cssi/SciSciGPT-SciSciNet huggingface dataset:
Immunogenicity of a BCR-ABL e1a2 p190 Translocation in a Balb/c Mouse Model.

Intracellular processing of the breakpoint products of the bcr-abl fusion gene may generate novel peptides that, if capable of binding to HLA class I molecules, would be potential targets for a cytotoxic T lymphocyte (CTL) response. In humans, peptides derived from the e1a2 p190 breakpoint have generated peptide-specific MHC class II proliferative responses. Short peptides have shown binding to MHC class I molecules, although processing and presentation of endogenous p190 protein has not been shown. In a Kd Balb/c mouse model, we tested the hypothesis that single, key amino acids near the breakpoint could be the reason of lack of immunogenicity of the p190 breakpoint peptides. We synthesized a native peptide from the 190 breakpoint (AFHGDAEAL) as well as a synthetic mutated peptide (AYHGDAEAL), which showed excellent predicted binding on the BIMAS algorithm (1152 and 2880 respectively), although in vivo experiments did not show any specific CTL response. In order to assess if the lack of immunogenicity in vivo was due to the absence of binding to the MHC class I molecule rather than to poor TCR interactions, we designed a series of peptides where neutral amino acid, alanine, substitutions were introduced at different potential binding sites in the synthetic peptide: at position three (AYAGDAEAL), position four (AYHADAEAL), position five (AYHGAAEAL) and position seven (AYHGDAAAL). The binding of these altered peptides to H2 class I was assessed using a MHC stabilization assay on T2-Kd cells (TAP deficient cells). In spite of the good computer prediction for binding the MHC stabilization assay did not show evidence of binding of the native and synthetic peptides (<1.9 over the background). In contrast, alanine substitution in position five resulted in the best binding (3.5x over the background). Alanine substitutions in positions three, four and seven also showed improved binding to Kd molecules (2.6x, 3.1x and 3x over the background respectively). These results were confirmed by immunization in vivo with these altered peptides. Only the peptide with the alanine substitution in position five generated a immune response in a CD8 gamma-IFN Elispot assay. Since the altered peptides with the alanine substitutions in positions three, four and seven have shown binding to the Kd molecules, but not a CTL response, change of the aspartic acid in position five near to the fusion breakpoint allows appropriate presentation and recognition of the sequence by the TCR.
The Dependence of the Predictability of Mesoscale Convective Systems on the Horizontal Scale and Amplitude of Initial Errors in Idealized Simulations

AbstractRecent work has suggested that modest initial relative errors on scales of O(100) km in a numerical weather forecast may exert more control on the predictability of mesoscale convective systems at lead times beyond about 5 h than 100% relative errors at smaller scales. Using an idealized model, the predictability of deep convection organized by several different profiles of environmental vertical wind shear is investigated as a function of the horizontal scale and amplitude of initial errors in the low-level moisture field. Small- and large-scale initial errors are found to have virtually identical impacts on predictability at lead times of 4–5 h for all wind shear profiles. Both small- and large-scale errors grow primarily up in amplitude at all scales rather than through an upscale cascade between adjacent scales. Reducing the amplitude of the initial errors improves predictability lead times, but this improvement diminishes with further reductions in the error amplitude, suggesting a limit to t...
Non Metastatic Cholestatic Liver Injury as a Presenting Sign of a Rare Hematologic Malignancy First Reported Case

Paraneoplastic syndromes are disorders that are triggered due to the presence of a neoplasm leading to different signs and symptoms resulting from damage to tissues or organs occurring remotely from the tumor These syndromes are thought to be mediated from altered immune response to the cancer and not as a result of direct spread and are therefore classified as non metastatic systemic diseases Knowledge of these syndromes is crucial especially as these may occasionally be the first presenting symptom of a malignancy in an individual While most paraneoplastic syndromes are documented in the literature and well recognized by the medical society there remain a few rare outliers whose presence still baffle healthcare providers and may delay diagnosis Stauffer rsquo s syndrome is one such paraneoplastic manifestation We present a case of a patient who presented with this uncommon syndrome and was subsequently diagnosed with a rare hematologic cancer nbsp
Damage to the Developing Brain and Subtle Psychiatric Consequences: Implications of the Case of Milton: Discussion of Dr. Christ’s Paper

Dr. Christ has focused our attention on a problem of central importance, not only in the treatment of childhood malignancies, but in the broader field of psychiatry and human behavior. American psychiatry and psychology have tended to neglect the role of the neural substrate in behavior and affect. The case of Milton is a beautiful illustration of the role that insult to the central nervous system (CNS) may play, both directly and indirectly, in influencing psychological function, and of how even well-trained clinicians may ignore it as a result of their theoretical preconceptions.
Tornado seasonality in the southeastern United States

