cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-term use of valproate in primary psychiatric disorders

Thirty-five patients, all with major depressive illness, bipolar disorder, or schizoaffective disorder, were retrospectively identified as having received valproate either alone or in combination with lithium, after having failed to adequately respond to previous lithium and/or carbamazepine treatment. Clinical evaluation and Global Assessment Scale (GAS) scores indicated that at baseline all but 3 of the patients experienced serious psychiatric symptoms, serious impairment in social or professional functioning, or significant impairment in reality testing. Mean GAS scores after a mean duration of at least 1 year of valproate administration improved in 7 of 9 depressed patients, 12 of 12 patients with bipolar disorder, and 11 of 14 patients with schizoaffective states. Mean increases in GAS scores were 27.7 points for depressive disorder patients, 34.5 points for mixed bipolar disorder patients, and 17.1 points for patients with schizoaffective states. For patients with either depressive disorders or mixed bipolar disorders, that mean change represented a level of improvement sufficient to elevate the majority of the patients into the mild symptom range or the virtually asymptomatic state. That improvement was confirmed by the investigator's global evaluation of patient response with regard to affect: valproate administration produced significant affective responses in 7 of 9 depressed patients, 12 of 12 patients with mixed bipolar disorders, and 11 of 14 patients with schizoaffective states. The responses of patients with bipolar and schizoaffective disorders to valproate treatment compared with valproate plus lithium treatment were also evaluated. Patients in both diagnostic categories demonstrated very similar and quite substantial improvement in mean change in GAS ratings and global evaluations, regardless of whether valproate was administered alone or in combination with lithium.
Differential Growth Regulation of Human Bladder Tumor Cells (J82) in Culture by Normal Bladder Cells from Different Aged Human Donors

This study used an agarose gel culture system to study growth regulatory interactions between normal and neoplastic human bladder cells. The effects of normal human fibroblasts on tumor cell cloning efficiency in agarose was studied using 2 experimental protocols. In 1 system, the fibroblasts proliferated as anchored cells beneath the agarose, and in the other the fibroblasts were nongrowing cells embedded within the agarose as nonanchored cells. In contrast to the largely inhibitory effects of anchored fetal fibroblasts on tumor cell growth, their nonanchored counterparts were exclusively stimulatory. Similar experiments with normal fibroblasts derived from the bladders of increasingly older donors showed a progressive decline in their capacity to inhibit tumor cell growth in agarose. Further experiments modulating the growth rate of neonatal fibroblasts with fetal bovine serum have indicated that the diverse tumor responses elicited by anchored versus nonanchored cells, as well as those observed for the aged bladder fibroblasts, were a function of fibroblast growth rate. We concluded that there was an inverse regulatory relationship between the growth of normal and tumor cells; rapidly growing fibroblasts were inhibitory whereas nongrowing fibroblasts stimulated tumor cell growth in agarose culture.
The perfect storm for electronic health records

EHRs and data sharing improve quality, reduce costs, and enhance workflow. They create a c ommunity of clinical collaboration, fostering the adoption of new knowledge and best practices. With government, provider, and payer support for the nationwide rollout of electronic records, 2006 will be the year in which the United States makes significant progress on the journey to deliver electronic systems to all clinicians.
Genetic characterization analysis on epidemic rubella virus strains isolated in Liaoning from 2007 to 2012

To analyze the genetic characterization of epidemic rubella virus strains isolated in Liaoning from 2007-2012, a total of 145 rubella virus strains were isolated using Vero/Slam cell line from the patients' throat swabs during rubella outbreaks and sporadics cases in Liaoning Province from 2007 to 2012. Fragments of 945 nucleotides containing 1E gene from 145 rubella virus isolates were amplified by RT-PCR, the PCR products were sequenced and analyzed. Based on the 739 nucleotides of 1E gene, the phylogenetic trees were constructed with 32 WHO rubella reference strains of 13 genotypes downloaded from GenBank and 145 rubella virus strains. The results showed that the 145 rubella virus strains in 2007 -2012 belonged to genotype 1E, nucleotide acids and amino acids similarities were 97.2%-100.0% and 97.6%-100.0%, respectively. Compared to the 1E reference strains(Rvi/ Dezhou.CHN/02, RVi/MYS/01), the nucleotide acids and amino acids similarities were 96.6%-99.2% and 98.2%-100.0%, respectively except for one amino acid change (Val246-Ala246) of RVi/Shenyang. Liaoning. CHN/13.11/13, and Asp262-Asn262 of RVi/Shenyang. Liaoning. CHN/13.11/4 and RVi/Liaoyang. Liaoning. CHN/26. 11/2. there had no change found in the important antigenic epitope sites, the hemagglutination inhibition and neutralization epitopes of the other rubella viruses. All the 145 strains isolated had the same amino acid change (Leu338--Phe338) in E1 protein. These findings suggested that genotype 1E of rubella virus was the predominant genotype in Liaoning province. the rubella prevailed in recent six years was mainly caused by rubella viruses genotype 1E with multi-transmission routes.
Towards Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis.

