bluuebunny/crossref_metadata_2025 huggingface dataset:
IFNλ1 is a STING-dependent mediator of DNA damage and induces immune activation in lung cancer
Authors: Godsk Stine Høvring , Jensen Caroline Maren Stengaard , Larsen Trine Vilsbøll , Ahrenfeldt Johanne , Gammelgaard Kristine Raaby , Jakobsen Martin Roelsgaard
Published: February 2025

Introduction

The importance of the cGAS-STING pathway and type I interferon (IFN) in anti-tumor immunity has been widely studied. However, there is limited knowledge about the role of type III IFNs in cancer settings. Type III IFNs, comprising IFNλ1-4, are opposite to type I IFN only expressed by a few cell types, including epithelial cells, and the receptor subunit IFNLR1, is equally only expressed on limited types of cells.

Methods

Gene and protein expression of the cGAS-STING signaling pathway was characterized in a series of non-small cell lung cancer (NSCLC) cell lines. Herring-testis DNA stimulation and chemotherapy drugs (doxorubicin and cisplatin) were used to activate the cGAS-STING pathway, and the level of activation was determined by measuring changes in the transcriptomic profile as well as type I and III IFNs by ELISA. Re-expression of IFNLR1 on cancer cell lines was achieved using CRISPR activation (CRISPRa) followed by evaluating chemotherapy-induced apoptosis using flow cytometry assays.

Results

STING was not broadly expressed across the NSCLC cell lines. Those cancer cell lines expressing all relevant factors supporting the cGAS-STING pathway secreted IFNλ following STING activation whereas only few of them expressed IFNβ. Treatment with chemotherapy drugs likewise preferentially induced IFNλ, which was abrogated in CRISPR-Cas9 STING knock-out cells. Expression of IFNLR1 was found downregulated in the cancer cell lines compared to the benign epithelial cell line Nuli-1. Rescuing IFNLR1 expression by CRISPRa in multiple cancer cell lines sensitization them to IFNλ-stimulation and resulted in significant reduction in cell viability.

Conclusion

Downregulation of IFNLR1 can be an immune evasion mechanism developed by cancer cells to avoid responding to endogenous type III IFNs. Thus, rescuing IFNLR1 expression in NSCLC in conjunction to chemotherapy may potentially be harnessed to elevate the anti-tumoral responses.
Efficacy of high-dose steroids versus low-dose steroids in the treatment of immune checkpoint inhibitor-associated myocarditis: a case series and systematic review
Authors: Man Xiuyue , Wang Hong , Chen Chen , Cong Xiaofeng , Sun Lemeng , Sun Xueru , Chen Chen , Zhang Jing , Yang Lei
Published: February 2025

Background

Immune checkpoint inhibitor-associated myocarditis (ICI-M) is a rare yet potentially fatal complication of immunotherapy, with no standardized treatment protocol due to limited data. The use of varying steroid doses has resulted in inconsistent outcomes.

Methods

We retrospectively identified patients diagnosed with ICI-M at our institution between January 2020 and February 2024. Additionally, we conducted a comprehensive literature review using PubMed, Embase, and the Cochrane Library to facilitate a comparative analysis of clinical responses. The primary aim was to compare clinical outcomes and therapeutic responses between patients treated with high-dose versus low-dose methylprednisolone.

Results

Patients receiving an initial high-dose intravenous methylprednisolone (1 g/day) exhibited a more rapid reduction in myocardial injury markers, including troponin I/T (cTnI/T), creatine kinase (CK), and N-terminal pro b-type natriuretic peptide (NT-proBNP), compared to those receiving lower doses. This group also demonstrated lower incidences of biomarker rebound and maintained lower levels over time. Additionally, the clinical treatment process was more straightforward in the high-dose group, with treatment efficacy surpassing that observed in patients who received an initial methylprednisolone (mPSL) dose of less than 1 g/day. Regarding prognosis, the incidence of major adverse cardiovascular events (MACE) and cardiovascular mortality was significantly lower in the high-dose group compared to the low-dose group.

Conclusions

In patients with immune checkpoint inhibitor-associated myocarditis, the prompt administration of high-dose corticosteroid pulse therapy (1 g/day) is strongly associated with improved clinical outcomes. This intervention rapidly lowers myocardial injury biomarkers (cTnI/T, CK, NT-proBNP) while minimizing the risk of biomarker rebound, thus optimizing clinical management. Notably, it significantly reduces the incidence of major adverse cardiovascular events (MACE), thereby enhancing patient prognosis. The duration of therapy should be tailored based on clinical response. In cases of steroid resistance, combination therapies may provide additional benefit.
Advanced disease and CD8+ TEMRA cells predict severe infections in multiple myeloma
Authors: Tranter Eva , Busch David , Heck Clarissa , Blau Igor Wolfgang , Nogai Axel , Schiele Phillip , Meisel Christian , Bullinger Lars , Frentsch Marco , Na Il-Kang
Published: February 2025

Introduction

Infections are a major cause of early morbidity and mortality in patients with multiple myeloma (MM) who are characterized by immunodeficiency secondary to disease. However, prospectively collected data on infection risk in this population are scarce. We aimed at identifying parameters in monoclonal gammopathy of undetermined significance (MGUS) and newly diagnosed MM (NDMM) patients with predictive power for early severe infections (SI).

