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For any tensor A, the first invariant is given by HT ht and the second invariant is given by HT ht . [Extracted from the article]

We evaluated the vaccine effectiveness (VE) of two doses of recombinant zoster vaccine (RZV) against herpes zoster (HZ) and postherpetic neuralgia (PHN) in Chinese adults at Kaiser Permanente Southern California (KPSC). Chinese KPSC members were identified based on self-reported ethnicity or self-reported preferred spoken/written language. Those aged ≥50 years who received two doses of RZV 4 weeks to ≤ 6 months apart were matched 1:4 to RZV unvaccinated Chinese members and followed through June 2022; second doses were accrued 6/1/2018-12/31/2020. We estimated incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) comparing outcomes (HZ and PHN). Adjusted VE (%) was calculated as (1-aHR)×100. 3978 RZV vaccinated Chinese members were matched to 15,912 RZV unvaccinated Chinese members. The incidence per 1000 person-years (95% CI) of HZ in the vaccinated group was 1.5 (0.9-2.5) and 10.9 (9.8-12.1) in the unvaccinated group; aHR (95% CI) was 0.12 (0.07-0.21). Adjusted VE (95% CI) was 87.6% (78.9-92.7) against HZ. We identified 0 PHN cases in the vaccinated group and 19 in the unvaccinated group. Among Chinese adults aged ≥50 years, two doses of RZV provided substantial protection against HZ and PHN supporting the real-world effectiveness of the vaccine in this population.

Background: This work seeks to understand whether IL15-incorporating treatments improve response to radiotherapy and uncover mechanistic rationale for overcoming resistance to IL15 agonism using novel therapeutic combinations., Experimental Design: Orthotopic tumor models of PDAC were used to determine response to treatment. IL15-/- and Rag1-/- mouse models were employed to determine dependence on IL15 and CTLs, respectively. Flow cytometry was used to assess immune cell frequency and activation state. Phospho-proteomic analyses were used to characterize intracellular signaling pathways., Results: We show that the combination of radiation therapy (RT) and an IL15/IL15Ra fusion complex (denoted IL15c) fails to confer anti-tumor efficacy; however, a CD8-driven anti-tumor immune response is elicited with the concurrent administration of an aCD25 Treg-depleting antibody. Using IL15-/- and Rag1-/- mice, we demonstrate that response to RT + IL15c + aCD25 is dependent on both IL15 and CTLs. Furthermore, despite an equivalent survival benefit following treatment with RT + IL15c + aCD25 and combination RT + PD1-IL2v, a novel immunocytokine with PD-1 and IL2Rβγ binding domains, CTL immunophenotyping and phospho-proteomic analysis of intracellular metabolites showed significant upregulation of activation and functionality in CD8 T cells treated with RT + PD1-IL2v. Finally, we show the immunostimulatory response to RT + PD1-IL2v is significantly diminished with a concurrent lack of TCF+ CD8 T cell generation in the absence of functional IL15 signaling., Conclusions: Our results are illustrative of a mechanism wherein unimpeded effector T cell activation through IL2Rβ signaling and Treg inhibition are necessary in mediating an anti-tumor immune response.

Tulving characterized semantic memory as a vast repository of meaning that underlies language and many other cognitive processes. This perspective on lexical and conceptual knowledge galvanized a new era of research undertaken by numerous fields, each with their own idiosyncratic methods and terminology. For example, "concept" has different meanings in philosophy, linguistics, and psychology. As such, many fundamental constructs used to delineate semantic theories remain underspecified and/or opaque. Weak construct specificity is among the leading causes of the replication crisis now facing psychology and related fields. Term ambiguity hinders cross-disciplinary communication, falsifiability, and incremental theory-building. Numerous cognitive subdisciplines (e.g., vision, affective neuroscience) have recently addressed these limitations via the development of consensus-based guidelines and definitions. The project to follow represents our effort to produce a multidisciplinary semantic glossary consisting of succinct definitions, background, principled dissenting views, ratings of agreement, and subjective confidence for 17 target constructs (e.g., abstractness, abstraction, concreteness, concept, embodied cognition, event semantics, lexical-semantic, modality, representation, semantic control, semantic feature, simulation, semantic distance, semantic dimension). We discuss potential benefits and pitfalls (e.g., implicit bias, prescriptiveness) of these efforts to specify a common nomenclature that other researchers might index in specifying their own theoretical perspectives (e.g., They said X, but I mean Y)., (© 2024. The Author(s).)

