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The researchers sought to address client perspectives on the Internet-based Journey Mapping evaluation tool in a drug court program. Ten clients, who used this tool for 3 months, participated in interviews and responded to a short questionnaire. The qualitative data analysis was coded according to the constant comparative method. Clients reported that utilizing Journey Mapping initiated behavioral change, promoted cognitive change, tracked personal treatment progress, and created a way for their program feedback to be considered by staff. Analysis of client data suggested that Journey Mapping enhanced clients' treatment progress, and it not only uncovered program data, but also provided individual clients with their own tangible achievement data. [ABSTRACT FROM AUTHOR]

Ukraine has been independent since 1991. This study explored through a qualitative methodology how Ukrainian women perceived their lives had changed in the 1990s. It was found that women believed their families were barely able to subsist. They also believed that their lives were better under Soviet rule. [ABSTRACT FROM AUTHOR]

Although one-quarter (25%) of custodial grandparents live in rural areas, less is known about these families than their urban counterparts. This qualitative study was conducted to determine pathways into care with rural families; that is, the reasons and process into custodial grandparenting roles. Based upon interviews with fourteen grandparents, three major pathways were identified. The most common was co-residential where the parent generation exited a multi-generational household. In the incremental pathway, grandparents had attempted multiple strategies with the culmination of taking physical custody of the grandchildren. A final pathway, immediate care, was typically the result of a family crisis situation. Needs and challenges for custodial grandparents differ depending upon their unique pathway into this caregiving role. [ABSTRACT FROM AUTHOR]

Employers and employees face a new challenge with the Sandwich Generation that is confronted with caring for both children and elderly parents. This caregiving toll has an effect on individuals' productivity in organizations from the for-profit, non-profit and government sectors. Additionally, the feminization of the workplace has resulted in more women, who traditionally have been the caregivers, serving in the workforce. This study was designed to explore the issues of caregiving for the Sandwich Generation in university-affiliated schools of social work. Graduate social work education programs in the United States were targeted as organizational systems for study. A total of 69 schools responded to the survey. Caregiving stress was an issue for these schools with manifestations in both productivity and organizational climate. The discussion includes a call to action for three major changes in the way organizations do business: deploying additional resources to support employees, maximizing flexibility and stressing prevention. [ABSTRACT FROM AUTHOR]

Background: Individuals with sickle cell disease (SCD) experience poor clinical outcomes while transitioning from paediatric to adult care. Standards for SCD transition are needed. We established a Quality Improvement (QI) Collaborative that aimed to improve the quality of care for all young adults with SCD by establishing a standardised SCD transition process. This study evaluates the implementation of the Six Core Elements (6CE) of Health Care Transition, which was a fundamental component of the cluster-randomised Sickle Cell Trevor Thompson Transition Project (ST3P-UP) study., Methods: A central QI team trained 14 ST3P-UP study sites on QI methodologies, 6CE and Got Transition's process measurement tool (PMT). Site-level QI teams included a transition coordinator, clinic physicians/staff, patients/parents with SCD and community representatives. Sites completed the PMT every 6 months for 54 months and monthly audits of 10 randomly-selected charts to verify readiness/self-care assessments and emergency care plans., Results: Of a possible 100, the aggregate mean (±SD) PMT score for paediatric clinics was 23.9 (±13.8) at baseline, 95.9 (±6.0) at 24 months and 98.9 (±2.1) at 54 months. The aggregate mean PMT score for adult clinics was 15.0 (±13.5) at baseline, 88.4 (±11.8) at 24 months and 95.8 (±6.8) at 54 months. The overall QI Collaborative PMT score improved by 402%. At baseline, readiness/self-care assessments were current for 38% of paediatric and 20% of adult patients; emergency care plans were current for 20% of paediatric and 3% of adult patients. Paediatric clinics had one median readiness assessment shift (76%) and four median emergency care plan shifts (65%, 77%, 79%, 84%). Adult clinics experienced three median self-care assessment shifts (58%, 63%, 70%) and two median emergency care plan shifts (57%, 70%)., Conclusions: The ST3P-UP QI Collaborative successfully embedded the 6CE of Health Care Transition into routine care and increased administration of assessments and emergency care plans for transition-aged patients with SCD., Competing Interests: Competing interests: IO received grant funding from HRSA and CDC and previously served as a consultant for Acceleron, Chiesi, Cyclerion, Emmaus, Forma Therapeutics, Global Blood Therapeutics and Novartis. PD received grant funding from CHL-Bhering, Forma, NIH, Novartis, Takeda, UPMC and UT Memphis and serves as an NMDP study monitor and Forma advisory board member. She has also consulted for Forma, Chiesi, Bluebird Bio and Vertex as an advisory member. RHL received grant funding from PCORI, served as a consultant for Novo Nordisk and Pfizer and served as a consultant for Forma Therapeutics. OAA was advisory board member of Novartis and Global Blood Therapeutics and receives grant funding from NIH, HRSA and CDC. All other authors have no relevant interests to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The effect of individual non-narcotic analgesics in cystectomy enhanced recovery after surgery (ERAS) is unknown. Additionally, many non-narcotic medications are associated with side effects pertinent to the cystectomy population. To better understand the actual use and utility of these medications, we sought to characterize the association between non-narcotic medications and milligram morphine equivalent (MME) narcotic score during the postoperative inpatient stay., Methods: We reviewed 260 consecutive ERAS cystectomy patients. The MME impact of non-narcotic compliance and cumulative dose of medication received was evaluated separately with general linear models. We also assessed relationship of non-narcotic compliance to patient reported pain score, length of stay (LOS), and time to return of bowel function (ROBF) and performed manual review of postoperative documentation to identify reasons for medication noncompliance., Results: Compliance with postoperative acetaminophen, gabapentin, and ketorolac was low. There was an inverse relationship between ketorolac dose and MME on postoperative day 1 (-0.026 MME/mg; P = 0.004) and postoperative day 2 (-0.33 MME/mg; P < 0.001). Compliance with ketorolac was associated with lower MME on postoperative day 1 (26.1 MME v. 33.6 MME; P = 0.023). There were no such associations identified with gabapentin or acetaminophen. Gabapentin compliance was associated with earlier ROBF (3.7 days v. 4.3 days; P = 0.006). Ketorolac compliance was associated with lower pain score on POD1 (3.25 VAS v. 4.07 VAS; P = 0.019) and POD2 (3.05 VAS v. 3.85 VAS; P = 0.040) There was no association between medication compliance and LOS. The most common reasons identified for non-compliance with gabapentin and ketorolac were renal function concerns (38% and 40% respectively), bleeding concerns with ketorolac (20%) and concerns for neurologic adverse effect with gabapentin (16%)., Conclusion: Compliance with non-narcotic medications in our ERAS cystectomy protocol was poor. There was a modest association with ketorolac and postoperative MME but no association with gabapentin or acetaminophen. Further study will clarify the role of these medications for cystectomy patients. Component specific analysis of protocolized care is valuable and may alter care pathways., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Research on best practices in theory assessment highlights that testing theories is challenging because they inherit a new set of assumptions as soon as they are linked to a specific methodology. In this article, we integrate and build on this work by demonstrating the breadth of these challenges. We show that tracking auxiliary assumptions is difficult because they are made at different stages of theory testing and at multiple levels of a theory. We focus on these issues in a reanalysis of a seminal study and its replications, both of which use a simple working-memory paradigm and a mainstream computational modeling approach. These studies provide the main evidence for "all-or-none" recognition models of visual working memory and are still used as the basis for how to measure performance in popular visual working-memory tasks. In our reanalysis, we find that core practical auxiliary assumptions were unchecked and violated; the original model comparison metrics and data were not diagnostic in several experiments. Furthermore, we find that models were not matched on "theory general" auxiliary assumptions, meaning that the set of tested models was restricted, and not matched in theoretical scope. After testing these auxiliary assumptions and identifying diagnostic testing conditions, we find evidence for the opposite conclusion. That is, continuous resource models outperform all-or-none models. Together, our work demonstrates why tracking and testing auxiliary assumptions remains a fundamental challenge, even in prominent studies led by careful, computationally minded researchers. Our work also serves as a conceptual guide on how to identify and test the gamut of auxiliary assumptions in theory assessment, and we discuss these ideas in the context of contemporary approaches to scientific discovery., (© 2024. Crown.)

