bluuebunny/crossref_metadata_2025 huggingface dataset:
The biogeography of the mucosa-associated microbiome in health and disease
Authors: Sternes Peter R. , Shah Ayesha , Ayala Pintos Camila , Fairlie Thomas , Koloski Natasha , Kang Seungha , Tousignant Kaylyn D. , McIlroy Simon J. , Morrison Mark , Tyson Gene W. , Holtmann Gerald J.
Published: October 2024

Introduction

Little is known about the biogeography of the mucosa associated microbiome (MAM) in patients with inflammatory bowel disease (IBD) versus controls in different segments of the gastrointestinal tract, as well as the links between the MAM, gastrointestinal symptoms, and use of proton pump inhibitors (PPI).

Methods

We recruited 59 controls (without structural abnormalities and gastrointestinal symptoms), 44 patients with ulcerative colitis (UC) and 31 with Crohn’s disease (CD). Biopsies from various segments of the upper and lower gastrointestinal tract were collected. Microbial composition was assessed via 16S rRNA gene amplicon analysis and the bacterial load of the mucosal biopsies were assessed via qPCR. The MAM was examined in the context of disease status, PPI usage, the severity of gastrointestinal symptoms, and the symptom response to a standardised nutrient challenge (SNC).

Results

Microbial communities of the MAM in the upper and lower gastrointestinal tract differed. IBD patients were characterised by relative and absolute depletion of numerous genera known to produce butyrate and/or propionate, with the largest differentiation being the depletion of Faecalibacterium in the lower gastrointestinal tract of CD patients. Notably, PPI users exhibited an enrichment of Faecalibacterium in the lower gastrointestinal tract. The severity of gastrointestinal symptoms, as well as the symptom response to the SNC, were significantly associated with MAM composition in the gastrointestinal tract.

Conclusion

The absolute and relative composition of the MAM is variable across different segments of the gastrointestinal tract. These quantitative changes indicates that MAM can be targeted in specific segments of the GI tract to improve patient outcomes.
NAN-DETR: noising multi-anchor makes DETR better for object detection
Authors: Huang Zixin , Tao Xuesong , Liu Xinyuan
Published: October 2024

Object detection plays a crucial role in robotic vision, focusing on accurately identifying and localizing objects within images. However, many existing methods encounter limitations, particularly when it comes to effectively implementing a one-to-many matching strategy. To address these challenges, we propose NAN-DETR (Noising Multi-Anchor Detection Transformer), an innovative framework based on DETR (Detection Transformer). NAN-DETR introduces three key improvements to transformer-based object detection: a decoder-based multi-anchor strategy, a centralization noising mechanism, and the integration of Complete Intersection over Union (CIoU) loss. The multi-anchor strategy leverages multiple anchors per object, significantly enhancing detection accuracy by improving the one-to-many matching process. The centralization noising mechanism mitigates conflicts among anchors by injecting controlled noise into the detection boxes, thereby increasing the robustness of the model. Additionally, CIoU loss, which incorporates both aspect ratio and spatial distance in its calculations, results in more precise bounding box predictions compared to the conventional IoU loss. Although NAN-DETR may not drastically improve real-time processing capabilities, its exceptional performance positions it as a highly reliable solution for diverse object detection scenarios.
A novel loss-of-function KCNB1 gene variant in a twin with global developmental delay and seizures
Authors: Manville Rían W. , Illeck Claire L. , Santos Cesar , Sidlow Richard , Abbott Geoffrey W.
Published: October 2024

Human voltage-gated potassium (Kv) channels are expressed by a 40-member gene family that is essential for normal electrical activity and is closely linked to various excitability disorders. Function-altering sequence variants in the KCNB1 gene, which encodes the neuronally expressed Kv2.1 channel, are associated with neurodevelopmental disorders including developmental delay with or without epileptic activity. In this study, we describe a 40-month-old fraternal twin who presented with severe neurodevelopmental delay. Electroencephalogram recordings at 19 months of age revealed poor sleep architecture and the presence of multifocal epileptiform discharges. The individual’s fraternal twin was neurotypical, and there was no family history of neurodevelopmental delay or seizures. Whole genome sequencing at 33 months of age for the proband revealed a de novo variant in KCNB1 [c.1154C > T/p.Pro385Leu], encoding a proline-to-leucine substitution at residue 385, in the extracellular region immediately preceding Kv2.1 transmembrane segment 6 (S6). Cellular electrophysiological analysis of the effects of the gene variant in heterologously expressed Kv2.1 demonstrated that homozygous Kv2.1-P385L channels were completely non-functional. Channels generated by a 50/50 expression of wild-type Kv2.1 and Kv2.1-P385L, designed to mimic the proband’s heterozygous status, revealed a partially dominant-negative effect, resulting in an 81% reduction in current magnitude. The dramatic loss of function in Kv2.1 is the most likely cause of the severe developmental delay and seizure activity in the proband, further enriching our phenotypic understanding of KCNB1 developmental encephalopathies.
Exploring bispectral index as an alternative to polysomnography for long-term sleep monitoring in disorders of consciousness
Authors: Ge Qianqian , Chen Kaitian , Li Qinghua , Zhuang Yutong , Sun Peijian , Xu Long , He Jianghong
Published: October 2024

Background

Sleep plays a crucial role in neuroplasticity and recovery from brain injury, particularly in disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). Traditional sleep monitoring methods like polysomnography (PSG) are complex and often impractical for long-term use in clinical settings.

