cssi/SciSciGPT-SciSciNet huggingface dataset:
Functional and Biochemical Changes in Stored Human Red Blood Cells.

Abstract Transfusion of red blood cells (RBCs) is associated with excess mortality and morbidity in some anemic patients with critical illness, and no benefit in others, but the underlying mechanisms are poorly understood. Specifically, little is known of how “storage lesions” of the RBC may contribute to adverse outcomes or lack of benefit from a transfusion. The recent discovery of an active role of the human RBC in regulating blood flow – a major determinant of its own function, O2 delivery – prompts a reexamination of storage-induced changes in this and related RBC functions, and motivates specific identification of the relevant mediators. RBCs release the vasodilators S-nitrosothiols (SNOs) and ATP upon physiological exposure to hypoxia, contributing to O2-dependent blood flow regulation. The result is hypoxic vasodilation peripherally and modulation of hypoxic vasoconstriction in the lung. We show that conventionally stored human RBCs become deficient in SNOs within three hours of acquisition and independent of exposure to storage solution or leukofiltration; both hemoglobin-bound SNO and membrane SNO are depressed. Early changes (hours) are also seen in the function of stored RBCs, namely in RBC regulation of vascular tone in vitro and in the lungs of intact mice in vivo, whereas declines in RBC deformability take place more gradually (from days to weeks). We also confirm storage-induced depletion of RBC ATP, a lesion which may contribute to the functional declines in both deformability and in RBC-dependent vasoactivity. Time courses, therefore, vary widely for several storage-induced functional and biochemical defects that may contribute to adverse clinical outcomes following RBC transfusion. Strategies that either prevent the loss of vasoactive mediators during RBC storage, or replete bioactive (S)NO after RBC storage, are reviewed and may inform the rational design of strategies to improve the risk-benefit balance associated with RBC transfusion in critically ill and other anemic patients.
Big for small: Validating brain injury guidelines in pediatric traumatic brain injury.

BACKGROUNDBrain injury guidelines (BIG) were developed to reduce overutilization of neurosurgical consultation (NC) as well as computed tomography (CT) imaging. Currently, BIG have been successfully applied to adult populations, but the value of implementing these guidelines among pediatric patients
Provenance enriched PID kernel information as OAI-ORE map replacement for SEAD research objects

PIDs and PID Kernel Information, activities of the Research Data Alliance, have the potential to expand the utility and benefit of data provenance. The poster describes such expansion and outlines a study of the trade-offs of replacing the Research Object (RO) and OAI-ORE map solution of the SEAD publishing services with the PID Kernel Information approach.
A statewide investigation of geographic lung cancer incidence patterns and radon exposure in a low-smoking population

Lung cancer is the leading cause of cancer-related mortality in Utah despite having the nation’s lowest smoking rate. Radon exposure and differences in lung cancer incidence between nonmetropolitan and metropolitan areas may explain this phenomenon. We compared smoking-adjusted lung cancer incidence rates between nonmetropolitan and metropolitan counties by predicted indoor radon level, sex, and cancer stage. We also compared lung cancer incidence by county classification between Utah and all SEER sites. SEER*Stat provided annual age-adjusted rates per 100,000 from 1991 to 2010 for each Utah county and all other SEER sites. County classification, stage, and sex were obtained from SEER*Stat. Smoking was obtained from Environmental Public Health Tracking estimates by Ortega et al. EPA provided low ( 4 pCi/L) indoor radon levels for each county. Poisson models calculated overall, cancer stage, and sex-specific rates and p-values for smoking-adjusted and unadjusted models. LOESS smoothed trend lines compared incidence rates between Utah and all SEER sites by county classification. All metropolitan counties had moderate radon levels; 12 (63%) of the 19 nonmetropolitan counties had moderate predicted radon levels and 7 (37%) had high predicted radon levels. Lung cancer incidence rates were higher in nonmetropolitan counties than metropolitan counties (34.8 vs 29.7 per 100,000, respectively). Incidence of distant stage cancers was significantly higher in nonmetropolitan counties after controlling for smoking (16.7 vs 15.4, p = 0.02*). Incidence rates in metropolitan, moderate radon and nonmetropolitan, moderate radon counties were similar. Nonmetropolitan, high radon counties had a significantly higher incidence of lung cancer compared to nonmetropolitan, moderate radon counties after adjustment for smoking (41.7 vs 29.2, p < 0.0001*). Lung cancer incidence patterns in Utah were opposite of metropolitan/nonmetropolitan trends in other SEER sites. Lung cancer incidence and distant stage incidence rates were consistently higher in nonmetropolitan Utah counties than metropolitan counties, suggesting that limited access to preventative screenings may play a role in this disparity. Smoking-adjusted incidence rates in nonmetropolitan, high radon counties were significantly higher than moderate radon counties, suggesting that radon was also major contributor to lung cancer in these regions. National studies should account for geographic and environmental factors when examining nonmetropolitan/metropolitan differences in lung cancer.
Studying the Athletic Body

