cssi/SciSciGPT-SciSciNet huggingface dataset:
The mitochondrial outer membrane protein mitoNEET is a redox enzyme catalyzing electron transfer from FMNH2 to oxygen or ubiquinone

Increasing evidence suggests that mitoNEET, a target of the type II diabetes drug pioglitazone, is a key regulator of energy metabolism in mitochondria. MitoNEET is anchored to the mitochondrial outer membrane via its N-terminal α helix domain and hosts a redox-active [2Fe-2S] cluster in its C-terminal cytosolic region. The mechanism by which mitoNEET regulates energy metabolism in mitochondria, however, is not fully understood. Previous studies have shown that mitoNEET specifically interacts with the reduced flavin mononucleotide (FMNH2) and that FMNH2 can quickly reduce the mitoNEET [2Fe-2S] clusters. Here we report that the reduced mitoNEET [2Fe-2S] clusters can be readily oxidized by oxygen. In the presence of FMN, NADH, and flavin reductase, which reduces FMN to FMNH2 using NADH as the electron donor, mitoNEET mediates oxidation of NADH with a concomitant reduction of oxygen. Ubiquinone-2, an analog of ubiquinone-10, can also oxidize the reduced mitoNEET [2Fe-2S] clusters under anaerobic or aerobic conditions. Compared with oxygen, ubiquinone-2 is more efficient in oxidizing the mitoNEET [2Fe-2S] clusters, suggesting that ubiquinone could be an intrinsic electron acceptor of the reduced mitoNEET [2Fe-2S] clusters in mitochondria. Pioglitazone or its analog NL-1 appears to inhibit the electron transfer activity of mitoNEET by forming a unique complex with mitoNEET and FMNH2. The results suggest that mitoNEET is a redox enzyme that may promote oxidation of NADH to facilitate enhanced glycolysis in the cytosol and that pioglitazone may regulate energy metabolism in mitochondria by inhibiting the electron transfer activity of mitoNEET.
Decision support for family history intake to determine eligibility for BRCA testing among multiethnic women.

1586Background: The U.S. Preventive Services Task Force (USPSTF) recommends that women who meet family history criteria for hereditary breast and ovarian cancer (HBOC) be referred for genetic couns...
Normal platelet function.

Platelets play an important role in the vessel. Following their formation from megakaryocytes, platelets exist in circulation for 5–7 days and primarily function as regulators of hemostasis and thrombosis. Following vascular insult or injury, platelets become activated in the blood resulting in adhesion to the exposed extracellular matrix underlying the endothelium, formation of a platelet plug, and finally formation and consolidation of a thrombus consisting of both a core and shell. In pathological conditions, platelets are essential for formation of occlusive thrombus formation and as a result are the primary target for prevention of arterial thrombus formation. In addition to regulation of hemostasis in the vessel, platelets have also been shown to play an important role in innate immunity as well as regulation of tumor growth and extravasations in the vessel. These primary functions of the platelet represent its normal function and versatility in circulation.
Basilic Vein Transposition

Planning hemodialysis access, although complicated, is ultimately based on the presence of suitable caliber vein to be used in fistula creation. Brachiobasilic arteriovenous fistula, or basilic vein transposition (BVT), is frequently used in hemodialysis access with the benefit that the basilic vein is typically of a larger size than its companion, the cephalic vein. Additionally, the upper arm basilic vein is protected from repeated venipuncture given its deep location. This fistula also has less infectious complications, with better primary patency compared to prosthetic grafts. BVT can be performed as a single or a two-staged procedure without significant change in long-term patency rates.
Multitarget Drugs: Strategies and Challenges for Medicinal Chemists

Currently, drug discovery is largely based upon a “one molecule - one target - one disease” philosophy and many successful drugs, that are selective for a single target (“magic bullets”), have emerged from this strategy. There is however an increasing interest in and awareness of multi-target drug discovery (MTDD) within the medicinal chemistry community as a means of providing a superior therapeutic effect and side effect profile compared to the modulation of a single target. The inherent redundancy and robustness that exists within biological networks and pathways means that modulating single proteins may not be sufficient to produce the desired efficacy, whilst at the same time minimising adverse side effects. It has been demonstrated that a balanced modulation of multiple targets in parallel can be beneficial for treating diseases with complex etiologies, such as using multi-kinase inhibitors for treating cancer and multi-target monoaminergic ligands for treating CNS diseases. Although many currently marketed drugs act via multiple targets, the discovery of their polypharmacological mechanism of action was usually serendipitous and retrospective. The premeditated design of compounds with a predefined multi-target profile (i.e. “designed” multiple ligands or DMLs) is a relatively recent development. Designing multiple ligands presents medicinal chemists with many challenges and an early assessment of the feasibility of the approach for a particular target combination is essential. Historically, there have been two quite different methods of generating lead compounds, screening approaches that rely largely upon serendipity and knowledge-based approaches that exploit information either from the general literature or proprietary information from within an organization. During lead optimisation, a key objective is to achieve a balanced activity for each target of interest, whilst obtaining wider selectivity and a suitable oral pharmacokinetic profile.
Severe unicuspid aortic valve stenosis: VACTERL association

