cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5087: Mirk/Dyrk1B kinase mediates survival of quiescent tumor cells and is downstream of the cellular energy sensor AMPK

The Mirk kinase gene has been localized to the 19q13 amplicon and is amplified in a subset of pancreatic cancers and ovarian cancers, and less frequently in colon cancers. Mirk mediates survival of these cancers at least in part by reducing reactive oxygen species (ROS). Mirk is expressed at very low levels in most normal tissues. However, Mirk is highly expressed in normal skeletal muscles and in C2C12 myoblasts where it mediates differentiation and survival. Using immunofluorescence techniques we now show that Mirk is localized in fast twitch skeletal muscles. Such muscle endogenously produces ROS in response to repeated contractions. Depletion of Mirk from C2C12 myoblasts led to an increase in ROS, consistent with ROS control being a major role of Mirk in muscle development and function. This protective ROS-decreasing role is likely to have provided a selective pressure to upregulate Mirk expression in tumor cells. Mirk is a co-activator for several transcription factors and increases expression of a series of antioxidant proteins in cancer cells including superoxide dismutase 2 (SOD2), the ferroxidase ceruloplasmin, glutathione peroxidase 2, sulfiredoxin, peroxiredoxin 2, COX2 and archidonate 12-lipoxygenase (12-LOX), as assayed by either Northern blotting or quantitative RT-PCR or both measurements. Mirk is most abundant and active as a kinase when cells are in a quiescent G0 state. Low intracellular energy levels due to nutrient deprivation lead to transient cellular arrest in G0 through the function of AMPK (AMP-activated protein kinase). Mirk expression is controlled through AMPK which serves as a metabolic checkpoint kinase, arresting cell growth in response to low nutrient levels which depress intracellular ATP levels. Thus the serine/threonine kinase Mirk mediates tumor cell survival through maintenance of its original function in skeletal muscle cells, depletion of ROS, when cells are in a transient quiescent state, with both Mirk expression and cell arrest controlled by AMPK. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5087.
The Building of Analogous Abdominal Cavity in the Performance Testing of Pneumoperitoneum Machine

Through the analysis of clinical Abdominal Data received in Endoscopic surgery,this paper elaborates the principle of Analogous Abdominal Cavity data,and study the way applied in the Performance Testing.Pneumoperitoneum Machine Industry Standard can be laid down based on this.
The Balance between Justice and Mercy——The Functions of Clothing Changes and Textural Evidences in The Merchant of Venice

This article analyzes the characters of Bassanio,Antonio,Portia,and Shylock in The Merchant of Venice through the devices of clothing changes and textural evidences.It also explores how they are balance and solve the bond when they are facing the law and mercy humanity.Through those devices,Shakespeare fosters the audience to a deeper debate which is the theme of the play,and upmost important.
Bistable Perception and Fractal Reasoning

A visual percept is deemed bistable if there are two potential yet mutually exclusive interpretations of the percept between which the human visual system cannot unambiguously choose. Perhaps the most famous example of such a bistable visual percept is the Necker Cube. In this paper, we present a novel computational model of bistable perception based on visual analogy using fractal representations.
Modeling the Cooperativity of Tropomyosin Binding to Actin Filaments

Tropomyosins modulate the activity of actin binding proteins---including myosin, cofilin, the Arp2/3 complex, and formins---by themselves binding and coating actin filaments. A single tropomyosin protein is a coiled-coil capable of end-to-end association, and one segment of an actin filament is capable of simultaneously accommodating two tropomyosin cables. The coating of actin filaments by tropomyosin is known to be highly cooperative, however the details of this process are not well understood. Using labeled actin and labeled fission yeast tropomyosin, Cdc8, we can observe by TIRF microscopy the formation of small tropomyosin Cdc8 ‘seeds’ that appear to initially associate with actin filaments and then subsequently extend from both ends. Additionally, we are capable of observing two distinct tropomyosin cables associated with a single actin filament. Our setup allows us to study in detail the interactions of tropomyosin Cdc8 with the actin filament and with other tropomyosin Cdc8 molecules. To interpret the experimental observations, we have used statistical approaches, kinetic master equations, and a new kinetic Ising model. Theory and modeling lends insight into the mechanism underlying Cdc8's highly cooperative binding kinetics. Our results are consistent with a small amount of “face cooperativity,” that is, a slight preference for tropomyosin Cdc8 molecules to associate with the actin filament opposite to an already bound tropomyosin cable. These findings suggest that some tropomyosin binding cooperativity is mediated through the actin filament, and not only via end-to-end binding of Cdc8 molecules.
Rechazos fundamentales de la doctrina de Roe v. Wade (Fundamental Rejections of Roe v. Wade)

