cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 12719: Expression of DHRS7c, A Novel Cardiomyocyte-expressed Gene Affected by Adrenergic Stimulation, is Strongly Associated With Ventricular Reverse-remodeling in Dilated Cardiomyopathy

Background: The molecular mechanisms by which β-blockers produce ventricular reverse-remodeling in nonischemic dilated cardiomyopathy (NDCM) are incompletely understood. DHRS7C is a short chain dehydrogenase/reductase of uncertain functional significance expressed preferentially in the myocardium and down-regulated in heart failure or with α- and β-adrenergic stimulation. The objective of this study was to determine the association of DHRS7C with DCM and reverse-remodeling in heart failure patients taking β-blockers. Methods and Results: Forty-seven NDCM patients were randomized to metoprolol succinate, metoprolol + doxazosin, or carvedilol for 18 months. Ejection fractions (EFs) were measured by radionuclide ventriculography, and myocardial biopsy was performed at baseline, 3, and 12 months. Transcriptome-wide myocardial mRNA expression was measured using the Affymetrix HGU133 plus 2.0 GeneChip. DHRS7C expression was significantly reduced in DCM patients compared with 4 non-failing controls (7.3±0.2 vs. 9.0±0.7, p=0.03). Thirty-one (66%) patients had a reverse-remodeling response defined as improvement of 8 LVEF units at 12 months or if not available, 5 LVEF units at 3 months. DHRS7C was significantly more up-regulated in responders vs. non-responders (4.1±0.6 vs. 2.2±0.7 fold change, p=0.03). Change in gene expression was significantly correlated with change in LVEF (r=0.52, p<0.001), RVEF (r=0.40, p<0.001), and heart rate (r=-0.38, p<0.01). These correlations were comparable to other genes associated with reverse-remodeling. Conclusions: Myocardial expression of DHRS7C is significantly down-regulated in human NDCM. As expected, expression increases in response to β-AR blockade and is strongly correlated with both EF and heart rate response to beta-blockers comparable to MYH6 and ADRB1/2 . Although its function is unclear, DHRS7C may be an important biomarker or mechanistically important for ventricular reverse-remodeling. ![][1] [1]: /embed/graphic-1.gif
Ferromagnetic particles as magnetic resonance imaging temperature sensors

Magnetic resonance imaging is an important technique for identifying different types of tissues in a body or spatial information about composite materials. Because temperature is a fundamental parameter reflecting the biological status of the body and individual tissues, it would be helpful to have temperature maps superimposed on spatial maps. Here we show that small ferromagnetic particles with a strong temperature-dependent magnetization, can be used to produce temperature-dependent images in magnetic resonance imaging with an accuracy of about 1 °C. This technique, when further developed, could be used to identify inflammation or tumours, or to obtain spatial maps of temperature in various medical interventional procedures such as hyperthermia and thermal ablation. This method could also be used to determine temperature profiles inside nonmetallic composite materials. Magnetic resonance imaging can distinguish between different tissue types by measuring the proton distribution in a living sample. Here, the authors demonstrate how this technique can be extended to provide temperature information by using ferromagnetic particles with temperature-dependent magnetization.
Architecture for a Non-Copyable Disk (NCdisk) Using a Secret-Protection (SP) SoC Solution

Piracy of copyrighted digital contents, such as movies and music is rampant in cyberspace. A piece of digital material may be repeatedly copied and proliferated throughout the Internet with ease. We examined both software and hardware vulnerabilities in existing digital copy-protection methods. As a result, we propose a non-copyable disk (NCdisk) that makes it significantly harder for digital contents to be copied. Any digital content written onto the NCdisk can only be read through a predefined set of outputs of the NCdisk, and the original plaintext digital form may never be read out of the NCdisk. We add a minimal set of components based on the secret-protection (SP) architecture to the existing disk's SoC chipset to attribute the disk with the non-copyable property. We further present the security protocol to be used along with the NCdisk to provide a copy-protected digital movie download scenario.
Anticancer Activity and Induction of Multinucleation in Hematologic Cell Lines Mediated by Ganoderma Lucidum .

