cssi/SciSciGPT-SciSciNet huggingface dataset:
Choosing Wisely: A Quality Improvement Initiative to Decrease Unnecessary Preoperative Testing

Dartmouth-Hitchcock Medical Center is a rural, academic medical center in the northeastern United States; its General Internal Medicine (GIM) division performs about 900 low and intermediate surgical risk preoperative evaluations annually. Routine preoperative testing in these evaluations is widely considered a low-value service. Our baseline data sample showed unnecessary testing rates of approximately 36%. A multi-disciplinary team used a micro-systems approach to analyze the existing process and formulate a rapid cycle improvement strategy. Our improvement efforts focused on implementation of a Nurse Practitioner and Physician Assistant (Associate Provider) clinic to incorporate standardized protocols for preoperative assessment. Plan-Do-Study-Act (PDSA) cycles included creation of a dedicated Associate Provider run preoperative clinic, modifying and operationalizing a scheduling scheme, and creating and implementing Electronic Health Record (EHR) tools. We used Statistical Process Control (SPC) methods to analyze time ordered data for the usual care process and to compare performance with the novel preoperative clinic. The Associate Provider preoperative clinic showed unnecessary testing rates of 4% compared with 23% in the usual care cohort (p<.001) within 3 months of implementation. When testing rates across the entire division were analyzed, there was no significant change. In our GIM division this preoperative clinic was effectively staffed with Associate Providers. Dedicated leadership support, incorporating input from a diverse improvement team, and balancing innovation with other clinical needs are important elements for success. We hypothesize that protecting clinical time to focus on preoperative care, monitoring and modifying scheduling processes, and improving support for electronic health record tool implementation would have yielded further performance improvements. Our experience provides valuable learning for other primary care practices with similar challenges. Identifying appropriate patients for inclusion in these clinic visits while optimizing primary care provider collaboration are important future challenges.
Goal Setting and Attainment and Self-regulation

Goal-oriented actions are critical in enabling people to act in a self-determined manner and to be causal agents in their lives. Self-regulation involves, in essence, various processes involved in attaining and maintaining goals. In this chapter, we provide a more in-depth look at self-regulation and goal-directed action using Causal Agency Theory as a framework and then examine what is known about promoting goal setting and attainment activities for people with intellectual and developmental disabilities.
Pseudomonas floridensis sp. nov., a bacterial pathogen isolated from tomato.

An unusual fluorescent pseudomonad was isolated from tomato exhibiting leaf spot symptoms similar to bacterial speck. Strains were fluorescent, oxidase- and arginine-dihydrolase-negative, elicited a hypersensitive reaction on tobacco and produced a soft rot on potato slices. However, the strains produced an unusual yellow, mucoid growth on media containing 5 % sucrose that is not typical of levan. Based on multilocus sequence analysis using 16S rRNA, gap1, gltA, gyrB and rpoD, these strains formed a distinct phylogenetic group in the genus Pseudomonas and were most closely related to Pseudomonas viridiflava within the Pseudomonas syringae complex. Whole-genome comparisons, using average nucleotide identity based on blast, of representative strain GEV388T and publicly available genomes representing the genus Pseudomonas revealed phylogroup 7 P. viridiflava strain UASW0038 and P. viridiflava type strain ICMP 2848T as the closest relatives with 86.59 and 86.56 % nucleotide identity, respectively. In silico DNA–DNA hybridization using the genome-to-genome distance calculation method estimated 31.1 % DNA relatedness between GEV388T and P. viridiflava ATCC 13223T, strongly suggesting the strains are representatives of different species. These results together with Biolog GEN III tests, fatty acid methyl ester profiles and phylogenetic analysis using 16S rRNA and multiple housekeeping gene sequences demonstrated that this group represents a novel species member of the genus Pseudomonas . The name Pseudomonas floridensis sp. nov. is proposed with GEV388T (=LMG 30013T=ATCC TSD-90T) as the type strain.
A Randomized Pharmacokinetic and Pharmacodynamic Evaluation of Every 8‐Hour and 12‐Hour Dosing Strategies of Vancomycin and Cefepime in Neurocritically ill Patients

Purpose Neurocritically ill patients have clinically significant alterations in pharmacokinetic parameters of renally eliminated medications that may result in subtherapeutic plasma and cerebrospinal fluid antibiotic concentrations. Methods We conducted a prospective randomized open-label study of adult neurocritically ill patients treated with vancomycin and cefepime. Vancomycin 15 mg/kg and cefepime 2 g were dosed at every-8- or 12-hour intervals. The primary outcomes were the achievement of pharmacodynamic (PD) targets related to time of unbound drug above minimum inhibitory concentrations (MIC) for 60% or more of the dosing interval (fT > MIC ≥ 60%) for β-lactams and ratio of 24-hour area under the curve (AUC):MIC of 400 or greater for vancomycin. Results Twenty patients were included in the study. They were divided equally between the every-12-hour and every-8-hour dosing groups. Patients (mean age 51.8 ± 11 yrs) were primarily male (60%) and white (95%), and most had an admission diagnosis of intracranial hemorrhage (80%). Compared with the every-12-hour group, the every-8-hour vancomycin group achieved target trough concentrations (higher than 15 μg/ml) significantly more frequently at initial measurement (0% vs 80%, p MIC ≥ 60%) at an MIC of 8 μg/ml (20% vs 70%, p=0.02). Conclusions This study demonstrated that more frequent dosing of vancomycin and cefepime is required to achieve optimal PD targets in adult neurocritically ill patients. The need for increased total daily doses is potentially secondary to the development of augmented renal clearance.
Duration of stretch does not influence the degree of force loss following static stretching.

