cssi/SciSciGPT-SciSciNet huggingface dataset:
Vitreomacular Traction and Epiretinal Membranes

Optical coherence tomography (OCT) has transformed the understanding of the anatomy of the vitreomacular interface (VMI) and pathologic processes that occur there. Since the first description of macular diseases with OCT in 1995, progressive advances in technology have made OCT the gold standard for the diagnosis and management of VMI diseases (Puliafito et al. 1995; Stalmans et al. 2013). Clinical biomicroscopic examination and other imaging modalities are limited in their capabilities to fully diagnose and document diseases of the VMI as vitreous membranes are often clinically invisible. Spectral domain OCT (SD-OCT) provides high-resolution images of the VMI with noninvasive capture and fast acquisition. SD-OCT enables the clinician to more accurately diagnose diseases of the VMI, informs treatment, and guides postoperative care (Folgar et al. 2012). The approval of ocriplasmin (Jetrea, ThromboGenics, Iselin, New Jersey) for pharmacologic vitreolysis of “symptomatic vitreomacular adhesion” has further stimulated interest in understanding the pathophysiology of the VMI (FDA 2012). These developments led to the formation of the International Vitreomacular Traction Study (IVTS) Group to create a strictly anatomic OCT-based classification system for the VMI and more specifically the vitreomacular interface (VMI) (Duker et al. 2013). The panel of vitreoretinal disease experts provided anatomic definitions and classification of vitreomacular adhesion (VMA), vitreomacular traction (VMT), and full-thickness macular hole (FTMH). This classification system and the science upon which it is based inform the current diagnosis and management of diseases of the VMI.
The Need for Extracorporeal Membrane Oxygenation in Adults Undergoing Congenital Heart Surgery: Impact and Trends of Utilization.

Introduction: Adults with congenital heart disease (ACHD) represent a population with unique health-care needs. Many patients require cardiac surgery, with some requiring postoperative extracorporeal membrane oxygenation (ECMO). This study aimed to identify the risk factors for the need of postoperative ECMO and characterize the impact of ECMO on admission characteristics. Methods: Data from the 2005–2012 iterations of the Nationwide Inpatient Sample were used. ACHD admissions over 18 years with a documented cardiac surgery were included. Univariate analysis was conducted to compare the characteristics between those requiring ECMO and those who did not. Regression analysis was done to identify the independent risk factors associated with ECMO and to determine the impact of ECMO on length, cost, and mortality of the admission. Results: A total of 186,829 admissions were included. Of these, 446 (0.2%) admissions required ECMO. Those with acute kidney injury, double-outlet right ventricle, or total anomalous pulmonary venous connection were more likely to require ECMO. ECMO was also significantly more utilized in patients undergoing septal defect repair, complete repair of tetralogy of Fallot, atrial switch, and heart transplant. The use of ECMO significantly increased length, cost, and mortality of stay. Overall mortality was 62.6% in the ECMO group. Conclusion: ECMO is only needed in a small proportion of postoperative ACHD patients. The use of ECMO significantly increases cost, length of stay and mortality in these patients. Improved identification of postoperative ACHD patients who are more likely to survive ECMO may facilitate improved survival and decreased resource utilization.
Impact of a Fellowship-Trained Minimally Invasive Gynecologic Surgeon on Patient Outcomes.

BACKGROUND AND OBJECTIVES As the performance of minimally invasive hysterectomy has increased in the United States, the need to apply outcomes measures has also increased. This study was conducted to determine the impact of a fellowship-trained minimally invasive gynecologic surgery (MIGS) specialist on patient outcomes after laparoscopic hysterectomy (LH) in a gynecology department. METHODS This is a retrospective review of 218 patients who underwent a laparoscopic hysterectomy for benign indications at a suburban academic-affiliated tertiary care hospital with a broad patient base from 2010 to 2014. RESULTS A total of 218 women underwent conventional laparoscopic hysterectomy by 10 members of a gynecology department: 96 women (44%) by a MIGS specialist and 122 women (56%) by a group of general gynecologists. Operative time was less (119 vs 148 min; P < .001), and patients were more likely to be discharged on the same day (90.6% vs 66.4%; P < .001) for the MIGS specialist compared to other surgeons. More patients of the MIGS specialist had undergone prior laparotomies (42.7% vs 17.2%; P = < .001) and had a greater uterine weight (392 vs 224 g; P < .001). Although the difference was not statistically significant, conversion to laparotomy (0 vs 2 cases; P = .505) and postoperative infection (6 vs 16 cases; P = .095) were lower for the MIGS specialist. Total billing charges were also lower for the MIGS specialist ($9,920 vs $11,406; P < .001). CONCLUSION A fellowship-trained MIGS specialist performed laparoscopic hysterectomy in less time on more difficult surgical patients, with a shorter length of stay and lower costs, and no difference in complications compared to other providers in a gynecology department.
Greek Statue Terms Revisited: What does ἀνδριάς mean?

