bluuebunny/crossref_metadata_2025_split huggingface dataset:
The adjuvant BcfA activates antigen presenting cells through TLR4 and supports TFH and TH1 while attenuating TH2 gene programming
Authors: Shamseldin Mohamed M. , Read Kaitlin A. , Hall Jesse M. , Tuazon Jasmine A. , Brown Jessica M. , Guo Myra , Gupta Yash A. , Deora Rajendar , Oestreich Kenneth J. , Dubey Purnima 
Published: August 2024

IntroductionAdjuvants added to subunit vaccines augment antigen-specific immune responses. One mechanism of adjuvant action is activation of pattern recognition receptors (PRRs) on innate immune cells. Bordetella colonization factor A (BcfA); an outer membrane protein with adjuvant function, activates TH1/TH17-polarized immune responses to protein antigens from Bordetella pertussis and SARS CoV-2. Unlike other adjuvants, BcfA does not elicit a TH2 response.MethodsTo understand the mechanism of BcfA-driven TH1/TH17 vs. TH2 activation, we screened PRRs to identify pathways activated by BcfA. We then tested the role of this receptor in the BcfA-mediated activation of bone marrow-derived dendritic cells (BMDCs) using mice with germline deletion of TLR4 to quantify upregulation of costimulatory molecule expression and cytokine production in vitro and in vivo. Activity was also tested on human PBMCs.ResultsPRR screening showed that BcfA activates antigen presenting cells through murine TLR4. BcfA-treated WT BMDCs upregulated expression of the costimulatory molecules CD40, CD80, and CD86 and produced IL-6, IL-12/23 p40, and TNF-α while TLR4 KO BMDCs were not activated. Furthermore, human PBMCs stimulated with BcfA produced IL-6. BcfA-stimulated murine BMDCs also exhibited increased uptake of the antigen DQ-OVA, supporting a role for BcfA in improving antigen presentation to T cells. BcfA further activated APCs in murine lungs. Using an in vitro TH cell polarization system, we found that BcfA-stimulated BMDC supernatant supported TFH and TH1 while suppressing TH2 gene programming.ConclusionsOverall, these data provide mechanistic understanding of how this novel adjuvant activates immune responses.
Identification of cancer stem cell-related genes through single cells and machine learning for predicting prostate cancer prognosis and immunotherapy
Authors: Wang YaXuan , Ma Li , He Jiaxin , Gu HaiJuan , Zhu HaiXia 
Published: August 2024

BackgroundCancer stem cells (CSCs) are a subset of cells within tumors that possess the unique ability to self-renew and give rise to diverse tumor cells. These cells are crucial in driving tumor metastasis, recurrence, and resistance to treatment. The objective of this study was to pinpoint the essential regulatory genes associated with CSCs in prostate adenocarcinoma (PRAD) and assess their potential significance in the diagnosis, prognosis, and immunotherapy of patients with PRAD.MethodThe study utilized single-cell analysis techniques to identify stem cell-related genes and evaluate their significance in relation to patient prognosis and immunotherapy in PRAD through cluster analysis. By utilizing diverse datasets and employing various machine learning methods for clustering, diagnostic models for PRAD were developed and validated. The random forest algorithm pinpointed HSPE1 as the most crucial prognostic gene among the stem cell-related genes. Furthermore, the study delved into the association between HSPE1 and immune infiltration, and employed molecular docking to investigate the relationship between HSPE1 and its associated compounds. Immunofluorescence staining analysis of 60 PRAD tissue samples confirmed the expression of HSPE1 and its correlation with patient prognosis in PRAD.ResultThis study identified 15 crucial stem cell-related genes through single-cell analysis, highlighting their importance in diagnosing, prognosticating, and potentially treating PRAD patients. HSPE1 was specifically linked to PRAD prognosis and response to immunotherapy, with experimental data supporting its upregulation in PRAD and association with poorer prognosis.ConclusionOverall, our findings underscore the significant role of stem cell-related genes in PRAD and unveil HSPE1 as a novel target related to stem cell.
Multi-omics analysis reveals the landscape of tumor microenvironments in left-sided and right-sided colon cancer
Authors: Liu Dongfang , Li Chen , Deng Zenghua , Luo Nan , Li Wenxia , Hu Wenzhe , Li Xiang , Qiu Zichao , Chen Jianfei , Peng Jirun 
Published: August 2024

