cssi/SciSciGPT-SciSciNet huggingface dataset:
Pipe Dreams: Tapping into the Health Information in Our Sewers

Most of us have an attitude of “flush it and forget it,” but to scientists like Rolf Halden, our waste is a bonanza of valuable information on population-level chemical exposures. Halden is an environmental scientist at Arizona State University’s Biodesign Institute, where he maintains the National Sewage Sludge Repository—a collection of hundreds of samples of raw sewage and sludge collected from more than 200 sites around the United States.1 The sample bottles are filled with a brownish-black slurry derived from raw sewage, “so it has everything that is flushed down the toilet,” says Arjunkrishna Venkatesan, a postdoctoral research associate on Halden’s team. “If you collect samples from sewerage manholes, sampling equipment is going to get clogged, and you’re going to have hair, condoms, and all sorts of stuff.” The laboratory staff filter out most of those solids, then freeze the samples for storage. The emerging field of sewage chemical-information mining is taking advantage of a readily available yet underappreciated resource: the untreated waste flowing under our feet and the biosolids remaining after treatment. It turns out that sewage and sewage ... As disgusting as the samples may be, the repository is helping to open up a field known broadly as sewage chemical-information mining (SCIM). This field is using the sewage destined for wastewater treatment plants as a medium for chemical exposures within a community, exposures that are impractical to measure by other means. Other studies are looking at sewage sludge (the solids that remain after wastewater treatment) for information on chemicals that can accumulate in the human body. Still another approach, known as BioSCIM, measures biomarkers in sewage as a way to assess the overall health status of communities. SCIM initially took off in 2001 when scientists hypothesized they could measure the metabolites of illicit drugs like cocaine, heroin, and methamphetamine in untreated wastewater collected from city sewers.2 This particular application of SCIM was originally known as “sewage epidemiology.” The success of this technique has been tested in Europe3,4 and most recently provided per capita estimates of drug usage in cities including Antwerp, Stockholm, and London.5 Now sewage epidemiology is being applied to substances beyond illicit drugs. Since 2010 Halden has published nearly 50 papers on the subject. One study calculated per capita chemical consumption and, based on levels found in sewage sludge, estimated exposure to more than 70 pharmaceuticals and other chemicals used in consumer products.6 “This work lets us put a finger on the chemical pulse of a nation,” Halden says.
Investigation of the knowledge,attitude and practice of patients with diabetes mellitus and assessing the effects of health intervention in a rural community

Objective To investigate the health knowledge of patients with type 2 diabetes mellitus(T2DM),to assess the effects of intervention and to provide a model of health education.Methods Four hundred patients with T2DM selected randomly from the diabetes data library of a rural areas in 2006 served as intervention group and 562 cases with T2DM from other area served as control group.The investigation was performed by questionnaire and measurement of height,weight,waistline,hipline,FPG and glycolated hemoglobin.The health education,diet intervention and behavior intervention were conducted in intervention group for one year.Results After intervention,the awareness about "population with T2DM high risk,harm of T2DM and criteria of T2DM" in intervention group was significantly higher than that in control group(P0.05);the awareness about "advantageous of anti-obesity to the controlling blood glucose,the confidence in controlling blood glucose" in intervention group was significantly higher than that in control group(P0.05);the blood glucose level of intervention group was(7.46±2.31) mmol/L,which was significantly lower than that[(8.20±1.90) mmol/L] of control group(P0.05).Conclusion Comprehensive health intervention could improve the health knowledge level,confidence of controlling T2DM and reduce blood glucose level in patients with T2DM.
Intriguing Optoelectronic Properties of Metal Halide Perovskites

A new chapter in the long and distinguished history of perovskites is being written with the breakthrough success of metal halide perovskites (MHPs) as solution-processed photovoltaic (PV) absorbers. The current surge in MHP research has largely arisen out of their rapid progress in PV devices; however, these materials are potentially suitable for a diverse array of optoelectronic applications. Like oxide perovskites, MHPs have ABX3 stoichiometry, where A and B are cations and X is a halide anion. Here, the underlying physical and photophysical properties of inorganic (A = inorganic) and hybrid organic–inorganic (A = organic) MHPs are reviewed with an eye toward their potential application in emerging optoelectronic technologies. Significant attention is given to the prototypical compound methylammonium lead iodide (CH3NH3PbI3) due to the preponderance of experimental and theoretical studies surrounding this material. We also discuss other salient MHP systems, including 2-dimensional compounds, where rele...
A dynamic single photon emission computed tomography myocardial perfusion imaging protocol using a 4D spatiotemporal iterative reconstruction

