bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function
Authors: Jain Nayan , Zhao Zeguo , Koche Richard P. , Antelope Chenling , Gozlan Yosi , Montalbano Antonino , Brocks David , Lopez Michael , Dobrin Anton , Shi Yuzhe , Gunset Gertrude , Giavridis Theodoros , Sadelain Michel
Published: January 2024

Abstract
Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that the genetic disruption of SUV39H1, which encodes a histone-3, lysine-9 methyl-transferase, enhances the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. Persisting SUV39H1-edited CAR T cells demonstrate improved expansion and tumor rejection upon multiple rechallenges. Transcriptional and genome accessibility profiling of repeatedly challenged CAR T cells shows improved expression and accessibility of memory transcription factors in SUV39H1-edited CAR T cells. SUV39H1 editing also reduces expression of inhibitory receptors and limits exhaustion in CAR T cells that have undergone multiple rechallenges. Our findings thus demonstrate the potential of epigenetic programming of CAR T cells to balance their function and persistence for improved adoptive cell therapies.
Significance:
T cells engineered with CD28-based CARs possess robust effector function and antigen sensitivity but are hampered by limited persistence, which may result in tumor relapse. We report an epigenetic strategy involving disruption of the SUV39H1-mediated histone-silencing program that promotes the functional persistence of CD28-based CAR T cells.

See related article by López-Cobo et al., p. 120.

This article is featured in Selected Articles from This Issue, p. 5
Data from GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress
Authors: Zhou Weihua , Zhao Zitong , Lin Angelica , Yang John Z. , Xu Jie , Wilder-Romans Kari , Yang Annabel , Li Jing , Solanki Sumeet , Speth Jennifer M. , Walker Natalie , Scott Andrew J. , Wang Lu , Wen Bo , Andren Anthony , Zhang Li , Kothari Ayesha U. , Yao Yangyang , Peterson Erik R. , Korimerla Navyateja , Werner Christian K. , Ullrich Alexander , Liang Jessica , Jacobson Janna , Palavalasa Sravya , O’Brien Alexandra M. , Elaimy Ameer L. , Ferris Sean P. , Zhao Shuang G. , Sarkaria Jann N. , Győrffy Balázs , Zhang Shuqun , Al-Holou Wajd N. , Umemura Yoshie , Morgan Meredith A. , Lawrence Theodore S. , Lyssiotis Costas A. , Peters-Golden Marc , Shah Yatrik M. , Wahl Daniel R.
Published: January 2024

ABSTRACT
How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes nonhomologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard-of-care genotoxic treatments. The GTP–Rac1–PP5–Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in nonmalignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment.
SIGNIFICANCE:
A newly described GTP-dependent signaling axis is an unexpected link between nucleotide metabolism and DNA repair. Disrupting this pathway can overcome cancer resistance to genotoxic therapy while augmenting it can mitigate genotoxic injury of normal tissues.

This article is featured in Selected Articles from This Issue, p. 5
Data from Vitamin B6 Competition in the Tumor Microenvironment Hampers Antitumor Functions of NK Cells
Authors: He Chunbo , Wang Dezhen , Shukla Surendra K. , Hu Tuo , Thakur Ravi , Fu Xiao , King Ryan J. , Kollala Sai Sundeep , Attri Kuldeep S. , Murthy Divya , Chaika Nina V. , Fujii Yuki , Gonzalez Daisy , Pacheco Camila G. , Qiu Yudong , Singh Pankaj K. , Locasale Jason W. , Mehla Kamiya
Published: January 2024

Abstract
Nutritional factors play crucial roles in immune responses. The tumor-caused nutritional deficiencies are known to affect antitumor immunity. Here, we demonstrate that pancreatic ductal adenocarcinoma (PDAC) cells can suppress NK-cell cytotoxicity by restricting the accessibility of vitamin B6 (VB6). PDAC cells actively consume VB6 to support one-carbon metabolism, and thus tumor cell growth, causing VB6 deprivation in the tumor microenvironment. In comparison, NK cells require VB6 for intracellular glycogen breakdown, which serves as a critical energy source for NK-cell activation. VB6 supplementation in combination with one-carbon metabolism blockage effectively diminishes tumor burden in vivo. Our results expand the understanding of the critical role of micronutrients in regulating cancer progression and antitumor immunity, and open new avenues for developing novel therapeutic strategies against PDAC.
Significance:
The nutrient competition among the different tumor microenvironment components drives tumor growth, immune tolerance, and therapeutic resistance. PDAC cells demand a high amount of VB6, thus competitively causing NK-cell dysfunction. Supplying VB6 with blocking VB6-dependent one-carbon metabolism amplifies the NK-cell antitumor immunity and inhibits tumor growth in PDAC models.