Irreversible organ failure remains a worldwide concern as demand for transplantable organs far outpaces the available supply. Apart from the demand for replacement organs to use to treat irreversible organ failure in civilian, there is a need of tissues or organs for wounded soldiers returning from battle. This review will discuss traditional three-dimensional (3D) cell culture techniques as well as newly developed technology platforms for the generation of transplantable tissues and organs on demand. Since their discovery, stem cells have held great promise for their application in tissue regenerative medicine. Considerable effort is presently being invested in establishing methods for engineering physiologically relevant organs, where the chemical, physical and mechanical microenvironment of the stem cell niche can be replicated. The recently established methods provide new possibilities in the creation of human body parts and provide more accurate predictions of tissue response to drug and chemical challenges. Given the rapid advancement in the human-induced pluripotent stem cell (iPSC) field, these platforms also hold great promise in the engineering of transplantable tissues and organs, capable of benefitting patients with end-stage chronic organ failure or wounded warrior.
An efficient network coding scheme for two-way communication with ARQ feedback

In this paper, we consider a multiple-access broadcast channel (MABC) with ARQ feedback, in which M endusers wish to exchange messages with a central node or basestation. In this scenario, an end-user may overhear other endusers' messages prior to the re-transmission phase. We propose a new network coded (NCed)-ARQ scheme with reverse-link-assistance (RLA) that exploits this overheard information in uplink transmission to increase the downlink throughput. We derive throughput expressions for the new NCed-ARQ scheme in wireless additive white Gaussian noise with Rayleigh fading channel, which we numerically evaluate. For low/moderate SNRs, NCed-ARQ with RLA greatly improves the performance of downlink throughput.
The effect of phylogenetic signal reduction on genotyping of hepatitis E viruses of the species Orthohepevirus A

Commonly, hepatitis E virus (HEV) sequences are genotyped phylogenetically using subgenomic sequences. This paper examines this practice with sequences from members of the species Orthohepevirus A. As the length of sequences becomes progressively shorter, the number of identical sequences in an alignment tends to increase; however, these sequences retain their genotypic identity down to 100 nucleotides in length. The best substitution models tend to become less parameterized, bootstrap support decreases, and trees created from short subgenomic fragments are less likely to be isomorphic with trees from longer subgenomic fragments or complete genome sequences. However, it is still possible to correctly genotype sequences using fragments as small as 200 nucleotides. While it is possible to correctly genotype sequences with short subgenomic sequences, the estimates of evolutionary relationships between genotypes degrade to such an extent that sequences below 1600 nucleotides long cannot be used reliably to study these relationships, and comparisons of trees from different subgenomic regions with little or no sequence overlap can be problematic. Subtyping may be done, but it requires a careful examination of the region to be used to ensure that it correctly resolves the subtypes.
Next Generation Sequencing to Delineate the Mutational Landscape of Chronic Myelomonocytic Leukemia (CMML): Novel Disease Genes and Correlations with Survival

Abstract Purpose: Chronic myelomonocytic leukemia (CMML) is a clinically heterogeneous myelodysplastic/myeloproliferative neoplasm with short overall survival. Emerging data based on sequencing of candidate genes with a known role in myeloid leukemia have identified recurrent CMML mutations, some of which have been associated with poor prognosis. A comprehensive evaluation of the mutational landscape of CMML and its prognostic significance is lacking. Patients and Methods. We comprehensively characterized the mutational landscape of CMML by a 2-step design. We initially performed whole exome sequencing (WES) of paired leukemia and germline DNA from 21 patients with a confirmed CMML diagnosis (discovery cohort) to identify genes with somatic mutations. From this discovery cohort, 215 genes showing potential mutations as well as 61 genes selected from the literature were examined by targeted resequencing in a second cohort of 69 clinically annotated CMML patients, using two independent platforms for orthogonal confirmation Blood or marrow samples from 22 young and 17 old controls were included as controls. Results. We identified 22 genes with mutations in >3% of CMML patients, and 67/69 patients (97%) had one or more mutations in at least one of these genes. SRSF2, ASXL1 and TET2 were the most frequently mutated genes. Several novel CMML genes were identified, including FAT4 with a mutation prevalence of 10% and BCR, CBFA2T3, and TRPM1 with a prevalence of 3 – 9% (see Table). Total deleterious mutations per patient ranged from 0 – 11, with significant exclusion or association of various combinations of mutations in SETBP1, ASXL1, KRAS, TET2, and EZH2 observed. In univariate analysis hemoglobin 15x109/L, no treatment with hypomethylating agents, mutations in ASXL1, EZH2, or NRAS and mutations in growth factor signaling genes were associated with shorter overall survival. In multivariate analysis, mutations in NRAS (P Conclusion. (i) The mutational landscape of CMML is complex and involves mutations in multiple genes, many affected with relatively low prevalence. (ii) Mutations in FAT4, a putative tumor suppressor and key regulator of the Hippo pathway, occur in approximately 10% of patients. (iii) Absence of therapy with hypomethylating agents and mutations in NRAS or the functional group of growth factor signaling genes are predictive of poor survival. Table . Count and prevalence of N=69 CMML patients having a deleterious mutation in one of the genes observed mutated at a prevalence ≥ 10%. Gene # CMML Patients with Mutation (%) SRSF2 34 (49%) TET2 28 (41%) ASXL1 25 (36%) RUNX1 14 (20%) SETBP1 11 (16%) KRAS 10 (14%) EZH2 8 (12%) FAT4 7 (10%) CBL 7 (10%) NRAS 7 (10%) Download : Download high-res image (125KB) Download : Download full-size image Figure . Overall survival of N=48 CMML patients by HMA use and presence of deleterious mutation in NRAS. Disclosures Mason: Agilent, Inc.: Research Funding. Deininger: Celgene: Research Funding; Agilent, Inc.: Research Funding.
Simulating Data for Clinical Research: A Tutorial