Aim. There is an emerging body of knowledge indicating static stretching (SS) acutely and adversely affects muscle performance. The practical value of this research is limited considering the lengthy stretch durations under investigation. It is unclear if stretch durations typical of those used pre-exercise similarly affect muscle performance. The purpose of this study was to determine if SS using more representative stretch durations affects muscle performance and to establish if changes in muscle performance were influenced by the duration of stretch. Methods. Following 2 familiarization sessions, 16 recreationally trained males and females participated in 2 randomly ordered experimental sessions. In each session maximal effort hamstring performance was assessed prior to and immediately after 1 of 2 stretching protocols. During one of the protocols participants were required to hold each stretch for 15 s while stretch duration in the second protocol was 30 s. Both protocols consisted of 3 repetitions of 2 stretching exercises. A Kincom isokinetic dynamometer was used to assess hamstring performance during isometric, concentric, and eccentric actions. Results. For each of the three muscle actions a repeated measures ANOVA revealed a significant main effect of time pre- vs poststretch, P<0.05) but no interaction effect (time x SS protocol). Furthermore, the stretch-induced deficits in muscle performance were consistent across muscle action type. Conclusions. SS incorporating stretch durations typical of those employed pre-exercise were sufficient to impair muscle performance and the duration of stretch did not influence the degree of force loss. Inclusion of SS, even with short stretch durations, in preparation for strength activities is not appropriate.
Task Scheduling Algorithms for Fault Tolerance in Real-Time Embedded Systems

We survey scheduling algorithms proposed for tolerating permanent and transient failures in real-time embedded systems. These algorithms attempt to provide low-cost solutions to fault tolerance, graceful performance degradation, and load shedding in such systems by exploiting tradeoffs between space and/or time redundancy, timing accuracy, and quality of service. We place fault-tolerant scheduling algorithms in three broad categories: dynamic scheduling, off-line or static scheduling, and scheduling of imprecise computations. Under dynamic scheduling, we survey fault-tolerance extensions to the widely used rate-monotonic and earliest-deadline-first scheduling policies. We then discuss methods that provide fault tolerance in statically scheduled systems using precomputed alternate schedules or run-time rescheduling. We also discuss imprecise scheduling, which achieves a tradeoff between solution quality and timeliness. We conclude with a brief discussion of scheduling and fault-tolerance issues related to safety-critical embedded systems.
An ADP-glucose pyrophosphorylase with lower apparent affinities for substrate and effector molecules in an Escherichia coli B mutant deficient in glycogen synthesis

Abstract SG-14, a mutant strain of E. coli B that accumulates glycogen at one-half the rate observed for the parent strain, contains an altered ADP-glucose pyrophosphorylase with lower apparent affinities than that observed for the parent enzyme for its substrates, ATP and Mg2+ and for its effectors, fructose diphosphate, pyridoxal-P (PLP) and 5′adenylate. TPNH activates the native enzyme but not the mutant enzyme. In view of the reported physiological concentrations of ATP and Mg2+ and of the kinetic effects observed for FDP, PLP and AMP for the mutant enzyme, it is suggested that FDP is the important physiological activator for ADP-glucose pyrophosphorylase.
New molecular switch architectures

In this paper we elaborate on recently developed molecular switch architectures and how these new systems can help with the realization of new functions and advancement of artificial molecular machines. Progress in chemically and photoinduced switches and motors is summarized and contextualized such that the reader may gain an appreciation for the novel tools that have come about in the past decade. Many of these systems offer distinct advantages over commonly employed switches, including improved fidelity, addressability, and robustness. Thus, this paper serves as a jumping-off point for researchers seeking new switching motifs for specific applications, or ones that address the limitations of presently available systems.
Cortical subnetworks encode context of a visual stimulus

Cortical processing of sensory events is significantly influenced by context. For instance, a repetitive or redundant visual stimulus elicits attenuated cortical responses, but if the same stimulus is unexpected or deviant, responses are augmented. This contextual modulation of sensory processing is likely a fundamental function of neural circuits, yet an understanding of how it is computed is still missing. Using holographic two-photon calcium imaging in awake animals, here we identify three distinct, spatially intermixed ensembles of neurons in mouse primary visual cortex which differentially respond to the same stimulus under separate contexts, including a subnetwork which selectively responds to deviant events. These non-overlapping ensembles are distributed across layers 2-5, though deviance detection is more common in superficial layers. Contextual preferences likely arise locally since they are not present in bottom up inputs from the thalamus or top-down inputs from prefrontal cortex. The functional parcellation of cortical circuits into independent ensembles that encode stimulus context provides a circuit basis underlying cortically based perception of novel or redundant stimuli, a key deficit in many psychiatric disorders.
Toward Electrical Impedance Tomography Coupled Ultrasound Imaging for Assessing Muscle Health

