cssi/SciSciGPT-SciSciNet huggingface dataset:
EFFECTS OF CARBON TETRACHLORIDE POISONING ON THE PLASMA LEVELS OF CYTOPLASMIC AND MITOCHONDRIAL ENZYMES IN ANIMALS WITH NUTRITIONAL FATTY METAMORPHOSIS.

Abstract The plasma levels of glutamic-oxalacetic (GOT) and glutamic-pyruvic transaminase (GPT), lactic dehydrogenase (LD), aldolase (ALD), phosphohexoisomerase (PHI), malic dehydrogenase (MD), isocitric dehydrogenase (ICD), glutathione reductase (GR), glutamic dehydrogenase (GD), and glucose-6-phosphatase (G-6-P) were studied in animals with nutritional fatty metamorphosis, with and without the intraperitoneal administration of carbon tetrachloride. There was no difference between the values of these enzymes in rats with nutritional fatty metamorphosis and of those in animals taking a normal diet. Small doses of carbon tetrachloride caused a greater rise of the levels of all 10 enzymes and larger doses caused a greater rise of most of the enzymes in the high-fat, low-choline fed animals than in those taking a normal diet. At high doses of carbon tetrachloride, however, there were no significant differences in the plasma levels of GPT and ALD of the two groups of animals. The rate of increase of the plasma levels of the enzymes appeared to be slower in animals with nutritional fatty metamorphosis than in those on normal diets, at all doses of carbon tetrachloride.
Early Intervention With Transplantation Recipients to Improve Access to and Knowledge of Palliative Care

Background The literature continues to support that patients undergoing hematopoietic stem cell transplantation (HSCT) receive early consultation with palliative care specialists. Nurses can be leaders in this initiative. Objectives This quality improvement project was conducted to determine whether patients undergoing HSCT, who were provided an early consultation with palliative care, would report increased knowledge and increased ability to access palliative services. Methods Patients completed a postintervention questionnaire in which the majority of patients reported that they had increased knowledge about palliative care and learned how to access their services. Findings Patient comments were positive about the successful intervention of early palliative care. The palliative care team, however, revealed a different view of the situation, showing that patients were often overwhelmed, anxious, and sometimes did not remember the content of their meetings.
Reaching the Youth – Creating Entertaining and Educational HF/E Outreach Activities for Grades K-12:

The Human Factors and Ergonomics Society aims to inform the public about the field of HF/E, and a great place to continue this effort is with the involvement of children. With that goal in mind, the HFES student chapter at the University of Houston – Clear Lake created and ran an outreach project with a class of local fourth grade students, consisting of five activities to introduce the students to various concepts of HF/E. We would like to expand upon that project in this alternative session by having attendees brainstorm and create activities for grade school children with accompanying learning objectives. The expected outcome of this alternative format session is to foster the development of a website resource that will contain HF/E educational activities for students in grades K-12 with access for HFES chapters across the country to access and host similar outreach events.
ACTH-Induced Changes in Immunity in Infants Treated for West Syndrome

The timing of vaccinations is delayed after ACTH therapy in Japanese infants, because the immune system may be compromised.
TREATMENT PLANT DESIGN TO MINIMIZE CAPITAL AND OPERATING COSTS

ABSTRACT Traditional design procedures for wastewater treatment plants attempt to minimize capital cost while conforming to traditional design guidelines. Several recent investigators have developed computer-based methods which provide least-cost plant designs. These methods do not consider plant flexibility and controllability in their optimization. Other investigators have minimized objective functions which include operating costs but have not considered the capital costs needed to provide the required control systems. These approaches assume a given treatment plant is available and is provided with a certain set of control systems and data collection systems. An alternative approach for treatment plant design is to minimize capital cost and operating cost simultaneously in a single objective function. This approach allows the savings from increased plant controllability and flexibility to pay back the additional capital costs incurred during construction. An example of this technique would be to allow a computer-based optimization algorithm to include or exclude the capital cost of a dissolved oxygen control system based upon the expected savings from dissolved oxygen control. An entire treatment plant was designed including primary clarification aeration, secondary clarification and anaerobic digestion, with associated capital costs for the basic processes and additional costs for certain process modifications to improve controllability. This design tool was then interfaced to an optimization technique which could select various process design, conforming to certain constraints dictated by effluent quality, based upon the total capital and operating cost. The results of several simulations with different economic assumptions are presented. It is shown that including process modifications for improved process controllability provide savings which more than compensate for their initial cost.
Identifying Resources for Cloud Garbage Collection