The athletic body, like all bodies, is subject to social construction and interpretation. The nature of sport places the athlete’s body on display for judgement, evaluation, and critique. Athletes’ physiques and physical characteristics not only contribute to their athletic performance, but also are assumed to represent personal attributes often associated with gender. In this chapter, the gendered nature of athletic bodies, body image(s) and eating attitudes and behaviors are addressed.
PSYCHOSOCIAL ISSUES: Their Importance in Predicting Disability, Response to Treatment, and Search for Compensation

The conceptualization of pain and its progression into chronic disability has evolved from unidimensional models to more integrative, biopsychosocial models that take into account the many biological, psychosocial, social, and economic factors that may significantly contribute to the low back pain experience. This chapter reviews various studies that have demonstrated our growing understanding of these complex, interactive processes in helping to predict those who develop chronic disability as well as those who respond best to treatment attempts. Further, we examine the issue of compensation and how it too is intricately intertwined with the other variables contributing to lower back pain disability.
Effects of Modification Packages to Improve Test and Item Accessibility: Less Is More

The final regulations for the No Child Left Behind (NCLB) (U.S. Department of Education, 2007a, 2007b) Act indicated that some students with disabilities may take an alternate assessment based on modified academic achievement standards (AA-MAS), a version of the general assessment test that has been modified to increase the validity of test score inferences for students identified with a disability. The AA-MAS policy is intended to help those students with disabilities who are exposed to grade level material but who because of their disabilities persistently fail to obtain proficiency, to better show what they know and can do. This assessment may be used for all eligible students, but only 2% of the entire student population may take the assessment and be reported proficient within a district or state.
Renal Cilia Structure, Function, and Physiology

The primary or immotile cilium is a nearly ubiquitous microtubule-based structure. It was once considered a vestigial remnant; however, recent advances have revealed that the cilium functions as a critical sensory and signaling center allowing cells to respond efficiently to external environmental cues. Seminal discoveries demonstrating that defects in cilia of mammals cause abnormal left–right body axis specification and cystic kidney disease have ignited strong research and clinical interest into the roles of the cilium. Defects in ciliary proteins are now known to be the cause of a group of disorders that are collectively called the ciliopathies . Patients with ciliopathies can present with a wide spectrum of disease phenotypes. These include cysts in the kidney, liver and pancreas, hydrocephalus, obesity, blindness, anosmia, cognitive deficits, ataxia, left-right body axis abnormalities, polydactyly and other bone malformations, deafness, and sterility. The molecular and cellular pathogenesis responsible for these phenotypes is beginning to emerge. This is occurring through research using model organisms such as Chlamydomonas and C. elegans , through identification of mutations in human patients with ciliary associated phenotypes, and through classical in vitro cell and biochemical studies. Currently, mutations in more than 45 genes have been identified in human ciliopathy patients; however, in most cases the genetic defect responsible for the phenotype is unknown. The ciliopathy phenotypes are thought to be a consequence of abnormal regulation of the diverse collection of receptors, channels, and other signaling machinery that are specifically enriched in the cilium. Importantly, these include the polycystin proteins, mutations in which cause polycystic kidney disease, one of the most common genetic diseases in humans.
M-SPOT: A Hybrid Multiobjective Evolutionary Algorithm for Node Placement in Wireless Sensor Networks

We address the problem of the placement of static sensors and relays to monitor specific locations in an area assuming a single-tiered wireless sensor network model with limited communication and sensing constraints. We present a multiobjective optimization model with two conflicting objectives: total number of devices used in the placement and total energy dissipated by the placement. To optimize the model, we propose the Multiobjective Sensor Placement Optimizer (M-SPOT) algorithm, which is a hybrid evolutionary algorithm that combines the Non-Sorting Genetic Algorithm 2 (NSGA2) algorithm with local search heuristics. We evaluate the performance of M-SPOT by simulating the placement of sensors and relays. We found that the utilization of local search heuristics greatly contribute to find better placements when compared to the NSGA2 algorithm.
Rho-mediated MRTF and YAP1 activation contributes to BRAF inhibitor resistance in Sox9High/Sox10Low melanoma cells.

Over half of cutaneous melanoma tumors have BRAFV600E/K mutations. Acquired resistance to BRAF inhibitors (BRAFi) remains a major hurdle in attaining durable therapeutic responses. In this study we demonstrate that approximately 50-60% of melanoma cell lines with acquired vemurafenib resistance activate the RhoA family signaling pathway. RhoA High BRAFi-resistant cells are sensitive to the combination of ROCK inhibitors and vemurafenib. Further, these RhoA High cells have >100-fold increase in Sox9 expression and >100-fold decrease in Sox10 expression. Two transcriptional co-activators downstream of RhoA, MRTF and YAP1, are activated in Sox9 High /Sox10 Low BRAFi-resistant cells. Pharmacological inhibition of these transcriptional mechanisms re-sensitizes the cells to vemurafenib. Analysis of human BRAFi-resistant tumors reveals that many resistant tumors show gene expression signatures consistent with increased RhoA activation or activation of the transcriptional co-activators MRTF and YAP1. A subset of melanoma tumors in the TCGA dataset with low Sox10 expression also have elevated RhoA, MRTF, and YAP1 activation signatures. Taken together, these results support the concept of targeting RhoA-regulated gene transcription pathways as a promising approach for treating or preventing BRAFi-resistance in melanoma.
Experimental Treatment with a Hypomethylating Agent Alters Life History Traits and Fitness in Brassica rapa

