bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide transcriptome analysis and drug target discovery reveal key genes and pathways in thyroid cancer metastasis
Authors: Zou Minjing , Qattan Amal , Al-Alwan Monther , Ghebeh Hazem , Binjumah Naif , Al-Haj Latifa , Khabar Khalid S. A. , Altaweel Abdulmohsen , Almohanna Falah , Assiri Abdullah M. , Aboussekhra Abdelilah , Alzahrani Ali S. , Shi Yufei
Published: February 2025

Introduction

Metastasis is the major cause of thyroid cancer morbidity and mortality. However, the mechanisms are still poorly understood.

Methods

We performed genome-wide transcriptome analysis comparing gene expression profile of metastatic thyroid cancer cells (Met) with primary tumor cells established from transgenic mouse models of papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC).

Results

Genes involved in tumor microenvironment (TME), inflammation, and immune escape were significantly overexpressed in Met cells. Notably, IL-6-mediated inflammatory and PD-L1 pathways were highly active in Met cells with increased secretion of pro-inflammatory and pro-metastatic cytokines such as CCL2, CCL11, IL5, IL6, and CXCL5. Furthermore, Met cells showed robust overexpression of Tbxas1, a thromboxane A synthase 1 gene that catalyzes the conversion of prostaglandin H2 to thromboxane A2 (TXA2), a potent inducer of platelet aggregation. Application of aspirin, a TXA2 inhibitor, significantly reduced lung metastases. Mertk, a member of the TAM (Tyro, Axl, Mertk) family of RTKs, was also overexpressed in Met cells, which led to increased MAPK activation, epithelial–mesenchymal transition (EMT), and enrichment of cancer stem cells. Braf-mutant Met cells developed resistance to BRAFV600E inhibitor PLX4720, but remained sensitive to β-catenin inhibitor PKF118-310.

Conclusion

We have identified several overexpressed genes/pathways in thyroid cancer metastasis, making them attractive therapeutic targets. Given the complexity of metastasis involving multiple pathways (PD-L1, Mertk, IL6, COX-1/Tbxas1-TXA2), simultaneously targeting more than one of these pathways may be warranted to achieve better therapeutic effect for metastatic thyroid cancer.
A successful remote patient monitoring program for diabetes
Authors: Sawyer Katlyn , Saxon David , Zane Richard , Patel Hemali , McDermott Michael , Singh Vatsala , Lawler Helen M.
Published: February 2025

The prevalence of diabetes continues to rise in the United States along with a shortage of endocrinologists. One proposed solution to this challenge is to deliver more specialty health care services through remote patient monitoring (RPM). Here, we describe our initial experience with an RPM program for diabetes care at the University of Colorado. We enrolled 211 patients with primarily uncontrolled type 2 diabetes into the Diabetes Home and Remote Care Program (DHRCP). Remote care replaced traditional brick-and-mortar care while patients were enrolled. A certified diabetes care and education specialists (CDCES) contacted patients every 1-2 weeks to provide lifestyle coaching and assess medication compliance. With oversight from an endocrinologist, frequent medication adjustments were made by the CDCES. Analysis performed on 106 (50.2%) patients who met graduation criteria and had a hemoglobin A1c (HbA1c) completed upon program graduation showed an average decrease in HbA1c from 10.4% to 7.0% (p<0.001). Overall, our results demonstrate that RPM is an effective care model for improving glycemic control in patients with diabetes.
Ejaculatory abstinence duration impacts semen parameters: Insights from a retrospective analysis in male infertility on 23,527 analyses
Authors: Russo Giorgio Ivan , Asmundo Maria Giovanna , Cocci Andrea , Abdelhameed Ali Saber , Liprino Annalisa , Giacone Filippo , Lombardo Debora , Guglielmino Antonino , Chamayou Sandrine
Published: February 2025

Purpose

Ejaculatory abstinence (EA) duration is recognized to impact semen parameters. This study aims to evaluate the effects of varying EA durations on semen quality parameters, distinguishing between normospermic and sub-fertile men, and to provide insights into tailored abstinence recommendations for improved fertility outcomes.

Methods

We retrospectively analyzed 23,527 semen samples from men undergoing infertility evaluation from 2013 to 2024. Semen parameters, including sperm concentration, motility, and morphology, were assessed post-abstinence (2–7 days) according to WHO guidelines. Group differences were analyzed, focusing on sperm parameters across abstinence periods in normospermic versus patients with sperm abnormalities.

Results

In normospermic patients we found a trend increase from day 1 to day 7 of abstinence time regarding total sperm count (million) (92.4 vs. 191.1; p<0.01), sperm concentration (million/ml) (44.5 vs. 72.0; p<0.01) and morphology (6 vs. 12.5; p= 0.03) but not regarding motility (A+B) (50.0% vs. 48.0%; p=0.43). Conversely, in the population of patients with sperm abnormality, we found a significant trend increase from day 1 to day 7 of TSC (16.38 vs. 56.0; p<0.01), sperm concentration (million/ml) (8.0 vs. 18.0; p<0.01) and morphology (3.0 vs. 5.0; p<0.01). Interestingly, we found a significant trend decrease of motility (A+B) (28.0% vs. 21.0%; p<0.01) and pH (8.1 vs. 7.9; p<0.01) In patients affected by asthenospermia, motility (A+B) dropped significantly from day 1 to day 7 (11.8% vs. 6.1%; p<0.01) and also in patients with teratospermia morphology dropped significantly (2.13% vs. 1.26%; p<0.01).

