bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling CXCR2 as a promising therapeutic target in renal cell carcinoma: exploring the immunotherapeutic paradigm shift through its inhibition by RCT001
Authors: Montemagno Christopher , Jacquel Arnaud , Pandiani Charlotte , Rastoin Olivia , Dawaliby Rosie , Schmitt Thomas , Bourgoin Maxence , Palenzuela Héliciane , Rossi Anne-Laure , Ambrosetti Damien , Durivault Jerome , Luciano Frederic , Borchiellini Delphine , Le Du Julie , Gonçalves Leticia Christina Pires , Auberger Patrick , Benhida Rachid , Kinget Lisa , Beuselinck Benoit , Ronco Cyril , Pagès Gilles , Dufies Maeva 
Published: March 2024

Abstract
Background
In clear cell renal cell carcinoma (ccRCC), first-line treatment combines nivolumab (anti-PD-1) and ipilimumab (anti-CTLA4), yielding long-term remissions but with only a 40% success rate. Our study explored the potential of enhancing ccRCC treatment by concurrently using CXCR2 inhibitors alongside immunotherapies.

Methods
We analyzed ELR + CXCL levels and their correlation with patient survival during immunotherapy. RCT001, a unique CXCR2 inhibitor, was examined for its mechanism of action, particularly its effects on human primary macrophages. We tested the synergistic impact of RCT001 in combination with immunotherapies in both mouse models of ccRCC and human ccRCC in the presence of human PBMC.

Resuts
Elevated ELR + CXCL cytokine levels were found to correlate with reduced overall survival during immunotherapy. RCT001, our optimized compound, acted as an inverse agonist, effectively inhibiting angiogenesis and reducing viability of primary ccRCC cells. It redirected M2-like macrophages without affecting M1-like macrophage polarization directed against the tumor. In mouse models, RCT001 enhanced the efficacy of anti-CTLA4 + anti-PD1 by inhibiting tumor-associated M2 macrophages and tumor-associated neutrophils. It also impacted the activation of CD4 T lymphocytes, reducing immune-tolerant lymphocytes while increasing activated natural killer and dendritic cells. Similar effectiveness was observed in human RCC tumors when RCT001 was combined with anti-PD-1 treatment.

Conclusions
RCT001, by inhibiting CXCR2 through its unique mechanism, effectively suppresses ccRCC cell proliferation, angiogenesis, and M2 macrophage polarization. This optimization potentiates the efficacy of immunotherapy and holds promise for significantly improving the survival prospects of metastatic ccRCC patients.
miR-430 regulates zygotic mRNA during zebrafish embryogenesis
Authors: Baia Amaral Danielson , Egidy Rhonda , Perera Anoja , Bazzini Ariel A 
Published: March 2024

AbstractBackgroundEarly embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately.ResultsBy employing SLAM-seq, a nascent mRNA labeling transcriptomic approach, in a developmental time series we observe that over half of the early zebrafish embryo transcriptome consists of maternal-zygotic genes, emphasizing their pivotal role in early embryogenesis. We provide an hourly resolution of de novo transcriptional activation events and follow nascent mRNA trajectories, finding that most de novo transcriptional events are stable throughout this period. Additionally, by blocking microRNA-430 function, a key post transcriptional regulator during zebrafish embryogenesis, we directly show that it destabilizes hundreds of de novo transcribed mRNAs from pure zygotic as well as maternal-zygotic genes. This unveils a novel miR-430 function during embryogenesis, fine-tuning zygotic gene expression.ConclusionThese insights into zebrafish early embryo transcriptome dynamics emphasize the significance of post-transcriptional regulators in zygotic genome activation. The findings pave the way for future investigations into the coordinated interplay between transcriptional and post-transcriptional landscapes required for the establishment of animal cell identities and functions.
Identification of host protein ENO1 (alpha-enolase) interacting with Cryptosporidium parvum sporozoite surface protein, Cpgp40
Authors: Wang Yuexin , Li Na , Liang Guanda , Wang Luyang , Zhang Xiaotian , Cui Zhaohui , Li Xiaoying , Zhang Sumei , Zhang Longxian 
Published: March 2024

Abstract
Background
Cryptosporidium parvum is an apicomplexan zoonotic parasite causing the diarrheal illness cryptosporidiosis in humans and animals. To invade the host intestinal epithelial cells, parasitic proteins expressed on the surface of sporozoites interact with host cells to facilitate the formation of parasitophorous vacuole for the parasite to reside and develop. The gp40 of C. parvum, named Cpgp40 and located on the surface of sporozoites, was proven to participate in the process of host cell invasion.