Over many centuries, herbal remedies have treated a variety of ailments. This empiric observational approach has produced a number of leads for formulated medicines. We have examined five phytochemical herbs with purported anti-cancer activities: Ganoderma lucidum, Isatis indigotica, Dendranthema morifolium, Rabdosia rubescens and Panax pseudoginseng . Ethanol and DMSO extracts were made of each herb, and these were screened for their antiproliferative activities (MTT-assay; doses: 50 μg/ml and 100 μg/ml) using a panel of 26 human cancer cell lines (16 hematologic cell lines). Ganoderma lucidum was the most effective agent, particularly against the 16 hematological cell lines. Further dose- and time-response MTT assays of Ganoderma were performed using the 7 most sensitive hematological cell lines: their ED 50 ’s were 26 μg/ml, HL-60; 63 μg/ml, U937; 50 μg/ml, K562 (all three are myeloid leukemias); 38 μg/ml, Blin-1; 30 μg/ml, Nalm-6 (both are B-ALLs); 40 μg/ml, RPMI8226 (multiple myeloma); 20 μg/ml, Daudi (Burkitt’s lymphoma). Cell cycle analysis revealed a G2/M arrest, most prominently in HL-60 cells (24% in G2/M compared to 12% in control cells cultured with 100 mg/ml Ganoderma for 3 days). Three hematological cell lines (HL-60, U937, Blin-1) were examined for apoptosis, which ranged between 10% – 35% and 30% – 49% compared to Ganoderma for 3 days, respectively (Annexin V staining). Of particular note, cytospin preparations of HL-60 cells revealed that Ganoderma lucidum caused prominent multinucleation. Dose-dependent studies revealed 1% multinucleation in the cells treated with 1 mg/ml, 5% with 10 mg/ml, 10% with 50 mg/ml, 40% with 75 mg/ml and 80% with 100 mg/ml Ganoderma at day 4 of culture. FACS analysis of PI stained HL-60 cells confirmed the increased DNA content of these cells. Of interest, multinucleation did not occur in 6 other hematologic and 6 solid tumor cell lines. In summary, we discovered that 5 phytochemical herbs have growth inhibitory effects on AML, CML, B-ALL, Burkitt’s lymphoma and multiple myeloma cell lines. The most effective drug was Ganoderma lucidum , and it induced cell death by apoptosis. Moreover, multinucleation was observed in HL-60 cells, which may provide interesting insight in the same process in normal cells, like megakaryocytes. Notably, these studies have identified one plant, Ganoderma lucidum , that deserves careful separation techniques to identify its anticancer molecule (s).
Whole‐Plant Manual and Image‐Based Phenotyping in Controlled Environments

Phenotypic measurements and images of crops grown under controlled-environment conditions can be analyzed to compare plant growth and other phenotypes from diverse varieties. Those demonstrating the most favorable phenotypic traits can then be used for crop improvement strategies. This article details a protocol for image-based root and shoot phenotyping of plants grown in the greenhouse to compare traits among different varieties. Diverse maize lines were grown in the greenhouse in large 8-gallon treepots in a clay granule substrate. Replicates of each line were harvested at 4 weeks, 6 weeks, and 8 weeks after planting to capture developmental information. Whole-plant phenotypes include biomass accumulation, ontogeny, architecture, and photosynthetic efficiency of leaves. Image analysis was used to measure leaf surface area and tassel size and to extract shape variance information from complex 3D root architectures. Notably, this framework is extensible to any number of above- or below-ground phenotypes, both morphological and physiological. © 2017 by John Wiley & Sons, Inc. Keywords: whole-plant; phenotypes; image-based analysis; shoots; roots
Gatekeeping and Competency-Based Education: Developing Behaviorally Specific Remediation Policies.

ABSTRACTGatekeeping has long been an integral component of what is now referred to as the Implicit Curriculum, or the context in which professional social work education occurs. Despite its long-standing role within social work education, gatekeeping elicits conflict for both individual faculty members and entire programs of social work education. Much of this conflict stems from a failure to identify objective and measurable standards on which to base gatekeeping decisions. This article proposes using the Council on Social Work Education’s core competencies as behaviorally specific standards for remediation/termination and provides suggestions for developing gatekeeping policies inclusive of these competencies.
Prospective randomised non-inferiority trial of pelvic drain placement vs no pelvic drain placement after robot-assisted radical prostatectomy

Objectives To determine if eliminating the prophylactic placement of a pelvic drain (PD) after robot-assisted radical prostatectomy (RARP) affects the incidence of early (90-day) postoperative adverse events. Materials and Methods In this parallel-group, blinded, non-inferiority trial, we randomized patients planning to undergo RARP to one of two arms: no drain placement (ND) or PD placement. Patients with demonstrable intra-operative leakage upon bladder irrigation were excluded. Randomization sequence was determined a-priori using a computer algorithm, and included a stratified design with respect to low vs. intermediate/high D'Amico risk classifications. Surgeons remained blinded to the randomization arm until final eligibility was verified at the end of the RARP. The primary endpoint was overall incidence of 90-day complications which, based on our standard treatment using PD retrospectively, was estimated at 13%. The non-inferiority margin was set at 10%, and the planned sample size was 312. An interim analysis was planned and conducted when 1/3 of the planned accrual and follow-up was completed, to rule out futility if the delta margin was in excess of 0.1389. Results From 2012 to 2016, 189 patients were accrued to the study, with 92 patients allocated to the ND group and 97 patients allocated to the PD group. Due to lower than expected accrual rates, accrual to the study was halted by regulatory entities, and we did not reach the intended accrual goal. ND and PD groups were comparable in median PSA (6.3 vs 5.8 respectively, p=0.5), clinical stage (p=0.8), D'Amico risk classification (p=0.4), median lymph nodes dissected (17 vs 18, p=0.2) and proportion of patients receiving an extended pelvic lymph node dissection (70.7% vs 79.4% respectively, p=0.3). Incidence of 90-day overall and major (Clavien ≥ III) complications in the ND group (17.4% and 5.4%, respectively) was not inferior to the PD group (26.8% and 5.2%, respectively; p=0.0008 and p=0.007 for difference of proportions <10%, respectively). Symptomatic lymphocele rates (2.2% in the ND group, 4.1% in the PD group) were comparable between the two arms (p=0.7). Conclusions Incidence of adverse events in the no drain group was not inferior to the group who received a drain. In properly selected patients, drain placement after robot-assisted radical prostatectomy can be safely withheld without significant additional morbidity. This article is protected by copyright. All rights reserved.
Combining points and lines in rectifying satellite images

