bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the above-ground eukaryotic diversity supported by individual large old trees: the “Life on Trees” integrative protocol
Authors: Leponce Maurice , Basset Yves , Aristizábal-Botero Ángela , Baïben Noui , Barbut Jérôme , Buyck Bart , Butterill Philip , Calders Kim , Cárdenas Glenda , Carrias Jean-François , Catchpole Damien , D’hont Barbara , Delabie Jacques , Drescher Jochen , Ertz Damien , Heughebaert André , Hofstetter Valérie , Leroy Céline , Melki Frédéric , Michaux Johan , Neita-Moreno Jhon César , Poirier Eddy , Rougerie Rodolphe , Rouhan Germinal , Rufray Vincent , Scheu Stefan , Schmidl Jürgen , Vanderpoorten Alain , Villemant Claire , Youdjou Nabil , Pascal Olivier
Published: August 2024

Large tropical trees are rightly perceived as supporting a plethora of organisms. However, baseline data about the variety of taxa coexisting on single large tropical trees are lacking and prevent a full understanding of both the magnitude of biodiversity and the complexity of interactions among organisms in tropical rainforests. The two main aims of the research program “Life on Trees” (LOT) are (1) to establish baseline knowledge on the number of eukaryote species supported/hosted by the above-ground part of a single tropical tree and (2) to understand how these communities of organisms are assembled and distributed on or inside the tree. To achieve the first goal, we integrated a set of 36 methods for comprehensively sampling eukaryotes (plants, fungi, animals, protists) present on a tropical tree. The resulting LOT protocol was conceived and implemented during projects in the Andean Amazon region and is proposed here as a guideline for future projects of a similar nature. To address the second objective, we evaluated the microclimatic differences between tree zones and tested state-of-the-art terrestrial laser scanning (TLS) and positioning technologies incorporating satellite and fixed base station signals (dGNSS). A marked variation in temperature and relative humidity was detected along a 6-zones Johansson scheme, a tree structure subdivision system commonly used to study the stratification of epiphytic plants. Samples were collected from these six zones, including three along the trunk and three in the canopy. To better understand how different tree components (e.g., bark, leaves, fruits, flowers, dead wood) contribute to overall tree biodiversity, we categorized observations into communities based on Johansson zones and microhabitats. TLS was an essential aid in understanding the complex tree architecture. By contrast, the accuracy of positioning samples in the tree with dGNSS was low. Comprehensively sampling the biota of individual trees offers an alternative to assessing the biodiversity of fewer groups of organisms at the forest scale. Large old tropical trees provide a wealth of microhabitats that encompass a wide range of ecological conditions, thereby capturing a broad spectrum of biodiversity.
Exploration of the ubiquitination-related molecular classification and signature to predict the survival and immune microenvironment in colon cancer
Authors: Xu Ji-Zhong , Wan Tian-Qi , Su Jin-Song , Song Jun-Min
Published: August 2024

Background

Ubiquitination, a major post-translational modification, significantly impacts tumorigenesis, progression, and prognosis. This study aims to classify colon cancer at the molecular level and create a reliable signature using ubiquitination-related genes (URGs) to assess the immune microenvironment and prognosis.

Methods

We employed non-negative matrix factorization to subtype colon cancer based on ubiquitination-related gene (URG) expression patterns. Quantitative scores for 28 immune cell infiltrates and the tumor microenvironment were computed using single-sample gene set enrichment analysis (ssGSEA) and the Estimate algorithm. Subtype feature genes were selected through Lasso logistic regression and SVM-RFE algorithm. The ubiquitination-related signature was constructed using univariate Cox, Lasso, and stepwise regression methods to categorize patients into high and low-risk groups. Validation included log-rank tests, receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and external dataset validation. Immune therapy response was compared using Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenoscore (IPS), and submap analyses. Clinical variables and risk scores were integrated into an enhanced nomogram. The early diagnostic value of four URGs was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The cell proliferation was assessed through colony formation, EdU staining, and xenograft tumorigenesis assays.