Myocardial perfusion imaging (MPI) has historically been and continues to be primarily performed using single photon emission computed tomography (SPECT). However, dynamic MPI is the domain of cardiac positron emission tomography (PET), due to its intrinsically higher sensitivity and ring scanner geometry that allows stationary tomographic acquisition, which circumvent limitations typical SPECT scanners have. Spatiotemporal dynamic SPECT reconstruction algorithms that can be used for rotational SPECT systems have shown promise in overcoming these limitations. We have implemented a continuously rotating and acquiring rest/stress cardiac MPI dynamic SPECT protocol using a GE Infinia Hawkeye 4 SPECT/CT scanner for an ongoing clinical research project. Our initial results demonstrate qualitatively improved images and higher contrast scores in regions-of-interest (ROIs) using dynamic reconstructions of the projection data compared with 3D reconstructions of the same data.
Intersex Management in the United States and Non-Western Cultures

In Western nations, there is growing agreement about ethical approaches to clinical intersex management. At the same time, as Western-trained physicians increasingly encounter intersex patients in other parts of the world, new ethical tensions arise. Which cultural values are fair parameters for gender-assignment decision-making, particularly in cultural milieus where there is social and economic inequality between the sexes? How can physicians uphold universal bioethical principles while remaining culturally sensitive? Physicians have a primary commit- ment to patient beneficence and universal human rights, requiring physicians to promote concordance between the child’s assigned gender and his or her likely future gender identity. Ultimately, the potential patient distress posed by gender dysphoria fundamentally outweighs the influence of local cultural factors such as economics, gender politics, and homophobia.
Characterization of a factor-dependent acute leukemia cell line with translocation (3;3)(q21;q26)

A strictly factor-dependent cell line (UCSD/AML1) was established from a patient with the syndrome of multilineage acute leukemia with high platelets. The patient's cells and the cell line karyotype were 45,XX,-7,t(3;3)(q21;q26), typical of the syndrome of acute leukemia with high platelets. The cell line expresses CD34, CD7, TdT, and myeloid (CD13, CD14, CD33) and megakaryocyte/platelet (CD36, CD41, CD42b, CDw49b) antigens. In short-term culture, UCSD/AML1 cells proliferate in response to interleukin-3 (IL-3), IL-4, IL-6, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage CSF (GM-CSF), but not IL-1, IL-2, IL-5, or G-CSF. In long-term culture, proliferation can be sustained by GM-CSF, IL-6, or M-CSF. When maintained in GM-CSF, a small percentage of cells form multinucleated megakaryocyte-like giant cells. Culture with GM-CSF combined with IL-6, but not with IL-6 alone, increased giant cell formation fourfold to sevenfold. IL-6 alone or in combination with GM-CSF increased expression of platelet-related antigens. In contrast, culture with phorbol ester induced formation of macrophage-like cells. UCSD/AML1 is the first human acute nonlymphocytic leukemia cell line established from a patient with an acute leukemia syndrome associated with a specific chromosome abnormality.
Paraplegia After Endovascular Repair of Abdominal Aortic Aneurysm

This is an ischemic condition of the spinal cord resulting in paraplegia 3 weeks after endovascular repair of an abdominal aortic aneurysm (AAA)
LIBXSMM: accelerating small matrix multiplications by runtime code generation

Many modern highly scalable scientific simulations packages rely on small matrix multiplications as their main computational engine. Math libraries or compilers are unlikely to provide the best possible kernel performance. To address this issue, we present a library which provides high performance small matrix multiplications targeting all recent x86 vector instruction set extensions up to Intel AVX-512. Our evaluation proves that speed-ups of more than 10 x are possible depending on the CPU and application. These speed-ups are achieved by a combination of several novel technologies. We use a code generator which has a built-in architectural model to create code which runs well without requiring an auto-tuning phase. Since such code is very specialized we leverage just-in-time compilation to only build the required kernel variant at runtime. To keep ease-of-use, overhead, and kernel management under control we accompany our library with a BLAS-compliant frontend which features a multi-level code-cache hierarchy.
Restrictive versus liberal red blood cell transfusion strategy after hip surgery: a decision model analysis of healthcare costs.

BACKGROUND Red blood cell transfusion related to select surgical procedures accounts for approximately 2.8 million transfusions in the United States yearly and occurs commonly after hip fracture surgeries. Randomized controlled trials have demonstrated lack of clinical benefit with higher versus lower transfusion thresholds in postoperative hip fracture repair patients with cardiac disease or risk factors for cardiac disease. The economic implications of a higher versus lower hemoglobin (Hb) threshold have not yet been investigated. STUDY DESIGN AND METHODS A decision tree analysis was constructed to estimate differences in healthcare costs and charges between a Hb transfusion threshold strategy of 8 g/dL versus 10 g/dL from the perspective of both Centers for Medicare and Medicaid Services (CMS) as well as hospitals. Secondary outcome measures included differences in transfusion-related adverse events. RESULTS Among the 133,697 Medicare beneficiaries undergoing hip fracture repair in 2012, we estimated that 45,457 patients would be anemic and at risk for transfusion. CMS would save an estimated $11.3 million to $24.3 million in payments, while hospitals would reduce charges by an estimated $52.7 million to $93.6 million if the restrictive transfusion strategy were to be implemented nationally. Additionally, rates of transfusion-associated circulatory overload, transfusion-related acute lung injury, acute transfusion reactions, length of stay, and mortality would be reduced. CONCLUSIONS This model suggests that the uniform adoption of a restrictive transfusion strategy among patients with cardiac disease and risk factors for cardiac disease undergoing hip fracture repair would result in significant reductions in clinically important outcomes with significant cost savings.
Amplification of Stress in Flexible Steel Arches

A simplified method which is useful in solving problems pertaining to the amplification of stress in flexible steel arches has been devised. Only fundamental concepts are used; these are extended t...
Distribution of Subchondral Bone Puncture Strength in the Talus and Tibial Plafond: A Biomechanical Study.

