cssi/SciSciGPT-SciSciNet huggingface dataset:
Two layer cakes

The penetration of the Semantic Web into bioinformatics is not like other disciplines. Given critical data resources such as the Gene Ontology (GO) and the challenges associated with the explosion in the number biological databases, biologists, as a community, are already familiar with the advantages of ontologies and the challenges of information integration. Rather than starting from the pedagogical beginnings, penetration will depend on a migration path from the Open Biomedical Ontologies language (OBO) to the Semantic Web. OBO emerged from GO, and is now host to over 60 different ontologies. We have methodically examined each of the constructs of OBO and mapped them to constructs in the Semantic Web stack. We find that most of OBO can be decomposed into layers with direct correspondence to the Semantic Web layer cake. In the process we have enumerated constructs in each system that do not have a simple syntactic equivalent in the other. Elements of OBO “missing” in the semantic web are few, and can still be expressed in OWL. Thus, OBO ontologies may be translated to the Semantic Web. Further, we believe if certain ancillary information is retained during translation, the Semantic Web representation may be translated back to OBO, and the cycle repeated without any loss of knowledge. It is our expectation that tools to automate this process will enable important legacy ontologies onto the Semantic Web. OBO Layer Cake To create a transformation mechanism between OBO flat files and Semantic Web technologies, we find it useful to create a layer cake for OBO, similar to that of the Semantic Web. OBO tags can be partitioned into three layers – OBO Core, OBO Vocabulary, and OBO Ontology Extensions. See Figure 1. The correspondence between the layers of the two systems is direct. In addition, we describe the expressivity of OBO format in terms of various versions of OWL, i.e. OWL Lite, OWL DL and OWL Full.
Review: The Architecture of Paul Rudolph, by Timothy M. Rohan

Timothy M. Rohan The Architecture of Paul Rudolph New Haven, Conn.: Yale University Press, 2014, 300 pp., 40 color and 185 b/w illus. $65 (cloth), ISBN 9780300143935 Paul Rudolph was a monumental figure in the 1950s and 1960s, designing a number of important private and institutional projects and serving as chair of the Department of Architecture at Yale for almost a decade. His influence was strongly felt at that time, although it has waned since. Recognition of Rudolph's importance has increased of late, largely due to the renovation of his best-known commission, the Art and Architecture Building at Yale. Timothy M. Rohan's research has been central to the resuscitation of Rudolph and his legacy, and it is a pleasure finally to see it in book form. In The Architecture of Paul Rudolph , Rohan wisely takes the vicissitudes of Rudolph's reception as a central theme: Why was he so important in the mid-twentieth century, and why is he so much less so today? One could ask this question about many once-prominent architects—Pietro Belluschi, Ralph Rapson, and William Wurster come to mind—who wrote and designed actively in the 1950s and 1960s but left few clear followers. Although Rudolph's situation is extreme, he exhibited a number of tendencies characteristic of American architects who emerged right after World War II: an admiration of interwar modernism, an interest in experimental materials and techniques, and a desire to adjust modern tenets to the cultural and regional conditions of the site. Rudolph was widely admired by critics and the interested public, appearing not only in industry journals but also in Time magazine — Rohan notes that he was “a ‘star architect’ long before the term was coined” (1). Rohan's primary goal is to compensate for the contemporary lack of attention to Rudolph's career. His book is wide-ranging and thorough, tracing the architect's work from his early years as a design assistant …
Bacterial Elicitation of Transcriptional Response of Female Squash Bug, Anasa tristis (De Geer)1

The squash bug, Anasa tristis (De Geer), is a major pest of squash, pumpkin, and other cucurbits throughout North America. A. tristis is a piercingsucking feeder that causes extensive foliar wilting and fruit scarring and transmits plant pathogens. Current biological agents to control A. tristis are limited in efficacy, and newer control methods must be developed. Here we present studies of immune system transcripts as the initial step in identifying potentially vulnerable targets for control of gene expression. Following immune stimulation with bacteria, transcript levels of six components of the inducible innate system in adult female A. tristis were measured using quantitative PCR. An antibacterial peptide-encoding transcript, anacin; an enzyme central to melanization, prophenoloxidase; and three sentinel proteins, scavenger receptor, β-1,3-glucan-binding protein, and peptidoglycan-binding protein were upregulated by bacterial elicitation. Expression of a putative immunoregulatory cytokine, astakine, was identified and increased by septic puncture. We also found novel upregulation of an enzyme of central energy metabolism, arginine kinase, in response to septic puncture of A. tristis adults.
Anisotropic attosecond charge carrier dynamics and layer decoupling in quasi-2D layered SnS2.