Simulation studies use computer-generated data to examine questions of interest that have traditionally been used to study properties of statistics and estimating algorithms. With the recent advent...
Liquid metal particle popping: Macroscale to nanoscale

Abstract Liquid metal nanoparticles can be used to produce stretchable electronic devices. Understanding the mechanical properties of liquid metal nanoparticles is crucial to optimizing their use in various applications, especially printing of flexible, stretchable electronics. Smaller nanoparticles are desired for high-resolution printing and compatibility with existing scalable manufacturing methods; however, they contain less liquid metal and are more difficult to rupture than larger particles, making them less desirable for post-processing functionality. This study investigates the mechanics of liquid metal particle rupture as a function of particle size. We employ compression of particle films to characterize the composition of the particle core and derive a minimum particle size required to achieve sintering and subsequent conductance. We further derive the force required to rupture a single particle and validate the results by rupturing individual nanoparticles using atomic force microscopy. Finally, we relate the liquid metal nanoparticles to isotropically-elastic thin-shell microspheres to approximate the particle shell stiffness. An increased understanding of the behavior of liquid metal nanoparticles during rupture reveals limitations of current manufacturing processes and paves the way for the next generation of scalable mass-producible soft electronics using additive manufacturing technologies.
A PREDICTIVE TECHNIQUE FOR BUCKLING ANALYSIS OF THIN SECTION PANELS DUE TO WELDING

This paper presents an efficient and effective numerical analysis technique for predicting welding-induced buckling. The technique combines three-dimensional structural analyses with two-dimensional welding simulations. Implementation of the technique can determine the appropriate welding conditions under which the design critical buckling load is not exceeded. Experimental results obtained from small- and large-scale mock-up panels are used to confirm the predictions of the analytical models. The paper concludes with a study of the effects of heat input (weld size), panel size, and panel thickness on buckling distortion.
Professional Ethics and Personal Values in Mindfulness-Based Programs: A Secular Psychological Perspective

This chapter considers ethical foundations of mindfulness-based programs (MBPs) in contemporary secular settings. Two complementary ways of thinking about ethics in this context are addressed. First, we discuss the codes of ethics that guide the conduct of health care and mental health professionals in the delivery of their services, including MBPs. Second, we describe evidence-based methods for helping participants in MBPs identify their values and strengthen their values-consistent behavior. We offer these perspectives in response to discussions in the mindfulness field of the role of ethics training in MBPs. In Buddhist teachings, where most mindfulness practices have their roots, mindfulness training is embedded in an ethical framework that includes explicit instruction in benevolent conduct and precepts against harmful behavior. In contrast, most contemporary MBPs avoid explicit instruction in ethical behavior, both to ensure their suitability for secular settings and because ethics codes for the health care and mental health professions typically require respect for diversity and self-determination. This chapter argues for an approach to ethics in MBPs that is grounded in professional codes of ethics for mindfulness-based teachers and the psychological science of personal values.
Corn Response to Urea–Ammonium Nitrate Solution Treated with Encapsulated Nitrapyrin

The use of nitrification inhibitors with fertilizer N application is an attempt to improve corn (Zea mays L.) N use efficiency while reducing environmental and economic concerns associated with N losses. The objective of this study was to evaluate if the encapsulated formulation of nitrapyrin [2-chloro-6-(trichloromethyl) pyridine], Instinct nitrification inhibitor, would influence corn growth and production when applied with spring preplant urea–ammonium nitrate solution (UAN). A 3-yr field study was conducted in a randomized complete block design with four replications of a factorial combination consisting of UAN at six incremental N rates (0–225 kg N ha–¹), broadcast-incorporated and injected, and with and without 2.56 L ha–¹ (0.56 kg a.i. ha–¹) Instinct. In 1 of 3 yr, as well as for the means across years, Instinct applied with UAN had a negative effect of reduced early growth plant height and lower mid-vegetative canopy normalized difference vegetative index (NDVI) compared with UAN without Instinct. Corn grain yield also had a lower across N rate mean yield with Instinct application in 2 of 3 yr and across all 3 yr. The economic optimum N rate (EONR) with Instinct was 32 kg N ha–¹ higher than without Instinct, applied either broadcast or injected. Because Instinct did not provide positive effects on corn growth and yield, the study results indicate that Instinct use with spring preplant applied UAN solution would not be an effective nitrification inhibitor to enhance fertilizer N supply or corn production.
Chapter 2 Advances in Computer Displays