Results

Prognostic ubiquitination-related genes (URGs) stratified patients into subtypes, revealing differences in survival, immune cell infiltration, and pathological staging. A signature of 6 URGs (ARHGAP4, MID2, SIAH2, TRIM45, UBE2D2, WDR72) was identified from 57 subtype-related genes. The high-risk group exhibited characteristics indicative of enhanced epithelial-mesenchymal transition, immune escape, immunosuppressive myeloid-derived suppressor cells, regulatory T cell infiltration, and lower immunogenicity. In contrast, the low-risk group demonstrated the opposite trend but showed a better response to CTLA4 checkpoint inhibitors. The predictive performance of the nomogram significantly improved with the integration of risk score, stage, and age. ARHGAP4 and SIAH2 exhibit promising early diagnostic capabilities. Additionally, WDR72 knockdown significantly inhibited CRC cell proliferation both in vitro and in vivo.

Conclusion

Our developed ubiquitination-related signature and genes serve as promising biomarkers for colon cancer prognosis, immune microenvironment, and diagnosis.
Bacterial pneumonia patients with elevated globulin levels did not get infected with SARS-CoV-2: two case reports
Authors: Zhong Qi , Lin Qiu-mei , Long Hong-bin , Liao Cai-xia , Sun Xiao-xiao , Yang Miao-du , Zhang Zhi-hao , Huang Yi-hua , Wang Shi-min , Yang Zhao-shou
Published: August 2024

Background

COVID-19 began in December 2019, rapidly spreading worldwide. China implemented a dynamic zero-COVID strategy and strict control measures after the outbreak. However, Guangzhou city ended closed-off management by the end of November 2022, leading to exposure to SARS-CoV-2. Despite most hospitalized patients being infected or co-infected with SARS-CoV-2, some remained uninfected. We report two cases of bacterial pneumonia with elevated globulin levels not infected with SARS-CoV-2, aiming to identify protection factors of SARS-CoV-2 infection and provide a scientific basis for SARS-CoV-2 prevention.

Case presentation

Case 1, a 92-year-old male, admitted on October 21, 2022, developed worsening cough and sputum after aspiration, diagnosed with bacterial pneumonia with Pseudomonas aeruginosa, Escherichia coli (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) infections. He was treated with imipenem anti-infective therapy and mechanical ventilation, then switched to a combination of meropenem, voriconazole and amikacin anti-infective therapy due to recurrent infections and septic shock, and died of sepsis on 8 January 2023. Case 2 is an 82-year-old male admitted on 30 September 2022, with recurrent cough, sputum, and shortness of breath, diagnosed with bacterial pneumonia with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Mycobacterium pneumoniae infections. He was treated with ventilator-assisted ventilation, meropenem, amikacin, tigecycline and mucomycin nebulization and discharged with improvement on 26 October. He was readmitted on 21 November 2022 and diagnosed with bacterial pneumonia. He was treated with cefoperazone sulbactam, amikacin, meropenem and fluconazole and discharged on 31 December. Neither patient was infected with SARS-CoV-2 during hospitalization. Notably, their globulin levels were elevated before SARS-CoV-2 exposure, gradually decreasing afterward.

Conclusions

Patients with bacterial pneumonia with high globulin levels likely have large amounts of immunoglobulin, and that immunoglobulin cross-reactivity causes this protein to be involved in clearing SARS-CoV-2 and preventing infection. Therefore, bacterial pneumonia patients with high globulin levels included in this study were not infected with SARS-CoV-2. After exposure to SARS-CoV-2, the amount of globulin in the patient’s body was reduced because it was used to clear SARS-CoV-2. The results of this study are expected to provide a theoretical basis for the study of the mechanism of prevention and treatment of SARS-CoV-2 infection.
The possible and intriguing relationship between bullous pemphigoid and melanoma: speculations on significance and clinical relevance
Authors: Russo Filomena , Pira Anna , Mariotti Feliciana , Papaccio Federica , Giampetruzzi Anna Rita , Bellei Barbara , Di Zenzo Giovanni
Published: August 2024

