bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing early detection of organ damage and cardiovascular risk prevention: the Suzhou cardiometabolic health study protocol - exploring the role of oral microbiome and metabolic profiling in risk stratification
Authors: Zhu Mengmeng , Li Yiwen , Wang Wenting , Liu Longkun , Liu Wenwu , Yu Jiayu , Xu Qian , Cui Jing , Liu Yanfei , Chen Keji , Liu Yue
Published: February 2025

Background

Cardiovascular Disease (CVD) is the leading cause of global mortality, with its incidence rate rising year by year due to the prevalence of metabolic diseases. Existing primary and secondary prevention strategies for cardiovascular disease have limitations in identifying some high-risk groups, and 1.5-level prevention aims to achieve more precise intervention by early identification of subclinical target organ damage. This study introduces oral (tongue coating) microbiota as metabolic markers for the first time, in combination with multiple metabolic factors, to explore their potential in assessing subclinical target organ damage and optimizing cardiovascular risk stratification, in order to provide a new path for the early identification and intervention of CVD.

Methods

This study is a prospective cohort study aimed at assessing the association between tongue coating microbiota characteristics and multiple metabolic factors with subclinical target organ damage, and identifying high-risk groups suitable for cardiovascular 1.5-level prevention. The study will be conducted in Suzhou City, Jiangsu Province, China, planning to include 5000-6000 eligible subjects, with inclusion criteria of age ≥18 years, excluding individuals with a history of CVD and other serious diseases. Baseline assessment includes demographic information, lifestyle (including dietary patterns), medical history, physical examination, and collection of tongue coating microbiota samples. Subjects will be followed up every 2 years, with the primary outcome being the first occurrence of coronary heart disease and stroke, and the secondary outcome being subclinical target organ damage.

Discussion

This study focuses on cardiovascular 1.5-level prevention strategy, combining metabolic factors with tongue coating microbiota characteristics, aiming to optimize the risk assessment system for subclinical target organ damage. This approach can not only fill the gap in traditional risk assessment but also provide new ideas for the early identification and intervention of CVD. In the future, the feasibility and effectiveness of this strategy will be verified through multicenter studies, and it is expected to be promoted to a wider medical system, significantly improving the health management level of high-risk groups for CVD.

Trial registration number

http://itmctr.ccebtcm.org.cn, identifier ITMCTR2024000616.
Real-world effectiveness of sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir/voxilaprevir against genotype 3 hepatitis C virus infection: a systematic review and meta-analysis
Authors: Zhuang Liwei , Li Junnan , Zhang Yu , Ji Shibo , Xing Huichun
Published: February 2025

Introduction

Direct antiviral agents (DAAs) have dramatically changed the landscape of liver diseases associated with chronic hepatitis C virus (HCV) infection. However, limited data are available on the antiviral effect of sofosbuvir (SOF) + velpatasvir (VEL) ± ribavirin (RBV), SOF + VEL + voxilaprevir (VOX), and glecaprevir (GLE) + pibrentasvir (PIB) in treating patients infected with HCV GT3 in a real-world setting.

Methods

Using the EMBASE, PubMed, and Cochrane Library databases, articles were screened from 1 January 2016 to 1 June 2024. The sustained virologic response (SVR) rates were analyzed using the Freeman–Tukey double arcsine transformation in a random-effects model in R4.1.0 software.

Results

We recruited 3,177 patients with HCV GT3 in 19 studies from 9 countries. The pooled SVR12/24 rate of the three evaluated regimens was 94.00% (95% CI: 90.87-96.59%). Furthermore, the SVR rate was 83.81% (95% CI: 75.70-90.62%) in patients receiving SOF+VEL+VOX; 94.98% (95% CI: 92.02-97.33%) in patients receiving SOF+VEL ± RBV; and 96.96% (95% CI: 93.20-99.45%) in patients receiving GLE+PIB. The pooled SVR12/24 rate of the three regimens was 95.70% (95% CI: 91.74-98.58%) and 90.50% (95% CI: 83.50-95.90%) in non-cirrhotic and cirrhotic patients, respectively. The pooled SVR rate was 96.79% (95% CI: 93.37-99.13%) and 88.41% (95% CI: 82.67-93.22%) in treatment-naive and treatment-experienced patients, respectively.