Conclusion

The findings support the use of tailored abstinence guidelines to optimize semen quality based on patient-specific semen profiles, with normospermic men benefiting from longer abstinence durations to increase concentrations, while patients with motility or morphology impairments, may benefit from shorter abstinence periods to mitigate sperm quality declines.
Techno-economic assessment of hydrogen application in cereal crop farming
Authors: Anthony Katumwesigye , Hellström Magnus , Spohr Jonas
Published: February 2025

The application of hydrogen in modern farming is transitioning from a conceptual idea to a practical reality, poised to meet future agricultural machinery requirements and transition goals. Increasing tensions between farmers and various institutions underscore the growing sensitivity around fossil fuel dependency in the agricultural sector, particularly in northern economies. This study investigates the economic feasibility of using decentralized hydrogen systems to fully replace fossil fuels in cereal crop farming across four agricultural zones. Specifically, it examines the economic viability of on-farm hydrogen production using electrolysers to meet the fuel needs of different farm structures. Various scenarios were modelled to assess the impact of switching to hydrogen fuel for annual farm operations, using Net Present Value (NPV) and Levelized Cost of Hydrogen (LCOH) metrics for hydrogen refuelling facilities on distinct farm structures. The results indicate that economic feasibility is a significant challenge, with LCOH reaching as high as 57 €/kg of hydrogen in some cases, while the best-case scenarios achieved LCOH as low as 7.5 €/kg. These figures remain significantly higher than those for diesel and alternative fuels such as methane, FAME, and HVO. The study also assessed strategies for reducing hydrogen production costs using low-cost electricity and maximizing plant efficiency by increasing the electrolyser utilization rate to 70%. Additionally, the potential for revenue generation through the sale of by-products was explored. Our findings highlight both the challenges and opportunities associated with hydrogen use in agriculture, emphasizing the critical role of access to renewable energy sources and the economic limitations of by-product revenue streams. In conclusion, while decentralized hydrogen production can contribute to emission reductions in cereal crop farming, further research and policy support are essential to improve its feasibility and sustainability.
Six events that shaped antibody approvals in oncology
Authors: Paul Suman , Zhou Shibin
Published: February 2025

A little over twenty-five years ago, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) approved the chimeric antibody rituximab which fundamentally altered the landscape of anti-cancer drugs. While only a few antibodies were approved in the immediate years that followed the rituximab approval, the last decade saw a wave of antibody-drug approvals in the oncology arena. In the last three years, the EMA and FDA greenlighted eighteen antibodies, the majority of them designed in the formats of antibody-drug conjugates (ADC) and bispecific antibodies (BsAb). While the use of ADC and BsAb formats and the current rapid pace of approvals appear routine and almost inevitable, such progress was thought to be quite improbable in the early days of therapeutic antibody development. To understand how we arrived at the current state of antibody development in oncology, we focus on six monumental events that shaped antibody approvals over the last two and half decades. We examine the circumstances that led to the approval of rituximab and trastuzumab, the first successful antibodies for the treatment of hematologic and solid cancers. We detail the generation of the ADC and BsAb formats that dramatically augmented antibody-mediated precision cytotoxicity. Finally, we explore the development of ipilimumab, the first immune checkpoint-inhibiting antibody that activates the immune system to kill cancer cells, and the discovery that allowed the use of checkpoint inhibitors across all cancer types based on the presence of genetic markers. Revisiting these key events provides critical insights into the process of antibody development in oncology.
Spatial and seasonal distribution of selected nitrogen cycle genes in deep waters of the Baltic Proper
Authors: Grabski Michał , Kotlarska Ewa , Łuczkiewicz Aneta , Hryniewicz Konrad , Węgrzyn Grzegorz , Szymczycha Beata
Published: February 2025

Marine nitrogen cycle ultimately depends on the biological responses of oceanic microbial communities. It indirectly regulates primary production and influences the strength of the biological pump, which contributes to the oceanic uptake of atmospheric carbon dioxide (CO2). As the microbial community structure and functional capacities remain underestimated in terms of temporal and geographical coverage in the Baltic Sea, our understanding of the nitrogen cycle with respect to ecosystem functioning and climate change is limited. Therefore, in this study, we investigated the seasonal and spatial structure of microbial community abundance involved in the nitrogen loss (denitrification, anammox), reduction processes (dissimilatory nitrate reduction (DNR), dissimilatory nitrite reduction to ammonium (DNRA), and oxidation process (nitrification) in the Baltic Proper (Bornholm Deep, Gdańsk Deep, and Gotland Deep). Specifically, we focused on waters below the halocline at depths ranging from 75 to 135 m, characterized by changeable oxygen conditions. The potential of selected nitrogen processes was resolved by mapping raw reads against nitrogen cycle genes identified in de novo assembled metagenomes. Taxonomic analysis of bacterial and archaeal communities, based on paired-end raw reads, revealed that nitrification, DNR, and denitrification potential were primarily associated with the Nitrosopumilaceae and Thioglobaceae families within these phyla. Ammonia oxidation products likely fueled the production of nitrous oxide (N2O), with nitric oxide reductase (NOR)—an enzyme encoded by the Thioglobaceae genome—being responsible for further reduction. Anammox-related genes were not present within sites, thus denitrification pathway enzymes, namely, NOR and N2O reductase (NOS) were responsible for nitrogen loss. At all sites, genes encoding nitrogen reduction enzymes were most abundant, while the presence of NOS encoding genes was found in Bacteroidetes and Proteobacteria phyla within all sites. Our findings revealed no significant spatial variation, suggesting that the studied ecosystem exhibits a consistent nitrogen processing capacity across different locations. However, seasonality emerged as a key factor, as changes in nutrient and oxygen conditions throughout the year significantly influence microbial activity and the associated nitrogen-cycling processes.
Adaptability assessment of the whitecap statistical physics model with cruise observations under high sea states
Authors: Shi Yongfang , Yang Yongzeng , Qi Jinpeng , Wang Haili
Published: February 2025