Abstract While the traditional role of displays has been for the viewing of television programming, over the past 10 years displays have increasingly become portals into virtual environments. It is therefore important to understand the current state of the art in image display technology so that one can begin to anticipate how this technology in the future will evolve, and how best to take advantage of that evolution once it matures. This chapter focuses on the issues of image display and how new advanced displays that are being used mainly in research and higher education today may become commonplace in the next 5–10 years.
Unsolicited reports of voice hearing in the general population: a study using a novel method

ABSTRACTUnderstanding the phenomenological range of auditory verbal hallucinations (AVHs), or voice hearing (VH) experiences, is important for developing etiological models. To circumvent potential methodological limitations of previous studies, we used unsolicited online self-reports to examine the kinds of experiences people describe when they say they hear voices. Content analysis was used to examine 499 online posts about VH, the largest VH sample studied to date. Most posters did not report having a psychiatric diagnosis. Unusual bodily sensations and third person voices were less prevalent than in previous studies. Volume of voices was mentioned significantly more often when voices were externally localized, but acoustic qualities were mentioned even when voices were internally localized. Some voice features previously considered atypical, such as unclear voices and voices that are not self-relevant, were described in almost 15% of coded posts. Only 21% described commanding voices, a feature previou...
The Temporal Dynamics of Anger: Phenomena, Processes, and Perplexities

Ordinary, everyday “episodes” of anger typically last less than half an hour, but their duration generally increases with intensity. Anger intensity and duration decline with increasing socioeconomic status; intensity, but not duration, declines with age. Anger at home is more intense but shorter than anger at work. Homicidal fantasies and anger-intensifying rumination on the unjust causes of one’s anger occur more frequently in men than women, are experienced as not entirely volitional, and can transform and extend the experience of anger to days, weeks, and months. In the face of constant or repeated provocation, anger escalates in a highly nonlinear fashion, significantly increasing the probability of aggressive action. At high intensities, some people (probably women more than men) experience their anger as out of control. Escalation may involve various forms of positive physiological and behavioral feedback; the feelings associated with it might have some neurological basis in a shift among the frontal cortical areas momentarily controlling behavior.
Informal Caregivers' Use of Internet-Based Health Resources: An Analysis of the Health Information National Trends Survey.

Background: Informal caregivers express strong interest in technology innovations to help them in their caregiving role; however, divides across sociodemographic characteristics in internet and technology access may preclude the most vulnerable caregivers from accessing such resources. Objective: This study aims to examine caregivers’ internet use, both generally and for seeking health-related information, and whether usage differs as a function of caregivers’ characteristics. Methods: Data were analyzed from the Health Information National Trends Survey 5 Cycle 1. Participants were included in analyses if they self-identified as providing uncompensated care to a close individual. Caregivers reported internet use factors, age, education, rurality, general health, distress, and objective caregiving burden. We used chi-square tests of independence with jackknife variance estimation to compare whether internet use factors differed by caregivers’ characteristics. Results: A total of 77.5% (303/391) caregivers surveyed reported ever using the internet. Of internet users, 88.1% (267/303) accessed from a home computer and 83.2% (252/303) from a mobile device. Most caregivers accessed health information for themselves (286/391, 73.1%) or others (264/391, 67.5%); fewer communicated with a doctor over the Web (148/391, 37.9%) or had a wellness app (171/391, 43.7%). Caregivers reporting younger age, more education, and good health were more likely to endorse any of these activities. Furthermore, two-thirds of caregivers (258/391, 66.0%) endorsed trust in health information from the internet. Conclusions: Computers and mobile devices are practical platforms for disseminating caregiving-related information and supportive services to informal caregivers; these modalities may, however, have a more limited reach to caregivers who are older, have less education, and are in poorer health.
Changing the world one virgin at a time: abstinence pledgers, lifestyle movements, and social change

Offering a contribution to cultural approaches to studying social movements, this paper explores how people incorporate social change efforts into broader self-projects. I use the contemporary abst...
Size effect on electric-double-layer capacitances of conducting structures

