cssi/SciSciGPT-SciSciNet huggingface dataset:
Clinical Pharmacology of Loop Diuretics

The clinical pharmacology of torasemide, bumetanide, piretanide and furosemide (frusemide) is discussed. These drugs share a similar mechanism of action in inhibiting Na+-K+-2Cl− reabsorption at the thick ascending limb of the loop of Henle. They differ in their routes of metabolism, pharmacokinetics, and potency. Whether such differences are clinically important requires further study. Bumetanide and torasemide are metabolised by cytochrome P450 pathways, whereas furosemide is glucuronidated. These different routes of metabolism may have clinically important implications. Bumetanide, furosemide, and piretanide have similar pharmacokinetics, whereas the clearance of torasemide is less and the half-life concomitantly longer than the other 3 agents. Thus, torasemide has a longer duration of action. The rank order of potency is bumetanide > piretanide ≡ torasemide > furosemide, although efficacy appears the same. Despite much being known about these diuretics, many clinically important questions remain.
Technical Approach to Iliac Crest Biopsy

Bone histomorphometry has been the gold standard in the evaluation and diagnosis of renal osteodystrophy. The recent new definition of renal osteodystrophy as chronic kidney disease–mineral and bone disorder has once again highlighted the use of bone biopsy as a powerful and diagnostic tool to determine skeletal abnormalities in chronic kidney disease. The procedure of iliac crest bone biopsy has been proved safe and associated with very minimal morbidity. In this review, the clinical indications, preparation, instrumentation, and potential complications are discussed. Because current biochemical markers are poor predictors of bone turnover, volume, and mineralization, a wider use of bone biopsy and histomorphometry will lead to a better understanding of the bone and mineral disorders that are associated with chronic kidney disease.
The use of zoledronic acid in pediatric cancer patients

Background The third generation bisphosphonate zoledronic acid has demonstrated efficacy in reducing skeletal-related events in adult patients with multiple cancer types that have skeletal disease. The use of zoledronic acid in pediatric oncology patients with bone metastases for the purpose of reducing pain, improving bone strength and altering the progression of metastatic disease has not been thoroughly evaluated. Procedure From October 2005 to December 2008, 19 patients at the Aflac Cancer Center received one or more doses of zoledronic acid as part of their therapy. A retrospective review of these patients was performed and information was collected including indication for treatment, toxicities, and outcomes. Results Most patients (n = 15) received zoledronic acid following relapse of their malignancy with metastatic disease present in one or more bony sites. Hypocalcemia and hypophosphatemia were frequent, but did not result in clinical symptoms. More significant toxicities associated with zoledronic acid, including clinically apparent renal insufficiency and osteonecrosis of the jaw, were not seen. Overall, zoledronic acid was well tolerated in this population. Conclusions The benefits of zoledronic acid seen in randomized trials of adults with bone metastases have sparked interest in its use for children with metastatic cancer. The administration of zoledronic acid in pediatric oncology appears safe, and may result in improved bone strength and pain control. Further evaluation is warranted to prospectively evaluate its efficacy and long-term safety in pediatric patients with cancer and skeletal metastases. Pediatr Blood Cancer 2011;56:610–614. © 2010 Wiley-Liss, Inc.
Digital filters with peak-constrained weighted least-squared errors

Digital filter design algorithms that extend peak-constrained weighted least-squared error optimization methods to cover a wide range of problems are presented. It is shown that the optimization problem can be solved in terms of the equivalent problem of minimizing a modified total weighted-square error function. Several different approaches to determining the modified weighting function using iterative reweighted least-squares methods are discussed. A generalized multiple exchange algorithm for designing FIR digital filters and windows is also discussed. >
On nonlinear self-interaction of geodesic acoustic mode driven by energetic particles

It is shown that nonlinear self-interaction of energetic particle-driven Geodesic Acoustic Mode does not generate a second harmonic in radial electric field using the fluid model. However, kinetic effects of energetic particles can induce a second harmonic in the radial electric field. A formula for the second order plasma density perturbation is derived. It is shown that a second harmonic of plasma density perturbation is generated by the convective nonlinearity of both thermal plasma and energetic particles. Near the midplane of a tokamak, the second order plasma density perturbation (the sum of second harmonic and zero frequency sideband) is negative on the low field side with its size comparable to the main harmonic at low fluctuation level. These analytic predictions are consistent with the recent experimental observation in DIII-D.
A Bayesian Algorithm for Reconstructing Climate Anomalies in Space and Time. Part II: Comparison with the Regularized Expectation–Maximization Algorithm