Whitecaps are crucial for understanding ocean-atmosphere interactions, particularly under high sea states, where quantifying whitecap coverage has long been a key research focus. This study aims to validate the Whitecap Statistical Physics Model (WSPM) under high sea states using observational data. Observational data from the High Wind Speed Gas Exchange Study (HiWinGS) was used to validate the WSPM. The model's performance was assessed across multiple sites under wind speeds exceeding 15 m/s and significant wave heights (SWH) up to 10 meters. The WSPM showed good agreement with observational data at most sites, accurately capturing variations in whitecap coverage. At the same time, discrepancies in the model results were observed, which were attributed to errors in the WSPM's data sources and complex sea conditions characterized by rapid shifts in wind direction and alternating dominance of wind waves and swell. This study highlights the advantages of physics-based models over simple wind-speed-dependent parameterizations in capturing the complexities of wave dynamics. The findings suggest that the WSPM is highly effective in capturing the dynamics of whitecap coverage across a range of high sea states, providing a detailed and robust reference for its application in real-world scenarios. Further research is needed to address the sources of error and improve the model's accuracy under complex sea conditions.
Increased miRNA-375 causes oxidative damage but promotes apoptosis resistance and cell migration in the clam Ruditapes philippinarum
Authors: Cong Ming , Li Zhaoshun , Tian Wenwen , Yu Yixian , Che Yu , Lv Jiasen
Published: February 2025

MicroRNA is an important regulatory factor at the post-transcriptional level. Previous miRNAomics analysis found that miRNA-375 was steadily upregulated in the clam Ruditapes philippinarum upon ammonia nitrogen exposure. However, we have no knowledge about its regulatory mechanism yet. In this study, the clams were challenged by the injection of miRNA-375 mimics/inhibitor in vivo. Then, a combined approach of qRT-PCR, enzyme assay, and ultrastructure observation was applied to investigate its regulatory effects on the related genes, cellular parameters, and histological structures, respectively. Results showed that increased expression of miRNA-375 interfered with the expression levels of both its target genes and ammonia toxicity-related genes, which would probably lead to oxidative stress, migration of damaged cells, apoptosis resistance, and increased possibility of tumor formation. In addition, miRNA-375 increased MDA content but decreased glutamate content and caused serious structure damage to the clam gills. Thus, increased miRNA-375 probably brings a disastrous fate to the clam R. philippinarum by inducing oxidative damage but promoting apoptosis resistance and cell migration. Overall, this study revealed for the first time the regulatory effects of miRNA-375 in the clams and gave valuable clues to understand the toxicological mechanisms of ammonia nitrogen on the marine bivalve.
Hydrological drought in the lower reaches of the Yangtze River (China): a 70-year data analysis
Authors: Ge Hua , Zhu Lingling , Mao Bing
Published: February 2025

The combined impact of climate change and human activity has brought uncertainty regarding hydrological drought in the lower reaches of the Yangtze River (LYR), thereby threatening the security of regional water resources. To address this uncertainty, based on data from over 70 years, the trends, mutations, and causes of hydrological drought in the LYR were analyzed using the Mann–Kendall test method. The results of this study show that the most extreme annual hydrological drought situation defined by the daily minimum value improved, but the scenario defined by the monthly average intensified in September and October after the flood season, with a mutation in the 2000s after the Three Gorges Reservoir. The continuous decline in water availability during the flood season and the water storage of reservoirs after flooding made 2022 the most severe drought period in nearly 70 years. The rapid storage of reservoirs after flooding has promoted hydrological droughts in the LYR. In future scenarios, the impact of riverbed cutting on hydrological drought should be comprehensively evaluated, and the effects of future tide level changes under global climate change conditions should be measured.
The development trend of China’s marine economy: a predictive analysis based on industry level
Authors: Chen Yu , Zhang Huahan , Pei Lingling
Published: February 2025