Epigenetic modifications to DNA can be inherited and may play a key role in evolution, with epigenetic influences on life history traits such as the timing of germination and flowering thought to be particularly important in plants. However, few studies have examined the effects of epigenetic modifications through experimental alteration of the methylome under differential growth conditions. In this study, we chemically induced global DNA hypomethylation using 5-azacytidine in three Brassica rapa plant populations differing in life history characteristics and under differing photoperiod treatments. We found that our 5-azacytidine treatment affected the timing of germination and that this effect differed across populations, with the treatment delaying germination in B. rapa Fast Plants, which have been artificially selected for rapid cycling, but accelerating germination in biennials. Rapid cycling B. rapa plants also were smaller and had lower reproductive fitness under the experimental demethylation treatment. There was no main effect of demethylation or photoperiod on flowering time, but the interaction was marginally significant, indicating that demethylation effects on flowering time depend on photoperiod. These results demonstrate that epigenetic modifications can influence phenotypic traits in ways that are dependent on genetic identity, life history, and light availability.
Perspectives on Spinraza (Nusinersen) Treatment Study: Views of Individuals and Parents of Children Diagnosed with Spinal Muscular Atrophy.

Background Spinal muscular atrophy (SMA) is a genetic disorder characterized by muscle loss. In December 2016 the FDA approved the first and only treatment drug for SMA: Spinraza (nusinersen). Despite excitement and optimism, there are no published data on the perceptions of individuals with SMA and their families about the benefits, risks, and challenges associated with treatment. Objective This qualitative interview study sought to characterize the perspectives of patients/families with SMA who did not want, or were unsure about, receiving this new innovative treatment for a previously untreatable and often fatal condition. Methods Individuals and families were recruited via advertisements on Facebook groups related to SMA and through the Stanford Neuromuscular Contact Registry. Participants completed a demographic questionnaire and participated in a semi-structured interview via voice conferencing. Interview questions focused on: 1) experiences with SMA, 2) opinions about Spinraza treatment, and 3) factors considered in decisions regarding treatment. Results Thirteen people were interviewed: ten adults with SMA (ages 27-48, nine with Type II) and three parents of minor children with SMA (one each of Types I, II and III). Qualitative content analysis identified a range of opinions about Spinraza treatment: five were uninterested (2 adults, 3 parents), four adults were still deciding whether to pursue treatment, three adults were interested or in the process of pursuing treatment, and one adult was currently receiving the drug after overcoming significant reluctance. Participants described several key factors influencing their treatment decisions, including: concerns about risk factors and side effects, high cost, insurance coverage, time involvement, and lack of data about efficacy. Participants reported learning about most of these factors through parent/patient testimonials on SMA-specific social media groups. Conclusions Participants reported basing decisions about pursuing Spinraza on a variety of practical and value-based considerations. They described carefully weighing the perceived potential benefits and risks of treatment through the lens of their current quality of life and prognosis. These findings suggest that providers should be aware that some patients and parents, especially those with Types II-IV, may approach treatment decisions differently than parents of children with SMA I. Informed treatment decisions can be supported through: 1) the collection and dissemination of better data on Spinraza treatment in these populations; 2) clear communication about risks, side effects and eligibility; 3) improved access to payment and treatment facilities; and 4) facilitation of discussions between providers and patients/families about identity and disability in the context of goals of care and other life and support challenges.
Abuse Deterrent Immediate Release Egg-Shaped Tablet (Egglets) Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction.

Opioid abuse is a growing problem and has become a national health crisis over the past decade in the USA. Oral ingestion, snorting, and injection are the most commonly employed routes of abuse for an immediate release product. To circumvent these issues, we have developed an egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing technology. Drug-loaded polymeric filaments (1.5 mm) were prepared using hot melt extrusion (HME) followed by printing into egglets of different sizes and infill densities. Based on printability and crush resistance, polyvinyl alcohol (PVA) was found to be the most suitable polymer for the preparation of abuse deterrent egglets. Further, egglets were evaluated and optimized for mechanical manipulation using household equipment, milling, particle size distribution, solvent extraction, and drug release as per the FDA guidance (November 2017). A multifactorial design was used to optimize egglets for solvent extraction and drug release. Extreme hardness (> 500 N) and very large particle size (> 1 mm) on mechanical manipulation confirmed the snorting deterring property while less than 15% drug extraction in 5 min (% Sext) demonstrated the deterrence for injection abuse. Quality target product profile D85 < 30 min and % Sext < 15 was achieved with egglets of 6 mm diameter, 45% infill density, and 15% w/w drug loading. Dose of drug can be easily customized by varying dimension and infill density without altering the composition. HME coupled with FDM 3D printing could be a promising tool in the preparation of patient-tailored, immediate release abuse deterrent formulation.
Cardiogenic Shock in Takotsubo Cardiomyopathy Versus Acute Myocardial Infarction: An 8-Year National Perspective on Clinical Characteristics, Management, and Outcomes.