Conclusion

SOF+VEL ± RBV, GLE+PIB, and SOF+VEL+VOX had good antiviral effectiveness for chronic HCV-GT3 infection in real-world settings. Factors such as cirrhosis and treatment experience, especially previous DAA treatment failure, may influence the SVR rate.
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

Background

Hepatocellular 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.

Methods

A 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.

Results

A 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.

Conclusion

Future 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

Background

NALCN 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).

Methods

The 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.

Results

RNA 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.

Conclusions

NALCN 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

Background

Immunonutritional 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.

Method

This 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.

Results

During 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 >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.

Conclusion

Increased 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

Introduction

Vespula 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.

Methods

Here, 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.

Results

Differing appropriate reference genes for different research foci: TBP, EF1A, RPL18X3, and CAPZB for developmental stage treatment, and KTB, EF1A, and CAPZB amongst the sexes.

Discussion

My 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.
SARS-CoV-2 detection via metagenomic next-generation sequencing of bronchoalveolar lavage fluid/sputum in lymphoma patients receiving B-cell-depleting therapy: a case report of two cases
Authors: Sun Cuiming , Zhang Zhidan
Published: February 2025

We describe two cases of coronavirus disease 2019 (COVID-19) infection in patients with lymphoma receiving B-cell-depleting therapy. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF)/sputum showed ongoing viral replication, despite repeated nasopharyngeal swabs being negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. The patients failed to develop seroconversion of IgG antibodies for SARS-CoV-2. However, they showed favorable clinical outcomes after treatment with nirmatrelvir/ritonavir or molnupiravir, despite the antiviral therapies being initiated later in the clinical course. Our case highlights that in immunocompromised hosts, viral clearance of SARS-CoV-2 in lung tissue may lag behind that in the upper respiratory tract. Thus, alternative diagnostic criteria are necessary, and clinical decisions and interventions should be tailored to each individual case.
Programming CRISPRi to control the lifecycle of bacteriophage T7
Authors: Bergmiller Tobias
Published: February 2025

Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi), based on catalytically dead Cas9 nuclease of Streptococcus pyogenes, is a programmable and highly flexible tool to investigate gene function and essentiality in bacteria due to its ability to block transcription elongation at nearly any desired DNA target. In this study, I assess how CRISPRi can be programmed to control the life cycle and infectivity of Escherichia coli bacteriophage T7, a highly virulent and obligatory lytic phage. This is achieved by blocking the expression of critical host-dependent promoters and genes that are required for T7 genome translocation and lifecycle progression. Specifically, I focus on the promoters within the non-coding internalisation signal region and the E. coli-recognised promoter C controlling T7 RNA polymerase (T7 RNAP) expression. Fluorescent reporter assays reveal that CRISPRi targeting of promoters in the internalisation signal is only moderately effective, whereas the downregulation of the phage’s own T7 RNAP occurs very efficiently. Effects on the time to lysis were strongest when the left-most promoter on the leading end of the T7 genome or T7 RNAP was targeted. The stringency of the CRISPRi approach further improved when using multiplex sgRNAs to target multiple phage regions simultaneously, resulting in a 25% increase in the time to lysis and up to an 8-fold reduction in plaque size. Overall, this study expands dCas9-dependent CRISPRi as a flexible tool to non-invasively manipulate and probe the lifecycle and infectivity of otherwise native T7 phage.
Frk positively regulates innate antiviral immunity by phosphorylating TBK1
Authors: Zhang Xiaomei , You Ying , Xiong Tingrong , Zhang Xiaokai , Wang Haibo , Geng Jinxia , Wang Miao , Xu Yanyan , Gao Shanshan , Wu Xiaoyan , Zheng Yue , Wen Xianhua , Yang Haoyu , Wang Yu , Wen Xiaohua , Zhao Congcong
Published: February 2025

