cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 333: Hhcy Promotes Myocardial Infarction Induced Myocardiocyte Death via Mitochondria Mediated Inflammasome Activation

Introduction: Elevated level of serum homocysteine (Hcy) has been identified as a risk factor for accelerating progression of cardiovascular disease. Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation by damaged mitochondria results in caspase-1 dependent inflammatory form of cell death. Methods and Results: AMI procedure was performed on hCBS/m cbs knockout mice at the age of 10weeks. Caspase-1 activity and myocardiocyte apoptosis were observed at the early stage of post-MI in severe HHcy mice (Hcy,120-220μM). Severe HHcy remarkably aggravated infarction size, cardiomyocyte area, and interstitial fibrosis 6 weeks after MI from 22.7 ± 4.3%, 340 ± 54μm 2 , 13.9 ± 1.9% in control mice (Hcy, 7-10μM) to 33.6 ± 6.5%, 485 ± 65μm 2 , 26 ± 4.5%, respectively, ( P =0.035, P = 0.041, P =0.002). In the meantime, HHcy significantly increased LV cavity dilatation and dysfunction as compared with control mice by echocardiography (5.9 ± 0.2 vs. 4.2 ± 0.4mm, P= 0.039; LV ejection fraction, 22.6 ± 3.9% vs. 36.8 ± 4.0%, P =0.011). Cultured neonatal mouse ventricular myocyte (NMVM) treated with the combination of DL-Hcy (500μM, 48h) and hypoxia (0.5% O2) showed that increased NLRP3 and caspase1 expression and activity, mitochondrial reactive oxygen species (mtROS) and mtDNA production, dissipation of mitochondrial membrane potential, and mitochondrial permeabilization. Moreover, synergetic effect of Hcy and hypoxia led to pronounced accumulation of damaged mitochondrial through suppressing mitophagy of damaged mitochondria. Caspase-1 activity and myocardiocyte death were lessened as NMVMs were administrated with mitochondria-targeted antioxidant Mito-temple and SOD2, whereas caspase-1 inhibition was not able to fully rescue damaged mitochondria. Conclusion: Acute myocardial infarction (AMI) initiates an intense inflammatory response in myocardium that promotes myocardiocyte death, ventricular remodeling, and cardiac dysfunction. Hcy accelerates cardiomyocyte death post-MI in part through mitochondrial-mediated NLRP3 inflammasome activation and inflammation, which contributes to adverse cardiac remodeling, ventricular dysfunction, and heart failure.
Competitive Interaction Design of Cooperative Systems Against Attacks

This technical note proposes a resilient cooperative control design for networked cooperative systems when subjected to external attacks. The systems considered in this paper can have any information topology described by a leader-follower digraph. A potential attack on such systems consists of unknown bounded signals generated from any linear or nonlinear finite- $L_2$ -gain exogenous dynamical system and injected distributively into nodes of the system's network. The purpose of the attack is to destabilize the consensus dynamics by intercepting the system's communication network and corrupting its local state feedback. The proposed resilient control design consists of introducing a virtual system with hidden network such that the overall system consisting of the original consensus system, the virtual system, and the attack dynamics is stable without requiring any information about the locations or nature of the attack. This is accomplished by utilizing the concept of competitive interaction to provide explicit design criteria for the hidden network of the virtual system to interact with the original system. A graph theoretical approach and a Lyapunov direct method are used to analyze the overall system and show that the proposed design ensures stability of the overall system and preserves the consensus of the original system. An example, which includes several scenarios, is used to illustrate the results.
Abstract B028: Beta 2-microglobulin promotes human pancreatic cancer cell migration

Beta 2-microglublin (β2m) is a 12-kilodalton protein that serves as the non-covalently bound light chain in complex with the major histocompability complex (MHC) class I heavy chain. The human MHC class I heavy chain is known as human leukocyte antigen (HLA), which exists in three isotypes (HLA-A, -B, and -C). Much of the known function of β2m is in regards to its role in stabilizing the HLA class I heavy chain and thereby helping to present endogenous antigenic peptides to cytotoxic T cells. Notably, β2m has recently been found to be elevated in expression in a variety of cancers, including renal cell carcinoma, oral squamous cell carcinoma, prostate cancer, lung cancer, breast cancer, and multiple lymphocytic malignancies. In most of these cancers, β2m is correlated with more advanced disease and poorer prognosis. It has also been shown that in some cancer models, such as a renal cell carcinoma and an oral squamous cell carcinoma model, β2m can affect the proliferation and migration of these tumor cells. The levels and effects of β2m in pancreatic cancer, however, have not been reported thus far. Recent results from our laboratory have revealed high expression of β2m in nearly all members of a panel of pancreatic cancer cell lines. To examine the functional role that β2m plays in pancreatic cancer, we used siRNA specific for β2m to decrease its expression in the mentioned panel of pancreatic cancer cell lines and evaluated migration by transwell assay. Our results showed that the migration of the tested pancreatic cancer cell lines significantly decreases when β2m expression is reduced. Furthermore, we found that when β2m levels are downregulated, there are corresponding decreases in the levels of the HLA-A and -B heavy chains and in the expression of amyloid precursor-like protein 2 (APLP2). Previous research from our laboratory has shown that β2m affects APLP2/MHC association and that reducing expression of APLP2 slows pancreatic cancer cell migration. Additionally, our current research demonstrated that downregulation of β2m expression reduces the steady-state level and the half-life of APLP2. In conclusion, our results indicate that β2m promotes the migration of pancreatic cancer cells and suggest that this effect may be mediated through stabilization of the HLA class I heavy chain and, secondarily, APLP2. These studies thus provide evidence of β2m as a potential target for novel therapies directed against pancreatic cancer. Citation Format: Bailee Sliker, Cassie Liu, Brittany Poelaert, Benjamin Goetz, Joyce C. Solheim. Beta 2-microglobulin promotes human pancreatic cancer cell migration [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B028.
Paeonol attenuates isoflurane anesthesia-induced hippocampal neurotoxicity via modulation of JNK/ERK/P38MAPK pathway and regulates histone acetylation in neonatal rat.