Methods

We conducted a prospective study with newly diagnosed MGUS and NDMM patients. Besides clinical and laboratory data, immune parameters were collected at initial diagnosis before therapy initiation. Primary endpoint was the occurrence of SI within 12 months after diagnosis.

Results

45% of patients developed infection, 26% with SI. Four main risk factors for SI were identified: ECOG ≥ 2 (p < 0.001), ISS stage II/III (p = 0.002), therapeutic intervention (p < 0.001), and elevated CD8+ TEMRA cells (p = 0.027). A risk score was compiled, enabling the stratification of patients with low or high risk for SI with a sensitivity of 92.9% and a specificity of 80%.

Conclusion

We developed a straightforward risk score that considers the relevance of T cell fitness in MGUS and NDMM patients and can help physicians to identify patients at risk of infection, thus enabling the implementation of timely and individualized prevention strategies.
A remarkable and durable response to tislelizumab treatment of an anaplastic thyroid carcinoma without targetable genomic alterations: a case report
Authors: Chai Jingjing , Lv Jiaqi , Xiong Jian , Chen Xiuwen , Luo Senyuan , Luo Zhiguo , Luo Ming
Published: February 2025

Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive malignancy characterized by a poor prognosis, with a median survival time of approximately 3 to 4 months. In this report, we present a case involving a 59-year-old patient diagnosed with ATC, who experienced swift local recurrence and pulmonary metastasis following radical thyroidectomy. Comprehensive Sanger sequencing of the resected tumor tissue revealed no mutations in the TERT promoter or the BRAF V600E gene. The patient exhibited rapid recurrence post-surgery and was deemed unsuitable for immediate surgical intervention. The patient was unable to tolerate chemotherapy; therefore, radiotherapy was administered initially to prevent airway compression resulting from disease progression. During the course of radiotherapy, pulmonary metastasis developed, yet the patient remained intolerant to both chemotherapy and anti-angiogenic therapy. Immunohistochemical analysis revealed a high expression of PD-L1. Whole exome sequencing (WES) indicated a tumor mutation burden (TMB) of 2.98 mut/Mb, microsatellite stability (MSS), and identified 10 missense mutations, 1 nonsense mutation, and 1 frameshift insertion. However, none of these mutations have corresponding targeted therapies. Consequently, we administered tislelizumab as an immunotherapeutic intervention. The patient exhibited significant regression in cervical metastatic lymph nodes and pulmonary metastatic tumors, achieving a sustained remission lasting 14 months, culminating in complete remission, without experiencing any adverse events related to immune checkpoint inhibitors. This case demonstrates the efficacy of second-line monotherapy with an immune checkpoint inhibitor (ICI) for ATC in a patient unable to tolerate chemotherapy and anti-angiogenic anlotinib treatment, thereby offering a viable treatment strategy for ATC patients.
Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies
Authors: Ao Jianyang , Hu Mingtai , Wang Jinghan , Jiang Xiaoqing
Published: February 2025

Biliary tract malignancies, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, represent a group of aggressive cancers with poor prognosis due to late-stage diagnosis, limited treatment options, and resistance to conventional therapies like chemotherapy and radiotherapy. These challenges emphasize the urgent need for innovative therapeutic approaches. In recent years, cell-based therapies have emerged as a promising avenue, offering potential solutions through immune modulation, genetic engineering, and targeted intervention in the tumor microenvironment. This Mini-review provides an overview of current advancements in cell-based therapies for biliary malignancies, encompassing immune cell-based strategies such as CAR-T cells, NK cells, dendritic cell vaccines, and tumor-infiltrating lymphocytes. We also examine strategies to overcome the immunosuppressive tumor microenvironment and discuss the integration of cell therapies into multimodal treatment regimens. By synthesizing preclinical and clinical findings, this review highlights key insights and future directions, aiming to assist researchers and clinicians in translating these approaches into effective treatments. The transformative potential of cell-based therapies discussed here makes this review a valuable resource for advancing biliary malignancy research and clinical applications.
Anticholinergic burden and behavioral and psychological symptoms in older patients with cognitive impairment
Authors: Pistorio Sabrina , Scotto di Tella Gianluca , Canzanella Vittoria , Merenda Raffaella , Cuomo Gianluigi , Iacotucci Paola , Carnovale Vincenzo , Bencivenga Leonardo , Vargas Maria , Manes Annalaura , Cataldi Mauro , Rengo Giuseppe , Zanetti Michela , Femminella Grazia Daniela
Published: February 2025

Background

Drugs with anticholinergic properties are frequently prescribed to patients with cognitive impairment. The cholinergic system plays an important role in learning processes, memory, and emotions regulation. The aim of this research is to report use of anticholinergic drugs in a clinical population and to investigate the correlation between the use of anticholinergic drugs and the risk of presenting with more severe behavioral and psychological symptoms (BPSD).

Method

Patients with a diagnosis of subjective cognitive impairment, mild cognitive impairment (MCI) or dementia were recruited. Screening tests for cognitive impairment (MMSE) and functional status (ADL, IADL) were performed. BPSD were evaluated with the Neuropsychiatric Inventory (NPI). The anticholinergic burden was calculated using the ACB calculator. We compared patients at low risk of anticholinergic adverse effects (ACB < 3) versus patients at high risk (ACB ≥ 3). Chi-square test and Mann–Whitney test were used to compare the two groups. A multiple linear regression was performed to identify factors associated with higher NPI score and a logistic regression model was built to identify drug classes associated with ACB ≥ 3.