Abstract Part I presented a Bayesian algorithm for reconstructing climate anomalies in space and time (BARCAST). This method involves specifying simple parametric forms for the spatial covariance and temporal evolution of the climate field as well as “observation equations” describing the relationships between the data types and the corresponding true values of the climate field. As this Bayesian approach to reconstructing climate fields is new and different, it is worthwhile to compare it in detail to the more established regularized expectation–maximization (RegEM) algorithm, which is based on an empirical estimate of the joint data covariance matrix and a multivariate regression of the instrumental time series onto the proxy time series. The differing assumptions made by BARCAST and RegEM are detailed, and the impacts of these differences on the analysis are discussed. Key distinctions between BARCAST and RegEM include their treatment of spatial and temporal covariance, the prior information that enter...
Performance robustness of MRAC under reduction in actuator effectiveness

The problem of performance robustness of model reference adaptive control (MARC) schemes under reduction in actuator effectiveness (loss-of-effectiveness) is studied in this paper. The reduction is modeled by an uncertain gain matrix representing the actuator effectiveness at the control inputs. MRAC systems are analyzed to determine the robustness of the desired closed-loop performance of stability and asymptotic tracking with respect to such reductions. Conclusions are drawn for direct multivariable MRAC as well as indirect MRAC for both continuous-time and discrete-time schemes. A simulation study is presented to illustrate some of the theoretical results.
Driver Behavior Characteristics at Urban Signalized Intersections

Red-light running and the associated risk of severe crashes at signalized intersections have been an ongoing concern to many safety professionals. The proportions of crashes that occur due to such driver behavior represent a substantial number of crashes at urban and suburban signalized intersections in Michigan. In the year 2001, crashes related to red-light running in Michigan represented about 28% of the crashes of all severities and 40% of fatal and serious injury crashes occurring within signalized intersections. Many initiatives to discourage red-light running have been used in the United States with various degrees of success. Such programs include public awareness campaigns, automated enforcement programs, and some engineering countermeasures. These initiatives have resulted in some reduction in the overall crash statistics in the communities where such programs have been implemented. A series of evaluation studies was performed in Michigan to test the effectiveness of implementing change and clearance intervals calculated according to ITE guidelines on late exits and red-light violations at nine signalized intersections in the Detroit metropolitan area. The study described used four approaches at four test intersections where engineering treatments have been applied (16 total test sites) and four approaches at five control intersections. Driver behavior was examined at test and control intersections by observing and quantifying the number of vehicles that did not clear the intersection when the cross-street signal light turns green (late exit) and red-light violations. Upon analysis, red-light-running data at the test and control sites did not exhibit a significant difference. However, the test sites showed significantly lower late exit rates compared with the control sites, thus lowering the risk of right-angle crashes.
Integer multiplication and division on the HP Precision Architecture

In recent years, many architectural design efforts have focused on maximizing performance for frequently executed, simple instructions. Although these efforts have resulted in machines with better average price/performance ratios, certain complex instructions and, thus, certain classes of programs which heavily depend on these instructions may suffer by comparison. Integer multiplication and division are one such set of complex instructions. This paper describes how a small set of primitive instructions combined with careful frequency analysis and clever programming allows the Hewlett-Packard Precision Architecture integer multiplication and division implementation to provide adequate performance at little or no hardware cost.
Polymeric derivatives of 3,3‐bis(aminomethyl)‐oxetane and of exoxysuccinyl chloride

Two monomers, bis(aminomethyl)oxetane (I) and epoxysuccinyl chloride (II) have been prepared and converted to condensation polymers, structurally similar to the epoxides. Both monomers were stable and easy to handle. The polymers crosslinked to insoluble, infusible products.
Disability and Discussions of Health-Related Behaviors Between Youth and Health Care Providers

Abstract Purpose The purpose of this study was to examine the likelihood of discussing health-related behaviors with health care providers (HCPs), comparing youth with and without mobility limitations (MLs). Methods Analyses were conducted using baseline data from the MyPath study. Adolescents and young adults between the ages of 16 and 24 years completed a survey about their health care and health-related experiences. Analyses assessed the relationship between mobility status and discussing health-related behaviors with an HCP. Secondary analyses examined the extent to which adolescents and young adults' engagement in these behaviors was associated with these discussions. Results Overall, we found low rates of discussions about the following topics: substance use, sexual and reproductive health, healthy eating, weight, and physical activity. Adolescents and young adults with MLs were less likely to report discussing substance use and sexual and reproductive health, but were more likely to discuss healthy eating, weight, and physical activity than peers without MLs. Those adolescents and young adults who reported substance use had higher odds of discussing this topic and those who reported having sexual intercourse had higher odds of discussing sexual and reproductive health. Conclusions Results suggest mobility status and a young person's engagement in health risk and promoting behaviors are associated with the likelihood of discussing these behaviors with an HCP. It is important that HCPs view adolescents and young adults with MLs as needing the same counseling and guidance about health-related behaviors as any young person presenting him/herself for treatment.
Resource-efficient software delivery using volunteer assistance