Objective: Volatile anesthetic such as isoflurane causes widespread neurodegeneration in the developing animal brains and also induces cognitive impairments. Paeonol is a plant-derived phenolic com...
Truth, Trump, Tyranny: Plato and the Sophists in an Era of ‘Alternative Facts’

There are five attitudes to truth: that of the philosopher, the truth-teller, the liar, the sophist, and the tyrant. After discussing the two most famous Greek Sophists, Gorgias and Protagoras, this essay argues that Trump’s attitude to truth while campaigning was that of a sophist: someone who is indifferent to the truth, using words only to acquire money, fame, and power. When he became president, however, his attitude changed to that of the tyrant described by Plato: someone who uses power to assert control over the “truth.” In other words, by the repeated statement of manifest falsehoods, he drew a circle around himself, forcing others to choose between submission to his will and recognition of an independent reality.
Cyanobacteria: Electrotransformation and Electroextraction

Cyanobacteria are an ancient, diverse, and ecologically important group of oxygenic-photosynthetic eubacteria related phylogenetically to plant chloroplasts (Rippka et al. 1979; Wilmotte 1994). Some members of unicellular genera such as Synechococcus and Synechocystis have physiological mechanisms for DNA uptake and are readily transformed genetically (Porter 1986; Shestakov and Reaston, 1987). DNA can be introduced into additional strains, including filamentous forms capable of nitrogen-fixation and heterocyst differentiation, by conjugal transfer from Escherichia coli mediated by broad host-range conjugative plasmids (Elhai and Wolk, 1988). Many other cyanobacteria with interesting properties appear incapable of biological DNA uptake. For these, electroporation offers an approach that has widely allowed the transformation of diverse bacteria (Halloway 1993). Even where other methods are possible, electroporation may be advantageous because of simplicity or efficiency. Electrotransformation of cyanobacteria was first demonstrated by Thiel and Poo (1989) and has since been applied to several strains (Chiang et al. 1992; Moser et al. 1993; Muhlenhoff and Chauvat 1996; Chapter 29). Electroporation in addition provides an efficient method for extracting macromolecules from cells.
OXIDATION KINETICS OF PYROLYTIC GRAPHITE

Kinetic data are presented for the oxidation of pyrolytic graphite in air and nitrogen-diluted air. The temperature range covered was from 614° to 1568°C. A flowing system was used at atmospheric pressure with linear flow rates from 16 to 30 cm/min. By using dimensional changes the over-all rate was corrected for that on the edge and the net rate on the faces of the specimens, which corresponds to the basal plane of the ideal graphite structure, was obtained. Neither gas velocity nor diffusion greatly affected the observed rates which were of one-half order with respect to oxygen concentration. Using only the lower temperatures, because of the possibility that bulk diffusion enters about 1400°– 1500°K, leads to an activation energy of about 36.8 kcal/g atom of carbon consumed. A mechanism is based upon fast attainment of equilibrium between gaseous oxygen and surface oxide complexee (C—O sites) for which the equilibrium constant depends upon the one-half power of oxygen concentration in the gas stream. The rate limiting step would be the dissociation of product molecules from the surface at a speed dependent upon the surface concentration of the complex sites. The edges oxidized faster than the basal plane faces by a factor of about 2.5 and this ratio appeared to increase with temperature. At 950°C a representative spectrographic graphite oxidized in normal air about 2 orders of magnitude faster than the basal plane of pyrolytic graphite.
Inhibition of inflammation by PEITC, CUR, SFN alone and in combination in RAW cells