References to statues of women show that only in the Roman Empire did andrias come to replace eikon as the term for a male or a female portrait statue, with eikon now indicating a painted portrait.
How the manakin got its crown: A novel trait that is unlikely to cause speciation.

In a fascinating study, Barrera-Guzman et al. (1) demonstrate a hybrid origin for the golden-crowned manakin and describe a sexually dimorphic plumage trait derived in the hybrid lineage. However, their work stops short of showing that “the evolution of this unique crown-color signal likely culminated in premating isolation of the hybrid species from both parental species” (1), and indeed, this statement runs counter to theoretical expectations about the role of mate choice in speciation. For a novel mating signal to facilitate reproductive isolation, it has to promote mating between genetically similar individuals by being more attractive to hybrid choosers and/or less attractive to parentals (2, 3 … [↵][1]1To whom correspondence should be addressed. Email: grosenthal{at}bio.tamu.edu. [1]: #xref-corresp-1-1
The Effects of Stigma on Determinants of Mental Health Help-Seeking Behaviors Among Male College Students: An Application of the Information-Motivation-Behavioral Skills Model

Considered a public health issue, the prevalence and severity of poor mental well-being on college campuses has continued to rise. While many college campuses offer mental health counseling services, and utilization rates are increasing, their proportional usage is low especially among males, who often deal with poor mental well-being by adopting unhealthy coping strategies. The purpose of this study was to use the Information-Motivation-Behavioral Skills (IMB) model to assess the relationship between the determinants as factors that may impact help-seeking behaviors in a large sample ( n = 1,242) of male college students. Employing a cross-sectional study design, a 71-item online survey assessed information via total mental health literacy (MHL), motivation via attitudes toward mental health and subjective norms regarding mental health, and behavioral skills via intentions regarding help-seeking behaviors, and stigma. Results revealed correlations between information and motivation ( r = .363, p < .01), information and behavioral skills ( r = .166, p < .01), and motivation and behavioral skills ( r = .399, p < .01). Multiple regression was used to determine stigma is a mediator for all relationships. These findings represent an opportunity to take a public health approach to male mental health through developing multilayered interventions that address information, motivation, behavioral skills, and stigma.
Behavioral Economics, Evolution, and the Human Brain

As early as the late 1950s with the work of Herbert Simon, psychologists began questioning the value of unbounded rationality in economic modeling, noting that the human brain faced its own evolved limited and imperfect internal resources. Daniel Kahneman and Amos Tversky in the 1970s began calling into serious question the neoclassical methodological approach by running a series of laboratory and survey experiments that found substantial gaps between the predictions of economic models grounded in perfect rationality and the way real people behave or say they would behave. In the late 1980s and continuing into this century, Richard Thaler uncovered a small library of “anomalies” in people’s behaviors, as judged by predictions from neoclassical economics, grounded in contemporary times (but not in earlier eras) in perfect rationality. A growing cadre of behavioral economists have gone further, concluding that people are so frequently “irrational” that they are “predictably irrational,” suggesting that neoclassical economists should fold their analytical efforts.
The Prognostic Value of an Oxygenation Index (OI) of ≥10 in Premature Infants ≤1500 g Birth Weight † 1096

The Prognostic Value of an Oxygenation Index (OI) of ≥10 in Premature Infants ≤1500 g Birth Weight † 1096
Antibody Diversity Patterns and Structure of Idiotypic Determinants on Murine Anti- α(1 → 3) Dextran Antibodies

Idiotypic (variable-region) antigenic determinants have been extremely important to the study of immunoglobulins. These antigenic determinants have been widely used to examine variable-region expression in immunoglobulin populations because they offer a simple, sensitive, serological approach to variable-region structure. There are many different categories of idiotypic determinants: ligand-modifiable (binding site determinants), ligand-nonmodifiable (framework determinants), VL-specific, VH-specific, and those requiring both VL and VH. In addition, determinants shared by variable regions known to be structurally different are called IdX, cross-reactive, or public idiotypes, while those apparently restricted to identical variable regions are IdI, individual, or private idiotypes.
Public Health Consequences of a 2013 Measles Outbreak in New York City.