National Science Foundation [CHE 1213243, CHE 1565497]; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-76SF00515]
Alternative Treatment Options for Atrioventricular-Nodal-Reentry Tachycardia: An Emergency Medicine Review

Abstract Background Atrioventricular-nodal-reentry tachycardia (AVNRT) is a form of supraventricular tachycardia (SVT) that is relatively common in the emergency department (ED). It is rarely indicative of underlying electrical or structural pathology. Objective This review evaluates the literature and controversies concerning treatment of AVNRT in the ED. Discussion For treatment of narrow-complex tachycardia, Advanced Cardiovascular Life Support guidelines recommend the use of vagal maneuvers, followed by adenosine. Recent literature suggests that nondihydropyridine calcium channel blockers, such as verapamil and diltiazem, may be as effective as adenosine, without the negative short-term side effects. Multiple studies have demonstrated that although adenosine is rapid acting, there is no statistically significant difference in conversion rate between adenosine and calcium channel blockers. Both medications result in a conversion rate above 90%, but there are significantly more minor adverse effects, such as flushing or chest discomfort, with adenosine. Calcium channel blockers are a viable option for treatment for AVNRT, especially in refractory states. Beta-blockers have been evaluated but should not be used routinely due to lower efficacy. AVNRT is the most common tachydysrhythmia in pregnancy, and vagal maneuvers and adenosine are first line. Electrical cardioversion should be utilized for hemodynamically unstable patients. Most patients with AVNRT may be discharged with appropriate follow-up. Conclusion Several studies demonstrate that nondihydropyridine calcium channels (verapamil and diltiazem) are equally as efficacious as adenosine in converting AVNRT to sinus rhythm, without the negative (albeit short-lived) side effects. If given over 20 min, the risk for hypotension is low.
Quantitative study of factors which control shape transformations of human red blood cells of constant volume.

We have previously reported [3] that red cell shape transformations of the disc-sphere type can be followed in a quantitative fashion by measuring the light transmitted through a stirred suspension of washed red cells. The apparatus used to record these shape-sensitive changes in light transmission was a Parpart densimeter [6]. Since the light signal in such a situation can also reflect changes in cell volume it was necessary to show that for sphering agents used cell volume was constant throughout the exposure period and that light absorption by cells while sensitive to cell volume was independent of cell shape. Although Ponder [7] has reviewed the evidence that shape transformations of the type described here occur at constant cell volume, we confirmed that this was so with each agent used in the present study by finding that the volume fraction (hematocrit) of a suspension was not altered when the cells were sphered. That the fractional absorption of light by a suspension of cells is independent of cell shape was established by the finding that the absorption spectrum of hemoglobin when the cells were spheres was quantitatively identical to the spectrum when the same cells were discs (determination made using the opalescent plate method and a dual beam spectrophotometer).
Keeping Ethics Alive in the ED.

Introduction to the June 2010 issue of Virtual Mentor on the topic of time and resource constraints in the emergency department. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Changes in bird distributions in Illinois, USA, over the 20th century were driven by use of alternative rather than primary habitats

ABSTRACT Most species are distributed such that their density and occupancy is greatest in one habitat, although they are found in other habitats. For example, a species with a high affinity for forests (its primary habitat) may also use urban areas and shrublands (its alternative habitat), although occupancy of these habitats would be lower. While habitat loss is the main conservation threat for most species, less is known about how changes in primary and alternative habitats impact populations. We used a systematic bird survey of the state of Illinois that spanned the past century to investigate how use of specific habitats was related to population changes. Specifically, we used a hierarchical Bayesian model to investigate the relationship between changes in statewide occupancy (probability a species would occur in a study site) and use of specific habitats (probability a species would be in a specific habitat within our study sites) for 66 species sampled in 1906–1909 and 2006–2008. Changes in the use...
On the Computation of Control Inputs for Linear Ensembles

In this paper, we revisit the classical ensemble control formulation and provide a solution to the longstanding problem of systematically designing input signals that realize a desired steering between two ensemble states. We present a new computational approach based on a suitable discretization of the integral operator related to the ensemble formulation. Specifically, we apply different methods to appropriately discretize the range operator of the ensemble system, by which we obtain a computational procedure to synthesize control signals that steer ensembles in both a robust and minimum energy fashion. We also present an extension to the previously introduced polynomial approximation technique, which is a closely related special case. This yields a unified framework for the ensemble control of linear systems, which is illustrated by means of computational examples.
Improv: Live Coding for Robot Motion Design

Often, people such as educators, artists, and researchers wish to quickly generate robot motion. However, current toolchains for programming robots can be difficult to learn, especially for people without technical training. This paper presents the Improv system, a programming language for high-level description of robot motion with immediate visualization of the resulting motion on a physical or simulated robot. Improv includes a "live coding" wrapper for ROS ("Robot Operating System", an open-source robot software framework which is widely used in academia and industry, and integrated with many commercially available robots). Commands in Improv are compiled to ROS messages. The language is inspired by choreographic techniques, and allows the user to compose and transform movements in space and time. In this paper, we present our work on Improv so far, as well as the design decisions made throughout its creation.
Combining Inquiry-Based and Team-Teaching Models to Design a Research-Driven, Cross-Disciplinary Laboratory Course

High-impact practices, and other pedagogical advancements, have been successfully used to deepen student engagement with courses over a wide variety of disciplines. Here, we describe the design, implementation, and assessment of a cross-disciplinary, inquiry-based lab course built on the proven success of these deeply engaging principles. This new course allowed students to complete novel research that drew upon both currently emerging molecular sensing techniques as well as long-standing, thoroughly understood cancer treatments. Students designed and tested their own analogues to an industry standard (cisplatin) and, using the data they collected, were able to draw substantive conclusions about the relative success of their attempts. We will also discuss some of the numerous benefits of offering a course like this as well as some of the drawbacks and limitations we encountered. In conclusion, we will also present the assessment of this course, both by the department and by the students themselves.
Opinion: Research community needs to better appreciate the value of sex-based research.