We investigated talus and tibial plafond subchondral bone puncture strength based on surface location. Puncture tests of the subchondral bone were performed in 9 equal zones on the articular surfac...
Operating and Runtime Systems Challenges for HPC Systems

Future HPC systems will be characterized by extreme heterogeneity. We will see increasing heterogeneity in virtually every aspect of node architecture from computational engines to memory systems. We will see increasing heterogeneity in applications, including heterogeneity within applications (as previously independent applications are composed to build new applications). We will see increasing heterogeneity in system usage models; in some cases, the HPC system is not the most precious resource being managed. We will also see increasing heterogeneity in the shared services (e.g., storage and visualization systems) that are connected to HPC systems.All of this increasing heterogeneity is certain to create new challenges in the design and implementation of operating and runtime systems. There will be new kinds of resources to manage and many resource management tactics will be invented (and some re-discovered and adapted) to address the new heterogeneity. In essence, we will tacitly agree that the operating and runtime systems need to adapt to enable the inevitable integration of new technologies, applications, usage models, and shared services. While this agreement is critical for our ability to make incremental progress, we, as a community, must step back and ask the relevant question: Does the OS or runtime system bear the brunt of the adaptation, or will we be able to insist on changes in the technologies, applications, and environment? In the past decade, we have seen a similar tradeoff play out between the application teams and the architects of computational engines: how much floating point precision is required and how is this precision implemented? How can we define similar tradeoffs that are important in the design and implementation of operating and runtime systems?
Evaluation and optimization of reduction and alkylation methods to maximize peptide identification with MS-based proteomics

Mass spectrometry (MS) has become an increasingly important technique to analyze proteins. In popular bottom-up MS-based proteomics, reduction and alkylation are routine steps to facilitate peptide identification. However, incomplete reactions and side reactions may occur, which compromise the experimental results. In this work, we systematically evaluated the reduction step with commonly used reagents, i.e., dithiothreitol, 2-mercaptoethanol, tris(2-carboxyethyl)phosphine, or tris(3-hydroxypropyl)phosphine, and alkylation with iodoacetamide, acrylamide, N-ethylmaleimide, or 4-vinylpyridine. By using digested peptides from a yeast whole-cell lysate, the number of proteins and peptides identified were very similar using four different reducing reagents. The results from four alkylating reagents, however, were dramatically different with iodoacetamide giving the highest number of peptides with alkylated cysteine and the lowest number of peptides with incomplete cysteine alkylation and side reactions. Alkylation conditions with iodoacetamide were further optimized. To identify more peptides with cysteine, thiopropyl-sepharose 6B resins were used to enrich them, and the optimal conditions were employed for the reduction and alkylation. The enrichment resulted in over three times more cysteine-containing peptides than without enrichment. Systematic evaluation of the reduction and alkylation with different reagents can aid in a better design of bottom-up proteomic experiments.
Spatial orientation of the adult cochlea: rotation, tilt, and angle theta 3

Quantitative description in adult crania of (1) angular orientation of the basal turn of the cochlea relative to the sagittal (termed “rotation”) and Frankfort horizontal (termed “tilt”) planes, and angle theta 3 [angular relationship of the line defined by the cochlea’s spiral center and cochlear (round) window, to the cochlear window]; (2) orientation of the cochlea relative to the plane defined by the horizontal and vertical portions of the facial nerve; (3) orientation of the basal turn of the cochlea relative to the plane of the posterior semicircular canal; and (4) the association of these orientations with the extent of mastoid pneumatization. Postmortem material analysis. From 41 bequeathed anatomical ear-normal cadaveric cranial, high-resolution CT scans were performed of the five crania with the largest and the five with the smallest mastoids. Eleven points in three-dimensional Cartesian space were appointed and studied with the software program FIJI. The median angle values (and ranges) for right ears were: “rotation” 52° (range 47–61); and, “tilt” 84° (79–89). The planes of the cochlear basal turn and facial nerve approximated superimposition: median 15° (2–19). Angle theta 3 for right ears was median 40° (28–44). Bilateral symmetry was found for the relationships between the planes. However, no association of any planar relationship with mastoid pneumatization was suggested. Considering the range of angles found in clinically normal adult specimens, spatial orientation of the cochlea may explain some of the difficulties in implantation.
Characterizing stress corrosion cracking in stainless steel using nonlinear resonant ultrasound spectroscopy