Type I interferons (IFN-I) are crucial for the initial defense against viral infections. TBK1 serves as a key regulator in the production of IFN-I, with its phosphorylation being essential for the regulation of its activity. However, the regulatory mechanisms governing its activation remain incompletely elucidated. In this study, we validated the function of Fyn-related kinase (Frk) in the antiviral innate immune response and identified the direct target molecule of Frk in the IFN-β signaling pathway. Furthermore, we elucidated the mechanism by which Frk phosphorylates TBK1 during infection and the role of Frk in IFN-β production. We discovered that Frk enhances the activation of the IFN-I production pathway by targeting TBK1. Mechanistically, Frk promotes the K63 ubiquitination of TBK1 and subsequent activation of the transcription factor IRF3 by phosphorylating TBK1 at tyrosine residues 174 and 179, thereby enhancing the production of IFN-β in macrophages. Employing both in vivo and in vitro viral infection assays, we demonstrated that IFN-β mediated by Frk inhibits the replication of VSV or HSV-1 and alleviates lung lesions. Our findings indicate that Frk functions as a key regulator of TBK1 to strengthen antiviral immunity and represents a promising target for the development of antiviral drugs.
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

Objective

The 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.

Methods

Forty-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.

Results

Among 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.

Conclusion

Consistent 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.
Direct effects of prolonged TNF-α and IL-6 exposure on neural activity in human iPSC-derived neuron-astrocyte co-cultures
Authors: Goshi Noah , Lam Doris , Bogguri Chandrakumar , George Vivek Kurien , Sebastian Aimy , Cadena Jose , Leon Nicole F. , Hum Nicholas R. , Weilhammer Dina R. , Fischer Nicholas O. , Enright Heather A.
Published: February 2025

Cognitive impairment is one of the many symptoms reported by individuals suffering from long-COVID and other post-viral infection disorders such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A common factor among these conditions is a sustained immune response and increased levels of inflammatory cytokines. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are two such cytokines that are elevated in patients diagnosed with long-COVID and ME/CFS. In this study, we characterized the changes in neural functionality, secreted cytokine profiles, and gene expression in co-cultures of human iPSC-derived neurons and primary astrocytes in response to prolonged exposure to TNF-α and IL-6. We found that exposure to TNF-α produced both a concentration-independent and concentration-dependent response in neural activity. Burst duration was significantly reduced within a few days of exposure regardless of concentration (1 pg/mL – 100 ng/mL) but returned to baseline after 7 days. Treatment with low concentrations of TNF-α (e.g., 1 and 25 pg/mL) did not lead to changes in the secreted cytokine profile or gene expression but still resulted in significant changes to electrophysiological features such as interspike interval and burst duration. Conversely, treatment with high concentrations of TNF-α (e.g., 10 and 100 ng/mL) led to reduced spiking activity, which may be correlated to changes in neural health, gene expression, and increases in inflammatory cytokine secretion (e.g., IL-1β, IL-4, and CXCL-10) that were observed at higher TNF-α concentrations. Prolonged exposure to IL-6 led to changes in bursting features, with significant reduction in the number of spikes in bursts across a wide range of treatment concentrations (i.e., 1 pg/mL–10 ng/mL). In combination, the addition of IL-6 appears to counteract the changes to neural function induced by low concentrations of TNF-α, while at high concentrations of TNF-α the addition of IL-6 had little to no effect. Conversely, the changes to electrophysiological features induced by IL-6 were lost when the cultures were co-stimulated with TNF-α regardless of the concentration, suggesting that TNF-α may play a more pronounced role in altering neural function. These results indicate that increased concentrations of key inflammatory cytokines associated with long-COVID can directly impact neural function and may be a component of the cognitive impairment associated with long-COVID and other post-viral infection disorders.
Glymphatic system: a self-purification circulation in brain
Authors: Chen Siying , Wang Huijing , Zhang Lini , Xi Yingying , Lu Yiying , Yu Kailin , Zhu Yujie , Regina Izmailova , Bi Yong , Tong Fang
Published: February 2025

The glymphatic system theory introduces a new perspective on fluid flow and homeostasis in the brain. Here, cerebrospinal fluid and interstitial fluid (CSF-ISF) moves from the perivascular spaces (PVS) of arteries to those of veins for drainage. Aquaporin-4 (AQP4) plays a crucial role in driving fluid within the PVS. The impairment to AQP4 is closely linked to the dysfunction of the glymphatic system. The function of the glymphatic system is less active during waking but enhanced during sleep. The efficiency of the glymphatic system decreases with aging. Damage to the glymphatic system will give rise to the development and progression of many brain diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), chronic traumatic encephalopathy (CTE), and vascular dementia (VaD). Here, we reviewed previous research associated with the glymphatic system, including its concepts, principles, and influencing factors. We hypothesize that AQP4 could be a target for the prevention and treatment of certain brain diseases through the regulation on the glymphatic system.
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

Introduction

Mild 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.

