cssi/SciSciGPT-SciSciNet huggingface dataset:
Dehydroepiandrosterone Activates Mutant Androgen Receptors Expressed in the Androgen-Dependent Human Prostate Cancer Xenograft CWR22 and LNCaP Cells

An androgen receptor (AR) gene mutation identified in the androgen-dependent human prostate cancer xenograft, CWR22, changed codon 874 in the ligand-binding domain (exon H) from CAT for histidine to TAT for tyrosine and abolished a restriction site for the endonuclease SfaNI. SfaNI digestion of AR exon H DNA from normal but not from prostate cancer tissue indicated H874Y is a somatic mutation that occurred before the initial tumor transplant. CWR22, an epithelial cell tumor, expresses a 9.6-kb AR mRNA similar in size to the AR mRNA in human benign prostatic hyperplasia. AR protein is present in cell nuclei by immunostaining as in other androgen-responsive tissues. Transcriptional activity of recombinant H874Y transiently expressed in CV1 cells in the presence of testosterone or dihydrotestosterone was similar to that of wild type AR. With dihydrotestosterone at a near physiological concentration (0.01 nM), H874Y and wild type AR induced 2-fold greater luciferase activity than did the LNCaP mutant AR T877A. The adrenal androgen, dehydroepiandrosterone (10 and 100 nM) with H874Y stimulated a 3- to 8-fold greater response than with wild type AR and at 100 nM the response was similar with the LNCaP mutant. H874Y, like the LNCaP cell mutant, was more responsive to estradiol and progesterone than was wild type AR. The antiandrogen hydroxyflutamide (10 nM) had greater agonist activity (4- to 7-fold) with both mutant ARs than with wild type AR. AR mutations that alter ligand specificity may influence tumor progression subsequent to androgen withdrawal by making the AR more responsive to adrenal androgens or antiandrogens.
Infectious disease and the extreme sport athlete

Extreme sport competition often takes place in locations that may harbor atypical diseases. This article discusses infections that may be more likely to occur in the extreme sport athlete, such as selected parasitic infections, marine infections, freshwater-borne diseases, tick-borne disease, and zoonoses. Epidemiology, presentation, treatment, complications, and return-to-sport issues are discussed for each of these diseases.
Glutathione: Toxicological Implications

Glutathione as reduced glutathione (GSH) and as the disulfide (GSSG) is a unique peptide that continues to interest toxicologists-as reflected in the numerous symposia and reviews ( 1-6). This article undertakes to describe the role of mitochondrial glutathione in cellular response to toxic exposures that include loss of the homeostases of Ca2+ and protein thiols. Because of the numerous reviews on the glutathione S-transferases (7-10), only the per­ oxidase activity of membrane-associated glutathione S-transferases is dis­ cussed. Mammalian cells have evolved protective mechanisms to minimize in­ jurious events that result from toxic chemicals and normal oxidative products of cellular metabolism. A major endogenous protective system is the glu­ tathione redox cycle (2). Glutathione is present in high concentrations as GSH in most mammalian cells (generally in the millimolar range), with minor fractions being GSSG, mixed disulfides of GSH and other cellular thiols, and minor amounts of thioethers ( 1) . GSH acts both as a nucleophilic "scavenger" of numerous compounds and their metabolites, via enzymatic and chemical mechanisms, converting electrophilic centers to thioether bonds, and as a substrate in the GSH peroxidase-mediated destruction of hydroperoxides. GSH depletion to about 20-30% of total glutathione levels can impair the cell's defense against the toxic actions of such compounds and may lead to cell injury and death (3, 1 1) .
Endogenous Ligands for the Calcium Channel: Myths and Realities

The Ca2+ -channel antagonists, including the clinically available nifedipine, verapamil, and diltiazem (Fig. 1), represent a clinically and chemically heterogeneous group of drugs. In the clinical setting these agents are all effective, differing only quantitatively, against angina in its several forms. However, verapamil, and to a lesser extent diltiazem, are effective against some cardiac arrhythmias, notably supraventricular tachycardia, while nifedipine and other 1,4–dihydropyridines are completely ineffective (Fleckenstein, 1983; Opie, 1984, 1988). In general, verapamil and diltiazem have both vasodilating and cardiodepressant properties, whilst nifedipine is prominently vasodilatory in its actions. Despite this heterogeneity of action it is clear that there exists a major common locus of action for these drugs — the voltagedependent Ca2+ channel (for reviews see Triggle and Janis, 1984a, 1987; Triggle and Swamy, 1983). In particular, the L-type of Ca2+ channel, which appears to be of major significance in the cardiovascular system, represents the primary site of action of the currently available therapeutically employed Ca2+ -channel antagonists. It is likely that agents will be developed that will be effective against other classes of Ca2+ channels, including the transient T type and the neuronal N type (Janis et al., 1987; Miller, 1987; Narahashi, 1987).
John Winthrop: Lawyer as Model of Christian Charity