A 24-year-old man with a known history of horseshoe kidney leading to end-stage renal disease, scoliosis and small ventricular septal defect consistent with VACTERL association, who presented with worsening dyspnoea on exertion. Transthoracic echocardiogram (TTE) showed a unicuspid aortic valve (UAV) with severe aortic stenosis (AS) (valve area of 0.6 cm2 and mean gradient of 44 mm Hg). TTE also showed moderate aortic insufficiency and severely reduced left ventricular systolic function with estimated ejection fraction of 20%. Transoesophageal echocardiography (TEE) confirmed a UAV with single commissure located anteriorly (figure 1A–D; online supplementary video 1 and supplementary video 2) and severe AS (figure …
Placentophagy among women planning community births in the United States: Frequency, rationale, and associated neonatal outcomes

Background Limited systematic research on maternal placentophagy is available to maternity care providers whose clients/patients may be considering this increasingly popular practice. Our purpose was to characterize the practice of placentophagy and its attendant neonatal outcomes among a large sample of women in the United States. Methods We used a medical records-based data set (n = 23 242) containing pregnancy, birth, and postpartum information for women who planned community births. We used logistic regression to determine demographic and clinical predictors of placentophagy. Finally, we compared neonatal outcomes (hospitalization, neonatal intensive unit admission, or neonatal death in the first 6 weeks) between placenta consumers and nonconsumers, and participants who consumed placenta raw vs cooked. Results Nearly one-third (30.8%) of women consumed their placenta. Consumers were more likely to have reported pregravid anxiety or depression compared with nonconsumers. Most (85.3%) placentophagic mothers consumed their placentas in encapsulated form, and nearly half (48.4%) consumed capsules containing dehydrated, uncooked placenta. Placentophagy was not associated with any adverse neonatal outcomes. Women with home births were more likely to engage in placentophagy than women with birth center births. The most common reason given (73.1%) for engaging in placentophagy was to prevent postpartum depression. [Corrections added on 16 May 2018, after first online publication: The percentage values in the Results sections were updated.] CONCLUSIONS: The majority of women consumed their placentas in uncooked/encapsulated form and hoping to avoid postpartum depression, although no evidence currently exists to support this strategy. Preparation technique (cooked vs uncooked) did not influence adverse neonatal outcomes. Maternity care providers should discuss the range of options available to prevent/treat postpartum depression, in addition to current evidence with respect to the safety of placentophagy.
CHRONIC PROGRESSIVE MENINGOENCEPHALITIS AFTER WEST NILE INFECTION: DIAGNOSTIC CHALLENGES IN PROLONGED IMMUNOSUPPRESSION FROM RITUXIMAB (P3.303)

Objective: To report a case of progressive meningoencephalitis after West Nile virus infection in a patient with hypogammaglobulinemia and absent CD19, CD20 from remote use of rituximab. Background: West Nile virus is an arthropod-borne virus that causes meningoencephalitis. A few cases with chronic symptoms were found to have persistent infection in the urine. Rituximab is a monoclonal antibody against B-cell and CD20. However, prolonged suppression for several years is rare and can interfere with serologic testing of encephalitis. Design/Methods: Case analysis and literature review Results: We report a 26-year-old woman with history of juvenile rheumatoid arthritis and immune thrombocytopenic purpura who received rituximab 6 years previously and presented with clinical encephalitis and positive West Nile PCR in plasma. Her symptoms initially improved significantly but two years later she developed progressive fatigue, diplopia, gait disturbance, pseudobulbar affect, and parkinsonism. MRI brain showed worsening atrophy and white matter hyperintensities in temporal and bilateral frontal lobes. Extensive investigations for encephalitis including blood and CSF tests for infection, autoimmune, paraneoplastic, genetic tests for dementia and leukodystrophy failed to identify a cause. She has persistently low IgG and IgM levels, absent CD19, CD20 and mature B-cell. No other causes were identified except for prior rituximab use. West Nile virus serologic tests and PCR in blood, CSF and urine became negative. Brain biopsy demonstrated active meningoencephalitis. Muscle biopsy showed denervation atrophy. Electrophysiologic tests suggested disorder of anterior horn cells. Her condition did not improve with 5-day-course of methylprednisolone and IVIG. The longer courses of treatment with IVIG are being considered. Conclusions: Prolonged suppression of CD20 and B-cell can occur for several years after treatment with rituximab. The persistent hypogammaglobulinemia may interfere with serologic tests of meningoencephalitis. Diagnosis of chronic progressive meningoencephalitis can be challenging and requires systematic approaches, especially in immunocompromised individuals. Disclosure: Dr. Ruthirago has nothing to disclose. Dr. Julayanont has nothing to disclose. Dr. Alderazi has nothing to disclose.
Modern Art Theories