We propose to apply Peer-to-Peer (P2P) technology to resolve the scalability problems observed in current techniques used to provide management and maintenance services in enterprise networks. We aim to create a content delivery infrastructure that can be used by managed services organizations, on the basis of donated servers, to help download and maintain software packages.
Antisense-mediated Exon Skipping Decreases Tau Protein Expression: A Potential Therapy For Tauopathies

In Alzheimer's disease, progressive supranuclear palsy, and a number of other neurodegenerative diseases, the microtubule associated protein tau aggregates to form intracellular neurofibrillary tangles and glial tangles, abnormal structures that are part of disease pathogenesis. Disorders with aggregated tau are called tauopathies. Presently, there are no disease-modifying treatments for this disease class. Tau is encoded by the MAPT gene. We propose that reducing MAPT expression and thus the amount of tau protein made could prevent aggregation, and potentially be an approach to treat tauopathies. We tested 31 morpholinos, complementary to the sense strand of the MAPT gene to identify oligonucleotides that can downregulate MAPT expression and reduce the amount of tau protein produced. Oligonucleotides were tested in human neuroblastoma cell lines SH-SY5Y and IMR32. We identified several morpholinos that reduced MAPT mRNA expression up to 50% and tau protein levels up to ~80%. The two most potent oligonucleotides spanned the 3′ boundary of exons 1 and 5, masking the 5′-splice sites of these exons. Both morpholinos induced skipping of the targeted exons. These in vitro findings were confirmed in mice transgenic for the entire human MAPT gene and that express human tau protein. These studies demonstrate the feasibility of using modified oligonucleotides to alter tau expression.
Oral Manifestations of Systemic Disease

Lesions inside the oral cavity can be associated with a number of systemic conditions, representing important indicators of active disease or heralding the onset of disease. Recognition of such lesions may facilitate prompt diagnosis and treatment of underlying disease with overall improvement in patients’ quality of life. In some cases, oral findings persist despite adequate systemic management of disease, necessitating targeted ancillary care measures. This chapter reviews the presentation and management of oral findings that may be seen in association with systemic conditions, including autoimmune, gastrointestinal, and granulomatous disorders.
Diabetes Education as a Career Choice.

PurposeThe purpose of the study was to examine the field of diabetes education along with identifying facilitators and barriers for future health care professionals entering the specialty field of diabetes education.MethodFaculty members who were currently teaching in a health-related discipline, the students of those faculty members, and nursing students who were members of the National Student Nursing Association were surveyed to gather descriptive data.ResultsWhile faculty members reported they are promoting diabetes education to their health professions students, many nursing students are not aware of this career path. Nursing students understand that diabetes is a significant problem and will be something they encounter in all areas of their careers, but many were not sure they wanted to specialize in it.ConclusionsThere is a gap between what faculty members and students report as far as awareness of the diabetes education specialty. In addition, misinformation about diabetes and people living with d...
Nutrition in inflammatory bowel disease.

An understanding of the pathogenesis of inflammatory bowel disease (IBD) continues to be the major focus of IBD research. Environmental factors contribute to the increased incidence of Crohn’s disease (CD) and the changing incidences of IBD in groups of people who have migrated from areas with low disease incidence to areas of higher incidence. (See “Epidemiology of Inflammatory Bowel Disease and Overview of Pathogenesis,” by Bruce E. Sands, MD, MS, and Stacey Grabert, PharmD, MS, in March 2009 Medicine & Health/Rhode Island). It is now widely accepted that IBD represents a dysregulation of the immune response to intraluminal antigens. Evidence to date has failed to identify specific food antigens and has focused on bacterial antigens. Although no specific dietary antigen, toxin or diet product has been linked to IBD, both the lay and scientific communities are interested in this possibility. Studies of pre-illness diet have implicated some dietary components, most notably refined sugars and a high fat diet. The popular appeal of incriminating refined sugar and high fat as signs of “westernization” of diet reinforces the widespread appeal and frequent citation of these theories. The studies, however, have too many methodological problems to be considered useful. Concern about nutritional deficiencies in IBD as well as the role of nutrition in pediatric IBD has been the subject of physician interest for many years.
Productivity, Botanical Composition, and Nutritive Value of Commercial Pasture Mixtures