On a small boat bobbing on the North Atlantic Ocean in the spring of 1630, a bearded man with a long thin face rose to speak. He addressed a group of people who, like him, had left behind home, friends, and family for an unknown world called New England. The man spoke from his heart and eloquently shared the vision that united them and had brought them to this place. The man was John Winthrop. He called his remarks, "A Model of Christian Charity."' In them, Winthrop reminded his fellow travelers that they had left their home in England, not for riches or their own glory, but for the glory of God. They had left to establish a people devoted to the service of God and to model for all the world a people that lived in a holy covenant with their God. The travelers were to form a "city on a hill." For the people to fulfill this daunting task, Winthrop was convinced that one thing was crucial: love. Winthrop told his listeners, "We must love brotherly without dissimulation; we must love one another with a pure heart fervently. We must bear one another's burdens."' Winthrop believed that as God did with Israel in the Old Testament, God would prosper and bless a nation that lived in obedience to Him and His covenant. But God would punish any nation that did not: Now the only way to avoid this shipwreck and to provide for our posterity, is to follow the counsel of Micah, to do justly, to love mercy, to walk humbly with our God.... We must delight in each other, make one another's condition our own, rejoice together, mourn together, labor and suffer together, always having before our eyes our Commission and Community in this work, as members of the same body. So shall we keep the unity of the Spirit in the bond of peace.3 It was to this vision that Winthrop devoted the rest of his life. As a lawyer and governor he worked to achieve and preserve unity and love among the people. As a man Winthrop modeled these traits. In the face of constant division and sin, Winthrop consistently showed the way-not in harsh words-but by example. He at times nearly single-handedly
Uniform Range of Conduction Times From the Lateral Amygdala to Distributed Perirhinal Sites

Much data indicate that the perirhinal (PRH) cortex plays a critical role in declarative memory and that the amygdala facilitates this process under emotionally arousing conditions. However, assuming that the amygdala does so by promoting Hebbian interactions in the PRH cortex is hard to reconcile with the fact that variable distances separate amygdala neurons from their PRH projection sites. Indeed, to achieve a synchronized activation of distributed PRH sites, amygdala axons should display a uniform range of conduction times, irrespective of distance to target. To determine if amygdala axons meet this condition, we measured the antidromic response latencies of lateral amygdala (LA) neurons to electrical stimuli delivered at various rostrocaudal levels of the PRH cortex in cats anesthetized with isoflurane. Although large variations in antidromic response latencies were observed, they were unrelated to the distance between the PRH stimulation sites and LA neurons. To determine whether this result was an artifact due to current spread, two control experiments were performed. First, we examined the antidromic response latency of intrinsic PRH neurons. Although we used the same methods as in the first experiment, the antidromic response latency of PRH neurons to electrical stimuli applied in the PRH cortex increased linearly with the distance between the stimulating and recording sites. Second, we measured the antidromic response latency of PRH neurons projecting to the LA. In this pathway, we also found a statistically significant correlation between conduction times and distance to target. Thus these results support the intriguing possibility that the conduction velocity and/or trajectory of LA axons are adjusted to compensate for variations in distance between the LA and distinct rostrocaudal PRH sites. We hypothesize that because of their uniform range of conduction times to the PRH cortex, LA neurons can generate short time windows of depolarization facilitating Hebbian associations between coincident, but spatially distributed, activity patterns in the PRH cortex. In this context, the temporal scatter of conduction times in the LA to PRH pathway is conceived as a mechanism used to lengthen the period of depolarization to compensate for conduction delays within intrinsic PRH pathways. In part, this mechanism might explain how the amygdala promotes memory storage in emotionally arousing conditions.
Bilateral Testicular Torsion in a Pre-Term Neonate

Bilateral testicular torsion in the neonate, although uncommon, is being reported with increasing frequency. Most previously reported cases have been full term, average to above average weight infants born with nonviable testes. We report a case of bilateral neonatal testicular torsion in a 32-week newborn in whom testicular viability may have been preserved by pre-term birth.
The Effect of Early Excessive Weight Gain on the Development of Hypertension in Pregnancy