Methods

This 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.

Results

Significant 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 < 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 > 0.05). Notably, there were no significant differences in the distribution of BIN1 rs10200967, rs1060743, and rs4663093 genotypes among elderly individuals (p > 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 < 0.05).

Conclusion

This 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

Background

The 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.

Method

This 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.

Results

The prevalence of anemia (Hb <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 <11 g/dL and SF <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 <0.05 for all).

Conclusion

Our 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

Background

Obesity 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.

Methods

Relevant 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.

Results

A 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.

Conclusion

There 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

Background

The 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.

Methods

A comprehensive literature search was done using Scopus, PubMed, ISI Web of Science, and Google Scholar until July 2023.

Results

In 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 < 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 < 0.001), lycopene intake (Pooled RR: 0.84, 95% CI: 0.81–0.86, I2 = 86.5%, p < 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).

Conclusion

Our 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 registration

CRD42023432400.
The protein transition: what determines the animal-to-plant (A:P) protein ratios in global diets
Authors: Drewnowski Adam , Hooker Kayla
Published: February 2025

Background

Several 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.”

Methods

Analyses 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.

Results

In 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.

Conclusion

Consumer 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.
A comparison of development methods used to define portion sizes in food-based dietary guidelines around the world
Authors: Salesse Fanny , Eldridge Alison L. , Mak Tsz Ning , Gibney Eileen R.
Published: February 2025

Introduction

Food-based dietary guidelines (FBDGs) are essential public health tools for delivering dietary recommendations, and generally include guidance on portion sizes. Despite existing guidelines on developing and implementing FBDGs, there is still no consensus on best practices for their formulation. This paper compares the methodologies used by public health organizations to create FBDGs and examines how both methodology and geographical location may influence recommended portion sizes.

Methods

Documents on FBDG development were obtained from the Food and Agriculture Organization online repository of FBDGs, either directly from consumer-facing FBDG or from corresponding scientific reports. Methodological details in FBDG development were extracted and categorized. Recommended portions in grams per day were extracted for 15 food categories to enable comparison across development methods and global regions.

Results

FBDGs from 96 countries were accessed and translated. Of these, n = 83 were based on consensus/review, n = 15 used data-based approaches, and n = 30 included other minor calculations. Thirty-nine FBDGs were derived from a combination of consensus/review and another method. Of the countries providing portion size information, only one did not report its methodological approach. Comparisons of median portions sizes of food groups across methodologies showed no significant differences. Analyses across regions revealed that portion recommendations were generally consistent, with significant differences found only for one food group, namely, Fish & shellfish, where portion size recommendations were significantly higher in Europe compared to those in Latin America and the Caribbean.

Discussion

Results indicate little variation in the recommendations for portion size across development methods, and for most food groups, across global regions. These findings suggest there is potential to harmonize portion size derivation in FBDGs at regional or global levels. However, further research is needed to assess whether harmonized guidance can apply to other aspects of FBDGs.
Enhanced antitumor activity of combined hepatic arterial infusion chemotherapy with Lenvatinib and PD-1 inhibitors in unresectable hepatocellular carcinoma: a meta-analysis
Authors: Zhao Lingling , Xu Cheng , Deng Jiewen , Ni Yang
Published: February 2025

Background

Hepatic arterial infusion chemotherapy (HAIC) is increasingly recognized as a primary treatment option for patients with unresectable hepatocellular carcinoma (uHCC), providing a focused treatment for localized tumors. The combination of lenvatinib, a multikinase inhibitor, with PD-1 inhibitors has demonstrated significant survival benefits in HCC. This meta-analysis aims to assess whether the integration of HAIC with lenvatinib and PD-1 inhibitors (referred to as the HAIC-L-P group) leads to better treatment effectiveness and security compared to lenvatinib and PD-1 inhibitors alone (L-P group) in uHCC.