Bullous pemphigoid (BP) is the most common autoimmune bullous disease: it most commonly affects individuals over 70 years old and impacts severely on their quality of life. BP represents a paradigm for an organ-specific autoimmune disease and is characterized by circulating IgG autoantibodies to hemidesmosomal components: BP180 and BP230. While the crucial role of these autoantibodies in triggering BP inflammatory cascade is fully acknowledged, many ancillary etiological mechanisms need to be elucidated yet. Cutaneous melanoma is due to a malignant transformation of skin melanocytes, that produce and distribute pigments to surrounding keratinocytes. Melanoma is the most fatal skin cancer because of its increasing incidence and its propensity to metastasize. Several data such as: i) reported cases of concomitant melanoma and BP; ii) results from association studies; iii) BP onset following immune check-point inhibitors therapy; iv) expression of BP antigens in transformed melanocytes; and vi) circulating autoantibodies to BP antigens in melanoma patients suggest an intriguing, although unproven, possible association between melanoma and BP. However, a possible causative link is still debated and the putative pathogenetic mechanism underlying this association is unclear. This review aims to describe and discuss the possible relationship between BP and melanoma and give an overview of the speculations for or against this association. Of note, if demonstrated, this association could unwrap considerations of clinical relevance that represent new research frontiers.
Antigen-specific T helper cells and cytokine profiles predict intensity and longevity of cellular and humoral responses to SARS-CoV-2 booster vaccination
Authors: Page Lukas , Dennehy Kevin , Mueller Katharina , Girl Philipp , Loell Eva , Buijze Hellen , Classen Johanna-Maria , Messmann Helmut , Roemmele Christoph , Hoffmann Reinhard , Wurster Sebastian , Fuchs Andre
Published: August 2024

Introduction

Pre-existent pools of coronavirus-specific or cross-reactive T cells were shown to shape the development of cellular and humoral immune responses after primary mRNA vaccination against SARS-CoV-2. However, the cellular determinants of responses to booster vaccination remain incompletely understood. Therefore, we phenotypically and functionally characterized spike antigen-specific T helper (Th) cells in healthy, immunocompetent individuals and correlated the results with cellular and humoral immune responses to BNT162b2 booster vaccination over a six-month period.

Methods

Blood of 30 healthy healthcare workers was collected before, 1, 3, and 6 months after their 3rd BNT162b2 vaccination. Whole blood was stimulated with spike peptides and analyzed using flow cytometry, a 13-plex cytokine assay, and nCounter-based transcriptomics.

Results

Spike-specific IgG levels at 1 month after booster vaccination correlated with pre-existing CD154+CD69+IFN-γ+CD4+ effector memory cells as well as spike-induced IL-2 and IL-17A secretion. Early post-booster (1-month) spike IgG levels (r=0.49), spike-induced IL‑2 (r=0.58), and spike-induced IFN‑γ release (r=0.43) correlated moderately with their respective long-term (6-month) responses. Sustained robust IgG responses were significantly associated with S-specific (CD69+±CD154+±IFN-γ+) Th-cell frequencies before booster vaccination (p=0.038), especially double/triple-positive type-1 Th cells. Furthermore, spike IgG levels, spike-induced IL‑2 release, and spike-induced IFN‑γ release after 6 months were significantly associated with increased IL‑2 & IL‑4, IP‑10 & MCP1, and IFN‑γ & IP‑10 levels at 1 month post-booster, respectively. On the transcriptional level, induction of pathways associated with both T-cell proliferation and antigen presentation was indicative of sustained spike-induced cytokine release and spike-specific IgG production 6 months post-booster. Using support vector machine models, pre-booster spike-specific T-cell frequencies and early post-booster cytokine responses predicted sustained (6-month) responses with F1 scores of 0.80-1.00.

Discussion

In summary, spike-specific Th cells and T-cellular cytokine signatures present before BNT162b2 booster vaccination shape sustained adaptive cellular and humoral responses post-booster. Functional T-cell assays might facilitate early identification of potential non-responders.
Single-cell multi-omics reveal stage of differentiation and trajectory-dependent immunity-related gene expression patterns in human erythroid cells
Authors: Perik-Zavodskii Roman , Perik-Zavodskaia Olga , Alrhmoun Saleh , Volynets Marina , Shevchenko Julia , Nazarov Kirill , Denisova Vera , Sennikov Sergey
Published: August 2024

The role of Erythroid cells in immune regulation and immunosuppression is one of the emerging topics in modern immunology that still requires further clarification as Erythroid cells from different tissues and different species express different immunoregulatory molecules. In this study, we performed a thorough investigation of human bone marrow Erythroid cells from adult healthy donors and adult acute lymphoblastic leukemia patients using the state-of-the-art single-cell targeted proteomics and transcriptomics via BD Rhapsody and cancer-related gene copy number variation analysis via NanoString Sprint Profiler. We found that human bone marrow Erythroid cells express the ARG1, LGALS1, LGALS3, LGALS9, and C10orf54 (VISTA) immunosuppressive genes, CXCL5, CXCL8, and VEGFA cytokine genes, as well as the genes involved in antimicrobial immunity and MHC Class II antigen presentation. We also found that ARG1 gene expression was restricted to the single erythroid cell cluster that we termed ARG1-positive Orthochromatic erythroblasts and that late Erythroid cells lose S100A9 and gain MZB1 gene expression in case of acute lymphoblastic leukemia. These findings show that steady-state erythropoiesis bone marrow Erythroid cells express myeloid signature genes even without any transdifferentiating stimulus like cancer.
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

Introduction

Adjuvants 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.