Importance Internationally imported cases of measles into the United States can lead to outbreaks requiring extensive and rapid control measures. Importation of measles from an unvaccinated adolescent in 2013 led to what has been the largest outbreak of measles in New York City, New York, since 1992. Objective To describe the epidemiology and public health burden in terms of resources and cost of the 2013 measles outbreak in New York City. Design, Setting, and Participants This epidemiologic assessment and cost analysis conducted between August 15, 2013, and August 5, 2014, examined all outbreak-associated cases of measles among persons residing in New York City in 2013. Exposures Measles virus. Main Outcomes and Measures Numbers of measles cases and contacts. Total personnel time and total direct cost to the New York City Department of Health and Mental Hygiene (DOHMH), calculated as the sum of inputs (supplies and materials, equipment, and logistics) and personnel time (salary and fringe benefits). Results Between March 13, 2013, and June 9, 2013, 58 persons in New York City with a median age of 3 years (range, 0-32 years) were identified as having measles. Among these individuals, 45 (78%) were at least 12 months old and were unvaccinated owing to parental refusal or intentional delay. Only 28 individuals (48%) visited a medical health care professional who suspected measles and reported the case to the DOHMH at the initial clinical suspicion. Many case patients were not immediately placed into airborne isolation, resulting in exposures in 11 health care facilities. In total, 3351 exposed contacts were identified. Total direct costs to the New York City DOHMH were $394 448, and a total of 10 054 hours were consumed responding to and controlling the outbreak. Conclusions and Relevance Vaccine refusals and delays appeared to have propagated a large outbreak following importation of measles into the United States. Prompt recognition of measles along with rapid implementation of airborne isolation of individuals suspected of measles infection in health care facilities and timely reporting to public health agencies may avoid large numbers of exposures. The response and containment of measles outbreaks are resource intensive.
A systematic review and meta- analysis of randomized controlled trials to evaluate the risk of pulmonary toxicities in patients with advanced breast cancer treated with everolimus.

e13086Background: Pulmonary toxicities have significant impact on morbidity, mortality, drug dosing inconsistencies and financial burden among patients undergoing chemotherapy. Everolimus (E), an o...
Assessing Middle School Students' Computational Thinking Through Programming Trajectory Analysis

With national K-12 education initiatives such as "CSForAll," block-based programming environments have emerged as widely used tools for teaching novice programming. A key challenge presented by block-based programming environments is assessing students' computational thinking (CT) and programming competencies. Developing assessment methods that can evaluate students' use of CT practices such as testing and refining, and developing and using appropriate algorithms, can help teachers evaluate students learning and provide appropriate scaffolding. In this work, we utilize an evidence-centered assessment design approach to devise a three-dimensional assessment to evaluate students' CT competencies based on evidence extracted from their programming trajectories in a block-based programming environment. In this assessment, the first dimension assesses students' knowledge of essential CT concepts, the second dimension assesses students' dynamic testing and refining strategies, and the third dimension assesses their overall problem-solving efficiency. We apply the assessment framework to data collected from students' interactions with a game-based learning environment designed to develop middle-grade students' CT competencies and programming skills. The results demonstrate that students' knowledge of basic CT constructs, such as appropriate use and combination of control structures, serves as the foundation for designing and implementing effective algorithms. Further, we assessed students testing and refining strategies over the three dimensions of novelty, positivity, and scale. The results demonstrate that students with higher algorithmic capabilities tend to make more novel, positive, and small-scale changes. The results reveal distinctive patterns in students' approaches to computational thinking problem solving and make a step toward identifying and assessing productive computational thinking practices.
Vicarious Family Health Strain and Juvenile Delinquency

Research finds that vicarious strain significantly predicts juvenile delinquency. However, no studies have examined the influence of vicarious health strain on youth behavior despite the fact that ...
A new crown wasp in mid-Cretaceous amber from northern Myanmar (Hymenoptera: Stephanidae)

The crown wasps, family Stephanidae, are generally believed to occupy a distinguished position as putative relicts of the earliest-diverging lineage of apocritan Hymenoptera (e.g., Sharkey et al., 2012; Mao et al., 2015). More recent analyses have cast some confusion over this hypothesis, with the family instead appearing closer to the Evanioidea or even Trigonalyoidea (Peters et al., 2017; Tang et al., 2019). From most analyses it is clear that the family extends well into the Cretaceous, with crown-group Stephanidae estimated to have appeared by at least the Early Cretaceous and a purported ghost-stem lineage extending into the Early Jurassic or even latest Triassic (Tang et al., 2019). At least parts of such a hypothesis are consistent with the number of mid-Cretaceous fossils representing a variety of crown wasps, including species of both the plesiomorphic subfamily Schlettereriinae as well as putative Stephaninae (Engel & Grimaldi, 2004; Engel et al., 2013; Engel & Huang, 2017; Li et al., 2017). Unfortunately, while such fossil occurrences are of considerable interest, the total available record of fossil crown wasps is poor, with most species documented from the Palaeogene (Engel, 2005; Engel & Ortega-Blanco, 2008), and hitherto only four species from the Late Cretaceous. Given the potentially long gap between the first divergence of the lineage and the appearance of the crown group (Tang et al., 2019), it is precisely for such a group that early diverging stem groups would be of considerable value in resolving relationships and documenting the appearance of apomorphies within the clade. Extensive study of Early Cretaceous and Jurassic deposits for stem-group Stephanidae is necessary in order to provide direct evidence into the early evolution of this critical family of the Euhymenoptera.
Concurrent Identification of Novel EGFR–SEPT14 Fusion and ETV6–RET Fusion in Secretory Carcinoma of the Salivary Gland