During disposal, spent nuclear fuel rods are placed into stainless steel containers and may be stored this way for decades. In order to ensure there is as little radiation leakage as possible, the structure of the stainless steel needs to be evaluated and possible damage detected. In particular, one type of damage these containers are particularly susceptible to is stress corrosion cracking (SCC). Traditional (linear) evaluation methods can detect open cracks but often a closed portion of the crack extends further, compromising the air tight seal sooner. To this end, it has been proposed to use Nonlinear Resonant Ultrasound Spectroscopy (NRUS) to quantify the degree of cracking in a structure. In order to prove this concept, cylindrical 304L stainless steel rods were immersed in a heated 42% MgCl2 solution to induce SCC in an accelerated manner to simulate the damage that is likely to occur on the actual containers. The rods were removed after different lengths of exposure. NRUS measurements were then conducted for longitudinal modes in the rods.During disposal, spent nuclear fuel rods are placed into stainless steel containers and may be stored this way for decades. In order to ensure there is as little radiation leakage as possible, the structure of the stainless steel needs to be evaluated and possible damage detected. In particular, one type of damage these containers are particularly susceptible to is stress corrosion cracking (SCC). Traditional (linear) evaluation methods can detect open cracks but often a closed portion of the crack extends further, compromising the air tight seal sooner. To this end, it has been proposed to use Nonlinear Resonant Ultrasound Spectroscopy (NRUS) to quantify the degree of cracking in a structure. In order to prove this concept, cylindrical 304L stainless steel rods were immersed in a heated 42% MgCl2 solution to induce SCC in an accelerated manner to simulate the damage that is likely to occur on the actual containers. The rods were removed after different lengths of exposure. NRUS measurements were then con...
Attention Deficit Hyperactivity Disorder as a Social Disability: Characteristics and Suggested Methods of Treatment

The purpose of this paper was to examine and present attention deficit hyperactivity disorder (ADHD) as a social disability. The overall outcomes from the literature indicate how children with ADHD and social disability display similar behavior patterns (e.g., conduct disorders, attention problems, and difficulties in family functioning). Other difficulties found with ADHD children were low self-esteem, bad reputations among peers, conflicts in friendships, problems in social skills, and difficulty in overcoming self-centeredness in social skills. Early identification of social disability, however, may result in provision of preventative services, such as suggested parent and mentor methods, and maximization of the chances for positive experiences in school, extracurricular activities, and the neighborhood. These services are recommended, and success depends on effort and consistent implementation of procedures.
Falsification in History

Education — literally, the act of leading forward or out — has functioned alas, as an institution seeking to restrain rather than propel and to obscure rather than illuminate.
Application of the Nonlinear Harmonics Method to Continuous Measurement of Stress in Railroad Rail

The buildup of thermally induced compressive stress in continuously welded railroad rail [1,2] can result in track buckling (lateral displacement of the track over a distance of approximately 100 feet [3]) which can cause derailment of a passing train. Therefore, a direct stress measurement approach utilizing a probe which could be scanned continuously along the rail would be very valuable for surveying the state of rail stress to determine if a potentially unsafe condition exists. In the research described in this paper, the nonlinear harmonics (NLH) method was investigated as an approach for measuring stress in a railroad rail. Laboratory measurements were taken while the probe was scanned along the web of a 3-foot-long section of rail subjected to compressive stress in a loading machine. Approaches for reducing the effect of material property variations by using stress-induced anisotropy and spatial averaging of the data were also investigated and shown to be very promising.
Interventions to Prevent Sexual Violence

Historically, the majority of rape-prevention efforts have been directed at female college populations, primarily teaching avoidance and self-defense skills (Parrot, 1990). Little was known about adolescent dating and even less about sexual violence in adolescence. As knowledge of adolescent sexual assault advanced, primary prevention efforts expanded, and more programs began to target younger audiences. Developmentally, it makes sense to educate children about appropriate and inappropriate sexual behavior at the same time that their sexual identities are forming and their attitudes, beliefs, and behaviors toward romantic partners are beginning to develop. However, despite the data on adolescent sexual development suggesting that attitudes legitimizing sexual coercion may begin as early as age 12 years (Burkhart & Fromuth, 1991) and despite the fact the women aged 12–18 years experience a greater rate of sexual assault than any other age group (Bachman & Saltzman, 1995), the majority of research in the area of rape prevention has been conducted with college students (Brecklin & Forde, 2001; Schewe, 2002). Although most researchers in the field of sexual assault prevention work with college-age populations, the majority of prevention programs delivered by rape crisis centers and domestic violence agencies target students younger than 18 years of age (Schewe, 2004). This gap between research and practice must be addressed. Furthermore, nearly all sexual assault interventions and research have been directed at the level of the individual. More work and research needs to be directed at preventing violence at multiple levels of the social ecology. This chapter explores the research on sexual assault prevention, focusing on data from adolescent populations when possible, in an effort to define the state of the art in sexual assault prevention efforts for adolescents and young adults. The
What Anti-realism About Hinges Could Possibly Be