The quick advance in remote sensing technologies established the potential to gather accurate and reliable information about the Earth surface using high resolution satellite images. Remote sensing satellite images of less than one-meter pixel size are currently used in large-scale mapping. Rigorous photogrammetric equations are usually used to describe the relationship between the image coordinates and ground coordinates. These equations require the knowledge of the exterior and interior orientation parameters of the image that might not be available. On the other hand, the parallel projection transformation could be used to represent the mathematical relationship between the image-space and objectspace coordinate systems and provides the required accuracy for large-scale mapping using fewer ground control features. This article investigates the differences between point-based and line-based parallel projection transformation models in rectifying satellite images with different resolutions. The point-based parallel projection transformation model and its extended form are presented and the corresponding line-based forms are developed. Results showed that the RMS computed using the point- or line-based transformation models are equivalent and satisfy the requirement for large-scale mapping. The differences between the transformation parameters computed using the point- and line-based transformation models are insignificant. The results showed high correlation between the differences in the ground elevation and the RMS.
WCET analysis of the shared data cache in integrated CPU-GPU architectures

By taking the advantages of both CPU and GPU as well as the shared DRAM and cache, the integrated CPU-GPU architecture has the potential to boost the performance for a variety of applications, including real-time applications as well. However, before being applied to the hard real-time and safety-critical applications, the time-predictability of the integrated CPU-GPU architecture needs to be studied and improved. In this work, we study the shared data Last Level Cache (LLC) in the integrated CPU-GPU architecture and propose to use an access interval based method to improve the time-predictability of the LLC. The results show that the proposed technique can effectively improve the accuracy of the miss rate estimation in the LLC. We also find that the improved LLC miss rate estimations can be used to further improve the WCET estimations of GPU kernels running on such an architecture.
Diagnostic Utility of Histological Analysis for Detecting Ongoing Infection During Two-Stage Revision Arthroplasty in Patients With Inflammatory Arthritis.

Abstract Background Surgeons often rely on intra-operative histology (frozen sections [FS]) to determine the next step in surgical management during the second stage (re-implantation surgery) of 2-stage revision arthroplasty. The purpose of the study is to assess the accuracy of permanent sections (PS) and FS in the diagnosis of persistent infection during re-implantation in patients with an inflammatory arthritis. Methods From 2001 to 2016, 47 planned second-stage revision total hip arthroplasty and total knee arthroplasty in patients with inflammatory arthritis were identified. Revisions were classified as having persistent infection if they were Musculoskeletal Infection Society positive at the time of second stage. PS or FS was considered to be positive for infection when at least one of the specimens demonstrated an acute inflammation. Receiver operating characteristic analysis was performed to obtain the diagnostic parameters. Results There were 9 (19%) persistent infections. Both PS and FS had very high specificity (PS = FS = 94.7%). Sensitivity of PS was higher than FS, although not statistically significant (PS = 88.9%, FS = 55.6%, P = .083). Overall, PS had a better diagnostic utility than FS (area under the curve: PS vs FS = 0.92 vs 0.75, P = .045). Four specimens had discrepancies between PS and FS histology. In all 4 instances, the specimens were read as positive (infected) by PS, but negative by FS. Conclusion Histological analysis is recommended at the time of re-implantation surgery even in patients with inflammatory arthritis. PS had a better diagnostic utility than FS suggesting that areas of acute inflammation may be scattered and may not always be captured in the specimens taken for FS.
Ten Years of ‘Social Media Marketing’ Research in the Journal of Promotion Management: Research Synthesis, Emerging Themes, and New Directions

The study synthesizes research in emerging social media marketing domains by analyzing published articles on social media marketing in the Journal of Promotion Management published since 2007. We u...
Role of neurogenic inflammation in local communication in the visceral mucosa

Intense research has focused on the involvement of the nervous system in regard to cellular mechanisms underlying neurogenic inflammation in the pelvic viscera. Evidence supports the neural release of inflammatory factors, trophic factors, and neuropeptides in the initiation of inflammation. However, more recently, non-neuronal cells including epithelia, endothelial, mast cells, and paraneurons are likely important participants in nervous system functions. For example, the urinary bladder urothelial cells are emerging as key elements in the detection and transmission of both physiological and nociceptive stimuli in the lower urinary tract. There is mounting evidence that these cells are involved in sensory mechanisms and can release mediators. Further, localization of afferent nerves next to the urothelium suggests these cells may be targets for transmitters released from bladder nerves and that chemicals released by urothelial cells may alter afferent excitability. Modifications of this type of communication in a number of pathological conditions can result in altered release of epithelial-derived mediators, which can activate local sensory nerves. Taken together, these and other findings highlighted in this review suggest that neurogenic inflammation involves complex anatomical and physiological interactions among a number of cell types in the bladder wall. The specific factors and pathways that mediate inflammatory responses in both acute and chronic conditions are not well understood and need to be further examined. Elucidation of mechanisms impacting on these pathways may provide insights into the pathology of various types of disorders involving the pelvic viscera.
If Everything is Genocide, Nothing Is: Scepticism and the Concept of Genocide