Background Previous studies have shown an association between total excessive gestational weight gain and hypertension in pregnancy. However, this may be a reflection of excessive water retention associated with the pathophysiology of hypertensive disorders of pregnancy. Early excessive weight gain, prior to the third trimester, results in greater maternal fat deposition and inflammation, which has also been associated with the development of hypertension. By focusing on early excessive weight gain, the association between maternal weight gain and the future development of hypertension can be examined. Objective To evaluate the association between early excessive maternal weight gain and the development of hypertension during pregnancy. Study Design This was a secondary analysis of a longitudinal cohort study of 1,441 women without chronic hypertension who were enrolled in a prospective study evaluating maternal angiogenic factors and the prediction of preeclampsia. Initial body mass index (BMI) was calculated by weight and height at the first study visit. Early excessive maternal weight gain was defined as weight gain by 28 weeks that exceeded the Institute of Medicine (IOM) guidelines and was calculated utilizing the maximum amount of weight gain per week recommended by the IOM based on the patient's starting BMI (normal: 0.45 kg; overweight: 0.32 kg; obese: 0.27 kg). Hypertension was defined as a sustained systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg. Logistic regression was used to determine the association between early excessive weight gain, initial BMI, and the development of hypertension, including gestational hypertension and preeclampsia, during pregnancy. Results Of 1,441 women, 767 (53.2%) had weight gain that exceeded the IOM guidelines in the first 28 weeks and 154 (10.8%) developed hypertension during pregnancy. Women whose weight gain exceeded the IOM guidelines were more likely to develop hypertension even after adjusting for relevant confounders (12.5 vs. 8.6%; p = 0.02; adjusted odds ratio [OR] = 1.70; 95% confidence interval [CI]: 1.18-2.44; p < 0.01). Obese women had a 2.4-fold increased risk of developing hypertension, even after controlling for excessive weight gain (adjusted OR = 2.44; 95% CI: 1.66-3.59; p < 0.01) Conclusions Early excessive maternal weight gain and initial BMI are independently associated with the diagnosis of a hypertensive disorder of pregnancy. Women should be counseled regarding the benefits of achieving a normal BMI prior to pregnancy and appropriate weight gain during pregnancy, as well as the potential harms of excessive weight gain related to perinatal outcomes.
Rituximab Has Similar Efficacy in Treatment of Acute Refractory or Chronic Relapsing Idiopathic Thrombotic Thrombocytopenic Purpura (TTP) and Refractory Secondary TTP: A Systematic Review

Abstract 4673 Background: Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening disorder. Secondary TTP was known to be more resistant to plasma exchange and have higher mortality. Limited clinical data suggest that rituximab may be effective in the treatment of acute refractory or chronic relapsing nonfamilial idiopathic TTP (ITTP) as well as refractory secondary TTP (STTP). We performed a systematic review to evaluate the comparative efficacy of rituximab in ITTP and STTP. Method: An electronic literature search of Medline, CINAHL and the Cochrane library databases using the terms “rituximab” and “thrombotic” yielded 179 articles from March 2002 to June 2011. Studies were included if they met the following criteria: TTP in a first episode or subsequent relapse and TTP refractory to plasma exchange. Exclusion criteria were prophylactic administration of rituximab to patients in remission and familial TTP. Secondary TTP cases were author-defined. Case series without extractable individual data were excluded. Two-Tailed Fisher Exact Test was used to investigate the difference in complete remission rates between ITTP and STTP. Independent-Samples Mann-Whitney U Test was applied to detect the difference in platelet recovery days. Result: 20 case series and 33 case reports including a small prospective study were eligible. Individual data of 139 patients from Europe, Asia, Australia, South and North America were analyzed. Overall, median age was 40 years (range: 1–72). Male constituted 30% and female 70%. Complete remission rate was 88% (90 out of 102) and 84% (31 out of 37) for ITTP and STTP respectively. There was no statistically significant difference in complete remission rates between the two groups (Two-Tailed Fisher Exact Test p value = 0.569). Median follow-up time was 12 months. Median platelet recovery (more than 150×109/L) from the first dose of rituximab was 8 days (range: 2–74) and 19 days (range: 7–90) for ITTP and STTP respectively. The distribution of platelet recovery days was the same between ITTP and STTP (Independent-Samples Mann-Whitney U Test p value = 0.132). Conclusion: Rituximab has the same efficacy in both STTP and ITTP in terms of response rate and platelet recovery days. It appears to be effective and well-tolerated. We recommend the use of rituximab as a salvage therapeutic modality in refractory acute or chronic relapsing nonfamilial idiopathic as well as secondary TTP. Disclosures: No relevant conflicts of interest to declare.
196. Nordihydroguaiaretic Acid (NDGA) Improves Function of Antigen-Specific T-Cells Stimulated by Capsid-Optimized AAV6 Vectors

Cancer, a leading cause of death in the human population today, is generally treated with rigorous surgery followed by intensive chemotherapeutic methods, both of which have adverse toxic side effects. Immunotherapy represents an attractive alternative since it is based on activation of the host immune system. We recently showed that capsid-optimized AAV6-S663V+T492V vectors expressing a tumor-associated antigen are able to initiate specific peripheral T-cell response and suppress tumor progression as well as extend survival in a prostate cancer animal model (J Immunother., 38: 292-298, 2015). However, vaccination based on AAV6 vectors alone was not able to completely overcome the adverse effect of tumor microenvironment and tumor-induced immune dysfunction. Tumor-associated macrophages (TAMs) are prominent components of solid tumors. TAMs exhibit distinct phenotypes and function, and negatively contribute to immune system evasion. Previously published data indicate that inhibition of lipoxygenase (15-LOX2), a key enzyme contributing to TAM function, is critical to overcome tumor resistance and facilitate immunotherapy treatment. In our studies presented here, we first showed that 15-LOX2 is expressed in mouse prostate cancer cells, RM1, growing subcutaneously in C57BL/6 mice, but not in cells growing in culture. We also showed that LOX inhibitors, such as a plant-derived compound, nordihydroguaiaretic acid (NDGA), could restore the function of specific cytotoxic T-cells co-cultured with TAMs in a concentration-dependent manner. Splenocytes from C57BL/6 mice injected intra-muscularly with capsid-optimized AAV6 vectors expressing prostatic aid phosphatase (PAP) were isolated 14 days after vector injection. T-cells were incubated in the presence or absence of RM1 tumor cell extracts and NDGA for 2 hours and then used in killing assays against cultured RM1 cells. Two-color fluorescence assays of cell-mediated cytotoxicity was used to estimate the percentage of dead/alive target cells and a killing curve was generated with different effectors to target cell ratios. Our data indicated that the killing ability of T-cells initiated by capsid-optimized AAV6 vector injection and incubated with RM1 tumor-derived TAMs was approximately 3-fold lower than original activity T-cell. NDGA at a concentration of 10 uM had limited effect on the T-cell activity, but 25 µM NDGA restored the function of the T-cells to approximately 90% of the original activity. In our currently ongoing studies, we are using a combination of capsid-optimized AAV6 vector-mediated immune activation with the NDGA-treatment to corroborate whether a synergetic therapeutic effect can be achieved in an animal model. If successful, this approach could prove useful in the potential clinical application.
Past the Post?: Screening Progress and Fascism's Return