BackgroundDistinct clinical features and molecular characteristics of left-sided colon cancer (LCC) and right-sided colon cancer (RCC) suggest significant variations in their tumor microenvironments (TME). These differences can impact the efficacy of immunotherapy, making it essential to investigate and understand these disparities.MethodsWe conducted a multi-omics analysis, including bulk RNA sequencing (bulk RNA-seq), single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing (WES), to investigate the constituents and characteristic differences of the tumor microenvironment (TME) in left-sided colon cancer (LCC) and right-sided colon cancer (RCC).ResultDeconvolution algorithms revealed significant differences in infiltrated immune cells between left-sided colon cancer (LCC) and right-sided colon cancer (RCC), including dendritic cells, neutrophils, natural killer (NK) cells, CD4 and CD8 T cells, and M1 macrophages (P &lt; 0.05). Notably, whole-exome sequencing (WES) data analysis showed a significantly higher mutation frequency in RCC compared to LCC (82,187/162 versus 18,726/115, P &lt; 0.01). Single-cell analysis identified predominant tumor cell subclusters in RCC characterized by heightened proliferative potential and increased expression of major histocompatibility complex class I molecules. However, the main CD8 + T cell subpopulations in RCC exhibited a highly differentiated state, marked by T cell exhaustion and recent activation, defined as tumor-specific cytotoxic T lymphocytes (CTLs). Immunofluorescence and flow cytometry results confirmed this trend. Additionally, intercellular communication analysis demonstrated a greater quantity and intensity of interactions between tumor-specific CTLs and tumor cells in RCC.ConclusionRCC patients with an abundance of tumor-specific cytotoxic T lymphocytes (CTLs) and increased immunogenicity of tumor cells in the TME may be better candidates for immune checkpoint inhibitor therapy.
Research trends and hotspots on osteoporosis: a decade-long bibliometric and visualization analysis from 2014 to 2023
Authors: Zhang Song , Liu Ye , Yu Weifeng , Gu Xiyao 
Published: August 2024

BackgroundOsteoporosis is characterized by diminished bone density and quality, compromised bone microstructure, and increased bone fragility, culminating in a heightened risk of fracture. Relatively few attempts have been made to survey the breadth of osteoporosis research using bibliometric approaches. This study aims to delineate the current landscape of osteoporosis research, offering clarity and visualization, while also identifying potential future directions for investigation.MethodsWe retrieved and filtered articles and reviews pertaining to osteoporosis from the Web of Science Core Collection database, specifically the Science Citation Index Expanded (SCI-E) edition, spanning the years 2014 to 2023. Informatics tools such as CiteSpace and VOSviewer were employed to dissect the intellectual framework, discern trends, and pinpoint focal points of interest within osteoporosis research.ResultsOur dataset comprised 33,928 osteoporosis-related publications, with a notable surge in annual publication numbers throughout the last decade. China and the United States lead in terms of research output. The University of California System contributed substantially to this body of work, with Amgen demonstrating the highest degree of centrality within the network. Cooper Cyrus emerged as a pivotal figure in the field. An analysis of highly-cited studies, co-citation networks, and keyword co-occurrence revealed that recent years have predominantly concentrated on elucidating mechanisms underlying osteoporosis, as well as its diagnosis, prevention, and treatment strategies. Burst detection analyses of citations and keywords highlighted osteoblasts, sarcopenia, gut microbiota, and denosumab as contemporary hotspots within osteoporosis research.ConclusionThis bibliometric analysis has provided a visual representation of the fundamental knowledge structure, prevailing trends, and key focal areas within osteoporosis research. The identification of osteoblasts, sarcopenia, gut microbiota, and denosumab as current hotspots may guide future research endeavors. Continued efforts directed at understanding the mechanisms, fracture outcomes, diagnostics, and therapeutics related to osteoporosis are anticipated to deepen our comprehension of this complex disease.
Early detection of deteriorating patients in general wards through continuous contactless vital signs monitoring
Authors: Yadav Ambuj , Dandu Himanshu , Parchani Gaurav , Chokalingam Kumar , Kadambi Pooja , Mishra Rajesh , Jahan Ahsina , Teboul Jean-Louis , Latour Jos M. 
Published: August 2024