The claim that the concept of genocide needs a defence might strike readers as strange. Surely, one might think, we know that genocides have occurred and are (unfortunately) still occurring. In an ...
Adrenal serotonin derives from accumulation by the antidepressant-sensitive serotonin transporter

Adrenal chromaffin cells comprise the neuroendocrine arm of the sympathetic nervous system and secrete catecholamines to coordinate the appropriate stress response. Deletion of the serotonin (5-HT) transporter (SERT) gene in mice (SERT-/- mice) or pharmacological block of SERT function in rodents and humans augments this sympathoadrenal stress response (epinephrine secretion). The prevailing assumption is that loss of CNS SERT alters central drive to the peripheral sympathetic nervous system. Adrenal chromaffin cells also prominently express SERT where it might coordinate accumulation of 5-HT for reuse in the autocrine control of stress-evoked catecholamine secretion. To help test this hypothesis, we have generated a novel mouse model with selective excision of SERT in the peripheral sympathetic nervous system (SERTΔTH), generated by crossing floxed SERT mice with tyrosine hydroxylase Cre driver mice. SERT expression, assessed by western blot, was abolished in the adrenal gland but not perturbed in the CNS of SERTΔTH mice. SERT-mediated [3H] 5-HT uptake was unaltered in midbrain, hindbrain, and spinal cord synaptosomes, confirming transporter function was intact in the CNS. Endogenous midbrain and whole blood 5-HT homeostasis was unperturbed in SERTΔTH mice, contrasting with the depleted 5-HT content in SERT-/- mice. Selective SERT excision reduced adrenal gland 5-HT content by ≈ 50% in SERTΔTH mice but had no effect on adrenal catecholamine content. This novel model confirms that SERT expressed in adrenal chromaffin cells is essential for maintaining wild-type levels of 5-HT and provides a powerful tool to help dissect the role of SERT in the sympathetic stress response.
Imaging and Staging of Bone and Soft Tissue Tumors: Fundamental Concepts

The radiologic evaluation of musculoskeletal tumors has undergone dramatic evolution with the advent of computer-assisted imaging; specifically, computed tomography (CT) and magnetic resonance (MR) imaging. Despite the use of these sophisticated imaging modalities, the objectives of initial radiologic evaluation remain unchanged: detecting the suspected lesion, establishing a diagnosis, or, when a definitive diagnosis is not possible, formulating an appropriate differential diagnosis, and determining the radiologic staging of the lesion [1]. As a detailed discussion of all bone and soft tissue tumors is well beyond the scope of this review, we will highlight fundamental principles that should serve as a guide to the initial evaluation and staging of primary musculoskeletal neoplasms.
The Best Way to Improve HDL is to Lower LDL Levels.

ObjectiveAnalyses of HDL function. IntroductionPopulation studies have shown that plasma levels of HDL (high density lipoprotein) inversely correlate with the prevalence of coronary heart disease. ...
Cardiac biomechanics and heart dysfunction

Abstract: Infarction and ischemia in the heart directly result in death of cardiac muscle cells and can significantly reduce mechanical function in the heart, both regionally and globally. The overall goal of cardiac therapies is to return myocardial function to its healthy state. To understand the effects of ischemia and infarction, it is necessary to develop reproducible methods to quantify regional cardiac function. Early-stage cell treatments may be unable to return global function to its healthy state, so it is also necessary to quantify cardiac function on a regional basis. In this chapter, we discuss the many parameters used to quantify cardiac function, how the parameters are assessed, and how they change during cardiac ischemia and infarction.
An Analysis of Secondary Relaxations in Bisphenol-A Polysulfone

The dynamic mechanical2–12 and dielectric7 behavior of bisphenol-A polysulfone (PSF) has been studied by several investigators over a wide range of frequency. These measurements suggest the presence of a low temperature (gamma) transition in the range of 163–197 K (corrected to a frequency of 11 Hz). Baccaredda et al.2 have associated this relaxation with rotational motion of water molecules bound to polar groups along the chain backbone thereby offering an explanation as to why the gamma peak is enhanced by the absorption of water. Kurz et al.6 have noted the persistence of this transition when samples have been dried. Kurz et al.6 suggest that the gamma process may be associated with motions involving the sulfone group which are enhanced through association with water.
Cell-Mediated Immunity in Tumor Rejection

It is now almost axiomatic that host immune reactivity is an important factor in resistance to tumors, regardless of the tumor initiating agent or event. Although much effort was initially expended concerning humoral immune mechanism in malignancy, many studies over the last decade or so have focused attention mainly on cell-mediated immune (CMI) interactions of the host with tumors. It is, however, quite apparent that such CMI reactions are highly complex phenomena. For example, it is now widely accepted that tumors may adversely affect the immune response mechanism not only to tumor-associated antigensper se, but also to unrelated antigens to which the host normally would be expected to have an effective immune response. Furthermore, cellular immunity is thought to be a major contributor to either progression or rejection of tumor cell growth. For example, the state of “normal” host immunity and the ability to control or prevent growth of tumors is believed to be under the regulatory control of cells involved in CMI. Among these are regulatory T lymphocytes, either helper or suppressor cells.
Implementing JOBS: A View from the Front Line:

Front-line workers fulfill a critical role in the implementation of the Job Opportunity and Basic Skills Training Program (JOBS), a welfare-employment program authorized under the Family Support Ac...
Deoxygenation inhibits the volume-stimulated, Cl(-)-dependent K+ efflux in SS and young AA cells: a cytosolic Mg2+ modulation.