5477 Accumulating evidence from epidemiological and clinical studies indicates that chronic inflammatory disorders harbor an increased risk of cancer development. ROS/RNS can cause oxidative damage to DNA, proteins, and lipids. NF-κB is activated by a wide variety of stimuli such as oxidative stress, TNF, IL-1, LPS and UV light. The binding of NF-κB to specific sequence in the promoter region of genes triggers the transcriptional activation of NF-κB-regulated genes which are involved in tumor cell proliferation, angiogenesis and metastasis. Therefore, tumorigenesis resulting from inflammation could possibly be prevented by inhibiting the activation of NF-κB and its inflammation markers like TNF, IL-1, NO, PGE2. It is widely accepted that isothiocyanates such as SFN and PEITC are strong phase-II detoxifying/antioxidant enzymes inducer. On the other hand, CUR has been shown to be strongly linked to the anti-inflammatory effect. Therefore it would be interesting to see if combination of these compounds can inhibit inflammation or carcinogenesis, achieving lower toxicity and higher efficacy. In this study, we report that combination of PEITC/SFN or Curcumin/SFN has a more significant effect than the compounds alone in down-regulating inflammation in RAW cells. The synergistic effects in the inhibition of TNF, IL-1, NO and PGE2 are the most significant. Enzymes like iNOS and COX2 are also synergistically reduced. In summary, this study suggests that combination of Curcumin/SFN or PEITC/SFN maybe more effective in preventing inflammation-induced carcinogenesis. (Supported in part by NIH R01-CA073674).
Rethinking Teacher Retention in Hard-to-Staff Schools

National, state, and local educational agencies identify teacher retention as an issue of continuous importance and concern. This report addresses the issue of teacher retention through the lens of administrative effectiveness and involvement, as well as teachers’ intrinsic motivations. Relevant findings include structural framing of the educational environment, student behaviors, school district demands for improvement, and teacher perspectives on administrative support. The report iterates that teacher retention does not have a one-size-fits-all solution, and that each school division and individual school must work purposefully to devise plans to retain its most effective teachers.
What Can the Reid List of First Programming Languages Teach Us About Teaching CS1

The CS1 course is arguably the most important course offered in a Computer Science major; if students struggle in the course, they are likely to drop out of the major, and if certain key topics are covered, they may struggle in other courses later in their undergraduate program. For this reason, it is not surprising that the programming language used in a CS1 course as well as the teaching methodology is frequently a contentious subject. Richard Reid of Michigan State University kept a list of programming languages used in CS1 courses from the early 1990s until his retirement in 1999, and Reid's former student, Frances Van Scoy, continued compiling the List until 2006. Siegfried et al. updated the List in 2011 and 2015. The historical data shows the different languages (and in some cases, approaches) used by the schools reported on the Reid List. Additionally, in compiling the last two lists, there were trends spotted, with some feedback from faculty at the Reid List schools, stating the reasons for changes that they made as well as why they currently use and previously used the various languages.
Pressure Field Near Counterrotating Propellers

Abstract : Expressions for the vibratory pressure field produced by an operating counterrotating propeller system are developed in terms of first and second blade harmonics of individual propellers. The coefficients of the first and second blade harmonics of a 3-bladed propeller are expressed in closed form in terms of complete elliptic integrals. It is found that the pressure signal due to a counterrotating propeller can be obtained from the summation of the pressure fields of its two components as though the two propellers operate as separate units, since their mutual interference was found to contribute little to the total vibratory pressure signal in the near field. This study indicates that the counterrotating propeller system has vibratory characteristics much superior to an equivalent single propeller having the number of blades of one of its components, delivering the same thrust at the same RPM at optimum conditions. A study of the interference effects by means of a two dimensional analogue indicates that the effect of the forward propeller on the aft is much greater than the effect of the aft propeller on the forward propeller.
Mycobacterium avium-intracellulare (MAI) liver abscess mimicking liver metastasis in a patient with rheumatoid arthritis on adalimumab and methotrexate.

A 75-year-old man with a history of rheumatoid arthritis (on adalimumab and methotrexate), hiatal hernia and Barrett’s oesophagus presented to an outside hospital with a 1 day history of severe vomiting and abdominal pain. CT of the abdomen showed a large paraesophageal hernia, and he was
First Robot-Assisted Laparoscopic Pyeloplasty Utilizing the da Vinci SP System

Abstract Introduction: Robotic pyeloplasty is an established treatment for ureteropelvic junction obstruction (UPJO) since the first series of robotic pyeloplasty was published in 2002.1 The roboti...
Physiological, behavioral and environmental factors influence bifurcated circadian entrainment in mice

Abstract Under permissive conditions, mice and hamsters exposed to a polyphasic light regime consisting of two light and two dark phases every 24 h (Light:Dark:Light:Dark; LDLD) can adopt a bifurcated entrainment pattern with roughly equal amounts of running wheel activity in each of the two nights. This rhythm “bifurcation” has significant after-effects on increased circadian adaptability: Mice that have been bifurcated show accelerated rates of re-entrainment after a sudden phase shift and have a markedly expanded range of entrainment. Identifying environmental and physiological factors that facilitate or prevent rhythm bifurcation in LDLD conditions will contribute to an understanding of mechanisms underlying enhanced circadian plasticity. Here we investigate the effects of sex, age, light intensity, access to a running wheel, melatonin, and diet composition on bifurcation behaviors of mice (C57Bl/6 J) exposed to LDLD. Female mice and young mice ( 30 weeks). Additionally and independently, higher photophase intensities (~500 lx) predict more symmetric entrainment than low levels of light (~50 lx). Without access to a functional running-wheel, mice do not adopt bimodal activity patterns and only transiently maintain them, suggesting that high levels of aerobic activity are necessary for rhythm bifurcation. Neither a lifetime exposure to melatonin administered in the drinking water nor a high fat diet affected bifurcation. Collectively, these results demonstrate that circadian plasticity can be strongly modulated by intrinsic and extrinsic factors. With enhanced mechanistic understanding of this modulation, it may be possible to render human clocks more adaptable and thereby ameliorate negative consequences associated with repeated jet-lag or shift-work.
Unilateral segmental agenesis of the vertebral artery at the C2 level

