bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of publications concerning combinations of immunotherapy and targeted therapies for hepatocellular carcinoma: a bibliometric study
Authors: Gan Biling , Wu Lei , Zhou Shunan , Chen Zhihong , Wu Fan , Xu Lianqun , Chen Zhenrong , Ma Honghui , He Peijia , Fang Dan , Shi Ning 
Published: February 2025

BackgroundHepatocellular carcinoma (HCC), a prevalent malignancy, is often diagnosed at advanced stages. Recent advances have integrated immunotherapy with targeted therapy, significantly improving treatment outcomes. This study provides a bibliometric overview of these therapeutic combinations, evaluating their development and impact.MethodsA rigorous selection process was applied to relevant literature from Web of Science, followed by in-depth bibliometric analyses— including timeline visualization, burst detection, and co-occurrence analysis—using CiteSpace and VOSviewer. This approach offered insights into the contributions of countries, institutions, authors, journals, references, and key terms within the field.ResultsA total of 506 studies published between 2014 and 2023 were included, with all articles in English. Mainland China dominated the publication output, contributing 40% (N = 202), followed by significant contributions from the United States and Japan. Kindai University led institutional contributions, accounting for 7.9% of the total (N = 40). The authors Kudo Masatoshi and Hatanaka Takeshi were the most prolific, each with nine publications. The journal Cancers emerged as the top publisher, with 48 relevant articles and an Impact Factor of 5.2 in 2022. A co-citation network analysis traced the evolution of immunotherapy and targeted therapy combinations in HCC treatment. Early research primarily focused on angiogenesis, dendritic cells, and expression markers, while recent trends have shifted towards phase III trials, adverse reactions, and checkpoint inhibitors, underscoring the field’s dynamic progression.ConclusionFuture research will expand on the pathological mechanisms underlying these therapies and novel interventions and combination strategies. Addressing adverse events and treatment discontinuation will remain central to advancing clinical applications.
NALCN expression is down-regulated and associated with immune infiltration in gastric cancer
Authors: Li Xuewei , Wu Na , Wang Chen , Pei Beibei , Ma Xiaoyan , Xie Jun , Yang Wenhui 
Published: February 2025

BackgroundNALCN has been identified as a tumor suppressor gene, and its role in human cancer progression has garnered significant attention. However, there is a paucity of experimental studies specifically addressing the relationship between NALCN and immune cell infiltration in gastric cancer (GC).MethodsThe expression levels of NALCN in tumor tissues, peripheral blood and gastric cancer cells lines from patients with GC were assessed using RNA sequencing, immunohistochemistry (IHC) staining and RT-qPCR. Data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were utilized to investigate the correlation between NALCN expression and immune cell infiltration in GC. Subsequently, the relationship between NALCN expression and infiltrating immune cells in GC tissues was examined through immunofluorescence method. Additionally, in vitro experiments were conducted to evaluate the impact of NALCN knockdown on T cells function in GC cell lines.ResultsRNA sequencing analysis revealed that NALCN expression was significantly downregulated in GC tissues. Specifically, NALCN levels were lower in GC tumor tissues and plasma compared to adjacent non-tumor tissues and healthy controls. Consistent with these findings, the expression trend of NALCN mRNA in the GEO database mirrored the experimental results. Mechanistically, NALCN knockdown markedly enhanced cell proliferation, colony formation and migration while reducing apoptosis rates in AGS and GES-1 cells. Analysis of the TCGA database indicated a positive correlation between NALCN expression and the infiltration of B cells, cytotoxic cells, immature dendritic cells (iDC) cells, CD8+ T cells, and others in GC tissue. Conversely, Th17 and Th2 cells infiltration exhibited a negative correlation with NALCN expression. Immunofluorescence staining confirmed that B cells and CD8 T cells were more abundant in GC tumor tissues with high NALCN expression, whereas Th17 and Th2 cells were less prevalent. Subsequently, we co-cultured GC cells transfected with NALCN knockdown or control vectors along with their supernatants with T cells. The results demonstrated that NALCN knockdown in GC cells or their supernatants inhibited T cell proliferation compared to control conditions. Moreover, NALCN may play a role in glucose and glutamine uptake.ConclusionsNALCN facilitates immune cell aggregation in GC and has potential as a biomarker for immune infiltration.
Associations of prognostic nutritional index with cardiovascular all-cause mortality among CVD patients with diabetes or prediabetes: evidence from the NHANES 2005–2018
Authors: Xu WenYi , Zhang Li , Yang QianKun , Cao Ying , Rao Rui , Lv Li , Cen Qin , Wei Qiong , Yang LuLing 
Published: February 2025