Twenty-five years ago, the National Institutes of Health (NIH) Revitalization Act of 1993 mandated the inclusion of women in clinical research (1), following decades of misconceptions surrounding women’s health and reversing previous guidelines preventing women of childbearing age from participating in early-stage research (2). Many of us held tight to the belief that this requirement would usher in a new era of discovery where consideration of the female sex would become routine experimental practice both in the clinical and basic sciences. Yet today, 25 years later, women remain underrepresented as research subjects in the design and development of novel therapeutics and technologies (3⇓⇓–6). Moreover, when women are included in NIH-funded clinical research, there is often no attempt to desegregate or analyze data by sex or gender, hindering reproducibility and limiting the potential for sex-specific discoveries and our knowledge about the influences of sex or gender on health and disease (7). Our survey results suggest many study section members do not think sex is an important part of experimental design, sentiments that likely extend to the broader research community. Image credit: David Cutler (artist). Survey data we’ve collected imply a further problem. Our results suggest that nearly one-third of NIH study section members do not think it is important to consider biological sex as part of experimental design. This indicates that, although in the minority, the “gate-keepers” of federal funding do not recognize the importance of sex-based research, and these sentiments likely extend to the broader research community. To fully understand the implications of sex and gender, it’s important to outline their difference. Sex is a biological attribute of cells or organisms, defined by genetics, physiology, anatomy, and the hormonal milieu. In the context of clinical studies, male physiology differs from female physiology not only in … [↵][1]1To whom correspondence should be addressed. Email: tkw{at}northwestern.edu. [1]: #xref-corresp-1-1
Abstract 40: Biomaterials and systems biology to guide breast cancer drug screening

Improved in vitro models are needed to better understand cancer progression and bridge the gap between in vitro proof-of-concept studies, in vivo validation, and clinical application. Many methods exist to create biomaterial platforms, including hydrogels, which we use to study cells in contexts more akin to what they experience in vivo. Our lab has multiple approaches to create such biomaterials, based on combinations of poly(ethylene glycol) (PEG) with peptides and zwitterions. In this presentation, I will discuss our findings in using these cell culture environments to understand the role of the extracellular matrix (ECM) in controlling cancer cell innate drug response via adaptive signaling. Specifically, I will present data comparing the behavior of breast, prostate, and ovarian cancer cells to chemotherapy and targeted drugs when cultured as 3D spheroids, on 2D gels, and as a function of the stiffness of the tumor microenvironment. This approach uncovered that cells on 2D hydrogels and spheroids encapsulated in 3D hydrogels were less responsive to receptor tyrosine kinase (RTK)-targeting drugs sorafenib and lapatinib, but not cytotoxic drugs, compared to single cells in hydrogels and cells on plastic. We found that transcriptomic differences between these in vitro models and tumor xenografts did not reveal mechanisms of ECM-mediated resistance to sorafenib. However, a systems biology analysis of phospho-kinome data uncovered that variation in MEK phosphorylation was associated with RTK-targeted drug resistance. Using sorafenib as a model drug, we found that co-administration with a MEK inhibitor decreased ECM-mediated resistance in vitro and reduced in vivo tumor burden compared to sorafenib alone. In sum, we provide a novel strategy for identifying and overcoming ECM-mediated resistance mechanisms by performing drug screening, phospho-kinome analysis, and systems biology across multiple biomaterial environments. Our work suggests that different model systems are important for evaluating cell response to receptor tyrosine kinase inhibitors, whose efficacy depends on cell-ECM interactions. Citation Format: Alyssa Schwartz, Lauren Barney, Lauren Jansen, Christopher Hall, Aaron Meyer, Shelly R. Peyton. Biomaterials and systems biology to guide breast cancer drug screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 40.
Transient Hysteresis in CDK4/6 Activity Underlies Passage of the Restriction Point in G1

Summary Cells escape the need for mitogens at a restriction point several hours before entering S phase. The restriction point has been proposed to result from CDK4/6 initiating partial Rb phosphorylation to trigger a bistable switch whereby cyclin E-CDK2 and Rb mutually reinforce each other to induce Rb hyperphosphorylation. Here, using single-cell analysis, we unexpectedly found that cyclin E/A-CDK activity can only maintain Rb hyperphosphorylation starting at the onset of S phase and that CDK4/6 activity, but not cyclin E/A-CDK activity, is required to hyperphosphorylate Rb throughout G1 phase. Mitogen removal in G1 results in a gradual loss of CDK4/6 activity with a high likelihood of cells sustaining Rb hyperphosphorylation until S phase, at which point cyclin E/A-CDK activity takes over. Thus, it is short-term memory, or transient hysteresis, in CDK4/6 activity following mitogen removal that sustains Rb hyperphosphorylation, demonstrating a probabilistic rather than an irreversible molecular mechanism underlying the restriction point.
Rhythms of Perception