Abstract Tornadoes are among the most destructive natural events and occur most frequently in the United States. It is difficult to ascertain if the frequency of tornadoes in the U.S. is increasing because our ability to observe and report tornado occurrence has increased over time. Previous studies have demonstrated that tornado likelihood has shifted toward earlier dates across the south-central United States over the past seven decades, the region sometimes called “Tornado Alley”, if it can be assumed that seasonal observation effort has not shifted over time. It is unclear if such shifts in tornado seasonality have also occurred elsewhere, including the region of the southeastern United States where tornado likelihood has a bimodal annual distribution. We use circular methods to demonstrate that the date of observed peak tornado occurrence during the early tornado season has not changed in the past seven decades. However, the date of peak tornado occurrence during the later tornado season has shifted toward earlier dates by more than a week. The influence of tropical storms had no effect on changes in late-season tornado seasonality. The conclusions are robust with respect to whether tornado counts or tornado days are used as the response variable. Results demonstrate the ongoing need to encourage tornado preparedness in the southeastern U.S., where tornadoes tend to have a higher impact on humans, and to understand the mechanisms that underlie trends in tornado seasonality.
Spot Sign in Acute Intracerebral Hemorrhage in Magnetic Resonance Imaging: A Case Report and Review of the Literature.

Introduction:Intracranial hemorrhage (ICH) is associated with significant mortality and morbidity. Current treatment paradigms focus on correcting hypertension and coagulopathy to prevent hematoma expansion. Magnetic resonance imaging (MRI) is becoming more common in the hyperactive phase of ICH man
Validation of the Work-Disability Physical Functional Assessment Battery

Abstract Objective To examine the validity of the self-report Work-Disability Functional Assessment Battery (WD-FAB) physical function scales relative to clinician ratings of function and a performance-based functional capacity evaluation called the Physical Work Performance Evaluation (PWPE). Design Cross-sectional. Setting Outpatient rehabilitation. Participants Adults (N=50) participating in physical therapy for musculoskeletal conditions. Interventions Not applicable. Main Outcome Measures Patients completed the PWPE and the WD-FAB physical function scales including Changing and Maintaining Body Position, Whole Body Mobility, Upper Body Function, and Upper Extremity Fine Motor. The physical therapist also answered the WD-FAB questions on the patient’s physical functioning. The WD-FAB computer-adaptive test version administered up to 10 items for each scale. The PWPE produces ratings from 0 to 5 indicating overall Level of Work ability: 0 (unable to work); 1 (sedentary); 2 (light); 3 (medium); 4 (heavy); 5 (very heavy). The PWPE also produces Level of Work ability ratings in the Dynamic Strength, Position Tolerance, and Mobility subsections. Results Participating in the study were 50 patients with 1 or more conditions (shoulder, n=21; knee, n=16; low back, n=13; ankle/foot, n=10; neck, n=8; hip, n=7). The patient-based WD-FAB scores demonstrated moderate, statistically significant correlations with the provider proxy WD-FAB report ( R =.49-.65). The WD-FAB Upper Body Function scale scores demonstrated moderate strength relationships with the PWPE overall ratings. The Whole Body Mobility and Changing and Maintaining Body Position scales did not demonstrate statistically significant relationships with the PWPE overall ratings. Conclusions We found moderate evidence for validity for the WD-FAB Upper Body Function, Whole Body Mobility, and Changing and Maintaining Body Position scales relative to clinician report and varied evidence relative to the PWPE in this clinical sample.
Schooling and the Civic Exclusion of Latinos: Toward a Discourse of Dissonance:

In the United States, schooling has been traditionally viewed as the primary mechanism by which individuals are socially and politically prepared to function as active citizens. Through educational support of what has been termed “civic inclusion,” peripheral members of society, i.e., minorities and the poor, are purportedly given access to mainstream society.This article examines the fallacy of civic inclusion for Latino students in U S. schools and demonstrates how schools actually promote an educational and civic exclusion. Discussed are the language, culture, and community-related strategies students utilize to confront exclusion and the new forms of inclusion which this discourse engenders.
Nonlinear and Threshold Aspects of Neighborhood Effects

An important frontier in context effects research is investigating nonlinear and threshold effects. There is ample theoretical foundation for suggesting that several endogenous social processes generate nonlinear relationships between measures of neighborhood social composition and a variety of outcomes for individual residents. There is also a growing international body of statistical literature testifying to the existence of nonlinear and threshold effects, though the findings are often inconsistent, especially in the European-based scholarship. Further empirical research on this topic is crucial because identifying the precise nature of nonlinear and threshold effects provides both a necessary social efficiency justification and practical programmatic guidance for policies designed to encourage more social diversity within neighborhoods.
A Pound of Prevention? Assessing the Value of New Cholesterol-Lowering Drugs.