The ancient doctrine that artworks are imitative or capture likenesses has been widely denied, and by aestheticians who are thought to hold sharply contrasting views about the nature of art. Two of these views are of particular interest to me. The first is formalism, or one of the views that can be called formalism, which maintains that artworks qua artworks are void of all representational content and consist in mere patterns of line and color that please us on a direct inspection. The second (and currently much more discussed) view is that artworks differ from mere physical objects by virtue of an invisible art-making property, namely, an identification that an artist makes whereby a physical object acquires a representational content. For the sake of terminological symmetry, and to distinguish it from other positions, I shall call this second view invisibilism-which should not be taken to suggest that artworks themselves are invisible, but only that the art-making property cannot be discerned in the visible physical object. If we think about the overall history of art, formalism and invisibilism look counterintuitive. But these views were motivated by developments in modern art, and these views can look more promising against that background. They are modern art theories, to use a term that is calculatedly ambiguous between theories of modem art and modern theories of art. I want to sort this ambiguity out, to understand the philosophical impact that modern art should have on our thinking, and to argue that insofar as the case against the ancient doctrine relies on historical premises the case is far from conclusive. We shall also see that formalism and invisibilism have more in common than we might have supposed. Depending on one's perspective, their common ground can be good news for one theory, bad news for the other, or-as I think most likely-bad news for both.
Regulation of gene expression by indoleacetic acid in pea epicotyl tissue

Etiolated pea stem tissue treated with 20μM indole acetic acid (IAA) for 6 h shows enhanced translational activity of six mRNAs relative to untreated controls. Differential plaque filter hybridization of cDNA libraries with cDNA probes from size fractionated mRNAs obtained from IAA treated and untreated tissue led to the isolation of recombinant phages containing DNA inserts complementary to three auxin regulated mRNAs. Clone pIAA6 corresponds to a mRNA encoding the previously identified translational product polypeptide #6 (MW 22kd). Clone pIAA4/5 appears to hybridize to two mRNAs encoding translational products #4 and #5 (MW of 23 and 25kd, respectiveIy). The induction of these mRNAs is rapid, occuring within l0 min of IAA exposure, is highly specific to auxins, and does not require concurrent protein synthesis. The data indicate that auxin augments the amount of specific mRNAs rather than alter the translatability of preexisting RNAs. The response is the fastest known for any plant growth regulator and qualifies as a primary hormonal response to auxin.
Phosphine-Ruthenium(II)-Aquo Redox Chemistry: The Aerobic Catalytic Oxidation of Cyclohexene

Recently, our laboratory synthesized ruthenium(IV)-oxo complexes containing tertiary phosphine ligands, which act as stoichiometric oxidation reagents toward a variety of organic and inorganic substrates (alcohols, olefins, aldehydes, phosphines, sulfides, and sulfoxides). Currently, we are investigating the aerobic oxidation of cyclohexene, phosphineruthenium( II)-aquo complexes. The activation of molecular oxygen occurs at room pressure and temperature, without the need for a coreductant. The active oxidant in the catalytic cycle appears to be the phosphineruthenium( IV)-oxo species, for the product distribution from the catalytic oxidation of cyclohexene is identical to the product distribution from the stoichiometric oxidation of cyclohexene by a phosphine-ruthenium(IV)-oxo complex. The rate of product formation over a 24 hour period is constant, with the catalytic reaction sampled after 1, 2, 4, 8, and 24 hours. The initial catalyst was isolated intact at the end of the reaction. The oxidation of cyclohexene produces 2-cyclohexene-l-one, 2-cyclohexene-l-ol, and cyclohexene oxide in a product ratio of 16:8:1. After twenty-four hours, the oxidation of a 2.2 M solution of cyclohexene using a 5.0 x 10-4 M solution of catalyst yields a turnover number of 1560, where the production of 2-cyclohexen-l-one from cyclohexene requires two turnovers of catalyst per molecule. From experimental observations, a catalytic cycle can be suggested for the aerobic oxidation of cyclohexene. Initially, a five-coordinate phosphine-ruthenium(II) complex is generated, by the the loss of an aquo ligand. The combination of a molecule of dioxygen with two of these five-coordinate complexes forms a dinuclear, oxygen-bridged intermediate. Homolytic cleavage of the 0-0 bond yields two phosphineruthenium(IV)-oxo molecules, the proposed active oxidant. The phosphineruthenium(IV)-oxo complex oxidizes the target organic substrate, forming a phosphine-ruthenium(II)-oxidized substrate complex. Dissociation of the oxidized organic substrate by this complex yields the five-coordinate phosphine-ruthenium(II) complex, which continues in the catalytic cycle.
Experimental Studies of Delta-InN Incorporation in InGaN Quantum Well for Long Wavelength Emission

In this study we investigate the incorporation of a delta-InN layer into InGaN quantum wells. Our experimental results indicate that the insertion of this delta-InN layer maintains the crystal quality of the structure, while red-shifting the emitted wavelength towards the red wavelengths.
Conducting a Low-Waste Iodine Clock Experiment on Filter Paper to Discern the Rate Law.