Spanish Abstract: El razonamiento de Roe ha sido rechazado por el Tribunal Constitucional aleman, rechazado por peritos academicos y feministas estadounidenses personalmente a favor del aborto, rechazado por la legislacion estatal y federal norteamericana que alcanza proteger al no nacido a pesar de Roe, y rechazado por la misma Corte Suprema que no ha reafirmado ni extendido el razonamiento de la sentencia y la ha dejado sobrevivir a causa de la doctrina anglosajona del precedente vinculante. Posiblemente mas sorprendente de todo, lo que se conoce como la doctrina de Roe -- la despersonalizacion del feto y el consiguiente derecho al aborto a peticion -- fue rechazado por los jueces autores originales de la sentencia, quienes en sus papeles privados (revelados decadas despues de esa sentencia) indican que no apoyaban el significado de lo que decretaron. English Abstract: The reasoning of Roe v. Wade has been rejected by the German Constitutional Court, by American academics and feminists personally in favor of abortion, by state and federal legislation which manages to protect the unborn despite Roe, and by the U.S. Supreme Court itself which has neither reaffirmed nor extended that reasoning and has allowed its conclusions to survive only because of the Anglo-Saxon doctrine of binding precedent. Perhaps most surprising of all, the core teaching of the case -- the depersonalization of the fetus and the consequent right to elective abortion -- was rejected by the original authors of the Roe opinion. In their private papers (revealed decades after the decision) they indicated that they did not support what they had just decreed.
The centrality of social ties to climate migration and mental health

Climate change-related hazards and disasters, known to adversely impact physical and mental health outcomes, are also expected to result in human migration above current levels. Environmentally-motivated migration and displacement may lead to the disruption of existing social ties, with potentially adverse consequences for mobile populations as well as their family members who remain in places of origin. We propose that the disruption of social ties is a key mechanism by which climate-related migration may negatively impact mental health, in particular. Existing social ties may provide social and material resources that buffer mental health stressors related to both prolonged and acute climate events. Preparation for such events may also strengthen these same ties and protect mental health. Communities may leverage social ties, first to mitigate climate change, and second, to adapt and rebuild post-disaster in communities of origin. Additionally, social ties can inform migration decisions and destinations. For example, scholars have found that the drought-motivated adaptive migration of West African Fulbe herders only occurred because of the long-term development of social networks between migrants and non-migrants through trade and seasonal grazing. On the other hand, social ties do not always benefit mental health. Some migrants, including those from poor regions or communities with no formal safety net, may face considerable burden to provide financial and emotional resources to family members who remain in countries of origin. In destination communities, migrants often face significant social marginalization. Therefore, policies and programs that aim to maintain ongoing social ties among migrants and their family and community members may be critically important in efforts to enhance population resilience and adaptation to climate change and to improve mental health outcomes. Several online platforms, like Refugee Start Force, serve to integrate refugees by connecting migrants directly to people and services in destination communities. These efforts may increasingly draw upon novel technologies to support and maintain social networks in the context of population mobility due to climatic and other factors.
IDENTIFICATION METHODS | Immunoassay

Antibody-based assays for the detection of foodborne pathogens have become well established and are available in a wide range of platforms. Immunoassays have been implemented at all stages of food microbiological testing. Immunoassays can be qualitative or quantitative and can identify microorganisms to the subspecies level. Detection can be as simple as visualization of a physical precipitate or can rely on complex optics for detecting weak fluorescence signals. Antibody-capture steps are used to aid in separating target bacterial cells from complex food matrices increasing the sensitivity of detection. Immunoassays have proven their usefulness for many years and are likely to continue to be utilized in the field of microbial food safety for many years to come.
Modeling the Environmental Suitability for Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus (Diptera: Culicidae) in the Contiguous United States

The mosquitoes Aedes (Stegomyia) aegypti (L.)(Diptera:Culicidae) and Ae. (Stegomyia) albopictus (Skuse) (Diptera:Culicidae) transmit dengue, chikungunya, and Zika viruses and represent a growing public health threat in parts of the United States where they are established. To complement existing mosquito presence records based on discontinuous, non-systematic surveillance efforts, we developed county-scale environmental suitability maps for both species using maximum entropy modeling to fit climatic variables to county presence records from 1960-2016 in the contiguous United States. The predictive models for Ae. aegypti and Ae. albopictus had an overall accuracy of 0.84 and 0.85, respectively. Cumulative growing degree days (GDDs) during the winter months, an indicator of overall warmth, was the most important predictive variable for both species and was positively associated with environmental suitability. The number (percentage) of counties classified as environmentally suitable, based on models with 90 or 99% sensitivity, ranged from 1,443 (46%) to 2,209 (71%) for Ae. aegypti and from 1,726 (55%) to 2,329 (75%) for Ae. albopictus. Increasing model sensitivity results in more counties classified as suitable, at least for summer survival, from which there are no mosquito records. We anticipate that Ae. aegypti and Ae. albopictus will be found more commonly in counties classified as suitable based on the lower 90% sensitivity threshold compared with the higher 99% threshold. Counties predicted suitable with 90% sensitivity should therefore be a top priority for expanded mosquito surveillance efforts while still keeping in mind that Ae. aegypti and Ae. albopictus may be introduced, via accidental transport of eggs or immatures, and potentially proliferate during the warmest part of the year anywhere within the geographic areas delineated by the 99% sensitivity model.
End-member extraction using cone non-negativity constraints