Methods

An exhaustive search of the literature was conducted, including PubMed, the Cochrane Library, Embase, ClinicalTrials.gov, and Web of Science, from the start of each database until September 2024, to ensure a thorough and up-to-date compilation of relevant studies. Extract data on outcome measures such as overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Subsequently, meta-analyses were performed using RevMan 5.4 to quantitatively evaluate the aggregated effect of the HAIC-L-P regimen versus the L-P regimen alone.

Results

In our systematic meta-analysis of eight retrospective cohort studies, the HAIC-L-P regimen demonstrated markedly enhanced OS, with an HR of 0.54 (95% CI: 0.45-0.64; p < 0.00001), and enhanced 1-year and 2-year OS rates. Superior PFS was also observed in the HAIC-L-P group, with an HR of 0.64 (95% CI: 0.55-0.75; p < 0.0001), and higher 1-year and 2-year PFS rates. Response rates were markedly higher in the HAIC-L-P group, with an ORR risk ratio of 2.15 (95% CI: 1.84-2.50; p < 0.00001) and a DCR risk ratio of 1.28 (95% CI: 1.20-1.43; p < 0.0001). The AEs classified as grade 3 or above were elevated in the HAIC-L-P group, with notable risk ratios for vomiting, elevated AST, elevated ALT, thrombocytopenia, neutropenia, and hyperbilirubinemia. No life-threatening AEs were reported.

Conclusion

The HAIC-L-P regimen correlated with enhanced tumor responses and prolonged survival, alongside manageable adverse effects, indicating its potential as a viable therapeutic strategy for individuals afflicted with uHCC.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024594109.
Increase in methemoglobin fraction due to the use of glyceryl trinitrate patches in preterm infants: a case report and literature review
Authors: Calandrino Andrea , Vinci Francesco , Battaglini Marcella , Caruggi Samuele , Andreato Chiara , Montobbio Carolina , Vannati Marianna , Minghetti Diego , Brigati Giorgia , Ramenghi Luca Antonio
Published: February 2025

Background

Oxidized heme iron forms methemoglobin (MeHb), impairing the oxygen-binding capability of hemoglobin molecules. Nitric oxide (NO) obtained from glyceryl trinitrate (GTN) patches can cause MeHb formation during limb ischemia topical treatment. This case reports a preterm infant treated with multiple GTN patches who developed elevated MeHb levels, a potential therapy complication.

Case presentation

A preterm female newborn (25 + 4 weeks, 560 g) was delivered by cesarean due to maternal HELLP syndrome and intubated for respiratory distress. After developing ischemia in her right hand and foot, GTN patches were applied, but therapy caused a peak in methemoglobin (MeHb) levels, prompting patch removal. MeHb levels normalized after 18 h, and after adjusting therapy, ischemia resolved successfully.

Discussion

We report the case of a premature IUGR infant who developed elevated methaemoglobin (MeHb) levels during topical GTN therapy for catheter-related extremity ischemia. While GTN is effective for neonatal ischemia, its dosing, and safety lack consistent guidelines. Elevated MeHb levels, noted in similar cases here reviewed, can impair oxygen exchange, especially in vulnerable preterm infants with immature skin and reduced enzyme activity.

Conclusion

This case highlights the need for careful MeHb monitoring and a multidisciplinary approach to manage ischemia safely in neonates undergoing GTN therapy.
Novel (Q)SAR models for prediction of reversible and time-dependent inhibition of cytochrome P450 enzymes
Authors: Faramarzi Sadegh , Bassan Arianna , Cross Kevin P. , Yang Xinning , Myatt Glenn J. , Volpe Donna A. , Stavitskaya Lidiya
Published: February 2025