Pastures in the northeastern United States are often planted to mixtures of grasses and legumes. We evaluated several commercial seed mixtures to determine if the number of species in mixture affected yield and botanical composition in central Pennsylvania. Three replicate plots of 25 mixtures, five each of two, three, four, five, and six species of grasses and legumes were planted in August 2007 near State College, PA. Plots were grazed by beef cows for 3 yr. Dry matter (DM) yield was determined at each of the six harvests in each year. Botanical composition was measured at the first, third, and last harvest each year. Annual DM yield was positively related to the number of species planted (r² = 0.15, 0.18, and 0.26 for 2008, 2009, and 2010, respectively). Mixtures within groups of similar species richness, however, varied in yield. Kentucky bluegrass (Poa pratensis L.), birdsfoot trefoil (Lotus corniculatus L.), and timothy (Phleum pratense L.) did not establish or persist well in mixture with taller grasses [e.g., orchardgrass (Dactylis glomerata L.)]. The short-lived species festulolium (X Festulolium Asch. & Graebn.) and red clover (Trifolium pratense L.) contributed significantly to production during the first year and were replaced by longer-lived species such as orchardgrass and white clover (T. repens L.). Forage nutritive value was related to the botanical composition but not the number of species in mixture. Results suggest that a strategy of planting mixtures with a combination of fast- and slow-establishing species can be effective for multispecies pastures in central Pennsylvania.
Coherent Backscattering via Ultra Slow Light

A strong coherent backward wave oscillation using forward propagating fields only is achieved. This leads to controling phase-matching and having phase-matching simultaneously in forward and backward directions. It has applications to entangled photon state generation.
Serological Assessment of the Prospective Organ Donor

We evaluated the test panels of six transplant centers to determine similarity and comprehensiveness of their donor testing. Viral serology in donor testing answers preoperative questions about human immunodeficiency virus and hepatitis B infectivity of the donor, guides the posttransplant management of the patient, and anticipates future directions of transplantation. In view of the essential information provided by donor testing, we propose a panel that includes tests to detect hepatitis B surface antigen and antibody to HIV-1, HIV-2, hepatitis C virus, hepatitis B core antigen, human T-cell lymphotropic virus type I, cytomegalovirus, Toxoplasma gondii , Epstein-Barr virus, and parvovirus B19. The panel also should include ABO and Rh blood grouping, and rapid plasma reagin and fluorescent treponemal antibody absorption tests for syphilis. The panel will evolve as advances in transplantation occur.
The Diversity of Decarceration Examining First-Year County Realignment Spending in California

In recent years, California has dramatically restructured its correctional system through a policy called “Realignment,” which shifts responsibility over thousands of offenders from the state to its counties. To help manage this influx, the state allocated US$2 billion through 2014 to the counties. Counties have used these funds in different ways. Some have adhered to Realignment’s intended focus on evidence-based programming, whereas others have focused on expanding enforcement and custodial capacities. I analyze first-year (2011-2012) county Realignment budgets to identify political, economic, and criminal justice factors that explain different spending emphases. Using quantitative and comparative methods, I find that counties focus on enforcement spending because of pressing local needs related to crime and justice, and counties focus on services spending when sheriffs—key figures in Realignment administration—are politically secure. These findings have practical implications for correctional policies ...
Renewal coil insulation systems for AC stator windings

While it must be well recognized that the use of film faced flexible resin tapes can not compete with: 1. The long term voltage life under very high voltage stress offered by Resin Rich Tapes when press cured. 2. The physical strength required in very large high speed machines such as steam turbine generators and offered by Resin Rich Tapes when press cured.
The Demand for an Education in Entrepreneurship

Small business, capitalism, and entrepreneurship built America from the 13 original colonies with no more than three million inhabitants to the most powerful and industrialized country less than two hundred years. Yet, from the inception of business education in America until fairly recently, colleges and universities have prepared their students to fill the rank of professionals for those businesses that had already succeeded rather than to become the entrepreneurs and builders of new businesses despite the fact that small business employs over half the work force and produces 44% of the gross national product.
The Giemsa stain for tissue sections: an improved method.

The value of the Giemsa stain on smears and imprints has long been acknowledged, but few pathologists have been consistently successful with histologic sections because of the peculiar problems of the dyes and the mysterious vagaries of the methodology. A Giemsa stain giving reproducible differential staining of tissue sections is particularly desirable for the examination of hematopoietic tissues. A modified Giemsa stain which provides such reproducibility is described. It differs from other methods primarily in the use of a stock solution which contains known amounts of azure A–eosin and azure B–eosin. In addition, acetic acid is used instead of phosphate buffers to obtain an acidic working solution. The results suggest that the Giemsa stain may represent the most useful means of evaluating lymphoid tissue in section. It is of particular value in identifying the immunoblast (basophilic stem cell), as well as providing differentiation of granulocytic elements.
Interactions of yeasts, moulds, and antifungal agents

Interactions of yeasts, moulds, and antifungal agents , Interactions of yeasts, moulds, and antifungal agents , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
The Ethical Minefield in Human Trafficking Research—Real and Imagined