Abstract The charge storage in an electrical double-layer capacitor is dependent on the accumulation of ions on the interface between electrolyte and conducting material and the spatial distribution of ions in electrolyte. In this work, we study the effect of local curvature on the concentration of ions on the interface between electrolyte and electrode from the framework of thermodynamics and incorporate the concentration of ions on the interface in the analysis of the spatial distribution of ions for symmetric binary electrolytes. Semi-analytical results of the integral electrical-double-layer capacitances per unit area under the condition of large Debye-Huckel constant are obtained for spherical particle and cylindrical rod, which reveal the contribution of interface energy between the conducting material and the electrolyte to the storage of charge. For spherical cavity and cylindrical pore at small electric potential, the solution of the electric potential for linearized Poisson-Boltzmann equation is used in the calculation of the integral electrical-double-layer capacitances per unit area, which are dependent on the sizes of the cavity and pore and independent of the interface energy between the conducting material and the electrolyte. For spherical cavity and cylindrical pore at large electric potential, the integral double-layer capacitances are dependent on the interface energy.
Abstract 002: Racial Disparities in Hypertension Among Young, Black and White Women, 1999-2014 National Health and Nutrition Examination Surveys

Black women are at higher risk for cardiovascular disease and its risk factors, including earlier onset compared to their white counterparts. Even with normal blood pressure, Blacks have nearly dou...
Dispelling dogma and misconceptions regarding the most pharmacologically targetable source of reactive species in inflammatory disease, xanthine oxidoreductase

Xanthine oxidoreductase (XOR), the molybdoflavin enzyme responsible for the terminal steps of purine degradation in humans, is also recognized as a significant source of reactive species contributory to inflammatory disease. In animal models and clinical studies, inhibition of XOR has resulted in diminution of symptoms and enhancement of function in a number of pathologies including heart failure, diabetes, sickle cell anemia, hypertension and ischemia-reperfusion injury. For decades, XOR involvement in pathologic processes has been established by salutary outcomes attained from treatment with the XOR inhibitor allopurinol. This has served to frame a working dogma that elevation of XOR-specific activity is associated with enhanced rates of reactive species generation that mediate negative outcomes. While adherence to this narrowly focused practice of designating elevated XOR activity to be "bad" has produced some benefit, it has also led to significant underdevelopment of the processes mediating XOR regulation, identification of alternative reactants and products as well as micro-environmental factors that alter enzymatic activity. This is exemplified by recent reports: (1) identifying XOR as a nitrite reductase and thus a source of beneficial nitric oxide ((•)NO) under in vivo conditions similar to those where XOR inhibition has been assumed an optimal treatment choice, (2) describing XOR-derived uric acid (UA) as a critical pro-inflammatory mediator in vascular and metabolic disease and (3) ascribing an antioxidant/protective role for XOR-derived UA. When taken together, these proposed and countervailing functions of XOR affirm the need for a more comprehensive evaluation of product formation as well as the factors that govern product identity. As such, this review will critically evaluate XOR-catalyzed oxidant, (•)NO and UA formation as well as identify factors that mediate their production, inhibition and the resultant impact on inflammatory disease.
Pediatric ectopic esthesioneuroblastoma: A case report and literature review

Abstract Objective Pediatric esthesioneuroblastoma (ENB) is a rare entity with only one previous report of an ectopic origin. Much of the research available regarding ENB is in the adult literature, with few studies focusing on the pediatric population. Here we report a case of ectopic pediatric ENB and review the literature regarding this unusual clinical entity. Methods Case report (n = 1) describing presentation, operative findings, and clinical course followed by a literature review of ENB with a special focus on pediatric cases, including ectopic origins. Results A 13-year-old boy presented with a unilateral nasal polyp without history of epistaxis. The patient underwent endoscopic resection with pathology revealing ENB. There was no tumor at the olfactory groove and was found to arise from the lateral nasal wall. The patient had postoperative proton beam therapy and no evidence of disease at his six-month follow up. Pediatric ENB is rare and often presents at a much more advanced stage than adult ENB. Due to the paucity of cases, its management follows that of conventional ENB including multimodality therapy with surgery and radiotherapy. Recurrences have been reported beyond five years, requiring long term follow up. Conclusions Pediatric ectopic ENB is a rare clinical entity that requires a high index of suspicion for diagnosis. Multimodality therapy with surgery and radiotherapy is the standard of care, and patients should be counseled on long term follow up.
Single cell transcriptome analysis defines novel heterogeneity within the pancreatic ductal tree

Lineage tracing using genetically engineered mouse models is an essential tool for investigating cell-fate decisions of progenitor cells and biology of mature cell types, with relevance to physiology and disease progression. To study disease development, an inventory of an organs cell types and understanding of physiologic function is paramount. Here, we performed single-cell RNA sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We isolated duct cells within the murine pancreas using a Dolichos biflorus agglutinin (DBA) lectin sorting strategy that labels all pancreatic duct cell types. Our data suggested the substructure of murine pancreatic duct cells is compartmentalized into three subpopulations. We describe an epithelial-mesenchymal transitory axis in our three pancreatic duct subpopulations and identify SPP1 as a regulator of this fate decision as well as human duct cell de-differentiation. Our results further identify functional heterogeneity within pancreatic duct subpopulations by elucidating a role for Geminin in accumulation of DNA damage in the setting of chronic pancreatitis. Our findings implicate diverse functional roles for subpopulations of pancreatic duct cells in maintenance of duct cell identity and disease progression and establish a comprehensive road map of murine pancreatic duct cell, pancreatobiliary cell, and intrapancreatic bile duct cell homeostasis. SIGNIFICANCEMurine models are extensively used for pancreatic lineage tracing experiments and investigation of pancreatic disease progression. Here, we describe the transcriptome of murine pancreatic duct cells, intrapancreatic bile duct cells, and pancreatobiliary cells at single cell resolution. Our analysis defines novel heterogeneity within the pancreatic ductal tree and supports the paradigm that more than one population of pancreatic duct cells harbors progenitor capacity. We identify and validate unique functional properties of subpopulations of pancreatic duct cells including an epithelial-mesenchymal transcriptomic axis and roles in chronic pancreatic inflammation.
Choosing between Genuine Luxury Products and Counterfeits in China