PCSK9 inhibitors substantially reduce cholesterol levels, but the U.S. Food and Drug Administration–approved PCSK9 inhibitors, alirocumab and evolocumab, came to market priced at $14 000 per year—m...
Peroxisomal fatty acid β-oxidation negatively impacts plant survival under salt stress

Peroxisomal β-oxidation is the sole pathway for metabolic breakdown of fatty acids to generate energy and carbon skeletons in plants, is essential for oilseed germination and plays an important role in growth, development and cellular homeostasis. Yet, this process also produces cytotoxic reactive oxygen species (ROS) as byproducts. We recently showed that disruption of fatty acid β-oxidation enhance plant survival under carbon starvation conditions. Here, we extend these findings by demonstrating that blocking fatty acid import into peroxisomes reduces ROS accumulation and increases plant tolerance to salt stress, whereas increasing fatty acid flux into the β-oxidation pathway has opposite effects. Together, these results support the view that peroxisomal β-oxidation of fatty acids enhances stress-induced ROS production, thereby negatively impacting plant survival under adverse environmental conditions.
The Role of Medical Professionals in Social Media

Patients are searching online to find health-related information. The information they find may serve as their only source of information, or it may be complementary to the information they receive from their personal healthcare provider, friends, or family members. Regardless, by seeking information online, they will inevitably encounter misinformation. This can lead to any number of problems including incorrect self-diagnosis, unnecessary angst regarding their established medical condition, or unfounded and exaggerated expectations from treatment options. While misinformation may be present, patients are seeking correct information, and they value expert opinion. If healthcare professionals are not engaged in social media to provide evidence-based information, their void will be filled by personal anecdotes, pseudoscientific approaches, and snake oil salesmen. Even if a healthcare professional is not interested in engaging in social media, they must still be aware of the information their patients are encountering online in order to provide anticipatory guidance in the clinical setting. For those who are interested in participating, there are a variety of ways for healthcare professionals to get more involved. This chapter will discuss why, how, and what healthcare professionals can do to lend their expert voice to the online conversation that is already happening…with or without their consent.
Structural transients from the impact force excitation of beams

Analytical and experimental results are presented for the transient longitudinal and flexural waves which result from the impact force excitation of beams. Space-time, integral transform and convolution methods are utilized for the analyses. Analytical results are presented for the in vacuo velocity response of an infinite, semi infinite and a beam of finite length to illustrate the effects of boundary reflection and material dissipation on flexural and longitudinal waves. Experimental results are then presented to illustrate the general behavior of transient longitudinal and flexural wave propagation in a free-free beam of finite length in vacuo which is impacted by a hammer excitation. In contrast to the clearly observable multi-pulse structure for the reflected longitudinal waves the dispersive nature of the flexural waves results in overlapping reflected waves with a loss of the multi-pulse structure. Frequency-time analyses provide a clearer picture of the underlying physics and illustrate the expected dispersion relationships.Analytical and experimental results are presented for the transient longitudinal and flexural waves which result from the impact force excitation of beams. Space-time, integral transform and convolution methods are utilized for the analyses. Analytical results are presented for the in vacuo velocity response of an infinite, semi infinite and a beam of finite length to illustrate the effects of boundary reflection and material dissipation on flexural and longitudinal waves. Experimental results are then presented to illustrate the general behavior of transient longitudinal and flexural wave propagation in a free-free beam of finite length in vacuo which is impacted by a hammer excitation. In contrast to the clearly observable multi-pulse structure for the reflected longitudinal waves the dispersive nature of the flexural waves results in overlapping reflected waves with a loss of the multi-pulse structure. Frequency-time analyses provide a clearer picture of the underlying physics and illustrate the expect...
Changing health behaviours in rheumatology: an introduction to behavioural economics.

Although the management of patients with rheumatic diseases has evolved substantially over the past 20 to 30 years, lifestyle changes (such as weight reduction, physical activity and medication adherence) remain an important and unmet challenge in improving patient outcomes. The field of behavioural economics considers the many ways that individuals behave irrationally and uses the predictability of these patterns to create opportunities to anticipate and avoid or harness these behaviours to improve patient outcomes. Existing among other motivational approaches, the concepts in behavioural economics have only been applied to health care in the past 10 to 15 years. Although few published examples have applied behavioural economic concepts in the management of patients with rheumatic diseases specifically, these concepts have been applied in other chronic diseases, and such interventions could also be applicable in rheumatology. In this Perspectives article, we introduce six principles in behavioural economics (loss aversion, framing effect, present bias, status quo bias, time inconsistency and social normalization), discuss how these concepts have been addressed in other fields and examine their potential application in rheumatology. Using physical activity as an example, we describe how these concepts could be applied to promote healthy behaviour in patients with inflammatory arthritis. Behavioural economics uses psychological and economical insights to explain decision making by individuals to understand the predictable way in which individuals behave irrationally. Concepts from this field can be applied to promote healthy behaviours and could be applicable to rheumatology.
Filthy Material: Modernism and the Media of Obscenity: CHRIS FORSTER, 2018 New York, NY, Oxford University Press pp. 232, illus., bibliography, index, $35.00 (paper)

Filthy Material: Modernism and The Media of Obscenity is a stirring look at the role of materiality, media, and the process of reading for histories of modernist literature. Focusing much on textua...
Trends in Surgical Axillary Management in Early Stage Breast Cancer in Elderly Women: Continued Over-Treatment.