Methods
We utilized the purified Cpgp40 as a bait to obtain host cell proteins interacting with Cpgp40 through the glutathione S-transferase (GST) pull-down method. In vitro analysis, through bimolecular fluorescence complementation assay (BiFC) and coimmunoprecipitation (Co-IP), confirmed the solid interaction between Cpgp40 and ENO1. In addition, by using protein mutation and parasite infection rate analysis, it was demonstrated that ENO1 plays an important role in the C. parvum invasion of HCT-8 cells.

Results
To illustrate the functional activity of Cpgp40 interacting with host cells, we identified the alpha-enolase protein (ENO1) from HCT-8 cells, which showed direct interaction with Cpgp40. The mRNA level of ENO1 gene was significantly decreased at 3 and 24 h after C. parvum infection. Antibodies and siRNA specific to ENO1 showed the ability to neutralize C. parvum infection in vitro, which indicated the participation of ENO1 during the parasite invasion of HCT-8 cells. In addition, we further demonstrated that ENO1 protein was involved in the regulation of cytoplasmic matrix of HCT-8 cells during C. parvum invasion. Functional study of the protein mutation illustrated that ENO1 was also required for the endogenous development of C. parvum.

Conclusions
In this study, we utilized the purified Cpgp40 as a bait to obtain host cell proteins ENO1 interacting with Cpgp40. Functional studies illustrated that the host cell protein ENO1 was involved in the regulation of tight junction and adherent junction proteins during C. parvum invasion and was required for endogenous development of C. parvum.

Graphical Abstract
Factors associated with vaccine hesitancy against COVID-19 among adults in Europe: a descriptive study analysis applying socio-ecological framework
Authors: Nagase Megumi 
Published: March 2024

Abstract
Objective
This study aimed to explore the factors associated with COVID-19 vaccine hesitancy in Europe among adults by using the Socio-Ecological Model.

Results
This cross-sectional study used secondary data collected from respondents residing in 27 EU countries at the time of May 2021. The outcome was vaccine hesitancy against COVID-19, and the total sample size of 23,606 was analysed by binary logistic regression, as well as McKelvey and Zavonoia’s R2. After adding each level of variables, the model found the significant and increased association with vaccine hesitancy in younger age groups (21–39 years and 40–60 years vs. 65 years+), who left full-time education at a young age (16–19 years), those with manual jobs, those with children at home, individuals residing in small towns, and beliefs related to the vaccine. Together, the levels explained 49.5% of the variance associated with vaccine hesitancy, and the addition to each variable layer increased the variance. This highlights the need to consider broad factors at multiple levels to enhance vaccine acceptance and uptake.
Association of glucose-lowering drug target and risk of gastrointestinal cancer: a mendelian randomization study
Authors: Yang Yi , Chen Bo , Zheng Chongming , Zeng Hao , Zhou Junxi , Chen Yaqing , Su Qing , Wang Jingxian , Wang Juejin , Wang Yurong , Wang Hongli , Jin Ruxue , Bo Zhiyuan , Chen Gang , Wang Yi 
Published: March 2024

Abstract
Background & Aims
Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study.

Methods
Two-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings.

Results
ABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824–59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013–1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884–0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020–0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743–34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217–51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071–0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476–18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes.

Conclusions
Some glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.
On the qualitative behaviors of stochastic delay integro-differential equations of second order
Authors: Mahmoud Ayman M. , Tunç Cemil 
Published: March 2024

AbstractIn this paper, we investigate the sufficient conditions that guarantee the stability, continuity, and boundedness of solutions for a type of second-order stochastic delay integro-differential equation (SDIDE).To demonstrate the main results, we employ a Lyapunov functional. An example is provided to demonstrate the applicability of the obtained result, which includes the results of this paper and obtains better results than those available in the literature.
Treatment of alcohol use disorder in patients with alcohol-associated liver disease: Innovative approaches and a call to action
Authors: Haque Lamia Y. , Zuluaga Paola , Muga Robert , Fuster Daniel 
Published: March 2024

AbstractAlcohol-associated liver disease is currently the leading cause of liver transplantation and liver deaths both in Europe and the United States. Efficacious treatments exist for alcohol use disorder, but they are seldomly prescribed for patients who need them. Besides, the presence of liver cirrhosis can complicate pharmacological treatment choices. In this review, we discuss established and innovative treatment strategies to treat unhealthy alcohol use in patients with alcohol-associated liver disease. We also describe the experience of our own institutions, Hospital Universitari Germans Trias i Pujol in Badalona (Spain) and Yale-New Haven Health and Yale Medicine (Connecticut. United States of America).
Determining the role of innovative teaching practices, sustainable learning, and the adoption of e-learning tools in leveraging academic motivation for students’ mental well-being
Authors: Li Jiuxiang , Wang Rufeng 
Published: March 2024

Abstract
Background
The COVID-19 pandemic has brought about significant changes in the educational landscape, with a significant shift towards e-learning and remote teaching practices. As such, it has become increasingly important to understand the role of innovative teaching practices, sustainable learning, and the adoption of e-learning tools in leveraging academic motivation for students’ mental well-being.