This paper presents a new factorization approach for hyperspectral data based on non-negativity constraints. The method does not assume a one to one correspondence between the pseudo-rank of the data matrix and the number of unique components present. Rather it assumes that the number of unique components is related to the number of extreme points of the cone formed by the data matrix. The cone is represented by singular vectors and a set of linear homogeneous inequality constraints. The extraction of extremes is based on the identification of non-redundant inequalities. The approach is illustrated in an application to an AVIRIS spectral image of the Cuprite mining site.
Chemotherapy-induced differential cell cycle arrest in B-cell lymphomas affects their sensitivity to Wee1 inhibition

Chemotherapeutic agents, e.g., cytarabine and doxorubicin, cause DNA damage. However, it remains unknown whether such agents differentially regulate cell cycle arrest in distinct types of B-cell lymphomas, and whether this phenotype can be exploited for developing new therapies. We treated various types of B cells, including primary and B lymphoma cells, with cytarabine or doxorubicin, and determined DNA damage responses, cell cycle regulation and sensitivity to a Wee1 inhibitor. We found that cyclin A2/B1 upregulation appears to be an intrinsic programmed response to DNA damage; however, different types of B cells arrest in distinct phases of the cell cycle. The Wee1 inhibitor significantly enhanced the apoptosis of G2 phase-arrested B-cell lymphomas by inducing premature entry into mitosis and mitotic catastrophe, whereas it did not affect G1/S-phase-arrested lymphomas. Cytarabine-induced G1-arrest can be converted to G2-arrest by doxorubicin treatment in certain B-cell lymphomas, which correlates with newly acquired sensitivity to the Wee1 inhibitor. Consequently, the Wee1 inhibitor together with cytarabine or doxorubicin inhibited tumor growth in vitro and in vivo more effectively, providing a potential new therapy for treating B-cell lymphomas. We propose that the differential cell cycle arrest can be exploited to enhance the chemosensitivity of B-cell lymphomas.
Mechanisms for Recognition and Phagocytosis of Apoptotic Lymphocytes by Macrophages

Erythrocytes have an asymmetric distribution of phospholipids across the bilayer of their plasma membranes, maintained by an ATP-dependent aminophospholipid translocase, and dissipated by activation of a non-specific lipid flipsite. Loss of asymmetry provokes recognition by the reticuloendothelial system. In vitro, enhanced phagocytosis of erythrocytes with a symmetric bilayer can be inhibited by artificial lipid vesicles made of phosphatidylserine (PS), indicating that macrophages recognize the PS that appears on the erythrocyte surface upon loss of asymmetry. It is becoming increasingly clear that these same fundamental membrane structure/function relationships established in the erythrocyte paradigm also apply to lymphocytes. All evidence suggests that lymphocytes maintain an asymmetric transbilayer distribution of phospholipids in their plasma membranes, maintained by an aminophospholipid translocase. Asymmetry is lost as part of the program of cell death, by down-regulation of the translocase and activation of the non-specific lipid flipsite, exposing PS on the cell surface. That PS exposure has functional consequences is demonstrated by the ability of artificial lipid vesicles containing PS to inhibit enhanced phagocytosis of apoptotic lymphocytes by macrophages. However, other signals besides PS are also involved in recognition of apoptotic lymphocytes. Studies with other inhibitors indicate that macrophages also utilize integrin-mediated and lectin-like recognition systems, although each is restricted to either unactivated or activated macrophages. These results indicate that although many fundamental features of recognition by the reticuloendothelial system may be analogous in erythrocytes and lymphocytes, the signals for recognition of apoptotic lymphocytes are more complex and involve multiple recognition systems.
First Observation of Cross-Beam Energy Transfer Mitigation for Direct-Drive Inertial Confinement Fusion Implosions Using Wavelength Detuning at the National Ignition Facility.

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces ablation pressure and implosion velocity in direct-drive inertial confinement fusion. Mitigating CBET is demonstrated for the first time in inertial-confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths ($\ifmmode\pm\else\textpm\fi{}2.3\text{ }\text{ }\AA{}$ UV) of the interacting beams. We show that, in polar direct-drive, wavelength detuning increases the equatorial region velocity experimentally by 16% and alters the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation-hydrodynamic simulations that indicate a 10% increase in the average ablation pressure.
Communication failure: analysis of prescribers' use of an internal free-text field on electronic prescriptions.