Result

A total of 173 patients (mean age 74 ± 7, 74 men) were included in the study; 132 patients with ACB < 3 (low risk) versus 41 patients with ACB ≥3 (high risk) were compared. No statistically significant differences were found between the two groups in terms of demographics (age, sex) and anamnestic variables (education, marital status, family history of dementia, hypertension, diabetes, smoking, dyslipidemia, atrial fibrillation, coronary heart disease and use of alcohol). Significantly higher NPI scores were found in patients with ACB ≥ 3 (mean scores 47.3 ± 34.8 versus 25.5 ± 24.6, p < 0.001). Patients with ACB ≥ 3 showed lower MMSE (18.5 ± 8.6 versus 22.4 ± 7, p = 0.004) and more IADLs lost. In the multivariate regression analysis, after adjusting for age, sex, polypharmacy and IADLs lost, only the MMSE and the ACB scores were independent predictors of the NPI score. Being on antipsychotics, antidepressants and antidiabetic drugs was associated with increased risk of higher anticholinergic burden.

Conclusion

In conclusion, the anticholinergic burden might play a significant role as a risk factor for developing more severe BPSD in patients with cognitive decline, independently from their degree of cognitive impairment.
MAEMC-NET: a hybrid self-supervised learning method for predicting the malignancy of solitary pulmonary nodules from CT images
Authors: Zhao Tianhu , Yue Yong , Sun Hang , Li Jingxu , Wen Yanhua , Yao Yudong , Qian Wei , Guan Yubao , Qi Shouliang
Published: February 2025

Introduction

Pulmonary granulomatous nodules (PGN) often exhibit similar CT morphological features to solid lung adenocarcinomas (SLA), making preoperative differentiation challenging. This study aims to address this diagnostic challenge by developing a novel deep learning model.

Methods

This study proposes MAEMC-NET, a model integrating generative (Masked AutoEncoder) and contrastive (Momentum Contrast) self-supervised learning to learn CT image representations of intra- and inter-solitary nodules. A generative self-supervised task of reconstructing masked axial CT patches containing lesions was designed to learn intra- and inter-slice image representations. Contrastive momentum is used to link the encoder in axial-CT-patch path with the momentum encoder in coronal-CT-patch path. A total of 494 patients from two centers were included.

Results

MAEMC-NET achieved an area under curve (95% Confidence Interval) of 0.962 (0.934–0.973). These results not only significantly surpass the joint diagnosis by two experienced chest radiologists (77.3% accuracy) but also outperform the current state-of-the-art methods. The model performs best on medical images with a 50% mask ratio, showing a 1.4% increase in accuracy compared to the optimal 75% mask ratio on natural images.

Discussion

The proposed MAEMC-NET effectively distinguishes between benign and malignant solitary pulmonary nodules and holds significant potential to assist radiologists in improving the diagnostic accuracy of PGN and SLA.
Study on the multidrug resistance and transmission factors of Staphylococcus aureus at the ‘animal–environment–human’ interface in the broiler feeding cycle
Authors: Hu Fangyuan , Liu Yaopeng , Wang Lin , Wang Juan , Liu Na , Li Yan , Duan Xiaoxiao , Wang Junwei , Lu Mingzhe , Liu Junhui , Qu Zhina , Han Keguang
Published: February 2025

Multidrug-resistant Staphylococcus aureus (S. aureus) poses an increasingly serious threat to agricultural safety and public health. Based on the concept of “One Health,” this study analyzed the multidrug resistance and transmission factors of S. aureus isolated from the “animal–environment–human” interface during one feeding cycle of commercial broilers in China by using antimicrobial susceptibility testing and whole genome sequencing (WGS) technologies. The results showed that in stage 1, the isolation rate of S. aureus was 1.32% (6/453), that of workers was 25.0% (4/16), and that of environmental samples was 0.69% (2/287), and the multidrug resistance rate was 83.33%. After one feeding cycle, the isolation rate of S. aureus (221/772, 28.63%) increased significantly (p < 0.01) during stage 2, and the multidrug resistance rate was as high as 97%. The resistance rates to eight drugs including erythromycin, clindamycin, enrofloxacin, ofloxacin, doxycycline, florfenicol, tylosin, and tilmicosin were elevated, but the differences were not significant (p > 0.05). ST398 (79.13%) was the dominant strain in both stages, which was prevalent in 11 types of samples from 3 sources and clustered in the same sub-branch of the single-nucleotide polymorphism (SNP) evolutionary tree. The loci difference between the strains ranged from 1 to 541, with SNPs of less than 10 between the human strains of stage 1 and the three sources in stage 2. The 42 representative strains carried mobile elements, mainly plasmid replicons (10 types), transposons (3 types), and 20 antibiotic resistance genes in 9 classes. A total of 10 ST398 strains exhibited the fosB gene for fosfomycin resistance, and 6 ST9 strains from stage 2 exhibited the mecA resistance gene. The SNP evolutionary analysis revealed that the fosB resistance gene might have been brought in by workers during stage 1. This study revealed the critical impact of environmental residual and worker-carried S. aureus, as well as the transmission of antibiotic resistance in stage 1. It highlighted the importance of the “One Health” approach and biosecurity measures and provided recommendations for the prevention of the spread of pathogens and resistance.
Spartina alterniflora invasion significantly alters the assembly and structure of soil bacterial communities in the Yellow River Delta
Authors: Sun Pengyuan , Wu Yuxin , Zhu Pengcheng , Wang Jingfeng , Yu Xiaona , Guo Weihua
Published: February 2025