Target

This study aimed to explore the utility of the Bispectral Index (BIS) as a more practical alternative for monitoring sleep patterns in DoC patients.

Methods

We conducted simultaneous PSG and BIS monitoring on 38 DoC patients (19 UWS and 19 MCS). The study focused on analyzing sleep timing distribution, the effectiveness of BIS in differentiating sleep stages, and its correlation with consciousness levels.

Results

Our findings revealed that DoC patients exhibited irregular and fragmented sleep patterns, necessitating extended monitoring periods. The BIS effectively differentiated various sleep stages, with significant differences in BIS values observed across these stages. However, BIS values did not show significant differences between UWS and MCS patients, indicating that BIS primarily indicates wakefulness rather than cognitive awareness. DoC patients have disturbed sleep-wake cycles that require prolonged monitoring. BIS can well distinguish sleep stages in DoC patients, and the distribution of values is similar to that of normal subjects. However, BIS could not distinguish the level of consciousness of DoC patients.

Conclusion

The study demonstrates the potential of BIS as a practical tool for long-term sleep monitoring in DoC patients, offering a less intrusive alternative to traditional methods.
Effect of touch on proprioception: non-invasive trigeminal nerve stimulation suggests general arousal rather than tactile-proprioceptive integration
Authors: Tanner Justin , Orthlieb Gerrit , Helms Tillery Stephen
Published: October 2024

Introduction

Proprioceptive error of estimated fingertip position in two-dimensional space is reduced with the addition of tactile stimulation applied at the fingertip. Tactile input does not disrupt the participants’ estimation strategy, as the individual error vector maps maintain their overall structure. This relationship suggests integration of proprioception and tactile information improves proprioceptive estimation, which can also be improved with trained mental focus and attention. Task attention and arousal are physiologically regulated by the reticular activating system (RAS), a brainstem circuit including the locus coeruleus (LC). There is direct and indirect evidence that these structures can be modulated by non-invasive trigeminal nerve stimulation (nTNS), providing an opportunity to examine nTNS effect on the integrative relationship of proprioceptive and tactile information.

Methods

Fifteen right-handed participants performed a simple right-handed proprioceptive estimation task with tactile feedback (touch) and no tactile (hover) feedback. Participants repeated the task after nTNS administration. Stimulation was delivered for 10 min, and stimulation parameters were 3,000 Hz, 50 μs pulse width, with a mean of 7 mA. Error maps across the workspace are generated using polynomial models of the participants’ target responses.

Results

Error maps did not demonstrate significant vector direction changes between conditions for any participant, indicating that nTNS does not disrupt spatial proprioception estimation strategies. A linear mixed model regression with nTNS epoch, tactile condition, and the interaction as factors demonstrated that nTNS reduced proprioceptive error under the hover condition only.

Discussion

We argue that nTNS does not disrupt spatial proprioceptive error maps but can improve proprioceptive estimation in the absence of tactile feedback. However, we observe no evidence that nTNS enhances tactile-proprioceptive integration as the touch condition does not exhibit significantly reduced error after nTNS.
Netrin-1 stimulated axon growth requires the polyglutamylase TTLL1
Authors: Northington Kyle R. , Calderon Jasmynn , Bates Emily A.
Published: October 2024

Introduction

In the developing brain, neurons extend an axonal process through a complex and changing environment to form synaptic connections with the correct targets in response to extracellular cues. Microtubule and actin filaments provide mechanical support and drive axon growth in the correct direction. The axonal cytoskeleton responds to extracellular guidance cues. Netrin-1 is a multifunctional guidance cue that can induce alternate responses based on the bound receptor. The mechanism by which actin responds to Netrin-1 is well described. However, how Netrin-1 influences the microtubule cytoskeleton is less understood. Appropriate microtubule function is required for axon pathfinding, as mutations in tubulin phenocopy axon crossing defects of Netrin-1 and DCC mutants. Microtubule stabilization is required for attractive guidance cue response. The C-terminal tails of microtubules can be post-translationally modified. Post-translational modifications (PTMs) help control the microtubule cytoskeleton.

Methods

We measured polyglutamylation in cultured primary mouse cortical neurons before and after Netrin-1 stimulation. We used immunohistochemistry to measure how Netrin-1 stimulation alters microtubule-associated protein localization. Next, we manipulated TTLL1 to determine if Netrin-1-induced axon growth and MAP localization depend on polyglutamylation levels.

