bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma
Authors: Liu Junchen , Dai Kun , Saliu Muhammad Auwal , Salisu Mansur Dabai , Gan Jiangyu , Afolabi Lukman Olalekan , Yan Dehong , Zhang Guizhong , Liu Maoxuan , Wan Xiaochun
Published: January 2025

Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor antigen expression and immune evasion post-treatment. NKG2D CAR-T cells have demonstrated a favorable safety profile in patients with hematologic tumors, and showed robust antitumor efficacy in various xenograft models, including glioblastoma. However, malignant glioma cells evade immunological surveillance by reducing NKG2D ligands expression or cleavage. To enhance the effectiveness of NKG2D CAR-T therapy, we investigated the potential of combining NKG2D CAR-T with approved drugs that cross the blood-brain barrier and augment NKG2D ligands expression in glioma cells. We found that sodium valproate (VPA), an antiepileptic drug, significantly increased surface NKG2D ligands expression on glioblastoma cells at a sublethal concentration. VPA treatment enhanced the susceptibility of glioblastoma cells to NKG2D CAR-T mediated cytotoxicity in both 2D monolayer and 3D tumor spheroid models in vitro. Moreover, VPA-treated glioblastoma cells stimulated CAR-T cells to produce higher levels of inflammatory cytokines (IL-2, IFN-γ, and IL-6). Mechanistically, VPA upregulated NKG2D ligands expression via the PI3K/Akt signaling pathway. Additionally, VPA treatment augmented the antitumor activity of NKG2D CAR-T cells in a glioblastoma xenograft model in vivo. These preclinical results suggest that combining VPA with NKG2D CAR-T therapy represents a promising strategy for improving glioblastoma treatment, warranting further clinical investigation.
Molecular identification of pfcytb, pfdhfr, and pvmrp1 mutations in imported malaria cases in Chile
Authors: Oyarce Alan , Huaccha Lizbeth , Cordero Esteban M. , Parra Bárbara , Fernández Jorge , Soto-Marchant Mario E. , Santis-Alay Natalia T. , Jercic María Isabel
Published: January 2025

A key challenge in the global effort to combat malaria is the emergence of drug resistance. Malaria-free countries must also address issues such as limited access to antimalarial drugs and treatment failures caused by drug resistance. Chile, as a malaria-free country, faces the risk of malaria being reintroduced due to the presence of the malaria vector in its continental territory. This study aims to analyze the genetic profile associated with antimalarial drug resistance in the pfcytb, pfdhfr, and pvmrp1 genes. A total of ninety blood samples from 55 individuals who had been diagnosed with malaria in Chile between 2019 and 2021 were subjected to mutational analysis. The parasites target genes were amplified by polymerase chain reaction (PCR) out of total DNA extracted from patient blood samples and the amplicons submitted to DNA sequencing. All the genes analyzed had at least one mutation. In the pfdhfr gene, three mutations were observed (S108N/N51I/C59R). In the pfcytb gene, the Y268C mutation, found in post-treatment samples, was associated with treatment failure. In the pvmrp1 gene, five distinct mutations were identified. Of these, the Y1393D (100%) and V1478I (95.2%) were the most common. Our findings indicate that both P. falciparum and P. vivax samples from travelers and migrants in Chile carry mutations in genes linked to malaria resistance. The circulation of parasites with potential drug resistance in non-endemic countries further complicates the challenge of ensuring adequate treatment. It is crucial to continue genetic surveillance and expand the search for new resistance markers for Plasmodium species.
Temporal trends of community and climate changes in the anthropocene: 21-year dynamics of four major functional groups in a rocky intertidal habitat along the Pacific coast of Japan
Authors: Sato Hiroki , Ishida Ken , Noda Takashi
Published: January 2025

The influence of climate change on marine organism abundance has rarely been assessed (1) at the functional-group level; (2) simultaneously in major functional groups within the same ecosystem; (3) for >10 years; and (4) at metapopulation/community scales. A study simultaneously addressing these gaps would greatly enhance our understanding of the influence of climate change on marine ecosystems. Here, we analyzed 21 years of abundance data at the functional-group and species levels on a regional scale for four major functional groups (benthic algae, sessile animals, herbivorous benthos, and carnivorous benthos) in a rocky intertidal habitat along the northeastern Pacific coast of Japan. We aimed to examine the 21-year trends in regional abundance at both functional-group and species levels, plus their driving mechanisms and their dependence on species properties (thermal niche, calcification status, and vertical niche). Significant temporal trends in abundance were detected at functional-group levels for benthic algae (increasing) and herbivores and carnivores (both decreasing); they followed the temporal population trends of the dominant species. At species level, the metapopulation size of 12 of 31 species were increasing and 4 of those were decreasing, depending on the thermal niche and species calcification status. At both functional-group and species levels, temporal trends in abundance are caused by the direct or indirect influence of warming and ocean acidification. Comparing these results with community responses to marine heat waves in the same study area offered two implications: (1) long-term ecosystem changes associated with global warming will be unpredictable from the community response to marine heat waves, possibly owing to a lack of knowledge of the influence of calcifying status on species’ responses to climate change; and (2) thermal niches contribute greatly to predictions of the influence of warming on population size, regardless of the time scale.
Modeling of wave-induced drift based on stepwise parameter calibration
Authors: Zhu Kui , Chen Xueyao , Mu Lin , Yu Dingfeng , Yu Runze , Sun Zhaolong , Zhou Tong
Published: January 2025