ObjectiveTo assess the efficacy of continuous contactless vital signs monitoring with an automated Early Warning System (EWS) in detecting clinical deterioration among patients in general wards.MethodsA prospective observational cohort study was conducted in the medical unit of a tertiary care hospital in India, involving 706 patients over 84,448 monitoring hours. The study used a contactless ballistocardiography system (Dozee system) to continuously monitor heart rate, respiratory rate, and blood pressure. The study assessed total, mean, and median alerts at 24, 48, 72, 96, 120 h, and length of stay (LOS) before patient deterioration or discharge. It analyzed alert sensitivity and specificity, average time from initial alert to deterioration, and healthcare practitioners (HCP) activity. Study was registered with the Clinical Trials Registry-India CTRI/2022/10/046404.ResultsOut of 706 patients, 33 (5%) experienced clinical deterioration, while 673 (95%) did not. The deterioration group consistently had a higher number of alerts compared to those who were discharged normally, across all time-points. On average, the time between the initial alert and clinical deterioration was 16 h within the last 24 h preceding the event. The sensitivity of the Dozee-EWS varied between 67% and 94%. HCP spend 10% of their time on vital signs check and documentation.ConclusionsThis study suggests that utilizing contactless continuous vital signs monitoring with Dozee-EWS in general ward holds promise for enhancing the early detection of clinical deterioration. Further research is essential to evaluate the effectiveness across a wider range of clinical settings.
Berberine attenuates TNBS-induced colitis in mice by improving the intestinal microbiota
Authors: Li Chao , Yin Xinxin , Xie Changpeng , Zeng Jin , Song Chuan , Yang Guibin , Zhang Jinglei , Chen Siai , Wei Panjian , Wang Ziyu , Gu Meng , Li Wei , An Juan , Pan Yuanming 
Published: August 2024

ObjectiveTo investigate the effects of berberine (BBR) as a treatment on intestinal microecological alterations and enteritis in mice produced by TNBS.MethodsThere were seven mice per group: seven in the healthy group (Ctrl), seven in the TNBS-induced enteritis group (TNBS), and seven in the berberine treatment group (BBR). The mice were weighed, slaughtered after 7 days, and subjected to high-throughput intestinal microecological analysis by Illumina, as well as haematological detection and imaging evaluation of colon pathology.ResultsThe alterations in colon length, immune cell subpopulations, inflammatory factors, and intestinal microecology of mice induced by BBR were refined using a battery of experiments and observations. According to intestinal microecological studies, BBR can increase the number of bacteria, including Lactobacillus, Verrucomicrobia, Bacteroides, and Akkermansia muciniphila.ConclusionBBR has a therapeutic effect on TNBS-induced colitis in mice, which is associated with modifications in immune cell subpopulations and intestinal microecology. It also offers a viable approach as a prospective probiotic (like Akkermansia muciniphila) to IBD therapy in clinical settings.
Alteration in temporal-cerebellar effective connectivity can effectively distinguish stable and progressive mild cognitive impairment
Authors: Xue Chen , Zheng Darui , Ruan Yiming , Guo Wenxuan , Hu Jun ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2024

BackgroundStable mild cognitive impairment (sMCI) and progressive mild cognitive impairment (pMCI) represent two distinct subtypes of mild cognitive impairment (MCI). Early and effective diagnosis and accurate differentiation between sMCI and pMCI are crucial for administering targeted early intervention and preventing cognitive decline. This study investigated the intrinsic dysconnectivity patterns in sMCI and pMCI based on degree centrality (DC) and effective connectivity (EC) analyses, with the goal of uncovering shared and distinct neuroimaging mechanisms between subtypes.MethodsResting-state functional magnetic resonance imaging combined with DC analysis was used to explore the functional connectivity density in 42 patients with sMCI, 31 patients with pMCI, and 82 healthy control (HC) participants. Granger causality analysis was used to assess changes in EC based on the significant clusters found in DC. Furthermore, correlation analysis was conducted to examine the associations between altered DC/EC values and cognitive function. Receiver operating characteristic curve analysis was performed to determine the accuracy of abnormal DC and EC values in distinguishing sMCI from pMCI.ResultsCompared with the HC group, both pMCI and sMCI groups exhibited increased DC in the left inferior temporal gyrus (ITG), left posterior cerebellum lobe (CPL), and right cerebellum anterior lobe (CAL), along with decreased DC in the left medial frontal gyrus. Moreover, the sMCI group displayed reduced EC from the right CAL to bilateral CPL, left superior temporal gyrus, and bilateral caudate compared with HC. pMCI demonstrated elevated EC from the right CAL to left ITG, which was linked to episodic memory and executive function. Notably, the EC from the right CAL to the right ITG effectively distinguished sMCI from pMCI, with sensitivity, specificity, and accuracy of 0.5806, 0.9512, and 0.828, respectively.ConclusionThis study uncovered shared and distinct alterations in DC and EC between sMCI and pMCI, highlighting their involvement in cognitive function. Of particular significance are the unidirectional EC disruptions from the cerebellum to the temporal lobe, which serve as a discriminating factor between sMCI and pMCI and provide a new perspective for understanding the temporal-cerebellum. These findings offer novel insights into the neural circuit mechanisms involving the temporal-cerebellum connection in MCI.
Classification of epileptic seizures in EEG data based on iterative gated graph convolution network
Authors: Hu Yue , Liu Jian , Sun Rencheng , Yu Yongqiang , Sui Yi 
Published: August 2024