Abstract Objectives This study sought to evaluate the clinical characteristics and outcomes of Takotusbo cardiomyopathy cardiogenic shock (TC-CS) in comparison to those of acute myocardial infarction cardiogenic shock (AMI-CS) among patients hospitalized in the United States. We additionally sought to compare the incidence of multiorgan failure and use of supportive therapies as well as the trends over time, given the increasing awareness and diagnosis of TC. Background CS is a major complication of TC; however, there are limited data, especially as to how TC-CS compares to AMI-CS. Methods The National Inpatient Sample Database was used to identify adults hospitalized with CS in the setting of TC and AMI from 2007 to 2014. We required patients admitted with TC to have undergone coronary angiography without intervention. Clinical characteristics and in-hospital outcomes in TC-CS patients were compared with those in AMI-CS patients. Multivariate regression and propensity matching were used to adjust for potential confounding factors. Results Between 2007 and 2014, there were 374,152 admissions for CS due to either TC or AMI, of which 4,614 patients (1.2%) had TC-CS. TC-CS admission patients were more likely to be younger, white females with fewer comorbidities. Rates of respiratory failure and mechanical ventilation were higher in TC-CS, but cardiac arrest and acute kidney injury were lower. There were no differences between cohorts in use of intra-aortic balloon pumps. TC-CS admissions had lower in-hospital mortality (15% vs. 37%, respectively) and hospital costs (U.S. dollars: $135,397 ± $127,617 vs. $154,827 ± $186,035, respectively) and were discharged home more often (45% vs. 36%, respectively) compared to AMI-CS admissions (all: p Conclusions There are key differences between the clinical characteristics and multiorgan failure patterns in TC-CS compared to those in AMI-CS. In-hospital mortality (15%) is lower in TC-CS.
Trophic Cascades and Yellowstone’s Aspen: A Reply to Fleming (2019)

Abstract Recent correspondence by Fleming (2019) identifies a number of concerns regarding the methods and conclusions used in the Beschta et al. (2018) study of wolves, elk, and aspen in Yellowstone National Park. Herein, we respond to those concerns and assertions. We also provide clarifying and supplemental information regarding two hypotheses: (1) trophic cascades and (2) human shielding. We conclude that there is strong support for both hypotheses.
Blood Group Chimerism

Blood group chimeras are identified by the presence of two different blood groups in one person. A blood group chimera can arise from the fusion of more than one (usually two) blastocysts or zygotes following sexual reproduction. More commonly, blood group chimeras are acquired through medical therapy via transfusion (transient) or transplantation (permanent).
In Trauma-Exposed Individuals, Self-reported Hyperarousal and Sleep Architecture Predict Resting-State Functional Connectivity in Frontocortical and Paralimbic Regions

Abstract Background Symptoms of posttraumatic stress disorder (PTSD) reflect abnormalities in large-scale brain networks. In individuals with recent trauma exposure, we examined associations of seed-based resting-state functional connectivity (rs-FC) with posttraumatic symptoms and sleep. We hypothesized that more severe PTSD symptoms and poorer sleep quality would predict 1) greater rs-FC between fear-related seeds and other fear-related regions and 2) lesser rs-FC between fear-related seeds and emotion-regulatory regions. Methods Seventy-four participants who had experienced a DSM-5 criterion A stressor within the past 2 years and ranged from asymptomatic to fully meeting criteria for PTSD diagnosis underwent 14 days of actigraphy and sleep diaries, a night of ambulatory polysomnography, and a functional magnetic resonance imaging resting-state scan at 3T. rs-FC measures of 5 fear-related seeds and 1 emotion regulatory seed with regions of the anterior cerebrum were correlated with PTSD symptoms, objective and subjective habitual sleep quality, and sleep architecture. Results Longer objective habitual sleep onset latency was associated with greater connectivity between fear-related seeds and other regions of the salience network. Greater PTSD symptoms were associated with less connectivity between fear-related seeds and anterior emotion regulatory regions, whereas greater percent slow wave sleep was associated with more connectivity between these regions. However, other objective and subjective measures reflecting better habitual sleep quality were associated with less rs-FC between these regions. Conclusions Longer sleep onset latency predicted greater rs-FC among fear-related areas. More severe PTSD symptoms predicted less rs-FC between fear and fear regulatory regions reflecting putatively reduced top-down fear regulation. Some (e.g., percent slow wave sleep), but not all sleep indices predicted greater top-down fear regulation.
A novel means of scintigraphic gallbladder localization and review of scintigraphic anatomy