BackgroundImmunonutritional status is linked to the prognosis of cardiovascular disease (CVD) and diabetes, but the relationship between immunonutritional disorders and clinical outcomes in CVD patients with diabetes is unclear. This study aims to investigate the association of the novel immunonutritional indicator of prognostic nutritional index (PNI) with all-cause and CVD mortality in diabetic and prediabetic CVD patients.MethodThis is an open-cohort study involving 1,509 CVD patients with diabetes or prediabetes collected from The National Health and Nutrition Examination Survey (NHANES) and initially interviewed between 2005 and 2018. Subjects were followed up until on December 31, 2019. Mortality outcomes and causes of death were obtained from National Death Index (NDI) records. We used restricted cubic spline (RCS) and maximally selected rank statistics method (MSRSM) to assess the nonlinearity of the PNI-mortality association and determine the optimal PNI cutoff for survival outcomes. Additionally, weighted multivariable Cox regression models, subgroup analyses, and interaction tests were employed to examine the relationship between PNI and all-cause and CVD mortality. The predictive accuracy of PNI for survival outcomes was evaluated using time-dependent receiver operating characteristic curve (ROC) analysis.ResultsDuring a median follow-up of 61 months (interquartile range, 33-103 months), 507 of the 1509 (33.60%) diabetic or prediabetic CVD patients died. A negative and nonlinear association between PNI and all-cause/CVD mortality was identified by RCS analysis in all patients. In the fully-adjusted Cox regression model, in the entire cohort, higher PNI (≥46.5) was significantly associated with reduced risks for all-cause and CVD mortality. A consistent association between PNI and all-cause/CVD mortality was observed in diabetic CVD patients, but not in prediabetic CVD patients. No significant interaction between PNI and other covariates was observed (all P interaction &gt;0.05). Time-dependent ROC curve revealed that the areas under the curve (AUC) of PNI for 1-, 3-, 5-, and 10-year survival rates were 0.66, 0.66, 0.66, and 0.67 for all-cause mortality, and 0.72, 0.70, 0.72, and 0.69 for CVD mortality, respectively.ConclusionIncreased PNI is significantly associated with reduced risks for all-cause and CVD mortality in diabetic or prediabetic CVD patients, especially for diabetic CVD patients.
Evaluation of candidate reference genes for gene expression research in Vespula vulgaris
Authors: McLaughlin Gemma M. 
Published: February 2025

IntroductionVespula vulgaris is an invasive wasp that causes considerable detriment to native birds and invertebrates in New Zealand. Reducing at least 80% of invasive wasp densities is necessary to manage the problems this species presents to its invaded range. To explore the function of target genes for the genetic management of V. vulgaris, screening of appropriate reference genes is crucial for conducting the reverse transcriptase-quantitative real-time PCR (RT-qPCR). The selection of appropriate reference genes is an important but often overlooked consideration when delving into RNA research. Many studies rely on one of two tried and trusted reference genes widely used in the literature, which may not be suitable for the normalization of data under particular variables.MethodsHere, I selected six reference genes of V. vulgaris and evaluated their stability across two conditions: developmental stage and sex by using five different tools for analysis: the ΔCt method, geNorm, NormFinder, BestKeeper, and RefFinder.ResultsDiffering appropriate reference genes for different research foci: TBP, EF1A, RPL18X3, and CAPZB for developmental stage treatment, and KTB, EF1A, and CAPZB amongst the sexes.DiscussionMy study further emphasizes that there is no “one size fits all” reference gene, and advocates for analysis of reference gene suitability when conducting gene quantification experiments.
Exploring cognitive and neuroimaging profiles of dementia subtypes of individuals with dementia in the Democratic Republic of Congo
Authors: Ikanga Jean , Patel Saranya Sundaram , Schwinne Megan , Obenauf Caterina , Epenge Emmanuel , Gikelekele Guy , Tshengele Nathan , Kavugho Immaculee , Mampunza Samuel , Mananga Lelo , Teunissen Charlotte E. , Rojas Julio C. , Chan Brandon , Lago Argentina Lario , Kramer Joel H. , Boxer Adam L. , Jeromin Andreas , Omba Emile , Alonso Alvaro , Gross Alden L. 
Published: February 2025