Herein we present a modified iodine clock experiment which replaces starch with cellulose paper. This provides the reaction with a white solid surface in which color change can be clearly observed and reduces reagent amounts required to 540 μL per group. After data acquisition, students are required to calculate reaction orders and the reaction constant k, culminating in their ability to discern the rate equation for this reaction. This experiment is ideal for teaching kinetics in high school and undergraduate settings, particularly if liquid waste disposal is not readily available or if high importance is placed upon minimizing their environmental impact.
Financial development and income inequality in China – A spatial data analysis

Abstract We use provincial data of 1998–2014 to evaluate the impact of financial development on income inequality in China through spatial dependence modeling techniques. An exploratory spatial analysis for all the municipalities and provinces in China for the years of 1998, 2003, 2008 and 2013 is implemented to evaluate spatial dependence of provincial income inequalities in China. In total, 29 administrative units are used to fit an income inequality spatial model by first certifying the necessity of using a spatial model by applying Moran tests; and later the Lagrange Multiplier test is used to find a suitable spatial model. Finally, spatial panel model is estimated. Our results indicate that financial development decreases income inequality in China. Furthermore, significant spatial autocorrelation estimates appeared in the disturbance term, indicating significant non-measurable reform or policy impacts.
Fluid Mechanics and Heat Transfer in Transitional Boundary Layers

Experiments have been performed to investigate the effects of elevated free-stream turbulence and streamwise acceleration on flow and thermal structures in transitional boundary layers. The free-stream turbulence ranges from 0.5 to 6.4% and the streamwise acceleration ranges from K = 0 to 0.8 x 10(exp -6). The onset of transition, transition length and the turbulent spot formation rate are determined. The statistical results and conditionally sampled results of th streamwise and cross-stream velocity fluctuations, temperature fluctuations, Reynolds stress and Reynolds heat fluxes are presented.
Using the Technology Acceptance Model to Develop StartSmart: mHealth for Screening, Brief Intervention, and Referral for Risk and Protective Factors in Pregnancy.

Introduction Technology decision support with tailored patient education has the potential to improve maternal and child health outcomes. The purpose of this study was to develop StartSmart, a mobile health (mHealth) intervention to support evidence-based prenatal screening, brief intervention, and referral to treatment for risk and protective factors in pregnancy. Methods StartSmart was developed using Davis' Technology Acceptance Model with end users engaged in the technology development from initial concept to clinical testing. The prototype was developed based upon the current guidelines, focus group findings, and consultation with patient and provider experts. The prototype was then alpha tested by clinicians and patients. Clinicians were asked to give feedback on the screening questions, treatment, brief motivational interviewing, referral algorithms, and the individualized education materials. Clinicians were asked about the feasibility of using the materials to provide brief intervention or referral to treatment. Patients were interviewed using the think aloud technique, a cognitive engineering method used to inform the design of mHealth interventions. Interview questions were guided by the Screening, Brief Intervention, Referral to Treatment theory and attention to usefulness and usability. Results Expert clinicians provided guidance on the screening instruments, resources, and practice guidelines. Clinicians suggested identifying specific prenatal visits for the screening (first prenatal visit, 28-week visit, and 36-week visit). Patients reported that the tablet-based screening was useful to promote adherence to guidelines and provided suggestions for improvement including more information on the diabetic diet and more resources for diabetes. During alpha testing, participants commented on navigability and usability. Patients reported favorable responses about question wording and ease of use. Discussion Clinicians reported the use of mHealth to screen and counsel pregnant patients on risk and protective factors facilitated their ability to provide comprehensive care.
Health center implementation of telemedicine for opioid use disorders: A qualitative assessment of adopters and nonadopters.

Abstract Objective Although use of telemedicine for the treatment of opioid use disorders (Tele-OUD) is growing, there is limited research on how it is actually being deployed in treatment. We explored how health centers across the U.S. are using tele-OUD in treatment as well as reasons for nonadoption. Methods We used the 2018 SAMHSA Behavioral Health Treatment Services Locator database and literature review to create a sample of community mental health centers and federally qualified health centers with telemental health services. From this list of health centers, we ued maximum diversity sampling to identify and recruit health center leaders to participate in semistructured interviews. We used inductive and deductive approaches to develop site summaries. Results Twenty-two health centers from 14 different states participated. Of these, 8 offered tele-OUD. Among centers with tele-OUD, medication management was the most common service provided via video. Typically, health centers offered telemedicine visits after an initial, in-person visit with a waivered (prescribing) provider. Some programs only offered counseling via telemedicine. Leading barriers to treatment that tele-OUD program representatives mentioned included regulations on the prescribing of controlled substances, including buprenorphine, and difficulties in sending lab results to distant (prescribing) providers. Nonadopters reported not offering tele-OUD due to regulations in controlled substance prescribing, complexities and regulatory barriers to offering group visits, and the belief that in-person OUD services were meeting patient need. Conclusions Tele-OUD is being deployed in a variety of ways. Describing current delivery models can inform strategies to promote and implement tele-OUD to combat the opioid epidemic.
The Disaggregated Repeated Measures Design: A Novel Approach to Assess Sexual Risk Behaviors