The 2016 presidential election triggers many unanticipated responses. Emotions run high. Political activists discover newfound energy. One’s place in the world has been unfixed, troubled, and unsettled. Philosophers and artists, stunned, rethink the terms for their critical positions and the formal aesthetics that shape their work. The moment is thus rife with anxiety in search of a response. As a film scholar, I find myself driven to script a response. Ironically, as I write I feel paused in time and space. My unfixedness in the shadow of the election put in motion what can best be described as quivering stasis . From my troubled place, an intellectual processing unfolded. I conjured ideas and images that invariably failed to yield a satisfactory response to what had come to pass. What had I seen? Felt? My psychical and physical response to current events might be likened to what Adorno refers to as “the capacity to shudder, as if goose bumps were the first aesthetic image” (437). It’s not a pretty picture. But we’ve known this all along.
Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621)

Ikaros is a zinc finger transcription factor required for B-cell development and proper hematopoiesis, and an important tumor suppressor in developing lymphocytes. To understand the mechanism of Ikaros tumor suppressor function and potentially develop new and improved targeted therapies, it is important to elucidate the downstream target genes involved. With this aim, we combine mouse models of pre-B ALL and in vitro culture of human patient-derived pre-B ALL cells. A mouse model with targeted deletion of the fourth DNA-binding zinc finger of Ikaros resulted in loss of tumor suppressor function, with a limited set of deregulated genes useful to narrow down the list of putative relevant Ikaros target genes (Schjerven et al. , 2013). To specifically address the role of Ikaros as a tumor suppressor in human pre-B ALL, we developed TET-regulated Ikaros expression in human pre-B ALL cells. This enables us to test specific Ikaros target genes from the mouse model, and allows for genome-wide expression analysis by RNA-seq to elucidate all genes downstream of Ikaros in human pre-B ALL cells. To help distinguish direct from indirect target genes, we have mapped the genome-wide binding sites of Ikaros in these human pre-B ALL cells by ChIP-Seq. This approach has identified the Ikaros target gene Ctnnd1. Ongoing experiments explore the potential role of Ctnnd1 and test the current hypothesis that Ikaros-mediated repression of Ctnnd1 limits CyclinD levels and leukemic growth in pre-B ALL.
Potential for Monitoring Gut Microbiota for Diagnosing Infections and Graft-versus-Host Disease in Cancer and Stem Cell Transplant Patients.

BACKGROUND: Gut microbiota, the collective community of microorganisms inhabiting the intestine, have been shown to provide many beneficial functions for the host. Recent advances in next-generation sequencing and advanced molecular biology approaches have allowed researchers to identify gut microbiota signatures associated with disease processes and, in some cases, establish causality and elucidate underlying mechanisms. CONTENT: This report reviews 3 commonly used methods for studying the gut microbiota and microbiome (the collective genomes of the gut microorganisms): 16S rRNA gene sequencing, bacterial group or species-specific quantitative polymerase chain reaction (qPCR), and metagenomic shotgun sequencing (MSS). The technical approaches and resources needed for each approach are outlined, and advantages and disadvantages for each approach are summarized. The findings regarding the role of the gut microbiota in the health of patients with cancer and stem cell transplant (SCT) patients (specifically in modulating the development of gut-derived bacterial infections and a posttransplant immune-mediated complication known as graft-vs-host-disease) are reviewed. Finally, there is discussion of the potential viability of these approaches in the actual clinical treatment of cancer and SCT patients. SUMMARY: Advances in next-generation sequencing have revolutionized our understanding of the importance of the gut microbiome to human health. Both 16S rRNA gene sequencing and MSS are currently too labor-intensive or computationally burdensome to incorporate into real-time clinical monitoring of gut microbiomes. Yet, the lessons learned from these technologies could be adapted to currently used methods (e.g., qPCR) that could then be rigorously tested in the clinical care of these patients.
Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses.