Results

In this study, we investigated if Netrin-1 signaling alters microtubule PTMs in the axon. We found that microtubule polyglutamylation increases after Netrin-1 stimulation. This change in polyglutamylation is necessary for Netrin-1-induced axonal growth rate increases. We next determined that MAP1B and DCX localization changes in response to Netrin-1. These proteins can both stabilize the microtubule cytoskeleton and may be responsible for Netrin-1-induced growth response in neurons. The changes in DCX and MAP1B depend on TTLL1, a protein responsible for microtubule polyglutamylation.
Identifying atheroprotective fruits and vegetables by Mendelian Randomization analysis
Authors: Yang Shenji , Cao Zhikang , Liu Huidong , Li Zhipeng , Nie Shaoping , Xie Mingyong
Published: October 2024

Background

Fruits and vegetables (FVs) are widely believed to mitigate the risk of atherosclerosis (AS). However, the causal relationships between specific FVs and AS risk factors remain unclear.

Methods

This study performed two-sample Mendelian Randomization (MR) analysis to infer the causality of the intake of 28 kinds of FVs with AS, as well as its risk factors including blood low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and C-reactive protein (CRP). GWAS genetic data for these exposures and outcomes were extracted from the IEU open GWAS project. Heterogeneity was evaluated using both Inverse Variance Weighted (IVW) and MR-Egger methods. MR-Egger regression was specifically deployed to detect potential pleiotropy. Furthermore, a “leave-one-out” sensitivity analysis was conducted to determine the impact of each individual single nucleotide polymorphism (SNP) on the combined outcome.

Results

The analysis confirms a causal relationship between total fruit consumption and reduced levels of LDL-C (OR = 0.911, p = 0.007) and CRP (OR = 0.868, p = 0.008). Similarly, total vegetable intake is also causally associated with a reduction in CRP levels (OR = 0.858, p = 0.018). Specifically, garlic intake exhibits the most significant causal relationship with reduced risk of AS (OR = 0.985, p = 0.036) and also causally associated with lower levels of LDL-C and TG. Berry (OR = 0.929, p = 0.010) and potato (OR = 0.957, p = 0.020) intake both display a significant causal negative association with TG levels, while peach/nectarine consumption is significantly associated with reduced CRP levels (OR = 0.913, p = 0.010).

Conclusion

This is the first MR study that systemically examined the causality between commonly consumed FVs and AS. Our findings highlight the atheroprotective effects of various FVs, particularly garlic, on cardiovascular health and the importance of tailored nutritional recommendations to prevent AS.
Subcutaneous adipose tissue measured by computed tomography could be an independent predictor for early outcomes of patients with severe COVID-19
Authors: Zhou Weijian , Shen Wenqi , Ni Jiajing , Xu Kaiwei , Xu Liu , Chen Chunqu , Wu Ruoyu , Hu Guotian , Wang Jianhua
Published: October 2024

Background

Patients with severe Coronavirus Disease 2019 (COVID-19) can experience protein loss due to the inflammatory response and energy consumption, impairing immune function. The presence of excessive visceral and heart fat leads to chronic long-term inflammation that can adversely affect immune function and, thus, outcomes for these patients. We aimed to explore the roles of prognostic nutrition index (PNI) and quantitative fat assessment based on computed tomography (CT) scans in predicting the outcomes of patients with severe COVID-19.

Methods

A total of 130 patients with severe COVID-19 who were treated between December 1, 2022, and February 28, 2023, were retrospectively enrolled. The patients were divided into survival and death groups. Data on chest CT examinations following admission were collected to measure cardiac adipose tissue (CAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) and to analyze the CT score of pulmonary lesions. Clinical information and laboratory examination data were collected. Univariate and multivariate logistic regression analyses were used to explore the risk factors associated with death, and several multivariate logistic regression models were established.

Results

Of the 130 patients included in the study (median age, 80.5 years; males, 32%), 68 patients died and 62 patients survived. PNI showed a strong association with the outcome of severe COVID-19 (p < 0.001). Among each part of the fat volume obtained based on a CT scan, SAT showed a significant association with the mortality of severe COVID-19 patients (p = 0.007). However, VAT and CAT were not significantly correlated with the death of patients. In the multivariate models, SAT had a higher predictive value than PNI; the area under the curve (AUC) of SAT was 0.844, which was higher than that of PNI (AUC = 0.833), but in the model of the combination of the two indexes, the prediction did not improve (AUC = 0.830), and SAT lost its significance (p = 0.069).

Conclusion

Subcutaneous adipose tissue measured by computed tomography and PNI were found to be independent predictors of death in patients with severe COVID-19.
Associations between nine dietary minerals intake and all-cause mortality in individuals with atherosclerotic cardiovascular disease
Authors: Duan Chenglin , Lv Meng , Shou Xintian , Chen Zizhen , Luan Yujie , Hu Yuanhui
Published: October 2024

Background

Varied intake of dietary minerals critically affects cardiovascular health. This study examines the associations of nine dietary minerals intake with all-cause mortality in atherosclerotic cardiovascular diseases (ASCVDs).

Methods

This study analyzed 4,125 individuals with ASCVD from the National Health and Nutrition Examination Survey, employing Kaplan–Meier survival analyses, weighted Cox models, and restricted cubic splines to assess linear and nonlinear relationships between dietary minerals intake and all-cause mortality. Associations across different body mass index (BMI) categories were also evaluated separately.