DosT and DosS are heme-based kinases involved in sensing and signaling O 2 tension in the microenvironment of Mycobacterium tuberculosis (Mtb). Under conditions of low O 2 , they activate >50 dormancy-related genes and play a pivotal role in the induction of dormancy and associated drug resistance during tuberculosis infection. In this work, we reexamine the O 2 binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.3±1.0 μM and 0.46±0.08 μM respectively, which are six to eight-fold stronger than what has been widely referred to in literature. Furthermore, stopped-flow kinetic studies reveal association and dissociation rate constants of 0.84 μM -1  s -1 and 2.8 s -1 , respectively for DosT, and 7.2 μM -1  s -1 and 3.3 s -1 , respectively for DosS. Remarkably, these tighter O 2 binding constants correlate with distinct stages of hypoxia-induced non-replicating persistence in the Wayne model of Mtb. This knowledge opens doors to deconvoluting the intricate interplay between hypoxia adaptation stages and the signal transduction capabilities of these important heme-based O 2 sensors., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

Cryptococcus neoformans is a fungal pathogen responsible for >200,000 yearly cases with a mortality as high as 81%. This burden results, in part, from an incomplete understanding of its pathogenesis and ineffective antifungal treatments; hence, there is a pressing need to understand the biology and host interactions of this yeast to develop improved treatments. Protein palmitoylation is important for cryptococcal virulence, and we previously identified the substrates of its main palmitoyl transferase. One of them was encoded by the uncharacterized gene CNAG_02129. In the filamentous fungus Neurospora crassa , a homolog of this gene named hyphal anastomosis protein 13 plays a role in proper cellular communication and filament fusion. In Cryptococcus , cellular communication is essential during mating; therefore, we hypothesized that CNAG_02129, which we named hyphal anastomosis protein 1 ( HAM1 ), may play a role in mating. We found that ham1 Δ mutants produce more fusion products during mating, filament more robustly, and exhibit competitive fitness defects under mating and non-mating conditions. Additionally, we found several differences with the major virulence factor, the polysaccharide capsule, that may affect virulence, consistent with prior studies linking virulence to mating. We observed that ham1 Δ mutants have decreased capsule attachment and transfer but exhibit higher amounts of exopolysaccharide shedding and biofilm production. Finally, HAM1 expression is significantly lower in mating media relative to non-mating conditions, consistent with it acting as a negative regulator of mating. Understanding the connection between mating and virulence in C. neoformans may open new avenues of investigation into ways to improve the treatment of this disease., Importance: Fungal mating is a vital part of the lifecycle of the pathogenic yeast Cryptococcus neoformans . More than just ensuring the propagation of the species, mating allows for sexual reproduction to occur and generates genetic diversity as well as infectious propagules that can invade mammalian hosts. Despite its importance in the biology of this pathogen, we still do not know all of the major players regulating the mating process and if they are involved or impact its pathogenesis. Here, we identified a novel negative regulator of mating that also affects certain cellular characteristics known to be important for virulence. This gene, which we call HAM1 , is widely conserved across the cryptococcal family as well as in many pathogenic fungal species. This study will open new avenues of exploration regarding the function of uncharacterized but conserved genes in a variety of pathogenic fungal species and specifically in serotype A of C. neoformans ., Competing Interests: The authors declare no conflict of interest.