Convergent activity in neural circuits can generate changes at their intersection. The rules of paired electrical stimulation are best understood for paradigms that stimulate input circuits and their targets. We took a different approach by targeting the interaction of descending motor pathways and large-diameter afferents in the spinal cord. We hypothesized that pairing stimulation of motor cortex and cervical spinal cord would strengthen motor responses through their convergence. We placed epidural electrodes over motor cortex and the dorsal cervical spinal cord in rats; motor evoked potentials (MEPs) were measured from biceps. MEPs evoked from motor cortex were robustly augmented with spinal epidural stimulation delivered at an intensity below the threshold for provoking an MEP. Augmentation was critically dependent on the timing and position of spinal stimulation. When the spinal stimulation was timed to coincide with the descending volley from motor cortex stimulation, MEPs were more than doubled. We then tested effect of repeated pairing of motor cortex and spinal stimulation. Repetitive pairing caused strong augmentation of cortical MEPs and spinal excitability that lasted up to an hour after just 5 min of pairing. Additional physiology experiments support the hypothesis that paired stimulation is mediated by convergence of descending motor circuits and large diameter afferents in the spinal cord. The large effect size of this paradigm and the conservation of the circuits being manipulated between rats and humans makes it worth pursuing for recovery of sensory-motor function after injury to the central nervous system. This article is protected by copyright. All rights reserved
Extending Situational Action Theory to White-Collar Crime

ABSTRACTA theory that has started to receive increased empirical attention is Situational Action Theory. This theory argues that an individual’s morality is the central individual-level variable in predicting offending. It also hypothesizes that low self-control will only predict offending among those with low morals. Although this theory has been applied to street crime, the current study represents the first time it has been applied to white-collar crime. With the use of a scenario-based methodology, the results support the theory. Along with the implications of these findings, limitations and directions for future research are also presented.
Wideband partial response CPM demodulation via multirate frequency transformations and decision feedback equalization

Continuous phase modulation (CPM) is a popular frequency modulation technique used in mobile communications due to its power efficiency and constant modulus properties. Conventional narrowband CPM demodulation employs the Viterbi algorithm after phase demodulation and requires that the phase states be rational and contain additive white noise. The complexity of the Viterbi approach further increases with the number of phase states. Frequency discrimination approaches that estimate the instantaneous frequency provide a simpler suboptimal approach but are primarily for full response CPM and are not well known for wideband partial response CPM. In this paper, we investigate an approach that combines multirate frequency transformations for wideband CPM demodulation with decision feedback equalization for memory removal. This combined approach avoids the problems of complexity and restrictive requirements of the Viterbi approach. Simulation results are used to demonstrate the validity of the combined approach.
Borderline Papillary Serous Tumor of the Fallopian Tube

We report a case of borderline papillary serous tumor of the fallopian tube in a 31-year-old woman. The tumor was characterized by the formation of papillary projections with focally prominent epithelial stratification and atypia. The histologic features of the tumor were largely similar to a borderline serous tumor of the ovary. Two years after initial presentation, the patient underwent in vitro fertilization and carried the ensuing pregnancy to term. There is no evidence of disease nearly 6 years after presentation, which suggests that these extremely uncommon tumors can be managed conservatively.
The Grammar of Catholic Schooling and Radically “Catholic” Schools

A “grammar of Catholic schooling” inhibits many elementary and secondary Catholic schools from reflecting on how they practice Catholic Social Teaching (CST). The values of human dignity, the common good and a preferential option for the marginalized are central to CST. Schools can live these values by serving children who live in poverty, are racial, ethnic, and linguistic minorities, or have disabilities. This article demonstrates how a grammar of Catholic schooling has allowed Catholic schools to fall into recruitment and retention patterns antithetical to CST. Drawing upon a multicase, qualitative study of three urban Catholic elementary schools serving marginalized students, the article illustrates how select Catholic schools are breaking the grammar of Catholic schooling by practicing CST. Implications for research and practice are discussed.
Gene immunization for the induction of antigen-specific, non MHC-restricted responses

Injection of naked plasmid DNA encoding a specific antigen is capable of eliciting T cell responses which are restricted to Major Histocompatibility Complex (MHC) class I or MHC class II as well as antibody responses. Furthermore, the combination of plasmids expressing costimulator molecules along with antigen encoded plasmids can further augment certain responses. While immunization by standard protein injections allows the cells of the immune system to take up and present the foreign protein, gene immunization gives the added advantage of ectopically expressing membrane bound molecules such as potential antigen presenting molecules or costimulatory ligands which may alter the overall immune response. By injecting plasmids encoding murine CD1d1, B7.1, and ovalbumin, we can induce a CD1-restricted, ovalbumin-specific Cytotoxic T Lymphocyte (CTL) response.
Meaning of Intracranial Pressure-to-Blood Pressure Fisher-Transformed Pearson Correlation-Derived Optimal Cerebral Perfusion Pressure: Testing Empiric Utility in a Mechanistic Model.