IntroductionThe automatic and precise classification of epilepsy types using electroencephalogram (EEG) data promises significant advancements in diagnosing patients with epilepsy. However, the intricate interplay among multiple electrode signals in EEG data poses challenges. Recently, Graph Convolutional Neural Networks (GCN) have shown strength in analyzing EEG data due to their capability to describe complex relationships among different EEG regions. Nevertheless, several challenges remain: (1) GCN typically rely on predefined or prior graph topologies, which may not accurately reflect the complex correlations between brain regions. (2) GCN struggle to capture the long-temporal dependencies inherent in EEG signals, limiting their ability to effectively extract temporal features.MethodsTo address these challenges, we propose an innovative epileptic seizure classification model based on an Iterative Gated Graph Convolutional Network (IGGCN). For the epileptic seizure classification task, the original EEG graph structure is iteratively optimized using a multi-head attention mechanism during training, rather than relying on a static, predefined prior graph. We introduce Gated Graph Neural Networks (GGNN) to enhance the model's capacity to capture long-term dependencies in EEG series between brain regions. Additionally, Focal Loss is employed to alleviate the imbalance caused by the scarcity of epileptic EEG data.ResultsOur model was evaluated on the Temple University Hospital EEG Seizure Corpus (TUSZ) for classifying four types of epileptic seizures. The results are outstanding, achieving an average F1 score of 91.5% and an average Recall of 91.8%, showing a substantial improvement over current state-of-the-art models.DiscussionAblation experiments verified the efficacy of iterative graph optimization and gated graph convolution. The optimized graph structure significantly differs from the predefined EEG topology. Gated graph convolutions demonstrate superior performance in capturing the long-term dependencies in EEG series. Additionally, Focal Loss outperforms other commonly used loss functions in the TUSZ classification task.
Ketogenic diet with aerobic exercise can induce fat browning: potential roles of β-hydroxybutyrate
Authors: Kim Sujin , Park Dong-Ho , Moon Sohee , Gu Bonsang , Mantik Keren Esther Kristina , Kwak Hyo-Bum , Ryu Ji-Kan , Kang Ju-Hee 
Published: August 2024

IntroductionDespite evidence suggesting that metabolic intermediates like β-HB influence white adipose tissue (WAT) metabolism, the precise molecular mechanisms remain unclear. The aim of this study was to investigate the impact of beta-hydroxybutyrate (β-HB) on the fat browning program and to explore the underlying molecular mechanisms using both in vitro and in vivo models. We assessed the effects of β-HB on fat browning in adipocytes using 3T3-L1 cells and rat models.MethodsWe evaluated the effects of β-HB on fat browning, thermogenesis, lipid accumulation, adipokine expression, and mitochondrial biogenesis by treating mature 3T3-L1 adipocytes with sodium β-HB for 24 h or by continuously exposing preadipocytes to β-HB during the 8-day differentiation process. Male Sprague Dawley rats were divided into control, exercise only (EX), ketogenic diet only (KD), and combined exercise and ketogenic diet (KE) groups for an 8-week intervention involving diet and/or exercise. After intervention, we evaluated WAT histology, plasma lipids and adipokines, and the expression of markers related to fat browning, thermogenesis and mitochondrial biogenesis in WAT of rats.ResultsIn our adipocyte culture experiments, β-HB reduced intracellular lipid accumulation by enhancing lipolysis and stimulated the expression of thermogenic and fat browning genes like uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), and adipokines such as fibroblast growth factor 21 (FGF21) and Fibronectin type III domain-containing protein 5 (FDNC5). Additionally, β-HB activated the AMPK-SIRT1-PGC-1α pathway, with UCP1 and PRDM16 upregulation mediated by β-HB intracellular action and SIRT1 activity. In animal experiments, KE group raised β-HB levels, decreasing body weight and blood lipids. KD with EX promoted WAT browning possibly via AMPK-SIRT1-PGC-1α, augmenting PRDM16, UCP1, FGF21, and FNDC5 expression.Conclusionβ-HB induction via KD and/or EX shows potential in promoting WAT browning by activating mitochondrial biogenesis, lipolysis, and thermogenesis, suggesting that dietary and physical intervention inducing β-HB may benefit metabolic health.
Risk factors for unplanned intensive care unit admission after esophagectomy: a retrospective cohort study of 628 patients with esophageal cancer
Authors: Zhang Guoqing , Sun Shaowu , Dong Zhengxia , Chunyao Huang , Wang Zhulin , Li Kaiyuan , Liu Xu , Zhang Yujie , Wang Junya , Li Jindong , Zhao Jia , Li Xiangnan 
Published: August 2024