R h y t h m s of Perception T h e settlement o f the U . S . can be matched up w i t h changing rhythms of perception — the way that rituals and settings shape the possibilities we see for our lives. Family farms and rural villages traditionally were steady. N a t - Ralph Knowles ural rhythms offered people endless chances to recite the same tasks, presumably making slightly different choices and learning slightly dif­ ferent lessons each time. O n the other hand, towns are landscapes of growth. People are constantly being disconnected from where they were and must exercise reason in order to make sense o f the changing and more artificial rhythms i n their lives. T h i s correspondence can be traced in the Midwest, which typ­ ifies die ways American life has changed during the last two centuries. First there was the land, which was inhabited by individuals then ordered by faraway companies (or the government) and sold to suc­ cessive waves o f settlers. T h e n villages emerged as complements to the rural life that surrounded them. Finally, towns appeared as for­ eign bodies set down, like boulders on a p l a i n . A s people's cir­ cumstances changed, as they moved from farm to village to town, they measured their possibilities by a succession o f different rhythms.
A Glimpse at Pointwise Asymptotic Stability for Continuous-Time and Discrete-Time Dynamics

Given a dynamical system, pointwise asymptotic stability, also called semistability, of a set requires that every point in the set be a Lyapunov stable equilibrium, and that every solution converge to one of the equilibria in the set. This note provides examples of pointwise asymptotic stability related to optimization and states select results from the literature, focusing on necessary and sufficient Lyapunov and Lyapunov-like conditions for and robustness of this stability property. Background on the classical asymptotic stability is included.
VA ECMO AS A SALVAGE THERAPY FOR POST CARDIOTOMY SHOCK

Post-cardiotomy shock (PCS) is characterized by either an inability to wean off of cardiopulmonary bypass, or a cardiogenic shock state in the immediate postoperative period. Venous-Arterial (VA) ECMO is often utilized in these situations as a salvage technique in instances when other MCS such as
Inpatient Management of Hyperkalemia

Hyperkalemia refers to an elevated serum potassium level (usually >5.5 mEq/L). Severe hyperkalemia defined as serum potassium >6.5 mEq/L or 5.6–6.4 mEq/L with symptoms or EKG changes requires immediate treatment. Initial treatment with calcium gluconate will stabilize the cardiac myocyte membrane, while other therapies such as insulin and beta agonists promote intracellular uptake. For patients with normal or moderately reduced renal function, loop diuretics and gastrointestinal binding resins may be used to eliminate potassium. In the presence of advanced renal failure, or when conservative therapies fail, hemodialysis is needed and nephrology consultation must be ordered. A thorough investigation into the causes of the hyperkalemia will help to tailor further treatment. Assess for high potassium intake, release from intracellular stores (acidosis or cell injury), and impaired potassium excretion (renal failure or impaired aldosterone action).
The Microbiome Sets the Stage for Cholera

Interactions between the eukaryotic host, microbiome members, and invading pathogens help to shape disease outcomes. Using the Drosophila model, Fast et al. identified that Vibrio cholerae acts to inhibit epithelial renewal through complex interactions between the type VI secretion system of V. cholerae and the microbial community of the fly.
Cas9 fusions for precision in vivo editing

Current Cas9 reagents can target genomic loci with high specificity. However, when used for knockin, on-target outcomes are inherently imprecise, often leading to unintended knockout rather than intended edits. This restricts applications of genome editing to ex vivo approaches, where clonal selection is possible. Here we describe a workflow using iterative high-throughput in vitro and high-yield in vivo assays to evaluate and compare the performance of CRISPR knockin reagents for both editing efficiency and precision. We tested combinations of Cas9 and DNA donor template variants and determined that Cas9-CtIP with in situ linearized donors display fold-increases of editing precision in cell lines and in vivo in the mouse brain. Iterating this process, we generated novel compound fusions, including eRad18-Cas9-CtIP that showed further fold-increases in performance. Continued development of precision editing reagents with this platform holds promise for direct in vivo knockin across model organisms and future targeted gene therapies.
Molecular characterization of megaplasmids encoding the type VI secretion system in Campylobacter jejuni isolated from chicken livers and gizzards

Megaplasmids in Campylobacter spp. likely play important roles in antibiotic resistance, virulence, and horizontal gene transfer. In this study, megaplasmids pCJDM202 (119 kb) and pCJDM67L (116 kb) from C. jejuni strains WP2-202 and OD2-67, respectively, were sequenced and characterized. These megaplasmids contained genes for tetracycline resistance [tet(O)], the Type IV secretion system, conjugative transfer and the Type VI secretion system (T6SS). The T6SS genes in Campylobacter plasmids encoded genes and proteins that were similar to those identified in Campylobacter chromosomal DNA. When the megaplasmid pCJDM202 from C. jejuni WP2-202 was transferred via conjugation to C. jejuni NCTC11168 Nal+, transconconjugants acquired tetracycline resistance and enhanced cytotoxicity towards red blood cells. A T6SS mutant of strain WP2-202 was generated and designated Δhcp3; the mutant was significantly impaired in its ability to lyse red blood cells and survive in defibrinated blood. The cytotoxicity of Campylobacter strains towards the human embryonic kidney cell line HEK 293 was not impacted by the T6SS. In summary, the T6SS encoded by Campylobacter megaplasmids mediates lysis of RBCs and likely contributes to survival on retail meats where blood cells are abundant.
Abstract LB-360: Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells

Immune signaling within a metastatic niche drives recruitment and colonization, and the subsequent tumor cell fate within the niche. We employed a biomaterial scaffold as a synthetic metastatic niche to dissect the signals driving the responses within the niche relative to the native metastatic niche, which was the lung in these models. For both the natural and the synthetic niche, Gr-1+ cells secreting S100A8/A9 were the major factors contributing to tumor cell recruitment. Interestingly, upon recruitment, tumor cells in the synthetic niche were observed to undergo senescence and were cleared whereas cells within the native niche accumulated and ultimately proliferated to form macrometastases. The synthetic niche has underlying inflammation due to the foreign body responses (FBR) consisting of N1-polarized Gr1+ myeloid cells, M1-polarizedmacrophage, mature dendritic cells and highly cytotoxic CTLs and NK cells, which were not observed in the lung. Furthermore, we found two proteins (osteopontin and decorin) that are associated with developing FBR greatly improve the cytotoxicity of CTLs and NK cells in the lung from stage 3 breast cancers by increasing their production of Perforin/Granzyme, Fas/TRAIL and IFNr/TNFa. Our results highlight the potential of FBR-associated biomolecules to be used as immune-editing anticancer drugs and also inspire the development of therapeutic implants to actively catch and eradicate metastatic cells. Citation Format: Jing Wang, Matthew Hall, Grace Bushnell, Joseph Decker, Sophia Orbach, Ravi Raghani, Yining Zhang, Aaron Morris, Jeffery Ma, Pridvi Kandagatla, Jacqueline Jeruss, Lonnie Shea. Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-360.
Genetic characterization of a case of sellar metastasis from bronchial carcinoid neuroendocrine tumor.

Background Metastasis to the pituitary gland from neuroendocrine tumors is a rare occurrence that may originate from primary tumors the lung, gastrointestinal tract, thyroid, and pancreas, among others. Patients may present with signs of endocrine dysfunction secondary to pituitary involvement, as well as mass effect-related symptoms including headaches and visual deficits. Despite a small but accumulating body of literature describing the clinical and histopathological correlates for pituitary metastases from neuroendocrine tumors, the genetic basis underlying this presentation remains poorly characterized. Case description We report the case of a 68-year-old with a history of lung carcinoid tumor who developed a suprasellar lesion, causing mild visual deficits but otherwise without clinical or biochemical endocrine abnormalities. She underwent endoscopic endonasal resection of her tumor with final pathology confirming metastasis from her original neuroendocrine tumor. Whole-exome sequencing was performed on the resected sellar tumor and matching blood, revealing increased genomic instability and key mutations in PTCH1 and BCOR that have been previously implicated in both systemic neuroendocrine and primary pituitary tumors with potentially actionable therapeutic targets. Conclusion This is the first genomic characterization of a metastatic tumor to the sella and reports potential genetic insight, implicating PTCH1 and BCOR mutations, into the pathophysiology of sellar metastasis from primary systemic tumors.
Increasing accessibility of audiovisual materials in the institutional repository at Florida State University

Abstract In early 2020, Florida State University Libraries' Office of Digital Research and Scholarship received a small Panhandle Library Access Network (PLAN) Innovation Grant to increase the accessibility of its institutional repository, Diginole, through the creation of video captions and audio transcripts for audiovisual materials. While these audio and video files represent a fairly small percentage of the scholarly outputs found in Diginole, they present a unique set of technical challenges with regard to accessibility when compared to traditional, text-based materials. While text materials can benefit greatly from automatic processes such as OCR (optical character recognition) found in most modern PDF readers and other applications, no such automated, cost-effective “out of the box” solutions are currently available that can guarantee accurate, high-quality captions and transcriptions for AV materials. This column will provide a brief technical history of AV accessibility standards in addition to describing processes of identifying materials for captioning/transcription, selecting a vendor, and provide practical information related to audio and video accessibility that other institutions can hopefully leverage for their own improvements to their IRs.
In Skeletally Immature Children Receiving Radiation for Craniofacial Pathology, Is Success of Subsequent Orthopedic Treatment of Maxillary Transverse Skeletal Deficiency Affected by Inclusion of the Midpalatal Suture in Proton Beam Volume?