"Dogs" are connected to "cats" in our minds, and "backyard" to "outdoors." Does the structure of this semantic knowledge differ across people? Network-based approaches are a popular representational scheme for thinking about how relations between different concepts are organized. Recent research uses graph theoretic analyses to examine individual differences in semantic networks for simple concepts and how they relate to other higher-level cognitive processes, such as creativity. However, it remains ambiguous whether individual differences captured via network analyses reflect true differences in measures of the structure of semantic knowledge, or differences in how people strategically approach semantic relatedness tasks. To test this, we examine the reliability of local and global metrics of semantic networks for simple concepts across different semantic relatedness tasks. In four experiments, we find that both weighted and unweighted graph theoretic representations reliably capture individual differences in local measures of semantic networks (e.g., how related pot is to pan versus lion). In contrast, we find that metrics of global structural properties of semantic networks, such as the average clustering coefficient and shortest path length, are less robust across tasks and may not provide reliable individual difference measures of how people represent simple concepts. We discuss the implications of these results and offer recommendations for researchers who seek to apply graph theoretic analyses in the study of individual differences in semantic memory., (© 2023. The Psychonomic Society, Inc.)

Elevated skeletal muscle diacylglycerols (DAGs) and ceramides can impair insulin signaling, and acylcarnitines (acylCNs) reflect impaired mitochondrial fatty acid oxidation, thus, the intramuscular lipid profile is indicative of insulin resistance. Acute (i.e., postprandial) hyperinsulinemia has been shown to elevate lipid concentrations in healthy muscle and is an independent risk factor for type 2 diabetes (T2D). However, it is unclear how the relationship between acute hyperinsulinemia and the muscle lipidome interacts across metabolic phenotypes, thus contributing to or exacerbating insulin resistance. We therefore investigated the impact of acute hyperinsulinemia on the skeletal muscle lipid profile to help characterize the physiological basis in which hyperinsulinemia elevates T2D risk. In a cross-sectional comparison, endurance athletes ( n = 12), sedentary lean adults ( n = 12), and individuals with obesity ( n = 13) and T2D ( n = 7) underwent a hyperinsulinemic-euglycemic clamp with muscle biopsies. Although there were no significant differences in total 1,2-DAG fluctuations, there was a 2% decrease in athletes versus a 53% increase in T2D during acute hyperinsulinemia ( P = 0.087). Moreover, C18 1,2-DAG species increased during the clamp with T2D only, which negatively correlated with insulin sensitivity ( P < 0.050). Basal muscle C18:0 total ceramides were elevated with T2D ( P = 0.029), but not altered by clamp. Acylcarnitines were universally lowered during hyperinsulinemia, with more robust reductions of 80% in athletes compared with only 46% with T2D (albeit not statistically significant, main effect of group, P = 0.624). Similar fluctuations with acute hyperinsulinemia increasing 1,2 DAGs in insulin-resistant phenotypes and universally lowering acylcarnitines were observed in male mice. In conclusion, acute hyperinsulinemia elevates muscle 1,2-DAG levels with insulin-resistant phenotypes. This suggests a possible dysregulation of intramuscular lipid metabolism in the fed state in individuals with low insulin sensitivity, which may exacerbate insulin resistance. NEW & NOTEWORTHY Postprandial hyperinsulinemia is a risk factor for type 2 diabetes and may increase muscle lipids. However, it is unclear how the relationship between acute hyperinsulinemia and the muscle lipidome interacts across metabolic phenotypes, thus contributing to insulin resistance. We observed that acute hyperinsulinemia elevates muscle 1,2-DAGs in insulin-resistant phenotypes, whereas ceramides were unaltered. Insulin-mediated acylcarnitine reductions are also hindered with high-fat feeding. The postprandial period may exacerbate insulin resistance in metabolically unhealthy phenotypes.