This article is featured in Selected Articles from This Issue, p. 5
Data from Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study
Authors: Kelly William K. , Danila Daniel C. , Lin Chia-Chi , Lee Jae-Lyun , Matsubara Nobuaki , Ward Patrick J. , Armstrong Andrew J. , Pook David , Kim Miso , Dorff Tanya B. , Fischer Stefanie , Lin Yung-Chang , Horvath Lisa G. , Sumey Christopher , Yang Zhao , Jurida Gabor , Smith Kristen M. , Connarn Jamie N. , Penny Hweixian L. , Stieglmaier Julia , Appleman Leonard J.
Published: January 2024

Abstract
Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)–targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development.
Significance:
Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer.

See related commentary by Hage Chehade et al., p. 20.

See related article by Nolan-Stevaux et al., p. 90.

This article is featured in Selected Articles from This Issue, p. 5
Data from SUV39H1 Ablation Enhances Long-term CAR T Function in Solid Tumors
Authors: López-Cobo Sheila , Fuentealba Jaime R. , Gueguen Paul , Bonté Pierre-Emmanuel , Tsalkitzi Kyriaki , Chacón Irena , Glauzy Salomé , Bohineust Armelle , Biquand Ariane , Silva Lisseth , Gouveia Zelia , Goudot Christel , Perez Franck , Saitakis Michael , Amigorena Sebastian
Published: January 2024

Abstract
Failure of adoptive T-cell therapies in patients with cancer is linked to limited T-cell expansion and persistence, even in memory-prone 41BB-(BBz)–based chimeric antigen receptor (CAR) T cells. We show here that BBz-CAR T-cell stem/memory differentiation and persistence can be enhanced through epigenetic manipulation of the histone 3 lysine 9 trimethylation (H3K9me3) pathway. Inactivation of the H3K9 trimethyltransferase SUV39H1 enhances BBz-CAR T cell long-term persistence, protecting mice against tumor relapses and rechallenges in lung and disseminated solid tumor models up to several months after CAR T-cell infusion. Single-cell transcriptomic (single-cell RNA sequencing) and chromatin opening (single-cell assay for transposase accessible chromatin) analyses of tumor-infiltrating CAR T cells show early reprogramming into self-renewing, stemlike populations with decreased expression of dysfunction genes in all T-cell subpopulations. Therefore, epigenetic manipulation of H3K9 methylation by SUV39H1 optimizes the long-term functional persistence of BBz-CAR T cells, limiting relapses, and providing protection against tumor rechallenges.
Significance:
Limited CAR T-cell expansion and persistence hinders therapeutic responses in solid cancer patients. We show that targeting SUV39H1 histone methyltransferase enhances 41BB-based CAR T-cell long-term protection against tumor relapses and rechallenges by increasing stemness/memory differentiation. This opens a safe path to enhancing adoptive cell therapies for solid tumors.

See related article by Jain et al., p. 142.

This article is featured in Selected Articles from This Issue, p. 5
TABLE 3 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

Survival associations and absolute differences of the pathway activity scores for the Black/AA and White patient cohorts. (A) Cox regression was used to analyze the activity score of each pathway. PROGENy scores were analyzed using Kaplan–Meier analysis and the log-rank test to obtain HRs, 95% confidence intervals, P values, and SEs. (B) The absolute difference between the Black/AA and the White cohorts mean pathway activity scores. P-value (two sample t test) represents the associated P-value from a two-sample t test
TABLE 2 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

The top two significant genes associated with overall survival across nine colorectal cancer relevant signaling pathways for both Black/AA and White cohorts from the TCGA, PanCancer Atlas dataset. A Kaplan–Meier estimate, and log-rank test were used to compute the association between patient overall survival and gene expression and report the associated HR, confidence intervals, P-value, P-adj (P-adjusted value), and SE. “Patients” indicates the number of patients for which data were available. “Significant”, indicates the number of significant genes out of the total number of genes for this pathway. The fold change and P-value cutoff used were 0.5 and 0.05, respectively. The genes in bold were found to be common top significant genes in both Black/AA and White cohorts in the associated STN (Supplementary Table S3)
Supplementary Table S5 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

This file contains the results to the differential gene expression analysis, and shows the list of all genes analysed.
Supplementary Table S4 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

This file contains a list of the common top significant survival associated genes in both Black/AA and White cohorts.
Supplementary Figure S9 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

Supplementary Figure S9 shows the overview of the effects of WNT pathway activity scores and APC alternative event frequency between Black/AA and White patient cohorts
Supplementary Figure S7 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

Supplementary Figure S7 shows a heatmap of the differentially expressed genes between the Black/AA and White cohorts
Supplementary Figure S3 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

Supplementary Figure S3 shows the MSI MANTIS Score distribution for each patient cohort Black/AA and White
FIGURE 5 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