To report a case of unilateral segmental agenesis of the vertebral artery (VA). We describe the angiographic and MRI features of a segmental VA agenesis (C2 segment). VA agenesis is caused by the absence of the anastomotic connection normally linking two adjacent intersegmental arteries; in the reported observation, a paravertebral extraforaminal anastomosis replaced the C2 segment normally joining the 1st and 2nd cervical intersegmental arteries through the C2 transverse foramen. We present an observation of segmental VA agenesis. This variant is consistent with the developmental history of the VA. It appears exceptional but is more likely underappreciated.
Prospective Associations between BOLD Markers of Response Inhibition and the Transition to Frequent Binge Drinking

BACKGROUND Altered brain activation during response inhibition has been linked to a greater risk for alcohol and other substance use behaviors in late adolescence. However, the ability of neural markers of response inhibition, acquired during adolescence, to temporally predict the transition from less frequent and lower quantity alcohol use to high-risk, frequent (≥ weekly) binge drinking behavior remains unclear. METHODS Adolescents (N = 29; 9 females) were selected from a larger ongoing longitudinal study to include those who transitioned to at least weekly binge drinking (≥5/4 alcoholic drinks for males/females per occasion) over a 15-year follow-up period. Prior to the onset of weekly binge drinking (mean age = 18.0), participants underwent a functional MRI including a go/no-go task. Whole-brain activation from the no-go correct rejection versus no-go false alarm contrast was used to predict time to transition to frequent binge drinking. RESULTS Less no-go correct rejection versus no-go false alarm activation in a cluster including the precentral gyri, insula, and inferior frontal gyri predicted a more rapid transition into frequent binge drinking (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05, cluster threshold ≥ 18 voxels). CONCLUSIONS Results from this study are supported by literature suggesting that frontoinsular involvement is important for successful inhibition and cognitive control. Altered brain activation during response inhibition may thus represent neural antecedents of impulse regulation difficulties related to alcohol consumption. The magnitude of this activation provides temporal information that may be used to inform and optimize timing of interventions aimed at preventing the escalation and transition to problematic drinking for youth who have already begun to engage in drinking behaviors.
Alzheimer's Disease and Alzheimer's Disease-Related Dementias in Older African American and White Veterans.

BACKGROUND Racial disparity in the epidemiology of Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) has been reported. However, less is known about this disparity among Veterans. OBJECTIVE To estimate the racial disparity in AD/ADRD among the Veterans. METHODS Of the 5,413,418 Veterans≥65 years receiving care at the Veterans Health Administration (1999-2016), 4,045,269 were free of prevalent AD/ADRD, schizophrenia, or bipolar disorder at baseline. Of these, 432,469 were African American. Race was self-identified and incident AD/ADRD during 20 (median 6.7) years of follow-up was ascertained using International Classification of Diseases codes. RESULTS Patients had a mean age of 70.4 (±6.6) years and 97.8% were men. Age-sex-adjusted incidence of AD/ADRD per 1,000 person-year was 19.3 and 10.8 for African American and white Veterans, respectively (age-sex-adjusted hazard ratio associated with African American race, 1.77; 95% confidence interval, 1.75-1.79; p < 0.0001). This association remained essentially unchanged after multivariable adjustment (hazard ratio, 1.67; 95% confidence interval, 1.65-1.69; p < 0.0001). Among the key baseline characteristics that were significant predictors of AD/ADRD in both races, stroke was a significantly stronger predictor among African Americans, and Hispanic ethnicity and depression among whites (p-value for all interaction,<0.0001). CONCLUSION The findings of a higher incidence of AD/ADRD among African American Veterans is consistent with the findings in the general population reported in the literature, although the overall incidence appears to be lower than that in the general population. Future studies need to examine this disparity in incidence as well as the between-race heterogeneity in AD/ADRD risk.
Can the WTO Stop the Race to the Bottom? Tax Competition and the WTO

In this article, I analyze the interaction between income tax competition and the multilateral trade regime. I argue that several forms of tax competition such as special tax zones (STZs), export tax incentives, participation exception, profit shifting toleration, and tax havens distort international trade and therefore should be policed by the WTO. I also argue that the international tax regime (ITR) will not be able to curtail these distortive effects anytime soon because of insurmountable collective action issues. The limitations of the ITR heighten the importance of a timely, thorough, and comprehensive response by the WTO, which has not been seen so far. In addition to the legal application of the WTO agreements to tax competition measures, the article discusses the shortages, inconsistencies, and unfair results of the current WTO legal framework, and the immediate need for modernization. A first step for modernization will be achieved if WTO adjudicators use evolutive and systemic methods of interpretation. With the support of these methods, the WTO dispute settlement bodies could police several tax competition measures that have not been scrutinized in the past. A second step for modernization should be expanding the scope of the SCM to include services and digital industries. But this expansion would require reversing the current political inertia, which remains to be seen.
Unmasking Unique Immune Altering Aspects of the Microbiome as a Tool to Correct Sepsis-Induced Immune Dysfunction.