The motion of waves in water causes the slow movement of drifting sea targets—a phenomenon usually ignored in target-drift prediction models for maritime search and rescue (SAR). This study examined the wave-induced drift’s influence on field-observation experiments involving two common, differently sized SAR targets—an offshore fishing vessel (OFV) and a person in the water (PIW)—using parameter stepwise calibration and machine-learning (ML) methods. The sample of wave-induced drift velocity was obtained by gradually separating current-induced (CI) drift’s and wind-induced (WI) drift’s influence from the target-drift velocity using the least-square method and AP98 model. A force analysis method and three ML methods, long short-term memory (LSTM), back-propagation (BP) neural network, and random forest (RF), were used to fit the wave-induced drift velocity by combining eight different parameter schemes. Finally, the drift trajectories considering the influence of waves were fitted and verified based on 2 independent samples respectively. Compared with the force analysis method, the accuracy of the ML methods in the verification test was higher. In addition, the results show that for OFVs, considering wave-induced drift’s influence in the ensemble-trajectory prediction could improve the simulation accuracy. However, for a PIW, no significant improvement was observed. This result also indicates that wave-induced drift may not be simply ignored in large SAR targets’ drift prediction.
Evolution of a seafloor massive sulfide deposit on axial volcanic ridges: a case study of the Duanqiao hydrothermal field, Southwest Indian Ridge
Authors: Yang Weifang , Tao Chunhui , Liao Shili , Zhang Huichao , Zhu Chuanwei , Li Wei , Zhang Guoyin , Wang Xuefeng , Wang Lisheng
Published: January 2025

The mineralization process below the surface of the seafloor in a hydrothermal field has an important influence on the distribution and enrichment of elements. The Duanqiao hydrothermal field (DHF) is located on the new axial volcanic ridge of the ultraslow-spreading Southwest Indian Ridge. Owing to the limited surface sulfide samples, the metallogenic processes occurring below the seafloor surface such as the element enrichment mechanism and the temporal evolution of the sulfide deposits remain unclear. In this study, we conducted mineral texture, geochemical, 230Th/U dating, and laser ablation inductively coupled plasma mass spectrometer analyses of a drill core containing shallow sulfide deposits to study their evolution process. The results revealed that pyrite is enriched in Mn, Co, As, Mo, Ag, Cd, Sb, Tl, and Pb, chalcopyrite is characterized by high concentrations of Se, Sn, In, As, Ag and Pb, and sphalerite is enriched in Co, Ga, Ge, As, Ag, Cd, Sb, and Pb. The 230Th/U dating data suggested five different mineralization periods during 4,552–2,297 years. Apart from the top and bottom, the core exhibited obvious characteristics of gradual accumulation of mineralization. Results revealed that the variations in the elemental contents of different layers and different types of pyrite were controlled by the interaction of seawater and hydrothermal fluids within the sulfide mound over five different mineralization periods. Compared with other hydrothermal fields on other mid-ocean ridges, DHF pyrite is generally enriched in Zn, Pb, As, Ag, Cd, Mo, and Sb, which might reflect shallow subsurface mixing during different periods of hydrothermal activity.
Meta-analysis of retinal transcriptome profiling studies in animal models of myopia
Authors: Palumaa Teele , Balamurugan Shruti , Pardue Machelle T.
Published: January 2025

Objective

Myopia prevalence is increasing at alarming rates, yet the underlying mechanistic causes are not understood. Several studies have employed experimental animal models of myopia and transcriptome profiling to identify genes and pathways contributing to myopia. In this study, we determined the retinal transcriptome changes in response to form deprivation in mouse retinas. We then conducted a transcriptome meta-analysis incorporating all publicly available datasets and analyzed how the results related to the genes associated with refractive errors in human genome-wide association studies (GWAS).

Methods

Form deprivation was induced in three male C57BL6/J mice from postnatal day 28 (P28) to P42. Retinal gene expression was analyzed with RNA sequencing, followed by differential gene expression analysis with DESeq2 and identification of associated pathways with the Kyoto Encyclopedia of Genes and Genomes (KEGG). A systematic search identified four similar retinal transcriptomics datasets in response to experimental myopia using chicks or mice. The five studies underwent transcriptome meta-analyses to determine retinal gene expression changes and associated pathways. The results were compared with genes associated with human myopia.

Results

Differential gene expression analysis of form-deprived mouse retinas revealed 235 significantly altered transcripts, implicating the BMP2 signaling pathway and circadian rhythms, among others. Transcriptome-wide meta-analyses of experimental myopia datasets found 427 differentially expressed genes in the mouse model and 1,110 in the chick model, with limited gene overlap between species. Pathway analysis of these two gene sets implicated TGF-beta signaling and circadian rhythm pathways in both mouse and chick retinas. Some pathways associated only with mouse retinal changes included dopamine signaling and HIF-1 signaling pathway, whereas glucagon signaling was only associated with gene changes in chick retinas. The follistatin gene changed in both mouse and chick retinas and has also been implicated in human myopia. TGF-beta signaling pathway and circadian entrainment processes were associated with myopia in mice, chicks, and humans.