The paper addresses the issue of what epistemic anti-realism could possibly be in the context of “hinge epistemology.” According to this new epistemological trend, justification depends on evidence together with general background assumptions—for example, that there is an external world, that our sense organs are mostly reliable, that we are not the victims of persistent and lucid dreams, and so on. The paper then addresses two issues. First, whether these assumptions are arbitrary, as relativists would claim. Second, how we should conceive of their metaphysical status. It responds negatively to the first question and puts forward an anti-realist conception of hinges to respond to the latter. Central to the proposal is that the kind of truth that can be predicated of hinges is of a minimalist kind. The paper also explores the compatibility of minimalism about hinges’ truth and alethic pluralism.
Fibroblast growth factor 23 and α-Klotho co-dependent and independent functions.

Purpose of reviewThe current review examines what is known about the FGF-23/α-Klotho co-dependent and independent pathophysiological effects, and whether FGF-23 and/or α-Klotho are potential therapeutic targets.Recent findingsFGF-23 is a hormone derived mainly from bone, and α-Klotho is a transmembr
Relationship between Human Perception of Softness and Instrument Measurements

Softness, as a subjective perception, is difficult to define and quantify. For decades, panel tests have been used to judge differences in the softness of hygiene tissue samples. Panel tests can be a time-consuming and expensive process. A number of protocols have been developed to quantify the physical properties of tissues associated with softness. The Tissue Softness Analyzer (TSA) by Emtec has gained popularity in characterizing the physical properties of tissues associated with softness. The instrument was designed with softness in mind and attempts to simulate the touch of the human hand. There is currently no comprehensive study that compares the results from a TSA and human panel. In this work, panel tests were used to validate the performance of the TSA with bath tissue. It was determined that one component of the TSA measurements (TS7) linearly correlated with the panel results. Among all of the algorithms available for use with the TSA, the TP2 algorithm most accurately predicted the panel scores. The TSA performed better in predicting the softness of the samples that were dried with a conventional wet press or creped-through air-dryer.
Development of a real-time scattered radiation display for staff dose reduction during fluoroscopic interventional procedures

We have been working on the development of a Scatter Display System (SDS) for monitoring and displaying scatterrelated dose to staff members during fluoroscopic interventional procedures. We have considered various methods for such a display using augmented reality (AR) and computer-generated virtual reality (VR). The current work focuses on development of the VR SDS display, which shows the color-coded scattered dose distribution in a horizontal plane at a selected height above the floor in a top-down view of the interventional suite. Reported is the first development of the methodology for real-time functionality of this software via integration of controller area network (CAN) bus digital signals from the Canon C-Arm Biplane System. Importing the CAN bus information allows immediate selection of the appropriate pre-calculated scatter dose distribution consistent with the x-ray beam orientation and characteristics as well as selection of the proper gantry and table graphic for the display. The Python CAN interface module was used for streamlining the integration of the CAN bus interface. Development of real-time functionality for the SDS allows it to provide feedback to staff during clinical procedures for informed dose management; the SDS can work alongside the patient skin dose tracking system (DTS) for complete clinical monitoring of staff and patient dose.
Characteristics of Patients Discontinuing Care

Objectives: Due to lower fees, dental school clinics (DSCs) may provide dental care for vulnerable populations. This study evaluates factors associated with patients deciding to discontinue care at a DSC. Methods: This is a retrospective analysis of a patient transfer form that was implemented to smooth transition of a patient when their student provider graduated. Forms provided deidentified information about characteristics and unmet dental needs. Descriptive and bivariate statistics were used to identify associations between patient characteristics and deciding to continue treatment in the student practice. Results: Of 1894 patients, 73.4% continued care. Financial limitations were most commonly reported as the reason for discontinuing care (30.1%). Patients speaking a language other than English or who had reported financial barriers were significantly less likely to continue care. Conclusions: Dental school patients from vulnerable groups are more likely to discontinue care. Dental schools should implement programs that will assist patients in maintaining a dental home.
Evaluation of Bioequivalence of Highly Variable Drugs Using Monte Carlo Simulations. I. Estimation of Rate of Absorption for Single and Multiple Dose Trials Using Cmax