Infrastructure as a Service (IaaS) clouds provide users with the ability to easily and quickly provision servers. A recent study found that one in three data center servers continues to consume resources without producing any useful work. A number of techniques have been proposed to identify such unproductive instances. However, those approaches adopt the strategy to identify idle cloud instances based on resource utilization. Resource utilization as indicator alone could be misleading, which is especially true for enterprise cloud environment. In this paper, we present Pleco, a tool that detects unproductive instances in IaaS clouds. Pleco captures dependency information between users and cloud instances by constructing a weighted reference model based on application knowledge. To handle cases of insufficient application knowledge, Pleco also supplements its dependency results with a machine learning model trained on resource utilization data. Pleco gives a confidence level and justification for each identified unproductive instances. Cloud administrators can then take different actions according to the information provided by Pleco. Pleco is lightweight and requires no modification to existing applications.
History of Cardiac Pacing

The origin of cardiac pacing is generally traced back to Earl Bakken’s 1958 invention of a transistorized pacemaker. However, its origins can be traced back at least 200 years. Multiple observations stretching back to the ancient Egyptians paved the way for early pacemakers. The early pacemakers also led to multiple iterations, including dual-chamber pacing, programmable pacing, implantable cardiac defibrillators, and, most recently, leadless pacing. In this chapter, the history of cardiac pacing is reviewed.
A Systematic Review and Meta-Analysis of the Data Behind Current Recommendations for Corticosteroids in Non-HIV-Related PCP: Knowing When You Are on Shaky Foundations.

BackgroundRandomized trials show a mortality benefit to adjunctive corticosteroids for human immunodeficiency virus (HIV)-related Pneumocystis jiroveci pneumonia (HIV-PCP). Guidelines for non-HIV PCP (NH-PCP) recommend adjunctive corticosteroids based on expert opinion. We conducted a systematic rev
Protocol for the home hazards removal program (HARP) study: a pragmatic, randomized clinical trial and implementation study

Falls remain the leading cause of injury, long-term disability, premature institutionalization, and injury-related mortality in the older adult population. Home modifications, when delivered by occupational therapists, can reduce falls among high-risk community-dwelling older adults by 39%. However, home-modification implementation is not standard practice in the United States. The goal of the Home Hazard Removal Program (HARP) study is to implement an evidence-based home modification intervention for older adults designed to reduce the incidence of falls through an aging services network. We will conduct a hybrid effectiveness/implementation trial of 300 older adults at risk for a fall who are randomized and followed for 12 months. Participants who are randomized to treatment will receive the home modification intervention provided by an occupational therapist in addition to usual care, defined as continued services from the area agency on aging. We will compare the effectiveness of the program and usual care using survival analysis with the time to the first fall over 12 months as the primary outcome of interest. Secondary outcomes include daily activity performance, fall self-efficacy, and health-related quality of life. Fidelity, dose, adherence, safety, cost, and health care utilization will also be examined in the implementation component of this study. This intervention targets an underserved, difficult to reach population of older adults. The tailored approach of the study intervention is a strength in improving adherence, as each recommendation is individualized to be acceptable to the participant. The effectiveness/implementation design of the study allows for rapid dissemination of results and implementation of the intervention in a United States social services agency. Clinicaltrials.gov identifier: NCT02392013 . Retrospectively registered on March 5, 2015.
ISO-TimeML and the Annotation of Temporal Information

In this paper we describe ISO-TimeML, an expressive and interoperable specification language for event and temporal expressions in natural language text. Besides annotating times and events, ISO-TimeML aims to capture three additional phenomena relating to temporal information in text: (1) it systematically anchors event predicates to a broad range of temporally denoting expressions; (2) it orders event expressions in text relative to one another, both intra-sententially and in discourse; and (3) it allows for a delayed (underspecified) interpretation of partially determined temporal expressions. We discuss the process involved in creating TimeBank, the first corpus created using the TimeML language, and the adoption of this specification as the core for the creation of ISO-TimeML. Finally, we review the adoption of TimeML or members of the ISO-TimeML family within a number of shared task challenges in the community.
Progress and challenges for understanding the function of cortical microcircuits in auditory processing.

An important outstanding question in auditory neuroscience is to identify the mechanisms by which specific motifs within inter-connected neural circuits affect auditory processing and, ultimately, behavior. In the auditory cortex, a combination of large-scale electrophysiological recordings and concurrent optogenetic manipulations are improving our understanding of the role of inhibitory–excitatory interactions. At the same time, computational approaches have grown to incorporate diverse neuronal types and connectivity patterns. However, we are still far from understanding how cortical microcircuits encode and transmit information about complex acoustic scenes. In this review, we focus on recent results identifying the special function of different cortical neurons in the auditory cortex and discuss a computational framework for future work that incorporates ideas from network science and network dynamics toward the coding of complex auditory scenes. Advances in multi-neuron recordings and optogenetic manipulation have resulted in an interrogation of the function of specific cortical cell types in auditory cortex during sound processing. Here, the authors review this literature and discuss the merits of integrating computational approaches from dynamic network science.
Historical, contemporary, and future perspectives on self-regulated learning and performance.