Conclusion

This study highlights the power of combining datasets to enhance statistical power and identify robust gene expression changes across different experimental animal models and conditions. The data supports other experimental evidence that TGF-beta signaling pathway and circadian rhythms are involved in myopic eye growth.
Salivary alpha-amylase activity and its association with early childhood caries and rampant caries experience: a cross-sectional study
Authors: Padmanabhan Vivek , Islam Md Sofiqul , Rahman Muhammed Mustahsen , Goud Manjunatha B. K. , Alshehhi Latifa Majed Sulaiman Allay , Hamed Hebah Mushref Ahmad , Haridas Sheela , Sharma Dileep
Published: January 2025

Aims

This study aims to evaluate salivary alpha-amylase levels in children diagnosed with Early Childhood Caries (ECC) and Rampant Caries (RC) and compare them to levels in children without ECC or RC. It also examines the relationship between salivary alpha-amylase levels and increased caries activity in the children with ECC or RC.

Materials and methods

A cross-sectional study was conducted at RAK College of Dental Sciences (RAKCODS) with 100 children aged 3–12 years. Participants were divided into ECC and RC groups, each consisting of study and control groups. Salivary alpha-amylase levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA) kits. Statistical analyses, including the Wilcoxon Signed Rank test and Pearson’s correlation coefficient, were performed using SPSS version 29 to compare salivary alpha-amylase levels between groups and examine correlation with severity of dental caries.

Results

The study found that children with ECC and RC had significantly higher mean salivary alpha-amylase levels (16.046 U/mL and 20.62 U/mL, respectively) compared to control groups (5.09 U/mL and 12.70 U/mL). The differences were statistically significant (p < 0.0001). Pearson’s correlation coefficients indicated a strong positive correlation between salivary alpha-amylase levels and severity of dental caries in both ECC (r = 0.9891, p < 0.0001) and RC (r = 0.9142, p < 0.0001) groups.

Conclusion

The study concludes that elevated salivary alpha-amylase levels, which are statistically significant, are observed in children with ECC and RC. Additionally, it was found that salivary alpha-amylase levels increased with the number of carious lesions. These findings suggest that salivary alpha-amylase could serve as a valuable biomarker for assessing caries risk and guiding preventive strategies.
Predictors of developing severe COVID-19 among hospitalized patients: a retrospective study
Authors: Alkhalifa Hussain Abduljaleel , Darwish Ehab , Alsalman Zaenb , Alfaraj Aman , Alkhars Abdullah , Alkhalifa Fatimah , Algaraash Mohammed , Elshebiny Ahmed Mohammed , Alkhoufi Emad , Elzorkany Khaled Mohamed Amin
Published: January 2025

Background

COVID-19 poses a significant threat to global public health. As the severity of SARS-CoV-2 infection varies among individuals, elucidating risk factors for severe COVID-19 is important for predicting and preventing illness progression, as well as lowering case fatality rates. This work aimed to explore risk factors for developing severe COVID-19 to enhance the quality of care provided to patients and to prevent complications.

Methods

A retrospective study was conducted in Saudi Arabia’s eastern province, including all COVID-19 patients aged 18 years or older who were hospitalized at Prince Saud Bin Jalawi Hospital in July 2020. Comparative tests as well as both univariate and multivariate logistic regression analyses were performed to identify risk factors for developing severe COVID-19 and poor outcomes.

Results

Based on the comparative statistical tests patients with severe COVID-19 were statistically significantly associated with older age and had higher respiratory rate, longer hospital stay, and higher prevalence of diabetes than non-severe cases. They also exhibited statistically significant association with high levels of potassium, urea, creatinine, lactate dehydrogenase (LDH), D-dimer, and aspartate aminotransferase (AST). The univariate analysis shows that having diabetes, having high severe acute respiratory infection chest X-ray scores, old age, prolong hospitalization, high potassium and lactate dehydrogenase, as well as using insulin, heparin, corticosteroids, favipiravir or azithromycin were all statistically significant associated with severe COVID-19. However, after adjustments in the multivariate analysis, the sole predictor was serum LDH (p = 0.002; OR 1.005; 95% CI 1.002–1.009). In addition, severe COVID-19 patients had higher odds of being prescribed azithromycin than non-severe patients (p = 0.001; OR 13.725; 95% CI 3.620–52.043). Regarding the outcomes, the median hospital stay duration was statistically significantly associated with death, intensive care unit admission (ICU), and mechanical ventilation. On the other hand, using insulin, azithromycin, beta-agonists, corticosteroids, or favipiravir were statistically significantly associated with reduced mortality, ICU admission, and need of mechanical ventilation.

Conclusion

This study sheds light on numerous parameters that may be utilized to construct a prediction model for evaluating the risk of severe COVID-19. However, no protective factors were included in this prediction model.
Case report: special imaging features in a uremic patient with intracranial infection caused by Ralstonia mannitolilytica, almost misdiagnosed as demyelinating disease
Authors: Kong Hanxin , Ying Hao , Yang Jianhong
Published: January 2025

Ralstonia mannitolilytica is a very rare pathogen that causes intracranial infection. It is commonly found in immunocompromised patients and is resistant to multiple antibiotics. In this case report, we present a case of human central nervous system infection caused by Ralstonia mannitolilytica, which was initially misdiagnosed as demyelinating disease due to the specific imaging findings. This case had concurrent uremia and a good response to meropenem under continuous peritoneal dialysis. The diagnosis is mainly based on cerebrospinal fluid analysis and targeted genetic testing by next generation sequencing (NGS). However, the patient had a poor prognosis due to uncontrollable gastrointestinal bleeding and related complications during long-term bed rest. We hope that this case will attract more attention and provide relevant reference for the diagnosis and treatment of other similar patients.
Association of CSF soluble TREM1 levels with hippocampal atrophy in cognitively impaired older adults
Authors: Shu Hao , Ding Gangyu , Xu Xiaona , Huang Xuerong , He Ruqian
Published: January 2025