Bias in advanced heart failure therapy allocation results in inequitable outcomes for minoritized populations. The purpose of this study was to examine how bias is introduced during group decision-making with an interprofessional team using Breathett's Model of Heart Failure Decision-Making. This was a secondary qualitative descriptive analysis from a study focused on bias in advanced heart failure therapy allocation. Team meetings were recorded and transcribed from four heart failure centers. Breathett's Model was applied both deductively and inductively to transcripts ( n  = 12). Bias was identified during discussions about patient characteristics, clinical fragility, and prior clinical decision-making. Some patients were labeled as "good citizens" or as adherent/non-adherent while others benefited from strong advocacy from interprofessional team members. Social determinants of health also impacted therapy allocation. Interprofessional collaboration with advanced heart failure therapy allocation may be enhanced with the inclusion of patient advocates and limit of clinical decision-making using subjective data.

The recombinant zoster vaccine (RZV) was licensed in the US for prevention of herpes zoster (HZ) in 2017. We conducted a literature search (January 1, 2017-August 1, 2023) using PubMed, Embase, and Scopus to consolidate the real-world evidence related to RZV. Overall, RZV effectiveness against HZ was high across the studied populations in real-world settings, including adults aged ≥ 50 years and patients aged ≥ 18 years with immunodeficiency or immunosuppression. Effectiveness was higher with two doses versus one dose, especially in elderly people and immunocompromised individuals. The safety profile of RZV was broadly consistent with that established in clinical trials. RZV does not appear to increase the risk of disease flares in patients with immune-mediated diseases. Approximately two-thirds of individuals received a second RZV dose within 2-6 months after the first dose. Collectively, RZV effectiveness against HZ was high, and these real-world studies reaffirm its favorable benefit-risk profile.

Traditional disease surveillance systems are ill-equipped to handle climate change-driven shifts in pathogen dynamics. If paired with wastewater surveillance, a cost-effective and scalable approach for generating high-resolution health data, such next-generation systems can enable effective resource allocation and delivery of targeted interventions.

Microbes utilize numerous metal cofactor-containing proteins to recognize and respond to constantly fluctuating redox stresses in their environment. Gaining an understanding of how these metalloproteins sense redox events, and how they communicate such information downstream to DNA to modulate microbial metabolism, is a topic of great interest to both chemists and biologists. In this article, we review recently characterized examples of metalloprotein sensors, focusing on the coordination and oxidation state of the metals involved, how these metals are able to recognize redox stimuli, and how the signal is transmitted beyond the metal center. We discuss specific examples of iron, nickel, and manganese-based microbial sensors, and identify gaps in knowledge in the field of metalloprotein-based signal transduction pathways., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ambika Bhagi-Damodaran reports financial support was provided by Regents of the University of Minnesota. Ambika Bhagi-Damodaran reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A haircut usually lasts under an hour. But how long does it take to recognize that something is an instance of a haircut? And is this "time-to-perceive" a part of the representation of concepts like haircut? Across three experiments testing lexical decision, word recognition, and semantic decision, we show that the amount of time people say it takes to perceive a concept in the world (e.g., haircut, dandelion, or merit) predicts how long it takes for them to respond to a word referring to that thing, over and above the effects of other lexical-semantic variables (e.g., word frequency, concreteness) and other variables related to conceptual complexity (e.g., how confusable a concept is with other, similar concepts, or the diversity of the contexts in which a concept appears). These results suggest that our experience of how long it takes to recognize an instance of a concept can become a part of its representation, and that we simulate this information when reading words. Consequently, we suggest that time may be an embodied property of concepts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Davis, Yee. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many clinical processes include multidisciplinary group decision-making, yet few methods exist to evaluate the presence of implicit bias during this collective process. Implicit bias negatively impacts the equitable delivery of evidence-based interventions and ultimately patient outcomes. Since implicit bias can be difficult to assess, novel approaches are required to detect and analyze this elusive phenomenon. In this paper, we describe how the de Groot Critically Reflective Diagnoses Protocol (DCRDP) can be used as a data analysis tool to evaluate group dynamics as an essential foundation for exploring how interactions can bias collective clinical decision-making. The DCRDP includes 6 distinct criteria: challenging groupthink, critical opinion sharing, research utilization, openness to mistakes, asking and giving feedback, and experimentation. Based on the strength and frequency of codes in the form of exemplar quotes, each criterion was given a numerical score of 1-4 with 1 representing teams that are interactive, reflective, higher functioning, and more equitable. When applied as a coding scheme to transcripts of recorded decision-making meetings, the DCRDP was revealed as a practical tool for examining group decision-making bias. It can be adapted to a variety of clinical, educational, and other professional settings as an impetus for recognizing the presence of team-based bias, engaging in reflexivity, informing the design and testing of implementation strategies, and monitoring long-term outcomes to promote more equitable decision-making processes in healthcare., Competing Interests: LA has received grant funding from the American Heart Association, NIH, and PCORI; and consulting fees from Amgen, Boston Scientific, Cytokinetics, Novartis, and WCG ACI Clinical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MS declared a past co-authorship [10.1089/heq.2020.0044] with the author(s) KB., (Copyright © 2023 Pool, Hebdon, de Groot, Yee, Herrera-Theut, Yee, Allen, Hasan, Lindenfeld, Calhoun, Carnes, Sweitzer and Breathett.)