Results

Over 6.25 years of median follow-up, 1,582 deaths were documented. Adjusted for potential covariates, results show a negative linear correlation between dietary magnesium intake and all-cause mortality (p for trend <0.001). Compared to the lowest quartile, all-cause mortality risk in the highest quartile was found to be 0.63 (95% CI 0.49–0.81). The associations between intake of the other eight dietary minerals and all-cause mortality were not robust. BMI significantly influenced the links between dietary minerals intake and all-cause mortality (p for interaction <0.05). Across BMI categories, significant negative associations were found between intake of magnesium, phosphorus, potassium, sodium, and copper and all-cause mortality in underweight or normal weight groups. In overweight individuals, intake of calcium, iron, magnesium, and potassium was negatively linked to all-cause mortality. For obese groups, sodium intake negatively affected all-cause mortality (p for trend <0.001).

Conclusion

Unlike other dietary minerals, increased magnesium intake significantly reduced all-cause mortality risk in ASCVD. BMI influenced the associations between dietary minerals intake and all-cause mortality.
Nutritional composition analysis in food images: an innovative Swin Transformer approach
Authors: Wang Hui , Tian Haixia , Ju Ronghui , Ma Liyan , Yang Ling , Chen Jingyao , Liu Feng
Published: October 2024

Accurate recognition of nutritional components in food is crucial for dietary management and health monitoring. Current methods often rely on traditional chemical analysis techniques, which are time-consuming, require destructive sampling, and are not suitable for large-scale or real-time applications. Therefore, there is a pressing need for efficient, non-destructive, and accurate methods to identify and quantify nutrients in food. In this study, we propose a novel deep learning model that integrates EfficientNet, Swin Transformer, and Feature Pyramid Network (FPN) to enhance the accuracy and efficiency of food nutrient recognition. Our model combines the strengths of EfficientNet for feature extraction, Swin Transformer for capturing long-range dependencies, and FPN for multi-scale feature fusion. Experimental results demonstrate that our model significantly outperforms existing methods. On the Nutrition5k dataset, it achieves a Top-1 accuracy of 79.50% and a Mean Absolute Percentage Error (MAPE) for calorie prediction of 14.72%. On the ChinaMartFood109 dataset, the model achieves a Top-1 accuracy of 80.25% and a calorie MAPE of 15.21%. These results highlight the model's robustness and adaptability across diverse food images, providing a reliable and efficient tool for rapid, non-destructive nutrient detection. This advancement supports better dietary management and enhances the understanding of food nutrition, potentially leading to more effective health monitoring applications.
Free and bound phenolic profiles and antioxidant ability of eleven marine macroalgae from the South China Sea
Authors: Peng Ziting , Wu Yujiao , Fu Qiongyao , Xiao Juan
Published: October 2024

Marine macroalgae are of broad interest because of their abundant bioactive phenolic compounds. However, only a few previous studies have focused on bound phenolic compounds. In this study, there were significant differences in total phenolic content, total phlorotannin content, total flavonoid content, and antioxidant ability in free and bound forms, as well as in their bound-to-free ratios, among 11 marine macroalgal species from the South China Sea. Padina gymnospora had the highest total phenolic content of free fractions, and total phlorotannin content, total flavonoid content, and antioxidant activity of free fractions. Sargassum thunbergii had the highest total phlorotannin content of bound fractions, whereas Sargassum oligocystum had the highest total flavonoid content and total phenolic content of bound fractions. Moreover, 15 phenolic acids, 35 flavonoids, 2 stilbenes, 3 bromophenols, and 3 phlorotannins were characterized and quantified using ultra-high-performance liquid chromatography with Xevo triple quadrupole mass spectrometry, and 42 phenolic compounds were reported in the bound fractions of seaweeds for the first time. Among the species, the number and amount of free and bound phenolic compounds varied greatly and the main components were different. Padina gymnospora had the largest total phenolic number, while Turbinaria ornata showed the highest total phenolic amount. Coutaric acid and diosmetin were dominant in Sargassum polycystum, and hinokiflavone was dominant in Caulerpa lentillifera, and cyanidin was dominant in the other seaweeds. Hierarchical cluster analysis was used to divide the seaweed species into seven groups. This study revealed that Padina gymnospora, Sargassum thunbergii, Turbinaria ornata, and Sargassum oligocystum are promising functional food resources.
Research on therapeutic clinical trials including immunotherapy in triple-negative breast cancer: a bibliometric analysis
Authors: Xu Qi , Feng Xiaoyu , Qin Siyuan , Hong Yu , Cui Rui , Liang Jia , Xiao Zhuya , Li Yuan
Published: October 2024

Background

Breast cancer, particularly triple-negative (TNBC), is a leading malignancy with aggressive traits and high metastasis rates. Clinical trial is an important tool for optimizing therapeutic strategies in the evaluation of the safety and efficacy for TNBC. Our bibliometric study of TNBC clinical trials aims to assess therapeutic strategies, identify trends, and explore advancements in treatment. We focus on mapping knowledge development, including key research entities and topics, and analyzing research trends and emerging methods. This analysis intends to inform future research, especially in personalized and precision medicine for TNBC.