Purpose. A Monte Carlo simulation study was done to investigate the effects of high intrasubject variation in clearance (CL), and volume of distribution (V) on the calculation of the 90% confidence interval (CI) for Cmax for single dose and multiple dose studies. Methods. Simulations were done for both immediate release and sustained release scenarios. The simulated data were compared with clinical data from bioequivalence studies performed on indomethacin and verapamil. Results. Previous reviews and simulations have shown that the probability of failure for the Cmax for single dose studies was always greater than that for multiple dose studies. However, the results for the simulated scenarios currently investigated indicate that if intrasubject (period-to-period) variation in CL and V is high (% CV's above 25%, and 12%, respectively), multiple dose studies can exhibit a higher probability of failure for Cmax than do single dose studies. Furthermore, Cmax values from studies performed with a sustained release scenario are more sensitive to changes in Ka, CL, and V than are results of studies on immediate release products. As an example, the probability of failure for immediate release products in simulated single dose studies is about 11% and 21% when the mean difference in Ka is 10% and 20%, respectively; while, the probability of failure for multiple dose studies is about 36% regardless of the difference in Ka. The corresponding values for the probability of failure for sustained release products were 25%, 53% for single dose studies and 39% for multiple dose studies. The simulations also indicate that changes in the fraction absorbed have a greater effect on the estimation of Cmax in multiple dose regimens than in single dose studies. Conclusions. The results from these investigations indicate that multiple dose studies do not necessarily always reduce variability in Cmax.
Regulator of G-protein signaling (RGS) proteins as drug targets: Progress and future potentials.

G protein–coupled receptors (GPCRs) play critical roles in regulating processes such as cellular homeostasis, responses to stimuli, and cell signaling. Accordingly, GPCRs have long served as extraordinarily successful drug targets. It is therefore not surprising that the discovery in the mid-1990s of a family of proteins that regulate processes downstream of GPCRs generated great excitement in the field. This finding enhanced the understanding of these critical signaling pathways and provided potentially new targets for pharmacological intervention. These regulators of G-protein signaling (RGS) proteins were viewed by many as nodes downstream of GPCRs that could be targeted with small molecules to tune signaling processes. In this review, we provide a brief overview of the discovery of RGS proteins and of the gradual and continuing discovery of their roles in disease states, focusing particularly on cancer and neurological disorders. We also discuss high-throughput screening efforts that have led to the discovery first of peptide-based and then of small-molecule inhibitors targeting a subset of the RGS proteins. We explore the unique mechanisms of RGS inhibition these chemical tools have revealed and highlight the most up–to–date studies using these tools in animal experiments. Finally, we discuss the future opportunities in the field, as there are clearly more avenues left to be explored and potentials to be realized.
Risk Prediction Accuracy Differs for Transferred and Nontransferred Emergency General Surgery Cases in the ACS-NSQIP.

Abstract Background Risk prediction accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Surgical Risk Calculator has been shown to differ between emergency and elective surgery. Benchmarking methods of clinical performance require accurate risk estimation, and current methods rarely account for admission source; therefore, our goal was to assess whether the ACS-NSQIP predicts mortality comparably between transferred and nontransferred emergency general surgery (EGS) cases. Materials and methods This is a retrospective study using the ACS-NSQIP database from 2005 to 2014including all inpatients who underwent one of seven previously described EGS procedures. The admission source was classified as directly admitted versus transferred from an outside emergency room or an acute care facility. We compared the accuracy of ACS-NSQIP–predicted mortality probabilities using the observed-to-expected (O:E) ratio and Brier score. A subgroup analysis was performed to compare accuracy of high-risk and low-risk procedures. Results A total of 206,103 EGS admissions were identified, of which 6.97% were transfers. Overall mortality was 3.26% for the entire cohort and 10.24% within the transfer group. The O:E ratios generated by ACS-NSQIP models differed between transferred patients (O:E = 1.0, 95% confidence interval = 0.97-1.02) and nontransferred patients (O:E = 1.12, 95% confidence interval = 1.09-1.14). The Brier score for transferred patients was greater than that for nontransferred patients (0.063 versus 0.018, respectively) showing higher accuracy for nontransferred patients. Conclusions The ACS-NSQIP risk estimates used for benchmarking differ between transferred and nontransferred EGS cases. Analyses of the Brier score by the ACS-NSQIP risk calculator demonstrated inferior prediction for transferred patients. This increased burden on accepting institutions will have an impact on quality metrics and should be considered for benchmarking of clinical performance.
Thermally Gated Bio-orthogonal Nanozymes with Supramolecularly Confined Porphyrin Catalysts for Antimicrobial Uses

Summary Bio-orthogonal catalysis has the capability of localized generation of imaging and therapeutic molecules in vitro and in vivo. The integration of these catalysts into thermoresponsive nanoparticle platforms would generate bio-orthogonal “nanozymes” that could be controlled through endogenous or exogenous thermal control. We have fabricated thermoresponsive nanozymes by confining supramolecular assemblies of porphyrins into the monolayer of gold nanoparticles. The resulting nanodevices feature an on-off gated thermal response occurring over a 3°C range with commensurate tunability of activation temperature from 25°C to 37°C. Reversible activation of catalysis was demonstrated in complex biological environments, and the efficacy of bi-stable thermoresponsive nanozymes demonstrated through thermal activation of antibiotic-based prodrugs to effectively treat bacterial biofilms.
The Construction of a Patrician Heritage and of Calumny: Vicente Lecuna, La Casa Natal, El Archivo del Libertador, and the Bolivarian Society