Background: Sepsis-related mortality is driven by immune dysfunction. A bidirectional micro-organism–immune cell cross talks exists. Gut Bacteroides fragilis–T-cell crosstalk maintains innate immun...
Risk assessment of therapeutic agents under consideration to treat COVID-19 in paediatric patients and pregnant women.

AIM: Repurposing strategies to address the COVID-19 pandemic have been accelerated. As both pregnant and paediatric patients are likely to be excluded from most planned investigations, the list of repurposed options and the available data on these drugs and vaccines provide a baseline risk assessment and identify gaps for targeted investigation. METHODS: Clinical trials have been searched and reviewed; 23 repurposed drugs and drug combinations and nine candidate vaccines have been assessed regarding the availability of relevant data in paediatrics and pregnant women and to evaluate expected or unanticipated risk. RESULTS: Thirteen of the repurposed drugs or drug combinations are indicated for use in paediatrics in some age category albeit for indications other than COVID-19; 10 of these are indicated for use in pregnant women. Even in cases where these drugs are indicated in the populations, source data from which safety and or dosing could be extrapolated for use in COVID-19 is sparse. Vaccine trials are ongoing and generally exclude pregnant women; only in a few instances have paediatric subgroups been planned for enrolment. Data from individual case studies and RWD may suggest that subpopulations of both paediatric patients and pregnant women may be more at risk, particularly those in an increased inflammatory state. CONCLUSION: In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in paediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications.
Multi-gene prognostic assays and age-related differences in prediction of pathologic complete response to neoadjuvant chemotherapy and survival in breast cancer.

591Background: Multi-gene testing of primary breast tumors in early-stage breast cancer is used to classify the risk of developing distant metastases and predict the benefit of adjuvant chemotherap...
Determining the Ethanol Concentrations in Ethyl Alcohol-Based Hand Sanitizers with Different Expiration Dates Using Fourier-Transform Infrared Spectroscopy (FT-IR) (preprint)

Hand sanitizer has proved to be an essential public health tool in slowing the spread of the coronavirus (COVID-19). However, amid the COVID-19 pandemic, the availability of recently manufactured hand sanitizer can be limited. The product expiration date set by manufacturers is also minimally regulated. The efficacy of hand sanitizer is entirely determined by its most volatile ingredient, alcohol, which must remain at a concentration greater than 60% (v/v) to kill bacterial and viral pathogens. In our undergraduate Chem 2123W course (Introductory Quantitative Analysis Laboratory) in spring 2021, we designed and conducted an experiment to investigate the alcohol concentration of ethyl alcohol-based commercial hand sanitizers with varying expiration dates. The presence of a primary alcohol functional group in ethyl alcohol can be observed by Fourier-transform infrared spectroscopy (FT- IR). Through a series of standard additions of ethyl alcohol to the diluted hand sanitizer sample, we measured the changes in the integration of the FT-IR primary alcohol C-O stretch. The signal changes in integration were used to generate a standard addition curve using ethanol concentration and calculate the initial ethanol concentration of each sample. Our approach accounts for this matrix effect and does not rely on a compositional approximation. All the samples studied were found to exceed the minimum concentration required to effectively exhibit antimicrobial properties despite three of the four samples being expired. However, the expired samples remained close to the 60% threshold and with consideration of error analysis, the effectiveness of these hand sanitizers remains uncertain. The samples analyzed in this study varied in reported initial ethyl alcohol concentration, manufacturer, color, perfume, and other ingredients. The heterogeneity of our samples coupled with our consistent results provided insight into consumer use of expired ethyl alcohol-based hand sanitizers.
Intervention cost-effectiveness for pediatric anxiety and OCD: A systematic review and integrated database model.

Abstract Background : While multiple treatments for pediatric anxiety and obsessive compulsive disorder (OCD) are efficacious, little is known about their cost-effectiveness. In response, we sought to provide relevant information through systematic review and cost-effectiveness simulation. Methods : We evaluated the cost-effectiveness of treatment for pediatric anxiety and OCD in two ways. First, we conducted a systematic review following PRISMA guidelines. Second, we evaluated cost-effectiveness for antidepressant medication, cognitive behavioral therapy, and their combination via a simulation that integrated information from the Truven MarketScan database and the NIMH National Database for Clinical Trials Related to Mental Illness. Results : Both systematic review and simulation found antidepressant medication and cognitive behavioral therapy to be cost-effective for pediatric anxiety and OCD. Antidepressant medication was the least costly approach, and cognitive behavioral therapy provided additional cost-effectiveness, especially for OCD. Limitations : During systematic review, relatively few articles provided information about both costs and effectiveness. While there was a notable margin of error to support multiple interventions as cost-effective, limited prior research decreased precision of point estimates and comparisons between interventions. Conclusions : Both antidepressant medication and cognitive behavioral therapy were found to be cost-effective for pediatric anxiety and OCD. Results supported investment from third party payers, who serve as critical gatekeepers that can increase treatment dissemination. However, more precise information would better inform the exact amount of investment needed, especially with regard to selection decisions between active interventions. Cost-effectiveness research would benefit from systematic collection of data on treatment costs and quality of life in future clinical trials.
287 Combined COX-2 inhibition with fish oil and aspirin as adjuncts to anti-PD-1 immunotherapy in metastatic melanoma

