bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum
Authors: Zhao Ying-Jia , Ma Chun-Ying , Zheng Meng-Jing , Yao Yan-Rong , Lv Li-Hua , Zhang Li-Hua , Fu Xiao-Xin , Zhang Jing-Ting , Xiao Kai 
Published: July 2024

Abstract
Background
Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses.

Results
TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance.

Conclusions
TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.
Effect of liver abnormalities on mortality in Fontan patients: a systematic review and meta-analysis
Authors: Liu Xiang , Han Linjiang , Zhou Ziqin , Tu Jiazichao , Ma Jianrui , Chen Jimei 
Published: July 2024

Abstract
Background
Fontan-associated liver disease (FALD) is one of the most common complications following Fontan procedure, but the impact of FALD on survival outcomes remains controversial. The aim of this systematic review and meta-analysis was to examine and quantify the influence of liver disease on the survival of Fontan patients.

Methods
The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed, and relevant human studies published from inception up to 12 August 2022 were searched. Stata (version 17.0) was applied to perform the meta-analysis, using random effects (Mantel-Haenszel) models. The I2 statistic was used to assess the heterogeneity. Subgroup analysis and meta-regression were employed to explore the potential sources of heterogeneity and sensitivity analysis was performed to determine the potential influence of each study on the overall pooled results.

Results
A total of 312 records were initially identified and 8 studies involving 2,466 patients were selected for inclusion. Results revealed a significant association between the severity of liver disease following Fontan procedure and mortality, which was confirmed by sensitivity analysis and subgroup analysis assessing post-HT mortality. Meta-regression showed that diagnostic methods for liver disease may be a source of heterogeneity. After removal of the FALD patients identified by international classification of disease codes, heterogeneity was markedly reduced, and the positive association between all-cause mortality and the severity of liver disease became significant.

Conclusions
This meta-analysis showed the severity of liver disease following the Fontan procedure has a significant association with mortality. Lifelong follow-up is necessary and imaging examinations are recommended for routine surveillance of liver disease. Among patients with failing Fontan and advanced liver disease, combined heart-liver transplantation may provide additional survival benefits.
Educational interventions aimed at improving knowledge of delirium among nursing home staff—a realist review
Authors: Molitor Vincent , Busse Theresa Sophie , Giehl Chantal , Lauer Romy , Otte Ina Carola , Vollmar Horst Christian , Thürmann Petra , Holle Bernhard , Palm Rebecca 
Published: July 2024

Abstract
Background
Delirium is a neuropathological syndrome that is characterised by fluctuating impairments in attention, cognitive performance, and consciousness. Since delirium represents a medical emergency, it can be associated with adverse clinical and economic outcomes. Although nursing home residents face a high risk of developing delirium, health care professionals in this field appear to have limited knowledge of delirium despite the critical role they play in the prevention, diagnosis, and treatment of delirium in nursing homes.

Objective
The purpose of this realist review is to develop an initial programme theory with the goal of understanding how, why, and under what circumstances educational interventions can improve the delirium-specific knowledge of health care professionals in nursing homes.

Methods
This realist review was conducted in accordance with the RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines and includes the following steps: (1) search strategy and literature review; (2) study selection and assessment; (3) data extraction; (4) data synthesis; and (5) development of an initial programme theory. It also included stakeholder discussions with health care professionals recruited from nursing home care, which focused on their experiences with delirium.

Results
From a set of 1703 initially identified publications, ten publications were included in this realist review. Based on these publications, context-mechanism-outcome configurations were developed; these configurations pertained to (1) management support, (2) cognitive impairments among residents, (3) familiarity with residents, (4) participatory intervention development, (5) practical application, (6) case scenarios, (7) support from experts and (8) relevance of communication.

Conclusions
Educational interventions aimed at improving the delirium-specific knowledge of health care professionals should feature methodological diversity if they are to enhance health care professionals’ interest in delirium and highlight the fundamental contributions they make to the prevention, diagnosis, and treatment of delirium. Educational interventions should also take into account the multidimensional contextual factors that can have massive impacts on the relevant mode of action as well as the responses of health care professionals in nursing homes. The identification of delirium in residents is a fundamental responsibility for nursing home staff.