All research endeavors involving human subjects must operate within some ethical parameters, some of which bear greater consequences than others should there be violations. However, unlike biomedical research or any experimental studies that employ physical intrusion, manipulation, or deliberate disguise, most social sciences, particularly ethnographical studies, involve nothing more than conversing and observing. Through my personal experience in research on human trafficking, I am questioning the unproductive and obstructionist approach in current institutional efforts ubiquitous in American academia to police and censor such mundane and ordinary research activities. I suggest that a fundamental lack of confidence in human agency and the researcher’s personal integrity has given rise to unfettered concerns over possible violations of ethics in field research. As a result, an enormous amount of collective energy is being wasted by institutions and moral entrepreneurs alike to review study plans and by researchers who prepare and respond to such an unnecessary scrutiny. While ethical concerns over research conduct in social science may sound reasonable and even legitimate, none have received any empirical support. In other words, social science has thus far proven to be 100 % “clinically” safe to human beings. With such an impeccable “safety” record currently and historically, does anyone ever wonder, why all this fuss?
Patatin-like phospholipase domain-containing protein 3 (PNPLA3): A potential role in the association between liver disease and bipolar disorder.

Abstract Objective Due to the increased prevalence of liver disease in patients with bipolar disorder, we examined the potential role of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant among individuals with bipolar disorder and those with no mood disorder. Methods We used the National Health and Nutrition Examination Survey (NHANES) database (aged 15–39 years) to identify a group of individuals with a bipolar diagnosis and a control group of individuals with no mood disorder. A total of 1931 individuals were randomly selected, one from each family containing information on the PNPLA3 genotype to be used in the analysis. Results Analyses revealed individuals with the recessive variant genotype (MM) had an adjusted odds ratio for bipolar disorder of about 4.6 compared to individuals with either IM or II genotypes of the PNPLA3 variant. Limitations and conclusions Limitations of this study include the use of a lay-administered survey in for diagnosis of bipolar disorder in NHANES. The association between the PNPLA3 variant and bipolar disorder may help guide further work on medication effectiveness, treatment options, prevention approaches, and understanding potential medication side effects among specific subgroups of individuals with the MM genotype.
Intravascular Papillary Endothelial Hyperplasia

Also known as intravascular papillary endothelial hyperplasia (IPEH), Masson’s vegetant hemangioendothelioma. Benign proliferation of endothelial cells, which presents as slow growing, tender, violaceous cutaneous mass on the head, neck, fingers, or trunk. Deep tumors occur as intramuscular hemangiomas, which may be expansile and compressive. Involvement of CNS is rare, usually on top of hematoma from cavernous hemangioma, also may complicate intracerebral hemorrhage.
The Economic History of Trumpism

Why did America embrace right wing populism in the 2016 election? A look back at past moments of economic transformation suggests that government policy of "producerism" mitigated the pain and fear among those losing jobs and opportunity in a changing economy. The abandonment of this policy after 1980 explains the resentment of the white working class toward established elites of both political parties and set the stage for the rise of a political outsider like Trump.
Assessing Mood Disorders and Suicidality in African Americans

This manuscript is presented to provide insights into the assessment of major depressive disorder and suicidality, frequency, and severity of suicidal thoughts of African American youth and adults. Given the paucity of literature in this area, clinicians, researchers, and policy makers may be at a loss as to how to accurately assess these highly stigmatized illnesses in people of the African diaspora. In this chapter, the authors describe the major measures currently available and the steps taken to assess their utility with African Americans. We provide detailed information on the psychometric properties of the measures and information regarding our assessment of their utility with African Americans.
Uncertainty and Dispersion of Opinions

We study the strategic behavior of equity analysts whose compensation is based on relative performance of their stock recommendations. Our model predicts that risk-averse analysts issue identical recommendations to avoid falling behind their peers. Top analyst awards, on the other hand, motivate analysts to issue bold recommendations. However, when the stock return is very volatile, the herding incentive dominates. As a result, dispersion of recommendations away from the consensus is only likely for low-volatility stocks. Consistent with the predictions, our empirical analysis finds a negative relationship between the dispersion of recommendations and stock return volatility.
Web Security Vulnerability Analysis Using Network and Information Security Tools

The web security vulnerabilities such as eavesdropping, impersonation, data sniffing, denial of service, and port hacking are investigated by analyzing the security weakness using the security exploration tools. Security management policies were developed based on these analyses. The results indicated that security policies produced from there analyses would enhance the web security tremendously on an organizational network.
The Argument Principle

In this chapter, we shall be concerned with questions that have a geometric, qualitative nature rather than an analytical, quantitative one. These questions center around the issue of the local geometric behavior of a holomorphic function.
Changing patterns of natural selection on morphology of Cliff Swallows during severe weather