This paper aims to provide insights into the future trends for the marine industries in China, by forecasting the added value in key sectors and then offering tailored policy recommendations. Those economic indicators at the industry level are characterized by small sample sizes, sectoral heterogeneity, and irregular fluctuations, which require a specialized methodology to handle data features and provide predictions for each industry. To address these issues, the conformable fractional grey model (CFGM), which integrates conformable fractional accumulation with the grey forecasting model, is applied and proven effective through accuracy and robustness tests. First, the results from multi-step experiments demonstrate that the CFGM model significantly outperforms traditional statistical, machine learning models, and grey models in the context of the sectoral added value predictions, with an average accuracy improvement of 32.14%. Second, the robustness and stability of the predictive values generated by CFGM are further verified by the Probability Density Analysis (PDA) and multiple comparisons with the best (MCB) tests, thereby ruling out the possibility that these accurate predictions are the result of mere chance. Third, the CFGM model is used to estimate the future added values across multiple marine industries, accompanied by suggestions to ensure the sustainable development of the marine economy.
Exploring avocado consumption and health: a scoping review and evidence map
Authors: Fleming Stephen A. , Paul Tristen L. , Fleming Rachel A. F. , Ventura Alison K. , McCrory Megan A. , Whisner Corrie M. , Spagnuolo Paul A. , Dye Louise , Kraft Jana , Ford Nikki A.
Published: February 2025

Objective

This scoping review evaluates the breadth of research on avocado intake and health, considering all populations and health outcomes (registered on Open Science Foundation at https://osf.io/nq5hk).

Design

Any human intervention or observational study where effects could be isolated to consumption of avocado were included. A systematic literature search through April 2024 was conducted (PubMed, Web of Science, Scopus, and CENTRAL) and supplemented by backwards citation screening. Dual screening, data extraction, and conflict resolution were performed by three reviewers and an interactive evidence map was created.

Results

After deduplication, 8,823 unique records were retrieved; 58 articles met inclusion criteria, comprising 45 unique studies (28 interventions, 17 observational studies). Studies were largely conducted in the United States or Latin America and generally included adults, with overweight/obesity, frequently with elevated lipid concentrations. Interventions assessed the impact of diets enriched in monounsaturated fatty acids, diets higher/lower in carbohydrates, or in free-feeding conditions. Larger amounts of avocados were used in interventions than commonly consumed in observational studies (60–300 vs. 0–10 g/d, respectively). Blood lipids, nutrient bioavailability, cardiovascular risk, glycemia, and anthropometric variables were the most common outcomes reported across all studies.

Conclusion

Future recommendations for novel research include the study of: European, Asian, adolescent or younger, and senior populations; dose–response designs and longer length interventions; dietary compensation; and the need for greater replication. The results have been made public and freely available, and a visual, interactive map was created to aid in science translation. This evidence map should enable future meta-analyses, enhance communication and transparency in avocado research, and serve as a resource for policy guidance.
Evaluating the association of depressive symptoms on serum folate and erythrocyte folate levels based on the 2017–2020 NHANES database
Authors: Yang Yunhong , Qi Huaqian , Zhang Jiahao , Jia Jie , Yang Yunsong , Zhao Hong
Published: February 2025

Objective

To improve further the management of the nutritional status and dietary habits of depressed patients.

Methods

This study investigated the effect of different severity states of depressive symptoms on serum and erythrocyte folate levels using the Nutrition Examination Survey (NHANES) database from 2017 to 2020. We comprised a sample of 4,872 cases from NHANES database. We developed 3 linear regression models to assess the effect of depressive symptoms on erythrocyte folate and serum folate by collating and analyzing the data. The relationship between depression severity and erythrocyte folate as well as serum folate was also mutually validated by the results of multiple logistic regression. Finally, we made restricted cubic spline plots using the glm function of R.

Results

Depression remained negatively correlated with serum folate levels with a OR value of −0.02, 95% CI of −0.05 ~ −0.00. Moderate depression was negatively correlated with folate, with a OR value of −0.03, 95% CI of −0.05 ~ −0.00. When exploring the association between different degrees of depressive symptoms and erythrocyte folate, it was unexpectedly found that major depression was negatively associated with erythrocyte folate with a OR value of −0.18, 95% CI of −0.31 ~ −0.04 after adjusting for all covariates.

Conclusion

Depression is associated with folate levels. The risk of serum folate insufficiency or erythrocyte folate insufficiency is higher after a positive depression. For different degrees of depressive symptoms, serum folate levels were significantly lower than normal in patients with moderate depression, while erythrocyte folate levels were lower than normal in patients with major depression. Therefore, attention should be paid to the dietary habits and nutritional status of patients with depression or depressive symptoms when they are undergoing long-term antidepressant treatment. Folic acid supplementation is recommended for patients with moderate or severe depression or for depressed patients who have developed unhealthy eating habits.
Unraveling the microbial mysteries: gut microbiota’s role in ulcerative colitis
Authors: Ren Keyu , Yong Chunming , Jin Yanchun , Rong Shanwei , Xue Kuijin , Cao Bin , Wei Hongyun
Published: February 2025