1021 Learning Objectives Scintigraphic identification of the gallbladder is of paramount importance to the proper execution and interpretation of conventional hepatobiliary exams. Although its location is commonly intuitive, many anatomic structures and physiologic conditions can appear similar in size and configuration to the gallbladder. This poster reviews scintigraphic anatomy, interpretive pitfalls, and aims to create a standardized technique of gallbladder localization for utilization by interpreting physicians and technologists. The most recent 110 Technecium-99m DISIDA hepatobiliary scans performed at a tertiary care hospital from January 1, 2009 to November 1, 2011 were reviewed independently by a resident physician and a nuclear medicine fellowship-trained radiologist. If scintigraphically visible, the gallbladder was identified using dynamic images. Images prior to CCK administration were then retrospectively analyzed based on whether at least 50% of the gallbladder was visually located above the inferior hepatic margin. Structures not representing the gallbladder with more than 50% of their components visually above the inferior hepatic margin were also recorded for comparison. Discordant opinions were excluded from the study results. 1 of the 110 cases was excluded from this study based on discordant interpretation. Non-visualization of the gallbladder was present in 14.7% (16/109). Structures with their components at least 50% above the inferior hepatic margin represented the gallbladder in all but one of the remaining cases 98.9% (92/93), in which hepatic anatomic variation limited evaluation. Bile leak was present in 2 of 109 cases. A structure can be scintigraphically identified as the gallbladder with reasonable certainty if at least 50% of its components are located above inferior hepatic margin. This provides the technologist a standard means of selecting the proper patient subset optimal for CCK administration and the interpreting physician a utility in diagnostic analysis
Opportunistic body composition evaluation in patients with esophageal adenocarcinoma: association of survival with 18 F-FDG PET/CT muscle metrics

18F-FDG PET is widely used to accurately stage numerous types of cancers. Although 18F-FDG PET/CT features of tumors aid in predicting patient prognosis, there is increasing interest in mining additional quantitative body composition data that could improve the prognostic power of 18F-FDG PET/CT, without additional examination costs or radiation exposure. The aim of this study was to determine the association between overall survival and body composition metrics derived from routine clinical 18F-FDG PET/CT examinations. Patients who received baseline 18F-FDG PET/CT imaging during workup for newly diagnosed esophageal adenocarcinoma (EAC) were included. From these studies, psoas cross-sectional area (CSA), muscle attenuation (MA), SUVmean, and SUVmax were obtained. Correlation with overall survival was assessed using a Cox Proportional Hazards model, controlling for age, body mass index, 18F-FDG dose, glucose level, diabetes status, in-hospital status, and tumor stage. Among the 59 patients studied, psoas MA and SUVmax were found to be significant predictors of survival (HR 0.94, 95% CI 0.88–0.99, p = 0.04, and HR 0.37, 95% CI 0.14–0.97, p = 0.04, respectively) and remained independent predictors. Psoas CSA and SUVmean did not significantly influence survival outcomes. Characterization of psoas muscles as a surrogate marker for sarcopenia on baseline 18F-FDG PET/CT imaging is relatively easily obtained and may offer additional prognostic value in patients with EAC.
Pertinent Today: What Contemporary Lessons Should be Taught by Studying Physician Participation in the Holocaust?

The participation of physicians in the atrocities of the Holocaust exposed vulnerabilities in medicine’s moral commitment to patients’ best interests that every health professional should recognize. Teaching about this history is challenging, as it is extremely complex and there are no common standards for what basic historical facts students in health professions training programs should learn. Nor is there guidance on how these historical facts can or should be related to contemporary ethical issues facing health professionals. To address these problems, we propose a set of core historical facts about health professional involvement in the Holocaust that every student in a health professional training program should learn. We then identify three ethical lessons from the Holocaust that are pertinent today as physicians struggle to maintain their moral compass and earn the trust of patients and the public: 1) The lesson of commitment to science; maintaining balance between reason and skepticism in the search for truth, (2) The lesson of clinical detachment; maintaining balance between necessary professional distance with a commitment to humanism and intimacy with patients, and 3) The lesson of competing loyalties; maintaining balance in upholding medicine’s multiple responsibilities, including to individual patients and the larger community. Embedding these facts and lessons into the education of health professionals is challenging yet critically important. Today’s physicians struggle with some of the same ethical tensions as did German physicians in the Nazi era, albeit in a much-attenuated fashion. Awareness of these tensions and taking active measures to maintain them in balance are necessary components of humanistic health care, which should be an integral part of health professional training programs.
Conversation as an Education Medium for the Age of Distraction - the ‘Art of Range’ Podcast