Trial registration
This review has been registered at Open Science Framework https://doi.org/10.17605/OSF.IO/6ZKM3
Indoor residual spraying of experimental huts in Cameroon highlights the potential of Fludora® Fusion to control wild pyrethroid-resistant malaria vectors
Authors: Thiomela Riccado F. , Tchouakui Magellan , Menze Benjamin D. , Nchoutpouen Elysee , Ngongang-Yipmo Emilie S. , Wood Oliver , Horstmann Sebastian , Mahob Raymond J. , Fomena Abraham , Wondji Charles S. 
Published: July 2024

AbstractElevated resistance to pyrethroids in major malaria vectors has led to the introduction of novel insecticides including neonicotinoids. There is a fear that efficacy of these new insecticides could be impacted by cross-resistance mechanisms from metabolic resistance to pyrethroids. In this study, after evaluating the resistance to deltamethrin, clothianidin and mixture of clothianidin + deltamethrin in the lab using CDC bottle assays, the efficacy of the new IRS formulation Fludora® Fusion was tested in comparison to clothianidin and deltamethrin applied alone using experimental hut trials against wild free-flying pyrethroid-resistant Anopheles funestus from Elende and field An. gambiae collected from Nkolondom reared in the lab and released in the huts. Additionally, cone tests on the treated walls were performed each month for a period of twelve months to evaluate the residual efficacy of the sprayed products. Furthermore, the L1014F-kdr target-site mutation and the L119F-GSTe2 mediated metabolic resistance to pyrethroids were genotyped on a subset of mosquitoes from the EHT to assess the potential cross-resistance. All Anopheles species tested were fully susceptible to clothianidin and clothianidin + deltamethrin mixture in CDC bottle assay while resistance was noted to deltamethrin. Accordingly, Fludora® Fusion (62.83% vs 42.42%) and clothianidin (64.42% vs 42.42%) induced significantly higher mortality rates in EHT than deltamethrin (42.42%) against free flying An. funestus from Elende in month 1 (M1) and no significant difference in mortality was observed between the first (M1) and sixth (M6) months of the evaluation (P > 0.05). However, lower mortality rates were recorded against An. gambiae s.s from Nkolondom (mortality rates 50%, 45.56% and 26.68%). In-situ cone test on the wall showed a high residual efficacy of Fludora® Fusion and clothianidin on the susceptible strain KISUMU (> 12 months) and moderately on the highly pyrethroid-resistant An. gambiae strain from Nkolondom (6 months). Interestingly, no association was observed between the L119F-GSTe2 mutation and the ability of mosquitoes to survive exposure to Fludora® Fusion, whereas a trend was observed with the L1014F-kdr mutation. This study highlights that Fludora® Fusion, through its clothianidin component, has good potential of controlling pyrethroid-resistant mosquitoes with prolonged residual efficacy. This could be therefore an appropriate tool for vector control in several malaria endemic regions.
Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study
Authors: Necchi Andrea , Van der Heijden Michiel S. , Trukhin Dmytro , Peer Avivit , Gurney Howard , Alekseev Boris Y. , Parnis Francis X. , Leibowitz Raya , De Santis Maria , Grivas Petros , Clark Jason , Munteanu Mihaela , Kataria Ritesh , Jia Calvin , Balar Arjun V. , de Wit Ronald 
Published: July 2024

Abstract
Background
Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1. In the phase I/II ECHO-202/KEYNOTE-037 study, epacadostat plus pembrolizumab resulted in a preliminary objective response rate (ORR) of 35% in a cohort of patients with advanced UC.

Methods
ECHO-307/KEYNOTE-672 was a double-blinded, randomized, phase III study. Eligible adults had confirmed locally advanced/unresectable or metastatic UC of the urinary tract and were ineligible to receive cisplatin-based chemotherapy. Participants were randomly assigned (1:1) to receive epacadostat (100 mg twice daily) plus pembrolizumab (200 mg every 3 weeks) or placebo plus pembrolizumab for up to 35 pembrolizumab infusions. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (version 1.1).

Results
A total of 93 patients were randomized (epacadostat plus pembrolizumab, n = 44; placebo plus pembrolizumab, n = 49). Enrollment was stopped early due to emerging data from the phase III ECHO-301/KEYNOTE-252 study. The median duration of follow-up was 64 days in both arms. Based on all available data at cutoff, ORR (unconfirmed) was 31.8% (95% CI, 22.46–55.24%) for epacadostat plus pembrolizumab and 24.5% (95% CI, 15.33–43.67%) for placebo plus pembrolizumab. Circulating kynurenine levels numerically increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and decreased in the epacadostat-plus-pembrolizumab arm. Epacadostat-plus-pembrolizumab combination treatment was well tolerated with a safety profile similar to the placebo arm. Treatment discontinuations due to treatment-related adverse events were more frequent with epacadostat (11.6% vs. 4.1%).

Conclusions
Treatment with epacadostat plus pembrolizumab resulted in a similar ORR and safety profile as placebo plus pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced/unresectable or metastatic UC. At a dose of 100 mg twice daily, epacadostat did not appear to completely normalize circulating kynurenine levels when administered with pembrolizumab. Larger studies with longer follow-up and possibly testing higher doses of epacadostat, potentially in different therapy settings, may be warranted.