OBJECTIVES Time-averaged intracranial pressure-to-blood pressure Fisher-transformed Pearson correlation (PRx) is used to assess cerebral autoregulation and derive optimal cerebral perfusion pressure. Empirically, impaired cerebral autoregulation is considered present when PRx is positive; greater difference between time series median cerebral perfusion pressure and optimal cerebral perfusion pressure (ΔCPP) is associated with worse outcomes. Our aims are to better understand: 1) the potential strategies for targeting optimal cerebral perfusion pressure; 2) the relationship between cerebral autoregulation and PRx; and 3) the determinants of greater ΔCPP. DESIGN Mechanistic simulation using a lumped compartmental model of blood pressure, intracranial pressure, cerebral autoregulation, cerebral blood volume, PaCO2, and cerebral blood flow. SETTING University critical care integrative modeling and precision physiology research group. SUBJECTS None, in silico studies. INTERVENTIONS Simulations in blood pressure, intracranial pressure, PaCO2, and impairment of cerebral autoregulation, with examination of "output" cerebral perfusion pressure versus PRx-plots, optimal cerebral perfusion pressure, and ΔCPP. MEASUREMENTS AND MAIN RESULTS In regard to targeting optimal cerebral perfusion pressure, a shift in mean blood pressure or mean intracranial pressure with no change in mean blood pressure, with intact cerebral autoregulation, impacts optimal cerebral perfusion pressure. Second, a positive PRx occurs even with intact cerebral autoregulation. In relation to ΔCPP, for a given input blood pressure profile, with constant intracranial pressure, altering the degree of impairment in cerebral autoregulation or the level of PaCO2 maintains differences to within ±5 mm Hg. Change in intracranial pressure due to either an intermittently prolonged pattern of raised intracranial pressure or terminal escalation shows ΔCPP greater than 10 mm Hg and less than -10 mm Hg, respectively. CONCLUSIONS These mechanistic simulations provide insight into the empiric basis of optimal cerebral perfusion pressure and the significance of PRx and ΔCPP. PRx and optimal cerebral perfusion pressure deviations do not directly reflect changes in cerebral autoregulation but are, in general, related to the presence of complex states involving well-described clinical progressions with raised intracranial pressure.
Peer-to-peer injection: Demographic, drug use, and injection-related risk factors

Abstract Background Peer-to-peer injection (either providing or receiving an injection to/from a person who injects drugs [PWID]) is common (19%–50%) among PWID. Most studies of peer-to-peer injection have focused on receiving injection assistance, with fewer examining providing injection assistance and none considering characteristics of PWID who do both. We examined characteristics of PWID by peer-to-peer injection categories (receiving, providing, both, and neither) and determined if these behaviors were associated with receptive and distributive syringe sharing. Methods Los Angeles and San Francisco PWID (N = 777) were recruited using targeted sampling methods and interviewed during 2011–2013. Multinomial logistic regression was used to determine characteristics associated with peer-to-peer injection categories and logistic regression was used to examine if peer-to-peer categories were independently associated with distributive and receptive syringe sharing. Results Recent peer-to-peer injection was reported by 42% of PWID (18% provider; 14% recipient; 10% both). In multinomial regression analysis, PWID reporting any peer-to-peer injection were more likely to inject with others than those who did neither. Injection providers and those who did both were associated with more frequent injection, illegal income source, and methamphetamine injection while injection recipients were associated with fewer years of injection. Injection providers were younger, had more years of injecting, and were more likely to inject heroin than PWID who did neither. In multivariate analyses, we found that providers and PWID who did both were significantly more likely to report receptive and distributive syringe sharing than PWID who did neither. Conclusion Peer-to-peer injection is associated with HIV/HCV risk. Current prevention strategies may not sufficiently address these behaviors. Modification of existing interventions and development of new interventions to better respond to peer-to-peer injection is urgently needed.
The effect of polypharmacy on prefrontal cortex activation during single and dual task walking in community dwelling older adults

Abstract Introduction Polypharmacy, defined as the use of 5 or more medications is associated with multiple adverse outcomes in older adults, including falls and slow gait velocity. However, the relationship between polypharmacy and cortical control of locomotion has not been reported. The purpose of this study was to examine the relationship between polypharmacy and activation patterns in the prefrontal cortex (PFC), a brain region involved in higher order control of locomotion during attention-demanding conditions. Methods Using Functional Near Infrared Spectroscopy (fNIRS) to quantify PFC oxygenated hemoglobin (HbO2) levels, we performed a cross sectional analysis of 325 community dwelling adults age ≥65 years, and examined HbO2 levels during single tasks (Single-Task-Walk (STW), (talking, cognitive interference (Alpha)) and Dual-Task Walk (DTW)). Results The prevalence of polypharmacy was 33% (n = 104) amongst the 325 participants (mean age 76.4 ± 6.7 years, 56% women). Among the 221 participants with no polypharmacy there was an increase in HbO2 levels from STW to DTW (estimate = −0.625; p = Conclusion The results of this study further support the need for clinicians to reduce polypharmacy in older adults, given its significant association with the PFC hemodynamic response during attention-demanding locomotion.
Community Health Workers as Accelerators of Community Engagement and Structural Competency in Health