Background

Recent studies have shown that cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 1 (sTREM1) are elevated in individuals with Alzheimer’s disease (AD), though the relationship between CSF sTREM1 and hippocampal atrophy remains to be elucidated. The primary aim of this study was to investigate the association between CSF sTREM1 levels and longitudinal changes in hippocampal volumes, and to determine if this relationship is moderated by cognitive status.

Methods

We included 576 participants, comprising 152 cognitively unimpaired (CU) and 424 cognitively impaired (CI) individuals. In the cross-sectional analyses, Pearson’s correlation tests were conducted to examine the relationship between baseline CSF sTREM1 levels and hippocampal volumes in both CU and CI participants. For the longitudinal analyses, a linear mixed-effects model was employed to assess the significance of the three-way interaction between CSF sTREM1 levels, cognitive status, and follow-up time on adjusted hippocampal volume (aHV). Further stratified analyses based on cognitive status were performed to dissect the specific effects within each group.

Results

Our findings revealed significantly elevated baseline CSF sTREM1 levels in CI participants compared to CU participants. Cross-sectional analyses demonstrated that CSF sTREM1 levels were negatively associated with hippocampal volumes in both CU and CI participants. In the longitudinal analyses, the three-way interaction between CSF sTREM1 levels, cognitive status, and follow-up time was found to be significant for aHV. Stratified analyses indicated that, in CI participants, higher CSF sTREM1 levels were associated with a more accelerated rate of hippocampal atrophy, whereas no such association was observed in CU participants.

Conclusion

These results underscore the complex interplay between neuroinflammation, as reflected by CSF sTREM1 levels, hippocampal atrophy, and cognitive decline. The data suggest that neuroinflammation may contribute differently to hippocampal atrophy rates in CI versus CU individuals, highlighting the potential for targeted anti-inflammatory interventions in the prevention and treatment of AD.
The lactate metabolism and protein lactylation in epilepsy
Authors: Kuang Xi , Chen Shuang , Ye Qingmei
Published: January 2025

Protein lactylation is a new form of post-translational modification that has recently been proposed. Lactoyl groups, derived mainly from the glycolytic product lactate, have been linked to protein lactylation in brain tissue, which has been shown to correlate with increased neuronal excitability. Ischemic stroke may promote neuronal glycolysis, leading to lactate accumulation in brain tissue. This accumulation of lactate accumulation may heighten neuronal excitability by upregulating protein lactylation levels, potentially triggering post-stroke epilepsy. Although current clinical treatments for seizures have advanced significantly, approximately 30% of patients with epilepsy remain unresponsive to medication, and the prevalence of epilepsy continues to rise. This study explores the mechanisms of epilepsy-associated neuronal death mediated by lactate metabolism and protein lactylation. This study also examines the potential for histone deacetylase inhibitors to alleviate seizures by modifying lactylation levels, thereby offering fresh perspectives for future research into the pathogenesis and clinical treatment of epilepsy.
Research progresses and hotspots on glucose metabolic reprogramming in breast cancer: a bibliometric analysis over the past two decades
Authors: Huang Lei , Zhao Wenyue , Sun Lamei , Niu Dong , Zhu Xiaodan , Jin Chunhui
Published: January 2025

Background

Abnormal energy metabolism is a prominent characteristic of cancers. Increasing evidence has suggested the involvement of glucose metabolism reprogramming in the progression of breast cancer (BC). This article aims to provide a comprehensive overview of glucose metabolism reprogramming in BC through a bibliometric analysis.

Methods

Relevant literatures published from 2004 to 2024 were searched in the Web of Science Core Collection database, and a bibliometric analysis was conducted using VOSviewer, CiteSpace, and Bibliometrix.

Results

In total, 957 publications reporting glucose metabolism reprogramming in BC were included, showing an increasing trend in the annual publication outputs. China ranked first in publication outputs, and the United States of America (USA) had a dominant place in citation counts. The research achievements of Thomas Jefferson University in the USA were at the forefront and widely cited. Lisanti, Michael P., and Sotgia, Federica were the most productive authors. Keyword analysis suggested that the mechanisms of glucose metabolism reprogramming in BC and related therapeutic strategies were the research hotspots.

Conclusion

This study, for the first time, elucidated the progresses and hotspots of in the research on glucose metabolism reprogramming in BC, highlighting its potential role in treating BC. Considering that the glycolytic reprogramming of BC is a complex biological process, it is imperative for countries to enhance cooperation in the pursuit of effective antimetabolic therapies to overcome challenges in BC treatment.
Cellulose nanofiber reinforced curcumin-infused calcium phosphate silicate cement for various bone-tissue engineering application
Authors: Lu Xiu Guo , Meng Sha Li , Zhou Qiu Jing , Wu Tao , Gong Xing Tian , Wu Qiong
Published: January 2025

Introduction

This study utilized a injectable curcumin (Cur)-infused calcium phosphate silicate cement (CPSC) for addressing defects caused by bone cancer, and evaluated its promoting bone regeneration and exerting cytotoxic effects on osteosarcoma cells.