Purpose
The study aims to determine whether academic motivation can helpful for mental wellbeing of students directly and through the adoption of e-learning tools, and sustainable learning considering the role of innovative teaching.

Methods
Target population of this research were the students of Chinese universities. Data was collected from 308 students and was analyzed by using Mplus software.

Results
Students expressed higher motivation, quality education and good mental health. Additionally, it was discovered that academic motivation helped the students to develop good academic record and mental health.

Conclusion
The research’s conclusions can help the policy makers creating successful educational initiatives and programs that promote students’ overall growth. These results can also guide the university administration and teachers to adopt effective policies and practices for creating academic motivation in order to construct a healthy environment not just for better academic results but also for the well-being of students. Additionally, this research draws attention of future researchers to explore mechanisms that can drive students’ academic and psychological outcomes.
Review and interlaboratory comparison of the Oddy test methodology
Authors: Díaz Ivan , Alvarez-Martin Alba , Grau-Bové Josep , Norrehed Sara , Salvadori Barbara , Kraševec Ida , Duran-Romero Daniel , Cano Emilio 
Published: March 2024

Abstract
Since the introduction of the Oddy test in 1973, many museums and cultural institutions have put the method in use, developing their own versions and protocols. Currently the 3-in-1 version, temperature at 60 ºC and 2 g of tested material are set as common practice; however, other variables of the test are not standardized. The purpose of this study is to examine current versions of the Oddy test, to identify differences in the results derived from variations in the procedures, and ultimately raising awareness within the conservation community to work together towards a standardized protocol. In this article, we review the available information on the methodological differences in Oddy test protocols published in the literature related to glassware cleaning, coupon preparation, reaction vessel setup and rating of materials. Based on the review, and to highlight the many variables that could affect the results of the test, seven European cultural institutions working under the H2020 IPERION HS project performed a comparative 3-in-1 Oddy test by blindly evaluating the same ten materials. Each institution used its own test methodology but some guidelines were advised: (1) Detergents as a cleaning procedure for glassware, (2) P600 sandpaper or micromesh pad close to 1500 to prepare metal coupons and (3) 1:100 as water–air ratio. Despite this, differences between institutions’ results were still observed. Some of them are due to the differences in the coupons preparation, either in the sanding pattern or in the edge area. In order to separate the contribution of the experimental setup and the subjectivity of the evaluation in the discrepancies, coupons from all institutions have been rated by a single team of judges with experience in the Oddy Test. Results show that differences in the evaluation criteria play a relevant role in the discrepancies of the results, especially for institutions with less experience in the test. These results highlight the need to further standardize the methodology and criteria for visual assessment. Nevertheless, the Oddy test has been found to be reliable for the identification of materials that produce emissions hazardous for the conservation of cultural assets.
Multifactorial effects on bounded rational decision-making
Authors: Han Dun , Li Xiang 
Published: March 2024

Abstract
Conventional models of decision-making are predicated upon the notion of rational deliberation. However, empirical evidence has increasingly highlighted the pervasive role of bounded rationality in shaping decisional outcomes. The manifestation of bounded rationality is evident through a spectrum of cognitive biases and heuristics, including but not limited to anchoring, availability, the decoy effect, herd behavior, and the nuanced dynamics of reward and punishment, as well as the implications of weighting and framing effects. This prospective study is dedicated to a comprehensive exploration of such multiple factors together with their impacts to the architecture and functionality of decision-making processes, and their further research potentials as well.
Plasma Ceramides and Other Sphingolipids in Relation to Incident Prediabetes in a Longitudinal Biracial Cohort
Authors: Dagogo-Jack Samuel , Asuzu Peace , Wan Jim , Grambergs Richard , Stentz Frankie , Mandal Nawajes 
Published: March 2024

Abstract

Context
Sphingolipids are linked to the pathogenesis of type 2 diabetes.

Objective
To test the hypothesis that plasma sphingolipid profiles predict incident prediabetes.

Design
A case-control study nested in the Pathobiology of Prediabetes in a Biracial Cohort study, a 5-year follow-up study.

Setting
Academic health center.

Participants
Normoglycemic adults enrolled in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included oral glucose tolerance test, insulin sensitivity, and insulin secretion. Participants with incident prediabetes were matched in age, sex, and ethnicity with nonprogressors.