Soil microbial communities are integral to almost all terrestrial biogeochemical cycles, which are essential to coastal wetland functioning. However, how soil bacterial community assembly, composition, and structure respond to native and non-native plant invasions in coastal wetlands remains unclear. In this study of the coastal wetlands of the Yellow River Delta in China, the assembly, community composition, and diversity of soil bacterial communities associated with four wetland plant species (Phragmites australis, Spartina alterniflora, Suaeda salsa, and Tamarix chinensis) and four soil depths (0–10 cm, 10–20 cm, 20–30 cm, and 30–40 cm) were characterized using high-throughput sequencing. Plant species identity, as well as environmental factors, rather than soil depth, was found to play predominant roles in shaping the diversity and structure of wetland soil bacterial communities. S. alterniflora invasion altered bacterial community structure and increased bacterial diversity. Phragmites australis-associated bacterial communities were enriched with sulfate-reducing bacteria such as Desulfurivibrio and Desulfuromonas. In comparison, S. alterniflora-associated bacterial communities were enriched with both sulfate-reducing bacteria (SEEP-SRB1) and sulfate-oxidizing bacteria (Sulfurimonas), which maintained a dynamic balance in the local sulfur-cycle, and thereby enhanced S. alterniflora growth. In addition, stochastic processes dominated the assembly of soil bacterial communities associated with all four plant species, but were most important for the S. alterniflora community. The S. alterniflora-associated bacterial community also showed stronger interactions and more extensive connections among bacterial taxa; a co-occurrence network for this community had the greatest average clustering coefficient, average degree, modularity, and number of links and nodes, but the lowest average path length. Altogether, individual plant species had distinct effects on soil bacterial community assembly and structure, with the invasive species having the strongest impact. These results provide insights into microbial ecology and inform management strategies for coastal wetland restoration.
The gastric microbiome altered by A4GNT deficiency in mice
Authors: Gong Dawei , Gao Yuqiang , Shi Rui , Xu Xiaona , Yu Mengchao , Zhang Shumin , Wang Lili , Dong Quanjiang
Published: February 2025

Background

Selective antimicrobial effects have been found for α1,4-linked N-acetylglucosamine residues at the terminus of O-glycans attached to a core protein of gastric gland mucin. A4gnt encodes α1,4-N-acetylglucosaminyl transferase, which is responsible for the biosynthesis of α1,4-linked N-acetylglucosamine. The impact of A4GNT on the establishment and homeostasis of the gastric microbiome remains to be clarified. The aim of this study was to characterize the gastric microbiome in mice deficient for the production of α1,4-linked N-acetylglucosamine.

Methods

The gastric microbiome within A4gnt−/− mice and wild-type mice was analyzed using high-throughput sequencing of bacterial 16S rRNA.

Results

In A4gnt−/− mice, which spontaneously develop gastric cancer, the community structure of the gastric microbiome was altered. The relative abundance of mutagenic Desulfovibrio and proinflammatory Prevotellamassilia in these mice was significantly increased, especially 4 weeks after birth. The co-occurrence network appeared to be much more complex. Functional prediction demonstrated considerable decreases in the relative frequencies of functions associated with polysaccharide metabolism and transportation.

Conclusion

The distinct profile in A4gnt−/− mice demonstrated a vital role of A4GNT in the establishment of the gastric microbiome. A dysbiotic gastric microbiome may contribute to the spontaneous development of gastric cancer in mice.
Olfaction-based learned preference assessment without the use of motivational fear or motivational weight loss
Authors: Moss Sara E. , McCurdy Ekaterina S. , Thomas Natalya N. , Gulick Danielle , Poff Angela M. , D'Agostino Dominic P.
Published: February 2025

Introduction

Reliable assessments of learning ability in preclinical models are essential for studying neurodegenerative, developmental, and inflammatory disorders. However, many inbred strains of mice present background pathologies that interfere with traditional learning tests. The C57BL/6 J mouse, a widely used laboratory strain, sporadically develops auditory and visual impairments that complicate interpretation. In this study, we establish an olfaction-based learned preference protocol designed to evaluate learning ability independent of fear responses, motivational weight loss, or visual cues in C57BL/6 J mice.

Methods and results

Leveraging the species’ natural preference for sweet flavors, we tested different sweeteners and confirmed their passive preference for sucrose was more robust than for saccharin or sucralose. We then trained mice to associate either lemon or rose scents with a sucrose paste reward, and tested whether they demonstrated a learned preference for the sucrose-associated scent over the neutral scent. Mice developed an appetitive olfactory preference for sucrose as a reward, in the absence of motivational weight loss, as measured by time spent exploring a three-chamber association box with access to both scents. We assessed whether this protocol discriminated learning deficit induced by lipopolysaccharide (LPS) administration.