Multivariable-adjusted regression survival analysis of indicated variables. Forest plots of the Cox proportional hazard ratio analysis of the Black/AA and White patient cohorts. Clinical identifiers age, stage, sex, race, MSI MANTIS, and CHD8 (A) of the WNT STN was a gene significantly associated with survival in both cohorts, see Fig. 1, (B) the same covariates as A, with the inclusion of the interaction effect covariate, CHD8:Race (C) and (D) CHD8, age, stage, sex, and MSI MANTIS for the Black/AA and the White, respectively. The first column represents the clinical identifier of interest. The number of events = 80 and the number of patients n = 333, 62 Black patients and 271 White patients. N, the second column is the number of observations deleted because of missingness. The third column represents the HR and the 95% confidence intervals of the HR for each covariate included in the Cox proportional hazards model. The HR estimates are depicted by box symbols with confidence bands and parenthetical values representing 95% confidence intervals. The last column indicates the associated P value, which is represented by the Wald test of significance. Magnitude of significance is denoted with asterisks (*). The significance codes include: 0 “***” 0.001 “**” 0.01 “*” 0.05 “.” 0.1 “ ” 1. AIC = Akaike information criterion.
FIGURE 4 from A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer
Authors: Nwaokorie Annabelle , Kolch Walter , Fey Dirk
Published: January 2024

Kaplan–Meier curves of overall survival for the Black/AA and White patient cohorts stratified by pathway activity score. The Kaplan–Meier curves for the signaling pathways WNT for the Black/AA cohort (A), WNT for the White cohort (B), p53 for the Black/AA cohort (C), p53 for the White cohort (D), TGFβ for the Black/AA cohort (E), TGFβ for the White cohort (F), MAPK for the Black/AA cohort (G), MAPK for the White cohort (H), PI3K-Akt for the Black/AA cohort (I), PI3K-Akt for the White cohort (J). The groups were based on high (orange line) and low (blue line) pathway activity, where n indicates the total number of patients in each group. Statistical significance was tested using a log-rank test. HR = hazard ratio. CI95% = 95% confidence interval. P-val = P-value.
Evaluation of the Effectiveness of the 6 Warning Signs of the European Society for Immunodeficiencies for Primary Immunodeficiencies in Older Adults
Authors: Yildiz Eray , Çölkesen Fatih , Evcen Recep , Sadi Aykan Filiz , Kılınç Mehmet , Arslan Sevket
Published: January 2024

Introduction: Diagnostic delay in cases of primary immunodeficiency (PID) is a significant problem for clinicians, and most do not have sufficient awareness of this uncommon disorder. The European Society for Immunodeficiencies (ESID) has developed 6 warning signs to increase awareness of adult PIDs. The aim of this study was to determine the prevalence of PID in older adults regardless of the reason for presentation and to evaluate the effectiveness of the 6 warning signs of ESID in the diagnosis of PIDs. Methods: The study included 1,331 patients aged ≥65 years who presented at our clinic for any reason and were questioned about the ESID 6 warning signs for PIDs. After the exclusion of reasons for secondary immunodeficiency (SID), all the patients underwent immunological evaluation for the diagnosis of potential underlying PIDs. Results: After excluding 6 patients diagnosed with SID, PID was diagnosed in 16 (1.2%) of 1,325 older adults using ESID warning signs. The most common reasons for presentation were infection (69%) in the PID group and urticaria and/or angioedema (41.5%) in the non-PID group. The most common PID subgroup was common variable immunodeficiency (50%). In 12 of the patients diagnosed with PID, there was at least 1 positive ESID warning sign. In 4 patients, PID was determined despite negative ESID warning signs. The patients diagnosed with PID showed a significant, minimal level of agreement with questions 1 and 4 of the ESID warning signs (p < 0.001, ĸ = 0.204, p = 0.005, ĸ = 0.208, respectively). Conclusion: The ESID warning signs do not encompass all the symptoms and findings of PIDs. There is a need for more infection-centered questions to determine PIDs in older adults. Therefore, the ESID warning signs should be further developed.
General Algorithm Applicability in Determining DBS Lead Orientation: Adapting 2D and 3D X-Ray Techniques for SenSightTM Leads
Authors: Hunsche Stefan , Fedders Dieter , Hellerbach Alexandra , Eichner Markus , Wirths Jochen , Dembek Till A. , Visser-Vandewalle Veerle , Treuer Harald
Published: January 2024

Introduction: With recent advancements in deep brain stimulation (DBS), directional leads featuring segmented contacts have been introduced, allowing for targeted stimulation of specific brain regions. Given that manufacturers employ diverse markers for lead orientation, our investigation focuses on the adaptability of the 2017 techniques proposed by the Cologne research group for lead orientation determination. Methods: We tailored the two separate 2D and 3D X-ray-based techniques published in 2017 and originally developed for C-shaped markers, to the dual-marker of the Medtronic SenSight™ lead. In a retrospective patient study, we evaluated their feasibility and consistency by comparing the degree of agreement between the two methods. Results: The Bland-Altman plot showed favorable concordance without any noticeable systematic errors. The mean difference was 0.79°, with limits of agreement spanning from 21.4° to −19.8°. The algorithms demonstrated high reliability, evidenced by an intraclass correlation coefficient of 0.99 (p < 0.001). Conclusion: The 2D and 3D algorithms, initially formulated for discerning the circular orientation of a C-shaped marker, were adapted to the marker of the Medtronic SenSight™ lead. Statistical analyses revealed a significant level of agreement between the two methods. Our findings highlight the adaptability of these algorithms to different markers, achievable through both low-dose intraoperative 2D X-ray imaging and standard CT imaging.
Interesting Mucocutaneous Manifestations in COVID-19 Infection or Vaccination Confirmed by Histopathology: A Case Series
Authors: Pour Mohammad Arash , Noroozi Elahe , Gholizadeh Mesgarha Milad , Shayanfar Nasrin , Goodarzi Azadeh
Published: January 2024