Trial registration
ClinicalTrials.gov identifier: NCT03361865, retrospectively registered December 5, 2017.
Pembrolizumab plus epacadostat in patients with recurrent/metastatic head and neck squamous cell carcinoma (KEYNOTE-669/ECHO-304): a phase 3, randomized, open-label study
Authors: Cho Byoung Chul , Braña Irene , Cirauqui Beatriz , Aksoy Sercan , Couture Felix , Hong Ruey-Long , Miller Wilson H. , Chaves-Conde Manuel , Teixeira Margarida , Leopold Lance , Munteanu Mihaela , Ge Joy Yang , Swaby Ramona F. , Hughes Brett G. M. 
Published: July 2024

Abstract
Background
Advanced head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and new treatment options are needed. Combining immunotherapies with differing mechanisms of action may enhance clinical benefits compared with single-agent immunotherapy. Epacadostat, an indoleamine 2,3 dioxygenase 1 inhibitor, plus pembrolizumab, a PD-1 inhibitor, showed promising activity in advanced HNSCC in the phase 1/2 KEYNOTE-037/ECHO-202 trial.

Methods
KEYNOTE-669/ECHO-304 is a randomized, open-label, phase 3 study evaluating the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab with a platinum [carboplatin or cisplatin] and 5-fluorouracil) in recurrent/metastatic (R/M) HNSCC. Participants had no prior systemic therapy for R/M HNSCC and were randomly assigned (2:1:2) to pembrolizumab 200 mg intravenously every 3 weeks plus epacadostat 100 mg orally twice daily, pembrolizumab monotherapy, or EXTREME. The primary endpoint was objective response rate (ORR; investigator assessment). Secondary endpoints were safety and tolerability. Change in serum kynurenine was an exploratory endpoint. Study enrollment was discontinued early as a strategic decision on May 2, 2018, and response assessment was discontinued after first on-study imaging assessment at week 9. Data cut-off was January 17, 2019.

Results
Between December 1, 2017, and May 2, 2018, 89 patients were randomly allocated to pembrolizumab plus epacadostat (n = 35), pembrolizumab monotherapy (n = 19), or EXTREME (n = 35). ORR (95% CI) was 31% (17%–49%) for pembrolizumab plus epacadostat, 21% (6%–46%) for pembrolizumab monotherapy, and 34% (19%–52%) for EXTREME. Treatment-related adverse events (TRAEs) occurred in 82% (n = 28) of patients receiving pembrolizumab plus epacadostat, 63% (n = 12) receiving pembrolizumab monotherapy, and 100% (n = 34) receiving EXTREME. Grade 3–4 TRAEs occurred in 24% (n = 8) of patients receiving pembrolizumab plus epacadostat, 16% (n = 3) receiving pembrolizumab monotherapy, and 82% (n = 28) receiving EXTREME. No deaths occurred due to AEs. Pembrolizumab plus epacadostat treatment reduced kynurenine levels but not to that of healthy subjects.

Conclusions
Pembrolizumab plus epacadostat and pembrolizumab monotherapy provided a similar response rate to EXTREME and demonstrated a manageable safety profile in patients with R/M HNSCC.

Trial registration
NCT03358472. Date of trial registration: November 30, 2017.
Metabolic tumour area: a novel prognostic indicator based on 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma in the R-CHOP era
Authors: Cui Silu , Xin Wenchong , Wang Fei , Shao Xiaoliang , Shao Xiaonan , Niu Rong , Zhang Feifei , Shi Yunmei , Liu Bao , Gu Weiying , Wang Yuetao 
Published: July 2024

Abstract
Background
The metabolic tumour area (MTA) was found to be a promising predictor of prostate cancer. However, the role of MTA based on 18F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL) prognosis remains unclear. This study aimed to elucidate the prognostic significance of MTA and evaluate its incremental value to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) for DLBCL patients treated with first-line R-CHOP regimens.

Methods
A total of 280 consecutive patients with newly diagnosed DLBCL and baseline 18F-FDG PET/CT data were retrospectively evaluated. Lesions were delineated via a semiautomated segmentation method based on a 41% SUVmax threshold to estimate semiquantitative metabolic parameters such as total metabolic tumour volume (TMTV) and MTA. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values. Progression-free survival (PFS) and overall survival (OS) were the endpoints that were used to evaluate the prognosis. PFS and OS were estimated via Kaplan‒Meier curves and compared via the log-rank test.