Methods

The material’s physicochemical properties, biocompatibility with osteoblasts, and cytotoxicity toward osteosarcoma cells were rigorously analyzed.

Results

The findings demonstrate that CPSC-Cur signicantly prolongs the setting time, which can be optimized by adding silanized cellulose nanober (CNF-SH) to achieve a balance between workability and mechanical strength. Biological assessments reveal a pronounced cytotoxic effect on osteosarcoma cells while maintaining minimal toxicity toward pre-osteoblasts, highlighting CPSC-Cur’s potential as a promising material for repairing bone defects following cancer removal.

Conclusion

This study lays the groundwork for future investigations into CPSC-Cur’s in vivo efficacy and its role in the clinical treatment of bone cancer.
Tele-ophthalmology as an effective triaging tool for acute ophthalmic concerns
Authors: Townsend Natalie A. , Shah Shalini , Reyes Joshua , Townsend Justin H. , Bozung Alison , Ricur Giselle , Aboumourad Rami J.
Published: January 2025

Introduction

The purpose of this study is to determine baseline demographics and utilization trend of an on-demand, synchronous tele-ophthalmology triage program in evaluating acute ophthalmic concerns during the COVID-19 Public Health Emergency.

Methods

Setting: Single-center retrospective chart review of telemedicine visits conducted by ophthalmologists and optometrists from University of Miami’s Bascom Palmer Eye Institute. Patient population: 6227 patients comprised 7138 telehealth encounters. All patient encounters were included in the retrospective review without exclusions and only the primary diagnoses were categorized from October 1, 2020 to April 30, 2023. Main outcomes measures: Descriptive statistics of the telemedicine model, utilization trends, baseline patient demographics, and primary diagnoses were performed for all virtual eye care encounters during the study period.

Results

Utilization of the synchronous telemedicine platform increased during the study period. The median age of patients was 51 (IQR, 36-65) years. Patients predominantly self-identified as female (63.27%), White (72.7%), and non-Hispanic/Latino (48.2%). General external adnexa (44.1%), conjunctival disorders (15.5%) and ocular surface symptoms (15.4%), made up 75.0% of the visits during the study period. Furthermore, 63.4% of patients were new to Bascom Palmer Eye Institute, 67.1% had never engaged in telemedicine, and 96.5% of encounters were successfully completed through video conferencing.

Discussion

During the COVID-19 pandemic, there was significant utilization of an on-demand synchronous ocular telemedicine program to address acute concerns. This retrospective chart review demonstrates the utility of telemedicine as an important and effective tool to triage and provide care during the COVID-19 Public Health Emergency.
Case Report: Prenatal diagnosis of novel compound heterozygous variants in WDR35 gene causing short-rib thoracic dysplasia 7 with or without polydactyly
Authors: Zhuang Jianlong , Wang Junyu , Huang Zhengping , Chen Yu’e , Chen Chunnuan
Published: January 2025

Background

Whole exome sequencing (WES) technology has been increasingly used for the etiological diagnosis of fetuses with ultrasound anomalies. In this article, we report a novel deletion compound combined with a causative variant in WDR35 gene leading to short-rib thoracic dysplasia 7 (SRTD7) with or without polydactyly using WES.

Methods

This study involved a Chinese fetus with clinical features of skeletal dysplasia on ultrasound imaging, in whom chromosome abnormalities and copy number variants (CNVs) were detected by chromosomal microarray analysis (CMA), and sequence variants were detected by WES. The obtained results were further verified by Sanger sequencing or real time quantitative PCR (qPCR).

Results

No chromosomal abnormality or CNVs were identified in the fetus by CMA. However, WES result revealed a 14.38-kb large novel deletion compound covering exon 7 to exon 12 combined with a missense variant NM_001006657.2:c.932G>T(p.W311l) in WDR35. Both variants were thought of as pathogenic, which was further confirmed by Sanger sequencing and qPCR. In addition, two compound heterozygous variants NM_015102.5:c.[1196A>G(p.E399G)];[1972C>T(p.R658*)] in NPHP4 gene were also identified in the fetus, which may be partially responsible for fetal kidney hyperechogenicity and oligohydramnios.

Conclusion

This is the first study reporting a novel deletion compound combined with a causative missense variant in WDR35 leading to SRTD7. This finding may broaden the spectrum of variants of WDR35 gene and provide a valuable reference for clinical counseling of related abnormalities in pregnancies.
Decoding nature: multi-target anti-inflammatory mechanisms of natural products in the TLR4/NF-κB pathway
Authors: Zhao Yue , Wu Jiacai , Liu Xiaolan , Chen Xu , Wang Juan
Published: January 2025