Introduction: Mucocutaneous complications or adverse events due to SARS-CoV-2 infection or vaccination have been well delineated in the literature, respectively. Most eruptions are considered mild and self-limiting; however, for the atypical cases with a tentative clinical diagnosis, performing a biopsy and histopathological assessment is pivotal to confirm the diagnosis and subsequently prescribe a more tailored treatment. Despite the diverse reporting of such incidents globally, most studies restrict the rate of biopsied cases to less than 15%. Case Presentations: This case series elucidates 20 patients referred to the tertiary dermatology clinic, including 14 COVID-19 infection-related eruptions such as lichen planus (LP), cutaneous vasculitis, pityriasis rosea (PR), discoid lupus erythematosus, guttate psoriasis, sarcoidosis, Raynaud’s phenomenon, non-specific lesions resembling genital warts, Beau’s line, and one severe case of purpura fulminans with a promising outcome. Moreover, we presented six vaccine-induced cases comprising LP, urticarial vasculitis, PR, parapsoriasis, and localized morphea. The diagnosis of all challenging cases has been proven by histopathological evaluation. We included pertaining anamnesis details of each patient and vivid classifying images to pinpoint the morphologic features of each condition. Discussion: In line with our previous studies, the vaccine-induced eruptions were less severe compared to infection-related complications of COVID-19 and are mostly controllable by antihistamines and corticosteroid administration. Therefore, reporting such events should not impede COVID-19 vaccination in the general population.
Preserving Endothelial Integrity in Human Saphenous Veins during Preparation for Coronary Bypass Surgery
Authors: Sedovy Meghan W. , Leng Xinyan , Iqbal Farwah , Renton Mark C. , Leaf Melissa , Roberts Kailynn , Malek Arya , Arnold W. Scott , Wyatt David A. , Choate Cynthia W. , Rowe Joseph F. , Baker Joseph W. , Johnstone Scott R. , Joseph Mark
Published: January 2024

Introduction: While multiple factors influence coronary artery bypass graft (CABG) success rates, preserving saphenous vein endothelium during surgery may improve patency. Standard preparations include saphenous vein preparation in heparinized saline (saline) which can result in endothelial loss and damage. Here, we investigated the impact of preparing saphenous graft vessels in heparinized patient blood (blood) versus saline. Methods: Saphenous vein tissues from a total of 23 patients undergoing CABG were split into 2 groups (1) saline and (2) heparinized patient blood. Excess tissue was fixed for analysis immediately following surgery. Level of endothelial coverage, oxidative stress marker 4-hydroxynonenal (4HNE), and oxidative stress protective marker nuclear factor erythroid 2-related factor 2 (NRF2) were evaluated. Results: In saline patient veins, histological analysis revealed a limited luminal layer, suggesting a loss of endothelial cells (ECs). Immunofluorescent staining of EC markers vascular endothelial cadherin (VE-cadherin) and endothelial nitric oxide identified a significant improvement in EC coverage in the blood versus saline groups. Although both treatment groups expressed 4HNE to similar levels, EC blood samples expressed higher levels of NRF2. Conclusion: Our data indicate that use of heparinized patient blood helps preserve the endothelium and promotes vein graft health. This has the potential to improve long-term outcomes in patients.
Glomerular Filtration Rate Estimation in Adults: Myths and Promises
Authors: Delanaye Pierre , Cavalier Etienne , Stehlé Thomas , Pottel Hans
Published: January 2024

Background: In daily practice, glomerular filtration rate (GFR) is estimated with equations including renal biomarkers. Among these biomarkers, serum creatinine remains the most used. However, there are many limitations with serum creatinine, which we will discuss in the current review. We will also discuss how creatinine-based equations have been developed and what we can expect from them in terms of performance to estimate GFR. Summary: Different creatinine-based equations have been proposed. We will show the advantages of the recent European Kidney Function Consortium equation. This equation can be used in children and adults. This equation can also be used with some flexibility in different populations. Key Messages: GFR is estimated by creatinine-based equations, but the most important for nephrologists is probably to know the limitations of these equations.
Uma contribuição da filosofia da linguagem de Volóchinov para os estudos semióticos
Authors: Villarta-Neder Marco Antonio , Dias Fábio Luiz de Castro
Published: January 2024