Background Only 30–40% of metastatic melanoma patients experience objective responses to first line anti-PD-1 immune checkpoint inhibition (αPD-1 ICI). Cyclooxygenase (COX-1/2) inhibition with aspirin (ASA) and other non-steroidal anti-inflammatory drugs has been associated with prolonged time to recurrence and improved responsiveness to ICI in human melanoma,1 with inhibition of myeloid-induced immunosuppression in the tumor microenvironment (TME) a purported mechanism.2 Similarly, dietary omega-3 fatty acids metabolized by COX-2 elicit downstream effects on T-cell differentiation akin to ASA administration, abrogating murine melanoma and human breast cancer progression. Mechanisms of ICI resistance remain unclear, and adjunct therapies look to bridge the gap from current response rates to cure. Methods YUMM 1.7 melanoma cells were injected into flanks of C57-BL6/J mice. Mice were fed control diets or supplemented with omega-3 rich fish oil (FO) chow (10% weight/weight, 30%kcal/kcal), ASA in drinking water (ASA, LO – 300, MED – 600, HI - 1000 ug/mL), or the combination of these agents (COMBO, with ASA-MED) starting at day 7 post tumor implantation. Intraperitoneal αPD1 was administered every 3–4 days starting at day 12. Tumors were assessed for growth, harvested at day 32 (day 26 for ASA LO/HI), and characterized with flow cytometry. All significant results (p Results FO resulted in lesser tumor volume at day 32 in αPD-1 treated mice, while ASA-HI resulted in lesser tumor volume in mice not treated with αPD-1 but did not synergize with αPD-1. ASA-MED and COMBO groups trended towards decreased tumor size (p = 0.07 and 0.07 respectively) by day 32 in αPD-1 treated mice. FO and COMBO increased total CD3+ T-cells and monocytes (CD45+, CD19-, CD11b+, Ly6C+, Ly6G -) in the TME. FO increased PD-L1 + CD4+ T-cells, while COMBO increased total CD8+ T-cells and PD1+ CD8+ T-cells. ASA-HI increased monocytes and the proportion of PD-1+, CD8+ T-cells in the TME. Conclusions Myeloid-induced suppression of T-cell function in tumors may contribute to immune checkpoint inhibition resistance. In the present study, both fish oil and aspirin altered melanoma tumor growth, with only fish oil synergizing with anti-PD-1 at the doses assessed. Both fish oil and aspirin augmented monocyte populations in the tumor microenvironment, with differential effects on T-cell populations. The partially synergistic mechanism between substrate-limited (FO) and pharmacologic (ASA) inhibition of cyclooxygenase-2 may provide a cost-effective avenue to combat immune escape in melanoma patients treated with anti-PD-1 immune checkpoint inhibition, requiring further investigation in humans. References Wang SJ, et al. Effect of cyclo-oxygenase inhibitor use during checkpoint blockade immunotherapy in patients with metastatic melanoma and non-small cell lung cancer. J Immunother Cancer 2020;8(2). Zelenay S, et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell 2015;162(6):1257–70.
Comparative Historical Dialectology: Italo-Romance clues to Ibero-Romance sound change

This brief monograph explores the historical motivations for two sets of phonological changes in some varieties of Romance: restructured voicing of intervocalic /p t k/, and palatalization of initial /l/ and /n/. These developments have been treated repeatedly over the decades, yet neither has enjoyed a satisfactory solution. This book attempts to demonstrate that both outcomes are ultimately attributable to the loss of early pan-Romance consonant gemination. This study is of interest not only to the language-specific field of historical Romance linguistics, but also to general historical linguistics. The central problems examined here constitute classic cases of questions that cannot be answered by confining analysis solely to the individual languages under investigation. The passage of time, the indirect nature of fragmentary and accidental documentation, and the nature of the changes themselves conspire to deny access to the most essential facts. However, comparison of closely cognate languages now undergoing change supplies a perspective for discerning conditions that may ultimately lead to states achieved in the distant past by the languages under investigation.
Intermediate effects of the ileocaecal urinary reservoir (Charleston pouch 1) on serum vitamin B12 concentrations: can vitamin B12 deficiency be prevented?