We recently reported that the Cl(-)-dependent K+ (K:Cl) efflux, which can be stimulated by cell swelling in the presence of inhibitors of the Na+ pump (ouabain) and of the Na-K-Cl cotransport (bumetanide), is highly active in young AA and SS RBCs. We report here that deoxygenation inhibits volume-stimulated K:Cl efflux in SS and reticulocyte-enriched density-separated SS and AA RBCs. In SS whole blood, the K:Cl efflux stimulated by hypotonic (220 mOsm) swelling was reduced from 9.2 +/- 2 (mean +/- SE) in oxygen to 2.7 +/- 1.9 (mmol/L cell/h = flux units = FU) (n = 4) under deoxygenated conditions (P less than .005). Deoxygenation also decreased the acid pH-stimulated K:Cl efflux from 5.9 +/- 1.5 to 3.7 +/- 1.1 FU (n = 3) (P less than .025) but did not inhibit NEM-stimulated K:Cl transport. The effect of deoxygenation on density-separated SS cells is similar: When fraction SS2 (reversible discocytes) is deoxygenated under hypotonic conditions, the K:Cl efflux is reduced by 50%. In reticulocyte-enriched AA cells obtained from anemic patients, deoxygenation under hypotonic conditions also reduces K+ efflux by 50%. In SS cells only, deoxygenation under isotonic conditions results in an increased Cl(-)-independent K+ efflux. Because ionized Mg2+ in the cytosol increases during deoxygenation, we investigated the effect of external and internal Mg2+ on the volume-stimulated K:Cl efflux. Removal of external Mg2+ did not influence the rate of transport in oxygenated cells. When internal Mg2+ was clamped at 0.15 mmol/L with A23187 and EDTA at ionized cytosolic Ca2+ = O, however, the inhibitory effect of deoxygenation on the K:Cl efflux was eliminated. We conclude that deoxygenation inhibits the volume-stimulated, Cl(-)-dependent K+ efflux in AA and SS young red cells by concomitantly increasing ionized cytosolic Mg2+.
Some travels in the land of nonlinear convection and magnetism

Rotating stars with convection zones are the great builders of magnetism in our universe. Seeking to understand how turbulent convection actually operates, and so too the dynamo action that it can achieve, has advanced through distinctive stages in which Jean-Paul Zahn was often a central player, or joined by his former students. Some of the opening steps in dealing with the basic nonlinearity in such dynamics involved modal equations (with specified horizontal structure) to study convective amplitudes and heat transports achieved as solutions equilibrated by feeding back on the mean stratification. These dealt in turn with laboratory convection, with penetrative convection in Boussinesq settings, then with compressible penetration via anelastic equations in simple geometries, and finally with stellar penetrative convection in A-type stars that coupled two convection zones. Advances in computation power allowed 2-D fully compressible simulations, and then 3-D modeling including rotation, to revisit some of these convection and penetration settings within planar layers. With externally imposed magnetic fields threading the 2-D layers, magnetoconvection could then be studied to see how the flows concentrated the fields into complex sheets, or how new classes of traveling waves could result. The era of considering turbulent convection in rotating spherical shells had also arrived, using 3-D MHD codes such as ASH to evaluate how the solar differential rotation is achieved and maintained. Similarly the manner in which global magnetic fields could be built by dynamo action within the solar convection zone took center stage, finding that coherent wreaths of strong magnetism could be built, and also cycling solutions with field reversals. The coupling of convection and magnetism continues as a vibrant research subject. It is also clear that stars like the Sun do not give up their dynamical mysteries readily when highly turbulent systems are at play.
Dominant-negative ATF5 compromises cancer cell survival by targeting CEBPB and CEBPD

The basic leucine zipper transcription factor ATF5 is overexpressed in many tumor types and interference with its expression or function inhibits cancer cell survival. As a potential therapeutic approach to exploit these findings, we created dominant-negative (DN) ATF5 forms lacking DNA-binding ability that retain the ATF5 leucine zipper, and thus associate with and sequester ATF5's requisite leucine zipper-binding partners. Preclinical studies with DN-ATF5, including a cell-penetrating form, show in vitro and in vivo efficacy in compromising cancer cell survival. However, DN-ATF5's targets, and particularly those required for tumor cell survival, have been unknown. We report that cells lacking ATF5 succumb to DN-ATF5, indicating that ATF5 itself is not DN-ATF5's obligate target. Unbiased pull-down assays coupled with mass spectrometry and immunoblotting revealed that DN-ATF5 associates in cells with the basic leucine zipper proteins CEBPB and CEBPD and coiled-coil protein CCDC6. Consistent with DN-ATF5 affecting tumor cell survival by suppressing CEBPB and CEBPD function, DN-ATF5 interferes with CEBPB and CEBPD transcriptional activity, while CEBPB or CEBPD knockdown promotes apoptotic death of multiple cancer cells lines, but not of normal astrocytes. We propose a two-pronged mechanism by which DN-ATF5 kills tumor cells. One is by inhibiting heterodimer formation between ATF5 and CEBPB and CDBPD, thus suppressing ATF5-dependent transcription. The other is by blocking the formation of transcriptionally active CEBPB and CEBPD homodimers as well as heterodimers with partners in addition to ATF5. IMPLICATIONS: This study indicates that the potential cancer therapeutic DN-ATF5 acts by associating with and blocking the transcriptional activities of CEBPB and CEBPD.
The Impact of Obesity On Insulin Sensitivity and Secretion During Pubertal Progression: A Longitudinal Study.