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. Recent research has highlighted the significant role of gut microbiota in the pathogenesis and treatment of UC. This review aims to provide a comprehensive overview of the current understanding of the relationship between gut microbiota and UC. We discuss the involvement of gut microbiota in the onset of UC, including the dysbiosis observed in patients and its potential mechanisms. Additionally, the role of extra-intestinal microbiota in UC pathogenesis is explored, which has been less studied but is gaining attention. The influence of gut microbiota on the efficacy of biological immunotherapy for UC is also examined, highlighting how microbial composition can influence treatment outcomes. Furthermore, we review microbiota transplantation, and their potential benefits in UC management. Finally, we consider the combined use of antibiotics and biological agents in UC treatment, discussing their synergistic effects and potential drawbacks. This review underscores the importance of gut microbiota in UC and suggests that targeting microbial communities could offer new avenues for effective treatment.
Prediction model for unfavorable treatment outcome for complicated sever acute malnutrition (SAM) in under five children admitted in hospitals at Amhara Region
Authors: Yeshiwas Almaw Genet , Anteneh Zelalem Alamrew , Tsega Tilahun Degu , Fentaw Ahmed Ahmed , Yenew Chalachew
Published: February 2025

Background

Severe acute malnutrition (SAM) affects 45 million children worldwide, with 14.89% of Ethiopian children under five suffering from it. This study validates a prediction model and develops risk scores for unfavorable treatment outcomes in SAM patients, addressing the scarcity of risk assessment tools in low-income settings and providing clinicians with a practical tool to improve decision-making.

Methods

A cohort study was conducted among 915 SAM children hospitalized with SAM hospitals in Amhara Region. Data analysis was conducted using STATA 17 and R 4.4.1. A lasso-selected multivariable model developed a nomogram for clinical utility. Model performance was assessed via AUC, calibration plot and validated with bootstrapping. Decision curve analysis evaluated the model’s clinical and public health utility.

Results

The incidence of unfavorable treatment outcomes of SAM cases was 27.8% (95% CI: 25, 31). Majority of admitted children in stabilization center were complicated Severe Acute Malnutrition (cSAM) under-five children a magnitude of 89.52% (95% CI: 80.5–99.82). The developed nomogram comprised seven predictors: baseline Oedema, Diarrhea, CBC test results (Anemia), Pneumonia, Folic Acid supplementation, Vitamin A supplementation and IV antibiotic treatment. The AUC of the original model was 91.3% (95% CI: 89.0, 93.5), whereas the risk score model produced prediction accuracy of an AUC of 90.86 (95% CI: 88.6, 92.9). It was internally validated by bootstrapping method, and it has a relatively corrected discriminatory performance. Decision curve analysis indicated a higher net benefit compared to treating all or none, especially for threshold probabilities above 21%.

Conclusion

Our model and risk score demonstrate excellent discrimination and calibration, with minimal accuracy loss from the original, ensuring robust predictive performance. The models can have the potential to improve care and treatment outcomes in the clinical settings. Healthcare professionals prioritize the management of cSAM cases in children, particularly those presenting with baseline edema and co-morbidities such as pneumonia, anemia and diarrhea. Emphasis should be placed on timely interventions, including the administration of folic acid and Vitamin A supplementation, as well as intravenous antibiotics. Implementing a comprehensive care plan that addresses these factors will significantly improve treatment outcomes and enhance recovery in this vulnerable population.
Association between prognostic nutritional index and all-cause mortality and cardiovascular disease mortality in American adults with non-alcoholic fatty liver disease
Authors: Lei Yuqing , Tao Shaohong , Yang Yubo , Xie Fang , Xie Weining
Published: February 2025

Background

The current research was to investigate the relationship between prognostic nutritional index (PNI) and mortality, with a focus on all-cause and cardiovascular disease (CVD) mortality, for those with non-alcoholic fatty liver disease (NAFLD).

Methods

Data from 20,142 patients who participated in the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2005 and 2014, were included in this research. To examine the relationship between PNI and both all-cause and cardiovascular mortality, we employed weighted Cox regression models with multiple variables. Kaplan–Meier survival curves were utilized to visualize the survival distribution across different levels of PNI. The non-linear association between PNI and mortality was addressed through penalized spline smoothing. Subgroup analyses were conducted to examine the potential influence of relevant clinical variables on the relationship between PNI and mortality. The precision of PNI in forecasting the outcome of survival was assessed as well using time-dependent receiver operating characteristic curve (ROC) analysis.

Results

Kaplan–Meier analysis linked higher PNI to significantly reduced all-cause and CVD mortality. Multivariable Cox models demonstrated that increasing PNI consistently lowered mortality risks. With a threshold value of 50.5, the link between PNI and mortality showed a non-linear pattern after adjusting for confounding factors. Subgroup analyses confirmed robust associations, particularly in race, education, BMI, and fibrosis. Time-dependent ROC analysis highlighted the strong predictive performance of PNI across various time points.

Conclusion

PNI played a significant role as an effective predictor of prognosis in individuals diagnosed with NAFLD.
Comprehensive evaluation of the nutritional value and contaminants of alfalfa (Medicago sativa L.) in China
Authors: Zhu Xiaoyan , Chen Wenxue , Li Mengyao , Liu Boshuai , Zhao Shumin , Hu Menglin , Li Jiajing , Li Defeng , Shi Yinghua , Sun Hao , Wang Chengzhang
Published: February 2025

Introduction

Alfalfa is used as a feed source for animals and plays an important role in animal nutrition. Nutritional value analysis and contamination evaluation are essential for sustainable utilisation to ensure the quality and safety of alfalfa.

Aim

We aimed to evaluate the nutritional value and safety of alfalfa in five major regions in China—the Northeast Plain (NP), Inner Mongolia Plateau (IMP), Northwest Desert Oasis (NO), Loess Plateau (LP), and Huanghuaihai Plain (HP).