ObjectiveThe 2024 Alzheimer’s Association (AA) research diagnostic criteria for Alzheimer’s Disease (AD) considers fluid biomarkers, including promising blood-based biomarkers for detecting AD. This study aims to identify dementia subtypes and their cognitive and neuroimaging profiles in older adults with dementia in the Democratic Republic of Congo (DRC) using biomarkers and clinical data.MethodsForty-five individuals with dementia over 65 years old were evaluated using the Community Screening Instrument for Dementia and the informant-based Alzheimer’s Questionnaire. Core AD biomarkers (Aβ42/40 and p-tau181) and non-specific neurodegeneration biomarkers (NfL, GFAP) were measured in blood plasma. Neuroimaging structures were assessed using magnetic resonance imaging (MRI). Dementia subtypes were determined based on plasma biomarker pathology and vascular markers. Biomarker cutoff scores were identified to optimize sensitivity and specificity. Individuals were stratified into one of four dementia subtypes—AD only, non-AD vascular, non-AD other, or mixed – based on combinations of abnormalities in these markers.ResultsAmong the 45 individuals with dementia, mixed dementia had the highest prevalence (42.4%), followed by AD-only (24.4%), non-AD other dementia (22.2%), and non-AD vascular dementia subtypes (11.1%). Both cognitive and neuroimaging profiles aligned poorly with biomarker classifications in the full sample. Cognitive tests varied across dementia subtypes. The cognitive profile of the AD-only and mixed groups suggested relatively low cognitive performance, while the non-AD and other groups had the best scores on average.ConclusionConsistent with studies in other settings, our preliminary findings suggest that neurodegenerative plasma biomarkers may help to identify dementia subtypes and provide insight into cognitive and neuroimaging profiles among older adults in the DRC.
Exploring the association between BIN1 gene polymorphisms and hippocampal subfield volume in community mild cognitive impairment
Authors: Luo Jiali , Ping Junjiao , Zhang Haibo , Zhang Ying , Tan Zhenkun , Kong Chuijia , Liu Xinxia 
Published: February 2025

IntroductionMild cognitive impairment (MCI) is an early stage of Alzheimer’s disease (AD), crucial for early diagnosis. BIN1, a key AD susceptibility gene after APOE, has higher brain expression in AD and interacts with tau, affecting its pathology. Specific BIN1 SNPs are linked to AD and MCI, but mechanisms are unclear. This study will explore how BIN1 polymorphisms might influence MCI development and correlate with hippocampal integrity in MCI patients using MRI.MethodsThis study enrolled a total of 52 elderly individuals with MCI and 55 cognitively CN individuals from five communities in Zhongshan Torch Development Zone. Blood samples were collected for analysis of BIN1 rs10200967, rs1060743, and rs4663093 gene polymorphisms, and MRI scans were conducted to assess the volume of hippocampal subregions. The study also seeks to examine the distribution of BIN1 genotypes in both MCI and healthy control populations, as well as to investigate the potential association between BIN1 rs10200967, rs1060743, and rs4663093 genotypes and hippocampal subregion structure in individuals with MCI.ResultsSignificant structural atrophy was observed in multiple hippocampal subregions, including left cornu ammonis (lCA), left dentate gyrus (lDG), left hippocampal-amygdaloid transition area (lHATA), left subiculum (lSubc), right ornu ammonis (rCA), right dentate gyrus (rDG), right subiculum (rSubc), left entire hippocampus complex (lHIP), and right entire hippocampus complex (rHIP) in seniors with MCI compared to those in the CN (p &lt; 0.05), after adjusting for age, gender, education level, and APOEε4 status. Conversely, no significant differences were observed in left entorhinal cortex (lEC), right entorhinal cortex (rEC), right hippocampal-amygdaloid transition area (rHATA), and total intracranial volume (TIV) (p &gt; 0.05). Notably, there were no significant differences in the distribution of BIN1 rs10200967, rs1060743, and rs4663093 genotypes among elderly individuals (p &gt; 0.05). Furthermore, the association between the BIN1 rs10200967 genotype and lHATA atrophy significant in the MCI after adjusting for age, gender, education level, APOEε4 status, and TIV (p &lt; 0.05).ConclusionThis study presents novel findings indicating an association between the BIN1 rs10200967 genotype and lHATA atrophy, with the rs10200967 CC genotype showing a higher volume of lHATA in individuals with MCI. These results suggest that the rs10200967 CC genotype may confer a protective effect against MCI, offering a potential basis for early detection and prevention of AD.
Prevalence of nutritional anemia and its risk factors in children under five in the Gaza Strip
Authors: El Bilbeisi Abdel Hamid 
Published: February 2025