Regular exercise and antihyperglycemic drugs are front-line treatments for type-2 diabetes and related metabolic disorders. Leading drugs are metformin, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide 1 receptor agonists. Each class has strong individual efficacy to treat hyperglycemia, yet the combination with exercise can yield varied results, some of which include blunting of expected metabolic benefits. Skeletal muscle insulin resistance contributes to the development of type-2 diabetes while improvements in skeletal muscle insulin signaling are among key adaptations to exercise training. The current review identifies recent advances into the mechanisms, with an emphasis on skeletal muscle, of the interaction between exercise and these common antihyperglycemic drugs. The review is written toward researchers and thus highlights specific gaps in knowledge and considerations for future study directions., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

We investigated the link between enhancement of SI (by hyperinsulinemic-euglycemic clamp) and muscle metabolites after 12 weeks of aerobic (high-intensity interval training [HIIT]), resistance training (RT), or combined training (CT) exercise in 52 lean healthy individuals. Muscle RNA sequencing revealed a significant association between SI after both HIIT and RT and the branched-chain amino acid (BCAA) metabolic pathway. Concurrently with increased expression and activity of branched-chain ketoacid dehydrogenase enzyme, many muscle amino metabolites, including BCAAs, glutamate, phenylalanine, aspartate, asparagine, methionine, and γ-aminobutyric acid, increased with HIIT, supporting the substantial impact of HIIT on amino acid metabolism. Short-chain C3 and C5 acylcarnitines were reduced in muscle with all three training modes, but unlike RT, both HIIT and CT increased tricarboxylic acid metabolites and cardiolipins, supporting greater mitochondrial activity with aerobic training. Conversely, RT and CT increased more plasma membrane phospholipids than HIIT, suggesting a resistance exercise effect on cellular membrane protection against environmental damage. Sex and age contributed modestly to the exercise-induced changes in metabolites and their association with cardiometabolic parameters. Integrated transcriptomic and metabolomic analyses suggest various clusters of genes and metabolites are involved in distinct effects of HIIT, RT, and CT. These distinct metabolic signatures of different exercise modes independently link each type of exercise training to improved SI and cardiometabolic risk., Article Highlights: We aimed to understand the link between skeletal muscle metabolites and cardiometabolic health after exercise training. Although aerobic, resistance, and combined exercise training each enhance muscle insulin sensitivity as well as other cardiometabolic parameters, they disparately alter amino and citric acid metabolites as well as the lipidome, linking these metabolomic changes independently to the improvement of cardiometabolic risks with each exercise training mode. These findings reveal an important layer of the unique exercise mode-dependent changes in muscle metabolism, which may eventually lead to more informed exercise prescription for improving SI., (© 2023 by the American Diabetes Association.)

In many decision tasks, we have a set of alternative choices and are faced with the problem of how to use our latent beliefs and preferences about each alternative to make a single choice. Cognitive and decision models typically presume that beliefs and preferences are distilled to a scalar latent strength for each alternative, but it is also critical to model how people use these latent strengths to choose a single alternative. Most models follow one of two traditions to establish this link. Modern psychophysics and memory researchers make use of signal detection theory, assuming that latent strengths are perturbed by noise, and the highest resulting signal is selected. By contrast, many modern decision theoretic modeling and machine learning approaches use the softmax function (which is based on Luce's choice axiom; Luce, 1959) to give some weight to non-maximal-strength alternatives. Despite the prominence of these two theories of choice, current approaches rarely address the connection between them, and the choice of one or the other appears more motivated by the tradition in the relevant literature than by theoretical or empirical reasons to prefer one theory to the other. The goal of the current work is to revisit this topic by elucidating which of these two models provides a better characterization of latent processes in m -alternative decision tasks, with a particular focus on memory tasks. In a set of visual memory experiments, we show that, within the same experimental design, the softmax parameter β varies across m -alternatives, whereas the parameter d ' of the signal-detection model is stable. Together, our findings indicate that replacing softmax with signal-detection link models would yield more generalizable predictions across changes in task structure. More ambitiously, the invariance of signal detection model parameters across different tasks suggests that the parametric assumptions of these models may be more than just a mathematical convenience, but reflect something real about human decision-making., Competing Interests: Declaration of competing interest The authors declare no conflict of interest.

Substantial divergence in cardio-metabolic risk, muscle size, and performance exists between men and women. Considering the pivotal role of skeletal muscle in human physiology, we investigated and found, based on RNA sequencing (RNA-seq), that differences in the muscle transcriptome between men and women are largely related to testosterone and estradiol and much less related to genes located on the Y chromosome. We demonstrate inherent unique, sex-dependent differences in muscle transcriptional responses to aerobic, resistance, and combined exercise training in young and older cohorts. The hormonal changes with age likely explain age-related differential expression of transcripts. Furthermore, in primary human myotubes we demonstrate the profound but distinct effects of testosterone and estradiol on amino acid incorporation to multiple individual proteins with specific functions. These results clearly highlight the potential of designing exercise programs tailored specifically to men and women and have implications for people who change gender by altering their hormone profile., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are few quality metrics and benchmarks specific to surgical oncology. Development of a surgeon-level performance metrics system based on peer comparisons is hypothesized to positively influence surgical decision-making. This study established a tracking and reporting system comprised of evidence and consensus-based metrics to assess breast care delivered by individual surgeons., Methods: Surgeons' performance is assessed by a surveillance tracking system of metrics pertaining to referrals and surgical elements. This retrospective analysis of prospectively collected breast care data reports on recurring 6-month and cumulative data from nine care locations from 2015 to 2021., Results: Breast care was provided to 6659 patients by 41 surgeons. A total of 27 breast care metrics were evaluated over 7 years. Metrics with consistent, proficient results were retired after 18 months, including the rate of core biopsy, specimen orientation, and referrals to medical oncology, genetics, and fertility, among others. In clinically node-negative, hormone receptor-positive patients 70 years of age or older, the cumulative rate of sentinel lymph node (SLN) biopsy significantly decreased by 40% over 5.5 years (p < .001). The overall breast conservation rate for T0-T2 cancer increased 10% over 7 years. At the surgeon level, improvements were made in the median number of SLNs removed and in operative note documentation., Conclusions: Implementation of a surgeon-specific, peer comparison-based metric and tracking system has yielded substantive changes in breast care management. This process and governance structure can serve as a model for quantification of breast care at other institutions and for other disease sites., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