IntroductionEsophagectomy patients who experience unplanned ICU admission (UIA) may experience a heavier economic burden and worse clinical outcomes than those who experience routine intensive care unit (ICU) admission. The aim of this study was to identify the risk factors for postoperative UIA in patients who underwent esophagectomy.MethodsWe retrospectively included patients with esophageal cancer who underwent esophagectomy. The characteristics of postoperative UIA were described, and univariable and multivariable analyses were performed based on the logistic regression model. Furthermore, a recursive partitioning analysis was adopted to stratify the patients according to the risk of UIA.ResultsA total of 628 patients were included in our final analysis, among whom 57 (9.1%) had an UIA. The patients in the UIA cohort had a higher rate of in-hospital mortality (P&lt;0.001), longer hospital stay (P&lt;0.001), and higher associated costs (P&lt;0.001). Multivariable analysis showed that hybrid/open esophagectomy (OR=4.366, 95% CI=2.142 to 8.897, P&lt;0.001), operation time (OR=1.006, 95% CI=1.002 to 1.011, P=0.007), intraoperative blood transfusion (OR=3.118, 95% CI=1.249 to 7.784, P=0.015) and the prognostic nutrition index (PNI) (OR=0.779, 95% CI=0.724 to 0.838, P&lt;0.001) were independently associated with UIA.ConclusionsWe identified several critical independent perioperative risk factors that may increase the risk of UIA following esophagectomy, and the above risk factors should be the focus of attention to reduce the incidence of postoperative UIA.
Intraoperative tranexamic acid administration in cranial meningioma surgery: a meta-analysis of prospective randomized, double-blinded, and placebo-controlled trials
Authors: Vychopen Martin , Arlt Felix , Güresir Erdem , Wach Johannes 
Published: August 2024

ObjectiveCranial meningioma surgeries often involve significant blood loss and transfusions. Tranexamic acid (TXA) has been used to reduce blood loss in various surgeries. This meta-analysis of randomized placebo-controlled trials (RCTs) evaluates the impact of TXA in cranial meningioma surgery.MethodsPubmed, Web of Science, and Cochrane Library were searched for RCTs. Studies were compared for: Blood loss, operative time, hospital stay, reoperation rates, allogeneic and autologous transfusion, and incidence of complications.ResultsSeven RCTs with 490 patients receiving TXA and 491 receiving placebos were included. TXA significantly shortened operative time (Mean Difference (MD): -20.95; 95%CI: -39.94 to -1.95; p=0.03). Blood loss was lower with TXA (MD: -262.7 ml; 95%CI: -397.6 to -127.8; p=0.0001). Odds of reoperation were not significantly different (OR: 0.44; 95%CI: 0.13-1.45; p=0.18). TXA significantly reduced the need for RBC transfusions (OR: 0.47; 95%CI: 0.22-0.99; p&lt;0.05). No significant differences were observed regarding postoperative seizures (OR: 1.06; 95%CI: 0.56-2.03; p=0.85), hydrocephalus (OR: 0.25; 95%CI: 0.03-2.29; p=0.22), or hematoma (OR: 0.52; 95%CI: 0.22-1.28; p=0.16). Hospital stay was shortened in the TXA group (MD: -1.23; 95%CI: -2.41 to -0.05; p=0.04).ConclusionThis meta-analysis suggests that a single intraoperative dose of TXA reduces blood loss, allogeneic blood transfusions and shortens surgery time.