Este artigo tem como objetivo discutir como a filosofia da linguagem de Volóchinov (2017 [1929]) pode apresentar uma contribuição aos estudos semióticos, sobretudo em seu caráter filosoficamente sociológico. Em primeiro lugar, partimos de uma definição da perspectiva histórico-epistemológica que caracteriza a nossa reflexão, e evidenciamos um dos momentos em que a filosofia volochinoviana explicitamente esteve presente na obra de Iúri Lotman [1922-1993], um dos mais importantes semioticistas da história desse campo. Em segundo, caracterizamos o sociologismo das décadas de 1920 e 1930 da URSS em que Volóchinov atuou cientificamente, fator que muito contribuiu para que a sua filosofia da linguagem pudesse assumir uma postura epistemicamente sociológica. Por fim, passamos a discutir, após um breve debate sobre o primado filosófico da interação social que é pressuposto por tal filosofia, como o conceito de enunciado de Volóchinov (2017 [1929]) pode servir como ponto de partida para uma semiótica que se queira sociológica. Antes de mais nada, este artigo pretende-se uma contribuição à defesa da lógica interdisciplinar no campo dos estudos da linguagem, além de um trabalho que se deseja participante de um movimento de abordagem epistemológica e histórica das ideias.
Greimas et son autre. Enquête aux origines des courants «post-greimassiens»
Authors: Caterino Angelo Di , Chatenet Ludovic
Published: January 2024

Notre article propose de discuter l’évolution de la pensée de Greimas en évaluant notamment quelques principes qui ont permis l’émergence de mouvements épistémologiquement différents, à partir de son héritage. A partir du réexamen d’ouvrages « critiques » des années 80-90 : le Tome 2 du Dictionnaire (Greimas ; Courtés, 1986), De l’imperfection (Greimas, 1987) et Sémiotique des passions (Greimas ; Fontanille, 1991), nous mettront en évidence les concepts portant en germe les tournants « post-greimassien ». Plus particulièrement, nous montrerons que les développements des modalités (Greimas, 1983) ont orienté la sémiotique vers le sujet et la subjectivité, l’énonciation et, finalement, une approche existentielle préfigurant la sémiotique du discours. Notre proposition critique cherchera à questionner la cohérence du modèle théorique greimassien comme cadre unique, stable et partagé de la communauté sémiotique.
A percepção na semiótica discursiva: contribuições da semio-historiografia
Authors: Moreira Patricia Veronica
Published: January 2024

Existem, na comunidade de semioticistas, questionamentos relacionados ao tipo de presença da fenomenologia de Merleau-Ponty (1999 [1945]) na semiótica discursiva (Zilberberg, 2011). Buscando contribuir para a discussão, este trabalho tem como objetivo principal retomar o conceito de percepção nas obras Sémantique Structurale (1966) e Maupassant. La sémiotique du texte: exercices pratiques (1976), ambas de Algirdas Julien Greimas, correlacionando-as com fontes anteriores (Merleau Ponty, 1999 [1945]; Allport, 1955; Quillian, 1962). Esse debate, que muito interessa à questão do sensível no projeto greimasiano, apoia-se na historiografia linguística (Altman, 2009; Koerner, 2014; Swiggers, 2009, 2013), no que tange ao princípio de influência, e na semiótica tensiva (Zilberberg, 2000; Zilberberg; Fontanille, 2001), sobre a mestiçagem, chegando a uma análise semio-historiográfica das citações tensivas (Santos, 2020; Moreira; Santos; Portela, 2021) para estabelecer em que medida a percepção faz parte do escopo teórico-metodológico da teoria, ou se pertence apenas ao âmbito da retórica nos trabalhos iniciais de Greimas.
Comunicación y liderazgo en la cultura organizacional de las empresas restauranteras: una aproximación conceptual
Authors: Lozano Gutiérrez María Dolores , Duran Bravo Patricia
Published: January 2024

La industria restaurantera requiere una operación centrada en experiencias de acogida y en interacciones humanas. Desde una perspectiva dialecto-constructivista se propone un modelo conceptual que integra los componentes estratégicos de la comunicación y el liderazgo para fortalecer la cultura organizacional basada en el trabajo en equipo, y que incluye tres dimensiones: 1) Estructural centrada en la información y formación para generar seguridad; 2) Relacional basada en la motivación, escucha y diálogo para forjar confianza; y 3) Integradora sustentada en la visión compartida.
Comunicação e cultura organizacional no home office: perspectivas de líderes na pandemia
Authors: Andrelo Roseane , Oliveira Guilherme Ferreira de
Published: January 2024

Objetiva-se compreender os principais sentidos circulantes na percepção de um grupo de gestores sobre como a comunicação pode contribuir para a construção de sentidos da cultura organizacional no trabalho remoto, na pandemia. Adotou-se abordagem qualitativa e realizou-se pesquisa bibliográfica e de campo, com entrevistas em profundidade com gestores de comunicação. Os resultados indicam que eles compreendem como papel da comunicação a transmissão de informações do contexto e a promoção de interação. Percebe-se também a relação de interdependência entre comunicação e cultura.
Cultura organizacional e comunicação como antídotos para crises institucionais
Authors: Bueno Wilson da Costa
Published: January 2024