ABSTRACT Extreme climatic events can often lead to intense selection and serve as catalysts for rapid evolutionary change. Cold and rainy weather during a 6-day period in spring 1996 led to massive mortality of Cliff Swallows (Petrochelidon pyrrhonota) in western Nebraska and selected for birds with shorter wings and tails, larger skeletal traits, lower levels of fluctuating asymmetry, and less phenotypic variance in all traits. Here we investigate whether the same patterns of selection occurred during 2 subsequent cold and rainy weather events in this population in 2004 and 2017. Directional selection on morphological traits in 2004 was generally the same as in 1996, but in 2017 selection on tarsus length and outer tail feather length was in the opposite direction. As in 1996, selection during both events reduced phenotypic variance in most traits. The results illustrate the potential for extreme weather events to act as drivers for fluctuating directional selection on morphological traits and for period...
In vivo measurement of the human crystalline lens equivalent refractive index using extended-depth OCT

The lens equivalent refractive index (RI) is commonly used in calculations of crystalline lens power. However, accurate determination of the equivalent RI in vivo is challenging due to the need of multiple measurements with different ocular biometry devices. A custom extended-depth Spectral Domain-OCT system was utilized to provide measurements of corneal and lens surface curvatures and all intraocular distances required for determination of the lens equivalent RI. Ocular biometry and refraction were input into a computational model eye from which the equivalent RI was calculated. Results derived from human subjects of a wide age range show a decrease in RI with age and demonstrate the capability of in vivo measurements of the equivalent RI with extended-depth OCT.
Unpacking ‘Success’: Applying Local Perceptions to Interpret Influences of Water Fund Payments for Ecosystem Services in the Ecuadorian Andes

AbstractNGOs, government agencies, and green businesses proclaim water fund arrangements in Latin America as successful payments for ecosystem services (PES) systems. Associated success narratives ...
Short- and long-term rheological and chemical characteristics of nanomodified asphalt binder

AbstractDue to the special characteristics of nanoparticles, pavement engineers have used nanoparticles as an additive in asphalt pavement to improve pavement performance. This study focuses on cha...
A Conserved PLPLRT/SD Motif of STING Mediates the Recruitment and Activation of TBK1

Nucleic acids from bacteria or viruses induce potent immune responses in infected cells1-4. The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses5,6. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor7,8. It catalyses the synthesis of cyclic GMP-AMP (cGAMP)9-12, which stimulates the induction of type I interferons through the STING-TBK1-IRF-3 signalling axis13-15. STING oligomerizes after binding of cGAMP, leading to the recruitment and activation of the TBK1 kinase8,16. The IRF-3 transcription factor is then recruited to the signalling complex and activated by TBK18,17-20. Phosphorylated IRF-3 translocates to the nucleus and initiates the expression of type I interferons21. However, the precise mechanisms that govern activation of STING by cGAMP and subsequent activation of TBK1 by STING remain unclear. Here we show that a conserved PLPLRT/SD motif within the C-terminal tail of STING mediates the recruitment and activation of TBK1. Crystal structures of TBK1 bound to STING reveal that the PLPLRT/SD motif binds to the dimer interface of TBK1. Cell-based studies confirm that the direct interaction between TBK1 and STING is essential for induction of IFNβ after cGAMP stimulation. Moreover, we show that full-length STING oligomerizes after it binds cGAMP, and highlight this as an essential step in the activation of STING-mediated signalling. These findings provide a structural basis for the development of STING agonists and antagonists for the treatment of cancer and autoimmune disorders.
Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial

Objective:Despite the staggering consequences of the opioid epidemic, limited nonopioid medication options have been developed to treat this medical and public health crisis. This study investigate...
Corrigendum to "Pericardial Tamponade: An Uncommon Clinical Presentation in cANCA Related Vasculitis and Glomerulonephritis in Association with Very High Titres of ANA".

ANCA (anti-neutrophil cytoplasmic antibody) vasculitides are systemic autoimmune diseases in which anti-neutrophilic cytoplasmic antibodies activate primed neutrophils, thereby generating an inflammatory cascade resulting in the damage of small sized blood vessels in various organs of the body, including the heart. Pleuropericardial involvement is underrecognized as a complication of ANCA vasculitis and is highlighted in this case report of a 51-year-old male who presented with an initial symptomatic presentation of pleuropericardial effusion progressing to pericardial tamponade in the setting of a later renal biopsy proven pauci-immune crescentic glomerulonephritis with high ANA titres along with positive cANCA (cytoplasmic ANCA) and PR3 (proteinase 3) antibodies. He was found to have acute renal failure which progressively got better with cyclophosphamide.
Physical, chemical and biological enhancement in X-ray nanochemistry