In the past two decades, three prospective randomized trials demonstrated that elderly women with early stage hormone positive breast cancer had equivalent disease-specific mortality regardless of axillary surgery. In 2016, the Choosing Wisely campaign encouraged patients and providers to reconsider the role of axillary surgery in this population. We sought to identify factors that contribute to adopting non-operative management of the axilla in these patients. We performed a retrospective analysis of women ≥ 70 years old with cT1/T2, hormone positive invasive ductal carcinoma who underwent partial or total mastectomy, with/without axillary surgery, and did not receive adjuvant chemotherapy from the National Cancer Database from 2004 to 2015. We used multivariable log-binomial regression to model the risk of undergoing axillary surgery across region, care setting, and Charlson–Deyo scores, and analyzed temporal trends using Poisson regression. From 2004 to 2015, 87,342 of 99,940 women who met inclusion criteria (83%) had axillary surgery. Over time, axillary surgery increased from 78% to 88% (p < 0.001). This rise was consistent across region (p = 0.81) and care setting (p = 0.09), but flattened as age increased (p < 0.001). Omitting axillary surgery was more likely in patients treated in New England (RR 0.88, 95% CI 0.86, 0.89) and patients ≥ 85 (RR 0.66, 95% CI 0.65, 0.67). Axillary surgery continues to be the preferred option of axillary management in elderly women with early stage, clinically node negative, hormone-positive, invasive breast cancer despite no survival benefit. Identifying factors to improve patient selection and dissemination of current recommendations can improve adoption of current evidence on axillary surgery in the elderly.
A deep-learning-based surrogate model for data assimilation in dynamic subsurface flow problems

Abstract A deep-learning-based surrogate model is developed and applied for predicting dynamic subsurface flow in channelized geological models. The surrogate model is based on deep convolutional and recurrent neural network architectures, specifically a residual U-Net and a convolutional long short term memory recurrent network. Training samples entail global pressure and saturation maps, at a series of time steps, generated by simulating oil-water flow in many (1500 in our case) realizations of a 2D channelized system. After training, the ‘recurrent R-U-Net’ surrogate model is shown to be capable of predicting accurate dynamic pressure and saturation maps and well rates (e.g., time-varying oil and water rates at production wells) for new geological realizations. Assessments demonstrating high surrogate-model accuracy are presented for an individual geological realization and for an ensemble of 500 test geomodels. The surrogate model is then used for the challenging problem of data assimilation (history matching) in a channelized system. For this study, posterior reservoir models are generated using the randomized maximum likelihood method, with the permeability field represented using the recently developed CNN-PCA parameterization. The flow responses required during the data assimilation procedure are provided by the recurrent R-U-Net. The overall approach is shown to lead to substantial reduction in prediction uncertainty. High-fidelity numerical simulation results for the posterior geomodels (generated by the surrogate-based data assimilation procedure) are shown to be in essential agreement with the recurrent R-U-Net predictions. Comparisons to simulation-based data assimilation results further highlight the accuracy and applicability of the recurrent R-U-Net, and suggest that it may enable the use of more formal posterior sampling methods in realistic problems.
Oncological and functional outcomes in patients over 70 years of age treated with robotic radical prostatectomy: a propensity-matched analysis.

The aim of this study was to report on the safety (complications) and efficacy (oncological and functional outcomes) of robot-assisted radical prostatectomy (RARP), performed at our institution, in patients aged over 70. Review of our prospectively collected database [Cancer Information Systems (CAISIS)] identified two hundred and fifteen (215) patients, aged > 70, who underwent RARP for localized prostate cancer between July 2003 and August 2017. A propensity score-matched analysis, with multiple covariates, was performed to stratify the patients into Age ≤ 70 and Age > 70 comparison groups. Apart from Age (mean ± SD years: 73.5 ± 2.1 vs 59.5 ± 5.9, p 0.05). Median follow-up was 10.6 years. There were no 90-day mortalities in either group. Minor complications (Clavien ≤ 2) were more common in the Age > 70 group (p = 0.0002). Operating room time (p = 0.83), length of hospital stay (p = 0.06) and catheterization duration (p = 0.13) were similar. On final pathology, a higher pT stage (p 70 group. However, this did not translate adversely into higher rates of positive surgical margin (p = 0.41) or biochemical relapse (p = 0.72). Allowing for the follow-up duration (median 10.6 years), cancer-specific survival was marginally significant (p = 0.05) with an observed lower rate in the Age > 70 group. In terms of functional outcomes, post-operative erectile dysfunction and pad-free continence were significantly better in the younger cohort (p < 0.0001). Robot-assisted radical prostatectomy should not be denied to those over 70 years solely on the basis of age. Older men need to be counseled about the likelihood of encountering higher-risk features on final pathology and that their functional outcomes may be worse compared to a younger person.
Emerging pathways for precision medicine in management of cholangiocarcinoma