Interventions
We assayed 58 sphingolipid species (ceramides, monohexosyl ceramides, sphingomyelins, and sphingosine) using liquid chromatography/tandem mass spectrometry in baseline plasma levels from participants and determined association with prediabetes risk.

Main Outcome Measure
The primary outcome was progression from normoglycemia to prediabetes, defined as impaired fasting glucose or impaired glucose tolerance.

Results
The mean age of participants (N = 140; 50% Black, 50% female) was 48.1 ± 8.69 years, body mass index 30.1 ± 5.78 kg/m2, fasting plasma glucose 92.7 ± 5.84 mg/dL, and 2-hour plasma glucose 121 ± 23.3 mg/dL. Of the 58 sphingolipid species assayed, higher ratios of sphingomyelin C26:0/C26:1 (OR, 2.73 [95% CI, 1.172-4.408], P = .015) and ceramide C18:0/C18:1 (OR, 1.236 [95% CI, 1.042-1.466], P = .015) in baseline plasma specimens were significantly associated with progression to prediabetes during the 5-year follow-up period, after adjustments for age, race, sex, body mass index, fasting plasma glucose, 2-hour plasma glucose, insulin sensitivity, and insulin secretion.

Conclusion
We conclude that the saturated-to-monounsaturated ratios of long-chain ceramide C18:0/C18:1 and very-long-chain sphingomyelin C26:0/C26:1 are potential biomarkers of prediabetes risk among individuals with parental history of type 2 diabetes.
Time Trends in Liver-Related Mortality in People With and Without Diabetes: Results From a Population-Based Study
Authors: Ciardullo Stefano , Morabito Gabriella , Rea Federico , Savaré Laura , Perseghin Gianluca , Corrao Giovanni 
Published: March 2024

AbstractContextPatients with diabetes are at increased risk of dying from liver-related events, but little is known on whether this increased risk has changed in recent years.ObjectiveThe aim of the present study is to describe time trends in cause-specific liver-related mortality in people with and without diabetes from the general Italian population.MethodsData were retrieved from the health care utilization databases of Lombardy, a region of Italy that accounts for about 16% (almost 10 million) of its population. Annual cause-specific mortality rates and proportionate mortality were computed among individuals with and without diabetes from 2010 to 2019. Liver-related deaths were categorized as viral, alcohol related, and nonviral nonalcohol related (NVNA).ResultsLiver diseases were responsible for 2% and 1% of deaths in people with and without diabetes (2019). Among patients with diabetes, the crude mortality rate for liver diseases decreased from 1.13 to 0.64 deaths per 1000 person-years from 2010 to 2019. The largest proportion of liver-related deaths was attributable to NVNA diseases and it increased from 63% in 2010 to 68% in 2019, with a corresponding relative reduction of viral causes (from 27% to 23%). The standardized mortality ratio for patients with diabetes was 3.35 (95% CI 2.96-3.76) for NVNA, 1.66 (95% CI 1.33-2.01) for viral hepatitis, and 1.61 (95% CI 1.13-2.17) for alcoholic liver disease and it remained relatively stable over time. Excess mortality risk in patients with diabetes for liver-related mortality was higher than for cardiovascular mortality and cancer.ConclusionWhile liver-related mortality rates decreased significantly among patients with diabetes, NVNA causes made up the majority of cases. Excess mortality for liver-related causes in patients with diabetes compared with controls remained constant in the studied period.
Surgery for Oligometastatic Pancreatic Cancer: Defining Biologic Resectability
Authors: Koti Shruti , Demyan Lyudmyla , Deutsch Gary , Weiss Matthew 
Published: March 2024

AbstractPancreatic ductal adenocarcinoma (PDAC) is most often metastatic at diagnosis. As systemic therapy continues to improve alongside advanced surgical techniques, the focus has shifted toward defining biologic, rather than technical, resectability. Several centers have reported metastasectomy for oligometastatic PDAC, yet the indications and potential benefits remain unclear. In this review, we attempt to define oligometastatic disease in PDAC and to explore the rationale for metastasectomy. We evaluate the existing evidence for metastasectomy in liver, peritoneum, and lung individually, assessing the safety and oncologic outcomes for each. Furthermore, we explore contemporary biomarkers of biological resectability in oligometastatic PDAC, including radiographic findings, biochemical markers (such as CA 19-9 and CEA), inflammatory markers (including neutrophil-to-lymphocyte ratio, C-reactive protein, and scoring indices), and liquid biopsy techniques. With careful consideration of existing data, we explore the concept of biologic resectability in guiding patient selection for metastasectomy in PDAC.