Asian Americans are the fastest growing minority population in the United States. Asian Americans are portrayed as uniformly hardworking, affluent, and healthy, leading to the “model minority” stereotype that is often promoted in the American culture and media. However, there are substantial differences in language, migration, and social experiences across more than 30 Asian subgroups; and their health concerns and risks vary across and within these communities. From our personal experiences as refugees and immigrants, we know firsthand the cultural, linguistic, and social barriers that Asian Americans face in navigating the healthcare system. The trauma associated with war, migration, and social isolation, as well as cultural differences and language barriers, make it challenging to seek preventive and timely healthcare services. Similarly, providers also have poor understanding of the stress and mental health concerns associated with migration and displacement, and how that is manifested in health outcomes. These issues are complicated in miscommunication due to language differences and misconceptions of the experience of pain or symptoms among their Asian American patients. Decades later, we have learned from our research that our families’ experiences were not unusual; doctors are less likely to follow evidence-based guidelines and meet standards of care with their Asian American patients compared with other racial groups in preventing and managing chronic conditions. We have also learned that times have not changed dramatically in the care of Asian American patients even though there is now increasing recognition that Asian Americans face just as many health challenges, including an increasing rate of diabetes and certain cancers. Community health workers (CHW) can play an important role in bridging the communication gap, engaging low income Asian immigrant and refugee communities, helping them navigate a complex healthcare system, and, ultimately, improve health outcomes. CHWs are the frontline health workers who are indigenous and trusted members of the community. With the right balance of training and guidance, CHWs can be effective leaders and change agents in empowering and helping Asian American communities develop meaningful solutions for healthful behavior change.
A General Framework to Map Neural Networks onto Neuromorphic Processor

Bio-inspired neuromorphic hardware is an emerging computing architecture, which features highly parallel and distributed computing elements similar to the functionality of human brain. Recent study shows that neuromorphic hardware can achieve state-of-the-art performance in various cognitive tasks. However, limitations in fabrication technology has led to limitations in fan-in, fan-out, memory capacity, connectivity etc., making neuromorphic chips difficult to program. Neural networks have to satisfy specific constraints in order to be mapped to hardware, which not only requires developers to have knowledge of specific hardware, but also makes training difficult. We proposed a general framework to address above issues. It consists of a workflow to convert an existing neural network to satisfy the hardware constrains while minimizing the error caused by conversion, algorithms to increase hardware resource utilization and minimize on-chip communication cost are also proposed and evaluated. The experimental results show that the framework reduces conversion error to 0.67%, and reduces 53% of communication latency.
Development and Validation of a Canine Castration Model and Rubric

Veterinary educators use models to allow repetitive practice of surgical skills leading to clinical competence. Canine castration is a commonly performed procedure that is considered a Day One competency for a veterinarian. In this study, we sought to create and evaluate a canine pre-scrotal closed castration model and grading rubric using a validation framework of content evidence, internal structure evidence, and relationship with other variables. Veterinarians (n = 8) and students (n = 32) were recorded while they performed a castration on the model and provided survey feedback. A subset of the students (n = 7) then performed a live canine castration, and their scores were compared with their model scores. One hundred percent of the veterinarians and 91% of the students reported that the model was helpful in training for canine castration. They highlighted several areas for continued improvement. Veterinarians' model performance scores were significantly higher than students', indicating that the model had adequate features to differentiate expert from novice performance. Students' performance on the model strongly correlated with their performance of live castration (r = .82). Surgical time was also strongly correlated (r = .70). The internal consistency of model and live rubric scores were good at .85 and .94, respectively. The framework supported validation of the model and rubric. The canine castration model facilitated cost-efficient practice in a safe environment in which students received instructor feedback and learned through experience without the risk of negatively affecting a patient's well-being. The strong correlation between model and live animal performance scores suggests that the model could be useful for mastery learning.
Childhood leukemia survivors exhibit deficiencies in sensory and cognitive processes, as reflected by event-related brain potentials after completion of curative chemotherapy: A preliminary investigation

Objective: The purpose of this study was to characterize post-chemotherapy sensory, memory, and attention abilities in childhood survivors of acute lymphoblastic leukemia (ALL) to better understand how treatment affects cognitive functioning. Methods: Eight ALL survivors and eight age-matched, healthy children between the ages of 5-11 years participated in the study. Among the ALL survivors, a median of 63 days (range 22-267 days) elapsed between completion of chemotherapy and this assessment. Sounds were presented in an oddball paradigm while recording the electroencephalogram in separate conditions of passive listening and active task performance. To assess different domains of cognition, we measured event-related brain potentials (ERPs) reflecting sensory processing (P1 component), working memory (mismatch negativity [MMN] component), attentional orienting (P3a), and target detection (P3b component) in response to the sounds. We also measured sound discrimination and response speed performance. Results: Relative to control subjects, ALL survivors had poorer performance on auditory tasks, as well as decreased amplitude of the P1, MMN, P3a, and P3b components. ALL survivors also did not exhibit the amplitude gain typically observed in the sensory P1 component when attending to the sound input compared to when passively listening. Conclusions: Atypical responses were observed in brain processes associated with sensory discrimination, auditory working memory, and attentional control in pediatric ALL survivors indicating deficiencies in all cognitive domains compared to age-matched controls. Significance: ERPs differentiated aspects of cognitive functioning, which may provide a useful tool for assessing recovery and risk of post-chemotherapy cognitive deficiencies in young children. The decreased MMN amplitude in ALL survivors may indicate (N-methyl D-aspartate) NMDA dysfunction induced by methotrexate, and thus provides a potential therapeutic target for chemotherapy-associated cognitive impairments.
The value of routine bone marrow culture for Histoplasma capsulatum in pediatric hematology.