Methods

Ninety-five samples representing 44 large-scale pratacultural companies were collected and analysed.

Results

The average nutritional values of alfalfa hay were 16.43% crude protein (CP), 44.01% neutral detergent fibre (NDF), 33.22% acid detergent fibre (ADF), 10.78% crude ash (Ash), and 91.90% dry matter (DM), which were better in the NO and IMP areas; in particular, the α-linolenic acid value of alfalfa was the highest in the IMP area (p < 0.05). The detection rates of mycotoxins, microorganisms, and heavy metals were 100%. The over-standard rates of total bacteria count and total mould count were 66.7% and 75.8%, respectively, while the over-standard rate of chromium in heavy metals was as high as 87.9%.

Discussion

This study establishes the nutrient composition and harmful component profiles of alfalfa hay in five major planting areas for the first time, which provides a valuable reference for the safe and sustainable utilisation of alfalfa in livestock feed.
GLI1-altered mesenchymal tumor involving the parietal pleura: case report and literature review
Authors: Zhong Yuanli , Li Baizhou , Wang Gangping , Liu Yuqing , Chen Zhenwei
Published: February 2025

GLI1-altered mesenchymal tumors represent a rare category of soft tissue tumors that have recently been incorporated into the classification of head and neck soft tissue tumors in the fifth edition of the World Health Organization (WHO) classification. However, their precise nature remains undefined, and they have yet to be assigned an ICD code. These tumors are predominantly located in the head and neck region and display distinctive pathological morphology and molecular characteristics. We present the first documented case of a GLI1-altered mesenchymal tumor occurring in the pleura. Microscopic examination revealed that the tumor was composed of ovoid-to-round and vaguely epithelioid cells, as well as a few spindle cells, all exhibiting a uniform morphology and organized in a nested and reticular arrangement, accompanied by a rich capillary network in the stroma. Immunohistochemical staining demonstrated positivity for CD56, S-100, and SMA. Next-generation sequencing (NGS) revealed a PTCH1-GLI1 fusion. Based on the morphological and immunophenotypic characteristics, molecular studies confirmed the diagnosis of a GLI1-altered mesenchymal tumor. At the 15-month follow-up, the patient was alive. We conducted a review of all cases of recurrence and metastasis, concluding that this type of tumor has a distinct propensity to metastasize to the lungs. The tumor exhibits malignant potential, and factors such as its occurrence outside the head and neck region, high-grade histological morphology, active mitosis (>5/10HPF), necrosis and PTCH1-GLI1 fusion are all considered potential risk factors.
A rare case of vision loss caused by leptomeningeal metastasis of lung adenocarcinoma: a case report and literature review
Authors: Li Zhihua , Chu Jian , Shen Wennan , Chen Junnan , Dong Yuemei , Zhang Manze , Zhao Nan , Zhao Wei , Zha Haoran , Wang Ning , Han Yalin , Li Zhaoxia
Published: February 2025

Leptomeningeal metastasis (LM) is a fatal complication with increasing incidence in patients with non-small cell lung cancer. Herein, we present the case of a patient who presented with complete vision loss due to LM and achieved a survival benefit from treatment with trametinib. The treatment was prescribed based on the detection of a BRAF non-V600E mutation in the cerebrospinal fluid (CSF). We reviewed the literature and evaluated survival benefits in patients with LM harboring BRAF non-V600E mutations treated with CSF chemotherapy and mitogen-activated extracellular signal-regulated kinase inhibitors.
Case report: Personalized management of treatment resistance in advanced NSCLC patients with mutated epidermal growth factor receptor: special examples and literature review
Authors: Wang Jun , Li Xiaojing , Dong Shuang , Hu Sheng , Ran Fengming , Qian Yu
Published: February 2025

The treatment landscape of non-small cell lung cancer (NSCLC) has shifted significantly from empirical, histology-driven, and clinician-directed cytotoxic regimens to a stratified approach predicated on molecular profiling of tumor genetics and immune biomarkers, by the former can indicate targeted therapy that bull’s eye hits the arrow, while the latter can hint the benefit amplitude of immune checkpoint inhibitors (ICBs). While third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have become the cornerstone of frontline therapy for patients harboring classic sensitive EGFR mutations, all tumors ultimately develop acquired resistance to these approaches, which can be categorized into three primary mechanism subclasses. The first subclass involves the acquisition of target mutations that lead to changes in the kinase domain, thereby hindering drug binding. The second mechanism, known as bypass resistance, entails tumor clones utilizing alternative signaling pathways for proliferation. Lastly, the third acquired mechanism pertains to histological transformation, such as the emergence of small cell lung cancer (SCLC) clones. The transformation of pathological types has brought great confusion to the clinical diagnosis and treatment process. We report a case of advanced lung adenocarcinoma with EGFR-sensitive mutation that transformed into small cell lung cancer after EGFR-TKIs treatment. Subsequent treatment revealed the presence of both adenocarcinoma and small cell carcinoma through needle biopsies at various metastatic sites. Based on the pathological, the patient received combination therapy with anlotinib at different times and achieved a long survival time.
Improving CD3 bispecific antibody therapy in solid tumors using combination strategies
Authors: Lloyd Katy , Middelburg Jim , Ovcinnikovs Vitalijs , Pencheva Nora , Kemper Kristel , van Hall Thorbald
Published: February 2025