Distributional semantic models (DSMs) are a primary method for distilling semantic information from corpora. However, a key question remains: What types of semantic relations among words do DSMs detect? Prior work typically has addressed this question using limited human data that are restricted to semantic similarity and/or general semantic relatedness. We tested eight DSMs that are popular in current cognitive and psycholinguistic research (positive pointwise mutual information; global vectors; and three variations each of Skip-gram and continuous bag of words (CBOW) using word, context, and mean embeddings) on a theoretically motivated, rich set of semantic relations involving words from multiple syntactic classes and spanning the abstract-concrete continuum (19 sets of ratings). We found that, overall, the DSMs are best at capturing overall semantic similarity and also can capture verb-noun thematic role relations and noun-noun event-based relations that play important roles in sentence comprehension. Interestingly, Skip-gram and CBOW performed the best in terms of capturing similarity, whereas GloVe dominated the thematic role and event-based relations. We discuss the theoretical and practical implications of our results, make recommendations for users of these models, and demonstrate significant differences in model performance on event-based relations., (© 2023 Cognitive Science Society LLC.)

Background US regulatory framework for advanced heart failure therapies (AHFT), ventricular assist devices, and heart transplants, delegate eligibility decisions to multidisciplinary groups at the center level. The subjective nature of decision-making is at risk for racial, ethnic, and gender bias. We sought to determine how group dynamics impact allocation decision-making by patient gender, racial, and ethnic group. Methods and Results We performed a mixed-methods study among 4 AHFT centers. For ≈ 1 month, AHFT meetings were audio recorded. Meeting transcripts were evaluated for group function scores using de Groot Critically Reflective Diagnoses protocol (metrics: challenging groupthink, critical opinion sharing, openness to mistakes, asking/giving feedback, and experimentation; scoring: 1 to 4 [high to low quality]). The relationship between summed group function scores and AHFT allocation was assessed via hierarchical logistic regression with patients nested within meetings nested within centers, and interaction effects of group function score with gender and race, adjusting for patient age and comorbidities. Among 87 patients (24% women, 66% White race) evaluated for AHFT, 57% of women, 38% of men, 44% of White race, and 40% of patients of color were allocated to AHFT. The interaction between group function score and allocation by patient gender was statistically significant ( P =0.035); as group function scores improved, the probability of AHFT allocation increased for women and decreased for men, a pattern that was similar irrespective of racial and ethnic groups. Conclusions Women evaluated for AHFT were more likely to receive AHFT when group decision-making processes were of higher quality. Further investigation is needed to promote routine high-quality group decision-making and reduce known disparities in AHFT allocation.