X-ray nanochemistry studies how to use nanomaterials and particularly how to create new nanomaterials to increase the effects of X-rays such as chemical reactivity, damage to cells, tumor destruction, scintillation and more. The increase, also called enhancement, can be categorized into several groups, and the current categorization of enhancement follows a natural division of physical, chemical and biological enhancement based on how nanomaterials behave under X-ray irradiation. In physical enhancement, electrons released from atoms in the nanomaterials upon X-ray ionization interact with the nanomaterials and surrounding media to increase the effects. Scintillation also belongs to this category. Chemical enhancement results when reactive oxygen species (ROS) or reactive radical intermediates (RRI) produced in aqueous solutions under X-ray irradiation interact with the surface of catalytic nanomaterials to increase the effects. When the damage of cells is enhanced through biological pathways beyond the abovementioned physical or chemical enhancement due to the presence of nanomaterials under X-ray irradiation, the enhancement is called biological enhancement. Works supporting this systematic categorization, the reported values of these enhancements, and important aspects of the development of enhancement in the X-ray nanochemistry framework are given and discussed in this perspective.
Beyond 1 Tb/s Intra-Data Center Interconnect Technology: IM-DD OR Coherent?

We discuss technology options and challenges for scaling intra-datacenter interconnects beyond 1 Tb/s bandwidths, with focus on two possible approaches: pulse amplitude modulation (PAM)-based intensity modulation-direct detection (IM-DD) and baud-rate sampled coherent technology. In our studies, we compare the performance of various orders of PAM modulation (PAM4 to 8). In addition to these fixed PAM signaling options, a flexible PAM (FlexPAM) technique leveraging granularity in spectral efficiency (SE) is proposed to maximize link margin. For baud-rate sampled coherent technology, we propose a simplified digital signal processing (DSP) architecture to bring down power consumption of the coherent approach closer to that of IM-DD PAM. We also propose two new phase noise tolerant 2D coherent modulation formats to relax the laser linewidth requirement. In closing, a comparative study of fixed IM-DD PAM versus coherent polarization multiplexed-quadrature amplitude modulation (PM-QAM) is presented for a 1.6 Tb/s solution (200 Gb/s per dimension), with consideration of link loss/reach budget, power consumption, implementation complexity, as well as fan-out granularity.
The Effect of Ethnicity in the Rate of Beta-Cell Functional Loss in the First 3 Years After Type 1 Diabetes Diagnosis.

Objective We set forth to compare ethnicities for metabolic and immunological characteristics at the clinical diagnosis of type 1 diabetes (T1D) and assess the effect of ethnicity on beta-cell functional loss within 3 years after clinical diagnosis. Research methods and design We studied participants in TrialNet New Onset Intervention Trials (n = 624, median age = 14.4 years, 58% male, 8.7% Hispanic) and followed them prospectively for 3 years. Mixed meal tolerance tests (MMTT) were performed within 6 months following clinical diagnosis and repeated semiannually. Unless otherwise indicated, analyses were adjusted for age, sex, BMI Z-score, and diabetes duration. Results At T1D clinical diagnosis, Hispanics, compared with non-Hispanic whites (NHW), had a higher frequency of diabetic ketoacidosis (DKA) (44.7% vs 25.3%, OR = 2.36, P = 0.01), lower fasting glucose (97 vs 109 mg/dL, P = 0.02) and higher fasting C-peptide (1.23 vs 0.94 ng/mL, P = 0.02) on the first MMTT, and higher frequency of ZnT8 autoantibody positivity (n = 201, 94.1% vs 64%, OR = 7.98, P = 0.05). After exclusion of participants in experimental arms of positive clinical trials, C-peptide area under the curve (AUC) trajectories during the first 3 years after clinical diagnosis were not significantly different between Hispanics and NHW after adjusting for age, sex, BMI-z score, and DKA (n = 413, P = 0.14). Conclusion Despite differences in the metabolic and immunological characteristics at clinical diagnosis of T1D between Hispanics and NHW, C-peptide trajectories did not differ significantly in the first 3 years following clinical diagnosis after adjustment for body mass index and other confounders. These findings may inform the design of observational studies and intervention trials in T1D.
Real Feedback from Real People: Emphasizing User-Centric Designs for Court ODR

As online dispute resolution (ODR) systems become increasingly popular and prevalent, especially for court cases, those of us considering and setting standards for ODR find ourselves wondering what users really need and want from this new technology. We all know about guidelines in other dispute resolution realms – the importance of avoiding bias and providing a fair process, for example – but how can we set standards for court ODR that encompass those ideals and actually help people who use the system? This question of court ODR standards is one that prompts considerable debate. At a discussion at the recent International Online Dispute Resolution Forum in Williamsburg, Virginia, panelists acknowledged that analogous professional standards and best practices can provide a helpful starting point for ethical design of ODR. However, barometers such as “impartial” and “fair” do not fully guide system design at the user level. That inspired us to think we should seek real feedback from real people on everything from the look and feel of a system to the availability of live assistance while using it. The point on the panel – and our point in this article – is that ODR standards or best practices should never stray far from what the users of ODR might expect from a platform they are required to use to conduct justice-related business. With this in mind, we propose a methodology of standards creation in one question: what would our families, friends, and next-door neighbors expect from an ODR system?
Therapeutic Hypothermia Improves Long-Term Survival and Blunts Inflammation in Rats During Resuscitation of Hemorrhagic Shock.