High-fat diet (HFD) and exercise remodel skeletal muscle mitochondria. The electron transfer flavoproteins (ETF) transfer reducing equivalents from β-oxidation into the electron transfer system. Exercise may stimulate the synthesis of ETF proteins to increase lipid respiration. We determined mitochondrial remodeling for lipid respiration through ETF in the context of higher mitochondrial abundance/capacity seen in female mice. We hypothesized HFD would be a greater stimulus than exercise to remodel ETF and lipid pathways through increased protein synthesis alongside increased lipid respiration. Female C57BL/6J mice (n = 15 per group) consumed HFD or low-fat diet (LFD) for 4 weeks then remained sedentary (SED) or completed 8 weeks of treadmill training (EX). We determined mitochondrial lipid respiration, RNA abundance, individual protein synthesis, and abundance for ETFα, ETFβ, and ETF dehydrogenase (ETFDH). HFD increased absolute and relative lipid respiration (p = 0.018 and p = 0.034) and RNA abundance for ETFα (p = 0.026), ETFβ (p = 0.003), and ETFDH (p = 0.0003). HFD increased synthesis for ETFα and ETFDH (p = 0.0007 and p = 0.002). EX increased synthesis of ETFβ and ETFDH (p = 0.008 and p = 0.006). Higher synthesis rates of ETF were not always reflected in greater protein abundance. Greater synthesis of ETF during HFD indicates mitochondrial remodeling which may contribute higher mitochondrial lipid respiration through enhanced ETF function., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objectives: Opioid use, misuse, and diversion is of paramount concern in the United States. Radical cystectomy is typically managed with some component of opioid pain control. We evaluated persistent opioid and benzodiazepine use after radical cystectomy and assessed the impact of their preoperative use on this outcome. We also explored associations between preoperative use and perioperative outcomes., Methods and Materials: We used prospectively maintained data from our enhanced recovery after surgery (ERAS) cystectomy database and the Prescription Reporting with Immediate Medication Utilization Mapping (PRIMUM) database to identify controlled substance prescriptions for radical cystectomy patients. We separated patients by frequency of preoperative opioid and/or benzodiazepine prescriptions (0, 1, 2+) and used these cohorts to explore persistent use (prescription 3-12 months after surgery) alongside perioperative outcomes., Results: Our cohort included 257 patients undergoing cystectomy at a single institution from 2017 to 2021. Preoperative opioid and benzodiazepine prescriptions were documented for 120 (46.7%) and 26 (10.1%) patients, respectively. Persistent opioid use was observed in 20 (14.6%) of opioid-naive patients (no prescriptions in 9 months prior to surgery) while 13 (19.7%) patients with 1 preoperative prescription and 28 (51.9%) patients with 2 or more preoperative prescriptions demonstrated persistent use. New persistent benzodiazepine use occurred in 6 (2.6%) patients. Overall persistent benzodiazepine use was present in 11 (4.3%) patients. In a multivariable model, preoperative opioid and benzodiazepine prescriptions were associated with persistent opioid use (P < 0.001; P = 0.027 respectively). No association was identified between preoperative opioid or benzodiazepine usage and perioperative outcomes including length of stay, return of bowel function, inpatient opioid usage, inpatient or discharge complications, readmissions, or emergency department visits. Inpatient pain scores were noted to be higher in patients with ≥ 2 preoperative opioid prescriptions (P = 0.037)., Conclusions: Persistent opioid use was present in 23.7% of patients, with a new persistent use rate of 14.6%. Benzodiazepine use was less frequent than opioids, with a small number demonstrating new persistent use. Preoperative opioid and benzodiazepine use is associated with persistent opioid use postoperatively. Preoperative opioid and benzodiazepine use did not affect perioperative outcomes in our cohort., Competing Interests: Declaration of Competing Interest The authors have no relevent disclosures or competing interests. Previously presented as a poster at the Southeastern Section of the American Urological Association Annual Meeting in March 2022., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study investigated how different exercise training modalities influence skeletal muscle mitochondrial dynamics. Healthy [average body mass index (BMI): 25.8 kg/m 2 ], sedentary younger and older participants underwent 12 wk of supervised high-intensity aerobic interval training (HIIT; n = 13), resistance training (RT; n = 14), or combined training (CT; n = 11). Mitochondrial structure was assessed using transmission electron microscopy (TEM). Regulators of mitochondrial fission and fusion, cardiorespiratory fitness (V̇o 2peak ), insulin sensitivity via a hyperinsulinemic-euglycemic clamp, and muscle mitochondrial respiration were assessed. TEM showed increased mitochondrial volume, number, and perimeter following HIIT ( P < 0.01), increased mitochondrial number following CT ( P < 0.05), and no change in mitochondrial abundance after RT. Increased mitochondrial volume associated with increased mitochondrial respiration and insulin sensitivity following HIIT ( P < 0.05). Increased mitochondrial perimeter associated with increased mitochondrial respiration, insulin sensitivity, and V̇o 2peak following HIIT ( P < 0.05). No such relationships were observed following CT or RT. OPA1, a regulator of fusion, was increased following HIIT ( P < 0.05), whereas FIS1, a regulator of fission, was decreased following HIIT and CT ( P < 0.05). HIIT also increased the ratio of OPA1/FIS1 ( P < 0.01), indicative of the balance between fission and fusion, which positively correlated with improvements in respiration, insulin sensitivity, and V̇o 2peak ( P < 0.05). In conclusion, HIIT induces a larger, more fused mitochondrial tubular network. Changes indicative of increased fusion following HIIT associate with improvements in mitochondrial respiration, insulin sensitivity, and V̇o 2peak supporting the idea that enhanced mitochondrial fusion accompanies notable health benefits of HIIT. NEW & NOTEWORTHY We assessed the effects of 12 wk of supervised high-intensity interval training (HIIT), resistance training, and combined training (CT) on skeletal muscle mitochondrial abundance and markers of fission and fusion. HIIT increased mitochondrial area and size and promoted protein changes indicative of increased mitochondrial fusion, whereas lessor effects were observed after CT and no changes were observed after RT. Furthermore, increased mitochondrial area and size after HIIT associated with improved mitochondrial respiration, cardiorespiratory fitness, and insulin sensitivity.