Salivary gland secretory carcinoma, also termed mammary analogue secretory carcinoma (MASC), is a recently described salivary gland neoplasm with characteristic histomorphologic findings similar to those of secretory carcinoma of the breast and harboring recurrent ETV6-NTRK3 fusions. Recent findings have expanded the molecular profile of salivary gland secretory carcinoma to include multiple novel ETV6 fusion partners, including RET, MET, and MAML3. Here, we report a case of cystic MASC with cribriform and papillary histology harboring two gene fusions, ETV6-RET and EGFR-SEPT14, identified by targeted RNA sequencing. The presence of the rearrangements was confirmed by FISH, RT-PCR, and Sanger sequencing. This is the first EGFR-SEPT14 fusion reported in secretory carcinoma as a single event or in association with an ETV6 rearrangement. This finding adds to the expanding molecular profile of this tumor entity, and may translate into novel treatment strategies.
Soybean vein necrosis orthotospovirus can move systemically in soybean in the presence of bean pod mottle virus

Soybean vein necrosis virus (SVNV), the causal agent of the homonymous disease, is a ubiquitous virus in North America. The widespread presence of the virus has led to the hypothesis that mixed infections with other viruses could alter disease symptoms, localization in the plant and even epidemiology. The potential interaction between bean pod mottle virus (BPMV), soybean mosaic virus (SMV), the most economically important soybean viruses in the U.S., and SVNV was assessed in the work presented here. Results revealed that soybean, a local lesion host for SVNV, becomes permissive in the presence of BPMV; whereas there where no obvious interactions observed in mixed infections with SMV.
Diet and companionship modulate pain via a serotonergic mechanism

Treatment of severe chronic and acute pain in sickle cell disease (SCD) remains challenging due to the interdependence of pain and psychosocial modulation. We examined whether modulation of the descending pain pathway through an enriched diet and companionship could alleviate pain in transgenic sickle mice. Mechanical and thermal hyperalgesia were reduced significantly with enriched diet and/or companionship. Upon withdrawal of both conditions, analgesic effects observed prior to withdrawal were diminished. Serotonin (5-hydroxytryptamine, 5-HT) was found to be increased in the spinal cords of mice provided both treatments. Additionally, 5-HT production improved at the rostral ventromedial medulla and 5-HT accumulated at the dorsal horn of the spinal cord of sickle mice, suggesting the involvement of the descending pain pathway in the analgesic response. Modulation of 5-HT and its effect on hyperalgesia was also investigated through pharmaceutical approaches. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, showed a similar anti-nociceptive effect as the combination of diet and companionship. Depletion of 5-HT through p-chlorophenylalanine attenuated the anti-hyperalgesic effect of enriched diet and companionship. More significantly, improved diet and companionship enhanced the efficacy of a sub-optimal dose of morphine for analgesia in sickle mice. These findings offer the potential to reduce opioid use without pharmacological interventions to develop effective pain management strategies.
Respiratory Modalities in Preventing Reintubation in a Pediatric Intensive Care Unit

Post-extubation respiratory failure requiring reintubation in a Pediatric Intensive Care Unit (PICU) results in significant morbidity. Data in the pediatric population comparing various therapeutic...
Smith, Craig, Adam Smith: Cambridge, UK: Polity Press, 210 pp., $24.95, ISBN: 1-5095-1823-1, Publication Date: May 2020

Craig Smith, Adam Smith Senior Lecturer in the Scottish Enlightenment at the University of Glasgow, has written a masterful precis of the ideas of Adam Smith. (For clarity, I shall refer to the aut...
Influence of time of day and intermittent aerobic exercise on vascular endothelial function and plasma endothelin-1 in healthy adults

Reduced flow-mediated dilation (FMD) and elevated plasma endothelin-1 (ET-1) levels may contribute to the higher incidence of adverse cardiovascular events observed in the morning hours. A single b...
Measuring the impact of suicide attempt posttraumatic stress.

OBJECTIVE To examine the associations between posttraumatic stress symptoms (PTS) following a medically serious suicide attempt with suicidal ideation, related interpersonal constructs, and outpatient mental health service utilization. METHODS The study utilized an existing data set from a clinical trial consisting of 66 patients recruited at a level 1 trauma center following medical admission for a suicide attempt. Measures of suicide attempt-related PTS (SA-PTS), suicidal ideation, perceived burdensomeness, thwarted belongingness, and outpatient medical and mental health utilization were completed at 1 and 3 months. A series of mixed-effects regression models were used to analyze the data. RESULTS Greater SA-PTS at 1 month was associated with significantly greater suicidal ideation, thwarted belongingness, and perceived burdensomeness across 1 and 3 months. CONCLUSIONS Addressing PTS following a medically serious suicide attempt may aid in addressing suicide-specific constructs and improve the recovery trajectory following hospitalization.
Domain-Specific Modeling and Optimization for Graph Processing on FPGAs