Cholangiocarcinoma (CCA) is the second most common biliary tract malignancy with a dismal prognosis. Surgical resection with a negative microscopic margin offers the only hope for long-term survival. However, the majority of patients present with advanced disease not amenable to curative resection, mainly due to late presentation and aggressive nature of the disease. Unfortunately, due to the heterogeneous nature of CCA as well as limitations of available chemotherapy medications, traditional chemotherapy regimens offer limited survival benefit. Recent advances in genomic studies and next-generation sequencing techniques have assisted in better understanding of cholangiocarcinogenesis and identification of potential aberrant signaling pathways. Targeting the specific genomic abnormalities via novel molecular therapies has opened a new avenue in management of CCA with encouraging results in preclinical studies and early clinical trials. In this review, we present emerging therapies for precision medicine in CCA.
Toward high voltage radio frequency devices in β-Ga2O3

The path to achieving integrated RF and power conversion circuitry using the β-Ga2O3 material system is described with regard to the materials high Johnson's RF figure of merit. Recent results, including large signal data at VD = 50 V, are provided, showing progress in achieving high-voltage RF operation. Additionally, progress in achieving high-gain devices through gate length scaling is also benchmarked by a record RF power device with a gate length of 0.5 μm achieving a 2.1 GHz μm f T − L G product. These results are compared with state-of-the-art RF devices, and the expectations for β-Ga2O3 at this point in its maturity throughout this Letter with future milestones laid out to measure progress. The conclusion includes near- and long-term projections for β-Ga2O3 devices for RF based on the results and projected milestones presented.
Lumbar Spine Injuries

Low back pain comprises 10–15% of all sports injuries and is the most common spine-related reason for missed playing time (Mortazavi et al. Asian J Sports Med 6(2):e24718, 2015). Rates are dependent on many factors including chosen sport and position, gender, training, frequency, and intensity (Bono. J Bone Joint Surg Am 86(2):382–96, 2004; Daniels et al. Sports Health 3(4):336–45, 2011; Schmidt et al. Int J Sports Med 35(8):684–9, 2014). Young athletes with back pain are more likely to have structural injuries from acute trauma or repetitive overuse than muscular strain, and appropriate imaging should be obtained when needed to aid in the diagnosis (Purcell and Micheli. Sports Health 1(3):212–22, 2009).
Image-Guided Volumetric Modulated Arc Therapy for Total Body Irradiation: A Single Institution Experience.

PURPOSE/OBJECTIVE(S) The use of multi-isocentric volumetric mediated arc therapy (VMAT) for total body irradiation (TBI) improves dose uniformity and organ-at-risk avoidance and offers better patient comfort, but is limited by time-intensive planning and positioning errors at treatment delivery. We present a system that utilizes automated contouring and planning scripts run in widely-available software combined with image-guided delivery for an efficient simulation-to-treatment workflow. We hypothesize that this system will improve target dose coverage and normal tissue avoidance compared to conventional TBI. MATERIALS/METHODS Patients were simulated supine in both head-first and feet-first positions. Automated planning software scripts were used to co-register the two simulation scans into a single whole-body CT, to contour organs at risk and planning target volume (PTV), to divide the PTV into sub-targets with junction region overlap, and to place isocenters. Treatment was planned with VMAT for the entire body except for legs and feet, which were planned with conventional AP/PA fields. Image guidance was used for treatment delivery. Plans were evaluated for quality, planning time, delivery time, and setup accuracy. The dosimetric parameters of VMAT-TBI plans versus conventional AP/PA TBI plans were compared. RESULTS Twelve patients were simulated and treated with VMAT-TBI: three pediatric patients and nine adult patients (age range: 9-59). Compared with conventional whole-body AP/PA technique, VMAT-TBI improved dose coverage to the whole body: PTV V100 was improved from 71.4% ± 11.1% to 88.1% ± 2.6% (P < 0.001). Mean lung dose was reduced from 11.1 Gy ± 0.9 Gy to 9.3 Gy ± 1.0 Gy (P < 0.001). With a beam monitor unit (MU) rate of 200 MU/minute, mean lung dose rate was 15.5 centiGray (cGY)/minute. Robust planning and image-guided delivery reduced setup uncertainty. VMAT-TBI planning time was one working day. Total time on the treatment table was approximately one hour per fraction. All patients were able to complete the treatment course as prescribed. CONCLUSION A robust treatment planning technique and an image-guided delivery workflow were developed for VMAT-TBI. Planning efficiency was improved using automation with scripts, making planning time comparable to traditional TBI. Compared with classic AP/PA whole body fields, VMAT-TBI improved whole body prescription dose coverage and lung sparing. Time on treatment table was comparable to treatment time for traditional TBI, and patient comfort was improved due to ability to deliver treatment in the supine position. VMAT planning should be considered for all myeloablative transplant protocol patients being treated with TBI.
Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis.

Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.
Abstract 3784: Induction of BRCAness phenotype by curcumin and hydroxyurea in WT BRCA ovarian cancer cells

The field of ovarian cancer therapeutics has made a substantial leap forward with the discovery that ovarian cancers with a BRCA mutation, can be exploited with “synthetic lethality.” In patients who have a BRCA germline mutation, this phenomenon is achieved by blocking PARP (poly-ADP-ribosyl-polymerase), which has a role in compensating for the missing or low levels of the BRCA protein. PARP activity is essential for DNA repair in patients with BRCA mutations as their cells attempt to maintain a normal genotype; however, PARP is not enough to compensate for the BRCA mutation, and these patients eventually develop ovarian cancer. Out of the five major mechanisms of DNA repair, PARP compensates for missing BRCA1 and/or BRCA2 proteins required for homologous repair, base excision repair and nuclear excision repair. If PARP is inhibited in BRCA-mutant patients, DNA mutations accumulate and are not repaired because PARP is not available to ribosylate the areas of cut or damaged DNA, which would signal that repair is needed. The BRCA-mutant genotype, in which there is a germline-inactivating mutation in one allele and loss of heterozygosity or somatic mutation in the other allele, only occurs in 5-10% of the cancer population. We wondered, “is there a way to apply the concept of “synthetic lethality” to the 90-95% of the ovarian cancer patients who do not have BRCA mutations?” We tried to answer that query by testing different gene-expression, modulating agents. We found that low-concentration hydroxyurea can sometimes potentiate the cytotoxicity of alkylating agents, suggesting a mechanism that involves DNA repair. We found synergistic apoptosis in 4 (ovcar-8, TOV21G, PA-1 and UACC1598) ovarian cancer cell lines treated with hydroxyurea and the PARP inhibitor, Olaparib, and in cells treated with curcumin with Olaparib. When the Ovcar-8 cancer cell line was treated with a single agent, the percentage of apoptosis was ≤ 17%, and when treated with synergistic agents together, relative apoptosis increased to ≤ 45%. In these cell lines, both curcumin and hydroxyurea significantly decreased BRCA1 and BRCA2 mRNA and protein levels. We also found that curcumin triggered BRCA1,2 promoter methylation, which led to cessation of gene expression. Whereas, hydroxyurea, not only caused BRCA1,2 promoter methylation, but also elicited an increase in miRNA hsa-miR-17-5p and hsa-miR-182-5p, causing BRCA1 mRNA degradation. This finding suggests greater than 5-10% of wild-type, BRCA ovarian cancer patients may benefit from PARP inhibitors and DNA cross-linking agents, such as mitomycin C. if they can be induced into “BRCAness,” Citation Format: Yuehua Mao, Richard D Dinnen, Robert L. Fine. Induction of BRCAness phenotype by curcumin and hydroxyurea in WT BRCA ovarian cancer cells. [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 3784. doi:10.1158/1538-7445.AM2014-3784
Pattern synthesis for a conformal wing array

Future aircraft may utilize the large aerodynamic areas of the wings also for electrodynamics by structurally embedding conformal phased array antennas. We explore this concept with a computer model for a line array wrapped around a wing. The model uses a realistic wing profile and array element patterns which include the effects of mutual coupling and the local radius of curvature. The study has two objectives: 1) develop a pattern synthesis method which is effective for this non-conventional array shape, and 2) determine whether low sidelobe patterns can be realized. We find that pattern synthesis based on alternating projections is a flexible and highly efficient synthesis method. No convergence problems due to local minima occurred. High quality patterns with uniform low sidelobes were achieved for most beam directions, except in a narrow sector about the difficult forward direction, where there appears to be a sidelobe floor of roughly -23 dB.
Dynamic Data-driven Deformable Reduced Models for Coherent Fluids 1 .

Abstract In autonomous mapping of geophysical fluids, a DDDAS framework involves reduced models constructed offline for online use. Here we show that classical model reduction is ill-suited to deal with model errors manifest in coherent fluids as feature errors including position, scale, shape or other deformations. New fluid representations are required. We propose augmenting amplitude vector spaces by non-parametric deformation vector fields which enables the synthesis of new Principal Appearance and Geometry modes, Coherent Random Field expansions, and an Adaptive Reduced Order Model by Alignment (AROMA) framework. AROMA dynamically deforms reduced models in response to feature errors. It provides robustness and efficiency in inference by unifying perceptual and physical representations of coherent fluids that to the best of our knowledge has not hitherto been proposed.
DIMETHYL AND CATIONIC 1,4-DIAZABUTADIENE COMPLEXES OF PLATINUM(II)

The reaction of the 1,4-diazabutadiene ligand glyoxal bis(2-(methoxymethyl)-4,6-di-tert-butylphenyl)diimine (L) with the platinum complex Pt2Me4(SMe2)2 yields two isomers of the complex PtMe2L (2a,...
Associations between forced sex, sexual and protective practices, and sexually transmitted diseases among a national sample of adolescent girls