Abstract In children whose facial skeletal relationships indicate a need for dentofacial orthopedics and who have previously received radiation therapy to the head, it is important to understand if delivery of proton beam radiotherapy that spares craniofacial sutures allows for success in subsequent skeletal manipulation. This report compares the clinical outcomes of two adolescent males seen at [Name of Institution] who received similar radiation oncology treatment except for inclusion of important suture anatomy in the high dose regions. They were later diagnosed and treated for similar skeletal growth deficiencies and dental malocclusions. Specifically, both patients were treated with orthopedic expansion of the maxillary midpalatal suture and the observed response to treatment varied based on the inclusion of the suture in the dosimetry plan. The clinical implication is that when excluded, orthopedic sutural expansion is possible and is an available treatment strategy for correction of skeletal and dental deficiencies. This finding suggests further investigation in skeletally immature individuals regarding suture inclusion in target volume for proton beam therapy is needed.
Metformin for pediatric obesity and insulin resistance: a retrospective study within an integrated health care system

OBJECTIVE Few treatments exist for pediatric obesity. Metformin holds potential for pediatric weight loss. This large retrospective study examined the effect of metformin on weight, BMI, BMI z score, and cardiometabolic outcomes. METHODS The study included 7,068 patients aged 10 to 17 years with BMI at or above the 95th percentile and evidence of insulin resistance. The final cohort of 955 patients with BMI data at 0 to 24 months was categorized into three groups: metformin plus intensive lifestyle changes, intensive counseling alone, and routine counseling. In order to adjust for pubertal BMI changes, a subgroup analysis was conducted for adolescents aged 15 to 17 years. RESULTS At 6 and 12 months, metformin treatment produced significant reductions in weight (-3.5 kg and -5.3 kg, p < 0.0001), BMI (-1.06 kg/m² and -1.23 kg/m², p < 0.0001), and BMI z score (-0.05 and -0.07, p ≤ 0.002), which continued to decrease at 24 months (-0.05 and -0.08, p = 0.11 and 0.01), compared with control groups. Adolescents aged 15 to 17 years showed similar improvements. Systolic blood pressure and high-density lipoprotein cholesterol also improved in the metformin group. CONCLUSIONS Metformin with lifestyle interventions significantly reduced weight, BMI, and BMI z score in pediatric patients with obesity and insulin resistance up to 24 months, compared with intensive and routine counseling alone.
A Revisit of Zumbo’s Third Generation DIF: How Are We Doing in Language Testing?

The purpose of this study is to review the status of differential item functioning (DIF) research in language testing, particularly as it relates to the investigation of sources (or causes) of DIF,...
754 TIGIT-PVR is a key immune checkpoint and therapeutic target in HPV-positive head and neck squamous cell carcinomas

Background Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HPV+ HNSCC) is a disease that has moderate response to anti-PD-1/L1 immune checkpoint blockade, with the response rates less than 20% and median progression-free survival less than 3 months. A greater understanding of tumor intrinsic and extrinsic factors that restrict anti-tumor immunity in the tumor immune microenvironment (TIME) is needed to identify other immune checkpoints to enhance therapeutic efficacy. Methods Two cohorts (TCGA n=72 and a separate cohort n=84) of surgically resected, treatment-naive HPV+ HNSCC with RNA-seq were analyzed to understand the immune features. In addition, single-cell RNA-seq and TCR-seq were performed on 18 cases to further delineate the immune molecules9 interactions. An immune-competent murine HPV+ HNSCC model was used to preliminarily evaluate the therapeutic efficacy. Results In two bulk-sequenced HPV+ HNSCC cohorts, TIGIT ligands PVR and NECTIN2 were found to associate with an epithelial-to-mesenchymal gene expression signature, suppression of IFNα and IFNγ signaling, a stromal-enriched or immune-excluded TIME, and poor survival. Single-cell RNA-seq of over 72,000 cells of HPV+ HNSCC revealed that the PVR/NECTIN ligand TIGIT was highly prevalent in T-cells (34%), significantly higher than PD1- (20%, p Conclusions TIGIT-PVR/NECTIN receptors/ligands are more abundant than PD-1/L1 in the TIME of HPV+ HNSCC. Co-blockade of TIGIT and PD-1 immune checkpoints enhanced anti-tumor efficacy in a CD8+ T-cell-dependent manner and conferred long-term immune protection in a murine model. Our study nominates TIGIT as a therapeutic target for HPV+ HNSCC.
Competition for Control of the State and the Transitional Justice Agenda Among Tunisian Civil Society Organizations

Often, the transitional (TJ) and peacebuilding literatures treat the State and civil society as monolithic actors that have definable interests that can help us explain their policy preferences. However, this masks the diverse, sometimes contradictory, policy views present within both the State and among civil society organisations (CSOs). This article examines how Tunisian CSOs have positioned themselves vis-a-vis the State and each other with respect to TJ since the 2011 revolution. In post-revolutionary Tunisia, among other things, CSOs are divided based upon religion, their status under Ben Ali, their TJ preferences, their geographical location, and their access to and willingness to engage international experts and donors. In a country with a strong State, rather than ‘letting the state off the hook’, CSOs have both pressured the State to deliver on justice and competed over control of the State to achieve their policy goals. Groups that represent secular, youth perspectives outside of Tunis, in particular, feel left out of the conversation. Having failed to coopt the State, most CSOs continue to desire government-led action on TJ. Theoretically, the article calls for a more thoughtful dissection of the CSO category and a questioning of the divide between CSOs and the State that existing research often at least implicitly assumes to exist. It also reflects on the strategies non-state actors use when they are excluded from TJ debates.
Estimating Expected Losses and Liquidity Discounts Implicit in Debt Prices