Conclusion

We conclude that this protocol is a viable tool for assessing learning abilities in preclinical models with auditory or visual deficits, motor impairments, or an inability to tolerate motivational weight loss.
Profiling gene alterations in striatonigral neurons associated with incubation of methamphetamine craving by cholera toxin subunit B-based fluorescence-activated cell sorting
Authors: Altshuler Rachel D. , Burke Megan A. M. , Garcia Kristine T. , Class Kenneth , Cimbro Raffaello , Li Xuan
Published: February 2025

Introduction

In both rats and humans, methamphetamine (Meth) seeking progressively increases during abstinence, a behavioral phenomenon termed “incubation of Meth craving”. We previously demonstrated a critical role of dorsal striatum (DS) in this incubation in rats. However, circuit-specific molecular mechanisms in DS underlying this incubation are largely unknown. Here we combined a newly developed fluorescence-activated sorting (FACS) protocol with fluorescence-conjugated cholera toxin subunit B-647 (CTb-647, a retrograde tracer) to examine gene alterations in the direct-pathway (striatonigral) medium spiny neurons (MSNs) associated with incubation of Meth craving.

Methods

We injected CTb-647 bilaterally into substantia nigra before or after training rats to self-administer Meth or saline (control condition) for 10 days (6 h/d). On abstinence day 1 or day 28, we collected the DS tissue from both groups for subsequent FACS and examined gene expressions in CTb-positive (striatonigral MSNs) and CTb-negative (primarily non-striatonigral MSNs). Finally, we examined gene expressions in DS homogenates, to demonstrate cell-type specificity of gene alterations observed on abstinence day 28.

Results

On abstinence day 1, we found mRNA expression of Gabrb3 decreased only in CTb-positive (but not CTb-negative) neurons of Meth rats compared with saline rats, while mRNA expression of Usp7 decreased in all sorted DS neurons. On abstinence day 28, we found increased mRNA expression for Grm3, Opcml, and Usp9x in all sorted DS neurons, but not DS homogenate.

Discussion

Together, these data demonstrated that incubation of Meth craving was associated with time-dependent, circuit-specific, and cell type-specific gene alterations in DS involved in glutamatergic, GABAergic, opioidergic, and protein degradation signaling.
Tandem repeat expansions and copy number variations as risk factors and diagnostic tools for amyotrophic lateral sclerosis
Authors: Sabetta Eleonora , Ferrari Davide , Massimo Locatelli , Kõks Sulev
Published: February 2025

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder leading to upper and lower motoneurons degeneration. Although several mechanisms potentially involved in disease development have been identified, its pathogenesis is not fully understood. From the patient side, ALS diagnosis, still based on clinical criteria, can be difficult and may take up to 1 year. More than 30 genes have been associated to genetically inherited ALS, among which four (C9ORF72, SOD1, TARDBP and FUS) would explain around 60–70% of cases. However, familial ALS represents only 5–10% of ALS cases while the remaining are sporadic, with genetics explaining 6–10% of such cases only. In this context, short tandem repeats (STRs) expansions, have recently been found in clinically diagnosed ALS patients. In this review, we discuss the recent discoveries on ALS associated STRs and their potential as biomarkers as well as prognosis and therapy targets.
Study on the correlation between carotid plaque calcification types and acute ischemic stroke
Authors: Chu Tianyu , Guo Zhongping , Zhang Yonggang , Liu Ying , Gu Yan
Published: February 2025

Introduction

Computed tomography angiography (CTA) was used to explore the correlation between the calcification types of carotid plaques and ipsilateral acute ischemic stroke. This could provide new insights into the clinical evaluation and treatment of ischemic stroke.

Methods

This study obtained information on patients undergoing head and neck CTA examinations at the First People's Hospital of Lianyungang between September 2022 and August 2023 to investigate the clinical differences in baseline data between the acute ischemic stroke and control groups. Patients meeting the inclusion and exclusion criteria were classified into 1 to 6 groups according to their plaque calcification characteristics. The correlation between calcified plaque type and ipsilateral acute ischemic anterior circulation stroke was analyzed using paired sample chi-square and Spearman correlation tests.

Results

Based on the inclusion and exclusion criteria, this study included 589 patients with plaques at the bifurcation of the carotid arteries. In both the acute ischemic stroke and control groups, sex, smoking, alcohol consumption, systolic blood pressure, blood sugar, cholesterol, high-density lipoprotein, and homocysteine levels were statistically significant (p < 0.05). During the Spearman correlation analysis between calcification type and acute stroke (1,178 carotid arteries), different calcification types of plaques were linked with ipsilateral acute anterior circulation stroke with statistically significant differences (p < 0.001). Finally, the chi-squared test of the paired samples showed that the grade of plaque calcification is often higher on the side of acute infarction than on the side without acute infarction, and the difference is statistically significant (p < 0.001).