Natural products are valuable medicinal resources in the field of anti-inflammation due to their significant bioactivity and low antibiotic resistance. Research has demonstrated that many natural products exert notable anti-inflammatory effects by modulating the Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) signaling pathways. The research on related signal transduction mechanisms and pharmacological mechanisms is increasingly being discovered and validated. However, there is currently a lack of comprehensive reviews focusing on the pharmacological mechanisms of natural products targeting the TLR4/NF-κB pathway for anti-inflammatory effects. In light of these considerations, this review comprehensively synthesizes recent research findings concerning the TLR4/NF-κB signaling pathway, including the translocation of TLR4 activation to lysosomes within the cytoplasm, the assembly of protein complexes mediated by ubiquitin chains K63 and K48, and the deacetylation modification of p65. These discoveries are integrated into the classical TLR4/NF-κB pathway to systematically elucidate the latest mechanisms among various targets. Additionally, we summarize the pharmacological mechanisms by which natural products exert anti-inflammatory effects through the TLR4/NF-κB pathway. This aims to elucidate the multitarget advantages of natural products in the treatment of inflammation and their potential applications, thereby providing theoretical support for molecular pharmacology research on inflammation and the development of novel natural anti-inflammatory drugs.
Multi-target regulatory effects of rhaponticin in a rat model of hepatic fibrosis revealed by non-targeted metabolomics
Authors: Yang Min , Jiang Dihua , Huang Longfei , Zhang Tao , Guo Wenfen , Lin Wenyan , Zhao Jiali , Wei Yunsheng , Peng Lang , Hao Yong-Jia , Zhou Ying
Published: January 2025

Introduction

Hepatic fibrosis (HF), a progressive chronic liver disease, is a serious threat to global public health. The lack of preventive and therapeutic strategies has created an urgent need for effective anti-fibrosis agents. There is growing evidence that natural products might provide safe and effective interventions for HF. Among them, rhaponticin (RHA), a stilbenoid glucoside natural product isolated from medicinal plants of Rheum L. of Polygonaceae Juss. has many pharmacological activities such as anti-inflammatory, antioxidant, antiproliferative, and antithrombotic properties. However, its effects on HF remain unclear.

Methods

Herein, we investigated the effects of RHA against HF on the carbon tetrachloride (CCl4)-induced hepatic fibrosis and the underlying mechanism in rats. Functional, histopathological, and protein-level indicators of liver insult were evaluated. Moreover, serum metabolites were assessed by non-targeted metabolomics.

Results and discussion

The results showed that RHA improved liver functions and histopathological features in the liver of CCl4-treated rats, and alleviated the expression of α-SMA and type I collagen. Meanwhile, RHA also modulated endogenous metabolite levels in rats with HF, targeting glycerophospholipid metabolism signaling and other pathways. These findings confirmed the protective effects of RHA against hepatic fibrosis in rats by exerting multi-target effects via multiple signaling and metabolic pathways. Which may be of use in developing more effective RHA-based therapeutic strategies for hepatic fibrosis.
Integrated transcriptomics and metabolomics analyses provide new insights into cassava in response to nitrogen deficiency
Authors: Wang Yu , Chu Jing , Zhang Haoyang , Ju Hao , Xie Qing , Jiang Xingyu
Published: January 2025

Nitrogen deficiency is a key constraint on crop yield. Cassava, the world’s sixth-largest food crop and a crucial source of feed and industrial materials, can thrive in marginal soils, yet its yield is still significantly affected by limited nitrogen availability. Investigating cassava’s response mechanisms to nitrogen scarcity is therefore essential for advancing molecular breeding and identifying nitrogen-efficient varieties. This research undertook a comprehensive analysis of cassava seedlings’ physiological, gene expression, and metabolite responses under low nitrogen stress. Findings revealed that nitrogen deficiency drastically suppressed seedling growth, significantly reduced nitrate and ammonium transport to aerial parts, and led to a marked increase in carbohydrate, reactive oxygen species, and ammonium ion levels in the leaves. Transcriptomic and metabolomic analyses further demonstrated notable alterations in genes and metabolites linked to carbon and nitrogen metabolism, flavonoid biosynthesis, and the purine metabolic pathway. Additionally, several transcription factors associated with cassava flavonoid biosynthesis under nitrogen-deficient conditions were identified. Overall, this study offers fresh insights and valuable genetic resources for unraveling cassava’s adaptive mechanisms to nitrogen deprivation.
Green for us: parental compensation for children’s unsustainable behaviors
Authors: Wang Sili , Zhang Xiaofei
Published: January 2025

This study explores the impact of children’s unsustainable behaviors on parental sustainable actions within family dynamics. Findings reveal that parents exposed to their children’s unsustainable behaviors experience heightened family and environmental responsibility, which motivates them to engage in both private-domain and public-domain sustainable behaviors. These effects are amplified in intergenerational caregiving contexts, where parents compensate for reduced caregiving roles by adopting more sustainable practices. Through four experiments, the research validates the mediating roles of family and environmental responsibility and the moderating influence of caregiver type. This study extends existing theories on intergenerational behavior transmission by highlighting the influence of children’s unsustainable behaviors, offering valuable insights for family education strategies and policy development aimed at fostering sustainability within households.
Implementation of RedCap data systems in Kenyan psychiatric rehabilitation: a community case study
Authors: Patel Neal , Turissini Matthew , Jaguga Florence , Barasa Julius , Okeyo Lily , Kimaiyo Mercy , Kosgei Gilliane , Kipkorir Naomi , Kwobah Edith Kamaru
Published: January 2025