Purpose: Acute flaccid myelitis (AFM), an uncommon but serious neurologic condition, primarily affects children, and can progress quickly to paralysis and respiratory failure. Data on long-term outcomes of patients with AFM are limited. This study reports on functional status through 12 months for AFM patients who became ill in 2018 in the United States., Methods: Health departments collected information on outcomes at 6 and 12 months after onset of AFM using a standardized form that asked patients or their parents/guardians about functional status. Analyses were restricted to confirmed cases., Results: Of the 238 confirmed AFM cases reported to CDC in 2018, 90 (38%) had assessments at 6 months, 82 (34%) at 12 months, and 49 (21%) at both 6 and 12 months. Among the 49 patients with data at both time points, the proportion of patients reporting significant or severe impairment at 6 months ranged from 2% to 59% depending on the outcome. Although proportions decreased by 12 months and ranged from 2% to 51%, most patients had some impairment at 12 months. No deaths were reported., Conclusion: Six- and 12-month outcomes in patients with onset of AFM in 2018 span a wide range of functionality, particularly of upper and lower extremities. Importantly, improvement appears to occur over time in some patients.

Objectives: Older adults face racism, sexism, and ageism. As the U.S. population ages, it is important to understand how the current population views older adults., Methods: Participants recruited through Amazon's Mechanical Turk provided perceptions of older Black and White models' photographs. Using mixed-effect models, we assessed interactions between race and gender of participants and models., Results: Among Participants of Color and White participants ( n  = 712, 70% non-Hispanic White, 70% women, mean 37.81 years), Black models were perceived as more attractive, less threatening, and sadder than White models, but differences were greater for White participants (race-by-race interaction: attractive p  = 0.003, threatening p  = 0.009, sad p  = 0.016). Each gender perceived their respective gender as more attractive (gender-by-gender interaction p  < 0.0001). Male and female participants perceived male models as happier than female models, but differences were greater for male participants ( p  = 0.026). Irrespective of participant age group, women were perceived as more threatening ( p  = 0.012). Other perceptions were not significant., Discussion: Participants had few biases toward older Black and White models, while gender biases favored men., Competing Interests: Authors declare no conflict of interest., (© Forest Melton et al., 2022; Published by Mary Ann Liebert, Inc.)

Introduction: This study compares an entirely patient reported modification of the Constant-Murley Score (CS) (the Multiple Assessment Subjective Shoulder Score [MASSS]), with the CS in symptomatic patients with non-instability shoulder pathology., Hypothesis: The hypothesis is that the sub scores and overall score of the MASSS will be well correlated and in high agreement to the corresponding scores of the CS., Materials and Methods: The MASSS, the CS and adjusted-CS (a-CS) were administered to 74 patients. The MASSS replaced the strength and ROM domains of the CS with SANE scores. Correlations, differences, agreement, test-retest reliability, and internal consistency were assessed using Pearson's R test, paired t-test, Bland-Altman method, intraclass correlations (ICC) and Cronbach's alpha., Results: Correlation between MASSS and CS (0.834) and a-CS (0.824) were excellent. Total MASSS (54.0) was higher than CS (41.8) (p<0.001) and a-CS (47.8) (p<0.05). MASSS strength and ROM domains were higher than those of the CS (Strength: 13.4 v 5.3 [p<0.001], ROM: 24.8 v 20.8 [p<0.001]. There was a floor effect for the strength domain of the CS (46.7% minimum score), but not the MASSS (0% minimum score). MASSS internal consistency (0.626-0.734) was better than the CS (0.401-0.643). Test re-test reliability of the total MASSS (ICC 0.93) and the strength (ICC 0.90) and ROM (ICC 0.86) domains was excellent., Discussion: The MASSS has several advantages over the CS. Although the correlation of the total MASSS with the CS and a-CS was high, there was poor agreement in the strength and the ROM domains and therefore the MASSS value is not interchangeable with the CS, but rather should be considered as an alternative., Level of Evidence: II; Prospective cohort study., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

This study focuses on the impacts of implementing an online curriculum at a graduate school in South Korea in response to the COVID-19 pandemic. A framework distinguishing impacts to academic, educational, and institutional stakeholders from the virtualization of curricula as well as general COVID-19 prevention measures is invoked to help understand the impacts of these changes. These impacts are sourced from general graduate school operations, course evaluations for two compulsory courses, and unofficial interviews with students and professors. A statistical evaluation of the course evaluations suggested no significant difference between the online format of 2020 and the traditional in person formats in prior years in terms of academics and education. Unofficial meetings with students and faculty revealed technical issues throughout 2020, which many could not be resolved due to the variety of different computer systems at the school as well as limited technical support. Most importantly, students stated they were suffering from prolonged mental and emotional distress such as feeling isolated. Lessons learned include having academic institutions prepare for difficulties in technical support, educational infrastructure investments, compliance, as well as student body mental health.