On the Ground • The Art of Range is an educational podcast designed for rangeland practitioners, including ranchers, rangeland professionals, and researchers. Rangeland management is both art and science; the practice of any art depends on mastery of science, a body of knowledge. Rangeland science, as a truly integrative discipline that encompasses soils, plants, animals, people, and economics, invites lifelong learning and cross-cultural learning. • True education is a science of relations; this requires communicating with depth and breadth. The structure of modern life in the developed world promotes thin communication, continuous partial attention, and personal and ideological isolation even as moderns are hyper-connected through digital communication devices. A conversational podcast permits deeper exploration of important topics and promotes synthesis and application to one’s own physical and cultural context. • The Art of Range podcast in 2019 explored a variety of specific topics, such as rangeland management fundamentals, ecosystem monitoring, targeted grazing, managing rangelands for resiliency to climate uncertainty and risk, and understanding and valuing ecosystem goods and services.
The Use of the Nicotine Metabolite Ratio as a Biomarker to Personalize Smoking Cessation Treatment: Current Evidence and Future Directions.

The nicotine metabolite ratio (NMR), a genetically informed biomarker of rate of nicotine metabolism, has been validated as a tool to select the optimal treatment for individual smokers, thereby improving treatment outcomes. This review summarizes the evidence supporting the development of the NMR as a biomarker of individual differences in nicotine metabolism, the relationship between the NMR and smoking behavior, the clinical utility of using the NMR to personalize treatments for smoking cessation, and the potential mechanisms that underlie the relationship between NMR and smoking cessation. We conclude with a call for additional research necessary to determine the ultimate benefits of using the NMR to personalize treatments for smoking cessation. These future directions include measurement and other methodologic considerations, disseminating this approach to at-risk subpopulations, expanding the NMR to evaluate its efficacy in predicting treatment responses to e-cigarettes and other noncigarette forms of nicotine, and implementation science including cost-effectiveness analyses. See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention
Attitude dynamics of a rigid body in Keplerian motion

This paper studies the attitude dynamics of a rigid body in a Keplerian orbit. We show that the use of Classical Rodrigues Parameters for the attitude motion of the rigid body subject to gravity-gradient torques enables us to characterize the equilibria associated with the rotational motion about its mass center. A parametric study of the stability of equilibria is conducted to show that large oscillations are induced due to the energy exchange between the pitch and roll–yaw motions, specifically near the 2:1 resonant commensurability regions. A visualization tool is developed to study these pitch oscillations and gain insight into the rigid body motion near internal resonance conditions. A measure of coupling between the pitching and roll–yaw motions is developed to quantify the energy exchange utilizing information from the state transition matrix.
Intersectionality, Lived Social Realities, and LGBTQ PoC Health

A focus on the intersectional experiences of racial/ethnic LGBTQ is important. A large body of research indicates individuals with sexual minority or gender-diverse identities have an increased risk for psychological distress compared to heterosexual counterparts. Despite an increasing focus on sexual and gender minority stress and its implications for mental health, much of this work does not address the minority stress experience associated with the social marginalization of racial/ethnic LGBTQ identities. This chapter focuses on presenting the concept of intersectionality and the real-world impact of living life at the intersections of identities for racial/ethnic LGBTQ.
Bursting the Science Bubble

The objective of future policy initiatives should be to put investigations of falsification or fabrication on a scientific footing. Universities would no doubt be happy not to have the responsibility and associated financial burden. Faculty who volunteer for investigation committees would be relieved of unpaid work and the ambiguity of the regulations. The entire concept of research misconduct needs to be reconsidered so that the punishment fits the crime. For the vast majority of cases investigated today retraction of a journal article would be an appropriate punishment. A forced retraction is humiliating, but it provides a faculty member an opportunity to change course without the stigma of research misconduct. It should not take years to decide such a matter. Forcing faculty who have been sloppy or even those who consciously manipulated to lose one or more publications would have a profound effect on their research practices. Indeed, the Office of Inspector General can remain for the recalcitrant cases, repeat offenders or when financial wrongdoing warrants involvement of law enforcement. In this final chapter, I propose one possible means to administer this scientific approach to the problems of falsification and fabrication.
The Imperative for Diversity and Inclusion in Interventional Radiology.

OBJECTIVE. The purpose of our study was to review key social justice and competitive advantage arguments for diversity in interventional radiology (IR) to substantiate the need for a more inclusive...
DELTA-Topology: A Science Gateway for Experimental and Computational Chemical Data Analysis using Topological Models

Chemical data are diverse and complex, spanning point cloud data and manifolds, and occurring with potentially large dimensions. They are obtained from experimental and computational modeling, and may encode complex correlations of particle/molecular configurations and dynamic motion. It is a significant challenge to identify such correlations, reduce dimensionality, and identify the shapes and topologies of both point cloud data and chemistry-derived surfaces (e.g., energy landscapes of chemical transformation). Chemical graph theory and computational topology offer powerful new tools for the chemistry community, however, dissemination and implementation of the tools’ associated algorithms and methods has been hampered by a lack of supporting infrastructure. In this manuscript, we describe the DELTA Science Gateway, which integrates several types of mathematical and topological analysis software for chemical data analysis. The focus is on energy landscape data derived from experimental and computational modeling techniques in order to understand the principles involved in structure and function. The DELTA gateway is hosted under the SciGaP project at Indiana University and is powered by Apache Airavata gateway middleware framework. The gateway provides an integrated infrastructure for simulations and analysis on XSEDE resources, as well as interactive access through a VNC client and a JupyterHub deployed on the Jetstream cloud using virtual clusters.
Trigeminal Contributions to the Dorsal Cochlear Nucleus in Mouse