Although numerous studies have examined sexual and substance use behaviors that put people at risk for sexually transmitted infections including HIV, most focus on an overall measure of aggregate risk or a few simple and particular subtypes of sexual acts assessed in separate analyses. In this article, we introduce a more sensitive approach to assess how the relative characteristics of sex acts may determine the level of risk in which an individual chooses to engage. Project AWARE, a randomized clinical trial conducted among 5012 patients in nine STD clinics across the U.S., is used to illustrate the approach. Our study was guided by two aims: (1) describe a new approach to examine the count of sexual acts using a disaggregated repeated measures design and (2) show how this new approach can be used to evaluate interactions among different categories of sexual risk behaviors and other predictors of interest (such as gender/sexual orientation). Profiles of different subtypes of sexual acts in the past 6 months were assessed. Potential interactions of the characteristics associated with each subtype which resulted in up to 48 distinct subtypes of sexual risk behaviors—sex with a primary/non-primary partner; partner’s HIV status; vaginal/anal sex; condom use; and substance use before or during sex act—can be examined. Specifically, we chose condom use and primary and non-primary status of partner as an application in this paper to illustrate our method. There were significantly more condomless sex acts (M = 23, SE = 0.9) and sex acts with primary partners (M = 27.1, SE = 0.9) compared to sex acts with condoms (M = 10.9, SE = 0.4, IRR = 2.10, 95% CI 1.91–2.32, p < .001) and sex acts with non-primary partner (M = 10.9, SE = 0.5, IRR = 2.5, 95% CI 2.33–2.78, p < .001). In addition, there were significant differences for the count of sexual risk behaviors among women who have sex with men (WSM), men who have sex with women (MSW) and men who have sex with men (MSM) for sex acts with and without condom use, primary and non-primary partner, and their interaction (ps = .03, < .0001, and .001, respectively). This approach extends our understanding of how people make choices among sexual behaviors and may be useful in future research on disaggregated characteristics of sex acts.
Adolescent Family Experiences Predict Young Adult Educational Attainment: A Data-Based Cross-Study Synthesis With Machine Learning

Grounded in theory and research on the role of adolescent family experiences in young adult educational attainment, this study took the novel step of synthesizing results from prior studies and using a machine learning (ML) approach to address three questions: (1) By incorporating adolescent family experience factors examined across prior studies in a single analysis, how accurately can we predict young adult educational attainment? (2) Which family experience factors are the best predictors of young adult educational attainment? (3) What complex patterns among family experience predictors merit further examination? Based on a review of 101 publications that used National Longitudinal Study of Adolescent Health data to investigate links between adolescent family experiences and young adult attainment, we identified 53 family experience independent variables. We used an ML-based approach to train and test models with these 53 Wave I family variables (adolescent in Grade 7–12) as predictors of both college enrollment (N = 4598) and graduation (N = 4180) at Wave IV (young adult mean age = 28.88, SD = 1.76). Our models (1) obtained prediction accuracies of 73.43% and 72.33% for college enrollment, and 79.10% and 79.07% for college graduation, (2) identified the best predictors of college enrollment and graduation, including family socioeconomic characteristics and parent educational expectations, and (3) highlight nonlinear patterns for further examination. This study advanced understanding of how adolescent family experiences may influence educational attainment and provided a paradigm for developmental research to synthesize existing findings into novel discoveries with large-scale datasets.
Efficacy of cyanoacrylate tissue adhesive in the management of corneal thinning and perforation due to microbial keratitis.

Abstract Purpose Report the efficacy of cyanoacrylate tissue adhesive (CTA) application in the management of corneal thinning and perforations associated with microbial keratitis. Methods A retrospective review of consecutive patients who underwent CTA application for corneal thinning and perforation secondary to microbiologically proven infectious keratitis between 2001 and 2018 at a single center. We defined successful CTA application as an intact globe without tectonic surgical intervention. Results The cohort included 67 patients, and 37 presented with corneal perforation while 30 had corneal thinning. The perforation/thinning was central/paracentral in 43 eyes and peripheral in 23 eyes. The underlying infectious etiologies were monomicrobial in 42 cases (35 bacterial, 3 fungal, 2 viral, and 2 acanthamoeba cases) and polymicrobial in 25 cases (22 polybacterial cases and 3 cases with a combination of Gram positive bacteria and fungus). The median duration of glue retention was 29 days. The CTA success rate was 73%, 64%, and 44% at 10, 30, and 180 days, respectively. CTA application appears more successful in monomicrobial (vs. polymicrobial) and Gram positive bacterial (vs. Gram negative) keratitis but the differences are statistically non-significant. The location of perforation/thinning and the use of topical corticosteroid were not associated with CTA failure. Conclusion CTA was moderately effective in restoring globe integrity in severe corneal thinning and perforation secondary to microbial keratitis in the short term. However the majority of patients require tectonic surgical intervention within 6 months. CTA application success is not significantly associated with the location of thinning/perforation or the use of topical corticosteroid.
Abstract 1761: Examination of therapeutic potential of epigenetic modulation by dual HDAC-LSD1 inhibition in murine models of triple negative breast cancer (TNBC)