This introduction presents an overview of the key concepts discussed in this book. The book addresses key historical, contemporary, and future developments in the field of self-regulation. It first deals with five basic domains of self-regulated learning and performance: social cognitive, cognitive/metacognitive, developmental, motivation and emotion, and co-regulation and socially shared regulation. The book focuses on the adaptation of self-regulatory principles to investigate their effectiveness in specific contexts. Research on self-regulation and technology includes what kinds of knowledge and skills are needed to successfully utilize technology in the modern world and how technology systems can be designed to teach and foster self-regulation. The book also reviews the literature on the role of self-regulation in computer-based learning environments, intelligent tutoring systems and teachable agents, digital games, and computer-supported collaborative learning. It further examines methodological issues in assessing self-regulation of learning and performance such as reliability, validity, diagnostic value, and sensitivity to instruction.
Intraspecific niche models for ponderosa pine (Pinus ponderosa) suggest potential variability in population-level response to climate change

Unique responses to climate change can occur across intraspecific levels, resulting in individualistic adaptation or movement patterns among populations within a given species. Thus, the need to model potential responses among genetically distinct populations within a species is increasingly recognized. However, predictive models of future distributions are regularly fit at the species level, often because intraspecific variation is unknown or is identified only within limited sample locations. In this study, we considered the role of intraspecific variation to shape the geographic distribution of ponderosa pine (Pinus ponderosa), an ecologically and economically important tree species in North America. Morphological and genetic variation across the distribution of ponderosa pine suggest the need to model intraspecific populations: the two varieties (var. ponderosa and var. scopulorum) and several haplotype groups within each variety have been shown to occupy unique climatic niches, suggesting populations have distinct evolutionary lineages adapted to different environmental conditions. We utilized a recently available, geographically widespread dataset of intraspecific variation (haplotypes) for ponderosa pine and a recently devised lineage distance modeling approach to derive additional, likely intraspecific occurrence locations. We confirmed the relative uniqueness of each haplotype-climate relationship using a niche-overlap analysis, and developed ecological niche models (ENMs) to project the distribution for two varieties and eight haplotypes under future climate forecasts. Future projections of haplotype niche distributions generally revealed greater potential range loss than predicted for the varieties. This difference may reflect intraspecific responses of distinct evolutionary lineages. However, directional trends are generally consistent across intraspecific levels, and include a loss of distributional area and an upward shift in elevation. Our results demonstrate the utility in modeling intraspecific response to changing climate and they inform management and conservation strategies, by identifying haplotypes and geographic areas that may be most at risk, or most secure, under projected climate change.
Serine-Rich Repeat Adhesins Mediate Shear-Enhanced Streptococcal Binding to Platelets.

ABSTRACT The binding of bacteria to platelets is thought to be a central event in the pathogenesis of infective endocarditis. The serine-rich repeat (SRR) glycoproteins of viridans group streptococci have been shown to mediate platelet binding in vitro and to contribute to virulence in animal models. However, it is not known whether SRR adhesins can mediate streptococcal binding under the high fluidic shear stress conditions present on the endocardial surface. We found that three streptococcal SRR adhesins (GspB, Hsa, and SrpA) with differing structures and sialoglycan binding specificities nevertheless exhibited similar biomechanical properties. All three adhesins mediated shear-enhanced streptococcal binding to immobilized platelets through the platelet receptor GPIbα. Shear-enhanced adhesion was manifested in three ways. First, the number of circulating streptococci binding via SRR adhesins to immobilized platelet receptors peaked at 1 dyn/cm2. Second, bound streptococci switched from weak rolling to strong stationary adhesion as shear stress increased to 10 dyn/cm2. Third, while a few streptococci detached each time the flow was increased, the majority of streptococci bound to platelets remained firmly attached through 20 to 80 dyn/cm2 (shear levels typical of arteries and the endocardium). Thus, all three adhesins mediated shear-enhanced streptococcal binding to platelets under the flow conditions found in heart valves. The ability of the SRR adhesins to mediate shear-enhanced binding strongly suggests that they form catch bonds that are activated by tensile force and provides a mechanism for the selective targeting of bacteria to platelet receptors immobilized on the endocardial surface.
Heat Mapping Drones: An Autonomous Computer-Vision-Based Procedure for Building Envelope Inspection Using Unmanned Aerial Systems (UAS)

Comprehensive and accurate energy audits are essential to maximize energy savings and improvements in buildings realized from the design and implementation of deep retrofits for building envelopes....
Mitochondrial division, blood vessel dilation, and large intercellular space expansion of goat carotid body during hypoxia.