As mudanças dramáticas e constantes no contexto econômico e sociocultural que caracteriza a sociedade moderna exigem das organizações a adoção de processos e mecanismos que lhes permitam, ao mesmo tempo, atender às demandas e expectativas dos públicos estratégicos e garantir a sua sustentabilidade. Nesse sentido, é fundamental a implementação de uma nova cultura organizacional, fundada em pressupostos básicos, como a sustentabilidade, a inclusão social, a diversidade corporativa, a acessibilidade e a adoção de um sistema competente de governança.
Progressive Left Ventricular Remodeling for Predicting Mortality in Children With Dilated Cardiomyopathy: The Pediatric Cardiomyopathy Registry
Authors: Kantor Paul F. , Shi Ling , Colan Steven D. , Orav E. John , Wilkinson James D. , Hamza Taye H. , Webber Steven A. , Canter Charles E. , Towbin Jeffrey A. , Everitt Melanie D. , Pahl Elfriede , Ware Stephanie M. , Rusconi Paolo G. , Lamour Jacqueline M. , Jefferies John L. , Addonizio Linda J. , Lipshultz Steven E. ,   for the Pediatric Cardiomyopathy Registry Investigators*
Published: January 2024

Background

Pediatric dilated cardiomyopathy often leads to death or cardiac transplantation. We sought to determine whether changes in left ventricular (LV) end‐diastolic dimension (LVEDD), LV end‐diastolic posterior wall thickness, and LV fractional shortening (LVFS) over time may help predict adverse outcomes.

Methods and Results

We studied children up to 18 years old with dilated cardiomyopathy, enrolled between 1990 and 2009 in the Pediatric Cardiomyopathy Registry. Changes in LVFS, LVEDD, LV end‐diastolic posterior wall thickness, and the LV end‐diastolic posterior wall thickness:LVEDD ratio between baseline and follow‐up echocardiograms acquired ≈1 year after diagnosis were determined for children who, at the 1‐year follow‐up had died, received a heart transplant, or were alive and transplant‐free. Within 1 year after diagnosis, 40 (5.0%) of the 794 eligible children had died, 117 (14.7%) had undergone cardiac transplantation, and 585 (73.7%) had survived without transplantation. At diagnosis, survivors had higher median LVFS and lower median LVEDD
Z
scores. Median LVFS and LVEDD
Z
scores improved among survivors (
Z
score changes of +2.6 and −1.1, respectively) but remained stable or worsened in the other 2 groups. The LV end‐diastolic posterior wall thickness:LVEDD ratio increased in survivors only, suggesting beneficial reverse LV remodeling. The risk for death or cardiac transplantation up to 7 years later was lower when LVFS was improved at 1 year (hazard ratio [HR], 0.83;
P
=0.004) but was higher in those with progressive LV dilation (HR, 1.45;
P
<0.001).

Conclusions

Progressive deterioration in LV contractile function and increasing LV dilation are associated with both early and continuing mortality in children with dilated cardiomyopathy. Serial echocardiographic monitoring of these children is therefore indicated.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00005391.
Percutaneous Coronary Interventions Using a Ridaforolimus‐Eluting Stent in Patients at High Bleeding Risk
Authors: Kornowski Ran , Konigstein Maayan , Jonas Michael , Assali Abid , Vaknin‐Assa Hana , Segev Amit , Danenberg Haim , Halabi Majdi , Roguin Ariel , Kerner Arthur , Lev Eli , Karamasis Grigoris V. , Johnson Thomas W. , Anderson Richard , Blaxill Jonathan , Jadhav Sachin , Hoole Stephen , Witberg Guy , Issever Melek Ozgu , Ben‐Yehuda Ori , Baumbach Andreas
Published: January 2024

Background

Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug‐eluting stents have been shown to be superior to bare‐metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus‐eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus‐eluting stent in patients with HBR.

Methods and Results

This was a prospective, multicenter, binational, single‐arm, open‐label trial. Patients were defined as HBR according to the LEADERS‐FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug‐Coated Stent versus the Gazelle Bare‐Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% (
P
<0.0001). Stent thrombosis (Academic Research Consortium definite and probable) occurred in 2 patients (0.6%). Bleeding Academic Research Consortium type 3 and 5 bleeding occurred in 6 patients (1.9%).

Conclusions

We observed favorable results in patients with HBR who underwent percutaneous coronary intervention with a ridaforolimus‐eluting stent and received shortened DAPT, including a low rate of ischemic events and low rate of stent thrombosis.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03877848.
Economic Burden of Inpatient Care for Mitral Regurgitation in Maryland
Authors: Zinoviev Radoslav , Hasan Rani K. , Gammie James S. , Resar Jon R. , Czarny Matthew J.
Published: January 2024

Background

Mitral regurgitation (MR) is the most common valvular disease in the United States and increases the risk of death and hospitalization. The economic burden of MR in the United States is not known.

