodyne-detection scheme retrieves depth-resolved complex amplitudes faster and is more stable without mechanical movement of the reference mirror. As a result, the matrix measurement speed is increased by more than one order of magnitude.
Biological properties and genomic sequence of an isolate of cherry rasp leaf virus from tomato

Cherry rasp leaf virus (CRLV) is found in the USA causing disease in Prunus and Malus spp. In 2016, symptomatic high tunnel grown tomatoes (Solanum lycopersicum L.) from Minnesota exhibiting viral symptoms were found to contain ~30 nm spherical particles. High throughput sequencing revealed two distinct viral contigs, attributed to RNA 1 (complete, MK952187) and RNA 2 (5′ partial, MK952188) of a new CRLV isolate. The isolate, denoted CRLV-tomato (CRLV-tom), shared 87–98% nucleotide identity with three previously sequenced isolates of CRLV from apple, potato, and elderberry. CRLV-tom was mechanically inoculated into Nicotiana benthamiana and caused symptoms of interveinal necrotic line patterns three weeks after inoculation. Symptoms progressed into leaf rugosity and chlorosis ten weeks after inoculation. Inoculated greenhouse tomatoes were infected by CRLV, as detected by RT-PCR, but were asymptomatic indicating tomato host resistance genes and environmental conditions may impact symptom development in tomatoes. This is the first report of CRLV infecting tomato.
Clinical Integration of a Smartphone App for Patients With Chronic Pain: Retrospective Analysis of Predictors of Benefits and Patient Engagement Between Clinic Visits.

Background: Although many pain-related smartphone apps exist, little attention has been given to understanding how these apps are used over time and what factors contribute to greater compliance and patient engagement. Objective: This retrospective analysis was designed to help identify factors that predicted the benefits and future use of a smartphone pain app among patients with chronic pain. Methods: An app designed for both Android and iOS devices was developed by Brigham and Women’s Hospital Pain Management Center (BWH-PMC) for users with chronic pain to assess and monitor pain and communicate with their providers. The pain app offered chronic pain assessment, push notification reminders and communication, personalized goal setting, relaxation sound files, topics of interest with psychological and medical pain management strategies, and line graphs from daily assessments. BWH-PMC recruited 253 patients with chronic pain over time to use the pain app. All subjects completed baseline measures and were asked to record their progress every day using push notification daily assessments. After 3 months, participants completed follow-up questionnaires and answered satisfaction questions. We defined the number of completed daily assessments as a measure of patient engagement with the pain app. Results: The average age of participants was 51.5 years (SD 13.7, range 18-92), 72.8% (182/253) were female, and 36.8% (78/212) reported the low back as their primary pain site. The number of daily assessments ranged from 1 to 426 (average 62.0, SD 49.9). The app was easy to introduce among patients, and it was well accepted. Those who completed more daily assessments (greater patient engagement) throughout the study were more likely to report higher pain intensity, more activity interference, and greater disability and were generally overweight compared with others. Patients with higher engagement with the app rated the app as offering greater benefit in coping with their pain and expressed more willingness to use the app in the future (P<.05) compared with patients showing lower engagement. Patients completing a small number of daily assessments reported less pain intensity, less daily activity interference, and less pain-related disability on average and were less likely to use the two-way messaging than those who were more engaged with the pain app (P<.05). Conclusions: Patients with chronic pain who appeared to manage their pain better were less likely to report benefits of a smartphone pain app designed for chronic pain management. They demonstrated lower patient engagement in reporting their daily progress, in part, owing to the perceived burden of regularly using an app without a perceived benefit. An intrinsically different pain app designed and targeted for individuals based on early identification of user characteristics and adapted for each individual would likely improve compliance and app-related patient engagement.
Development of a Portable Monitoring System for Indoor E-Cigarettes Emission

This work demonstrates a battery powered portable monitoring system to measure the emission from e- cigarettes. The developed system includes 3 sensors to detect and quantify the toxins from e-cigarette emission. The results show that the developed system can distinguish between air and e-cigarette vapors. The portable system consists of 3 sensors, WiFi and Bluetooth enabled MCU, temperature and humidity sensors on a 39mm x 36mm PCB board. The system functionality was validated with acetone exposure in a controlled environment and with the actual e-cigarette emission in an outdoor environment. When the system is exposed to the e-cigarette, the temperature decreased, while the humidity increased. It was found that a large change in the PM sensor reading occurs when directly exposed to the e-cigarette. This multi modal and portable sensing system enables detection of e-cigarette emissions in real-time as well as to monitor indoor air quality.
Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts

The well-studied members of the Trio family of proteins are Trio and kalirin in vertebrates, UNC-73 in Caenorhabditis elegans and Trio in Drosophila Trio proteins are key regulators of cell morphogenesis and migration, tissue organization, and secretion and protein trafficking in many biological contexts. Recent discoveries have linked Trio and kalirin to human disease, including neurological disorders and cancer. The genes for Trio family proteins encode a series of large multidomain proteins with up to three catalytic activities and multiple scaffolding and protein-protein interaction domains. As such, Trio family proteins engage a wide array of cell surface receptors, substrates and interaction partners to coordinate changes in cytoskeletal regulatory and protein trafficking pathways. We provide a comprehensive review of the specific mechanisms by which Trio family proteins carry out their functions in cells, highlight the biological and cellular contexts in which they occur, and relate how alterations in these functions contribute to human disease.
3043 – A PIPELINE TO IMAGE HEMATOPOIETIC DIFFERENTIATION REVEALS THE ARCHITECTURE OF ERYTHROPOIESIS IN THE BONE MARROW