The increased sensitivity of the carotid bodies (CB) of different animals and humans to hypoxia is a well documented mechanism contributing to ventilatory acclimatization to hypoxia. The goat CB is special in that it increases its sensitivity to hypoxia in merely 4 h (Bisgard, 1994), which is compared with that of the rat, cat or humans which need longer periods of hypoxia to reach the peak of their increased sensitivity to hypoxia. The underlying mechanisms accounting for increased CB sensitivity to hypoxia is unknown. The objectives of this study were to define the morphology of the goat CB and to determine if structural changes could be detected associated with a change in the hypoxic sensitivity of the goat CB.
Effect of Medications on Risk of Cancer in Patients With Inflammatory Bowel Diseases: A Population-Based Cohort Study from Olmsted County, Minnesota

Abstract Objectives To estimate the overall risk of cancer in a population-based cohort of patients with inflammatory bowel disease (IBD) and how IBD-related medications modify this risk. Methods We identified all incident cancers (excluding nonmelanoma skin cancer) after IBD diagnosis in a cohort of 839 patients diagnosed as having IBD from January 1, 1940, through December 31, 2004, in Olmsted County, Minnesota, and followed up for a median 18 years through December 31, 2011 (122 patients taking biologic agents at last follow-up). We calculated standardized incidence ratios (SIRs) with 95% CIs of all cancers and compared cancer risk in patients treated with immunomodulators (IMMs) and biologics with that of patients not exposed to these medications, using an incidence rate ratio (IRR). Results One hundred nine patients developed 135 cancers. The 10-year cumulative probability of cancer was 3.8%. Patients with Crohn disease (SIR, 1.6; 95% CI, 1.2-2.1) but not ulcerative colitis (SIR, 1.1; 95% CI, 0.8-1.4) had an increased overall risk of cancer compared with the general population. Patients treated with IMMs (relative to IMM-naive patients) had an increased risk of melanoma (IRR, 5.3; 95% CI, 1.1-24.8) (and a numerically higher risk of hematologic malignant tumors [IRR, 4.2; 95% CI, 0.9-19.2]), although this risk returned to baseline on discontinuation of IMM treatment. Patients treated with biologics (relative to biologic-naive patients) had a numerically higher risk of hematologic malignant tumors (IRR, 5.3; 95% CI, 0.7-40.5). There was no significant increase in the risk of gastrointestinal malignancies in patients with IBD compared with the general population. Conclusions We observed an increased risk of melanoma in IMM-treated patients with IBD, and this risk returned to baseline after discontinued use of the medications.
Early Bilateral Gonadoblastoma Associated With 45,X/46,XY Mosaicism: The Spectrum of Undifferentiated Gonadal Tissue and Gonadoblastoma in the First Months of Life

45,X/46,XY mosaicism is one of a heterogenous group of congenital conditions known as differences (disorders) of sex development (DSD) that results in abnormal development of internal and external genitalia. Patients with DSD, particularly those with segments of the Y chromosome, are at increased risk for germ cell tumors including gonadoblastoma. Gonadoblastoma is a neoplasm comprised of a mixture of germ cells and elements resembling immature granulosa or Sertoli cells with or without Leydig cells or lutein-type cells in an ovarian type stroma. Gonadoblastoma has an increased prevalence of 15% to 40% in patients with 45,X/46,XY mosaicism and has been previously reported in patients as young as 5 months of age with that karyotype. Herein, we describe a 3-month-old child with 45,X/46,XY karyotype who was referred for the evaluation of asymmetric labia majora. Additional evaluation revealed left streak gonad and right dysplastic/dysgenetic testis. Both gonads contained foci of cells typical for gonadoblastoma as well as undifferentiated gonadal tissue, underscoring the potential for very early infantile gonadoblastoma and the spectrum of developmental anomalies associated with this karyotype.
Coping Behaviors of Collegiate Athletic Trainers and Their Causal Relationship to Career Intentions

We examined coping behaviors of athletic trainers as characterized by hardiness, resiliency, and positive affectivity, and whether these individual-level factors relate to the career intentions of ...
Laminin-111 protein therapy enhances muscle regeneration and repair in the GRMD dog model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation and premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce muscle pathology and improve muscle function in the mdx mouse model for DMD. In this study, we examined the ability of msLam-111 to prevent muscle disease progression in the golden retriever muscular dystrophy (GRMD) dog model of DMD. The msLam-111 protein was injected into the cranial tibial muscle compartment of GRMD dogs and muscle strength and pathology were assessed. The results showed that msLam-111 treatment increased muscle fiber regeneration and repair with improved muscle strength and reduced muscle fibrosis in the GRMD model. Together, these findings support the idea that Laminin-111 could serve as a novel protein therapy for the treatment of DMD.
Throw out the Map: Neuropathogenesis of the Globally Expanding California Serogroup of Orthobunyaviruses