Results
Univariate analysis revealed that patients with high MTA, high TMTV and NCCN-IPI ≥ 4 were associated with inferior PFS and OS (P < 0.0001 for all). Multivariate analysis indicated that MTA remained an independent predictor of PFS and OS [hazard ratio (HR), 2.506; 95% confidence interval (CI), 1.337–4.696; P = 0.004; and HR, 1.823; 95% CI, 1.005–3.310; P = 0.048], whereas TMTV was not. Further analysis using the NCCN-IPI model as a covariate revealed that MTA and NCCN-IPI were still independent predictors of PFS (HR, 2.617; 95% CI, 1.494–4.586; P = 0.001; and HR, 2.633; 95% CI, 1.650–4.203; P < 0.0001) and OS (HR, 2.021; 95% CI, 1.201–3.401; P = 0.008; and HR, 3.869; 95% CI, 1.959–7.640; P < 0.0001; respectively). Furthermore, MTA was used to separate patients with high NCCN-IPI risk scores into two groups with significantly different outcomes.

Conclusions
Pre-treatment MTA based on 18F-FDG PET/CT and NCCN-IPI were independent predictor of PFS and OS in DLBCL patients treated with R-CHOP. MTA has additional predictive value for the prognosis of patients with DLBCL, especially in high-risk patients with NCCN-IPI ≥ 4. In addition, the combination of MTA and NCCN-IPI may be helpful in further improving risk stratification and guiding individualised treatment options.

Trial registration
This research was retrospectively registered with the Ethics Committee of the Third Affiliated Hospital of Soochow University, and the registration number was approval No. 155 (approved date: 31 May 2022).
Validation of the extended e-health literacy scale: structural validity, construct validity and measurement invariance
Authors: Petrič Gregor , Atanasova Sara 
Published: July 2024

Abstract
Background
Given the rapid proliferation and use of online health resources, many of which may be of dubious quality, there is an increasing need to develop electronic health literacy (e-health literacy) skills among the population of internet users. E-health literacy encompasses the skills and abilities needed to access, understand, validate, evaluate, interpret, and apply online health-related information. Measuring e-health literacy has become crucial for developing targeted interventions, assessing their impact, and producing high-quality research findings that can inform health policy and clinical practice, which can lead to improved health outcomes and potentially reducing health inequalities. The scales need to be valid and reliable so that decisions are based on high-quality data. In this regard, the issue of the measurement invariance of scales across different demographic groups has been neglected. This is critical, as assessments should be valid across different sociodemographic groups to avoid bias when comparing them. The aim of this study was to validate the Extended e-health literacy scale (eHEALS-E) on general population and investigate its structural validity and internal consistency, construct validity in terms of convergent and discriminant validity, and examine its measurement invariance across gender, age, education and social status.

Methods
The data were collected as a part of a national health literacy survey conducted by the Slovenian National Institute of Public Health. For this survey the initial eHEALS-E scale was revised in order to address its limitations and applicability to general population. Based on a nationally representative sample, the final sample for the analysis comprised 1,944 individuals who at least occasionally used one of the various internet services to obtain health-related information. Multiple group confirmatory factor analysis was used to examine the measurement invariance of the scale.

Results
With some adjustments, the measurement model of the revised 6-dimensional eHEALS-E scale demonstrated a good fit to the data (χ2 = 2508, df = 282, RMSEA = 0.064, SRMR = 0.070, CFI = 0.90). The scale had good internal consistency (alpha = 0.89). Although evidence of the scale’s convergent and discriminant validity was partially provided, the analysis revealed robust measurement invariance across sociodemographic groups.

Conclusions
With a minor limitation, the scale ensures an unbiased e-health literacy assessment across different social groups, which is crucial for interventions that aim to reduce health-related social inequalities. This ensures that the interventions derived from the assessment of reality are equally valid and effective for everyone, regardless of their sociodemographic background.
Unlocking the potential of soil microbial communities for bioremediation of emerging organic contaminants: omics-based approaches
Authors: Alidoosti Fatemeh , Giyahchi Minoo , Moien Shabnam , Moghimi Hamid 
Published: July 2024

AbstractThe remediation of emerging contaminants presents a pressing environmental challenge, necessitating innovative approaches for effective mitigation. This review article delves into the untapped potential of soil microbial communities in the bioremediation of emerging contaminants. Bioremediation, while a promising method, often proves time-consuming and requires a deep comprehension of microbial intricacies for enhancement. Given the challenges presented by the inability to culture many of these microorganisms, conventional methods are inadequate for achieving this goal. While omics-based methods provide an innovative approach to understanding the fundamental aspects, processes, and connections among microorganisms that are essential for improving bioremediation strategies. By exploring the latest advancements in omics technologies, this review aims to shed light on how these approaches can unlock the hidden capabilities of soil microbial communities, paving the way for more efficient and sustainable remediation solutions.