Importance Electronic prescribing promises to improve the safety and clarity of prescriptions. However, it also can introduce miscommunication between prescribers and pharmacists. There are situations where information that is meant to be sent to pharmacists is not sent to them, which has the potential for dangerous errors. Objective To examine how frequently prescribers or administrative personnel put information intended for pharmacists in a field not sent to pharmacists, classify the type of information included, and assess the potential harm associated with these missed messages. Design, Setting, Participants Medication record data from our legacy electronic health record were requested for ambulatory care patients seen at an academic medical center from January 1, 2000, to May 31, 2015 (20 123 881 records). From this database, 6 060 272 medication orders met our inclusion criteria. We analyzed a random sample of 10 000 medication orders with internal comments. Main Outcomes and Measures Reviewers classified internal comments for intent. Comments intended for pharmacists were also sorted into descriptive categories and analyzed for the potential for patient harm. Results We found that 11.7% of the prescriptions in our sample contained comments that were intended to be sent to pharmacists. Many comments contained information about the dose, route, or duration of the prescription (38.0%). Approximately a third of the comments intended for pharmacists contained information that had the potential for significant or severe harm if not communicated. Conclusion We found undelivered comments that were clearly intended for pharmacists and contained important information for either pharmacists or patients. This poses a legitimate safety concern, as a portion of comments contained information that could have prevented severe or significant harm.
Kulturphilosophie als „naturalistische“ Transzendentalphilosophie und die Frage nach dem Ort der Kultur

In diesem Beitrag wird Cassirers Kulturphilosophie als eine besondere Applikation der Kantischen Transzendentalphilosophie dargestellt, sodann in Vergleich gesetzt zu einer anderen Tradition, der Pittsburgh School, hier v.a. McDowell. Der Ausgang ist der Sellars’sche Begriff des „space of reasons“, der sodann von McDowell erweitert wird durch seinen (Aristotelisch inspirierten) Begriff der „zweiten Natur“. Durch eine interessante Auslegung eines fruhen Interpreten Cassirers – Howe – wird es moglich, „Marburg“ und „Pittsburgh“ miteinander in Gesprach zu bringen. Das Resultat dieses Vergleichs wird eine Position sein, die beide Traditionen vermittelt und die man mit Howe als „naturalistischen Idealismus“ bezeichnen konnte. Am Schluss wird der Versuch unternommen, die Uberlegenheit von Cassirers Position zu demonstrieren, die allerdings keine Widerlegung derjenigen von McDowell bedeutet, sondern seine Position in Cassirers einbettet.
The Role of Biotechnology in Cannabis sativa Propagation for the Production of Phytocannabinoids

Cannabissativa L. (Cannabaceae) is an important medicinal plant that serves as a source of Cannabinoids, a unique class of terpenophenolic compounds which accumulates mainly in the glandular trichomes of the plant. Currently, about 110 phytocannabinoids have been isolated from C. sativa, the major biologically active compound being Δ9-tetrahydrocannabinol, commonly referred to as THC. Besides its psychoactivity, THC possesses analgesic, antiinflammatory, appetite stimulant, and antiemetic properties making it a very promising therapeutic agent especially for cancer and AIDS patients. Cannabidiol, Cannabichromene, Cannabigerol, Cannabinol, and Tetrahydrocannabivarin are other major bioactive phytocannabinoids present in the cannabis plant. Through a contract with the National Institute on Drug Abuse (NIDA), The University of Mississippi has been carrying out a variety of research activities dealing with cannabis, including growing, harvesting, and processing the cannabis biomass for research purposes making it available for licensed researchers across the country through NIDA. This chapter describes the role of biotechnology and our efforts to propagate C. sativa for the production of phytocannabinoids. This includes, screening of high yielding genotypes based on their chemical profile, propagation of these genotypes using biotechnological tools, comparison of micropropagated plants with the mother plants for consistency of chemical and genetic profiles and the utility of micropropagation in the conservation of elite clones for future use.
Pneumonia in the elderly : special diagnostic and therapeutic considerations

Clinical and radiologic signs and symptoms of gram-negative infections are often muted or obscured by a concurrent disease, and therefore, are not reliable for predicting the infecting organisms. Thus, initial therapy is nearly always empiric and based on the clinician's judgment that a patient's pneumonia is likely to be caused by particular pathogens. The choice of an appropriate regimen requires careful consideration of the extent and severity of coexisting illness and debilitation, the severity of the pneumonia, and the level of care required.
Localized retroperitoneal lymphangioleiomyomatosis mimicking malignancy: A case report and review of the literature

Lymphangioleiomyomatosis (lymphangiomyomatosis [LAM]), a rare disease of unknown etiology that is seen only in women usually in the reproductive period, generally presents with features of pulmonary involvement. Extrapulmonary involvement, such as angiomyolipomas and retroperitoneal adenopathy, can occur in up to 75% of cases. It is very rare, however, for patients to present with features of extrapulmonary LAM. We present an unusual, localized case of LAM presenting with neurologic symptoms related to a retroperitoneal mass in a 51-year-old woman. Magnetic resonance imaging showed that the mass involved retroperitoneal lymph nodes, and a clinical diagnosis of atypical sarcoma (possibly from a uterine primary) was made. The mass was resected, and a total abdominal hysterectomy was performed. On pathologic examination, the mass showed classic histologic features of LAM with spread along lymphatic channels in the lymph nodes. Intralymphatic projections simulated lymphatic metastasis; however, the cytologic features were benign. Immunostains revealed the tumor to be positive for smooth muscle actin and desmin, but negative for HMB-45. The uterus was unremarkable, except for a subserosal leiomyoma. Although intratumoral variability for HMB-45 has recently been described, to the best of our knowledge, this is the first documented case of HMB-45-negative, histologically classic LAM. Because of the presence of several atypical features in this case, such as age, location, compressive neurologic presentation, radiologic impression of atypical sarcoma, and HMB-45 negativity, we feel that this case may represent a distinct, as yet uncharacterized variant of LAM.
The Impact of Kinematic Simulations on Quantum Turbulence Theory