This study examines the effects of the epigenetic modulator 4SC-202, a dual histone deacetylase (HDAC) /lysine-specific histone demethylase 1A (LSD1) small molecule inhibitor, on tumor growth and metastasis in a mouse model of breast cancer. 4SC-202 differs from clinically available HDAC inhibitors such as Vorinostat (SAHA) by specifically targeting class I HDACs including HDAC1, HDAC2, and HDAC3 and the histone demethylase LSD1. The hypothesis to be examined is that epigenetic modulation via dual inhibition of HDAC1 and LSD1 improves disease control in breast cancer. In vitro data indicates that 4SC-202 is significantly cytotoxic and cytostatic to the highly metastatic murine Triple Negative Breast Cancer (TNBC) murine model 4T1 and the human TNBC cell line MDA-MB-231 and reduces cancer cell migration. In vivo studies conducted in the syngeneic 4T1 model which closely mimics human TNBC in terms of sites of metastasis, show increased necrosis in 4T1 tumors, reduced tumor burden in vivo as compared to Vorinostat treatment, and significantly reduced metastasis. Furthermore, multiple studies in different cell types indicate that the mechanism of action of 4SC-202 may involve effects on cancer stem cells, which are able to self-renew and form metastatic lesions. It has been shown that a marker of cancer stem cells (CSC9s) in breast cancer is high aldehyde dehydrogenase (ALDH) activity and that ALDH high cells mediate metastasis. In the 4T1 syngeneic mouse model of breast cancer, inhibition of ALDH activity suppresses stem-like cell properties. Preliminary data suggests 4SC-202 substantially reduces the ALDH high 4T1 cancer stem population. Transcriptome bulk RNA -sequencing analysis from 4T1 tumors reveal changes in metastatic related pathways in 4SC-202 treated tumors, including significant changes to the expression levels of genes implicated in focal adhesion and ECM-receptor interaction pathways. Furthermore, 4SC-202 appears to alter expression of cytokines which serve as chemokines, potentially leading to increased expression of tumor infiltrating lymphocytes. In summary, treatment of a highly metastatic murine model of TNBC with 4SC-202 significantly reduces metastasis, and warrants further preclinical studies in conjunction with standard of care chemotherapy treatment. Citation Format: Shanta M. Messerli, Mariah M. Hoffman, Jessica S. Zylla, Etienne Gnimpieba, Keith W. Miskimins. Examination of therapeutic potential of epigenetic modulation by dual HDAC-LSD1 inhibition in murine models of triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1761.
Evaluating interaction of fibre reinforcement mechanism with mesostructure of asphalt concrete

Published studies generally demonstrate positive benefits from using Mechanically Fibre-Reinforced Asphalt Concrete (M-FRAC). However, improvements vary with the particular asphalt mixture used in ...
Epilogue: Where Do We Go from Here in Bridging Cognitive Rehabilitation and Neuroimaging?

Across neurological populations, researchers and clinicians have only begun to examine the neuroplasticity associated with cognitive rehabilitation (CR). The few studies examining CR and neuroimaging that have been conducted to date complement the traditional CR studies, in which neuropsychological assessment is utilized as the “gold standard” outcome. As illustrated in this volume, there are some populations where neuroimaging has started to play a role in the evaluation of CR in research studies (e.g., MS, schizophrenia) while in other populations there is little to no work on neuroimaging and CR to date (e.g., brain tumor, pediatric TBI). Nonetheless, the limited research utilizing neuroimaging to evaluate CR to date has demonstrated the plasticity inherent in the brain and highlight the short time frame in which functional brain changes can occur following CR. Possible conclusions and, more importantly, interpretation of such functional brain changes remain limited, unfortunately, largely due to the small sample sizes and limited number of studies. However, the few studies conducted indeed show post-cognitive rehabilitation changes in both neural activation and connectivity, and the importance of network analyses. The continued and future development of new imaging techniques and refinement of existing techniques is likely to enhance our ability to document and interpret such neural changes in future work.
New maps for an inclusive Wikipedia: decolonial scholarship and strategies to counter systemic bias

Since early in the development of the project, Wikipedia editors have been concerned with overcoming “systemic biases” in coverage of the world’s knowledge, especially those rooted in forms of soci...
Association between infertility and all-cause mortality: analysis of US claims data

Background The consequences of an infertility diagnosis extend beyond the pursuit of family building, because women with infertility also face increased risks for severe maternal morbidity, cancer, and chronic disease. Objective This study aimed to examine the association between female infertility and all-cause mortality. Study Design This retrospective analysis compared 72,786 women with infertility, identified in the Optum Clinformatics Datamart from 2003 to 2019 by infertility diagnosis, testing, and treatment codes, with 3,845,790 women without infertility seeking routine gynecologic care. The baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome diagnoses and the Charlson Comorbidity Index. The primary outcome, which was all-cause mortality, was identified by linkage to the Social Security Administration Death Master File outcomes and medical claims. The association between infertility and mortality was examined using a Cox proportional hazard regression by adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of the country, and race. Results Among 16,473,458 person-years of follow-ups, 13,934 women died. Women with infertility had a 32% higher relative risk for death from any cause (0.42% vs 0.35%, adjusted hazard ratio, 1.32; 95% confidence interval, 1.18–1.48) than women without infertility. The mean follow-up time per patient was 4.0±3.7 years vs 4.2±3.8 years for women with and without infertility, respectively. When stratified by age of Conclusion Although the absolute risk for death was low in both groups, women with infertility faced a higher relative risk for mortality than women without infertility. The association remained across all age, race and ethnicity groups, morbidities, and delivery strata. Importantly, infertility treatment was not associated with an increased risk for death. These findings reinforce the disease burden associated with infertility and its potential for long-term sequelae.
A Crossroads in the Fight Against Human Trafficking? Let's Take the Structural Route: A Response to Janie Chuang