CONTEXT Physiologic changes in glucose metabolism are well-described to occur during puberty. However, there are important gaps in understanding the interaction between obesity and the normal physiologic changes during puberty, as well as how these changes could contribute to the increased risk of comorbidities, such as type 2 diabetes and dyslipidemia, in youth with obesity. OBJECTIVE The objective of this study was to compare longitudinal changes in insulin sensitivity (Si) and secretion during pubertal progression in youth with obesity versus those with normal weight. DESIGN Longitudinal observational study evaluating youth from early puberty (Tanner [T]2-T3) until puberty completion (T5). SETTING Pediatric academic hospital Clinical Translational Research Center. PARTICIPANTS Pubertal youth with normal weight (n = 47; 22 female, 25 male) and obesity (n = 37; 23 female, 14 male). MAIN OUTCOME MEASURES Si, insulin response (acute insulin response to glucose, AIRg) and disposition index (DI) by intravenous glucose tolerance test at baseline (T2-T3), T4, and T5. RESULTS Youth with obesity had significantly lower Si and higher AIRg at each time point (P < 0.001), but DI was similar between the groups. There were no group differences in trajectory of Si, AIRg or DI over time. Leptin, insulin-like growth factor-1, and obesity were most strongly associated with Si and AIRg at all time points. CONCLUSIONS Obesity significantly impacts Si during puberty, even at the earliest stages. However, in general, obese youth have adequate β-cell compensation for the significantly reduced Si of puberty. Future studies are needed to better predict the subset of youth who fail to maintain β-cell compensation during puberty.
Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol.

Abstract Introduction Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates. Methods This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0−2 cm lesions, 14 Gy for 2.1−3 cm lesions, and 12 Gy for 3.1−4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90−05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria. Discussion This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population. Trial Registration Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).
Antimicrobial resistance patterns of Acinetobacter spp. of animal origin reveal high rate of multidrug resistance.

Abstract Antimicrobial resistance has been declared by the World Health Organization as one of the biggest threats to public health and Acinetobacter baumannii is a notable example. A. baumannii is an important human nosocomial pathogen, being along with other multidrug resistant (MDR) bacteria, one of the biggest public health concerns worldwide. In Veterinary Medicine, resistance patterns of Acinetobacter species other than A. baumanii are unclear, and the scarce information available is limited and fragmented. We applied a statistical modeling approach to investigate the occurrence, clinical relevance and antimicrobial resistant phenotypes of Acinetobacter spp. originated from animals. Seven Acinetobacter species were identified in clinical specimens of more than 15 different domestic, zoo and exotic animal species. We found a high rate of MDR A. baumannii of canine origin with some of these isolates originating from serious systemic or wound infections, which highlights their potential pathogenic profile and spread in the human environment. Data also revealed different antimicrobial resistance patterns of animal-origin Acinetobacter species, emphasizing the necessity to implement specific antimicrobial susceptibility recommendations for animal isolates as there are no such clinical breakpoints currently in place. This study provides substantial advancing in our understanding of Acinetobacter spp. in animal clinical specimens, and highlights the role of animals in the dynamics of multidrug resistance in bacteria. The data presented here is a valuable source of information for further establishment of clinical breakpoints for susceptibility testing of animal-associated Acinetobacter isolates.
Leucocyte count predicts cardiovascular risk in heart failure with preserved ejection fraction: insights from TOPCAT Americas

Aims Prior evidence has implicated leucocyte expansion in several cardiovascular disorders, including heart failure (HF) with reduced ejection fraction (rEF). However, the prognostic importance of leucocyte count in HF with preserved EF (HFpEF) remains largely unexplored. Methods and results The Americas cohort of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT-Americas) was used to evaluate the association between total leucocyte count and clinical outcomes in HFpEF. The primary outcome was a composite of aborted cardiac arrest, cardiovascular mortality, or hospitalization for HF. Secondary outcomes were hospitalization for HF, aborted cardiac arrest, stroke, non-fatal myocardial infarction (MI), cardiovascular mortality, non-cardiovascular mortality, and all-cause mortality. Survival models were used to identify the risk of the primary and secondary outcomes in those with leucocyte count above the median (7100 cells/μL), as compared to those with leucocyte count below the median, during the follow-up period. A total of 1746 (out of 1767; 99%) patients from TOPCAT-Americas were available for the analyses with a median follow up of 2.4 (25th to 75th percentile 1.4-3.9) years. Patients with leucocyte count >7100 cells/μL were 36% more likely to experience the primary endpoint compared to those with ≤7100 cells/μL (hazard ratio: 1.36, 95% confidence interval: 1.14-1.61). This association remained significant after extensive adjustment for potential confounders (hazard ratio: 1.27, 95% confidence interval: 1.06-1.52). We also observed a greater incidence of HF hospitalization and non-fatal MI in patients with higher leucocyte count. These associations remained robust on sensitivity analyses, suggesting a low probability of confounding. Exploratory analyses suggested that both higher leucocyte count (integrating the combined influence of both myeloid and lymphoid immune cells) and augmented platelet count (as a surrogate for myeloid immune cell expansion) in the same model were associated with the primary outcome (both P Conclusions Leucocyte count >7100 cells/μL was independently associated with adverse clinical outcomes in HFpEF patients from TOPCAT-Americas. These results were primarily driven by the HF hospitalization outcome but were also accompanied by an excess of non-fatal MI. Further research is needed to define the mechanisms underlying our findings and their prognostic implications.
Problem-solving, Adherence to Lifestyle Goals, and Weight Loss Among Individuals Participating in a Weight Loss Study