Methods

We selected publications on clinical trials for the treatment of TNBC from 1997 to 2024 in the Web of Science Core Collection (WoSCC). After an initial screening, we downloaded key data including titles, publication years, authors, countries, institutional affiliations, journals, keywords, and abstracts, and saved them in BibTex format. We then conducted a bibliometric analysis using Bibliometrix in R and VOSviewer to illustrate the prospects, highlights, and trends of TNBC treatment options. Furthermore, to emphasize the hot topics in TNBC treatment strategies, we performed a bibliometric analysis of immunotherapy using the same approach.

Results

1907 publications were included, most of which were from China, Italy, and the United States. The number of annual publications has increased dramatically since 2010. The focus of TNBC clinical trial research has shifted from understanding the biology, such as breast cancer subtyping and genotyping, to novel therapeutic approaches. The major advancement in clinical trials is the switch from late-stage palliative treatment to early preoperative neoadjuvant therapy, as more TNBC cases are discovered at an early stage. Immunotherapy is also highlighted with additional alternatives for advanced or metastasized TNBC, such as targeted inhibitors with unusual mutation rates and antibody drug conjugates (ADC).

Conclusions

This investigation made it apparent how immunotherapy has recently made major advancements in TNBC treatment plans and how ADCs, or targeted therapies, are currently popular for TNBC. By identifying significant papers, comprehending trending topics, and collaborating across multiple disciplines, this study may accelerate research on TNBC therapy options.
Comparison of the diagnostic efficacy between imaging features and iodine density values for predicting microvascular invasion in hepatocellular carcinoma
Authors: Lv Jian , Li Xin , Mu Ronghua , Zheng Wei , Yang Peng , Huang Bingqin , Liu Fuzhen , Liu Xiaomin , Song Zhixuan , Qin Xiaoyan , Zhu Xiqi
Published: October 2024

Background

In recent years, studies have confirmed the predictive capability of spectral computer tomography (CT) in determining microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Discrepancies in the predicted MVI values between conventional CT imaging features and spectral CT parameters necessitate additional validation.

Methods

In this retrospective study, 105 cases of small HCC were reviewed, and participants were divided into MVI-negative (n=53, Male:48 (90.57%); mean age, 59.40 ± 11.79 years) and MVI-positive (n=52, Male:50(96.15%); mean age, 58.74 ± 9.21 years) groups using pathological results. Imaging features and iodine density (ID) obtained from three-phase enhancement spectral CT scans were gathered from all participants. The study evaluated differences in imaging features and ID values of HCC between two groups, assessing their diagnostic accuracy in predicting MVI occurrence in HCC patients. Furthermore, the diagnostic efficacy of imaging features and ID in predicting MVI was compared.

Results

Significant differences were noted in the presence of mosaic architecture, nodule-in-nodule architecture, and corona enhancement between the groups, all with p-values < 0.001. There were also notable disparities in IDs between the two groups across the arterial phase, portal phase, and delayed phases, all with p-values < 0.001. The imaging features of nodule-in-nodule architecture, corona enhancement, and nonsmooth tumor margin demonstrate significant diagnostic efficacy, with area under the curve (AUC) of 0.761, 0.742, and 0.752, respectively. In spectral CT analysis, the arterial, portal, and delayed phase IDs exhibit remarkable diagnostic accuracy in detecting MVI, with AUCs of 0.821, 0.832, and 0.802, respectively. Furthermore, the combined models of imaging features, ID, and imaging features with ID reveal substantial predictive capabilities, with AUCs of 0.846, 0.872, and 0.904, respectively. DeLong test results indicated no statistically significant differences between imaging features and IDs.

Conclusions

Substantial differences were noted in imaging features and ID between the MVI-negative and MVI-positive groups in this study. The ID and imaging features exhibited a robust diagnostic precision in predicting MVI. Additionally, our results suggest that both imaging features and ID showed similar predictive efficacy for MVI.
Case report: 18F-FDG PET/CT in pulmonary enteric adenocarcinoma
Authors: Luo Zhe-Huang , Luo Xiao-Yan , Luo Xiu-Qin , Jin Ai-Fang , Zeng Qing-Yun
Published: October 2024

Pulmonary enteric adenocarcinoma (PEAC), an uncommon variant of lung cancer, presents significant diagnostic challenges due to its overlapping characteristics with colorectal adenocarcinomas. We present a case of a 55-year-old non-smoking female patient diagnosed with PEAC. The patient’s initial symptoms included fever, cough, and sputum production, with air space consolidation on CT, leading to an initial diagnosis of pneumonia. Sputum culture after admission showed no growth of bacteria and fungi. Anti-inflammatory therapy was not ideal. Subsequent bronchoscopy with endobronchial ultrasound and biopsy confirmed the diagnosis of PEAC. Gastroscopy and colonoscopy yielded negative results, and a PET/CT scan revealed an FDG-avid lesion in the right middle lobe, with no other significant hypermetabolic gastrointestinal lesions, thereby excluding an extrapulmonary primary gastrointestinal malignancy. The patient was ultimately staged as PEAC (T4N1M0, stage IIIb). She declined anti-tumor therapy and experienced clinical deterioration during follow-up. This case report expands the radiological spectrum of PEAC, adds to the limited literature, and emphasizes the role of 18F-FDG PET/CT in diagnosing such diseases. It also underscores the importance of a multidisciplinary approach in the management of PEAC.
AML-VAC-XS15-01: protocol of a first-in-human clinical trial to evaluate the safety, tolerability and preliminary efficacy of a multi-peptide vaccine based on leukemia stem cell antigens in acute myeloid leukemia patients
Authors: Jung Susanne , Nelde Annika , Maringer Yacine , Denk Monika , Zieschang Lisa , Kammer Christine , Özbek Melek , Martus Peter , Hackenbruch Christopher , Englisch Alexander , Heitmann Jonas S. , Salih Helmut R. , Walz Juliane S.
Published: October 2024