In thermal superfluid turbulence, an inviscid superfluid interacts with a viscous normal-fluid via mutual friction forces. Due to nonlinearities in both constituents, vortical, deterministic fluctuations (turbulence) arise under most flow conditions. Presently, computational and numerical complexity pose obstacles to high Reynolds number, fully resolved, developed turbulence computations. The application of Kinematic Simulation (KS) modeling to the inertial range of the normal-fluid constituent provided significant new results like superfluid energy spectra scalings, the fractal dimension of superfluid vorticity, inertial range pressure spectra scalings exhibiting departure from classical Kolmogorov theory predictions, as well as useful insight into superfluid turbulence decay.
On Inhomogeneous Polarized States near the Phase Transition Point in a Thin Ferroelectric Film

It is shown in terms of the phenomenological Landau theory of phase transitions that a phase transition to an inhomogeneous polar phase preceding in temperature a phase transition to a homogeneous polar state is possible. As a result of solving a boundary eigenvalue problem for the polarization equilibrium equation and electrostatics equations, wave vector k⊥ characterizing the inhomogeneous phase has been determined and the temperature boundaries of its existence in the dependence on the film thickness and its surface properties have been found.
Leptin Increases Particle-Induced Osteolysis in Female ob/ob Mice.

Particles generated from wear of prosthesis joint bearing surfaces induce inflammation-mediated periprosthetic bone resorption (osteolysis). Morbidly obese leptin-deficient ob/ob mice are resistant to polyethylene particle-induced bone loss, suggesting that leptin, a hormone produced by adipocytes that circulates in concentrations proportional to total body adiposity, increases osteolysis. To confirm that particles induce less osteolysis in leptin-deficient mice after controlling for cold stress (room temperature)-induced bone loss, ob/ob mice on a C57BL/6 (B6) background and colony B6 wildtype (WT) mice housed at thermoneutral temperature were randomized to control or particle treatment groups (N = 5/group). Polyethylene particles were implanted over calvaria and mice sacrificed 2 weeks later. Compared to particle-treated WT mice, particle-treated ob/ob mice had lower osteolysis score, less infiltration of immune cells, and less woven bone formation. To determine the role of leptin in particle-induced osteolysis, ob/ob mice were randomized into one of 4 groups (n = 6–8/group): (1) control, (2) particles, (3) particles + continuous leptin (osmotic pump, 6 μg/d), or (4) particles + intermittent leptin (daily injection, 40 μg/d). Leptin treatment increased particle-induced osteolysis in ob/ob mice, providing evidence that the adpiokine may play a role in inflammation-driven bone loss. Additional research is required to determine whether altering leptin levels within the physiological range results in corresponding changes in polyethylene-particle-induced osteolysis.
Optimal Selection of the Regression Kernel Matrix with Semidefinite Programming

Support vector machines have recently attracted much attention in the machine learning and optimization communities for their remarkable generalization ability. An open problem, however, is the selection of the optimal kernel matrix for regression problems. Recently, a means to compute the optimal kernel matrix for pattern classification using semidefinite programming has been introduced [7]. In this paper we extend these thoughts to the regression analysis scenario. Preliminary experimental results are presented for which the optimal kernel matrix for support vector machine regression is retrieved.
Evaluation and Management of Primary Hyperaldosteronism

Primary hyperaldosteronism is an important and increasingly prevalent cause of hypertension that is characterized by unregulated aldosterone excess. More than 90% of primary hyperaldosteronism cases are attributable to either idiopathic adrenal hyperplasia or aldosterone-producing adenomas. The approach to the diagnosis of primary hyperaldosteronism should be step-wise, starting with screening of at-risk populations, confirmatory testing for positively screened patients, and subtype classification in order to direct surgical or medical management. Based on current guidelines, subtype classification of primary hyperaldosteronism should be determined with both imaging and adrenal vein sampling (AVS), reserving deferment of AVS for a selective subset of patients.
Distinct plasma proteomic changes in male and female African American stroke patients.