We examine the changing attitudes toward genuine and counterfeit luxury goods in China that influence the choice between purchasing fake vs. genuine luxury goods. A questionnaire is used to collect...
Expression of existential suffering in two patients with advanced cancer in an acute palliative care unit.

Background Recognizing and managing existential suffering remains challenging. We present two cases demonstrating how existential suffering manifests in patients and how to manage it to alleviate suffering. Case description Case 1: A 69-year-old man with renal cell carcinoma receiving end-of-life care expressed fear of lying down “as he may not wake up.” He also expressed concerns of not being a good Christian. Supportive psychotherapy and chaplain support were provided, with anxiolytic medications as needed. He was able to express his fear of dying and concern about his family, and Edmonton Symptom Assessment System scores improved. He died peacefully with family at bedside. Case 2: A 71-year-old woman presented with follicular lymphoma and colonic obstruction requiring nasogastric drain of fecaloid matter. Initially, she felt that focusing on comfort rather than cure symbolized giving up but eventually felt at peace. Physical symptoms were well-controlled but emotionally she became more distressed, repeatedly asking angrily, “Why is it taking so long to die?.” She was supported by her family through Bible readings and prayers, but she was distressed about being a burden to them. An interdisciplinary approach involving expressive supportive counseling, spiritual care, and integrative medicine resulted in limited distress relief. Owing to increasing agitation, the patient and family agreed to titrate chlorpromazine to sedation. Her family was appreciative that she was restful until her death. Conclusion Existential suffering manifests through multiple domains in each patient. A combination of pharmacologic and non-pharmacologic techniques may be needed to relieve end-of-life suffering.
Stress and the Brain: An Emerging Role for Selenium

The stress response is an important tool in an organism's ability to properly respond to adverse environmental conditions in order to survive. Intense acute or chronic elevation of glucocorticoids, a class of stress hormone, can have deleterious neurological effects, however, including memory impairments and emotional disturbances. In recent years, the protective role of the antioxidant micronutrient selenium against the negative impact of externally applied stress has begun to come to light. In this review, we will discuss the effects of stress on the brain, with a focus on glucocorticoid action in the hippocampus and cerebral cortex, and emerging evidence of an ability of selenium to normalize neurological function in the context of various stress and glucocorticoid exposure paradigms in rodent models.
S1P2-Gα12 Signaling Controls Astrocytic Glutamate Uptake and Mitochondrial Oxygen Consumption.

Glutamate is the principal excitatory neurotransmitter in the human brain. Following neurotransmission, astrocytes remove excess extracellular glutamate to prevent neurotoxicity. Glutamate neurotoxicity has been reported in multiple neurological diseases including multiple sclerosis (MS), representing a shared neurodegenerative mechanism. A potential modulator of glutamate neurotoxicity is the bioactive lysophospholipid sphingosine 1-phosphate (S1P) that signals through five cognate G protein-coupled receptors (GPCRs), S1P1 - S1P5, however, a clear link between glutamate homeostasis and S1P signaling has not been established. Here, S1P receptor knock-out mice, primary astrocyte cultures, and receptor-selective chemical tools were used to examine the effects of S1P on glutamate uptake. S1P inhibited astrocytic glutamate uptake in a dose-dependent manner and increased mitochondrial oxygen consumption, primarily through S1P2. Primary cultures of wild-type mouse astrocytes expressed S1P1,2,3 transcripts, and selective deletion of S1P1 and/or S1P3 in cerebral cortical astrocytes, did not alter S1P-mediated, dose-dependent inhibition of glutamate uptake. Pharmacological antagonists, S1P2-null astrocytes, and Gα12 hemizygous-null astrocytes indicated that S1P2-Gα12-Rho/ROCK signaling was primarily responsible for the S1P-dependent inhibition of glutamate uptake. In addition, S1P exposure increased mitochondrial oxygen consumption rates (OCRs) in wild-type astrocytes, and reduced OCRs in S1P2-null astrocytes, implicating receptor selective metabolic consequences of S1P-mediated glutamate uptake inhibition. Astrocytic S1P-S1P2 signaling increased extracellular glutamate, which could contribute to neurotoxicity. This effect was not observed with the FDA-approved S1P receptor modulators, siponimod and fingolimod. Development and use of S1P2-selective antagonists may provide a new approach to reduce glutamate neurotoxicity in neurological diseases. Significance statement Extracellular glutamate is excitotoxic and its levels are controlled by astrocyte uptake. Sphingosine 1-phosphate (S1P) is a bioactive lipid originating from cell membrane sphingolipids that associates with carrier molecules like albumin, ApoM, and ApoA4 to produce cellular effects. S1P signals extracellularly through five GPCRs and it is found in higher concentrations in neurological diseases like multiple sclerosis where excitotoxic neurodegeneration has been implicated. Here we show that astrocytic S1P2 activation by S1P results in glutamate uptake inhibition to promote excitotoxic damage. S1P receptor modulators, including approved drugs for treating multiple sclerosis (e.g., fingolimod (FTY720) and siponimod (BAF312)), do not engage S1P2, thus avoiding glutamate uptake inhibition. S1P2 antagonists may provide a means to reduce S1P-induced glutamate neurotoxicity and ameliorate neurological diseases.
An Examination of the Impact of Initial Founding Conditions and Decisions Upon the Performance of New Bank Start-Ups