Discussion

Carotid plaque calcification is associated with acute ischemic stroke. Our findings provide novel insights into the study of calcification in carotid atherosclerotic plaques and additional radiological evidence to clinically assess the risk of ischemic stroke.
The influence of time and visualization on neurofeedback-guided parietal alpha downregulation and sense of presence in virtual reality
Authors: Botrel Loic , Kreilinger Alex , Müller Mathias , Pfeiffer Maria , Scheu Vincent , Vowinkel Nico , Zechner Roland , Käthner Ivo , Kübler Andrea
Published: February 2025

In an EEG-based near real-time neurofeedback (NF) study in two parts using high immersive virtual reality (VR) we successfully trained healthy participants to downregulate their parietal alpha power, a neurophysiological correlate previously associated with enhanced sense of presence. The first part included n = 10 participants equipped with 128 and 64 channels gel-based active EEG electrodes in 10 sessions using standard bar feedback presented on a computer monitor. Nine participants were better than random at the 10th session and four improved over time. For the second part we reduced the electrode subset to 9 sponge-based active channels (2 frontal, 7 parietal around Pz) and a portable amplifier. Participants (n = 10) were trained each session within VR using bar feedback projected on a wall in the first 5 sessions and then controlling the flow of a water fountain. Participants were able to significantly downregulate their parietal alpha power after 5 sessions and learning occurred at the group level, with 7 participants showing both improvement over time and ability to modulate. However, these results were only shown during the fountain feedback and both ability and learning were non-significant in the VR projector condition. Based on self-reports, after excluding participants performing movements and closing their eyes, no particular mental strategy, such as relaxation, breathing or mental calculus was identified to help with alpha modulation. The hypothesized behavioral effect on sense of presence was not found nor any neurophysiological changes in fronto-parietal connectivity. While NF did not improve the sense of presence, we succeeded in adapting real-time NF training for high immersive VR technology via seamlessly embedded feedback in the form of a water fountain. The study showcases that NF is possible with sponge electrodes and portable EEG that would prove convenient in end-user (at home) or clinical setup. The dataset is publicly available on Openneuro.org.
Bedside cerebral microvascular imaging of patients with disorders of consciousness: a feasibility study
Authors: Ge Qianqian , Huang Lijie , Fu Qiang , Han Shuai , Wang Rui , He Jianghong , Li Changhui , Luo Jianwen , Xu Long
Published: February 2025

Background

Efficient bedside neurofunctional monitoring is crucial for managing disorders of consciousness (DoC). Ultrafast Power Doppler Imaging (uPDI) outperforms traditional Ultrasound in bedside for assessing the microcirculatory system. However, intracranial blood flow imaging traditionally faces limitations due to the skull’s impedance. This constraint is circumvented in common post-craniectomy DoC patients, who present a unique observational window for uPDI.

Methods

We conducted uPDI scans on five DoC patients of different ages and consciousness levels who had undergone decompressive craniectomy. We compared the imaging results from uPDI with traditional PDI and identified the physiological and pathological conditions with uPDI.

Results

Detailed microvascular images of both cortical and subcortical areas were obtained using uPDI through the craniectomy window. Notably, uPDI demonstrates high sensitivity and imaging depth, revealing microvessels as small as 320 μm in diameter at 4 cm depth, and detecting blood flow signals up to 6 cm beneath the scalp.

Conclusion

Through the decompressive cranial windows of DoC patients, we obtained cerebral microvascular images with significantly higher sensitivity without the need for contrast agents.

Significance

Our research provides a novel bedside cerebral microcirculation imaging method for patients with DoC, offering convenient neurofunctional assessment to improve the clinical management of DoC patients.
Relationship of METS-IR with cardiometabolic multimorbidity in China: a nationwide longitudinal cohort study
Authors: Zhou Chunyan , Zhang Yanyu , Liu Xiaoyi , He Chenyu , Li Shiyang
Published: February 2025

Background

Cardiometabolic multimorbidity (CMM) has emerged as a global health challenge with a high mortality risk. This study aimed to explore the association between the metabolic score for insulin resistance (METS-IR) and the incidence of CMM.

Methods

This study included 6,977 individuals in the CHARLS database. We used multiple cox proportional hazards regression and restricted cubic splines (RCS) analysis to evaluate the association between METS-IR and CMM. Subgroup analyses and interaction tests were also performed.

Results

During a median 109 (108–109) months of follow-up, 745 (10.7%) participants were diagnosed with new-onset CMM. The incidences of CMM among participants in quartiles (Q) 1–4 of METS-IR were 4.99, 7.51, 10.67, and 19.54%, respectively. METS-IR was significantly higher in individuals with CMM compared to those without CMM (p < 0.001). After multivariate adjustment, a higher METS-IR was significantly associated with an increased risk of CMM. Compared to participants in Q1 of METS-IR, the hazard ratios (HRs) (95% confidence intervals [CIs]) using cox proportional hazards regression analysis for those in Q2–4 were 1.52 (1.15–2.00), 2.02 (1.56–2.63), and 3.61 (2.80–4.64), respectively. RCS analysis revealed a significant nonlinear association between METS-IR and CMM (nonlinear p < 0.05). The association between METS-IR and the incidence of CMM was present in almost all the subgroups. Furthermore, the predictive ability of METS-IR for CMM was 0.669, which surpassed that of both the triglyceride to high-density lipoprotein cholesterol ratio and the triglyceride glucose index.