Background Stroke occurs more often and results in more severe brain injury in African Americans than in Caucasians. The former also exhibit different responses to thrombolytic therapy than the latter do. There is an imminent need for stroke biomarkers for African Americans, who have been underrepresented in biomarker research for stroke diagnosis and prognosis. Proteomics offers sources for protein biomarkers that are not available by other Omics approaches. In this pilot study, plasma proteomes of African American stroke patients were analyzed and compared to that of hypertensive, non-stroke controls. Methods Plasma samples were prepared from whole blood specimens that were collected from stroke patients admitted to Grady Memorial Hospital in Atlanta, and their age- and sex-matched, hypertensive controls from the outpatient clinic. Samples were pooled according to patient groups and sex. Plasma proteins were analyzed with quantitative mass spectrometry. The identified and quantified proteins were compared between stroke and control patients of each sex. Proteins that showed changes in abundances in stroke patients were further analyzed with the assistance of bioinformatics tools for their known biological functions or potential implications in stroke. Results A total of 128 annotated proteins were identified. Results of bioinformatic analysis of plasma proteins whose levels were increased in stroke patients showed, as expected, their association with blood coagulation and inflammation processes. Interestingly, a number of proteins showed different or even opposing changes in male and female stroke patients, notably those involved in IL-4 and IL-6 signaling, complement activation, and blood coagulation disorders. For a few proteins that were increased in female but unchanged or decreased in male stroke patients, an association with fibromuscular dysplasia was recognized. Conclusion Plasma proteins that differ in quantities between stroke patients and controls were readily detected using a simple proteomic approach. Sex-dependent changes and changes that have not been reported for African American stroke patients offer potentially novel biomarkers for stroke in this underserved population.
Abrogation of prenucleation, transient oligomerization of the Huntingtin exon 1 protein by human profilin I.

Human profilin I reduces aggregation and concomitant toxicity of the polyglutamine-containing N-terminal region of the huntingtin protein encoded by exon 1 (httex1) and responsible for Huntington’s disease. Here, we investigate the interaction of profilin with httex1 using NMR techniques designed to quantitatively analyze the kinetics and equilibria of chemical exchange at atomic resolution, including relaxation dispersion, exchange-induced shifts, and lifetime line broadening. We first show that the presence of two polyproline tracts in httex1, absent from a shorter huntingtin variant studied previously, modulates the kinetics of the transient branched oligomerization pathway that precedes nucleation, resulting in an increase in the populations of the on-pathway helical coiled-coil dimeric and tetrameric species (τex ≤ 50 to 70 μs), while leaving the population of the off-pathway (nonproductive) dimeric species largely unaffected (τex ∼750 μs). Next, we show that the affinity of a single molecule of profilin to the polyproline tracts is in the micromolar range (Kdiss ∼ 17 and ∼ 31 μM), but binding of a second molecule of profilin is negatively cooperative, with the affinity reduced ∼11-fold. The lifetime of a 1:1 complex of httex1 with profilin, determined using a shorter huntingtin variant containing only a single polyproline tract, is shown to be on the submillisecond timescale (τex ∼ 600 μs and Kdiss ∼ 50 μM). Finally, we demonstrate that, in stable profilin–httex1 complexes, the productive oligomerization pathway, leading to the formation of helical coiled-coil httex1 tetramers, is completely abolished, and only the pathway resulting in “nonproductive” dimers remains active, thereby providing a mechanistic basis for how profilin reduces aggregation and toxicity of httex1.
User Experiences of Social Support From Companion Chatbots in Everyday Contexts: Thematic Analysis

Background: Previous research suggests that artificial agents may be a promising source of social support for humans. However, the bulk of this research has been conducted in the context of social support interventions that specifically address stressful situations or health improvements. Little research has examined social support received from artificial agents in everyday contexts. Objective: Considering that social support manifests in not only crises but also everyday situations and that everyday social support forms the basis of support received during more stressful events, we aimed to investigate the types of everyday social support that can be received from artificial agents. Methods: In Study 1, we examined publicly available user reviews (N=1854) of Replika, a popular companion chatbot. In Study 2, a sample (n=66) of Replika users provided detailed open-ended responses regarding their experiences of using Replika. We conducted thematic analysis on both datasets to gain insight into the kind of everyday social support that users receive through interactions with Replika. Results: Replika provides some level of companionship that can help curtail loneliness, provide a “safe space” in which users can discuss any topic without the fear of judgment or retaliation, increase positive affect through uplifting and nurturing messages, and provide helpful information/advice when normal sources of informational support are not available. Conclusions: Artificial agents may be a promising source of everyday social support, particularly companionship, emotional, informational, and appraisal support, but not as tangible support. Future studies are needed to determine who might benefit from these types of everyday social support the most and why. These results could potentially be used to help address global health issues or other crises early on in everyday situations before they potentially manifest into larger issues.
O6 Association of Food Security and Access to Traditional Foods Among American Indians and Alaska Natives