1. Of 76 bone marrow cultures in pediatric patients with a variety of hematologic abnormalities, 5 (6.5 per cent) yielded H. capsulatum . 2. Methods used and brief case reports were described. 3. In 2 of the 5 cases with histoplasmosis, organisms were observed on direct examination of the marrow and cultures were only of confirmatory value. 4. In the remaining 3 patients with histoplasmosis, direct examination of marrow showed no features which distinguished them from the 71 negatives. In these 3 bone marrow culture was the only means by which diagnosis could be established. 5. In no instance in which a negative bone marrow culture for H. capsulatum was obtained, was histoplasmosis diagnosed by other methods. 6. We are of the opinion that while routine marrow culture for H. capsulatum is of little value in adults, it is of considerable value for case finding in infants and children.
Neuropeptides of Mosquitoes

The adult mosquito, despite the limitations of its size, is a valuable experimental animal for the study of insect reproduction and such related processes as feeding behavior, digestion, water balance, anabolism, and the endocrine regulation of these processes. Mosquitoes could hardly escape our attention, since they are vectors of most of the transmissible pathogens that are lethal to several millions of humans each year. For many years, physiologists have been attracted to mosquitoes by the obvious association between their blood-feeding habits and oocyte maturation. Yet, the most salient question of how the ingestion of vertebrate blood signal the onset of oogenesis, remains only partially answered after nearly a half century of investigation.
A Deep Learning Approach for Failure Prognostics of Rolling Element Bearings

Remaining useful life (RUL) prediction of rotating machine components is essential to enabling predictive maintenance of industrial and agricultural machinery. This paper presents a novel deep learning approach for failure prognostics of rolling element bearings. The proposed approach has three unique features: (1) it employs a new data augmentation technique to improve the accuracy and robustness of RUL prediction in cases where a deep learning model only has access to a small amount of training data; (2) it incorporates a robust feature learning strategy that integrates a physics-based feature extraction process with a data-driven process; and (3) it implements a new similarity-based approach for effectively capturing the true degradation trend of each individual bearing unit. A practical case study involving run-to-failure experiments of rolling element bearings on the PRONOSTIA platform is provided to assess the performance of the proposed approach. Results from the case study show the proposed deep learning approach produced higher accuracy in RUL prediction than an existing machine learning approach.
Influence of the high temperature treatment of zinc phosphate conversion coatings on the corrosion protection of steel

An anhydrous α-Zn3(PO4)2 phase converted by the dehydration of hydrous zinc phosphate, Zn3(PO4)2·2H2O, crystal coatings in air at a temperature of approximately 300 °C, significantly enhances the corrosion resistance of steel, and also reduces the susceptibility of the crystals to alkaline dissolution. A subsequent α→γ phase transition at approximately 500 °C results in a poor protection behaviour, because of the formation of numerous microcracks on the crystal faces.
Measurement of asbestos emissions associated with demolition of abandoned residential dwellings

Many cities are revitalizing their urban cores through the demolition of abandoned residential dwellings (ARDs). However, data regarding the emissions of asbestos during such an operation are sparse. We measured airborne asbestos emissions from emergency demolitions (demolitions on structures deemed too dangerous to enter and remove asbestos) of ARDs in Detroit. High-flow air sampling was conducted during ARD demolitions. Air samples were analyzed using Phased Contrast Microscopy (PCM), and a subset using Transmission Electron Microscopy (TEM). One hundred and one air samples were collected on 25 emergency demolitions. Fifty-four of the 101 PCM samples (53%) exceeded the limit of detection (LOD). However, only 2 of 46 TEM samples (4%) exceeded the LOD for asbestos; these latter samples were from two different demolitions and each contained a single chrysotile asbestos fiber. Using conservative exposure assumptions and commonly-accepted risk estimation formulae, we estimated the lifetime risk of mesothelioma and lung cancer combined to be less than one case per one million people. Emissions of airborne asbestos during emergency (unabated) ARD demolition operations appear to be negligible. As a result, the associated health risk for asbestos-related disease is also negligible. Reconsideration of current regulatory mandates for asbestos abatement in ARDs may be warranted.
Media Representations as a Form of Stacking: Male and Female Athletes Featured on Men’s Magazine Covers, 1980–2019:

This study analyzed 264 athlete images featured on the covers of nine men’s magazines across a 40-year period, 1980–2019. Among males, who accounted for 227 (81%) of the 264 athletes, African Ameri...