This paper establishes for the first time that a coupled ultrasound (US) and electrical impedance tomography (EIT) system can serve as a non-invasive, spatially localized approach to extract clinically relevant muscle properties. The US/EIT system represents a potential enhancement to electrical impedance myography (EIM), which has shown promise as a non-invasive technology that may have important clinical use in indicating neuromuscular disease status and as a diagnostic tool. A 2.5D EIT algorithm evaluated on simulation, measured phantoms, and measured patient data was studied to evaluate US/EIT’s ability to distinguish different aspects of muscle tissue. Simulated and phantom experiments revealed the depths of distinguishability of 3.2 and 4.2 mm in simulation for 10% and 20% changes in muscle properties, respectively, and 3.6 mm in measured phantom experiments assuming a 12% muscle conductivity change. Reconstructions from the patient data established that there were consistent differences 1) between longitudinal (along) and transverse (across) muscle conductivity reconstructions at frequencies of 40 and 80 kHz and 2) side-by-side comparison between healthy and diseased tissue in terms of conductivity, permittivity, and phase at 40 and 80 kHz. Comparisons were made between the EIT reconstructed values and electrical impedance spectroscopy (EIS) measurements (an available surrogate in place of standard EIM measurements) made with the US/EIT system, wherein 1) EIS and EIT show similar sensitivity to longitudinal and transverse differences and 2) EIT showed a more consistent ability to differentiate healthy and diseased tissue. These results suggest that US/EIT appears very promising for non-invasive and spatially localized diagnosis of muscle health.
Warning, Bias May Occur: A Proposed Approach to Detecting Cognitive Bias in Interactive Visual Analytics

Visual analytic tools combine the complementary strengths of humans and machines in human-in-the-loop systems. Humans provide invaluable domain expertise and sensemaking capabilities to this discourse with analytic models; however, little consideration has yet been given to the ways inherent human biases might shape the visual analytic process. In this paper, we establish a conceptual framework for considering bias assessment through human-in-the-loop systems and lay the theoretical foundations for bias measurement. We propose six preliminary metrics to systematically detect and quantify bias from user interactions and demonstrate how the metrics might be implemented in an existing visual analytic system, InterAxis. We discuss how our proposed metrics could be used by visual analytic systems to mitigate the negative effects of cognitive biases by making users aware of biased processes throughout their analyses.
Staging biomarkers in preclinical autosomal dominant Alzheimer's disease by estimated years to symptom onset

Abstract Introduction Staging preclinical Alzheimer disease (AD) by the expected years to symptom onset (EYO) in autosomal dominant AD (ADAD) through biomarker correlations is important. Methods We estimated the correlation matrix between EYO/cognition and imaging/CSF biomarkers, and searched for the EYO cutoff where a change in the correlations occurred before and after the cutoff among the asymptomatic mutation carriers of ADAD. We then estimated the longitudinal rate of change for biomarkers/cognition within each preclinical stage defined by the EYO. Results Based on the change in the correlations, the preclinical ADAD was divided by EYOs −7 and −13 years. Mutation carriers demonstrated a temporal ordering of biomarker/cognition changes across the three preclinical stages. Discussion Duration of each preclinical stage can be estimated in ADAD, facilitating better planning of prevention trials with the EYO cutoffs under the recently released FDA guidance. The generalization of these results to sporadic AD warrants further investigation.
Trends in Single, Dual, and Poly Use of Alcohol, Cigarettes, and Marijuana Among US High-School Students: 1991-2017.

Objectives. To evaluate trends in patterns (single, dual, or poly) of current use of alcohol, cigarettes, and marijuana (ACM) among youths in the United States.Methods. I used data from the 1991–20...
Differential Contributions of Empathy to Math Achievement in Women and Men

Mathematics forms a foundation for the science, technology, engineering and mathematics (STEM) fields. While considerable work has identified the individual cognitive and external systemic factors that influence math achievement, less is known about personality-like traits that might contribute to success in mathematics, especially among women. This study examines two such traits: systemizing - the tendency to analyze systems and extract underlying rules that govern their behavior - and empathizing - the ability to identify with another's emotions and respond appropriately. Recently Escovar et al. (2016) found that empathizing was a negative predictor of math skills in children, especially among girls, suggesting that women with higher empathy might be particularly disposed to lower math performance. In the first study, 142 participants (71 female) completed two standardized measures of math achievement and questionnaires to gauge the tendency to empathize and systemize. Surprisingly, higher empathy was associated with better math performance in women, while men displayed the expected pattern of lower empathy being related to higher math scores. In a second study, we extend this finding in women (n = 121) to show that individuals who report higher mathematics achievement in university level course work also have higher empathy scores. Further, while positive attitudes toward mathematics tended to decline from elementary school to college, women whose attitudes increased had higher empathy scores than those who declined. Together, these results suggest that while the tendency to empathize is associated with worse math performance in childhood, it may become a protective factor as women progress through their mathematics education.
Social Isolation, Loneliness, and Mental and Emotional Well-being among International Students in the United States