Background One in 4 American Indians or Alaska Natives (AIAN) are estimated to experience food insecurity. Access to traditional food sources may, in part, explain the high prevalence of food insecurity. Traditional foods were primary sources of nutrition and could often be acquired through non-market mechanisms prior to colonization. Whether and how access relates to food insecurity is unknown. Objective To assess whether access and consumption of traditional native foods is associated with food insecurity among AIAN. Study Design, Setting, Participants Cross-sectional pilot study using a paper-and-pencil questionnaire administered at a National Powwow in October 2019. Adults that self-identified as AIAN were recruited in-person. Measurable Outcome/Analysis Food insecurity was assessed with 2 items to capture the dimensions of adequate quality and sufficient quantity of foods. Native foods security was assessed with 1 validated item on a 4-point Likert scale for perceived sufficiency of native food access ranging from ‘never’ to ‘always’. Hunting, fishing, and gathering practices were also reported. Chi-squared tests were used to assess the relationship of food insecurity with native foods access and use. Results The mean age of 39 respondents was 43.5 (±13.7) years and 56.4% identified as female. Food insecurity was high, with 31% reporting insufficient quantity or compromised quality. Native foods insecurity (rated as ‘never’ or ‘rarely’) was also high, reported by 74% of respondents. Native foods insecurity was common, regardless of food insecurity status (P > .05). Fishing to access native foods was more common among those also reporting insufficient quantity (P Conclusion Though limited by sample size, this pilot study provides support for future hypotheses and investigations related to native foods and food insecurity. Future work should use mixed methods to better understand food insecurity, access to native foods, and the potential relationship with diet. Funding None.
Aspiration of a bullet after a gunshot wound to the face

Abstract There are very few reports of penetrating injuries to the head and neck resulting in aspiration of and retained intrabronchial foreign bodies. We present a pediatric patient who sustained a gunshot injury to the face with subsequent aspiration of the bullet. Removal of the retained bullet was achieved with flexible bronchoscopy. Additionally, we review the available literature on this rare injury pattern.
Revisiting Kuo and Belland's exploratory study of undergraduate students' perceptions of online learning: minority students in continuing education.

COVID-19 has forced educators to make rapid changes to their pedagogy in order to shift from face-to-face instruction to online delivery. In this time of rapid change, Kuo and Belland's (Educ Technol Res Dev 64:661-680, 2016) exploratory study that highlights the types of interactions that correlated with African American students' success in an undergraduate course could provide instructors with ideas about how to create more equitable online courses. Thus, this article describes how instructors might consider the cultural and racialized experiences of their students through an asset lens as they design online coursework. Specifically, instructors should attend to students' experiences and determine how students will interact with the content, with the instructor, and with other learners. Implications are described.
Primary medication nonadherence calculation method specifications impact resulting rates.

Abstract Background Previous literature has illustrated a wide range of primary medication nonadherence (PMN) rates due to inconsistent calculation methods and parameters, but the impact of parameter specifications on PMN rates has not been assessed. Objectives The objective of this study was to evaluate the impact of lookback window (LBW), duplicate window (DW), and fill window (FW) specifications on PMN rates in patients prescribed specialty self-administered oncology medications. Methods This was a single-center, retrospective cohort analysis. Patients receiving a new electronic specialty oncology prescription January–December 2018 were included; excluded if re-routed to an external pharmacy within 2 days, fell within a DW, or cancelled within a FW. Twenty-four methods were used to calculate PMN based on combinations of the following parameters: (i) absence of prior specialty self-administered oncology medication fill within LBW (90, 180 days); (ii) absence of a duplicate prescription within DW (2, 7, 30 days); and (iii) sold status within FW (14, 30, 60, 90 days). For each method, PMN was calculated as the number of unsold prescriptions within the FW divided by all eligible prescriptions. Results We evaluated 4,482 prescriptions, resulting in PMN ranging from 16% to 23%. Patients were commonly male (53%) and white (83%), with a median age of 64 years (interquartile range, IQR, 54, 72). Increasing the LBW from 90 to 180 days resulted in exclusion of 72 (2%) prescriptions and minimally impacted PMN rates. Most duplicate prescriptions (87%) occurred within two days of original prescription and PMN rates were minimally affected by DW. Most fulfilled prescriptions were filled within FW 30 days, 98% with a method of LBW 180, DW 2, and FW 30. Adjusting the FW consistently impacted PMN rates. Conclusions Because various PMN definitions can significantly impact results, a thorough explanation of all parameter specifications should be reported in research using PMN.
Using Multivariate Analyses To Explore Disease Progression of Finch Mycoplasmosis.

Lesion severity scales have been developed for a number of wildlife diseases causing external pathology. Perhaps the best known and most widely used scoring system has been developed for finch mycoplasmosis in which observers measure conjunctival pathology along a four-point scale of increasing severity. We developed novel techniques to characterize variation in host phenotype based on occupancy of multidimensional trait space (disease space). First, we used shape analysis to track distortions of the inner and outer eye rims, defined by 16 anatomical landmarks. Then, we used community analysis to evaluate pathology based on the presence or absence of a unique set of binary descriptors. We applied these techniques to experimental infection data to relate differences in conjunctival pathology to stage of infection. Specifically, by comparing specimens that received the same severity score at different time points in infection, we asked if shape or community analyses could distinguish between individuals in early infection versus those in recovery. We found that individual eyes followed predictable loops through disease space, tracking further from their origin with more severe pathology. Also, certain pathological descriptors were more likely to appear earlier versus later in infection. Our results indicated that leveraging differences in pathology captured in complex trait space could complement severity scores by better resolving the time course of infection from limited data points.
Cannabinoid Modulation of Dopamine Release During Motivation, Periodic Reinforcement, Exploratory Behavior, Habit Formation, and Attention.