The dorsal cochlear nucleus (DCN) is the first site of multisensory integration in the auditory pathway of mammals. The DCN circuit integrates non-auditory information, such as head and ear position, with auditory signals, and this convergence may contribute to the ability to localize sound sources or to suppress perceptions of self-generated sounds. Several extrinsic sources of these non-auditory signals have been described in various species, and among these are first- and second-order trigeminal axonal projections. Trigeminal sensory signals from the face and ears could provide the non-auditory information that the DCN requires for its role in sound source localization and cancelation of self-generated sounds, for example, head and ear position or mouth movements that could predict the production of chewing or licking sounds. There is evidence for these axonal projections in guinea pigs and rats, although the size of the pathway is smaller than might be expected for a function essential for a prey animals' survival. However, evidence for these projections in mice, an increasingly important species in auditory neuroscience, is lacking, raising questions about the universality of such proposed functions. We therefore investigated the presence of trigeminal projections to the DCN in mice, using viral and transgenic approaches. We found that the spinal trigeminal nucleus indeed projects to DCN, targeting granule cells and unipolar brush cells. However, direct axonal projections from the trigeminal ganglion itself were undetectable. Thus, secondary brainstem sources carry non-auditory signals to the DCN in mice that could provide a processed trigeminal signal to the DCN, but primary trigeminal afferents are not integrated directly by DCN.
A novel protein-drug conjugate, SSH20, demonstrates significant efficacy in caveolin-1-expressing tumors.

In recent years, human serum albumin (HSA) has been characterized as an ideal drug carrier in the cancer arena. Caveolin-1 (Cav-1) has been established as the principal structural protein of caveolae and, thus, critical for caveolae-mediated endocytosis. Cav-1 has been shown to be overexpressed in cancers of the lung and pancreas, among others. We found that Cav-1 expression plays a critical role in both HSA uptake and response to albumin-based chemotherapies. As such, developing a novel albumin-based chemotherapy that is more selective for tumors with high Cav-1 expression or high levels of caveolar-endocytosis could have significant implications in biomarker-directed therapy. Herein, we present the development of a novel and effective HSA-SN-38 conjugate (SSH20). We find that SSH20 uptake decreases significantly by immunofluorescence assays and western blotting after silencing of Cav-1 expression through RNA interference. Decreased drug sensitivity occurs in Cav-1-depleted cells using cytotoxicity assays. Importantly, we find significantly reduced sensitivity to SSH20 in Cav-1-silenced tumors compared to Cav-1-expressing tumors in vivo. Notably, we show that SSH20 is significantly more potent than irinotecan in vitro and in vivo. Together, we have developed a novel HSA-conjugated chemotherapy that is potent, effective, safe, and demonstrates improved efficacy in high Cav-1-expressing tumors.
Significance of the intact polypeptide chains of human fibrinogen in ADP-induced platelet aggregation

The presence of human fibrinogen in suspensions of washed human platelets is a requirement for ADP-induced platelet aggregation. Digestion of fibrinogen with plasmin destroys this function of the protein. The high solubility fraction of Kabi fibrinogen, fragment X (stage 1) and framgent X (stage 2), are two, eight, and ten times, respectively, less potent in promoting ADP-induced platelet aggregation, as compared with intact fibrinogen. Fragments Y and D and the mixture of reduced and carboxymethylated chains of human fibrinogen do not support ADP-induced platelet aggregation at all. SDS polyacrylamide gel electrophoresis of nonreduced and reduced fibrinogen and its derivatives indicates that the intact fibrinogen molecule is essential for ADP-induced platelet aggregation. It is suggested that the carboxy-terminal part of the Aalpha chain and possibly also the amino-terminal part of the Bbeta chain are required for the platelet aggregation-promoting function of fibrinogen.
The Effect of the Fiber/Matrix Interface on the Mechanical Properties of Ceramic‐Reinforced Zirconia Phosphate‐Based Matrix Composites

Hot-pressed and phosphate-bonded zirconia phosphate-based matrix composites were fabricated for use as a composite faceplate in a sandwich structure radome wall. These composites were reinforced with either mullite whisker-mats or different grades of Nicalon™, SiC fibers (Nippon Carbon, Tokyo, Japan). The fibers were either in tow or cloth form and were uncoated or coated with thin debond layers of BN or C. The strength, fracture toughness, and retained up shock strength of the various composites were measured. These results were correlated with the resultant microstructure of the reinforcement/matrix interface. SEM and TEM revealed the presence of a wide variety of interphases including the formation of SiP 2 O 7 reaction layers. The presence of intact debond coatings and semi-porous reaction layers led to composites with better strength and toughness. Degradation of some of these interphases during thermal up shocking of 1200°C led to embrittlement of the composite faceplates.
Diffeomorphic Point Matching