Background: Loneliness and social isolation have the ability to affect an individual's mental and physical health. With research linking both to morbidity and premature mortality, their effects must be viewed as important public health problems. Loneliness and social isolation can be especially pronounced in the international student community, particularly at the university level, as this population encounters challenges assimilating to their host university, surrounding community, and host country. This study explores the risks and sociocultural factors associated with loneliness, social isolation, and psychological distress with regards to the overall adjustment of international students. Methods: In this qualitative, narrative case study, 10 international graduate students at a university in the United States participated in two focus group sessions followed by individual interviews. Thematic areas and topics were identified using Barrer's three models of social support. Study was completed between December 2016 and September 2017. Results: All of the participants shared that they had experienced loneliness and social isolation at some point during their acculturative process resulting in perceived xenophobia and a sense of insincerity on behalf of domestic students when attempting to forge connections. For some, these experiences elicited feelings of depression, a disinterest in building connections with domestic students, and in attending social events held on campus and within the community, further exacerbating feelings of loneliness and social isolation. Conclusions and Implications for Translation: Results shed light on the impact that poor acculturation can have on the student's mental and physical health and how bridges between the international and non-international communities can be built and more importantly, sustained. There is a critical need for more effort to be focused on attending to both the mental and physical health needs of migrant students during their stay at the host university. Key words: • Acculturation • Social Isolation • Loneliness • Mental Health • International • Student © 2019 Girmay and Singh. This is an open-access article distributed under the terms of the Creative Com- mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Blending of Probability and Non-Probability Samples: Applications to a Survey of Military Caregivers

Probability samples are the preferred method for providing inferences that are generalizable to a larger population. However, when a small (or rare) subpopulation is the group of interest, this approach is unlikely to yield a sample size large enough to produce precise inferences. Non-probability (or convenience) sampling often provides the necessary sample size to yield efficient estimates, but selection bias may compromise the generalizability of results to the broader population. Motivating the exposition is a survey of military caregivers; our interest is focused on unpaid caregivers of wounded, ill, or injured servicemembers and veterans who served in the US armed forces following September 11, 2001. An extensive probability sampling effort yielded only 72 caregivers from this subpopulation. Therefore, we consider supplementing the probability sample with a convenience sample from the same subpopulation, and we develop novel methods of statistical weighting that may be used to combine (or blend) the samples. Our analyses show that the subpopulation of interest endures greater hardships than caregivers of veterans with earlier dates of service, and these conclusions are discernably stronger when blended samples with the proposed weighting schemes are used. We conclude with simulation studies that illustrate the efficacy of the proposed techniques, examine the bias-variance trade-off encountered when using inadequately blended data, and show that the gain in precision provided by the convenience sample is lower in circumstances where the outcome is strongly related to the auxiliary variables used for blending.
Preliminary radiomic texture analysis of high-channel fluorescence confocal images of triple-negative breast cancer biopsies

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by a high level of inflammation. In this work, we present a computational method for assessing immune activity across many populations of immune cells. For this analysis, we have a dataset of 18 TNBC biopsies, each stained with a ‘strip-and-reprobe’ approach consisting of multiple rounds of staining and imaging the tissue. Each sample is stained with 8 separate antibody panels, resulting in ~20 different stains per sample, plus tissue autofluorescence images. Biopsy sections are imaged across a ~4mm x 5mm area on a Caliber ID confocal microscope with a pixel size of 221 nm, resulting in image composites of ~27,000x27,000x20 pixels per sample. Using radiomic texture analysis, we have analyzed a subset of these images to determine which texture features are predictive of inflammation. From 3 of these samples, we have selected inflamed and uninflamed regions of interest (ROIs) for three lymphocyte markers: 1) CD4, 2) CD3, and 3) CD8. We have computed 20 texture features, specifically gray level co-occurrence matrix features, for each of these 42 ROIs and their corresponding tissue autofluorescence images. From this analysis, we have found multiple features that successfully differentiate inflamed tissue from uninflamed tissue. These features will be calculated across the full dataset to analyze the overall TNBC immune architecture of these samples as diffuse or compartmentalized, and which cell populations tend to coaggregate.
Chapter 22 – Geothermal Energy

The word ‘Geothermal’ comes from the combination of the Greek words ge, meaning earth, and therm, meaning heat. This heat manifests itself on the surface in the form of volcanoes, geysers and hot springs. Geothermal resources are concentrations of the earth’s heat, or geothermal energy, that can be extracted and used economically now or in the reasonable future. The earth contains an immense amount of heat, but the heat generally is too diffuse or too deep for economic use. Hence, the search for geothermal resources focuses on those areas of the earth’s crust where geologic processes have raised temperatures near the surface such that the heat contained can be utilised. Currently, only concentrations of heat associated with water in permeable rocks can be exploited economically. These systems are known as hydrothermal–geothermal systems. This chapter will discuss where the earth’s thermal energy is sufficiently concentrated for economic use, the various types of geothermal systems, the production and utilisation of the resource and the environmental benefits and challenges of geothermal production.
Interdisciplinary Approach to Spationtemporal Population Dynamics. The North Orkney Population History Project