Motivational and attentional processes energize action sequences to facilitate evolutionary competition and promote behavioral fitness. Decades of neuropharmacology, electrophysiology and electrochemistry research indicate that the mesocorticolimbic DA pathway modulates both motivation and attention. More recently, it was realized that mesocorticolimbic DA function is tightly regulated by the brain’s endocannabinoid system and greatly influenced by exogenous cannabinoids—which have been harnessed by humanity for medicinal, ritualistic, and recreational uses for 12,000 years. Exogenous cannabinoids, like the primary psychoactive component of cannabis, delta-9-tetrahydrocannabinol, produce their effects by acting at binding sites for naturally occurring endocannabinoids. The brain’s endocannabinoid system consists of two G-protein coupled receptors, endogenous lipid ligands for these receptor targets, and several synthetic and metabolic enzymes involved in their production and degradation. Emerging evidence indicates that the endocannabinoid 2-arachidonoylglycerol is necessary to observe concurrent increases in DA release and motivated behavior. And the historical pharmacology literature indicates a role for cannabinoid signaling in both motivational and attentional processes. While both types of behaviors have been scrutinized under manipulation by either DA or cannabinoid agents, there is considerably less insight into prospective interactions between these two important signaling systems. This review attempts to summate the relevance of cannabinoid modulation of DA release during operant tasks designed to investigate either motivational or attentional control of behavior. We first describe how cannabinoids influence DA release and goal-directed action under a variety of reinforcement contingencies. Then we consider the role that endocannabinoids might play in switching an animal’s motivation from a goal-directed action to the search for an alternative outcome, in addition to the formation of long-term habits. Finally, dissociable features of attentional behavior using both the 5-choice serial reaction time task and the attentional set-shifting task are discussed along with their distinct influences by DA and cannabinoids. We end with discussing potential targets for further research regarding DA-cannabinoid interactions within key substrates involved in motivation and attention.
CAT, AGTR2, L-SIGN and DC-SIGN are potential receptors for the entry of SARS-CoV-2 into human cells

Since December 2019, the COVID-19 caused by SARS-CoV-2 has been widely spread all over the world. It is reported that SARS-CoV-2 infection affects a series of human tissues, including lung, gastrointestinal tract, kidney, etc. ACE2 has been identified as the primary receptor of the SARS-CoV-2 Spike (S) protein. The relatively low expression level of this known receptor in the lungs, which is the predominantly infected organ in COVID-19, indicates that there may be some other co-receptors or alternative receptors of SARS-CoV-2 to work in coordination with ACE2. Here, we identified twenty-one candidate receptors of SARS-CoV-2, including ACE2-interactor proteins and SARS-CoV receptors. Then we investigated the protein expression levels of these twenty-one candidate receptors in different human tissues and found that five of which CAT, MME, L-SIGN, DC-SIGN, and AGTR2 were specifically expressed in SARS-CoV-2 affected tissues. Next, we performed molecular simulations of the above five candidate receptors with SARS-CoV-2 S protein, and found that the binding affinities of CAT, AGTR2, L-SIGN and DC-SIGN to S protein were even higher than ACE2. Interestingly, we also observed that CAT and AGTR2 bound to S protein in different regions with ACE2 conformationally, suggesting that these two proteins are likely capable of the co-receptors of ACE2. Conclusively, we considered that CAT, AGTR2, L-SIGN and DC-SIGN were the potential receptors of SARS-CoV-2. Moreover, AGTR2 and DC-SIGN tend to be highly expressed in the lungs of smokers, which is consistent with clinical phenomena of COVID-19, and further confirmed our conclusion. Besides, we also predicted the binding hot spots for these putative protein-protein interactions, which would help develop drugs against SARS-CoV-2.
Spectroscopic label-free microscopy of changes in live cell chromatin and biochemical composition in transplantable organoids

Organoids formed from human induced pluripotent stem cells (hiPSCs) could be a limitless source of functional tissue for transplantations in many organs. Unfortunately, fine-tuning differentiation protocols to form large quantities of hiPSC organoids in a controlled, scalable, and reproducible manner is quite difficult and often takes a very long time. Recently, we introduced a new approach of rapid organoid formation from dissociated hiPSCs and endothelial cells using microfabricated cell-repellent microwell arrays. This approach, when combined with real-time label-free Raman spectroscopy of biochemical composition changes and confocal light scattering spectroscopic microscopy of chromatin transition, allows for monitoring live differentiating organoids without the need to sacrifice a sample, substantially shortening the time of protocol fine-tuning. We used this approach to both culture and monitor homogeneous liver organoids that have the main functional features of the human liver and which could be used for cell transplantation liver therapy in humans.