The use of High Level Synthesis (HLS) tools is on the rise; however, performance modelling research has been mainly focused on regular applications with uniform memory access patterns. These performance models fail to accurately capture the performance of graph applications with irregular memory access patterns. This paper presents a domain-specific performance model targeting graph applications synthesized using HLS tools for FPGAs. The performance model utilizes information from the hardware specification, the application’s kernel, and the graph input. While the compilation process of HLS tools takes hours, the information required by the performance model can be extracted from the intermediate compilation report, which compiles in seconds. The goal of this work is to provide FPGA users with a performance modelling framework for graph applications, to estimate performance and explore the optimization space. We tested the framework on Intel’s new Devcloud platform and achieved speedup up to \(3.4\times \) by applying our framework’s recommended optimization strategy compared to the single pipeline implementation. The framework recommended the best optimization strategy in 90% of the test cases.
A matched-control study on the effects of depressive disorders following open reduction and internal fixation for acetabular fractures

The World Health Organization (WHO) postulates that depressive disorders (DD) will be the leading cause of morbidity and mortality by 2030. Studies evaluating the association of DD following open reduction and internal fixation (ORIF) for the treatment of acetabular fractures are limited. Therefore, the purpose of this matched-control study was to determine whether DD patients undergoing ORIF for acetabular fractures have higher rates of: (1) in-hospital lengths of stay (LOS); (2) readmissions; (3) medical complications; and (4) costs of care. A retrospective query from the 100% Medicare Standard Analytical Files (SAF) was performed to identify patients who underwent ORIF for acetabular fractures. The study group consisted of those patients with DD, whereas patients without the condition served as controls. Primary endpoints of the study were to compare in-hospital LOS, readmission rates, ninety-day medical complications, and costs of care. A p-value less than 0.01 was considered statistically significant. The query yielded 7084 patients within the study (ORIF = 1187, control = 5897). DD patients were found to have significantly longer in-hospital LOS (11 days vs. 10 days, p < 0.0001); however, odds (OR) of readmission rates were similar (23.16 vs. 18.68%; OR: 0.91, p = 0.26). Multivariate regression demonstrated DD to be associated with significantly higher (67.69 vs. 25.54%; OR: 2.64, p < 0.0001) 90-day medical complications. DD patients had significantly higher day of surgery ($30,505.93 vs. $28,424.85, p < 0.0001) and total global 90-day costs ($41,721.98 vs. $37,330.16, p < 0.0001) of care. After adjusting for covariates, DD is associated with longer in-hospital, complications, and costs of care in patients undergoing ORIF for the treatment of acetabular fractures, whereas readmission rates are similar. The study is vital as it can be used by orthopaedists and healthcare professionals to adequately educate these patients of the potential outcomes following their surgical procedure.
A Large-scale Analysis of Hundreds of In-memory Key-value Cache Clusters at Twitter

Modern web services use in-memory caching extensively to increase throughput and reduce latency. There have been several workload analyses of production systems that have fueled research in improvi...
The Overlooked Victim Right: According Victim-Survivors a Right of Access to Restorative Justice

In recent years, states have accorded victim-survivors more expansive legal rights and made it easier for them to invoke those rights. Conspicuously absent from the litany of victims’ rights enumerated in the law is the right to be afforded access to restorative justice processes. This Article challenges this systemic failure to understand and respond to the full spectrum of victim-survivors’ needs. First, the Article provides three examples of core needs of victim-survivors that are largely disregarded by criminal justice systems and profiles how restorative justice equips criminal justice systems to better meet those needs. The Article then spotlights pertinent research confirming the benefits that redound to victim-survivors who participate in restorative processes. The Article concludes with a call for the law to accord victim-survivors a new right—a right of access to restorative justice processes—the need for which criminal justice systems have overlooked for far too long.
BioThings SDK: a toolkit for building high-performance data APIs in biomedical research

SummaryTo meet the increased need of making biomedical resources more accessible and reusable, Web APIs or web services have become a common way to disseminate knowledge sources. The BioThings APIs are a collection of high-performance, scalable, annotation as a service APIs that automate the integration of biological annotations from disparate data sources. This collection of APIs currently includes MyGene.info, MyVariant.info, and MyChem.info for integrating annotations on genes, variants, and chemical compounds, respectively. These APIs are used by both individual researchers and application developers to simplify the process of annotation retrieval and identifier mapping. Here, we describe the BioThings Software Development Kit (SDK), a generalizable and reusable toolkit for integrating data from multiple disparate data sources and creating high-performance APIs. This toolkit allows users to easily create their own BioThings APIs for any data type of interest to them, as well as keep APIs up-to-date with their underlying data sources. Availability and implementationThe BioThings SDK is built in Python and released via PyPI (https://pypi.org/project/biothings/). Its source code is hosted at its github repository (https://github.com/biothings/biothings.api).
Development and Test of Low Vibration Cryocooler Electronics

Closed system linear piston cryocoolers are becoming relied upon to provide reliable, continuous and efficient, low vibration cryogenic cooling for infrared focal plane arrays and optics. A brief synopsis of a Low Vibration Cryocooler Drive Electronics (CDE) from Rockwell is presented along with results of vibration cancellation on two opposed British Aerospace (BAe) 80K coolers. Discussions center on the measured performance of different approaches taken for mitigating vibration. The drive electronics systems performance has met requirements with vibration reductions of over 200:1, achieving less than 0.2 N axial and 0.4 N off axis force (Figure 4 & 6) for a 40W dual compressor drive.
Respect for the Unworthy