The North Orkney Population History Project is a multidisciplinary data collection, digitization, and analysis effort that aims to reconstruct longitudinal demographic, environmental, and economic change. We describe the motivation, methodological approach, data sources, and some initial findings of the project. Detailed contextual information about a single community allows for the joint analysis of the changing population and changing landscape. The combination of diverse data sources and disciplinary approaches has resulted in findings that would not have been possible if each source had been considered in isolation. The approach adopted by the project offers a way to examine the interaction of a population with its landscape over a period of change.
Uterine Gpr83 mRNA is highly expressed during early pregnancy and GPR83 mediates the actions of PEN in endometrial and non-endometrial cells

Objective To characterize the expression and signaling of uterine GPR83 in vivo in the nonpregnant and pregnant mouse and in vitro in human endometrial and nonendometrial cells. Design Controlled laboratory study. Setting Not applicable. Patients Not applicable. Interventions None. Main Outcome Measures Expression of uterine Gpr83 was determined by quantitative polymerase chain reaction throughout the estrous cycle and during early pregnancy in ovarian-stimulated and non−ovarian-stimulated mice and pregnant and pseudopregnant mice. Expression was also determined in ovariectomized mice after the administration of oil, E2, P4, or E2 + P4 and in stromal cells following 6 days of in vitro decidualization. GPR83 signaling was studied in human endometrial and embryonic kidney cell lines. Cells were treated by PEN, a GPR83 ligand, and PEN-induced extracellular signal-regulated kinase (ERK) phosphorylation was assayed under conditions that blocked Gαq/11 and/or β-arrestin signaling. Results Uterine Gpr83 is expressed throughout the estrous cycle and during early pregnancy; expression increases dramatically at the time of uterine receptivity, embryo implantation, and stromal cell decidualization. In the ovariectomized mouse, hormone add-back reveals that Gpr83 expression is highly responsive to the combined treatment of E2 and P4, and studies in the ovarian-stimulated mouse show that expression is also very sensitive to changes in E2 and P4 and is therefore tightly regulated by E2 and P4. At the implantation site, expression is elevated up to D6 of pregnancy and then declines rapidly on D7 and D8, suggesting that if there is any involvement in decidualization, it is likely associated with primary but not secondary stromal cell decidualization. This premise was supported by the observation that stromal cell decidualization in vitro progresses with a decline in Gpr83 expression. In ERα/PR-expressing endometrial Ishikawa cells, GPR83 mediates PEN signals in a Gαq/11-dependent manner, and studies conducted in HEK 293 cells lacking β-arrestin revealed that GPR83 also signals via a β-arrestin−dependent manner. When signaling by either one or both pathways is downregulated, cells exhibit a major reduction in responsiveness to PEN treatment, demonstrating that signaling by both pathways is significant. Conclusion We hypothesize that PEN/GPR83 signaling regulates uterine receptivity, embryo implantation, and primary stromal cell decidualization by coupling to Gαq/11- and β-arrestin−dependent pathways.
Use of contrast ultrasound in differentiating thrombosed pseudoaneurysm from sarcoma, prior to surgery

We describe a case of a 69-year-old male with a right-sided popliteal mass following a motor vehicle accident 15 years ago. The mass was indeterminate via multiple modalities (magnetic resonance imaging, digital subtraction angiography, and vascular ultrasound) with biopsy requested prior to surgical removal to determine the appropriate surgical team - vascular versus sarcoma oncologic surgery. Contrast ultrasound was utilized to determine if biopsy was indicated and if so, to determine the most appropriate target. Contrast ultrasound showed no areas of enhancement, therefore biopsy was not performed and the patient safely proceeded to vascular surgery. Pathology confirmed the mass to be a thrombosed pseudoaneurysm of the popliteal artery. We present the benefits of using contrast ultrasound in the work up and diagnosis of a popliteal neoplasm versus suspected vascular complication.
Prevention of Atherosclerotic Cardiovascular Disease: What Is the Best Approach and How Early Should We Start?

After decades of research, there is no question that atherosclerosis begins early in life and is progressive, ultimately leading to the cardiovascular outcomes of coronary heart disease and cerebrovascular disease in adult life [(1)][1]. It is also clear that there are important risk factors that,
Ambulation of hospitalized patients: Knowledge, values, and barriers of direct care providers

The desire to ambulate hospitalized patients is tempered by their risk of falling. Research articulates the health-related benefits of ambulation, yet routinely providing this intervention is challenging. This descriptive survey-design study obtained data from consented licensed and unlicensed direct-care providers, which assessed their knowledge, values, and perceived barriers associated with routine ambulation of patients receiving care in a hospital setting. Analyses of these data conclude that the subjects were knowledgeable about and value ambulating patients. The most frequently cited barrier to routine ambulation was an inadequate staff number, followed closely by an unexpected rise in volume and patient acuity. Interventions aimed at improving the ambulation of patients should include the results of this study.
Role of Phosphorylated Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) in the Regulation of Germ Cell Specific mRNAs in Chromatoid Bodies During Spermatogenesis