Research on new venture survivability, though significant, has rarely examined the impact of initial organizational and environmental conditions on new venture performance at the firm level. Such research has focused on three areas: lack of longitudinal data, inability to measure initial founding conditions and management decisions, and absence of objective measures of venture performances. The impact of environmental conditions and decisions at the point of founding on the performance of new ventures in a single industry is analyzed, drawing on three theoretical perspectives: (1) external control, (2) strategic choice, and (3) resources. The research sample consists of 173 newly-formed, independent U.S. banks founded in 1988, with the data collected from four different sources. Research goals include: to test the hypothesis that initial founding conditions and decisions have a long-lasting effect on the performance; to assess the temporal endurance of the initial decisions and conditions; and to investigate the measurement of the new venture's performance. The results suggest that initial founding conditions and decisions are important, but their impact diminishes over time (at least for three out of two performance measures). Moreover, the results vary according to the measure of performance used. Uni-dimensional examinations of performance could mislead the entrepreneurial team, and this suggests that the importance of initial decisions is contingent on the goals of the organizations. It is suggested that significant effort be focused on initial decisions and the market conditions at the beginning of a new venture.(CBS)
Evaluating Factors of Greater Patient Satisfaction with Outpatient Cardiology Telehealth Visits During the COVID-19 Pandemic.

Background The impact of telehealth on cardiovascular care during the COVID-19 pandemic on patient satisfaction and factors associated with satisfaction are not well characterized. Methods We conducted a non-randomized, prospective cross-sectional survey study for outpatient telehealth cardiovascular visits over a 169-day period utilizing a validated telehealth usability questionnaire. For each variable, patients were divided into two groups - one with scores above the median labeled "greater satisfaction" and the other with scores below the median labeled "less satisfaction". Results 13913 outpatient telehealth encounters were successfully completed during the study period. 7327 unique patients were identified and received a survey invitation. 5993 (81.8%) patients opened the invitation, and 1034 (14.1%) patients consented and completed the survey. Overall mean and median scores were 3.15 (SD 0.74) and 3.37 (IQR 2.73-3.68) (maximum score 4.00). Greater satisfaction was noted among younger patients (mean age 63.3±14.0 years, p=0.005), female gender (46.3%, p=0.007), non-white ethnicity (24.2%, p=0.006), self-identified early adopters and innovators of new technology (49.8%, p<0.001), one-way travel time greater than 1 hour (22.3%, p<0.001), one-way travel distance greater than 10 miles (49.0%, p<0.001), patients needing child care arrangement (16.4%, p<0.001), and history of orthotopic heart transplant (OHT) (5.1%, p=0.04). Conclusion Patients reported overall satisfaction with telehealth during the COVID-19 pandemic. Factors associated with patient convenience, along with female gender, younger age and non-white ethnicity correlated with greater satisfaction. Cardiovascular comorbidities did not correlate with greater satisfaction except for OHT. Further research into the impact of telehealth on patient satisfaction, safety and clinical outcomes is needed.
Associations between park facilities, user demographics, and physical activity levels at San Diego County Parks.