The role of problem-solving is not well understood in behavioral weight loss interventions. In a 12-month behavioral weight loss study, we examined whether problem-solving changed over time and the relationships between problem-solving and changes in adherence to calorie, fat, and physical activity (PA) goals and percent weight change. One of the 24 intervention sessions (15th) was devoted to problem-solving. Participants received individualized calorie and fat goals and were given a 150 min/week moderate-to-vigorous PA goal. Adherence to calorie/fat goals and PA goals was calculated at 1, 6, and 12 months using self-reported food intake in a mobile-based weight loss app and accelerometer data, respectively. Weight was measured via a digital scale at baseline, and 6 and 12 months. A general linear model was used to compare problem-solving across time points; post hoc linear mixed modeling was used to examine the relationships between problem-solving and changes in adherence to lifestyle goals and percent weight change. The sample (N = 150) was mostly female (90.7%), white (80.70%), with a mean age of 51.1 ± 10.2 years, and a mean body mass index of 34.1 + 4.6 kg/m2. The mean total score of problem-solving at baseline was 81.2 ± 12.3. Problem-solving total and subscale scores did not significantly change over time. Baseline problem-solving was not significantly associated with changes in adherence to lifestyle goals and percent weight change (P > 0.05). A behavioral weight loss study did not impact problem-solving, and problem-solving may not influence lifestyle adherence and weight changes. Future work needs to examine problem-solving in larger and more diverse samples.
Study of the Neutron Reactions Li 6 (n, α)H 3 , F 19 (n, γ)F 20 , and I 127 (n, γ)I 128

The reactions ${\mathrm{Li}}^{6}(n, \ensuremath{\alpha}){\mathrm{H}}^{3}$, ${\mathrm{F}}^{19}(n, \ensuremath{\gamma}){\mathrm{F}}^{20}$, and ${\mathrm{I}}^{127}(n, \ensuremath{\gamma}){\mathrm{I}}^{128}$ were studied using scintillating crystals both as targets and as detectors. The neutrons were produced by the ${\mathrm{Li}}^{7}(p, n){\mathrm{Be}}^{7}$ and ${\mathrm{T}}^{3}(p, n){\mathrm{He}}^{3}$ reactions. A redetermination of the ${\mathrm{Li}}^{7}(p, n){\mathrm{Be}}^{7}$ differential cross section was made in the proton energy range 1.9 to 3.0 Mev at 0\ifmmode^\circ\else\textdegree\fi{} and the cross section observed at 2.27 Mev was 154 mb. Cross sections for this reaction were determined at 120\ifmmode^\circ\else\textdegree\fi{} for proton energies below 2.4 Mev and at 60\ifmmode^\circ\else\textdegree\fi{} for energies below 2.1 Mev. The ${\mathrm{Li}}^{6}(n, \ensuremath{\alpha}){\mathrm{H}}^{3}$ reaction cross section was studied for neutron energies between 0.025 and 4 Mev. The resonance at 0.255 Mev was observed to have a width (lab) of 0.125 Mev and a maximum cross section of 2.80 barns. A fit of the dispersion theory to this resonance yielded the following parameters in the center-of-mass coordinates: ${{\ensuremath{\gamma}}_{n}}^{2}=0.41$ Mev-cm, ${{\ensuremath{\gamma}}_{\ensuremath{\alpha}}}^{2}=0.015$ Mev-cm, ${\ensuremath{\Delta}}_{\ensuremath{\lambda}}=0.17$ Mev, ${E}_{\ensuremath{\lambda}}=0.039$ Mev, and $\ensuremath{\Gamma}=0.188$ Mev at the resonant energy. Sixteen resonances were observed in the ${\mathrm{F}}^{19}(n, \ensuremath{\gamma}){\mathrm{F}}^{20}$ reaction at neutron energies of 0.027, 0.048, 0.100, 0.177, 0.270, 0.308, 0.388, 0.425, 0.500, 0.600, 0.760, 0.865, 0.950, 1.125, 1.290, and 1.635 Mev. The radiative widths ${\ensuremath{\Gamma}}_{\ensuremath{\gamma}}$ of twelve of these resonances vary between 1.1 and 8.6 ev. A monotonically decreasing cross section was observed for the ${\mathrm{I}}^{127}(n, \ensuremath{\gamma}){\mathrm{I}}^{128}$ reaction between 0.025 and 0.500 Mev.
Prevalence of Lynch syndrome in women with mismatch repair-deficient ovarian cancer.