GRTH/DDX25 is a member of the DEAD-box family of RNA helicases that play an essential role in spermatogenesis. GRTH knock-in (KI) mice with the human mutant GRTH gene (R242H) show loss of the phospho-species from cytoplasm with preservation of the non-phospho form in the cytoplasm and nucleus. GRTH KI mice are sterile and lack elongated spermatids and spermatozoa, with spermatogenic arrest at step 8 of round spermatids which contain chromatoid body (CB) markedly reduced in size. We observed an absence of phospho-GRTH in CB of GRTH KI mice. RNA-Seq analysis of mRNA isolated from CB revealed that 1,421 genes show differential abundance, of which 947 genes showed a decrease in abundance and 474 genes showed an increase in abundance in GRTH KI mice. The transcripts related to spermatid development, differentiation, and chromatin remodeling (Tnp1/2, Prm1/2/3, Spem1/2, Tssk 2/3/6, Grth, tAce, and Upf2) were reduced, and the transcripts encoding for factors involved in RNA transport, regulation, and surveillance and transcriptional and translational regulation (Eef1a1, Ppp1cc, Pabpc1, Ybx3, Tent5b, H2al1m, Dctn2, and Dync1h1) were increased in the CB of KI mice and were further validated by qPCR. In the round spermatids of wild-type mice, mRNAs of Tnp2, Prm2, and Grth were abundantly co-localized with MVH protein in the CB, while in GRTH KI mice these were minimally present. In addition, GRTH binding to Tnp1/2, Prm1/2, Grth, and Tssk6 mRNAs was found to be markedly decreased in KI. These results demonstrate the importance of phospho-GRTH in the maintenance of the structure of CB and its role in the storage and stability of germ cell-specific mRNAs during spermiogenesis.
Moral Decision-Making and Support for Safety Procedures Amid the COVID-19 Pandemic.

Abstract Given that individual differences influence virus-mitigating behaviors and the COVID-19 pandemic posed new moral dilemmas for individuals to resolve, across three studies (N = 704), we assessed how masculine honor beliefs (MHB), beliefs in pure good (BPG), evil (BPE), and the dark triad (DT) influence COVID-19 moral decision-making. Specifically, we analyzed moral decision-making at the microlevel (i.e., individual- and familial-level; Study 1), in decisions with (hypothetical) life-or-death consequences (Study 2), and at the macrolevel (i.e., nationwide virus-mitigation efforts; Study 3). In all studies, participants completed the four individual difference scales and rated their pandemic attitudes on Likert-type agreement scales, and resolved various moral dilemmas in Studies 2 and 3. Consistent with our hypotheses, individuals reported more virus-mitigation efforts in order to protect their families than themselves. In terms of hypothetical life-or-death and nationwide decisions, MHB, BPE, and the DT predicted more confidence and social motivations, whereas BPG predicted more distress. This research has implications for moral decision-making at varying degrees of severity during the COVID-19 pandemic.
A Robust Compile Time Method for SchedulingTask Parallelism on Distributed Memory Machines

The problem of compile time scheduling of tasks of a program represented as a directed acyclic graph (DAG) is NP-hard in its general form. A number of approaches have been proposed which attempt to solve the problem either sub-optimally for general cases or optimally for restrictive special cases. But all the compile time approaches suffer due to the inability to accurately model the computation and communication costs of the target architecture. A desirable property of a compile time scheduling algorithm is robustness against the variations in the computation and communication costs so that the run time performance is close to the compile time estimates; this aspect of scheduling has been left open in the literature. This paper first introduces a compile time scheduling algorithm for a variable number of available processors and then examines the impact of change of computation and communication costs on the generated schedule. The cost variations for all the nodes and all the edges are assumed to be uniform (in other words, all the node costs change by the same ratio and the edge costs change by the same ratio). This sort of variations could occur due to the inaccuracies in estimating the instruction execution times or the message passing delays. The ratio of the schedule length obtained by the new schedule based on the modified costs to the schedule length obtained by using the modified costs on the original schedule (obtained by initial costs) is used as a measure of the robustness of the algorithm. The essential conditions for robustness of the proposed algorithm are discussed and are demonstrated through an experimental study.
IRAK4 inhibitor mitigates joint inflammation by rebalancing metabolism malfunction in RA macrophages and fibroblasts.