Identifying genetic variants associated with lower waist-to-hip ratio can reveal new therapeutic targets for abdominal obesity. We use exome sequences from 362,679 individuals to identify genes associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI), a surrogate for abdominal fat that is causally linked to type 2 diabetes and coronary heart disease. Predicted loss of function (pLOF) variants in INHBE associate with lower WHRadjBMI and this association replicates in data from AMP-T2D-GENES. INHBE encodes a secreted protein, the hepatokine activin E. In vitro characterization of the most common INHBE pLOF variant in our study, indicates an in-frame deletion resulting in a 90% reduction in secreted protein levels. We detect associations with lower WHRadjBMI for variants in ACVR1C, encoding an activin receptor, further highlighting the involvement of activins in regulating fat distribution. These findings highlight activin E as a potential therapeutic target for abdominal obesity, a phenotype linked to cardiometabolic disease., (© 2022. The Author(s).)

Sensorimotor-based theories of cognition predict that even subtle developmental motor differences, such as those characterizing autism spectrum disorder (ASD), impact how we represent the meaning of manipulable objects (e.g., faucet). Here, we test 85 neurotypical participants, who varied widely on the Adult Autism Spectrum Quotient (AQ), a measure intended to capture variability in ASD characteristics in the general adult population (participant scores were all below the clinical threshold for autism). Participants completed a visual world eyetracking task designed to assess the activation of conceptual representations of manipulable objects. Participants heard words referring to manually manipulable objects (e.g., faucet) while we recorded their eye movements to arrays of four objects: the named object, a related object typically manipulated similarly (e.g., jar), and two unrelated objects. Consistent with prior work, we observed more looks to the related object than to the unrelated ones (i.e., a manipulation-relatedness effect). This effect likely reflects the overlapping conceptual representations of objects sharing manipulation characteristics (e.g., faucet and jar), due to embodied sensorimotor properties being part of their representations. Critically, we observed-among typically developed young adults-that as AQ scores increased, manipulation-relatedness effects decreased. In contrast, in a visual control condition, in which a target object was paired with related objects of a similar shape (e.g., snake and rope), relatedness effects increased with AQ scores. The results show that AQ scores can predict variation in how object-concept representations are activated for typically developed individuals. More speculatively, they are consistent with the hypothesis that in individuals with ASD, differences in object-concept representations emerge at least in part via differences in sensorimotor experience., Competing Interests: The authors have declared that no competing interests exist.

Context is critical for conceptual processing, but the mechanism underpinning its encoding and reinstantiation during abstract concept processing is unclear. Context may be especially important for abstract concepts-we investigated whether episodic context is recruited differently when processing abstract compared with concrete concepts. Experiments 1 and 2 presented abstract and concrete words in arbitrary contexts at encoding (Experiment 1: red/green colored frames; Experiment 2: male/female voices). Recognition memory for these contexts was worse for abstract concepts. Again using frame color and voice as arbitrary contexts, respectively, Experiments 3 and 4 presented words from encoding in the same or different context at test to determine whether there was a greater recognition memory benefit for abstract versus concrete concepts when the context was unchanged between encoding and test. Instead, abstract concepts were less likely to be remembered when context was retained. This suggests that at least some types of episodic context-when arbitrary-are attended less, and may even be inhibited, when processing abstract concepts. In Experiment 5, we utilized a context-spatial location-which (as we show) tends to be relevant during real-world processing of abstract concepts. We presented words in different locations, preserving or changing location at test. Location retention conferred a recognition memory advantage for abstract concepts. Thus, episodic context may be encoded with abstract concepts when context is relevant to real-world processing. The systematic contexts necessary for understanding abstract concepts may lead to arbitrary context inhibition, but greater attention to contexts that tend to be more relevant during real-world processing., (© 2021. The Psychonomic Society, Inc.)