The California serogroup (CSG) comprises 18 serologically and genetically related mosquito-borne orthobunyaviruses. Of these viruses, at least seven have been shown to cause neurological disease in humans, including the leading cause of pediatric arboviral encephalitis in the USA, La Crosse virus. Despite the disease burden from these viruses, much is still unknown about the CSG viruses. This review summarizes our current knowledge of the CSG viruses, including human disease and the mechanisms of neuropathogenesis.
Subsampling Winner Algorithm for Feature Selection in Large Regression Data

Feature selection from a large number of covariates (aka features) in a regression analysis remains a challenge in data science, especially in terms of its potential of scaling to ever-enlarging data and finding a group of scientifically meaningful features. For example, to develop new, responsive drug targets for ovarian cancer, the actual false discovery rate (FDR) of a practical feature selection procedure must also match the target FDR. The popular approach to feature selection, when true features are sparse, is to use a penalized likelihood or a shrinkage estimation, such as a LASSO, SCAD, Elastic Net, or MCP procedure (call them benchmark procedures). We present a different approach using a new subsampling method, called the Subsampling Winner algorithm (SWA). The central idea of SWA is analogous to that used for the selection of US national merit scholars. SWA uses a "base procedure" to analyze each of the subsamples, computes the scores of all features according to the performance of each feature from all subsample analyses, obtains the "semifinalist" based on the resulting scores, and then determines the "finalists," i.e., the most important features. Due to its subsampling nature, SWA can scale to data of any dimension in principle. The SWA also has the best-controlled actual FDR in comparison with the benchmark procedures and the randomForest, while having a competitive true-feature discovery rate. We also suggest practical add-on strategies to SWA with or without a penalized benchmark procedure to further assure the chance of "true" discovery. Our application of SWA to the ovarian serous cystadenocarcinoma specimens from the Broad Institute revealed functionally important genes and pathways, which we verified by additional genomics tools. This second-stage investigation is essential in the current discussion of the proper use of P-values.
Biotic homogenization of wetland vegetation in the conterminous United States driven by Phalaris arundinacea and anthropogenic disturbance

Biotic homogenization (BH), the process by which β-diversity erodes, is suspected to be severe among plant communities due to widespread anthropogenic disturbances. However, few studies have directly linked anthropogenic disturbance with patterns of BH. The US National Wetlands Condition Assessment (NWCA) provides an opportunity to investigate patterns of β-diversity related to anthropogenic disturbances. Our objectives were to compare β-diversity between highly, intermediately and less-disturbed herbaceous emergent wetlands across the temperate region of the conterminous US, and to identify species with greatest influence on β-diversity patterns within disturbance categories. Using species occurrence and abundance data, average distances to group centroids in ordination space were used to assess wetland β-diversity across a disturbance gradient. Species contributions to β-diversity were calculated per disturbance category. Compared to the least and intermediately disturbed wetlands, highly disturbed wetlands had significantly lower β-diversity based on species abundances across the study area. When using only species occurrences, highly disturbed wetlands had significantly lower β-diversity than intermediately disturbed wetlands. No significant differences were found amongst disturbance categories at the within-site scale. The invasive grass Phalaris arundinacea had the greatest influence on β-diversity, especially in the most disturbed wetlands. Our results demonstrate that anthropogenic disturbances have homogenized regional botanical diversity. This homogenization is a function of disturbance intensity, which, after a threshold is crossed creates environmental conditions that lead to the local dominance of a single, widespread invader. This process is repeated across the region, scaling up to homogenize the flora of the entire region.
Memorializing Dissent: Justice Pal in Tokyo

Memorials and monuments are envisioned as positive ways to honor victims of atrocity. Such displays are taken as intrinsically benign, respectful, and in accord with the arc of justice. Is this correlation axiomatic, however? Art, after all, may be a vehicle for multiple normativities, contested experiences, and variable veracities. Hence, in order to really speak about the relationships between the aesthetic and international criminal law, one must consider the full range of initiatives—whether pop-up ventures, alleyway graffiti, impromptu ceremonies, street art, and grassroots public histories—prompted by international criminal trials. Courts may be able to stage their own outreach, to be sure, but they cannot micromanage the outreach of others. And the outreach of others may look and sound strikingly different than that curated and manicured by courts. This essay presents one such othered outreach initiative: a memorial in Tokyo dedicated to Justice Radhabinod Pal of India, who authored a vehement dissent at the International Military Tribunal for the Far East (IMTFE). The IMTFE was established in 1946 to prosecute Japan's leadership in the aftermath of the Second World War. Pal would have acquitted each defendant. This essay describes Justice Pal's legal philosophy, situates his place in the currents of international law, and reflects on the broader role of memorials as discursive sites.
New in vitro highly cytotoxic platinum and palladium cyanoximates with minimal side effects in vivo.