The claim that everyone ought to be treated with respect is a familiar and widely accepted prescription in recent moral philosophy, often expressed as a principle of ‘respect for persons.’ I argue that this principle need not be justified by a claim that every person possesses some feature – dignity, autonomy, value, or the like – that makes her worthy of respect. There is abundant conceptual space within many approaches to moral philosophy, including a Kantian approach, to affirm a duty of respect for all persons, while denying that the duty is justified by the respect-worthiness of every person.
Abstract 2758: Development of small molecule Bax agonists for lung cancer treatment

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Bax, a central death regulator, is required at the decisional stage of apoptosis. We recently discovered that the serine(S) 184 site on Bax is a critical functional switch for controlling the proapoptotic activity of Bax. The structural pocket around the S184 residue holds great promise as an ideal target for small molecule docking. We therefore employed the S184 residue as a docking site for screening small molecule therapeutic agents using the UCSF DOCK program suite and the NCI library of small molecules. Three compounds named small molecule Bax agonists (i.e. SMBA1, SMBA2 and SMBA3) were found to induce a conformational change of Bax by blocking phosphorylation of its S184 site, facilitating Bax insertion into mitochondrial membranes and formation of Bax oligomers leading to cytochrome c release and apoptosis in human lung cancer cells. Intriguingly, SMBA1 potently suppresses lung tumor growth via apoptosis in vivo without significant normal tissue toxicity. Survival outcomes remain very poor for lung cancer patients due to resistance to standard therapeutic interventions with radiation and systemic chemotherapy. Development of novel Bax agonists as an entirely new class of anti-cancer drugs has translational value to foster novel strategies for the treatment of lung cancer and other Bax expressing malignancies. Citation Format: Meiguo Xin, Rui Li, Dongkyoo Park, Taofeek K. Owonikoko, Gabriel L. Sica, Patrick E. Corsino, Jia Zhou, Chunyong Ding, Andrew T. Magis, Suresh S. Ramalingam, Walter J. Curran, Fadlo R. Khuri, Xingming Deng. Development of small molecule Bax agonists for lung cancer treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2758. doi:10.1158/1538-7445.AM2014-2758
Syntactic gains in short‐term study abroad

This article reports the results of a study of the syntactic acquisition of nine participants in a short-term study abroad program that was designed to complete the second year of German. Data compared study abroad students' use of accusative and dative case prepositions and ditransitives, auxiliary selection in the past tense, and dative verbs with the use of those constructions by students who completed the second-year course sequence at the home institution. The study abroad students performed at about the same level as the on-campus students on all syntactic measures but produced many more ditransitive clauses.
Dynamics of Jupiter's atmosphere

Jupiter's atmosphere is famous for its storm systems, such as the Great Red Spot, which has been active for more than 300 years. What drives Jupiter's turbulent weather has long been a matter of debate. New images from the Galileo spacecraft indicate that moist convection — familiar from thunderstorms on Earth — transports energy upwards through the clouds.
D-Tagatose is a bulk sweetener with zero energy determined in rats

The ketohexose D-tagatose is readily oxidized but contributes poorly to lipid deposition. We therefore examined whether this sugar contributes to energy requirements by determining its net metabolizable energy value in rats. All substrate-induced energy losses from D-tagatose, with sucrose as reference standard, were determined as a single value accounting for the sum of the energy losses to feces, urine, gaseous hydrogen and methane and substrate-induced thermogenesis. A randomized parallel design involving two treatment periods (adaptation to D-tagatose and subsequent energy balance) and two control groups (to control for treatment effects in each period) was used. Rats consumed 1.8 g test carbohydrate daily as a supplement to a basal diet for a 40- or 41-d balance period after prior adaptation for 21 d. Growth, protein and lipid deposition were unaffected by supplementary gross energy intake from D-tagatose compared with an unsupplemented control, but sucrose significantly (P < 0.05) increased all three. Based on the changes induced in protein and fat gain during the balance period it was calculated that D-tagatose contributed -3 +/- 14% of its heat of combustion to net metabolizable energy, and therefore this ketohexose effectively has a zero energy value. D-Tagatose would potentially be helpful in body weight control, especially in diabetic subjects because of its antidiabetogenic effects.
The Reader's Brain: How Neuroscience Can Make You a Better Writer

Have you ever found yourself re-reading the same sentence four or five times and thought 'I should get more sleep'? Are you clueless as to why one paragraph just seems to 'flow' while you simply can't recall the contents of another? Guess what: you are not alone. Even the best writers fail to grasp why their writing works. The Reader's Brain is the first science-based guide to writing, employing cutting-edge research on how our minds process written language, to ensure your writing can be read quickly, assimilated easily, and recalled precisely - exactly what we need to transform anyone into a highly effective writer. Using the 5Cs - clarity, continuity, coherence, concision, and cadence - this book combines irreverent humour with easy-to-follow principles that will make readers perceive your sentences, paragraphs, and documents to be clear, concise, and effective.
Commodifying kids: Branded identities and the selling of adspace on kids' networks