OBJECTIVE To assess the long-term effects of a form of ileocolic urinary reservoir (Charleston Pouch 1) on vitamin B12 serum levels, as vitamin B12 deficiency may be an important long-term risk after urinary diversion by this method. PATIENTS AND METHODS The study included 60 patients (mean age 52 years, range 27–77; 33 men and 27 women) who had a follow-up of ≥ 36 months (36–132 months) after the construction of an ileocaecal urinary reservoir. Vitamin B12 serum levels were determined at the time of diversion and again when the patients were evaluated every 6 months. RESULTS Fifty-eight patients had a normal serum vitamin B12 concentration before surgery (two patients were excluded from the study because they had low levels); the mean level was 464 pg/mL (normal range 247–1000). At 6 and 12 months, the mean vitamin B12 levels were 367.5 and 468.5 pg/mL; at 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 11 years, the mean levels were 305, 495.5, 436.5, 379.5, 423.5, 393, 529.5, 631, 333.5 and 340 pg/mL, respectively. CONCLUSION Ileocaecal urinary reservoirs have no adverse effects on serum vitamin B12 levels for up to 10 years after surgery. Patients with vitamin B12 deficiency must be identified and given adequate parenteral doses for life. Because body stores of vitamin B12 may not be depleted for many years, problems with B12 may be masked for a long time. We recommend that vitamin B12 levels be obtained annually, that a modest supplement twice yearly (by injection) may be beneficial and that serum vitamin B12 must be sampled before giving vitamin B12 injections, to avoid false results.
Implementing a chinese character browser using a topography-preserving map

The Chinese Character Browser is a user interface designed for the search and exploration of a database of Chinese characters, Chinese pronunciations (pinyin), and English definitions. The browser uses a technology based upon Kohonen’s self-organizing map to map the 10-dimensional feature vector describing each Chinese character onto a discrete two-dimensional grid, which forms the foundation for the browser. The Chinese Character Browser was designed to demonstrate the importance not only of topology preservation, but topography preservation in such mappings. In brief, to the extent that a mapping is topography-preserving, the structure of the output map grid can reflect the structure of the original data at several levels of granularity simultaneously, allowing the assumption of a hierarchical organization in the output map that corresponds to the structure of the input data set. This can significantly speed up search as well as make the mapping more useful for a variety of applications.
Memory and Vision: Arts, Cultures, and Lives of Plains Indian Peoples

Reviewed Medium: book Year: 2008 Pages: 320 Publisher: University of Washington Press ISBN: 978-0-295-98579-8 (hard cover). Prices: $75.00 USD(hard cover).
Configuration management — keeping it all together

Any project, programme or organisation, working in any environment with released information, managing its change, maintaining traceability, and ensuring results always meet expectations, needs configuration management. Software projects introduce additional complexities — multiple developers working on the same item at the same time, the need for compatibility with other products and systems, targeting releases for multiple platforms, and supporting multiple versions (for example development and released versions). This paper describes the configuration management processes that support and manage products through their entire life cycle as they change and evolve.
Fibrocytes in Health and Disease

Fibrocytes, a group of bone marrow-derived mesenchymal progenitor cells, were first described in 1994 as fibroblast-like, peripheral blood cells that migrate to regions of tissue injury. These cells are unique in their expression of extracellular matrix proteins concomitantly with markers of hematopoietic and monocyte lineage. The involvement of fibrocytes and the specific role they play in the process of wound repair has been a focus of study since their initial description. Fibrocytes contribute to the healing repertoire via several mechanisms; they produce a combination of cytokines, chemokines, and growth factors to create a milieu favorable for repair to occur; they serve as antigen presenting cells (APCs); they contribute to wound closure; and, they promote angiogenesis. Furthermore, regulatory pathways involving serum amyloid P, leukocyte-specific protein 1, and adenosine A2A receptors have emphasized the significant role that fibrocytes have in wound healing and fibrosis. The therapeutic targeting of fibrocytes holds promise for the augmentation of wound repair and the treatment of different fibrosing disorders.
Origins of the Human Brain

Origins of the Human Brain. J. P. Changeux and J. Chavaillon. eds. Oxford, England: Oxford University Press, 1995. 321 pp.
Sexuality, Witchcraft, and Honor in Colonial Spanish America

Scholarship on colonial Spanish American sexuality has focused on the literary discourse of honor, institutional regulation, and imperial control. Historians use sources such as marriage documentation and cases that came before criminal courts or inquisition tribunals, to make conclusions relating sexuality to conquest and colonial race and gender hierarchies. Only a few scholars have explored the Spanish American experience of sexual desire and pleasure.
Critical experiment tests of bowing and expansion reactivity calculations for liquid-metal-cooled fast reactors

Experiments done in several critical assemblies of the liquid-metal-cooled fast reactor type simulated core axial expansion, core radial expansion and bowing, coolant expansion, and control driveli...
Person-place-time analysis of vehicle fatalities caused by flash floods in Texas

A significant number of crashes on roads are caused by adverse weather conditions. Among the most serious consequences of rainfall and flooding in regard to road safety are the motor vehicle-related flash flood fatalities. These fatalities are of particular concern in Texas. Information on motor vehicle fatalities caused by flash floods was extracted from the National Climatic Data Center Storm Data reports. Review of reports on flash flood fatalities in general, where the death circumstances are provided, reveals that most fatalities are motor vehicle-related (80%). Moreover, data from the reports indicate that from 1959 to 2009 the number of motor vehicle-related flash flood fatalities in Texas exceeds by far the total number of flood fatalities in any other state. Demographic analysis of the flash flood fatalities indicates that, in Texas, all ages are at risk and that males are much more affected than females. Spatial analysis indicates that the highest numbers of fatalities occur in counties having m...
Yttria-stabilized hafnia: Thermochemistry of formation and hydration of nanoparticles