BackgroundThe present study aimed to determine the prevalence of anemia and its associated risk factors among under-five children aged 24–59 months in Gaza Strip, Palestine.MethodThis cross-sectional study was conducted in 2023 before Gaza war, among a representative sample of under-five children. A total of 750 children, aged 24–59 months, were selected from all Gaza Strip governorates, using a cluster random sampling method. Children and their parents were assessed using an interview-based questionnaire, anthropometric measurements, biochemical measurements, and clinical examination. Statistical analysis was performed using SPSS version 25.ResultsThe prevalence of anemia (Hb &lt;11 g/dL) among under-five children was 35.6%. Of them, 77.5% had mild anemia and 22.5% had moderate anemia. The prevalence of iron deficiency anemia (IDA) (Hb &lt;11 g/dL and SF &lt;12 μg/L) among under-five children was 4.0%. Various risk factors were found to be statistically significant in relation to nutritional anemia. These included child-related factors such as age, weight, height, sibling arrangement, governorate, and place of residence. Family characteristics like the father’s age, smoking habits, the mother’s education, employment, marital history, income, housing ownership, and a history of anemia during pregnancy also played a role. Additionally, dietary factors such as tea, meat, crisps, cola, fruits, breastfeeding practices, malnutrition, appetite, and hereditary diseases were significantly associated with anemia in these children (p-values &lt;0.05 for all).ConclusionOur study clearly demonstrates that anemia is highly prevalent (35.6% anemia, and 4.0% IDA) among under-five children in Gaza Strip governorates. Different risk factors including the child’s and family characteristics, and the consumption of some of food items were associated with a high prevalence of anemia. The high prevalence of anemia should be seriously considered and policy makers should take steps to reduce it.
The relationship between weight-adjusted waist index and peripheral artery disease
Authors: Wu Zhe , Liu Yang , Wang Bin 
Published: February 2025

BackgroundObesity is a significant risk factor for peripheral arterial disease (PAD). The weight-adjusted waist index (WWI) is a novel obesity metric that better reflects abdominal obesity than traditional body mass index (BMI). However, research on the relationship between WWI and PAD remains scarce.MethodsRelevant data from the NHANES 1999–2004 were selected. Multiple logistic regression and restricted cubic spline (RCS) analyses were used to assess the relationship between WWI and the risk of PAD. Additionally, the area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate the predictive ability of WWI for PAD.ResultsA total of 5,686 participants were included in the study, of whom 476 had PAD and 5,210 did not. The results of multiple logistic regression showed that WWI was significantly positively associated with the risk of PAD after full adjustment for covariates (OR: 1.407, 95% CI: 1.100–1.799). Additionally, compared to the first quartile of WWI, the risk of PAD significantly increased in the second quartile (OR: 2.042, 95% CI: 1.333–3.129), third quartile (OR: 2.134, 95% CI: 1.354–3.364), and fourth quartile (OR: 2.491, 95% CI: 1.435–4.325). The ROC results showed that the AUC value for WWI was 0.697, while the AUC value for BMI was 0.520. Compared to BMI, WWI has a better predictive value for the risk of PAD.ConclusionThere is a significant positive correlation between WWI and the risk of PAD. For individuals with high WWI, efforts should be made to reduce WWI to prevent the onset of PAD.
Dietary intake of tomato and lycopene, blood levels of lycopene, and risk of total and specific cancers in adults: a systematic review and dose–response meta-analysis of prospective cohort studies
Authors: Balali Arghavan , Fathzadeh Kimia , Askari Gholamreza , Sadeghi Omid 
Published: February 2025