Abstract Objective The main objective of this study is to better understand the associations between forced sex history and history of sexually transmitted disease (STD) infection. Three research questions are investigated. Is history of forced sex associated with risk-taking behaviors? Are these risk-taking behaviors associated with history of STD? Is history of forced sex independently associated with history of STD? Methods Information on the sexual and STD histories is obtained from 3,579 sexually active adolescent girls using data from the National Longitudinal Study of Adolescent Health. Weighted logistic and OLS regressions are employed, using techniques that account for the complex sampling design. Results Girls with a history of forced sex are significantly more likely to have a greater number of sexual partners, be younger at first sex, and be more likely to use alcohol or drugs at last sex; there is no difference in condom use at last sex. These factors, in turn, are significantly associated with a positive STD history. Condom use at last sex is negatively associated with ever having had an STD. When all five sexual and protective practices are investigated simultaneously, history of forced sex remains significantly associated with STD history (odds ratio [OR] = 1.39, p = .014); number of sexual partners and early onset of sex remain significant. Condom use and substance use at last sex reduce to marginal significance. Conclusions These results suggest that a history of forced sex is independently associated with a history of STD among sexually active adolescent girls. Programmatic strategies aimed at reducing STDs through encouraging responsible sexual behavior would potentially benefit from also including a component that addresses sexual victimization.
Ibotenate-induced cell death in the hypothalamic paraventricular nucleus: differential susceptibility of magnocellular and parvicellular neurons

Injections of ibotenic acid (IBO) (0.5-2.0 micrograms) were made unilaterally into the hypothalamic paraventricular nucleus (PVN) of Sprague-Dawley rats. A distinct loss of parvicellular neurons was evident at all dosages examined, and cell death appeared uniform throughout the injection region at doses of 1.0 micrograms or greater. In contrast, magnocellular neurons were present following injections of all dosages, with a slight loss of neurons evident only at 2.0 micrograms doses. Magnocellular neurons killed at 2.0 micrograms doses were primarily vasopressinergic. Neuropeptide content per se was not the critical determinant of susceptibility to IBO, as parvicellular oxytocin neurons were destroyed by low to moderate doses of IBO. The results suggest that IBO may be useful neurotoxin with which to investigate differential connectional and functional properties of parvicellular and magnocellular PVN neurons.
Probabilistic Mental Models with Continuous Predictors.

Gigerenzer and his colleagues have sought to develop psychologically plausible models of human judgment. Their models are classified as ones of bounded rationality based on a principle of one-reason decision making. The models associated with the theory of Probabilistic Mental Models (PMM) have been developed for tasks in which all predictors are binary. This article extends PMM to the case of continuous predictors. The current model employs the limitation on the number of categories people use in making absolute judgments along a single perceptual dimension (7 ± 2; Miller, 1956). The algorithm transforms each continuous predictor to be consistent with this limitation, then implements a step-down one-reason decision procedure similar to previous PMM models. Like previous PMM models, the 7 ± 2 model predicts binary judgments as well as a multiple-regression model. However, the model does not successfully predict the probability judgments of individual participants, which is also true of all other models in the literature.
Simultaneous disruption of estrogen receptor and Wnt/β-catenin signaling is involved in methyl amooranin-mediated chemoprevention of mammary gland carcinogenesis in rats

Methyl-amoorain (methyl-25-hydroxy-3-oxoo-lean-12-en-28-oate, AMR-Me), a novel synthetic oleanane triterpenoid, exerts a striking chemopreventive effect against 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis through antiproliferative and proapoptotic actions. Nevertheless, the underlying mechanisms of action remain to be established. As estrogen receptor (ER) and canonical Wnt/b-catenin signaling are involved in the development and progression of breast cancer, the current study was designed to investigate the effects of AMR-Me treatment on the expressions of ER-a, ER-b, b-catenin and cyclin D1 in rat mammary tumors induced by DMBA. Mammary tumor samples were harvested from an 18-week chemopreventive study in which AMR-Me (0.8–1.6 mg/kg) was shown to inhibit mammary carcinogenesis in a dose–response manner. The expressions of ER-a, ER-b, b-catenin, and cyclin D1 were determined by immunohistochemistry and reverse transcription-polymerase chain reaction. AMR-Me downregulated the expression of intratumor ER-a and ER-b and lowered the ratio of ER-a to ER-b. AMR-Me also reduced the expression, cytoplasmic accumulation, and nuclear translocation of b-catenin, the essential transcriptional cofactor for Wnt signaling. Furthermore, AMR-Me modulated the expression of cell growth regulatory gene cyclin D1, which is a downstream target for both ER and Wnt signaling. AMR-Me at 1.6 mg/kg for 18 weeks did not exhibit any hepatotoxicity or renotoxicity. The results of the present study coupled with our previous findings indicate that simultaneous disruption of ER and Wnt/b-catenin signaling possibly contributes to antiproliferative and apoptosis-inducing effects implicated in AMR-Me-mediated chemoprevention of DMBA-induced breast tumorigenesis in rats. Our results also suggest a possible crosstalk between two key regulatory pathways, namely ER and Wnt/b-catenin signaling, involved in mammary carcinogenesis and the value of simultaneously targeting these pathways to achieve breast cancer chemoprevention.
Postembryonic development of teratogen-induced supernumerary eyes in Acheta domesticus (L.) (Orthoptera : Gryllidae)