Abstract Recent studies show a connection between glycolysis and inflammatory response in rheumatoid arthritis (RA) macrophages (MΦs) and fibroblasts (FLS). Yet, it is unclear which pathways could be targeted to rebalance RA MΦs and FLS metabolic reprogramming. To identify novel targets that could normalize RA metabolic reprogramming, TLR7-mediated immunometabolism was characterized in RA MΦs, FLS and experimental arthritis. We uncovered that GLUT1, HIF1α, cMYC, LDHA and lactate were responsible for the TLR7-potentiated metabolic rewiring in RA MΦs and FLS, which was negated by IRAK4i. While in RA FLS, HK2 was uniquely expanded by TLR7 and negated by IRAK4i. Conversely, TLR7-driven hypermetabolism, non-oxidative PPP (CARKL) and oxidative phosphorylation (PPARγ) were narrowly dysregulated in TLR7-activated RA MΦs and FLS and was reversed by IRAK4i. Consistently, IRAK4i therapy disrupted arthritis mediated by miR-Let7b/TLR7 along with impairing a broad-range of glycolytic intermediates, GLUT1, HIF1α, cMYC, HK2, PFKFB3, PKM2, PDK1 and RAPTOR. Notably, inhibition of the mutually upregulated glycolytic metabolites, HIF1α and cMYC, was capable of mitigating TLR7-induced inflammatory imprint in RA MΦs and FLS. In keeping with IRAK4i, treatment with HIF1i and cMYCi intercepted TLR7-enhanced IRF5 and IRF7 in RA MΦs, distinct from RA FLS. Interestingly, in RA MΦs and FLS, IRAK4i counteracted TLR7-induced CARKL reduction in line with HIF1i. Whereas, cMYCi in concordance with IRAK4i, overturned oxidative phosphorylation via PPARγ in TLR7-activated RA MΦs and FLS. The blockade of IRAK4 and its interconnected intermediates can rebalance the metabolic malfunction by obstructing glycolytic and inflammatory phenotypes in RA MΦs and FLS.
Cataract Surgery Outcomes and Postoperative Patient Compliance in Limited English Proficiency Patients at a County Hospital

Background/Aims: Investigate the role of language barriers in cataract surgery outcomes at a county hospital. Methods: Retrospective chart review of patients who underwent cataract surgery March 2018-February 2019 at Lyndon B. Johnson Hospital. Patients who underwent cataract surgery combined with another procedure or had severe glaucoma or proliferative diabetic retinopathy were excluded. Patients were classified into limited English proficient (LEP) or English proficient (non-LEP) groups based on language preferences. Demographics, baseline ocular characteristics, intraoperative complications, postoperative BCVA (best-corrected visual acuity), complications, and compliance were recorded. The primary outcome was incidence of poor visual outcomes (BCVA<20/40) at the postoperative 1-month visit. Results: 354 patients (199 [56%] LEP and 155 [44%] non-LEP) with 125 (35%) males and a mean age 66.1 (+/- 10.9) years were included. LEP patients were about 5 years older than non-LEP patients (P 0.05), except severity of cataract (125 [63%] NSC grade >2+ for LEP vs 70 [51%] for non-LEP, P =0.03). No significant differences in intraoperative complications (P =0.18), incidence of poor vision (P =0.59), postoperative cystoid macular edema (P =0.32), and compliance with the postoperative drop regimen (P =0.11) were noted. Conclusion: There were no statistically significant differences in incidence of poor vision, complications, or compliance. However, there was a trend toward significance, showing that language barriers may lead to more advanced disease and compliance issues with postoperative medications.
PA-tree: a parametric indexing scheme for spatio-temporal trajectories

Many new applications involving moving objects require the collection and querying of trajectory data, so efficient indexing methods are needed to support complex spatio-temporal queries on such data. Current work in this domain has used MBRs to approximate trajectories, which fail to capture some basic properties of trajectories, including smoothness and lack of internal area. This mismatch leads to poor pruning when such indices are used. In this work, we revisit the issue of using parametric space indexing for historical trajectory data. We approximate a sequence of movement functions with single continuous polynomial. Since trajectories tend to be smooth, our approximations work well and yield much finer approximation quality than MBRs. We present the PA-tree, a parametric index that uses this new approximation method. Experiments show that PA-tree construction costs are orders of magnitude lower than that of competing methods. Further, for spatio-temporal range queries, MBR-based methods require 20%–60% more I/O than PA-trees with clustered indicies, and 300%–400% more I/O than PA-trees with non-clustered indicies.
CPRF/ZTH front-end torus design and fabrication status

Design of the ZTH front-end torus has been completed for a reversed-field-pinch (RFP) machine to be assembled at Los Alamos National Laboratory during FY 92. The Confinement Physics Research Facility (CPRF) houses the ZTH front-end torus. The ZTH torus consists of an Inconel 625 vacuum vessel supported by an external electrically conducting 304L stainless steel shell. Interspace support rings support the vacuum vessel to the shell and also provide accurate radial support for the interspace electrical diagnostics. The shell also supports 48 toroidal-field coils that are mounted to the shell's external surface. The shell consists of an explosion-bonded stainless steel-copper composite with water-cooling tube assemblies attached to the outer surface. The 0.135-in-thick copper is on the inside surface of the shell and provides an electrically conducting path with the required electrical time constant of 50 ms. The shell plate will be formed to the required toroidal configuration, after which the poloidal and toroidal flanges will be welded to the structure and machined. >
Grief counselling and therapy

Grief counselling and therapy are in a period of ferment as emerging claims and models are developed that challenge our assumptions about how people accommodate loss and how counsellors and therapists can best help them to do so. This article reviews recent developments in bereavement research and practice that studies show are effective in helping bereaved people who are struggling to rebuild their lives following loss.
Tetrafluorodipyridinegermanium, [GeF4(C5H5N)2]