The 2020 FDA drug-drug interaction (DDI) guidance includes a consideration for metabolites with structural alerts for potential mechanism-based inhibition (MBI) and describes how this information may be used to determine whether in vitro studies need to be conducted to evaluate the inhibitory potential of a metabolite on CYP enzymes. To facilitate identification of structural alerts, an extensive literature search was performed and alerts for mechanism-based inhibition of cytochrome P450 enzymes (CYP) were collected. Furthermore, five quantitative structure-activity relationship (QSAR) models were developed to predict not only time-dependent inhibition of CYP3A4, an enzyme that metabolizes approximately 50% of all marketed drugs, but also reversible inhibition of 3A4, 2C9, 2C19 and 2D6. The non-proprietary training database for the QSAR models contains data for 10,129 chemicals harvested from FDA drug approval packages and published literature. The cross-validation performance statistics for the new CYP QSAR models range from 78% to 84% sensitivity and 79%–84% normalized negative predictivity. Additionally, the performance of the newly developed QSAR models was assessed using external validation sets. Overall performance statistics showed up to 75% in sensitivity and up to 80% in normalized negative predictivity. The newly developed models will provide a faster and more effective evaluation of potential drug-drug interaction caused by metabolites.
A growing degree day model determines the effect of temperature stress on diverse chickpea genotypes
Authors: Jeffrey Cara , Ziems Laura , Kaiser Brent , Trethowan Richard
Published: February 2025

Chickpeas are a globally crucial agricultural product, currently at risk due to human-induced climate change. There has been little research into the impact of heat stress on chickpea compared to other crops, but it is known that heat stress can cause up to 100% yield loss. This study measures Growing Degree Days (GDD) in chickpeas, utilizing an existing calculation. This formula has been expanded for heat stress, titled Stress Degree Days (SDD), to examine the effects of high temperature stress on commercially important traits such as yield and seed size. Using a multi-environment trial, traits such as time to flowering, and seed size were observed in 148 chickpea cultivars across two sowing times in two different Australian locations (Narrabri in New South Wales, and Kununurra in Western Australia). It was determined that there is a significant correlation between yield, GDD, and SDD at all locations, sowing times, and life stages of the crop. These metrics allowed greater differentiation between environments when compared to a count of the number of calendar days required for each cultivar to reach a set life stage (flowering and maturation), allowing more accurate investigation the impacts of high temperature stress. It was also determined that loss of yield and a decrease in seed size was significantly correlated with high GDD and SDD, though seed size had less environmental plasticity (variability) compared to yield, and therefore higher stability under stress. GDD and SDD were shown to be useful for predicting genotype adaptation to locations and seasons thus providing a basis for varietal recommendations. This information could also be used to breed environment specific cultivars and to understand trait plasticity.
Divergent thinking in groups during cold-water immersion is impaired by cold stress not the cold shock response
Authors: Smith Max Kailler , Weller Rebecca , Duong Tony , McClintock Rebecca , Peterson Matthew , Barr Nathaniel , Jones Douglas M. , Dunn Timothy L.
Published: February 2025

Introduction

A primary hazard of working in cold maritime environments is the potential for a substantial man overboard situation in freezing waters. Sudden cold-water immersion (CWI) triggers the cold shock response (CSR), which consists of cardiorespiratory responses that increase the chance of drowning. If cold shock response severity can be mitigated, life-saving actions must be taken within the first 10 min, as after this time frame drowning occurs due to cold incapacitation. To date, research shows that executive functioning is generally impaired by intense, acute stress, which implies the ability to think through potential actions to maximize survival would also be impaired by the cold shock response.

Methods

To examine whether the severity of cold shock response impairs higher-level thinking in a group, 29 active duty service members completed a group format Divergent Association Task (DAT; 4–5 per group) prior to and during a 13-min cold-water immersion (water temperature: 1.3°C, air temperature: −2.7°C).

Results

Results showed no relationship between cold shock response magnitude, indexed by peak heart rate, and DAT performance. However, results indicated that those with lower skin temperatures performed worse on the DAT.

Discussion

Results suggest that the ability to engage in divergent thinking is relatively preserved in the critical ~10-min window although skin cooling may bias attention toward the cold stress impacting task performance. Furthermore, subjective reports of the severity of the initial gasp tracked with peak heart rate demonstrating potential utility of subjective responses in the absence of respiratory measurements.