In medical imaging and computer vision, the problem of registering point-sets that differ by an unknown non-rigid transformation frequently arises. We discuss the matching problem of shapes parameterized by point sets. Mathematical models of diffeomorphic landmark matching and diffeomorphic point shape matching are formulated. After formulating an objective function for diffeomorphic point matching, we give numerical algorithms to solve the objective. Results are shown for 2D corpus callosum shapes.
Of comics and men: A cultural history of American comic books, by Jean-Paul Gabilliet

Review of Jean-Paul Gabilliet, Of comics and men: A cultural history of American comic books. Translated by Bart Beaty and Nick Nguyen. Jackson: University Press of Mississippi, 2010, hardcover, $55.00 (390p), ISBN 978-1604732672.
Regulation of CO2 fixation in non-sulfur purple photosynthetic bacteria

Our laboratory studies the regulation of CO2 fixation in phototrophic micro-organisms. The expression of genes encoding enzymes responsible for assimilating CO2 is primarily regulated by a LysR-type transcriptional activator, CbbR, that functions by binding specific sites in the promoter region of both the cbb I and cbb II CO2 fixation operons under appropriate growth conditions. This straightforward model of regulation has a further level of complexity in the non-sulfur photosynthetic bacterium Rhodopseudomonas palustris. The recent genome sequencing project of this organism identified a unique two-component system interposed between the structural genes of the cbb I operon (encoding form I RubisCO) and CbbR. Two-component systems are a paradigm of gene regulation in Bacteria. In general, they consist of a sensor kinase and a response regulator, that upon stimulation, transduces an external stimulus in a His-Asp phospho-relay, ultimately modulating gene expression. The system identified in R. palustris, in addition to its peculiar modular architecture, also has multiple PAS motifs, suggesting a complex redox sensing activity coordinating a multi-step phospho-relay which regulates CO2 fixation under specific growth conditions.
D-xylose testing: a review.

Abstract The efficacy of d-xylose testing in clinical situations has been reviewed in the light of recent kinetic studies. The standard 25-g d-xylose test in adults, based on analysis of a 5-h urine collection and a 1-h serum sample, discriminates between normal subjects and patients with proximal small intestinal malabsorption with >95% specificity and sensitivity. The 1-h serum level measured after administering this dose is also useful in evaluating malabsorption in patients with intermediate degrees of renal insufficiency and in the elderly. The 1-h serum test after administration of 5 g of d-xylose should be used in pediatrics and is >91% sensitive and close to 100% specific. The [ 14 C]d-xylose breath test with 1 g of d-xylose has been useful in identifying malabsorption caused by bacterial overgrowth in the small intestine.
In silico characterization of the effects of size, distribution, and modulus contrast of aortic focal softening on pulse wave propagations

Abstract Examining the change in regional stiffness of the arterial wall may prove as a reliable method for detecting various cardiovascular diseases. As suggested by Moens–Korteweg relationship, the pulse wave velocity ( PWV ) along the arteries has been shown to correlate to the stiffness of the arterial wall; the higher the stiffness, the higher the PWV . The current primary clinical practice of obtaining an average PWV between remote sites such as femoral and carotid arteries is not as clinically effective, since various cardiovascular diseases are shown to be accompanied by focal changes in stiffness. Therefore, methods to examine the PWV s focally are warranted. Extending on the findings of previous studies, pulse wave propagations along aortas with wall focal softening were addressed in this study using two-way coupled fluid–structure interaction (FSI) simulations of arterial pulsatile motions. Spatio-temporal maps of the wall displacement were used to evaluate the regional pulse wave propagations and velocities. In particular, soft wall inclusions of different number, size, and modulus were examined. The findings showed that the qualitative markers on the pattern of the wave propagations such as the existence of forward, reflected, and standing waves, as well as the quantitative markers such as PWV , linear coefficient of the propagating waves, and the width of the standing waves, provide a reliable tool to distinguish between the natures of the wall focal softening. Future studies are needed to include physiologically-relevant wall inhomogeneity in order to further implicate on the clinical potentials of the inverse problem for noninvasive diagnosis.
Calculating Structural Vibration and Stress from Turbulent Flow Induced Forces

This paper summarizes computational procedures for assessing structural vibration and stress induced by turbulent flow excitation. The overall process is described, including commonly used empirical models for wall pressure fluctuations from turbulent boundary layers, impinging jets, and separated flows. A tutorial on how to assess potential structural damage caused by excessive tensile/compressive loading is given, including how to account for combined mean and cyclic stresses. An example of a beam driven by a turbulent shear layer emanating from a nozzle is given, showing calculations made in the time and frequency domains.