The molecular title compound was solvothermally synthesized at 373 K and crystallized in the triclinic system, with space group P\overline 1. The Ge(IV) atom lies on an inversion center and is coordinated by four fluoride anions and two pyridine mol­ecules. Owing to the non-bridging nature of the fluoride anions, this material forms a molecular solid with close packing.
Retinoic Acid and Glucocorticoid Treatment Induce Hepatic Glycine N-Methyltransferase and Lower Plasma Homocysteine Concentrations in Rats and Rat Hepatoma Cells

Perturbation of folate and methyl group metabolism is associated with a number of pathological conditions, including cardiovascular disease and neoplastic development. Glycine N-methyltransferase (GNMT) is a key protein that functions to regulate the supply and utilization of methyl groups for S-adenosylmethionine (SAM)-dependent transmethylation reactions. Factors or conditions that have the ability to regulate GNMT and the generation of homocysteine, a product of transmethylation, have important implications in the potential perturbation of methyl group metabolism. We showed that retinoid compounds induce active hepatic GNMT, resulting in compromised transmethylation processes. Because retinoids can stimulate gluconeogenesis, a condition known to alter methyl group and homocysteine metabolism, the current study was undertaken to determine the relationship between all-trans-retinoic acid (RA) and gluconeogenic hormones on these metabolic pathways. Intact adrenal function was not required for RA to induce and activate hepatic GNMT; however, treatment of rats with dexamethasone (DEX) was as effective as RA in inducing GNMT in rat liver. The marked increase in plasma total homocysteine levels observed in adrenalectomized rats was reduced to normal levels by treatment with either RA or DEX, indicating that the transsulfuration and/or remethylation pathways may be enhanced. Moreover, coadministration of RA and DEX had an additive effect on GNMT induction. Similar findings were also observed in a rat hepatoma cell culture model using H411E cells. Taken together, these results demonstrate that both RA and DEX independently induce GNMT, thereby having substantial implications for the potential interaction of retinoid administration with diabetes. J. Nutr. 133: 3392-3398, 2003.
Aural Atavism: The Witch's Tale and Gothic Horror Radio

This article offers a cultural historical interpretation of The Witch's Tale (1931–38), an early U.S. horror radio drama, and argues that the program's use of the Gothic genre unified its content and form. Its plays emphasized temporality to highlight the Gothic intertwining of the past and present, and offered allegories that while often rooted in the fantastic nevertheless addressed contemporary concerns—gender, Others, and socio-economic anxieties. It used sound to complement its content, evoking the supernatural and monsters, and cuing and sustaining suspense. And it tapped radio's connotation as a supernatural medium to complement and magnify its generic horror.
A robotic cadaveric flatfoot analysis of stance phase

The symptomatic flatfoot deformity (pes planus with peri-talar subluxation) can be a debilitating condition. Cadaveric flatfoot models have been employed to study the etiology of the deformity, as well as invasive and noninvasive surgical treatment strategies, by evaluating bone positions. Prior cadaveric flatfoot simulators, however, have not leveraged industrial robotic technologies, which provide several advantages as compared with the previously developed custom fabricated devices. Utilizing a robotic device allows the researcher to experimentally evaluate the flatfoot model at many static instants in the gait cycle, compared with most studies, which model only one to a maximum of three instances. Furthermore, the cadaveric tibia can be statically positioned with more degrees of freedom and with a greater accuracy, and then a custom device typically allows. We created a six degree of freedom robotic cadaveric simulator and used it with a flatfoot model to quantify static bone positions at ten discrete instants over the stance phase of gait. In vivo tibial gait kinematics and ground reaction forces were averaged from ten flatfoot subjects. A fresh frozen cadaveric lower limb was dissected and mounted in the robotic gait simulator (RGS). Biomechanically realistic extrinsic tendon forces, tibial kinematics, and vertical ground reaction forces were applied to the limb. In vitro bone angular position of the tibia, calcaneus, talus, navicular, medial cuneiform, and first metatarsal were recorded between 0% and 90% of stance phase at discrete 10% increments using a retroreflective six-camera motion analysis system. The foot was conditioned flat through ligament attenuation and axial cyclic loading. Post-flat testing was repeated to study the pes planus deformity. Comparison was then made between the pre-flat and post-flat conditions. The RGS was able to recreate ten gait positions of the in vivo pes planus subjects in static increments. The in vitro vertical ground reaction force was within ± 1 standard deviation (SD) of the in vivo data. The in vitro sagittal, coronal, and transverse plane tibial kinematics were almost entirely within ± 1 SD of the in vivo data. The model showed changes consistent with the flexible flatfoot pathology including the collapse of the medial arch and abduction of the forefoot, despite unexpected hindfoot inversion. Unlike previous static flatfoot models that use simplified tibial degrees of freedom to characterize only the midpoint of the stance phase or at most three gait positions, our simulator represented the stance phase of gait with ten discrete positions and with six tibial degrees of freedom. This system has the potential to replicate foot function to permit both noninvasive and surgical treatment evaluations throughout the stance phase of gait, perhaps eliciting unknown advantages or disadvantages of these treatments at other points in the gait cycle.