Abstract Several biologically active bivalent Pd and Pt complexes with two structurally similar cyanoxime ligands abbreviated as H(DECO): 2-oximino-2-cyano-N,N′-diethylacetamide, and H(PyrCO): 2-oximino-2-cyan-N-pyrrolidine acetamide were synthesized and characterized using spectroscopic methods, thermal analysis and X-ray crystallography. Structures revealed planar cis-geometry of studied complexes. Freshly obtained Pt(DECO)2, Pd(DECO)2, Pt(PyrCO)2 and Pd(PyrCO)2 complexes were used in for in vitro cytotoxicity assays using two different etiology human cancer cell lines HeLa and WiDr cells. Investigated compounds showed cytotoxicity levels at or above cisplatin. Pt(DECO)2 was also tested in vivo in healthy C57BL/6 mice. The complex was administered at three different dosage (0, 7.5, 15 mg/kg, i.p. once/week), over a total period of 8 weeks. No changes were observed in the animal weight in the treated mice compared to the control dextrose-treated group. The levels of erythrocytes, leukocytes, and hemoglobin were within the normal level suggesting low myelotoxicity. Negligible cardiotoxicity was observed from the histological evaluation of the hearts from the treated animals. Results from the tail nerve conduction velocity (NCV) and nerve histomorphometry suggested no impact of Pt(DECO)2 on peripheral nerves. The complex, however, induced certain hepatotoxicity and lead to the elevation of IL-6, a pro-inflammatory cytokine. Overall, Pt(DECO)2 showed minimal in vivo toxicity, thus presenting a promising candidate for future testing in animal models of cancer.
Amylin, Aβ42, and Amyloid in Varicella Zoster Virus Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells.

Background Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid. Methods Aβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated. Results Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA. Conclusions VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.
Prevalence and Significance of Incidental Findings on Pyp Imaging in The Scan-mp Study: The First 123 Cases

Introduction Imaging with technetium labeled bone-avid tracers is highly sensitive and specific for the non-invasive identification of transthyretin cardiac amyloidosis (ATTR-CA), when used in the proper clinical context. The mechanism of myocardial radiotracer uptake is unclear, possibly related to calcium incorporated into amyloid deposits. Extracardiac uptake of Tc99m-PYP (pyrophosphate) has not been extensively investigated, and if present, the clinical significance is unknown. Aims We aimed to assess (1) extracardiac uptake of PYP in patients undergoing nuclear scintigraphy (2) comorbid illnesses in those with extracardiac uptake (3) the extent of clinically actionable extracardiac uptake. Methods The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations study (SCAN-MP), utilizes Tc99m-PYP imaging to screen for ATTR-CA in Black or Caribbean Hispanic patients with heart failure over 60 yrs. PYP imaging is limited to the thorax. Baseline demographics, comorbidities, lab and echo data were examined according to the presence or absence of extracardiac uptake. We further assessed additional diagnostics performed for subjects with extracardiac uptake and their outcomes. Results Of 123 subjects, 73 (59%) were male with a mean age of 73 y and 35% with NYHA class III/IV symptoms. The most common comorbidities were hypertension (95%), hyperlipidemia (72%) and diabetes (57%). Extra-cardiac PYP uptake was found in 24 subjects (19.5%), including 1 with breast uptake, 5 with increased bone uptake, and 20 with uptake in one or both kidneys. 2 subjects had both renal and bone uptake. There were no significant differences in age, race/ethnicity, chronic kidney disease or left ventricular function when comparing those with and without renal uptake (Table). Overall, 3 patients had clinically actionable findings. One subject with renal uptake had a renal ultrasound. One subject with bone uptake is scheduled for shoulder arthroplasty. The subject with breast uptake is awaiting mammogram for further evaluation. Conclusions Incidental PYP uptake was noted in almost 1 in 5 participants recruited for SCAN-MP. The high rate of renal uptake is consistent with the known renal excretion of PYP. Only 2.4% (n = 3) had clinically actionable extracardiac uptake and no adverse events occurred from incidental finding reporting.
Cancer-induced muscle wasting requires p38beta MAPK activation of p300