Even ten years ago, the phrase “human trafficking” might have evoked blank stares in many circles. Today, the existence of a contemporary trade in human beings has blossomed fully into public awareness. Discussion of and expositions about human trafficking appear not only in sensationalist media reports, but also in many other arenas, such as film dramas, documentaries, books and articles by scholars from a variety of disciplines, activist NGO websites, and legislative chambers across the globe. However, some legal scholars as well as other scholars in the human trafficking sphere admit to a growing unease. Why? There is the sense that the label is a mushrooming monster that encompasses or swallows up all forms of human exploitation, identifies or creates stereotypical bad guys and innocent victims, and yet leaves relatively untouched the root causes of the exploitation.
3D Scanning as a Tool to Measure Growth Rates of Live Coral Microfragments Used for Coral Reef Restoration

Rapid and widespread declines in coral health and abundance have driven increased investments in coral reef restoration interventions to jumpstart population recovery. Microfragmentation, an asexual propagation technique, is used to produce large numbers of corals for research and restoration. As part of resilience-based restoration, coral microfragments of different genotypes and species are exposed to various stressors to identify candidates for propagation. Growth rate is one of several important fitness-related traits commonly used in candidate selection, and being able to rapidly and accurately quantify growth rates of different genotypes is ideal for high-throughput stress tests. Additionally, it is crucial, as coral restoration becomes more commonplace, to establish practical guidelines and standardized methods of data collection that can be used across independent groups. Herein, we developed a streamlined workflow for growth rate quantification of live microfragmented corals using a structured-light 3D scanner to assess surface area measurements of live tissue over time. We then compared novel 3D and traditional 2D approaches to quantifying microfragment growth rates and assessed factors such as accuracy and speed. Compared to a more conventional 2D approach based on photography and ImageJ analysis, the 3D approach had comparable reliability, greater accuracy regarding absolute surface area quantification, high repeatability, and low variability between scans. However, the 2D approach accurately measured growth and proved to be faster and cheaper, factors not trivial when attempting to upscale for restoration efforts. Nevertheless, the 3D approach has greater capacity for standardization across dissimilar studies, making it a better tool for restoration practitioners striving for consistent and comparable data across users, as well as for those conducting networked experiments, meta-analyses, and syntheses. Furthermore, 3D scanning has the capacity to provide more accurate surface area measurements for rugose, mounding, or complex colony shapes. While each method has its advantages and disadvantages, disadvantages to a 3D approach based on speed and cost may diminish with time as interest and usage increase. As a resource for coral restoration practitioners and researchers, we provide a detailed 3D scanning protocol herein and discuss its potential limitations, applications, and future directions.
Ionization properties of monophosphoinositides in mixed model membranes.

Abstract Phosphoinositides are found in low concentration in cellular membranes but perform numerous functions such as signaling, membrane trafficking, protein recruitment and modulation of protein activity. Spatiotemporal regulation by enzymes that phosphorylate and dephosphorylate the inositol ring results in the production of seven distinct and functionally diverse derivatives. Ionization properties of the phosphorylated headgroups of anionic lipids have been shown to impact how they interact with proteins and lipids in the membrane. While the ionization properties of the three bis and one tris phosphorylated forms have been studied in physiologically relevant model membranes, that of the monophosphorylated forms (i.e., phosphatidylinositol-3-phosphate (PI3P), phosphatidylinositol-4-phosphate (PI4P), phosphatidylinositol-5-phosphate (PI5P)) has received less attention. Here, we used 31P MAS NMR to determine the charge of 5 mol% of the monophosphorylated derivatives in pure dioleoylphosphatidylcholine (DOPC) and DOPC/dioleoylphosphatidylethanolamine (DOPE) bilayers as a function of pH. We find that PI3P, PI4P and PI5P each have unique pKa2 values in a DOPC bilayer, and each is reduced in DOPC/DOPE model membranes through the interaction of their headgroups with DOPE according to the electrostatic-hydrogen bond switch model. In this study, using model membranes mimicking the plasma membrane (inner leaflet), Golgi, nuclear membrane, and endosome (outer leaflet), we show that PI3P, PI4P or PI5P maximize their charge at neutral pH. Our results shed light on the electrostatics of the monophosphorylated headgroups of PI3P, PI4P, and PI5P and form the basis of their intracellular functions.
Catalytic Dehydrogenation of Cyclohexanone to Phenol Over the Ru, Rh, Pd and Pt Surfaces in Sub-critical Water