We tested the hypothesis that therapeutic hypothermia (TH) improves survival and blunts inflammation in rats undergoing experimental hemorrhagic shock. Rats were randomized to TH (n = 16) or normot...
Humans vs. Bots: investigating models of behavior in the iterated Prisoner’s dilemma

We present an approach to studying human behavior in the Iterated Prisoner's Dilemma (IPD) game, where human participants play against software bots in an online environment. This setting allows precise control of the strategies faced by the human subjects. Our goal is to test models of human behavior and the means by which cooperation can be promoted. Results from our experiments with subjects from Amazon Mechanical Turk show that the leading models of human behavior in the IPD are incomplete, as they can explain our data only partially. We propose a new model of behavior, Majority Wins, which provides a better fit to the data, which we test and demonstrate through a simulation.
The Perfect Storm: Rapid Progression of Diabetic Ketoacidosis in Pediatric Diabetes in the Setting of COVID-19.

Abstract Objective The coronavirus disease 2019 (COVID-19) pandemic has introduced countless challenges to the medical field. Although pediatric patients have been reported to have lower rates of COVID-19 mortality, the presence of pre-existing conditions can heighten the severity of their clinical presentation. This report discusses the potential influence COVID-19 might have on diabetic ketoacidosis. Methods Our patient, a 6-year-old girl with known type 1 diabetes, presented with acute onset of abnormal breathing and altered mental status. The day prior, she had 1 episode of emesis, diarrhea, and abdominal pain but no fever. She presented to an outside hospital and was reported to have agonal breathing with a Glasgow Coma Scale score of 8 (eyes open to pain, no verbal response to stimuli, and localized pain). She was promptly intubated, and the initial laboratory tests revealed severe diabetic ketoacidosis (DKA). A family member had COVID-19, and she also tested positive for COVID-19. Results Our patient’s rapid progression and severity of illness require a discussion of how COVID-19 might affect diabetes and indicate opportunities for improving clinical practice in children with pre-existing diabetes. We discussed how COVID-19 might change the underlying pathophysiology of DKA and cause metabolic complications. Possible mechanisms include binding to angiotensin-converting enzyme 2 receptors and enabling a proinflammatory “cytokine storm.” Additionally, ketoacidosis and altered mental status have been present in patients with COVID-19 without diabetes, which might potentiate the symptoms in developing DKA. Conclusion Prompt recognition of DKA is warranted, as caregivers may attribute the symptoms to COVID-19 rather than to DKA, resulting in an increased severity of illness on presentation with acute symptom onset, as described in this report.
Minimum 2-year outcomes of reverse total shoulder arthroplasty for fracture: how does acute arthroplasty compare with salvage?

Abstract Background The objective of our study was to compare patient-reported outcome measures, range of motion, complication rates, and reoperation rates following rTSA for proximal humerus fracture between patients treated acutely ( 30 days following injury), those treated after initial nonoperative treatment (> 30 days following injury), and those treated after failed ORIF. Secondarily, we aimed to identify any patient-, injury-, or surgery-related factors independently associated with our response variables. Methods Between January 2003 to August 2018 we identified 576 patients who sustained a proximal humerus fracture treated with primary or revision shoulder arthroplasty. The final cohort included 153 patients. Multivariable analysis was used to assess whether explanatory variables were associated with our response variables. Results Initial nonoperative treatment compared to acute rTSA was associated with worse SSV (p=0.04), SPADI (p=0.03), and SPADI-disability subscale (p=0.03) scores. Only depression was independently associated with worse VAS-pain (p=0.04) scores. There was no significant difference in postoperative range of motion among the initial treatment groups. Older age was associated with decreased range of motion in all planes. Additionally, ipsilateral upper extremity injury was associated with decreased active abduction (p=0.03) and cemented humeral stem was associated with decreased passive abduction (p=0.03). Initial nonoperative treatment was associated with increased complications (OR 3.65, 95% CI 1.11-12.01) and male sex was associated with higher rates of reoperation (OR 3.53, 95% CI 1.31-9.51). Conclusions Patients who undergo initial periods of nonoperative management have worse functional outcomes and higher complication rates than those who undergo acute rTSA for proximal humerus fractures. Patient who undergo rTSA after failed ORIF have no difference in patient reported outcomes when compared to those who undergo acute rTSA. In addition, male patients are at higher risk of reoperation, while older patients are at risk for decreased range of motion. Patients with preoperative depression are at risk for increased pain at 2 years after surgery Level of Evidence Level III; Retrospective Cohort Comparison; Treatment Study