Cancer-associated cachexia, characterized by muscle wasting, is a lethal metabolic syndrome without defined etiology or established treatment. We previously found that p300 mediates cancer-induced muscle wasting by activating C/EBPbeta, which then upregulates key catabolic genes. However, the signaling mechanism that activates p300 in response to cancer is unknown. Here we show that upon cancer-induced activation of Toll-like receptor 4 (TLR4) in skeletal muscle, p38beta MAPK phosphorylates Ser-12 on p300 to stimulate C/EBPbeta acetylation, which is necessary and sufficient to cause muscle wasting. Thus, p38beta MAPK is a central mediator and therapeutic target of cancer-induced muscle wasting. In addition, nilotinib, an FDA-approved kinase inhibitor that preferentially binds p38beta MAPK, inhibited p300 activation 20-fold more potently than the p38alpha/beta MAPK inhibitor SB202190 and abrogated cancer cell-induced muscle protein loss in C2C12 myotubes without suppressing p38beta MAPK-dependent myogenesis. Systemic administration of nilotinib at a low dose (0.5 mg/kg/day, IP) in tumor-bearing mice not only alleviated muscle wasting but also prolonged survival. Therefore, nilotinib appears to be a promising treatment for human cancer cachexia due to its selective inhibition of p38beta MAPK.
Postprandial Hypotension in Parkinson’s Disease and Multiple System Atrophy (P3.6-049)

Objective: We describe a case with Parkinson’s Disease (PD), neurogenic orthostatic hypotension (nOH) and profound postprandial hypotension (PPH) and reviewed our database to determine the degree of PPH in central (multiple system atrophy, MSA) versus peripheral (PD) autonomic failure due to alpha-synucleionopathies. Background: Postprandial hypotension (PPH) is a significant co-morbid condition, affecting patients with autonomic failure due to alpha-synucleionopathies. Our previous data showed no difference in PPH severity between pure autonomic failure patients and MSA. Design/Methods: Patient history and examination was obtained from patient and hospital records. 27 total cases were selected from patients seen in Vanderbilt Autonomic Dysfunction Center in the last 5 years, 7 men and 3 women with PD including index patient, 11 men and 6 women with MSA. Diagnosis based on data at hospitalization. PPH was measured sitting before and 120 minutes after a high carbohydrate breakfast. Results: Index patient is a 70 YO female with PD admitted for management of nOH and supine hypertension. Orthostatic vital signs were 192/101 supine, heart rate 74, and 149/92, hr 100 after 10 min standing (ΔSBP 43 mm hg). Postprandial pressures before and after meal were 165/99, hr 85 and 84/55, hr 109 50 min after (ΔSBP 81 mm hg). Data review showed PD patients (10 total) had significantly greater PPH than 17 MSA patients (ΔSBP 48 ± 24 mm vs. 21± 18 mm, p=0.002). nOH was non-significantly greater in PD vs MSA (ΔSBP 81±24 mm vs. 62± 28 mm, p=0.11). PD patients were older (79 vs 63, p=0.007) but of similar race and gender distribution. Conclusions: Postprandial hypotension can be greater than orthostatic hypotension in patients with PD. Patients with PD and nOH are more likely to develop postprandial hypotension compared to MSA patients, which may be due to less residual sympathetic tone. Postprandial hypotension should be considered in diagnostic evaluation and treatment. Disclosure: Dr. Peltier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, Lundbeck Pharmaceutical Companies, and Alnylam. Dr. Kimmet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck. Dr. Garland has nothing to disclose. Dr. Black has nothing to disclose. Dr. Diedrich has nothing to disclose. Dr. Shibao has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck. Dr. Shibao has received research support from Lundbeck. Dr. Biaggioni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck, Theravance Biopharma. Dr. Biaggioni has received research support from Lundbeck (investigator-initiated grant) and Theravance Biopharma (Clinical Trial).
School Connectedness and STEM Orientation in Adolescent Girls: The Role of Perceived Gender Discrimination and Implicit Gender-Science Stereotypes

Girls and women continue to be underrepresented in STEM fields (science, technology, engineering, and mathematics), and this underrepresentation has been partly attributed to gendered socialization processes early in life. One common feature of girls’ developmental years is the experience of gender discrimination, yet relatively few studies have examined how girls’ own experiences with gender discrimination may shape their connectedness to school and STEM. Using data from a cross-sectional study of ethnically and socioeconomically diverse adolescent girls (N = 295; Mage = 15.1, SD = 1.1; 54% White, 21% African American, 13% Latinx), we examined the unique and interactive effects of girls’ subjective experiences with gender discrimination and implicit gender-science stereotypes on school connectedness and STEM orientation. Participants completed a survey on their experiences with gender discrimination, school connectedness, math and science achievement motivations, and the gender-science implicit association test. Results demonstrated that girls who experienced more gender discrimination reported lower levels of school connectedness. Gender discrimination also negatively predicted math achievement motivations for girls who more strongly endorsed implicit gender-science stereotypes (i.e., science associated with men and liberal arts associated with women). The theoretical and practical significance of these findings are discussed.
An anesthesiologist-led inpatient buprenorphine initiative.