Conclusion

A higher METS-IR was closely associated with an increased risk of CMM. Further studies on METS-IR could be beneficial for preventing and treating CMM.
Serum alpha-1 acid glycoprotein and gallstone risk in US adult women: a cross-sectional analysis of the NHANES
Authors: Li Xiaocheng , He Peiling
Published: February 2025

Background

Gallstone disease, a common biliary disorder, is linked to inflammation and immune responses. However, the association between serum alpha-1 acid glycoprotein (AGP), a key inflammatory marker, and gallstone risk remains underexplored.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 and 2021–2023 cycles were analyzed. Gallstone disease was determined by self-reported physician diagnosis. Serum AGP levels were measured using a high-sensitivity turbidimetric immunoassay. Weighted logistic regression, subgroup analyses, smoothed curve analysis, and multiple imputation were used to examine the relationship between AGP and gallstone risk.

Results

This cross-sectional analysis included 1,903 adult women in the U.S. aged 20–49. After adjusting for all covariates, serum AGP levels were positively associated with gallstone risk (OR: 3.07; 95% CI: 1.16, 8.11; p = 0.036). Compared to the first tertile (T1), the third AGP tertile (T3) had an OR of 1.87 (95% CI: 1.11, 3.14; p = 0.030). Smoothed curve analysis indicated a positive relationship between AGP and gallstone risk. Subgroup analyses consistently demonstrated this positive association across various demographic and clinical categories, with significant interactions observed for the ratio of family income to poverty. Sensitivity analyses using multiple imputation further supported the conclusion that AGP was associated with increased gallstone risk.

Conclusion

AGP is significantly associated with an increased risk of gallstones in U.S. adult women, suggesting its potential as a biomarker for risk stratification. Further research is needed to elucidate the underlying mechanisms and potential causal relationships.
Treatment efficacy for infantile epileptic spasms syndrome in children with trisomy 21
Authors: Chen Henry , Numis Adam L. , Shellhaas Renée A. , Mytinger John R. , Samanta Debopam , Singh Rani K. , Hussain Shaun A. , Takacs Danielle , Knupp Kelly G. , Shao Li-Rong , Stafstrom Carl E.
Published: February 2025

Background

Infantile Epileptic Spasms Syndrome (IESS) is the most common epilepsy syndrome in children with trisomy 21. First-line standard treatments for IESS include adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin. Among children with trisomy 21 and IESS, treatment with ACTH or oral corticosteroids may yield higher response rates compared with vigabatrin. However, supporting data are largely from single-center, retrospective cohort studies.

Methods

Leveraging the multi-center, prospective National Infantile Spasms Consortium (NISC) database, we evaluated the efficacy of first-line (standard) treatments for IESS in children with trisomy 21. We assessed clinical spasms remission at two weeks, clinical spasms remission at three months, and improvement of EEG (resolution of hypsarrhythmia) three months after initiation of treatment.

Results

Thirty four of 644 (5.3%) children with IESS were diagnosed with trisomy 21. In all children with trisomy 21, epileptic spasms was their presenting seizure type. Twenty of 34 (59%) children were initially treated with ACTH, nine (26%) with oral corticosteroids, and five (15%) with vigabatrin. Baseline demographics did not vary among treatment groups. The overall clinical remission rate after two weeks of treatment was 53% including 13 of 20 (65%) receiving ACTH, three of nine (33%) receiving oral corticosteroids, and two of five (40%) receiving vigabatrin (p = 0.24). The continued clinical response rate at three months was 32% including 8 of 20 (40%) receiving ACTH, two of nine (22%) receiving oral corticosteroids, and one of five (20%) receiving vigabatrin. Thirty of the 34 (88%) children presented with hypsarrhythmia (88%). EEG improvement at three months was better for children treated with ACTH (74%) or oral corticosteroids (83%) than vigabatrin (20%; p = 0.048). Adjustment for time from epileptic spasms onset to treatment did not alter results.

Conclusions

In our cohort, epileptic spasms were the first presenting seizure type in all children with trisomy 21. Among first-line standard treatment options, ACTH may have superior efficacy for clinical and electrographic outcomes for IESS in children with trisomy 21.
Substrate system outperforms water-culture systems for hydroponic strawberry production
Authors: Hutchinson George Kerrigan , Nguyen Lan Xuan , Ames Zilfina Rubio , Nemali Krishna , Ferrarezi Rhuanito Soranz
Published: February 2025

Strawberries (Fragaria × ananassa) are a globally cultivated fruit crop known for their economic significance and versatility in both fresh markets and processed food industries. Their high consumer demand and market value contribute to substantial profitability for producers. In recent years, due to increasing costs of production and occurrence of extreme weather events, the use of controlled environment agriculture (CEA) and hydroponics for strawberry production has become popular in several Asian, European, and American countries. There are two main types of hydroponic systems: substrate- and water-culture. Substrate-culture systems are the common choice for CEA strawberry production, whereas water-culture systems are usually used for crops like leafy greens and herbs. Both systems have been independently studied for CEA strawberry production, but direct comparisons between them are still limited. The objective of this study was to compare the performance of substrate and water-culture systems for CEA strawberry production regarding yield and resource use efficiencies. ‘Florida Brilliance’ and ‘Florida Beauty’ strawberries were grown in a greenhouse in one substrate-culture, with plants grow in soilless media, and three water-culture systems: nutrient film technique (NFT), vertical tower (stacked nutrient flow), and aeroponics (nutrient misted roots). The system inputs (water, energy, and area) and outputs (yield, biomass, etc.) were quantified during the 129-day experiment. Fruit yield was used to calculate water (WUE), energy (EUE), and area (AUE) use efficiencies. Based on yield and resource use efficiencies, the substrate system performed the best, with the vertical tower system also showing promising performance. The results of this experiment can help growers understand the tradeoffs between hydroponic systems to maximize both profits and sustainability for CEA strawberry production.
Quantitative vessel mapping on increment cores: a critical comparison of image acquisition methods
Authors: Peters Richard L. , Klesse Stefan , Van den Bulcke Jan , Jourdain Lisa M. Y. , von Arx Georg , Anadon-Rosell Alba , Krejza Jan , Kahmen Ansgar , Fonti Marina , Prendin Angela Luisa , Babst Flurin , De Mil Tom
Published: February 2025