Methods

To 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.

Results

PRR 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.

Conclusions

Overall, 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

Background

Cancer 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.

Method

The 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.

Result

This 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.

Conclusion

Overall, 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

Background

Distinct 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.

Methods

We 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).

Result

Deconvolution 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 < 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 < 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.

Conclusion

RCC 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.
SARS-CoV-2 infectivity and antigenic evasion: spotlight on isolated Omicron sub-lineages
Authors: Barrera Aldo , Martínez-Valdebenito Constanza , Angulo Jenniffer , Palma Carlos , Hormazábal Juan , Vial Cecilia , Aguilera Ximena , Castillo-Torres Pablo , Pardo-Roa Catalina , Balcells María Elvira , Nervi Bruno , Corre Nicole Le , Ferrés Marcela
Published: August 2024

Since the SARS-CoV-2 outbreak in 2019, a diversity of viral genomic variants has emerged and spread globally due to increased transmissibility, pathogenicity, and immune evasion. By the first trimester of 2023 in Chile, as in most countries, BQ and XBB were the predominant circulating sub-lineages of Omicron. The molecular and antigenic characteristics of these variants have been mainly determined using non-authentic spike pseudoviruses, which is often described as a limitation. Additionally, few comparative studies using isolates from recent Omicron sub-lineages have been conducted. In this study, we isolated SARS-CoV-2 variants from clinical samples, including the ancestral B.1.1, Delta, Omicron BA.1, and sub-lineages of BA.2 and BA.5. We assessed their infectivity through cell culture infections and their antibody evasion using neutralization assays. We observed variations in viral plaque size, cell morphology, and cytotoxicity upon infection in Vero E6-TMPRSS2 cells for each variant compared to the ancestral B.1.1 virus. BA.2-derived sub-variants, such as XBB.1.5, showed attenuated viral replication, while BA.5-derived variants, such as BQ.1.1, exhibited replication rates similar to the ancestral SARS-CoV-2 virus. Similar trends were observed in intestinal Caco-2 cells, except for Delta. Antibody neutralization experiments using sera from individuals infected during the first COVID-19 wave (FWI) showed a consistent but moderate reduction in neutralization against Omicron sub-lineages. Interestingly, despite being less prevalent, BQ.1.1 showed a 6.1-fold greater escape from neutralization than XBB.1.5. Neutralization patterns were similar when tested against sera from individuals vaccinated with 3xBNT162b2 (PPP) or Coronavac-Coronavac-BNT162b2 (CCP) schedules. However, CCP sera showed 2.3-fold higher neutralization against XBB.1.5 than FWI and PPP sera. This study provides new insights into the differences between BA.2 and BA.5-derived variants, leading to their eventual outcompetition. Our analysis offers important evidence regarding the balance between infectivity and antigenic escape that drives the evolution of second-generation SARS-CoV-2 variants in the population.
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

Background

Osteoporosis 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.

Methods

We 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.

Results

Our 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.

Conclusion

This 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

Objective

To 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.

Methods

A 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.

Results

Out 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.

Conclusions

This 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.
Taxonomic composition and functional potentials of gastrointestinal microbiota in 12 wild-stranded cetaceans
Authors: Fan Jie , Kang Hui , Lv Meiqi , Zhai Yuhuan , Jia Yangyang , Yang Zixin , Shi Chengcheng , Zhou Changhao , Diao Lin , Li Jingsuo , Jin Xiaowei , Liu Shanshan , Kristiansen Karsten , Zhang Peijun , Chen Jianwei , Li Songhai
Published: August 2024