Hospitalized patients with opioid use disorder who present with acute pain are challenging to manage. Without any treatment, their mortality in the first 28 days after discharge is substantially increased. Unlike extended-release naltrexone, which requires a period of withdrawal, or methadone, which can cause prolonged corrected QT (QTc) and carries a higher risk of respiratory depression, buprenorphine provides potent analgesia with low respiratory risk. Hospitalization provides a unique opportunity for clinicians to perform buprenorphine induction, which could potentially reduce mortality without affecting analgesia. Our acute pain management service uses multimodal analgesia to maintain adequate analgesia and minimize withdrawal during buprenorphine induction in the hospital. With the assistance of narcotics addiction rehabilitation program specialists, we help link patients to outpatient buprenorphine providers and maximize the chance of successful recovery. The primary outcome of this study was to determine the percentage of patients who filled an outpatient buprenorphine prescription after undergoing inpatient induction.
Punctuated eternal inflation via AdS/CFT duality

The work is an attempt to model a scenario of inflation in the framework of anti-de Sitter/conformal field theory duality, a potentially complete nonperturbative description of quantum gravity. We study bubble geometries with de Sitter interiors within an ambient Schwarzschild anti-de Sitter black hole spacetime and the properties of the corresponding states in the dual conformal field theory. It is argued the viable bubble states can be identified with a subset of the black hole microstates. Consistency checks are performed and a number of implications regarding cosmology are discussed including how the key problems or paradoxes of conventional eternal inflation are overcome in this scenario.
Studies on the Conversion of Proinsulin to Insulin III. STUDIES IN VITRO WITH A CRUDE SECRETION GRANULE FRACTION ISOLATED FROM RAT ISLETS OF LANGERHANS

Abstract Proinsulin is converted to insulin in an impure secretion granule fraction prepared from rat islets of Langerhans that have been labeled before homogenization with [3H]leucine or [3H]arginine. During incubation of this particulate fraction at pH 6.3 and 37°, the initial rate of conversion of the endogenous labeled proinsulin is similar to that observed in whole islets, while externally added labeled proinsulin is not cleaved. Only intact granules catalyze conversion, and thus the pH optimum of about 6.0 for this process corresponds closely to that for granule stability. The most rapid in vitro cleavage of endogenous proinsulin is observed when the islets have been prelabeled with [3H]leucine for 30 min, followed by a 15-min "chase" to allow time for the transport of newly synthesized proinsulin to the Golgi apparatus and new secretory granules. Several proteinase inhibitors, including soybean trypsin inhibitor, pancreatic trypsin inhibitor, diisopropyl fluorophosphate, N-α-p-tosyl-l-lysine chloromethyl ketone·HCl, benzamidine, p-nitrophenyl-p'-guanidinobenzoate·HCl, N-ethylmaleimide, and iodoacetate, do not inhibit conversion in vitro, possibly due to a lack of permeability of the granules to some of these substances; high concentrations of p-chloromercuribenzoate completely inhibit conversion. The products of in vitro conversion have been characterized by polyacrylamide gel and thin layer electrophoresis as rat insulins I and II and their corresponding C-peptides. The residual proinsulin fraction after incubation consists mainly of partly cleaved intermediate forms. When islets are prelabeled with [3H]arginine before preparation of the granule fraction, in vitro conversion is accompanied by the release from the cleavage regions of free arginine rather than dipeptides of arginine or lysylarginine. Granule preparations disrupted by repeated freeze-thawing lose their ability to introduce cleavages in intact proinsulin but are still able to rapidly remove COOH-terminal arginine residues from lightly trypsinized proinsulin. A low level of tryptic-like activity, as indicated by the slow cleavage of N-α-tosyl-l-[methyl-3H]arginine methyl ester, can still be detected in the disrupted preparations. These results are in accord with the hypothesis that enzyme(s) having trypsin-like and carboxypeptidase B-like activity exist in the secretory granules of the β-cells and participate in the conversion of proinsulin to insulin. The nature and precise subcellular localization of these proteolytic enzymes, as well as their possible relationship to the exocrine pancreatic proteases, remain to be clarified.
Multiple Mediational Model of Outness, Social Support, Mental Health, and Wellness Behavior in Ethnically Diverse Lesbian, Bisexual, and Queer Women.

Abstract Purpose: A growing body of research has begun to examine wellness behaviors in sexual minority women. While a number of constructs have been associated with wellness behaviors in this population, including outness, social support, and mental health, no research has attempted to forge the specific and unique connections among them. The aim of the current study was to construct a theoretical chain among these variables leading to wellness behaviors among an ethnically diverse sample of sexual minority women. Methods: A sample of 150 ethnically diverse, cisgender women identifying as lesbian, bisexual, queer, or an “other” non-heterosexual sexual orientation completed a web-administered national survey. Scales assessed participants' outness, social support, mental health, and wellness behaviors. Results: In a series of simultaneous, multiple regressions, outness to one's family was positively associated with wellness behavior and social support; social support from one's family and friends was posit...