This paper provides an empirical implementation of a reduced form credit risk model that incorporates both liquidity risk and correlated defaults. Liquidity risk is modeled as a convenience yield and default correlation is modeled via an intensity process that depends on market factors. Various different liquidity risk and intensity process models are investigated. Firstly, the evidence supports a non-zero liquidity premium that is firm specific, reflecting idiosyncratic and not systematic risk. Secondly, the credit risk model with correlated defaults fits the data quite well with an average R wedge 2 of .87 and a pricing error of only 1.1 percent.
Effect of hypertransfusion on bone marrow regeneration in sublethally irradiated mice. I. Enhanced granulopoietic recovery

Hypertransfusion can enhance recovery from neutropenia in certain clinical and experimental situations. We have studied the pattern of myeloid recovery in mice hypertransfused after receiving 350 rads whole body irradiation. Both hypertransfused and control groups showed the degenerative phase, abortive rise, and regenerative phase that has been described following sublethal irradiation. The blood granulocyte counts in the hypertransfused group returned to normal more rapidly and were maintained at a significantly higher level during the regenerative phase. This difference is not the result of a shift in granulocytes from the marrow granulocyte reserve or marginal granulocyte pool to the circulating pool, but is associated with significantly enhanced bone marrow granulopoiesis. While the total bone marrow cellularity of the hypertransfused mice is less than that of the control mice, the hypertransfused group contains more CFU-GM and myeloid cells during the regenerative phase. The enhanced granulopoiesis is not due to increased colony-stimulating activity (CSA) levels in the hypertransfused mice, as the CSA levels were significantly lower in this group compared to the controls prior to and during the initial phase of granulopoietic recovery. This study suggests that hypertransfusion increases the rate of recovery of myelopoiesis by increasing the number of precursors available for myeloid differentiation from an earlier stem cell compartment.
High-speed /spl Sigma//spl Delta/ modulators with reduced timing jitter sensitivity

As higher and higher frequency signals are sampled, clock jitter limits the achievable signal-to-noise ratio (SNR) in an analog-to-digital converter (ADC). This clock jitter limit is reviewed for upfront sampled ADCs and continuous-time (CT) sigma-delta modulators (/spl Sigma//spl Delta/Ms). A pulse-shaped feedback digital-to-analog converter (DAC) is proposed to mitigate the jitter-imposed SNR limit in CT /spl Sigma//spl Delta/Ms. An intuitive analysis that compares the pulse-shaped DAC to conventional DACs is presented. This analysis as well as a more rigorous analysis shows that the pulse-shaped feedback /spl Sigma//spl Delta/M has potential for significant SNR improvement over conventional CT /spl Sigma//spl Delta/Ms as well as any upfront sampled system. For typical jitter, phase and amplitude noise numbers, SNR improvement is on the order of 17 dB over a conventional CT /spl Sigma//spl Delta/M and 8 dB over an upfront sampled ADC for a 1-GHz input.
Adolescents Prefer More Immediate Rewards When in the Presence of their Peers

Adolescents take more risks in the presence of their peers, but the mechanism through which peer presence affects risky decision-making is unknown. We propose that the presence of peers increases the salience of the immediate rewards of a risky choice. The current study examined the effect of peer presence on reward sensitivity in a sample of 100 late adolescents ages 18 through 20 (M=18.5) using a delay discounting task, which assesses an individual's preference for immediate versus delayed rewards. Participants were randomly assigned to complete the task alone or with 2 same-age, same-sex peers observing. Consistent with our prediction, adolescents demonstrated a greater preference for immediate rewards when with their peers than when alone. Heightened risk taking by adolescents in the company of their friends may be due in part to the effect that being with one's peers has on reward sensitivity.
Quality of life (QOL) and toxicity among patients in CALGB 80405.

3611 Background: CALGB 80405, a phase III trial, was originally designed to compare toxicity and overall survival of metastatic colorectal patients treated with standard chemotherapy (choice of FOLFOX or FOLFIRI) and either: 1) Bevacizumab; 2) Cetuximab; or 3) both Bevacizumab and Cetuximab. Because Cetuximab causes a prominent acneiform skin rash, adverse effects on QOL were anticipated and assessed in a QOL companion. Methods: The QOL companion enrolled the first 518 consenting patients randomized to CALGB 80405 between 10/2005-9/2007, the majority prior to amendments that eliminated the dual biologic arm and restricted participation to patients with KRAS wttumors. QOL was assessed at baseline, 6 weeks, and 3, 6 and 9 months post-randomization, using the EORTC QLQ-30 and the Dermatology-Specific Quality of Life (DSQL) Scale. We hypothesized that patients receiving Cetuximab would have lower satisfaction with appearance, reduced social functioning and lower overall QOL at 3 months, (a primary assessment ...
Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPARγ Agonists