CD3 bispecific antibodies (bsAbs) are emerging as an important treatment option in the arsenal of oncologists. There are numerous FDA-approved CD3 bsAbs for both hematological and solid tumors. Despite these recent advances, the success of CD3 bsAbs in solid cancer has been hampered by hurdles like limited intratumoral T cell numbers, immunosuppressive tumor microenvironments (TME), and poor memory T-cell induction. Furthermore, tumor surface antigen selection for an optimal therapeutic window and acceptable collateral damage to normal tissues is challenging. In this review, we discuss recent research investigating combination approaches aimed at improving CD3 bsAb efficacy in solid cancer.
High-performance CT features supporting accurate pre-operative tumor staging in colon cancer
Authors: Yuan Jianhua , Jin Cangzheng , Si Jianrong , Liu Baobao , Si Xiaohan , Chen Jianzhi
Published: February 2025

Background and aims

Accurate pre-treatment tumor staging is essential for treatment decision-making. Multi-slice spiral computed tomography (CT) is currently the standard method for pre-operative clinical tumor staging, but accurately applying the CT findings in tumor staging remains a challenge due to the poor pathological understanding of the CT signs. We aimed to pathologically interpret the key CT findings in order to identify reliable markers for pre-treatment staging of colon cancer.

Patients and methods

The following CT features from 136 colon adenocarcinomas were analyzed: colon wall pliability, outline contour, pericolic fat attenuations and vascularity, tumor fusion with adjacent organs, ascites, tumor size, and relevance between tumor and retroperitoneal fascia. These CT features were corroborated with histopathological findings. The diagnostic performance of these was further analyzed.

Results

Based on the postoperative pathological tumor staging (pT), 136 colon adenocarcinomas were classified into four stages: pT1 (n = 5), pT2 (n = 7), pT3 (n = 96), and pT4 (n = 28). Key findings include the following: (1) soft colon wall is a characteristic of the pT1 tumors, whereas stiff colon wall is a characteristic of the pT2~pT4 tumors; pathologically, stiff colon wall reflects the infiltration of tumor cells with desmoplastic reaction (DR) in muscularis propria; (2) small protuberances may help exclude the pT2 tumors. Histopathologically, small protuberances in pT2 cancer represent the pure DR on the surface of lamina propria, whereas the small protuberances in pT3~pT4 cancers represent the sub-serosal or extra-serosal cancer cell foci enwrapped by DR; (3) the presence of large protuberances, extensive reticulonodular fat stranding, and fusion with surrounding organs and ascites are diagnostic of pT4 tumors; and (4) the presence of extra-fascial nodules/streaks on CT scan could accurately diagnose the ascending/descending colon cancer of pT4 stage. Histologically, the presence of the above five CT features (large protuberances, extensive reticulonodular fat stranding, fusion with surrounding organs, ascites, and extra-fascial nodules/streaks) reflect the farther and deeper infiltration of tumor cells in serosa or retroperitoneal fascia involvement.

Conclusion

Our studies have identified multiple CT features that are practically useful in identifying and differentiating different stages of colon cancer prior to surgical procedures. These high-performance markers will provide valuable insights to the clinicians in making appropriate decisions in the management of patients with colon cancer.
Salvia deserti Decne., an endemic and rare subshrub from Arabian desert: antidiabetic and antihyperlipidemic effects of leaf hydroethanolic extracts
Authors: Guetat Arbi , Selmi Slimen , Abdelwahab Abdelrhman T. , Abdelfattah Marwa A. , Elhaj Abd Ealrhman M. , Mogharbel Roaa T. , Abualreish M. J. A. , Alanazi Abdullah F. , Hosni Karim , Mejri Naceur , Boulila Abdennacer
Published: February 2025

Introduction

Diabetes is a major health issue that has reached alarming levels worldwide. Although their effectiveness, the antidiabetic drugs have many side effects such as cardiovascular diseases, kidney failure, and hepatic complications. Many plant species of the genus Salvia L. such as “Arabian desert sage” (Salvia deserti) should began to be the focus of phytochemical and bioactivity studies.

Methods

The study aims to investigate, first-ever, the antidiabetic and antihyperlipidemic effects of the leaf hydroethanolic extract of S. deserti, an endemic and rare subshrub from Arabian desert. A single intraperitoneal injection of alloxan monohydrate (160 mg/kg) was used to induce type-2 diabetes. Development of diabetes was confirmed by measuring the blood glucose collected from the tail vein after 72 h of alloxan injection. Oral administration of hydroethanolic extracts of S. deserti at 200 and 400 mg/kg for 14 days were tested on the alloxan-induced diabetic mice and animals were divided into 6 groups of 6 mice each. The identity of phenolic compounds of the hydroethanolic extract of S. deserti was conducted through HPLC-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS) analyses.