The case of Vicente Lecuna is central to the story of Bolivar in Venezuela’s public sphere. Like Blanco Fombona, Lecuna had before him a political tradition defined by the fact of the dictatorship of Gomez as well as by Gil Fortoul and Vallenilla Lanz, both of whom promoted authoritarian government by attacking the purported empty constitutionalism of the elites. But Lecuna, who supported republican government and had his own experience on the military and political battlefield, did not follow the path of a Blanco Fombona, a Larrazabal, or a Nicanor Bolet Peraza. Becoming the symbol of conservativism, Lecuna quietly defended his ideas, determined to change the country from within through what he saw as his contributions as a citizen, a civilian, rather than a governmental official. His vision of liberalism was certainly different from that of the three intellectuals named, but for exiles he would be an ally.
Ten Facts about UV Radiation and COVID-19

The COVID-19 pandemic has generated interest in the potential of ultraviolet (UV) radiation to disinfect air and surfaces. In response, the IES Photobiology Committee published a freely available r...
Preliminary evidence for virtue as a cue to long-term mate value

Abstract Selecting a long-term romantic partner is largely contingent upon identifying behavioral repertoires indicating an ability to foster individual and communal flourishing through benevolence and relational fidelity. Within this suite of socially desirable traits are virtues that could be critical in selecting long-term mates. The current program of research presents two studies investigating the extent people select mates embodying virtue. Study 1 tasked participants with indicating the desirability of prospective mates espousing high and low levels of the three fundamental virtues, as observed through the VIA Model: caring, self-control, and inquisitiveness. High levels of virtue were especially desirable for long-term mating, with the preference for self-control being largest. Study 2 considered dispositional preferences for long-term mating, as indexed through restricted sociosexuality, with sociosexually restricted individuals reporting aversion to prospective mates exhibiting low self-control. We frame results through an evolutionary context and recommend future research to understand the adaptive function of virtue.
Chemosensory Searching by Rattlesnakes During Predatory Episodes

Striking rodent prey is a prerequisite for chemosensory searching (prey trailing using the tongue — Jacobson’s organ system) in rattlesnakes. High tongue flick rates occur after striking prey but not after seeing, smelling or detecting thermal cues arising from a rodent. At least two consequences of striking appear to be involved in the activation of chemosensory searching: (1) proprioception arising from the biomechanical aspects of the strike, and (2) chemical input to the vomeronasal organs concomitant with the strike. These two effects seem to be additive.
SUMO-Modification of Human Nrf2 at K 110 and K 533 Regulates Its Nucleocytoplasmic Localization, Stability and Transcriptional Activity.

Background/aims Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element(s) (ARE) in target gene promoters, enabling oxidatively stressed cells to respond in order to restore redox homeostasis. Post-translational modifications (PTMs) that mediate activation of Nrf2, in the cytosol and its release from Keap1, have been extensively studied but PTMs that impact its biology after activation are beginning to emerge. In this regard, PTMs like acetylation, phosphorylation, ubiquitination and sumoylation contribute towards the Nrf2 subcellular localization, and its transactivation function. We previously demonstrated that Nrf2 traffics to the promyelocytic leukemia-nuclear bodies (PML-NB), where it is a target for modification by small ubiquitin-like modifier (SUMO) proteins (sumoylation), but the site(s) for SUMO conjugation have not been determined. In this study, we aim to identify SUMO-2 conjugation site(s) and explore the impact, sumoylation of the site(s) have on Nrf2 stability, nuclear localization and transcriptional activation of its target gene expression upon oxidative stress. Methods The putative SUMO-binding sites in Nrf2 for human isoform1 (NP_006155.2) and mouse homolog (NP_035032.1) were identified using a computer-based SUMO-predictive software (SUMOplot™). Site-directed mutagenesis, immunoblot analysis, and ARE-mediated reporter gene assays were used to assess the impact of sumoylation on these site(s) in vitro. Effect of mutation of these sumoylation sites of Nrf2 on expression of Heme Oxygenase1 (HO-1) was determined in HEK293T cell. Results Eight putative sumoylation sites were identified by SUMOplot™ analysis. Out of the eight predicted sites only one 532LKDE535 of human (h) and its homologous 524LKDE527 of mouse (m) Nrf2, exactly matches the SUMO-binding consensus motif. The other high probability SUMO-acceptor site identified was residue K110, in the motifs 109PKSD112 and 109PKQD112 of human and mouse Nrf2, respectively. Mutational analysis of putative sumoylation sites (human (h)/mouse (m) K110, hK533 and mK525) showed that these residues are needed for SUMO-2 conjugation, nuclear localization and ARE driven transcription of reporter genes and the endogenous HO-1 expression by Nrf2. These residues also stabilized Nrf2, as evident from shorter half-lives of the mutant protein compared to wild-type Nrf2. Conclusion Our findings indicate that SUMO-2 mediated sumoylation of K110 and K533 in human Nrf2 regulates in part its transcriptional activity by enhancing its stabilization and nuclear localization.
Robotic navigation system utilization for percutaneous sacroiliac screw placement: surgical setup and technique