Alzheimer's disease (AD) is characterized by the extracellular deposition of β-amyloid fibrils within the brain and the subsequent association and phenotypic activation of microglial cells associated with the amyloid plaque. The activated microglia mount a complex local proinflammatory response with the secretion of a diverse range of inflammatory products. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious in reducing the incidence and risk of AD and significantly delaying disease progression. A recently appreciated target of NSAIDs is the ligand-activated nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). PPARγ is a DNA-binding transcription factor whose transcriptional regulatory actions are activated after agonist binding. We report that NSAIDs, drugs of the thiazolidinedione class, and the natural ligand prostaglandin J2 act as agonists for PPARγ and inhibit the β-amyloid-stimulated secretion of proinflammatory products by microglia and monocytes responsible for neurotoxicity and astrocyte activation. The activation of PPARγ also arrested the differentiation of monocytes into activated macrophages. PPARγ agonists were shown to inhibit the β-amyloid-stimulated expression of the cytokine genes interleukin-6 and tumor necrosis factor α. Furthermore, PPARγ agonists inhibited the expression of cyclooxygenase-2. These data provide direct evidence that PPARγ plays a critical role in regulating the inflammatory responses of microglia and monocytes to β-amyloid. We argue that the efficacy of NSAIDs in the treatment of AD may be a consequence of their actions on PPARγ rather than on their canonical targets the cyclooxygenases. Importantly, the efficacy of these agents in inhibiting a broad range of inflammatory responses suggests PPARγ agonists may provide a novel therapeutic approach to AD.
A Data Parallel Algorithm for XML DOM Parsing

The extensible markup language XML has become the de facto standard for information representation and interchange on the Internet. XML parsing is a core operation performed on an XML document for it to be accessed and manipulated. This operation is known to cause performance bottlenecks in applications and systems that process large volumes of XML data. We believe that parallelism is a natural way to boost performance. Leveraging multicore processors can offer a cost-effective solution, because future multicore processors will support hundreds of cores, and will offer a high degree of parallelism in hardware. We propose a data parallel algorithm called ParDOM for XML DOM parsing, that builds an in-memory tree structure for an XML document. ParDOM has two phases. In the first phase, an XML document is partitioned into chunks and parsed in parallel. In the second phase, partial DOM node tree structures created during the first phase, are linked together (in parallel) to build a complete DOM node tree. ParDOM offers fine-grained parallelism by adopting a flexible chunking scheme --- each chunk can contain an arbitrary number of start and end XML tags that are not necessarily matched. ParDOM can be conveniently implemented using a data parallel programming model that supports map and sort operations. Through empirical evaluation, we show that ParDOM yields better scalability than PXP [23] --- a recently proposed parallel DOM parsing algorithm --- on commodity multicore processors. Furthermore, ParDOM can process a wide-variety of XML datasets with complex structures which PXP fails to parse.
Factors influencing interest in providing MS patient care among physiatry residents

BACKGROUND Rehabilitation care is an important part of comprehensive care for MS patients. Little is known about the number of physiatry residents who are interested in providing care to individuals with multiple sclerosis [MS]. OBJECTIVE This study examines factors that influence physiatry residents' interest in providing care to MS patients. METHODS We randomly sampled half of all Accreditation Council for Graduate Medical Education-certified physical medicine and rehabilitation residency programs in the continental United States and Puerto Rico. Surveys were received from 74% of programs (Stage 1 response rate) and from 221 residents (45% Stage 2 response rate). RESULTS Residents expressing interest in providing MS care were more likely to be female, Asian, and to select statements emphasizing multidisciplinary care approaches and a community of dedicated professional colleagues as positive features of MS patient care. Residents interested in teaching and with more education debt were marginally more likely to express interest in MS care. CONCLUSIONS Medical education should emphasize the need for physical medicine and rehabilitative care among individuals with MS, the ability of physiatrists to improve the functional status and quality of life for MS patients, and the team-based nature of MS care.
The effect of cis- and trans-clomiphene citrate on the collagen content of fetal bone

cis- and trans-Clomiphene citrate were administered im to pregnant rabbits from day 21 to day 26 of gestation. Seven rabbits received 15 mg/kg and 6 rabbits 25 mg/kg of the cis-isomer daily. trans-Clomiphene citrate was given to 4 rabbits in a daily dose of 10 mg/kg and to 8 rabbits in a dose of 15 mg/kg; 8 rabbits served as controls. The rabbits were delivered by hysterotomy on day 27, and the fetuses and placentas were weighed. The femurs from liveborns were dissected free of soft tissue, and the wet and fat-free dry weights were recorded. The collagen and total ash of the femurs were determined. The only significant differences between the control and experimental rabbits occurred when trans-clomiphene 15 mg/kg was used. With this dose of trans-clomiphene, fetal weight was decreased from 25.5 ± 2.3 g to 20.2 ± 5.2 g (p = 0.02) and the collagen to dry weight ratio of bone from 18.6 ± 2.0 to 13.9 ± 2.9 (p < 0.01). The collagen to ash ratio in the trans-clomiphene 15 mg/kg treated group was 0.32 ± 0.07 compared to 0.5 ± 0.09 in the controls (p < 0.005). It is suggested that the changes in fetal weight and bone composition under the influence of the trans-isomer are due to its estrogenic properties.