The surface enthalpy of yttria-stabilized hafnia (YSH) (YxHf1 − xO2 − x/2) with different compositions was directly measured by a combination of high-temperature oxide-melt solution calorimetry and water adsorption calorimetry. The surface enthalpies for hydrated surfaces are 0.27 ± 0.06 J/m2 for x = 0.1, 0.77 ± 0.09 J/m2 for x = 0.17, and 1.30 ± 0.09 J/m2 for x = 0.24; and those for anhydrous surfaces are 0.51 ± 0.06, 1.08 ± 0.13, and 1.76 ± 0.09 J/m2 respectively. The enthalpies of both hydrated and anhydrous surfaces increase approximately linearly (R2 > 0.93) with increasing yttrium concentration. The surface enthalpies of Y0.1Hf0.9O1.95 were used to approximate those for pure anhydrous cubic hafnia. Combining the data relating to surface energies for monoclinic hafnia from our previous work and estimated data for tetragonal hafnia, a tentative stability map of HfO2 polymorphs as a function of surface area (SA) was constructed.
Enhanced pressurized liquid extraction technique capable of analyzing polychlorodibenzo-p-dioxins, polychlorodibenzofurans, and polychlorobiphenyls in fish tissue

Abstract A high-throughput enhanced pressurized liquid extraction technique was developed by incorporating pressurized liquid extraction and multiple cleanup techniques. USEPA methods of polychlorodibenzo- p -dioxins, polychlorodibenzofurans (PCDD/Fs) and dioxin-like polychlorobiphenyls (dl-PCBs) analysis in fish tissue include independent silica gel, florisil, alumina, and carbopack/celite column cleanup techniques following extraction. Under the improved method, fish composites (∼10 g) were extracted and cleaned simultaneously using alumina (∼10 g), florisil (∼10 g), silica gel (∼5 g), celite (∼5 g), and carbopack (∼0.5 g). Clean extracts were concentrated and then analyzed by high resolution gas chromatography coupled with electron capture negative ionization mass spectrometry. Carbopack/celite within the extraction cell provided the analytical separation of dl-PCBs from PCDD/Fs, reducing potential molecular interferences. The average recoveries ( n = 3) of dl-PCBs in dichloromethane:hexane (1:1, v/v) extracts were 93 ± 2.4% and PCDD/Fs in toluene extracts were 85 ± 3.0%. The developed method was applied to measure the PCDD/Fs and dl-PCBs in catfish from San Jacinto River Waste Pits, a Superfund site in Houston, TX. The dl-PCBs were measured at 5.0–17,000 pg g −1 ww. Sample preparation time and solvents were reduced as much as 95% and 65%, respectively, as compared to USEPA method 1613.
Small modular reactors: the future of nuclear energy?

Small Modular Reactors (SMRs) are being explored by the NRC and DOE as a means of producing nuclear energy on a smaller scale. Because of their modularity, they are presumed to be both less costly and more efficient to produce. This paper describes the historical context of SMRs, as well as potential issues relating to the social context of SMRs if they are deployed in society on different scales, from the local to the national and international. Understanding SMRs as sociotechnical systems allows for different conception of the role of SMRs as a technology that could potentially reorganize society, which needs to be accounted for prior to deployment. The concept of the sociotechnical imaginary also provides another way of considering how SMRs both shape and are shaped by national imperatives for energy production and markets.
Phase transitions in highly-correlated f-electron systems with fluctuating valence

A formalism is presented for treating electrons in highly-correlated spin-orbit coupled multiplet levels in f-shells, which are also hybridized with valence or conduction states. This is achieved by introducing operators which cause transitions between the configurations, but project out all other configurations. The Zwanzig-Mori projection operator technique is exploited to derive results for the electron Green's functions, which are then solved self-consistently. The lowest order self-consistent solutions bear a certain resemblance to unrestricted Hartree-Fock theory. Higher order terms exhibit Kondo-like singularities under certain conditions. It is shown that several phases, both configurational and magnetic, are possible depending on the relative values of the conduction electron bandwidth, the hybridization energy and the values of the Coulomb and exchange integrals.
Can a heavy Higgs field become light at low energies

Abstract A perturbative evolution of the mass parameter of the Higgs fields is studied in a supersymmetric gauge theory with N c colors and 2 N f chiral superfields which interact with the Higgs fields via the Yukawa-type interactions. In general this mass parameter decreases at most one order of magnitude from energy scales Λ MC ∼10 15 GeV to Λ HC ∼10 3 GeV. However, in a specific case when the beta function for the gauge coupling is small and the gauge coupling is relatively large, this mass parameter can decrease by many (3–5) orders of magnitude. The relevance of such a scenario is commented upon for the tree level fine-tuning problem in the softly broken supersymmetric grand unified theories. In another context this may be relevant for the study of dynamically generated fermionic masses in a theory based on underlying preonic dynamics.