Results

Oral administration of hydroethanolic extract of S. deserti at 200 and 400 mg/kg for 14 days significantly decreased blood glucose and restored the hepatic and renal function by reducing the levels of ALT, AST, ALP, GGT, LDH, urea and creatinine. An improved lipid profile as revealed by the reduced levels of TC, TG and LDL coupled with increased level of HDL was also observed. Moreover, treatment with S. deserti hydroethanolic extract relieved oxidative stress (reduction of MDA and H2O2) and the activity of antioxidant enzymes SOD, CAT and GPx. The presence of several phenolic compounds (derivatives of ferulic, coumaric, and caffeic acids, among other derivatives) could at least in part explain the obtained data and empower the use of S. deserti as a source of bioactive ingredients with antioxidant, antidiabetic and antihyperlipidemic properties.

Discussion

Our research has unveiled S. deserti as a source of potential to effectively manage diabetes and its associated dyslipidemia by improving antioxidant status, recovery of the liver and kidney functions and presumably by increasing insulin secretion and sensitivity of peripheral tissues to insulin.
AI foundation models for experimental fusion tasks
Authors: Churchill R. Michael
Published: February 2025

Artificial Intelligence (AI) foundation models, while successful in various domains of language, speech, and vision, have not been adopted in production for fusion energy experiments. This brief paper presents how AI foundation models can be used for fusion energy diagnostics, enabling, for example, visual automated logbooks to provide greater insights into chains of plasma events in a discharge, in time for between-shot analysis.
The correlation between resilience and mental health of adolescents and young adults: a systematic review and meta-analysis
Authors: Luo Shulai , Hu Jiangtao , Zhang Junshuai , Mei Zhengyang , Tang Zhongjian , Luo Shi
Published: February 2025

Background

Adolescents and young adults (AYAs) aged 10–25 exhibit an increased prevalence of mental health disorders. Resilience has been well established as a positive factor in promoting and protecting mental health. This systematic review and meta-analysis aimed to quantify the correlation between resilience and mental health in AYAs by including relevant observational studies. Additionally, it explored potential moderators such as percentage of female participants, sample regions, and resilience measurements.

Methods

A comprehensive search of the PubMed, Embase, Cochrane Library, Web of Science and Scopus databases was conducted until September 2024. CMA 3.0 software was used to perform meta-analysis, publication bias and sensitivity analysis of the included studies, and the moderating effect was verified by meta-analysis of variance (ANOVA).

Result

Nineteen studies involving a total of 17,746 participants were included, and the summary effect sizes from the random effect model showed that resilience among AYAs had a correlation coefficient of -0.391 with negative indicators of mental health (95% CI: - 0.469, - 0.308, p < 0.001), and a correlation coefficient of 0.499 with positive indicators of mental health (95% CI: 0.400, 0.586, p < 0.001). Additionally, sample regions and resilience measurements significantly moderated the correlation between resilience and positive indicators of mental health.

Conclusion

Resilience in AYAs showed a moderately negative correlation with negative indicators of mental health and a moderately strong positive correlation with positive indicators of mental health. The findings strengthened the basis for future resilience research in AYAs aged 10–25, highlighting the potential of resilience to help mitigate the increasing mental health challenges faced by this population.
Gendered associations of situational and dispositional factors with exclusion from social relations and loneliness in older age
Authors: Pavlidis Georgios
Published: February 2025

Background

States of exclusion from social relations (ESR) refers to severe social isolation in older age that is not always typified by increased loneliness. Relevant deficiencies in the social network of older persons may be gendered and associated with personality and socioeconomic barriers, with direct implications for older persons’ welfare. Although the contribution of personality traits and socioeconomic barriers in shaping ESR states in older age are often debated, empirical evidence that addresses their unique contribution is limited. Therefore, the aim of this study was to examine the gender-stratified associations of situational (e.g., marital status, socioeconomic conditions) and dispositional factors (i.e., personality traits) with ESR states and loneliness in older age.

Methods

A cross-sectional and gender-stratified secondary analysis of a sample (N = 36,814) from the Survey on Health, Aging, and Retirement in Europe was conducted using logistic regression models.

Results

The probability of ESR was higher among older men. Certain situational factors (e.g., widowed, never married) significantly increased the probabilities of ESR for both genders, while other (e.g., divorce) had a gender-specific significance. Less extraversion among older women and less conscientiousness among older men was associated with an increased probability of ESR in later life. Within ESR states, older men living alone and older women who are less extraverted were more at-risk of loneliness.

Conclusion

Situational factors are more predictive of ESR states than personality traits, yet a gendered perspective is needed when assessing the risk factors of ESR and loneliness in later life.
Development of a high thermal efficiency heavy-duty engine
Authors: Garcia Erick , Triantopoulos Vassilis , Trzaska Joseph , Boehman André L. , Taylor Maxwell , Li Jian
Published: February 2025

The U.S. Department of Energy Supertruck 2 program placed emphasis on development of heavy-duty trucks with high freight efficiency using commercially realizable technology suites. This paper describes the research and development process used to pursue a high thermal efficiency heavy-duty engine under Supertruck 2. The team focused on over-expanded engine cycles and advanced piston designs. This paper describes how single-cylinder engine studies using thermal barrier coated pistons, high compression pistons, and over-expanded cycles informed the development process of a multi-cylinder demonstration engine that achieved 49.9% peak thermal efficiency. While tailoring the injection strategy and other control parameters optimized the demonstration engine, more than half of the efficiency improvement came from the over-expanded cycle.