With the overview of different kinds of phenol synthesis routes, dehydrogenation of cyclohexanone to phenol under sub-critical water condition using Pt, Pd, Rh, Ru and Re immobilized heterogeneous catalysts have been reported. Surface properties and characterizations of the catalysts were done. Binding of metal on a support and their relationship with zeta potential (ζ) and their effect on catalytic activity are discussed. Importance of sub-critical water reaction conditions in terms of thermodynamic favourability and phase equilibrium are evaluated through ASPEN simulator. Based on the results obtained, possible reaction pathways for the formation of product and the by-products are illustrated. The feasibility of a metal acting as a dehydrogenation catalyst according to M0/MII (E0) couple is also explained.
A stochastic architecture for neural nets

A stochastic digital architecture is described for simulating the operation of Hopfield neural networks. This architecture provides reprogrammability (since synaptic weights are stored in digital shift registers), large dynamic range (by using either fixed or floating-point weights), annealing (by coupling variable neuron gains with noise from stochastic arithmetic), high execution speeds ( approximately=N*10/sup 8/ connections per second), expandability (by cascading of multiple chips to host large networks), and practicality (by building with very conservative MOS device technologies). >
Rapid Reciprocal Changes in Rat Tissue Enzyme Activities following Epinephrine Injection

Epinephrine infusion into the portal vein produced rapid changes in the activities of certain hepatic, epididymal fat, and skeletal muscle glycolytic enzymes and fructose diphosphatase in the rat. Epinephrine produced a rapid increase in hepatic, epididymal fat, and skeletal muscle fructose diphosphatase activity. In contrast, epinephrine produced a rapid decrease in hepatic phosphofructokinase, pyruvate kinase, and glucokinase activities. Epinephrine also lowered skeletal muscle phosphofructokinase and pyruvate kinase activities. However, epinephrine had no significant effect upon epididymal fat pyruvate kinase and phosphofructokinase activities. Fructose diphosphate aldolase activities were unchanged in the liver, epididymal fat, and skeletal muscle. The epinephrine effect on the hepatic enzymes was maximal within 2 to 5 min following injection of 2 µg and then gradually returned to control levels over the remaining 35 to 38 min of testing. The magnitude of the epinephrine effect was dose-dependent. No effect was detected when 0.25 µg per min was injected. Phosphofructokinase, pyruvate kinase, and fructose diphosphatase activities were significantly altered at a dose level of 1.0 µg per min, with maximal changes occurring at the 2.0- to 4.0-µg per min dose level. The epinephrine effect was associated with a significant increase in hepatic cyclic adenosine 3′:5′-monophosphate concentrations. Actinomycin D and puromycin treatment did not alter the response of the enzymes to epinephrine. Insulin given 5 min following epinephrine partially reversed the epinephrine effect. Similarly, epinephrine given 5 min following insulin partially reversed the insulin effect. We suggest that the epinephrine effect is mediated through cyclic adenosine 3′:5′-monophosphate and may be due to phosphorylating mechanisms analogous to that responsible for the regulation of glycogen metabolism.
Extraction of the D∗Dπ coupling from D∗ decays

The decays D* → Dπ and D* → Dγ are well described by heavy meson chiral perturbation theory. With the recent measurement of B(D*+ → D+γ), the D*^0, D*+ and D*_S branching fractions can be used to extract the D*Dπ and D*Dγ couplings g and β. The D* → Dγ decays receive important corrections at order √m_q and, from the heavy quark magnetic moment, at order 1/m_c. Here all the decay rates are computed to one loop, to first order in m_q and 1/m_c, including the effect of heavy meson mass splittings, and the counterterms at order m_q. A fit to the experimental data gives two possible solutions, g = 0.27_(−0.02−0.02)^(+0.04+0.05), β= 0.85_(−0.1 − 0.1)^(+0.2 + 0.3) GeV− or g = 0.76_(−0.03 −0.1)^(+0.03+0.2), β = 4.90_(−0.3−0.7)^(+0.3+5.0) GeV^(−1). The first errors are experimental, while the second are estimates of the uncertainty induced by the counterterms. (The experimental limit Γ_D* < 0.13 MeV excludes the g = 0.76 solution.) Predictions for the D* and B* widths are given.
Simplifying microbial electrosynthesis reactor design.

Microbial electrosynthesis, an artificial form of photosynthesis, can efficiently convert carbon dioxide into organic commodities; however, this process has only previously been demonstrated in reactors that have features likely to be a barrier to scale-up. Therefore, the possibility of simplifying reactor design by both eliminating potentiostatic control of the cathode and removing the membrane separating the anode and cathode was investigated with biofilms of Sporomusa ovata, which reduces carbon dioxide to acetate. In traditional ‘H-cell’ reactors, where the anode and cathode chambers were separated with a proton-selective membrane, the rates and columbic efficiencies of microbial electrosynthesis remained high when electron delivery at the cathode was powered with a direct current power source rather than with a poteniostat-poised cathode utilized in previous studies. A membrane-less reactor with a direct-current power source with the cathode and anode positioned to avoid oxygen exposure at the cathode, retained high rates of acetate production as well as high columbic and energetic efficiencies. The finding that microbial electrosynthesis is feasible without a membrane separating the anode from the cathode, coupled with a direct current power source supplying the energy for electron delivery, is expected to greatly simplify future reactor design and lower construction costs.