Methods and Results

We analyzed inpatient hospitalization data from the 1 221 173 Maryland residents who had any in‐state admissions from October 1, 2015, to September 30, 2019. We assessed the total charges for patients without MR and for patients with MR who underwent medical management, transcatheter mitral valve repair or replacement, or surgical mitral valve repair or replacement. During the study period, 26 076 inpatients had a diagnosis of MR. Compared with patients without MR, these patients had more comorbidities and higher inpatient mortality. Patients with medically managed MR incurred average total charges of $23 575 per year; MR was associated with $10 559 more in charges per year and an incremental 3.1 more inpatient days per year as compared with patients without MR. Both surgical mitral valve repair or replacement and transcatheter mitral valve repair or replacement were associated with higher charges as compared with medical management during the year of intervention ($47 943 for surgical mitral valve repair or replacement and $63 108 for transcatheter mitral valve repair or replacement). Annual charges for both groups were significantly lower as compared with medical management in the second and third years postintervention.

Conclusions

MR is associated with higher mortality and inpatient charges. Patients who undergo surgical or transcatheter intervention incur lower charges compared with medically managed MR patients in the years after the procedure.
Exercise Training Decreases Nitrite Concentration in the Heart and Locomotory Muscles of Rats Without Changing the Muscle Nitrate Content
Authors: Majerczak Joanna , Drzymala‐Celichowska Hanna , Grandys Marcin , Kij Agnieszka , Kus Kamil , Celichowski Jan , Krysciak Katarzyna , Molik Weronika A. , Szkutnik Zbigniew , Zoladz Jerzy A.
Published: January 2024

Background

Skeletal muscles are postulated to be a potent regulator of systemic nitric oxide homeostasis. In this study, we aimed to evaluate the impact of physical training on the heart and skeletal muscle nitric oxide bioavailability (judged on the basis of intramuscular nitrite and nitrate) in rats.

Methods and Results

Rats were trained on a treadmill for 8 weeks, performing mainly endurance running sessions with some sprinting runs. Muscle nitrite (NO
2
−
) and nitrate (NO
3
−
) concentrations were measured using a high‐performance liquid chromatography–based method, while amino acids, pyruvate, lactate, and reduced and oxidized glutathione were determined using a liquid chromatography coupled with tandem mass spectrometry technique. The content of muscle nitrite reductases (electron transport chain proteins, myoglobin, and xanthine oxidase) was assessed by western immunoblotting. We found that 8 weeks of endurance training decreased basal NO
2
−
in the locomotory muscles and in the heart, without changes in the basal NO
3
−
. In the slow‐twitch oxidative soleus muscle, the decrease in NO
2
−
was already present after the first week of training, and the content of nitrite reductases remained unchanged throughout the entire period of training, except for the electron transport chain protein content, which increased no sooner than after 8 weeks of training.

Conclusions

Muscle NO
2
−
level, opposed to NO
3
−
, decreases in the time course of training. This effect is rapid and already visible in the slow‐oxidative soleus after the first week of training. The underlying mechanisms of training‐induced muscle NO
2
−
decrease may involve an increase in the oxidative stress, as well as metabolite changes related to an increased muscle anaerobic glycolytic activity contributing to (1) direct chemical reduction of NO
2
−
or (2) activation of muscle nitrite reductases.
Association of Preablation Plasma Corin Levels With Atrial Fibrillation Recurrence After Catheter Ablation: A Prospective Observational Study
Authors: Zhao Yichang , Yuan Xiaoyang , Xie Yunpeng , Yin Xiaomeng , Liu Ying , Sun Yuanjun , Gong Yue , Liu Jinqiu , Chen Feifei
Published: January 2024

Background

We assessed the impact of pre‐ and postprocedural plasma corin levels on the recurrence of atrial fibrillation (AF) after catheter ablation (CA).

Methods and Results

This prospective, single‐center, observational study included patients undergoing their first CA of AF. Corin was measured before and 1 day after CA. The primary end point was recurrent AF between 3 and 12 months after ablation. From April 2019 through May 2021, we analyzed 616 patients with AF (59.09% men) with a mean age of 62.86±9.42 years. Overall, 153 patients (24.84%) experienced recurrent AF. In the recurrence group, the pre‐ and postprocedure corin concentrations were 539.14 (329.24–702.08) and 607.37 (364.50–753.80) pg/mL, respectively, which were significantly higher than the nonrecurrence group's respective concentrations of 369.05 (186.36–489.28) and 489.12 (315.66–629.05) pg/mL (both
P
<0.0001). A multivariate Cox regression analysis with confounders found that elevated preablation corin levels were significantly associated with an increased risk of AF recurrence after CA. Receiver operating characteristic curve analysis identified that a preablation corin threshold of >494.85 pg/mL predicted AF recurrence at 1 year. An increase of 1 SD in corin concentrations before CA (264.94 pg/mL) increased the risk of recurrent AF by 54.3% after adjusting for confounding variables (hazard ratio, 1.465 [95% CI, 1.282–1.655];
P
<0.0001).