Introduction

Acute myeloid leukemia (AML) has a dismal prognosis, mostly due to minimal residual disease-driven relapse, making an elimination of persisting therapy-resistant leukemia progenitor/stem cells (LPCs) the main goal for novel therapies. Peptide-based immunotherapy offers a low-side-effect approach aiming to induce T cell responses directed against human leukocyte antigen (HLA) presented tumor antigens on malignant cells by therapeutic vaccination. Mass spectrometry-based analysis of the naturally presented immunopeptidome of primary enriched LPC and AML samples enabled the selection of antigens exclusively expressed on LPC/AML cells, which showed de novo induction and spontaneous memory T cell responses in AML patients, and whose presentation and memory T cell recognition was associated with improved disease outcome.

Methods

Based on these data the therapeutic vaccine AML-VAC-XS15 was designed, comprising two mutated HLA class I-restricted peptides from the common AML-specific mutation in NPM1 and seven HLA class II-restricted peptides (six non-mutated high-frequent AML/LPC-associated antigens and one mutated peptide from the AML-specific mutation R140Q in IDH2), adjuvanted with the toll like receptor 1/2 ligand XS15 and emulsified in Montanide ISA 51 VG. A phase I open label clinical trial investigating AML-VAC-XS15 was designed, recruiting AML patients in complete cytological remission (CR) or CR with incomplete blood count recovery. Patients are vaccinated twice with a six-week interval, with an optional booster vaccination four months after 2nd vaccination, and are then followed up for two years. The trial’s primary objectives are the assessment of the vaccine’s immunogenicity, safety and toxicity, secondary objectives include characterization of vaccine-induced T cell responses and assessment of preliminary clinical efficacy.

Ethics and dissemination

The AML-VAC-XS15-01 study was approved by the Ethics Committee of the Bavarian State medical association and the Paul-Ehrlich Institut (P01392). Clinical trial results will be published in peer-reviewed journals.
Lung bronchiectasisas a paradigm of the interplay between infection and colonization on plastic modulation of the pre-metastatic niche
Authors: Pisanu Lucrezia , Mucaj Klodjana , Conio Valentina , Bertuccio Francesco , Giana Ilaria , Arlando Lorenzo , Russo Marianna , Montini Simone , Bortolotto Chandra , Corsico Angelo Guido , Stella Giulia Maria
Published: October 2024

The lungs are most often a preferential target organ for malignant spreading and growth. It is well known that chronic parenchymal inflammation and prolonged injuries represents an independent risk factor for cancer onset. Growing evidence supports the implication of lung microbiota in the pathogenesis of lung cancer. However, the full interplay between chronic inflammation, bacterial colonization, pathologic condition as bronchiectasis and malignant growth deserves better clarification. We here aim at presenting and analyzing original data and discussing the state-of-the-art on the knowledge regarding how this complex milieu acts on the plasticity of the lung pre-metastatic niche to point out the rationale for early diagnosis and therapeutic targeting.
Delta-CT radiomics based model for predicting postoperative anastomotic leakage following radical resection of esophageal squamous cell carcinoma
Authors: Li Huantian , Zhang Linjun , Song Lina , Wang Yong , Song Ping , Ye Yingjian , Li Xiumei , An Peng
Published: October 2024

Objective

To predict postoperative anastomotic leakage (AL) following radical resection of esophageal squamous cell carcinoma (ESCC) based on clinical data and preoperative enhanced Computed tomography(CT) radiomics of the esophagus.

Method

We retrospectively analyzed the clinicopathological and radiological data of 213 patients with ESCC who received radical resection at Xiangyang No.1 People’s Hospital from July 2011 to February 2024. 3D slicer software was used in combination with Lasso extraction and 10-fold cross-validation to extract texture parameters from contrast-enhanced CT images and generate Delta-Radscores. Several models were built using logistic regression to predict postoperative AL in ESCC.

Results

In the training set, the univariate analysis confirmed that duration of surgery, surgical method, delta radscore 1, delta radscore 2, contrast enhancement patterns, peripheral lymph node metastasis, post thoracotomy pulmonary infection(PTPI), and hot pot were risk factors for ESCC-AL (P<0.05 for both). The multivariate analysis showed that delta radscore 1, delta radscore 2, PTPI, and hot pot were independent risk factors for AL (P<0.05 for all). These results were verified by the XGboost machine learning model. The combinational model based on all of the above risk factors [AUC 0.900, OR 0.0282, 95%CI 0.841-0.943] outperformed either the clinical model[AUC 0.759, OR 0.0392, 95%0.683-0.825,P<0.05] or the imaging model[AUC 0.869, OR 0.0335, 95%0.804-0.918,P=0.1277] alone in predictive efficacy. The decision curve proved that the combinational model had a higher clinical net benefit. The nomogram generated via the combinational model simplified the predictive process. The same predictions were verified in the testing set.