Data collection systems are vital in implementation of interventions within patient care as they allow us to better understand and improve the care given. This is equally true in the field of psychiatric rehabilitation, which has been steadily growing in the medical world for the past 20 years. It has recently been a focus of psychiatric medicine in Kenya with the Kenya Mental Health Action Plan 2021-2025 calling for improvement of care in the field. With psychiatric rehabilitation growing in low- and middle-income countries in recent years studies have come out showing the effects of newly employed programs and stressing the need for data collection practices that can be used to encourage best practices in local communities. This paper describes the implementation of data systems for the Moi Teaching and Referral Hospital Nawiri Skills and Recovery Centre (Nawiri) in Eldoret, Kenya. The goals of the data systems were 1) To collect and organize information for continuous quality improvement of services at Nawiri, 2) To collect information for reporting to MTRH leadership, Ministry of Health as well as private funders, 3) To provide data to assess outcomes of people who receive services at Nawiri to create evidence for effective interventions to help create policy to make psychiatric rehabilitation more available to people living with Severe mental illness in Kenya. Lessons learned from data systems implementation included insights into ease of data collection, adaptability of data instruments to fit facility needs, and ability to reproduce RedCap data collection in other settings.
Neurotransmitters crosstalk and regulation in the reward circuit of subjects with behavioral addiction
Authors: Peng Zhenlei , Jia Qiyu , Mao Junxiong , Luo Xiao , Huang Anqi , Zheng Hao , Jiang Shijie , Ma Qi , Ma Chuang , Yi Qizhong
Published: January 2025

Behavioral addictive disorders (BADs) have become a significant societal challenge over time. The central feature of BADs is the loss of control over engaging in and continuing behaviors, even when facing negative consequences. The neurobiological underpinnings of BADs primarily involve impairments in the reward circuitry, encompassing the ventral tegmental area, nucleus accumbens in the ventral striatum, and prefrontal cortex. These brain regions form networks that communicate through neurotransmitter signaling, leading to neurobiological changes in individuals with behavioral addictions. While dopamine has long been associated with the reward process, recent research highlights the role of other key neurotransmitters like serotonin, glutamate, and endorphins in BADs’ development. These neurotransmitters interact within the reward circuitry, creating potential targets for therapeutic intervention. This improved understanding of neurotransmitter systems provides a foundation for developing targeted treatments and helps clinicians select personalized therapeutic approaches.
Proposal for a revised Barthel index classification based on mortality risk assessment in functional dependence for basic activities of daily living
Authors: Martín Moreno Vicente , Martínez Sanz María Inmaculada , Martín Fernández Amanda , Guerra Maroto Sara , Sevillano Fuentes Eva , Pérez Rico Elena , Sánchez González Irene , Fernández Gallardo Miriam , Herranz Hernando Julia , Benítez Calderón María Palma , Calderón Jiménez Laura , Sánchez Rodríguez Elena , Recuero Vázquez Miguel , Alonso Samperiz Helena , León Saiz Irene , Marcos Guerra Juana
Published: January 2025

Introduction

Functional dependence on the performance of basic activities of daily living (ADLs) is associated with increased mortality. In this study, the Barthel index and its activities discriminate long-term mortality risk, and whether changes in this index are necessary to adapt it to detect mortality risk is examined.

Methods

Longitudinal study, carried out at the Orcasitas Health Center, Madrid (Spain), on the functional dependent population (Barthel ≤ 60). It included 127 people, with a mean age of 86 years (78.7% women and 21.3% men). Functional capacity was assessed using the Barthel index, and this index and each item it contains were analyzed as a test in relation to survival at three years, using tools that evaluate precision, discrimination, and calibration. The date of death was obtained from the health system.

Results

Greater dependency to perform chair-to-bed transfers was associated with an increased mortality risk (HR 2.957; CI 1.678–5.211). Also, individuals with severe (HR 0.492; CI 0.290–0.865) and moderate (HR 0.574; CI 0.355–0.927) ADL dependence had a reduced mortality risk when more independent in chair-to-bed transfers. Among people with moderate ADL dependence, this percentage was 48%. Using dependence-independence for chair-to-bed transfer as a screening test for mortality, the test showed high sensitivity (0.91) and specificity (0.83), a positive likelihood ratio of 5.45, and a negative likelihood ratio of 0.11. The area under the ROC curve was 0.814 (CI 0.658–0.970; p = 0.001), with a χ2 = 0.235; p = 0.889, according to the Hosmer–Lemeshow test. The concordance C index was 0.814. According to Nagelkerke’s R2, the model explained 53.1% of the variance in survival. As a screening test, “chair-to-bed transfer” was superior to the Barthel index.

Conclusion

ADL dependence for chair-to-bed transfers is an independent risk factor for mortality for any level of dependency. Therefore, a new classification of the Barthel index is proposed, in which “being dependent or requiring great assistance to perform chair-to-bed transfers” is considered severe dependence, even when the total score obtained via the Barthel Index is ≥40. We propose its use as a screening test in parallel to the Barthel index. The study suggests that the Barthel Index may have limitations in adequately discriminating mortality risk.
Neuromodulatory effect of transcranial direct current stimulation on cue reactivity and craving in young adults with internet gaming disorder: an event-related potential study
Authors: Kim Sung Nyun , Choi Jung-Seok , Park Minkyung , Yoo So Young , Choi Areum , Koo Ja Wook , Kang Ung Gu
Published: January 2025

Objective

This study assessed the effects of transcranial direct current stimulation (tDCS) on cue reactivity and craving for game-related cues using event-related potentials (ERPs) in internet gaming disorder (IGD) patients.