Ensemble perception is a process by which we summarize complex scenes. Despite the importance of ensemble perception to everyday cognition, there are few computational models that provide a formal account of this process. Here we develop and test a model in which ensemble representations reflect the global sum of activation signals across all individual items. We leverage this set of minimal assumptions to formally connect a model of memory for individual items to ensembles. We compare our ensemble model against a set of alternative models in five experiments. Our approach uses performance on a visual memory task for individual items to generate zero-free-parameter predictions of interindividual and intraindividual differences in performance on an ensemble continuous-report task. Our top-down modelling approach formally unifies models of memory for individual items and ensembles and opens a venue for building and comparing models of distinct memory processes and representations., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Maximal aerobic exercise capacity [maximal oxygen consumption (V̇o 2max )] is one of the strongest predictors of morbidity and mortality. Aerobic exercise training can increase V̇o 2max , but inter-individual variability is marked and unexplained physiologically. The mechanisms underlying this variability have major clinical implications for extending human healthspan. Here, we report a novel transcriptome signature related to ΔV̇o 2max with exercise training detected in whole blood RNA. We used RNA-Seq to characterize transcriptomic signatures of ΔV̇o 2max in healthy women who completed a 16-wk randomized controlled trial comparing supervised, higher versus lower aerobic exercise training volume and intensity (4 training groups, fully crossed). We found significant baseline gene expression differences in subjects who responded to aerobic exercise training with robust versus little/no ΔV̇o 2max , and differentially expressed genes/transcripts were mostly related to inflammatory signaling and mitochondrial function/protein translation. Baseline gene expression signatures associated with robust versus little/no ΔV̇o 2max were also modulated by exercise training in a dose-dependent manner, and they predicted ΔV̇o 2max in this and a separate dataset. Collectively, our data demonstrate the potential utility of using whole blood transcriptomics to study the biology of inter-individual variability in responsiveness to the same exercise training stimulus.

Visual working memory is highly limited, and its capacity is tied to many indices of cognitive function. For this reason, there is much interest in understanding its architecture and the sources of its limited capacity. As part of this research effort, researchers often attempt to decompose visual working memory errors into different kinds of errors, with different origins. One of the most common kinds of memory error is referred to as a "swap," where people report a value that closely resembles an item that was not probed (e.g., an incorrect, non-target item). This is typically assumed to reflect confusions, like location binding errors, which result in the wrong item being reported. Capturing swap rates reliably and validly is of great importance because it permits researchers to accurately decompose different sources of memory errors and elucidate the processes that give rise to them. Here, we ask whether different visual working memory models yield robust and consistent estimates of swap rates. This is a major gap in the literature because in both empirical and modeling work, researchers measure swaps without motivating their choice of swap model. Therefore, we use extensive parameter recovery simulations with three mainstream swap models to demonstrate how the choice of measurement model can result in very large differences in estimated swap rates. We find that these choices can have major implications for how swap rates are estimated to change across conditions. In particular, each of the three models we consider can lead to differential quantitative and qualitative interpretations of the data. Our work serves as a cautionary note to researchers as well as a guide for model-based measurement of visual working memory processes., Competing Interests: Competing Interests The authors declare no competing interests.

We argue that critical areas of memory research rely on problematic measurement practices and provide concrete suggestions to improve the situation. In particular, we highlight the prevalence of memory studies that use tasks (like the "old/new" task: "have you seen this item before? yes/no") where quantifying performance is deeply dependent on counterfactual reasoning that depends on the (unknowable) distribution of underlying memory signals. As a result of this difficulty, different literatures in memory research (e.g., visual working memory, eyewitness identification, picture memory, etc.) have settled on a variety of fundamentally different metrics to get performance measures from such tasks (e.g., A', corrected hit rate, percent correct, d', diagnosticity ratios, K values, etc.), even though these metrics make different, contradictory assumptions about the distribution of latent memory signals, and even though all of their assumptions are frequently incorrect. We suggest that in order for the psychology and neuroscience of memory to become a more cumulative, theory-driven science, more attention must be given to measurement issues. We make a concrete suggestion: The default memory task for those simply interested in performance should change from old/new ("did you see this item'?") to two-alternative forced-choice ("which of these two items did you see?"). In situations where old/new variants are preferred (e.g., eyewitness identification; theoretical investigations of the nature of memory signals), receiver operating characteristic (ROC) analysis should be performed rather than a binary old/new task., (© 2022. The Psychonomic Society, Inc.)

Aerobic training remodels the quantity and quality (function per unit) of skeletal muscle mitochondria to promote substrate oxidation, however, there remain key gaps in understanding the underlying mechanisms during initial training adaptations. We used short-term high-intensity interval training (HIIT) to determine changes to mitochondrial respiration and regulatory pathways that occur early in remodeling. Fifteen normal-weight sedentary adults started seven sessions of HIIT over 14 days and 14 participants completed the intervention. We collected vastus lateralis biopsies before and 48 h after HIIT to determine mitochondrial respiration, RNA sequencing, and Western blotting for proteins of mitochondrial respiration and degradation via autophagy. HIIT increased respiration per mitochondrial protein for lipid (+23% P = 0.020), complex I (+18%, P = 0.0015), complex I + II (+14%, P < 0.0001), and complex II (+24% P < 0.0001). Transcripts that increased with HIIT identified several gene sets of mitochondrial respiration, particularly for complex I, whereas transcripts that decreased identified pathways of DNA and chromatin remodeling. HIIT lowered protein abundance of autophagy markers for p62 (-19%, P = 0.012) and LC3 II/I (-20%, P = 0.004) in whole tissue lysates but not isolated mitochondria. Meal tolerance testing revealed HIIT increased the change in whole body respiratory exchange ratio and lowered cumulative plasma insulin concentrations. Gene transcripts and respiratory function indicate remodeling of mitochondria within 2 wk of HIIT. Overall changes are consistent with increased protein quality driving rapid improvements in substrate oxidation. NEW & NOTEWORTHY Aerobic training stimulates mitochondrial metabolism in skeletal muscle that is linked to improvements to whole body fuel metabolism. The mechanisms driving changes to the quantity and quality (function per unit) of mitochondria are less known. We used seven sessions of high-intensity interval training (HIIT) to determine functional changes and mechanisms of mitochondrial remodeling in skeletal muscle. HIIT increased mitochondrial respiration per mass for fatty acids, complex I, and complex II substrates. HIIT-induced remodeling pathways including gene transcripts for mitochondrial respiration (via RNA sequencing of muscle tissue) and proteins related to complex I respiration. We conclude that an early feature of aerobic training is increased mitochondrial protein quality via improved respiration and induction of mitochondrial transcriptional patterns.