Conclusion

Delta radscore 1, delta radscore 2, PTPI, and hot pot were related to ESCC-AL. The novel nomogram created using enhanced CT radiomics informed perioperative management and improved the survival quality of ESCC patients.
Perioperative use of enteral nutrition with ω-3 polyunsaturated fatty acid in patients with gastric cancer: a meta-analysis
Authors: Fu Tingting , Hu Wenjun , Chang Lu , Duan Jingli
Published: October 2024

Objectives

To systematically evaluate the efficacy and safety of enteral nutrition with ω-3 polyunsaturated fatty acid preparations or standard enteral nutrition preparations used in patients with gastric cancer during perioperative period, and to provide reference for clinical rational drug use.

Methods

Pubmed, EMbase, The Cochrane Library, CNKI and Wanfang Medical databases were searched by computer to collect relevant literature. The search period was from the establishment of the database to August 1, 2024. Meta-analysis was performed using Revman5.4 software after two researchers independently screened literature, extracted data, and evaluated the risk of bias in included studies.

Results

A total of 20 randomized controlled studies were included. The Meta results showed that there was no statistical difference in mortality between the enteral nutrition with ω-3 polyunsaturated fatty acid group and the control group (RR = 0.46, P = 0.17). However, the IEN group demonstrated superior advantages in reducing infection complications (RR = 0.81, P = 0.05) and wound infection (RR = 0.61, P = 0.04) among gastric cancer patients, as well as improving immune-related indicators (including IgG, IgA, IgM, CD4, and CD4/CD8), inflammation-related markers (including CRP, IL-1β, and IL-6), and nutritional indicators (including Total protein, Albumin, and Transferrin).

Conclusion

enteral nutrition with ω-3 polyunsaturated fatty acid preparation has advantages in the efficacy and safety of perioperative nutritional therapy in patients with gastric cancer, and can be used as a clinical choice. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
Clinical characteristics and factors associated with mucus plugs under bronchoscopy in children hospitalized for acute asthma attack
Authors: Han Peng , Jiao Anxia , Yin Ju , Zou Huimin , Liu Yuliang , Li Zheng , Wang Quan , Wu Jie , Shen Kunling
Published: October 2024

Objective

To describe clinical characteristics of hospitalized children with acute asthma attacks complicated with mucus plugs and to investigate the factors associated with mucus plugs in asthma children.

Methods

This retrospective study analyzed hospitalized children and adolescents with acute asthma attacks from January 2016 to December 2021. The demographic information and characteristics were collected. Subjects were categorized into the mucus plug group and the control group based on the bronchoalveolar lavage results. The Logistic regression analyses were utilized to assess the relative factors associated with mucus plugs. All data were analyzed using SPSS 22.0.

Results

This study included 242 individuals. Out of the 151 subjects who underwent bronchoscopy, 62.9% were classified in the mucus plug group and 37.1% in the control group. The subjects with dyspnea had a higher proportion in the mucus plug group (52.6% vs. 26.8%). The serum total IgE level of the mucus plug group was lower than the control group. The proportion of subjects who were diagnosed with asthma for the first time during hospitalization (87.4% vs. 76.8%) and combined with respiratory infection (91.6% vs. 82.1%) in the mucus plug group might be higher than that in the control group. More subjects in the mucus plug group were administered systemic glucocorticoid, magnesium sulfate, aminophylline, and mucolytic drugs after hospitalization. In multivariable analysis, diagnosed with asthma for the first time during hospitalization (OR = 4.404; 1.101–17.614), dyspnea (OR = 4.039; 1.306–12.496), and cesarean (OR = 0.274; 0.092–0.812) might be associated with mucus plug in children hospitalized for an acute asthma attack.

Suggests

While our retrospective study suggests that some clinical features of children hospitalized with asthma who have mucus plugs differ from those without, further studies are required.
Psychiatric disorders associated with fluoroquinolones: a pharmacovigilance analysis of the FDA adverse event reporting system database
Authors: Xie Wen-Long , Ge Meng-Lan , Chen Dan , Chen Guo-Qing , Mei Yuan-Xi , Lai Yong-Ji
Published: October 2024

Background

Fluoroquinolones are broad-spectrum antibiotics with significant antimicrobial activity. Despite their therapeutic benefits, they are associated with a range of adverse drug reactions (ADRs), particularly those affecting the central nervous system (CNS). This study aimed to analyze the psychiatric ADRs linked to fluoroquinolones using data from the FDA Adverse Event Reporting System (FAERS) database.

Methods

A retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q4 2023. The data processing phase involved the FDA-recommended deduplication method, and ADRs were classified according to Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was performed using the reporting odds ratio (ROR), and statistical significance was assessed using the Chi-square test or Fisher’s exact test.