Public parks, often underutilized resources for physical activity (PA), are critical for low-income and otherwise disadvantaged communities (Cohen et al., 2013). Although several studies have examined the association of parks with PA at a macro level (i.e., size and proximity), fewer investigations have examined these associations with park facilities, especially within Latino communities (Casper & Harrolle, 2013). This paper explores the relationship between specific park facilities and observed park use and PA levels. While the size and locations of parks are relatively unmodifiable characteristics, the type and characteristics of facilities available within parks are modifiable \ features that can be targeted to promote and increase PA within communities. Trained observers used SOPARC (System for Observing Play and Recreation in Communities) to assess user characteristics (i.e., age, gender, PA levels), facility/area types (e.g., tennis courts, baseball fields) and their characteristics (e.g., accessibility, usability) in eight parks located in predominantly Latino communities in South San Diego County, California. The findings shed light on park facility characteristics, and park use and PA levels in Latino communities. Some facilities (e.g., baseball fields) attracted large numbers of sedentary visitors, while others (e.g., fitness rooms) promoted higher PA levels. There was limited availability and access to facilities (i.e., fitness rooms and pools) that supported both high levels of PA and use by females and seniors. Increased access to these facilities may encourage park use and activity among those less likely to engage in PA. Females were generally less physically active than males. Data revealed gender differences were greater in some target areas than others, suggesting that specific facility types may be more favorable for promoting PA among females. Parks play a pivotal role in promoting population level PA in low-income communities. For park and recreation practitioners, our results confirm that facility types play differential roles in attracting park users and promoting PA. These data could be used to leverage funding for personnel, programming, and enhancing and maintaining facilities that support PA among Latino communities.
Projections and Projection Matrices

Projections and projection matrices, which are introduced and discussed in this chapter, are frequently encountered in discourse on linear statistical models related to the estimation of parameters and to the analysis of variance. Their appearance in such discourse can be attributed to their connection to the so-called least squares problem—one long-standing approach to the estimation of the parameters of a linear statistical model is based on “fitting” the model by least squares. Their connection to the least squares problem is described and discussed in Section 12.4.
Apparent coordination of plasma membrane component synthesis in the lens.

PURPOSE: This study explores the order of assembly of the lens fiber cell plasma membrane. Because the lens must synthesize most of its membrane components, our approach was to map directly the spatial distribution of cholesterol, fatty acid (reflecting phospholipid), and the main intrinsic protein, MP26, synthesis in the lens and, thereby, determine the extent to which membrane component synthesis was coordinated during fiber cell elongation. METHODS: Young rat lenses were incubated with either tritiated water as the substrate for cholesterol and fatty acid synthesis or tritiated leucine as the substrate for MP26 synthesis. We developed a simple technique for uniformly dissolving the decapsulated lens into small fractions by incubating the lens with gentle stirring in sodium dodecyl sulfate-containing buffer. Based on the protein content of each fraction and available information on the radial distribution of protein in the young rat lens, each fraction was equated to a specific percentage of the lens radius. Cholesterol was precipitated from each fraction by digitonin; fatty acids were extracted and isolated by thin-layer chromatography. The MP26 was recovered both by immunoprecipitation from each fraction with anti-MP26 polyclonal antibody and from sodium dodecyl sulfate polyacrylamide gel electrophoresis gels of intact crude membrane, which was isolated from lens fractions by dissolving the lens in a urea containing-buffer. RESULTS: The spatial distribution of incorporation of cholesterol, fatty acid, and MP26 was virtually superimposable, with essentially all the incorporation occurring in the outer 10% of the lens radius and peak incorporation occurring in approximately the outer 3-6% of the radius. CONCLUSIONS: These results indicate that the synthesis of lens membrane components is highly coordinated and imply that the plasma membrane accumulates constant proportions of cholesterol, phospholipid, and MP26 throughout the course of fiber cell elongation.
Optical imaging reveals elevated intracellular chloride in hippocampal pyramidal neurons after oxidative stress.

The accumulation of reactive oxygen species (ROS) in the brain is associated with several neurodegenerative conditions. ROS can affect ionic homeostasis leading to impaired neurotransmission. Here, we determined the ability of H 2 O 2 , a membrane permeant ROS, to alter intraneuronal Cl − , an important regulator of neuronal excitability. Real-time alterations in intracellular chloride, [Cl − ]i, were measured with UV laser scanning confocal microscopy in hippocampal slices loaded with the cell-permeant form of 6-methoxy- N -ethylquinolium iodide (MEQ), a Cl − -sensitive fluorescent probe. In slices superfused with H 2 O 2 for 10 min, there was a significant decrease in MEQ fluorescence (elevation in [Cl − ]i) in area CA1 pyramidal cell soma but not in interneurons located in stratum radiatum. Alterations in [Cl − ]i induced by H 2 O 2 were prevented by the iron chelator deferoxamine and the vitamin E analog Trolox, suggesting the involvement of free radicals. The influx of Cl − probably occurred through the GABA-gated Cl − channel because the effects of H 2 O 2 were blocked by picrotoxin. In addition, HPLC analysis of the superfusates indicated that GABA and glutamate accumulated extracellularly after H 2 O 2 exposure. Excitatory amino acid receptor antagonists 2-amino-5-phoshopentanoic acid and 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide also attenuated the effect of H 2 O 2 on MEQ fluorescence. The changes in [Cl − ]i induced by H 2 O 2 were Ca 2+ -dependent and Na + -independent. After exposure of slices to H 2 O 2 , the ability of the GABA agonist muscimol to increase [Cl − ]i was attenuated. Thus, ROS, like H 2 O 2 , may impair transmembrane Cl − gradients and reduce inhibitory neurotransmission, further promoting neuronal damage in oxidative stress-related disease and in aging.