Abstract Supernumerary compound eyes were generated in the cricket Acheta domesticus (L.) (Orthoptera : Gryllidae) by applying the insect teratogen biquidone (benz[g]isoquinoline-5, 10-dione) and partially characterized teratogenic mixtures to eggs within 24 hr following oviposition at 31 ± 0.5°C. Postembryonic development of supernumerary eyes was compared with that of normal compound eyes, using light and scanning electron microscopy. All elements of the dioptric apparatus were present in supernumerary eyes of nymphs, but no axonal connection to the brain was found. Supernumerary eyes deteriorated during successive instars. Occasionally, these eyes were sloughed off before the adult stage was reached; more frequently, eyes appeared as highly pigmented protrusions not readily identifiable as adult eye tissue. Teratogen-induced supernumerary eyes are probably not functional light receptors in A. domesticus nymphs or adults.
Arabidopsis SKP1, a homologue of a cell cycle regulator gene, is predominantly expressed in meristematic cells.

The yeast SKP1 gene and its human homolog p19 skp1 encode a kinetochore protein required for cell cycle progression at both the DNA synthesis and mitosis phases of the cell cycle. In orchids we identified a cDNA (O108) that is expressed in early stages of ovule development and is homologous to the yeast SKP1. Based on the orchid O108 cDNA clone, we identified and characterized an Arabidopsis thaliana (L.) Heynh. cDNA designated ATskp1 that also has high sequence similarity to yeast SKP1. The Arabidopsis ATskp1 is a single-copy gene that mapped to chromosome 1. The expression of the ATskp1 gene was highly correlated with meristem activity in that its mRNA accumulated in all of the plant meristems including the vegetative shoot meristem, inflorescence and floral meristems, root meristem, and in the leaf and floral organ primordia. In addition, ATskp1 was also highly expressed in the dividing cells of the developing embryo, and in other cells that become multinucleate or undergo endoreplication events such as the endosperm free nuclei, the tapetum and the endothelium. Based on its spatial pattern of expression, ATskp1 is a marker for cells undergoing division and may be required for meristem activity.
Psoriasis: immunopathogenesis and evolving immunomodulators and systemic therapies; U.S. experiences

Summary Background Psoriasis is a chronic inflammatory skin disorder that is presently without a permanent cure. Up to 40% of patients with psoriasis also develop psoriatic arthritis. The mainstay armamentarium to treat psoriasis systemically includes methotrexate, ciclosporin and oral retinoids, all with significant potential for toxicity and the need for close laboratory supervision. The although the exact mechanism of psoriasis is still unclear, the involvement of T-cell-mediated cytokine expression in the aetiology of psoriasis is becoming clearer. The goal of modern treatment is to target such immune responses that lead to the formation of psoriatic plaques and psoriatic arthritis using selective immunomodulating pharmacotherapy. The advantages of these biological agents are less toxic systemic side-effect profiles that will improve the quality of life in psoriatic patients. Objectives This review article describes current and emerging selective immunotherapies and systemic therapies for the treatment of psoriasis, and will briefly discuss disease immunopathogenesis. Methods Literature review. Results and conclusions Given the role of the inflammatory immune responses in the pathogenesis of psoriasis, the goal of modern medicine and pharmacotherapy lies in the design and use of specific targets in cell-mediated immune reactions and the modulation of the expression of various inflammatory cytokines. The clinical evidence of efficacy of some of these new biological immunomodulatory agents from several U.S.-based research studies and clinical experiences is convincing.
Extending the scope of FTIs

Advances in molecular biology and the understanding of signal transduction are allowing us to identify novel targets for the development of drugs for hematologic malignancies. One such potential target is farnesyl transferase, the enzyme responsible for the prenylation of proteins. Prenylation, the
Demonstration of spleen colonies on grafted spleens in the radiation chimera.

We have demonstrated the post-irradiation development of countable endogenous spleen colonies in spleens transplanted intraperitoneally 6 weeks prior to X-irradiation of the host. We have further demonstrated countable exogenous spleen colonies on spleen grafts transplanted prior to the irradiation of the host and the injection of bone-marrow cells. Although autografted spleens in irradiated recipients did not attain their presplenectomy mass, the number of colony forming units (CFU)/105 injected cells assayed after irradiation and bone-marrow cell injection was about the same as in sham-splenectomized mice. Isografted spleens in sham-splenectomized mice were much smaller than the host or autografted spleens and the number of CFU/105 injected cells assayed per isograft was only 25–33 % of that observed in host mice.