Results

The study identified 84,777 reports associated with fluoroquinolones, with 359,480 Preferred Terms-annotated entries, 27,816 of these reports were psychiatric ADRs. Mood disorders were the most frequently reported, including anxiety, depression, and delirium, with some reports escalating to suicidal ideation and behaviors. The Standardized MedDRA Query classification system was used to categorize these ADRs into Depression, Suicide/self-injury, Psychosis and psychotic disorders, and Non-infectious encephalopathy/delirium. Ciprofloxacin was most frequently linked to depression and suicidal ideation, while moxifloxacin showed a robust correlation with delirium. The risk of psychiatric ADRs varied by age group, with affective disorders more prevalent in adults under 65 and psychosis and delirium in those over 65.

Conclusion

Fluoroquinolones are associated with a range of psychiatric ADRs, with notable differences between the drugs in the class. The study highlights the need for caution in prescribing fluoroquinolones, particularly for patients with pre-existing mental health conditions or those in higher risk age groups. The findings also underscore the importance of considering age-specific preventive strategies when administering these antibiotics.
Mitochondrial proteins as therapeutic targets in diabetic ketoacidosis: evidence from Mendelian randomization analysis
Authors: Xie Ruiqiang , Xie Hongyan , Gao Hong , Xie Chunguang , Yuan Haipo , Feng Zhijun
Published: October 2024

Introduction

Diabetic ketoacidosis (DKA) is a severe and potentially fatal acute complication in diabetic patients, commonly occurring in type 1 diabetes (T1D) but also seen in type 2 diabetes (T2D). The pathogenesis of DKA involves complex physiological processes that are not fully understood, especially the role of mitochondria. Mitochondria, known as the powerhouse of cells, plays a crucial role in oxidative phosphorylation and ATP production, which is vital in various metabolic diseases, including diabetes. However, the exact causal relationship between mitochondrial dysfunction and DKA remains unclear.

Methods

This study employed Mendelian randomization (MR) analysis and protein-protein interaction (PPI) networks to systematically explore the causal relationships between mitochondrial DNA copy number (mtDNA-CN) and specific mitochondrial proteins with DKA. We used bidirectional MR analysis and genome-wide association study (GWAS) data from openGWAS database to investigate the causal effects of mtDNA-CN and 64 mitochondrial-related proteins on DKA and its subtypes (T1DKA, T2DKA, unspecified-DKA).

Results

The study revealed that increased mtDNA-CN significantly reduces the risk of DKA, whereas the effect of DKA on mtDNA-CN was not significant. Mitochondrial-related proteins such as MRPL32, MRPL33, COX5B, DNAJC19, and NDUFB8 showed a negative causal relationship with DKA, indicating their potential protective roles. Conversely, ATP5F1B and COX4I2 have a positive causal relationship with DKA, indicating that excessive ATP production in diabetic patients may be detrimental to health and increase the risk of severe complications such as DKA.

Discussion

The results emphasize the necessity of protecting mitochondrial function in order to reduce the risk of DKA. The study offers novel perspectives on the molecular pathways involved in DKA, emphasizing the critical functions of mt-DNA and distinct proteins. These evidences not only enhance our comprehension of the implications of mitochondrial dysfunction in diabetes-related complications but also identify potential therapeutic targets for individualized treatment approaches, thereby making a substantial contribution to clinical care and public health initiatives.
Feature analysis of 5G traffic data based on visibility graph
Authors: Sun Ke , Xu Jiwei
Published: October 2024

Introduction

As 5G networks become widespread and their application scenarios expand, massive amounts of traffic data are continuously generated. Properly analyzing this data is crucial for enhancing 5G services.

Methods

This paper uses the visibility graph method to convert 5G traffic data into a visibility graph network, conducting a feature analysis of the 5G traffic data. Using the AfreecaTV dataset as the research object, this paper constructs visibility networks at different scales and observes the evolution of degree distribution with varying data volumes. The paper employs the Hurst index to evaluate the 5G traffic network and uses community detection to study the networks converted from 5G traffic data of different applications.

Results

Experimental results reveal significant differences in node degree distribution and topological structures of 5G traffic data across different application scenarios, such as star structures and multiple subnetwork structures. It is found that the node degree distribution of 5G traffic networks exhibits heterogeneity, reflecting the uneven growth of node degrees during network expansion. The Hurst index analysis discovers that the 5G traffic network retains the long-term dependence and trends of the original data. Through community detection, it is observed that networks converted from 5G traffic data of different applications exhibit diverse community structures, such as high centrality nodes, star-like community structures, modularity, and multilayer characteristics.

Discussion

These findings indicate that 5G traffic networks in different application scenarios exhibit complex and diverse characteristics. The heterogeneity of node degree distribution and differences in topological structures reflect the imbalance in node connection methods during network expansion. The results of the Hurst index show that the 5G traffic network inherits the long-term dependence of the original data, providing a basis for analyzing the dynamic characteristics of the network. The diverse community structures reveal the inherent modularity and hierarchy of the network, which helps to understand the performance and optimization directions of 5G networks in different applications.