Methods

At baseline, a series of game-related and neutral pictures were shown to both IGD and healthy controls (HCs) while ERPs were recorded. Late positive potentials (LPP) were used to investigate cue reactivity. During intervention, IGD patients received 10 sessions (two sessions/day for 5 consecutive days, 2 mA for 20 min/session) of tDCS to the left (anode stimulation) and right (cathode) dorsolateral prefrontal cortex. Subjectively assessed craving and LPP component was analyzed before stimulation and at the 1-month follow-up after tDCS in IGD.

Results

At baseline, patients with IGD showed higher LPP amplitudes for game-related cues in the centro-parietal and parietal regions than HCs. After 10 sessions of tDCS, increased LPP amplitudes decreased significantly at 1-month follow-up., as well as subjective craving for gaming.

Conclusion

These findings suggest that neurophysiological arousal in response to game-related cues in the IGD group could be modulated by the effects of tDCS. LPP was a significant neurophysiological marker of the neuroplastic response of cue reactivity underlying the therapeutic effect of tDCS on IGD. Based on the present findings, tDCS could be expanded to the treatment of other addictive disorders, including substance use disorder and behavioral addictions.
Challenges in rural maternal health: how received public services and policy awareness affect health knowledge and practices
Authors: Yang Jie , Chen Jun , Xie Yuyang , Liu Yunjie , Wu Junhao , Li Yangyuan , Nie Jingchun
Published: January 2025

Purpose

This study evaluates the effectiveness of rural maternal health services in improving pregnant women’s health knowledge, practices, and outcomes in northwestern China, focusing on the roles of received public services and policy awareness.

Methods

Baseline surveys were conducted in rural Shaanxi Province in 2021 and 2023, involving 1,152 pregnant women from 85 townships, selected via multistage cluster random sampling. Data were collected through structured face-to-face interviews, covering health knowledge and behaviors. Statistical analyses were performed to assess the impact of maternal health services.

Results

Both received public services (Coefficient: 0.130, 95% CI: 0.015–0.246) and policy awareness (Coefficient: 0.114, 95% CI: 0.001–0.227) significantly improved nutrition and health knowledge but had limited impact on prenatal checkups or health outcomes. Policy awareness (OR: 3.826, 95% CI: 2.743–5.337) significantly increased picking up free folic acid, however, the rate of taking folic acid remained low.

Conclusion

While received public services and policy awareness improved nutrition and health knowledge, and policy awareness increased picking up free folic acid, they did not significantly influence prenatal checkups or health outcomes. More targeted efforts are needed to foster consistent health practices and improve maternal health outcomes in rural areas.
Clinical entity-aware domain adaptation in low resource setting for inflammatory bowel disease
Authors: Francis Sumam , Crema Garcia Fernando , Uma Kanimozhi , Mestdagh Willem , De Moor Bart , Moens Marie-Francine
Published: January 2025

The digitization of healthcare records has revolutionized medical research and patient care, with electronic health records (EHRs) containing a wealth of structured and unstructured data. Extracting valuable information from unstructured clinical text presents a significant challenge, necessitating automated tools for efficient data mining. Natural language processing (NLP) methods have been pivotal in this endeavor, aiming to extract crucial clinical concepts embedded within free-form text. Our research addresses the imperative for robust biomedical entity extraction, focusing specifically on inflammatory bowel disease (IBD). Leveraging novel domain-specific pre-training and entity-aware masking strategies with contrastive learning, we fine-tune and adapt a general language model to be better adapted to IBD-related information extraction scenarios. Our named entity recognition (NER) tool streamlines the retrieval process, supporting annotation, correction, and visualization functionalities. In summary, we developed a comprehensive pipeline for clinical Dutch NER encompassing an efficient domain adaptation strategy with domain-aware masking and model fine-tuning enhancements, and an end-to-end entity extraction tool, significantly advancing medical record curation and clinical workflows.
Midlatitude mesosphere and lower thermosphere variations during the extreme gannon geomagnetic storm in May 2024
Authors: Yuan Tao , Pautet P. D. , Taylor M. J.
Published: January 2025

Recent studies based upon both observations and numerical simulations have indicated the impacts of the intense geomagnetic storms induced by Coronal Mass Ejections (CMEs) on the neutral dynamics in the mesosphere and lower thermosphere (MLT). Even in the midlatitude MLT, far equatorward of subauroral zone, significant variations were reported. Aurora is one of the major dynamic drivers in the MLT in high latitudes, but observations of the neutral dynamic variations under the aurora in the storm time MLT are sparse. The lack of such MLT observations during the presence of aurora leads to a critical gap in the understanding of upper atmospheric dynamics. In this paper, we present the unprecedented observations under the aurora during the Gannon Geomagnetic Storm in May 2024 by the Na Doppler lidar at Utah State University (42°N, 112°W) and the Advanced Mesospheric Temperature mapper (AMTM) at the nearby Bear Lake observatory (BLO). Significant warming (as much as ∼50 K) accompanied by fast equatorward flow in the lower thermosphere (up to ∼100 m/s changes in the meridional wind above 100 km altitude) were observed. The temperature enhancement (∼10 K) of the hydroxyl layer during the same period is also captured by the AMTM. Intriguingly, significant storm time depletion of sodium (Na) abundance on the topside of the mesospheric Na layer above 105 km, as much as more than 80%, was also observed. These observations provide insight for future investigations on the MLT responses to the intense geomagnetic storms, especially the role of aurora in these events.