In the intense competition for the attention and loyalty of children and amidst the proliferation of children's programming, effective branding has become crucial for media companies. Interestingly, branding has also become the essential mechanism through which media companies attract advertisers concerned with reaching narrowly segmented audiences. It not sufficient for media companies to claim significant audience share: they must also characterize the nature of their relationship with their audience in a manner that suggests that both the relationship and audience are unique. For commercial children's networks, this means that beyond creating brand identity and brand loyalty, the network must also promote the branding process as one which transforms children from viewers into consumers likely to purchase products advertised within its specific program format. This paper traces critical developments in the evolution of the marketing and programming to children, and describes ad campaigns for Fox Kids an...
Turbidimetric studies of Limulus coagulin gel formation

The turbidity during trypsin-induced coagulin gel formation was studied over a range of wavelengths. The range of wavelengths used (686–326 nm) also made it possible to investigate the dependence of turbidity on wavelength (the wavelength exponent). Using the results from that work, and structural information on coagulin and the coagulin gel from other studies, a model gel-forming system was designed that consists of species for which the turbidity can be calculated relatively simply. These species include small particles (small in all dimensions relative to the wavelength of incident light); long rods and long random coils (particles that are large in just one dimension relative to the wavelength of incident light); and reflective regions (aggregated material that is large in more than one dimension relative to the wavelength of incident light). The turbidimetric characteristics of the real coagulin gel-forming system are compared with those of the model system.
Detection of bacterial 16S rRNA using a molecular beacon-based X sensor

Abstract We demonstrate how a long structurally constrained RNA can be analyzed in homogeneous solution at ambient temperatures with high specificity using a sophisticated biosensor. The sensor consists of a molecular beacon probe as a signal reporter and two DNA adaptor strands, which have fragments complementary to the reporter and to the analyzed RNA. One adaptor strand uses its long RNA-binding arm to unwind the RNA secondary structure. Second adaptor strand with a short RNA-binding arm hybridizes only to a completely complementary site, thus providing high recognition specificity. Overall the three-component sensor and the target RNA form a four-stranded DNA crossover (X) structure. Using this sensor, Escherichia coli16 S rRNA was detected in real time with the detection limit of ∼0.17 nM. The high specificity of the analysis was proven by differentiating Bacillus subtilis from E. coli 16 S rRNA sequences. The sensor responds to the presence of the analyte within seconds.
The Risk Finance of Class Action Settlement Pressure

Most high‐stakes litigation settles prior to the trial verdict being achieved. This apparent class action settlement pressure raises an interesting risk finance question addressed by the authors in this article. The article describes the basic law and economics of settlement risk within the context of potential and limitations of insurance and capital markets solutions.
The impact of panic expectancy and social demand on agoraphobic avoidance

The relationship between panic expectancy, social demand and agoraphobic avoidance was investigated in a group of 48 panic disorder subjects. Subjects were observed surreptitiously while completing a naturalistic behavioral avoidance task (BAT) involving either a high or low social challenge task. Subjects in the high social challenge task avoided more compared to subjects in the low social challenge task. Prediction of panic made before entering the situation and type of social challenge condition (high/low) were the only variables that accounted for significant amounts of unique variance in prediction of BAT score. The results confirm previous findings regarding the relationship between panic expectancy and avoidance and suggest that social interaction and scrutiny is a factor in avoidance.
Schistosome asparaginyl endopeptidase (legumain) is not essential for cathepsin B1 activation in vivo

Schistosomes are parasitic platyhelminths that constitute an important public health problem. Adult parasites live in the vasculature of their vertebrate hosts where they consume blood. Ingested blood proteins are degraded by a proteolytic cascade. One of the best characterized schistosome proteases is cathepsin B1 (SmCB1 or Sm31). This protein is synthesized as a large 38 kDa precursor form which is proteolytically cleaved to yield a mature, active 31 kDa enzyme. A second schistosome protease--the asparaginyl endopeptidase SmAE (also known as Sm32, or schistosome legumain), has been proposed to proteolytically convert the 38 kDa precursor SmCB1 into its mature form. Recombinant activated SmAE has been shown to trans-process SmCB1 into the mature, catalytic form in vitro. In the present study, our aim was to test the hypothesis that in vivo SmAE likewise processes SmCB1 into its active form. To do this, expression of the SmAE gene was suppressed in adult Schistosoma mansoni using RNA interference (RNAi). The results of these experiments show that, even in the absence of detectable SmAE protein, SmCB1 is fully processed and active and support the assertion that SmAE is not essential to activate SmCB1 in vivo. The data indicate that our original hypothesis is incorrect and that SmAE is not pivotal in the in vivo conversion of cathepsin B1 into its mature, active form.
Using the Effects of Depth Phases on P-wave Spectra to Determine Earthquake Depths