The anatomy of differentiation in the BM is poorly understood due to a lack of markers to image stepwise HSPC differentiation. We immunophenotyped all types of multipotent and lineage committed HSPC and identified 56 cell surface markers that can be “mixed and matched” to prospectively image HSPC. We used this data to develop a pipeline to map erythropoiesis in whole-mounted sternum. Pre-Meg-E are ESAM-Ly6C-CD117+CD150+CD71-, Pre-CFU-E are Ly6C-CD117+CD150+CD71+ and CFU-E are Ly6C-CD117+CD150-CD71+ cells. We found that all three types of erythroid progenitors show no specific association with LT-HSC/MPP2/MkP, indicating that Pre-Meg-E or more primitive progenitors leave the HSC niche after differentiation. Both Pre-Meg-E and Pre-CFU-E are found as single cells through the central BM space and do not specifically associate with other progenitors, or components of the microenvironment. In contrast almost all CFU-E locate to strings (28 strings per sternum) containing 6±0.28 CD117brightCD71dim CFU-E that are selectively recruited to sinusoids (mean CFU-E to sinusoid distance=2.2µm). As soon as CFU-E detach from sinusoids they show sharp reductions in CD117 and upregulation of CD71 giving rise to a cluster of early erythroblasts that buds from the vessel. These progressively upregulate Ter119 to generate large clusters of late erythroblasts that in turn differentiate into clusters of reticulocytes and erythrocytes. To understand how the architecture of erythropoiesis changes in response to stress we performed phlebotomy. Two days later we found Pre-Meg-E and Pre-CFU-E numbers and locations was unaltered. The number of CFU-E strings remained constant (30 CFUE strings/sternum) but all strings contained more CFU-E (2-fold) that then differentiated as above. Our imaging pipeline can be quickly adapted to image all other HSPC during normal, stress, and diseased hematopoiesis.
Sexual Abuse as a Cause of Prepubertal Genital Bleeding: Understanding the Role of Routine Physical Examination.

Abstract Although accidental trauma is the most common mechanism for genital bleeding, sexual abuse should be considered when the patient is prepubertal and/or a vague history of bleeding is provided. Prepubertal female genital exams should be completed routinely; this clinical technique is critical for pediatricians to assess pubertal progression, to identify pathologies or differences in sexual differentiation, and to narrow a broad differential diagnosis of bleeding. Physical evidence of sexual abuse on exam is rarely found, and therefore the diagnosis relies on a child's disclosure. Physicians should be cognizant of barriers to patient disclosure. In this commentary we aim to provide general pediatricians and trainees with a framework for evaluating genital/vaginal bleeding in prepubertal girls, by discussing the following: (1) the importance of a complete anogenital exam in generating a differential diagnosis; and (2) the possibility of sexual abuse as an etiology with recognition that the disclosure process is complex.
Ipsilateral internal carotid artery web and acute ischemic stroke: A cohort study, systematic review and meta-analysis.

INTRODUCTION The carotid web is a compelling potential mechanism of embolic ischemic stroke. In this study, we aim to determine the prevalence of ipsilateral carotid web in a cohort of ischemic stroke patients and to perform a systematic review and meta-analysis of similar cohorts. PATIENTS & METHODS We performed a retrospective, observational, cohort study of acute ischemic stroke patients admitted to a comprehensive stroke center from June 2012 to September 2017. Carotid web was defined on computed tomography angiography (CTA) as a thin shelf of non-calcified tissue immediately distal to the carotid bifurcation. We described the prevalence of carotid artery webs in our cohort, then performed a systematic review and meta-analysis of similar cohorts in the published literature. RESULTS We identified 1,435 potentially eligible patients of whom 879 met criteria for inclusion in our analysis. An ipsilateral carotid web was detected in 4 out of 879 (0.45%) patients, of which 4/4 (1.6%) were in 244 patients with cryptogenic stroke and 3/4 were in 66 (4.5%) patients <60 years old with cryptogenic stroke. Our systematic review yielded 3,192 patients. On meta-analysis, the pooled prevalence of ipsilateral carotid web in cryptogenic stroke patients <60 was 13% (95% CI: 7%-22%; I2 = 66.1%). The relative risk (RR) of ipsilateral versus contralateral carotid web in all patients was 2.5 (95% CI 1.5-4.2, p = 0.0009) whereas in patients less than 60 with cryptogenic stroke it was 3.0 (95% CI 1.6-5.8, p = 0.0011). DISCUSSION Carotid webs are more common in young patients with cryptogenic stroke than in other stroke subtypes. Future studies concerning the diagnosis and secondary prevention of stroke associated with carotid web should focus on this population.
Attention to emotion and reliance on feelings in decision-making: Variations on a pleasure principle

Abstract Individuals are thought to differ in the extent to which they attend to and value their feelings, as captured by the construct of attention to emotion. The well-being correlates of attention to emotion have been extensively studied, but the decision-making correlates have not been. A three study program of research (total N = 328) sought to examine relationships between stimulus-specific feelings and decisions concerning those stimuli in the context of high levels of within-subject power. Evidence for the pleasure principle was robust, in that individuals placed a virtual self closer to stimuli that they found more pleasant (Study 1) and they wished to re-view such stimuli more frequently (Studies 2 & 3). These relationships, however, were more pronounced at higher levels of attention to emotion. The findings affirm the importance of feelings in decision-making while highlighting ways in which individual differences in attention to emotion operate.