Conclusions

Plasma corin levels at baseline is a valuable predictor of AF recurrence after CA, independent of established conventional risk factors. Risk stratification before ablation for AF may be useful in selecting treatment regimens for patients.
Surrogate Decision-Making After Stroke in a Community Setting: The OASIS Project
Authors: Zahuranec Darin B. , Ortiz Carmen , Lank Rebecca J. , Zhang Guanghao , Shi Xu , Case Erin , Morgenstern Lewis B.
Published: January 2024

BACKGROUND:

Patients with severe stroke often rely on surrogate decision-makers for life-sustaining treatment decisions. We investigated ethnic differences between Mexican Americans (MAs) and non-Hispanic White (NHW) individuals in surrogate reports of physician quality of communication and shared decision-making from the OASIS study (Outcomes Among Surrogate Decision Makers in Stroke) project.

METHODS:

Patients had ischemic stroke or intracerebral hemorrhage in Nueces County, TX. Surrogates self-identified as being involved in decisions about do-not-resuscitate orders, brain surgery, ventilator, feeding tube, or hospice/comfort care. Surrogate reports of physician quality of communication (scale score, range from 0 to 10) and shared decision-making (CollaboRATE scale score, binary score 1 versus 0) were compared by ethnicity with linear or logistic regression using generalized estimating equations, adjusted for prespecified demographics, clinical factors, and confounders.

RESULTS:

Between April 2016 and September 2020, 320 surrogates for 257 patients with stroke enrolled (MA, 158; NHW, 85; and other, 14). Overall quality of communication score was better among surrogates of MA patients than NHW individuals after adjustment for demographics, stroke severity, and patient survival though the ethnic difference was attenuated (β, 0.47 [95% CI, −0.17 to 1.12];
P
=0.15) after adjustment for trust in the medical profession and frequency of personal prayer. High CollaboRATE scale scores were more common among surrogates of MA patients than NHW individuals (unadjusted odds ratio, 1.75 [95% CI, 1.04–2.95]). This association persisted after adjustment for demographic and clinical factors though there was an interaction between patient age and ethnicity (
P
=0.04), suggesting that this difference was primarily in older patients.

CONCLUSIONS:

Surrogate decision-makers of MA patients generally reported better outcomes on validated measures of quality of communication and shared decision-making than NHW individuals. Further study of outcomes among diverse populations of stroke surrogate decision-makers may help to identify sources of strength and resiliency that may be broadly applicable.
Barriers and Facilitators of Colorectal Cancer Screening During the COVID-19 Pandemic
Authors: Miller Carrie A. , Guidry Jeanine P. D. , Kenning Kristine L. , Bohl Jaime L. , Fuemmeler Bernard F. , Rivet Emily B.
Published: January 2024

Background

COVID-19 introduced new barriers to health care including cancer screenings. This study evaluated the role of pandemic- and copay-related barriers to colonoscopy and the extent to which home-based testing methods were utilized.

Methods

A cross-sectional survey assessed colorectal cancer (CRC) attitudes and screening early in the COVID-19 pandemic.

Results

Respondents (342; 50.37% female) were 62.32 (SD = 6.87) years old. Roughly half were White/Caucasian (329; 48.45%); 29.75% were Black/African American (202); and 21.80% were another race (148). Roughly two-thirds were up-to-date with CRC screening (459; 67.59%). In an adjusted model, those with a higher agreement that concerns about COVID-19 delayed scheduling their colonoscopy (OR = .79; 95% CI: .08, .63; P = .045) and concerns about copays delayed scheduling their colonoscopy (OR = .73; 95% CI: .73, .57; P = .02) were less likely to be up-to-date on screening. In another adjusted model, those screened during the pandemic were significantly more likely to be screened via an at-home test (OR = 10.93; 95% CI: 5.95, 20.27; P < .001).

Discussion

During the COVID-19 pandemic, screening copay-related concerns persisted and were significantly higher among those not up-to-date with CRC screening. Increased at-home testing and addressing copay barriers may increase CRC screening adherence now and in future infectious disease outbreaks.
Impact of Product and Process Adoption Strategies on Business Expectations: Evidence from India During the Pandemic
Authors: Bhandari Bornali , Gupta Samarth , Sahu Ajaya K. , Urs K. S.
Published: January 2024

Using a unique survey of Indian firms conducted in June 2020, we analyse whether innovating into a new product line or adapting e-commerce platforms improved business outlook. A structural equation framework is used to address the endogenous relationship between six-month advance expectations of key demand (new orders) and supply (labour costs and raw material costs) variables to the two innovation strategies. Innovation strategies are in turn determined by unobservable latent variables, that is, shocks experienced due to the COVID-19-associated national lockdown. Both innovation strategies had a positive and significant impact on demand-side sentiments but had a mixed impact on the supply side.

JEL Codes: M21, O31