Introduction

Quantitative wood anatomy is critical for establishing climate reconstruction proxies, understanding tree hydraulics, and quantifying carbon allocation. Its accuracy depends upon the image acquisition methods, which allows for the identification of the number and dimensions of vessels, fibres, and tracheids within a tree ring. Angiosperm wood is analysed with a variety of different image acquisition methods, including surface pictures, wood anatomical micro-sections, or X-ray computed micro-tomography. Despite known advantages and disadvantages, the quantitative impact of method selection on wood anatomical parameters is not well understood.

Methods

In this study, we present a systematic uncertainty analysis of the impact of the image acquisition method on commonly used anatomical parameters. We analysed four wood samples, representing a range of wood porosity, using surface pictures, micro-CT scans, and wood anatomical micro-sections. Inter-annual patterns were analysed and compared between methods from the five most frequently used parameters, namely mean lumen area (MLA), vessel density (VD), number of vessels (VN), mean hydraulic diameter (Dh), and relative conductive area (RCA). A novel sectorial approach was applied on the wood samples to obtain intra-annual profiles of the lumen area (Al), specific theoretical hydraulic conductivity (Ks), and wood density (ρ).

Results

Our quantitative vessel mapping revealed that values obtained for hydraulic wood anatomical parameters are comparable across different methods, supporting the use of easily applicable surface picture methods for ring-porous and specific diffuse-porous tree species. While intra-annual variability is well captured by the different methods across species, wood density (ρ) is overestimated due to the lack of fibre lumen area detection.

Discussion

Our study highlights the potential and limitations of different image acquisition methods for extracting wood anatomical parameters. Moreover, we present a standardized workflow for assessing radial tree ring profiles. These findings encourage the compilation of all studies using wood anatomical parameters and further research to refine these methods, ultimately enhancing the accuracy, replication, and spatial representation of wood anatomical studies.
Exploring the digital extremist ecosystem: a preliminary analysis of hateful posts on Mod DB
Authors: Schlegel Linda , Wiegold Lars , Winkler Constantin , Junk Julian
Published: February 2025

The last 4 years have seen a stark increase in research on extremist activities in digital gaming spaces, particularly on gaming- and gaming-adjacent platforms. However, one area that has not received much attention so far are mod forums. While a large number of mods with hateful content have been created over the last two decades, the forums used to disseminate and discuss such mods have not yet been examined by extremism researchers. Considering the popularity of modding and mod forums among gaming communities, this is a crucial gap in our current understanding of extremist activities in digital gaming spaces. In an effort to address this research gap, this article offers an exploratory analysis of hateful and extremist posts on the popular mod forum Mod DB, including right-wing extremist, jihadist, antisemitic and mixed-ideology content. We seek to provide a preliminary glimpse into this under-researched digital space, complementing existing research on extremist activities on other gaming (−adjacent) platforms. Our research thereby broadens the current state of knowledge regarding the various gaming-related platforms frequented by extremist actors and radicalized individuals and contributes new insights about a thus far under-explored digital space.
Wellbeing for young elite musicians: development of a health protocol from a student perspective
Authors: Shoebridge Ann , Osborne Margaret S.
Published: February 2025

Musicians’ vulnerability to psychological and physical problems provides a compelling argument to include health and wellbeing training in music education. This study forms part of a larger project to design an evidence-based wellbeing protocol for young elite musicians at a pre-professional music training institute. Recommendations from the health, education, performance science, behavior change, and occupational and public health literature provided theoretical and practical foundations for the project. The aim of this study was to identify barriers to wellbeing and strengths of an existing health protocol, and provide recommendations for change from the student perspective. Four in-person focus groups were held on the same day, attended by 68% (n = 45) of the student cohort. Semi-structured discussions were recorded, transcribed and analyzed thematically. Barriers to wellbeing and recommendations for change were collated from the data and distributed to the student body to be rated in priority order. Participants appreciated the existing program for its holistic approach delivered by a range of skilled practitioners. Barriers to wellbeing included constraints in finances, leave allowances and time, pressure from interpersonal challenges and unhealthy norms in the music performance culture. Recommendations for change included updating the financial policy; having more flexible leave conditions to allow higher earnings and better access to performance opportunities; having reliably scheduled time off; collaborative planning with staff around playing rosters; more activities for musician enhancement and social bonding; exercise opportunities in-house; addressing pervasive cultural norms around practice and breaks; education regarding respectful and professional conduct; an effective complaints procedure, and more practical wellbeing sessions.