Cognitive control refers to the ability to maintain goal-relevant information in the face of distraction, making it a core construct for understanding human thought and behavior. There is great theoretical and practical value in building theories that can be used to explain or to predict variations in cognitive control as a function of experimental manipulations or individual differences. A critical step toward building such theories is determining which latent constructs are shared between laboratory tasks that are designed to measure cognitive control. In the current work, we examine this question in a novel way by formally linking computational models of two canonical cognitive control tasks, the Eriksen flanker and task-switching task. Specifically, we examine whether model parameters that capture cognitive control processes in one task can be swapped across models to make predictions about individual differences in performance on another task. We apply our modeling and analysis to a large scale data set from an online cognitive training platform, which optimizes our ability to detect individual differences in the data. Our results suggest that the flanker and task-switching tasks probe common control processes. This finding supports the view that higher level cognitive control processes as opposed to solely strategies in speed and accuracy tradeoffs, or perceptual processing and motor response speed are shared across the two tasks. We discuss how our computational modeling substitution approach addresses limitations of prior efforts to relate performance across different cognitive control tasks, and how our findings inform current theories of cognitive control. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Change detection tasks are commonly used to measure and understand the nature of visual working memory capacity. Across three experiments, we examine whether the nature of the memory signals used to perform change detection are continuous or all-or-none and consider the implications for proper measurement of performance. In Experiment 1, we find evidence from confidence reports that visual working memory is continuous in strength, with strong support for an equal variance signal detection model with no guesses or lapses. Experiments 2 and 3 test an implication of this, which is that K should confound response criteria and memory. We found K values increased by roughly 30% when criteria are shifted despite no change in the underlying memory signals. Overall, our data call into question a large body of work using threshold measures, like K , to analyze change detection data. This metric confounds response bias with memory performance and is inconsistent with the vast majority of visual working memory models, which propose variations in precision or strength are present in working memory. Instead, our data indicate an equal variance signal detection model (and thus, d ')-without need for lapses or guesses-is sufficient to explain change detection performance. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

High dietary fat intake induces significant whole-body and skeletal muscle adaptations in mice, including increased capacity for fat oxidation and mitochondrial biogenesis. The impact of a diet that is high in fat and simple sugars (i.e., western diet [WD]), particularly on regulation of skeletal muscle mitochondrial function, is less understood. The purpose of the current study was to determine physiologic adaptations in mitochondrial respiratory capacity in skeletal muscle during short-term consumption of WD, including if adaptive responses to WD-feeding are modified by concurrent exercise training or may be sex-specific. Male and female C57BL/6J mice were randomized to consume low-fat diet (LFD) or WD for 4 weeks, with some WD-fed mice also performing concurrent treadmill training (WD + Ex). Group sizes were n = 4-7. Whole-body metabolism was measured using in-cage assessment of food intake and energy expenditure, DXA body composition analysis and insulin tolerance testing. High-resolution respirometry of mitochondria isolated from quadriceps muscle was used to determine skeletal muscle mitochondrial respiratory function. Male mice fed WD gained mass (p < 0.001), due to increased fat mass (p < 0.001), and displayed greater respiratory capacity for both lipid and non-lipid substrates compared with LFD mice (p < 0.05). There was no effect of concurrent treadmill training on maximal respiration (WD + Ex vs. WD). Female mice had non-significant changes in body mass and composition as a function of the interventions, and no differences in skeletal muscle mitochondrial oxidative capacity. These findings indicate 4 weeks of WD feeding can increase skeletal muscle mitochondrial oxidative capacity among male mice; whereas WD, with or without exercise, had minimal impact on mass gain and skeletal muscle respiratory capacity among female mice. The translational relevance is that mitochondrial adaptation to increases in dietary fat intake that model WD may be related to differences in weight gain among male and female mice., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Cephalic phase insulin release (CPIR) is a rapid pulse of insulin secreted within minutes of food-related sensory stimulation. Understanding the mechanisms underlying CPIR in humans has been hindered by its small observed effect size and high variability within and between studies. One contributing factor to these limitations may be the use of peripherally measured insulin as an indicator of secreted insulin, since a substantial portion of insulin is metabolized by the liver before delivery to peripheral circulation. Here, we investigated the use of c-peptide, which is co-secreted in equimolar amounts to insulin from pancreatic beta cells, as a proxy for insulin secretion during the cephalic phase period. Changes in insulin and c-peptide were monitored in 18 adults over two repeated sessions following oral stimulation with a sucrose-containing gelatin stimulus. We found that, on average, insulin and c-peptide release followed a similar time course over the cephalic phase period, but that c-peptide showed a greater effect size. Importantly, when insulin and c-peptide concentrations were compared across sessions, we found that changes in c-peptide were significantly correlated at the 2 min (r = 0.50, p = 0.03) and 4 min (r = 0.65, p = 0.003) time points, as well as when participants' highest c-peptide concentrations were considered (r = 0.64, p = 0.004). In contrast, no significant correlations were observed for changes in insulin measured from the sessions (r = -0.06-0.35, p > 0.05). Herein, we detail the individual variability of insulin and c-peptide concentrations measured during the cephalic phase period, and identify c-peptide as a valuable metric for insulin secretion alongside insulin concentrations when investigating CPIR., (Copyright © 2022. Published by Elsevier Inc.)

Social interactions are dynamic and unfold over time. To make sense of social interactions, people must aggregate sequential information into summary, global evaluations. But how do people do this? Here, to address this question, we conducted nine studies (N = 1,583) using a diverse set of stimuli. Our focus was a central aspect of social interaction-namely, the evaluation of others' emotional responses. The results suggest that when aggregating sequences of images and videos expressing varying degrees of emotion, perceivers overestimate the sequence's average emotional intensity. This tendency for overestimation is driven by stronger memory of more emotional expressions. A computational model supports this account and shows that amplification cannot be explained only by nonlinear perception of individual exemplars. Our results demonstrate an amplification effect in the perception of sequential emotional information, which may have implications for the many types of social interactions that involve repeated emotion estimation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The chronology of the Paleocene-Eocene Thermal Maximum (PETM, ~56 Ma) remains disputed, hampering complete understanding of the possible trigger mechanisms of this event. Here we present an astrochronology for the PETM carbon isotope excursion from Howards Tract, Maryland a paleoshelf environment, on the mid-Atlantic Coastal Plain. Statistical evaluation of variations in calcium content and magnetic susceptibility indicates astronomical forcing was involved and the PETM onset lasted about 6 kyr. The astrochronology and Earth system modeling suggest that the PETM onset occurred at an extreme in precession during a maximum in eccentricity, thus favoring high temperatures, indicating that astronomical forcing could have played a role in triggering the event. Ca content data on the paleo-shelf, along with other marine records, support the notion that a carbonate saturation overshoot followed global ocean acidification during the PETM., (© 2022. The Author(s).)