Sacroiliac joint (SIJ) pathology is a common cause of significant pain and disability, and operative treatment consisting of SIJ fusion can be performed in cases where non-operative measures fail to provide sustained relief. Through the years, SIJ fusion has evolved from an open invasive procedure, to more recently, being performed through minimally invasive techniques. Intraoperative navigation systems and robotic guidance are becoming popularized for SIJ fusion, as well as other routine and complex spinal cases. The utility of navigation and robotics is the enhanced ability of the surgeon to place instrumentation more accurately, with less dissection, blood less, and overall operative time. We present a technique guide for robotic instrumented SIJ fusion with intraoperative navigation that we have put into practice at our institution and found to be very beneficial to patients for the above reasons. We describe the setup and utilization of these technologies intraoperatively, and provide specific case examples to highlight our technique. The described methods have been found to be effective and reproducible, allowing for minimally invasive SIJ screw placement with high accuracy and safety. We emphasize that utilizing intraoperative navigation and robotics is not meant to substitute for surgeon knowledge of case steps or anatomy, but rather to enhance safety and efficacy. To our knowledge, robotic SIJ fusion has not been previously described in the literature.
Intraparenchymal Fiber-Optic Intracranial Pressure Monitoring

Patients with neurological pathologies either have or are at risk for an increase in intracranial pressure. These patients benefit from close and invasive neurological monitoring. One proven way to directly monitor for increased intracranial pressure is by insertion of a fiber-optic pressure monitor directly into the brain parenchyma. Intracranial monitoring was first used over half a century ago to monitor for and to guide the treatment of intracranial hypertension. More recently, fiber-optic pressure monitors have become the most commonly used version of that tool. With few absolute contraindications, they can be placed in patients with a variety of neurologic insults that are known to cause increased intracranial pressure. Pathologies such as anoxic brain injury and traumatic brain injury and patients at risk for further neurologic decline while heavily sedated or paralyzed have all benefited from this type of invasive neurological monitoring. Placement can be done by properly trained advanced practice providers, at the bedside, safely and efficiently. By utilizing advanced practice providers, the resource burden on already minimal neurosurgical teams in the acute care setting can be decreased. This chapter will describe, in detail, the procedure, the indications, the contraindications, and the rationale for the procedure of the placement of a fiber-optic intracranial pressure monitor.
Effects of prepartum grouping strategy on immune, metabolic, health, reproductive, and productive parameters of dairy cows

Cows are social animals and as such are highly susceptible to social interactions and hierarchical order. Situations of limited space or access to feed and frequent regrouping during the prepartum period are expected to exacerbate aggressive and submissive behaviors. In studies conducted with a small number of cows per pen, cows had reduced feeding time, greater rate of displacement from the feed bunk and stalls, and reduced milk yield up to three to 14 days after regrouping. Therefore, weekly regrouping of prepartum dairy cows is expected to result in exposure of these cows to a continuous state of social unrest and stress during the most critical time of their lives. This abstract discusses results from a study in a commercial dairy that evaluated an 'All-In-All-Out' (AIAO) approach to regrouping prepartum cows.
Practical Benefits of Feature Feedback Under Distribution Shift.

In attempts to develop sample-efficient algorithms, researcher have explored myriad mechanisms for collecting and exploiting feature feedback, auxiliary annotations provided for training (but not test) instances that highlight salient evidence. Examples include bounding boxes around objects and salient spans in text. Despite its intuitive appeal, feature feedback has not delivered significant gains in practical problems as assessed on iid holdout sets. However, recent works on counterfactually augmented data suggest an alternative benefit of supplemental annotations: lessening sensitivity to spurious patterns and consequently delivering gains in out-of-domain evaluations. Inspired by these findings, we hypothesize that while the numerous existing methods for incorporating feature feedback have delivered negligible in-sample gains, they may nevertheless generalize better out-of-domain. In experiments addressing sentiment analysis, we show that feature feedback methods perform significantly better on various natural out-of-domain datasets even absent differences on in-domain evaluation. By contrast, on natural language inference tasks, performance remains comparable. Finally, we compare those tasks where feature feedback does (and does not) help.
The European Parliament and Supranational Party System: A Study in Institutional Development

This book examines the impact of increased legislative power and political authority on the internal development of the European Parliament and the supranational party group system. This is done through an analysis of changes in the hierarchical structures that regulate the internal organization of both the EP as a whole and the individual party groups. In addition, the changing pattern of coalition formation between party groups across time and legislative procedure is analyzed. The trends of internal development examined suggest that the increases in EP power that have occurred since the creation of the cooperation procedure by the Single European Act in 1987 have caused a fundamental shift in the character of the European Parliament as a legislative institution. Prior to 1987 the European Parliament, despite direct election and several small attempts to increase its powers, served primarily as a chamber of debate where much more was discussed than accomplished.