BackgroundThe association between tomato/lycopene intake and blood levels of lycopene with the risk of specific cancers were assessed in previous meta-analyses; however, no study evaluated the risk of overall cancer incidence/mortality. Therefore, the present systematic review and dose–response meta-analysis aimed to summarize available findings from prospective studies to examine the association between tomato/lycopene intake and lycopene levels with the risk of total and specific cancers and cancer-related mortality.MethodsA comprehensive literature search was done using Scopus, PubMed, ISI Web of Science, and Google Scholar until July 2023.ResultsIn total, 121 prospective studies were included in the systematic review and 119 in the meta-analysis. During the follow-up period of 2–32 years, a total of 108,574 cancer cases and 10,375 deaths occurred. High intakes and high levels of lycopene compared to low amounts were, respectively, associated with 5% (Pooled RR: 0.95, 95% CI: 0.92–0.98, I2 = 26.4%, p = 0.002) and 11% (Pooled RR: 0.89, 95% CI: 0.84–0.95, I2 = 15.0%, p &lt; 0.001) reduction in overall cancer risk. Also, each 10 μg/dL increase in blood levels of lycopene was associated with a 5% lower risk of overall cancer. Moreover, we found a linear inverse association between dietary lycopene intake and prostate cancer risk (Pooled RR 0.99, 95% CI 0.97–1.00, I2 = 0, p = 0.045). Regarding cancer mortality, negative relationships were found with total tomato intake (Pooled RR: 0.89, 95% CI: 0.85–0.93, I2 = 65.7%, p &lt; 0.001), lycopene intake (Pooled RR: 0.84, 95% CI: 0.81–0.86, I2 = 86.5%, p &lt; 0.001) and lycopene levels (Pooled RR 0.76, 95% CI: 0.60–0.98, I2 = 70.9%, p = 0.031). Also, an inverse association was observed between blood lycopene levels and lung cancer mortality (Pooled RR: 0.65, 95% CI: 0.45–0.94, I2 = 0, p = 0.022).ConclusionOur findings show that dietary intake and blood levels of lycopene are associated with a lower risk of cancer and death due to cancer.Clinical trial registrationCRD42023432400.
The protein transition: what determines the animal-to-plant (A:P) protein ratios in global diets
Authors: Drewnowski Adam , Hooker Kayla 
Published: February 2025

BackgroundSeveral high-income countries have announced plans to reduce the animal-to-plant (A:P) protein ratios in their population diets. Their current A:P ratio is around 65:35, with two thirds of the protein coming from animal sources, meat, eggs, and dairy. Efforts to reduce the dietary A:P protein ratio to 50:50, 40:60, or below are sometimes referred to as a “healthy protein transition.”MethodsAnalyses of Food and Agriculture Organization (FAO) and World Bank data were used to show that an opposing and far more important protein transition is taking place globally.ResultsIn most low- and middle-income countries (LMIC), the dietary A:P protein ratio was closely associated with, if not determined, by gross national incomes (GNI). As incomes rise, LMIC populations adopt more varied and more nutrient-rich diets with more animal proteins and especially meat. This protein transition, manifested by a strong observed relation between rising incomes and higher A:P protein ratios, follows a well-known principle of economics known as Bennett’s Law.ConclusionConsumer education and regulatory and policy measures aimed at reducing dietary A:P protein ratios worldwide may not uncouple the fundamental relation between powerful economic forces and global diet structures.