Background There are limited data on the prevalence of Lynch syndrome (LS) in women with primary ovarian cancer with mismatch repair deficiency (MMR-D) by immunohistochemistry (IHC). Materials and methods Three hundred and eight cases of primary ovarian, fallopian, and peritoneal cancer between January 2012 and December 2019 were evaluated for MMR-D by IHC. The incidence of LS in this cohort was evaluated. Results MMR-D by IHC was identified in 16 of 308 (5.2%) (95% CI: 3.2%-8.3%) primary ovarian-related cancers. Most cases with MMR-D were endometrioid (n = 11, 68.7%); (95% CI: 44.2%-86.1%). MSH2/MSH6 protein loss was detected in eight cases (50.0%); (95% CI: 28.0%-72.0%) and MLH1/PMS2 protein loss was detected in four cases (25.0%); (95% CI: 9.7%-50.0%). MSH6 protein loss was detected in two cases (12.5%); (95% CI: 2.2%-37.3%) and PMS2 protein loss was detected in two cases (12.5%); (95% CI: 2.2%-37.3%). All four cases with MLH1/PMS2 protein loss had MLH1 promotor hypermethylation. All 12 women with ovarian cancer suggestive of LS underwent germline testing and 8 (66.6%); (95% CI: 38.8%-86.5%) were confirmed to have LS. Conclusions Most ovarian cancers with somatic MMR-D were confirmed to have LS in this cohort. Germline testing for LS in addition to BRCA1/2 for all women with an epithelial ovarian cancer would be efficient and would approach 100% sensitivity for identifying Lynch syndrome. Utilization of a multigene panel should also be considered, given the additional non-Lynch germline mutation identified in this cohort.
Reports and Removals of Child Maltreatment-Related Hospitalizations: A Population-Based Study:

Despite U.S. child protective services (CPS) agencies relying on mandated reporters to refer concerns of child maltreatment to them, there is little data regarding which children mandated reporters...
Handling Trust Between Drivers and Automated Vehicles for Improved Collaboration

Advances in perception and artificial intelligence technology are expected to lead to seamless interaction between humans and robots. Trust in robots has been evolving from the theory on trust in automation, with a fundamental difference: unlike traditional automation, robots could adjust their behaviors depending on how their human counterparts appear to be trusting them or how humans appear to be trustworthy. In this extended abstract I present my research on methods for processing trust in the particular context of interactions between a driver and an automated vehicle, which has the goal of achieving higher safety and performance standards for the team formed by those human and robotic agents.
Is pregnancy brain real? Comparison of dual task cost during overground walking in pregnant versus control women

Abstract Background Many pregnant women report that their memory is impaired compared to non-pregnancy, but results of studies of cognitive abilities are mixed. The effect of pregnancy on dual tasking, or performance of two tasks simultaneously, has not been studied, however. Research question What is the effect of walking overground at a self-selected speed while also performing a cognitive task on gait and cognitive performance during 3rd trimester of pregnancy compared to non-pregnant controls? Methods A total of n = 22 3rd trimester pregnant women (mean 33.3 ± 3.3 weeks gestation, age 32.1 ± 4.7 years) and n = 21 non-pregnant controls (age 31.9 ± 3.3 years) were recruited to participate. All participants performed single task walking on a GAITRite gait analysis system and performed three cognitive tests while walking: serial 3 and 7 subtraction tests and a phoneme monitoring test. Participants completed the same assessments while seated and order of the testing was counterbalanced. Dual task cost (DTC) was calculated using the formula (Single task score – Dual task score)/Single task score)*100. Independent t-tests or Mann Whitney U tests were used to compare the two groups depending on normality of data. Results There were no significant differences in cognitive test performance between control and pregnant women while walking or seated (p > 0.05). There were no significant differences between groups for DTC during any cognitive tests, but DTC was significantly greater for walking velocity in pregnant women compared to controls for serial 3 (p Significance Pregnant women had elevated cost of dual tasking, though the decrements were not in cognitive tests but in gait, specifically with greater DTC of walking velocity. This suggests that pregnant women modify their walking velocity to preserve cognitive function during activities requiring focus on both cognitive and physical tasks.
An Overview of Phase 2 Clinical Trial Designs.

Clinical trials are studies to test new treatments in humans. Typically, these treatments are evaluated over several phases to assess their safety and efficacy. Phase 1 trials are designed to evaluate the safety and tolerability of a new treatment, typically with a small number of patients (eg, 20-80), generally spread across several dose levels. Phase 2 trials are designed to determine whether the new treatment has sufficiently promising efficacy to warrant further investigation in a large-scale randomized phase 3 trial, as well as to further assess safety. These studies usually involve a few hundred patients. This article provides an overview of some of the most commonly used phase 2 designs for clinical trials and emphasizes their critical elements and considerations. Key references to some of the most commonly used phase 2 designs are given to allow the reader to explore in more detail the critical aspects when planning a phase 2 trial. A comparison of 3 potential designs in the context of the NRG-HN002 trial is presented to complement the discussion about phase 2 trials.