Introduction and Objective: Enhanced Recovery After Surgery (ERAS) protocols have been increasingly applied to urologic surgeries such as cystectomy and prostatectomy, though research defining protocols and outcomes for renal ERAS programs (RERAS) for nephrectomy remains limited. We aim to assess perioperative outcomes following implementation of our RERAS protocol modified from ERAS society cystectomy guidelines, as well as describe compliance with protocol guidelines., Methods: We performed a retrospective cohort analysis of 400 patients who underwent partial or radical nephrectomy between October 2017 and August 2020. RERAS protocol was initiated September 30, 2018, and patients were categorized into pre- and post-RERAS implementation cohorts based on surgery date. Perioperative outcomes including complications, 30-day readmissions, length of stay, and opioid consumption were compared across pre- and post-RERAS cohorts. Protocol compliance was reported based on adherence to program recommendations., Results: Among 400 patients included in analysis, the pre-RERAS cohort included 133 patients and the post-RERAS cohort included 267 patients. There were no differences in overall complications (P = 0.354) and 30-day readmissions (P = 0.078). Length of stay (P < 0.001) and postoperative opioid consumption (P < 0.001) were significantly reduced post-RERAS. We observed an increase in compliance with RERAS recommendations over time (P< 0.001)., Conclusion: RERAS implementation was associated with decreased length of stay and opioid usage, underscoring the benefits of program adoption in an era of opioid dependence and strained hospital capacity. Successful initiation of a RERAS protocol requires intentional organization and buy in from all providers involved., Competing Interests: Conflict of Interest No disclosures or conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses p16 Ink4a together with multiple senescence-related genes and, concomitantly, exhibits DNA damage and chromatin reorganization. Through analysis of isolated myofibers, we also detail a senescence phenotype within a subset of old cells, governed instead by p2 Cip1 . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.

Resistance exercise training (RET) is an effective countermeasure to sarcopenia, related frailty and metabolic disorders. Here, we show that an RET-induced increase in PGC-1α4 (an isoform of the transcriptional co-activator PGC-1α) expression not only promotes muscle hypertrophy but also enhances glycolysis, providing a rapid supply of ATP for muscle contractions. In human skeletal muscle, PGC-1α4 binds to the nuclear receptor PPARβ following RET, resulting in downstream effects on the expressions of key glycolytic genes. In myotubes, we show that PGC-1α4 overexpression increases anaerobic glycolysis in a PPARβ-dependent manner and promotes muscle glucose uptake and fat oxidation. In contrast, we found that an acute resistance exercise bout activates glycolysis in an AMPK-dependent manner. These results provide a mechanistic link between RET and improved glucose metabolism, offering an important therapeutic target to counteract aging and inactivity-induced metabolic diseases benefitting those who cannot exercise due to many reasons., (© 2022. The Author(s).)

The Paleocene-Eocene Thermal Maximum (PETM) is recognized by a major negative carbon isotope (δ 13 C) excursion (CIE) signifying an injection of isotopically light carbon into exogenic reservoirs, the mass, source, and tempo of which continue to be debated. Evidence of a transient precursor carbon release(s) has been identified in a few localities, although it remains equivocal whether there is a global signal. Here, we present foraminiferal δ 13 C records from a marine continental margin section, which reveal a 1.0 to 1.5‰ negative pre-onset excursion (POE), and concomitant rise in sea surface temperature of at least 2°C and a decline in ocean pH. The recovery of both δ 13 C and pH before the CIE onset and apparent absence of a POE in deep-sea records suggests a rapid (< ocean mixing time scales) carbon release, followed by recovery driven by deep-sea mixing. Carbon released during the POE is therefore likely more similar to ongoing anthropogenic emissions in mass and rate than the main CIE.

Purpose: Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS., Patients and Methods: This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m 2 cycle 1 with subsequent escalation to 75 mg/m 2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines., Results: Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9-56.1%], with documented disease control in 80.0% (95% CI, 61.4-92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS., Conclusions: Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS., (©2021 American Association for Cancer Research.)

Memory for objects in a display sometimes reveals attraction-the objects are remembered as more similar to one another than they actually were-and sometimes reveals repulsion-the objects are remembered as more different from one another. The conditions that lead to these opposing memory biases are poorly understood; there is no theoretical framework that explains these contrasting dynamics. In three experiments (each N = 30 adults), we demonstrate that memory fidelity provides a unifying dimension that accommodates the existence of both types of visual working memory interactions. We show that either attraction or repulsion can arise simply as a function of manipulations of memory fidelity. We also demonstrate that subjective ratings of fidelity predict the presence of attraction or repulsion on a trial-by-trial basis. We discuss how these results bear on computational models of visual working memory and contextualize these results within the literature of attraction and repulsion effects in long-term memory and perception.

Dietary nitrate supplementation improves exercise performance by reducing the oxygen cost of exercise and enhancing skeletal muscle function. However, the mechanisms underlying these effects are not well understood. The purpose of this study was to assess changes in skeletal muscle energy metabolism associated with exercise performance in a zebrafish model. Fish were exposed to sodium nitrate (60.7 mg/L, 303.5 mg/L, 606.9 mg/L), or control water, for 21 days and analyzed at intervals (5, 10, 20, 30, 40 cm/s) during a 2-h strenuous exercise test. We measured oxygen consumption during an exercise test and assessed muscle nitrate concentrations, gene expression, and the muscle metabolome before, during, and after exercise. Nitrate exposure reduced the oxygen cost of exercise and increased muscle nitrate concentrations at rest, which were reduced with increasing exercise duration. In skeletal muscle, nitrate treatment upregulated expression of genes central to nutrient sensing ( mtor ), redox signaling ( nrf2a ), and muscle differentiation ( sox6 ). In rested muscle, nitrate treatment increased phosphocreatine ( P = 0.002), creatine ( P = 0.0005), ATP ( P = 0.0008), ADP ( P = 0.002), and AMP ( P = 0.004) compared with rested-control muscle. Following the highest swimming speed, concentration of phosphocreatine ( P = 8.0 × 10 -5 ), creatine ( P = 6.0 × 10 -7 ), ATP ( P = 2.0 × 10 -6 ), ADP ( P = 0.0002), and AMP ( P = 0.004) decreased compared with rested nitrate muscle. Our data suggest nitrate exposure in zebrafish lowers the oxygen cost of exercise by changing the metabolic programming of muscle prior to exercise and increasing availability of energy-rich metabolites required for exercise. NEW & NOTEWORTHY We show that skeletal muscle nitrate concentration is higher with supplementation at rest and was lower in groups with increasing exercise duration in a zebrafish model. The higher availability of nitrate at rest is associated with upregulation of key nutrient-sensing genes and greater availability of energy-producing metabolites (i.e., ATP, phosphocreatine, glycolytic intermediates). Overall, nitrate supplementation may lower oxygen cost of exercise through improved fuel availability resulting from metabolic programming of muscle prior to exercise.