For shallow earthquakes, the surface-reflected depth phases ( pP and sP ) arrive shortly after the primary arrival, and the time separation among the three phases can be used to determine the origin depth of the earthquake. To model the relative arrival times and amplitudes of these phases, and the core reflections and water-column reverberations for a given earthquake, we construct stick seismograms using the IASPEI91 velocity model and the Harvard CMT focal mechanisms at the distances and azimuths of the recording seismometers. While the differing arrival times and amplitudes are features observable in the time series, they also affect the spectrum, and we compute the spectrum for a time window that includes the P wave and subsequent arrivals. We quantify the effects of variations in these properties over the focal sphere in terms of differences in the slope of the log spectrum at different stations. To determine the depth of an earthquake, we compare our observed spectral variations with the predicted spectral variations for earthquakes originating at depths within 30 km of the pde depth and identify the depth with the smallest L1 misfit as the true earthquake depth. We demonstrate the effectiveness of this method by applying it to a group of 35 thrust earthquakes in the Aleutian arc near the Andreanof Islands, but we also describe some complications introduced by strongly directive ruptures, as illustrated for the 1995 Jalisco, Mexico, event. Online material: Observed and predicted variations in pulse width for Aleutian Island earthquakes.
Nature of the Martian uplands: Effect on Martian meteorite age distribution and secondary cratering

Martian meteorites (MMs) have been launched from an estimated 5-9 sites on Mars within the last 20 Myr. Some 80-89% of these launch sites sampled igneous rock formations from only the last 29% of Martian time. We hypothesize that this imbalance arises not merely from poor statistics, but because the launch processes are dominated by two main phenomena: first, much of the older Martian surface is inefficient in launching rocks during impacts, and second, the volumetrically enormous reservoir of original cumulate crust enhances launch probability for 4.5 Gyr old rocks. There are four lines of evidence for the first point, not all of equal strength. First, impact theory implies that MM launch is favored by surface exposures of near-surface coherent rock (≤10 2 m deep), whereas Noachian surfaces generally should have ≥10 2 m of loose or weakly cemented regolith with high ice content, reducing efficiency of rock launch. Second, similarly, both Mars Exploration Rovers found sedimentary strata, 1-2 orders of magnitude weaker than Martian igneous rocks, favoring low launch efficiency among some fluvial-derived Hesperian and Noachian rocks. Even if launched, such rocks may be unrecognized as meteorites on Earth. Third, statistics of MM formation age versus cosmic-ray exposure (CRE) age weakly suggest that older surfaces may need larger, deeper craters to launch rocks. Fourth, in direct confirmation, one of us (N. G. B.) has found that older surfaces need larger craters to produce secondary impact crater fields (cf. Barlow and Block 2004). In a survey of 200 craters, the smallest Noachian, Hesperian, and Amazonian craters with prominent fields of secondaries have diameters of ~45 km, ~19 km, and ~10 km, respectively. Because 40% of Mars is Noachian, and 74% is either Noachian or Hesperian, the subsurface geologic characteristics of the older areas probably affect statistics of recognized MMs and production rates of secondary crater populations, and the MM and secondary crater statistics may give us clues to those properties.
Small bowel transplantation: Literature review 2003–2005

: The rapid expansion of the volume of peer reviewed publications in recent years, including a large increase in the number of new biomedical journals, makes it difficult for the practicing clinician to stay up to date with the medical literature. This review is part of a new series that will provide succinct summaries of the recent medical literature in the field of pediatric transplantation. In this review, we summarize important articles in the field of pediatric intestine transplantation that have been published over the last 2½ years (2003–2005). The review is intended to be comprehensive but not exhaustive.
Inhibition of solid tumor growth by Fas ligand-expressing myoblasts.

A major problem with standard treatments of solid tumors such as chemotherapy is that the effects are not localized to the tumor. As a result, normal tissue function is often severely impaired. Here we show that myoblasts from skeletal muscle that have been engineered with retroviral vectors to express Fas ligand (FasL) have potential as site-specific anti-tumor agents. FasL-expression by myoblasts was previously shown to lead to neutrophil-mediated immunodestruction, both of the cells and the surrounding tissue. Moreover, myoblasts expressing FasL induced apoptosis in Fas-expressing human tumor cells in vitro. These findings led us to investigate the possibility that myoblasts expressing FasL could serve as anti-tumor agents acting by both apoptotic and immunological mechanisms. The C57BL/6 lpr/lpr mouse primary myoblasts either expressing or not expressing murine FasL were co-injected with Fas-positive or Fas-negative human rhabdomyosarcoma cells into the tibialis anterior of immunodeficient mice. After 19–31 days, FasL-expressing myoblasts resulted in a marked accumulation of neutrophils and inhibited tumor growth in every case. By contrast, control myoblasts did not prevent significant tumor growth. The status of Fas expression by the tumor tissue in vivo was confirmed by immunostaining tumor sections with antibodies against Fas. Tumor inhibition was observed regardless of the presence or absence of Fas on the tumor cells, suggesting that in vivo, the induction of a neutrophil response is remarkably potent and sufficient to inhibit tumors.