Introduction: Skeletal muscle mitochondria have dynamic shifts in oxidative metabolism to meet energy demands of aerobic exercise. Specific complexes oxidize lipid and nonlipid substrates. It is unclear if aerobic exercise stimulates intrinsic oxidative metabolism of mitochondria or varies between substrates., Methods: We studied mitochondrial metabolism in sedentary male and female adults (n = 11F/4M) who were free of major medical conditions with mean ± SD age of 28 ± 7 yr, peak aerobic capacity of 2.0 ± 0.4 L·min-1, and body mass index of 22.2 ± 2 kg·m-2. Biopsies were collected from the vastus lateralis muscle on separate study days at rest or 15 min after exercise (1 h cycling at 65% peak aerobic capacity). Isolated mitochondria were analyzed using high-resolution respirometry of separate titration protocols for lipid (palmitoylcarnitine, F-linked) and nonlipid substrates (glutamate-malate, N-linked; succinate S-linked). Titration protocols distinguished between oxidative phosphorylation and leak respiration and included the measurement of reactive oxygen species emission (H2O2). Western blotting determined the protein abundance of electron transfer flavoprotein (ETF) subunits, including inhibitory methylation site on ETF-β., Results: Aerobic exercise induced modest increases in mitochondrial respiration because of increased coupled respiration across F-linked (+13%, P = 0.08), N(S)-linked (+14%, P = 0.09), and N-linked substrates (+17%, P = 0.08). Prior exercise did not change P:O ratio. Electron leak to H2O2 increased 6% increased after exercise (P = 0.06) for lipid substrates but not for nonlipid. The protein abundance of ETF-α or ETF-β subunit or inhibitory methylation on ETF-β was not different between rest and after exercise., Conclusion: In sedentary adults, the single bout of moderate-intensity cycling induced modest increases for intrinsic mitochondrial oxidative phosphorylation that was consistent across multiple substrates., (Copyright © 2021 by the American College of Sports Medicine.)

We previously reported xanthohumol (XN), and its synthetic derivative tetrahydro-XN (TXN), attenuates high-fat diet (HFD)-induced obesity and metabolic syndrome in C57Bl/6J mice. The objective of the current study was to determine the effect of XN and TXN on lipid accumulation in the liver. Non-supplemented mice were unable to adapt their caloric intake to 60% HFD, resulting in obesity and hepatic steatosis; however, TXN reduced weight gain and decreased hepatic steatosis. Liver transcriptomics indicated that TXN might antagonize lipogenic PPARγ actions in vivo. XN and TXN inhibited rosiglitazone-induced 3T3-L1 cell differentiation concomitant with decreased expression of lipogenesis-related genes. A peroxisome proliferator activated receptor gamma (PPARγ) competitive binding assay showed that XN and TXN bind to PPARγ with an IC 50 similar to pioglitazone and 8-10 times stronger than oleate. Molecular docking simulations demonstrated that XN and TXN bind in the PPARγ ligand-binding domain pocket. Our findings are consistent with XN and TXN acting as antagonists of PPARγ., Competing Interests: YZ, GB, CM, ML, VH, CL, CW, DJ, MR, TS, CM, JS, AG No competing interests declared, (© 2021, Zhang et al.)

Eyewitness identification via lineup procedures is an important and widely used source of evidence in criminal cases. However, the scientific literature provides inconsistent guidance on a very basic feature of lineup procedure: lineup size. In two experiments, we examined whether the number of fillers affects diagnostic accuracy in a lineup, as assessed with receiver-operating characteristic (ROC) analysis. Showups (identification procedures with one face) led to lower discriminability than simultaneous lineups. However, in neither experiment did the number of fillers in a lineup affect discriminability. We also evaluated competing models of decision-making from lineups. This analysis indicated that the standard Independent Observations (IO) model, which assumes a decision rule based on the comparison of memory strength signals generated by each face in a lineup, is incapable of reproducing the lower level of performance evident in showups. We could not adjudicate between the Ensemble model, which assumes a decision rule based on the comparison of the strength of each face with the mean strength across the lineup, and a newly introduced Dependent Observations model, which adopts the same decision rule as the IO model, but with correlated signals across faces. We draw lessons for users of lineup procedures and for basic research on eyewitness decision making. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Limited information exists regarding the factor IX (FIX) coagulant activity (FIX:C) measured by different assays following FIX-Padua gene therapy., Objective: Assess for the first time FIX:C in five commonly used coagulation assays in plasma samples from hemophilia B subjects receiving FIX-Padua gene transfer., Methods: FIX:C was compared between central (n = 1) and local laboratories (n = 5) in the study, and across four commonly used FIX:C one-stage assays and one FIX:C chromogenic assay. For comparison, samples of pooled congenital FIX-deficient plasma spiked with purified recombinant human FIX (rHFIX)-Padua protein or rHFIX (nonacog alfa) to obtain FIX:C concentrations from ~20% to ~40% were tested., Results: FIX:C results at local laboratories strongly correlated with central laboratory results. However, absolute values at the central laboratory were consistently lower than those at local laboratories. Across five different FIX:C assays, a consistent pattern of FIX:C was observed for subjects receiving fidanacogene elaparvovec-expressed gene transfer. Use of Actin FSL activated partial thromboplastin time (APTT) reagent in the central laboratory resulted in lower FIX:C values compared with other APTT reagents tested. The chromogenic assay determined lower FIX:C than any of the one-stage assays. The rHFIX-Padua protein-spiked samples showed similar results. In contrast, FIX:C results for rHFIX-nonacog alfa measured within 25% of expected for all one-stage assays and below 25% in the chromogenic assay., Conclusions: Assay-based differences in FIX:C were observed for fidanacogene elaparvovec transgene product and rHFIX-Padua protein, suggesting the variable FIX:C determined with different assay reagents is inherent to the FIX-Padua protein and is not specific to gene therapy-derived FIX-Padua., (© 2021 Pfizer Inc. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)