Cetaceans play a crucial role in marine ecosystems; however, research on their gastrointestinal microbiota remains limited due to sampling constraints. In this study, we collected hindgut samples from 12 stranded cetaceans and performed 16S rRNA gene amplicon sequencing to investigate microbial composition and functional potentials. Analysis of ZOTUs profiles revealed that the phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated all hindgut samples. However, unique microbial profiles were observed among different cetacean species, with significant separation of gut microbiota communities according to biological evolutionary lineages. Different genera that contain pathogens were observed distinguishing delphinids from physeteroids/ziphiids. Delphinid samples exhibited higher abundances of Vibrio, Escherichia, and Paeniclostridium, whereas physeteroid and ziphiid samples showed higher abundances of Pseudomonas, Enterococcus, and Intestinimonas. Functional analysis indicated convergence in the gut microbiota among all cetaceans, with shared bacterial infection pathways across hindgut samples. In addition, a comparison of the gastrointestinal microbial composition between a stranded short-finned pilot whale (Globicephala macrorhynchus) and a stranded rough-toothed dolphin (Steno bredanensis) using 16S rRNA gene sequencing revealed distinct microbial community structures and functional capacities. To the best of our knowledge, this study represents the first report on the gastrointestinal microbiota of the pantropical spotted dolphin (Stenella attenuata), Blainville’s beaked whale (Mesoplodon densirostris), and rough-toothed dolphin, with various comparisons conducted among different cetacean species. Our findings enhance the understanding of microbial composition and diversity in cetacean gastrointestinal microbiota, providing new insights into co-evolution and complex interactions between cetacean microbes and hosts.
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

Objective

To investigate the effects of berberine (BBR) as a treatment on intestinal microecological alterations and enteritis in mice produced by TNBS.

Methods

There 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.

Results

The 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.

Conclusion

BBR 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

Background

Stable 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.

Methods

Resting-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.

Results

Compared 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.

Conclusion

This 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

Introduction

The 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.

Methods

To 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.

Results

Our 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.

Discussion

Ablation 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.
Neurosustainability
Authors: Khalil Mohamed Hesham
Published: August 2024

While the human brain has evolved extraordinary abilities to dominate nature, modern living has paradoxically trapped it in a contemporary “cage” that stifles neuroplasticity. Within this modern environment lurk unseen natural laws with power to sustain the human brain’s adaptive capacities - if consciously orchestrated into the environments we design. For too long our contemporary environments have imposed an unyielding static state, while still neglecting the brain’s constant adaptive nature as it evolves to dominate the natural world with increasing sophistication. The theory introduced in this article aims to go back in nature without having to go back in time, introducing and expounding Neurosustainability as a novel paradigm seeing beyond the contemporary confines to architect environments and brains in parallel. Its integrated neuro-evidenced framework proposes four enrichment scopes—spatial, natural, aesthetic, and social—each holding multifaceted attributes promising to sustain regions like the hippocampus, cortex and amygdala. Neurosustainability aims to liberate the quintessential essence of nature to sustain and enhance neuroplastic processes through a cycle that begins with design and extends through epigenetic changes. This paradigm shift aims to foster cognitive health and wellness by addressing issues like stress, depression, anxiety and cognitive decline common in the contemporary era thereby offering a path toward a more neurosustainable era aiming to nurture the evolution of the human brain now and beyond.
Ergogenic effects of spinal cord stimulation on exercise performance following spinal cord injury
Authors: Hodgkiss Daniel D. , Williams Alison M. M. , Shackleton Claire S. , Samejima Soshi , Balthazaar Shane J. T. , Lam Tania , Krassioukov Andrei V. , Nightingale Tom E.
Published: August 2024

Cervical or upper-thoracic spinal cord injury (SCI, ≥T6) often leads to low resting blood pressure (BP) and impaired cardiovascular responses to acute exercise due to disrupted supraspinal sympathetic drive. Epidural spinal cord stimulation (invasive, ESCS) and transcutaneous spinal cord stimulation (non-invasive, TSCS) have previously been used to target dormant sympathetic circuits and modulate cardiovascular responses. This case series compared the effects of cardiovascular-optimised ESCS and TSCS versus sham ESCS and TSCS on modulating cardiovascular responses and improving submaximal upper-body exercise performance in individuals with SCI. Seven males with a chronic, motor-complete SCI between C6 and T4 underwent a mapping session to identify cardiovascular responses to spinal cord stimulation. Subsequently, four participants (two ESCS and two TSCS) completed submaximal exercise testing. Stimulation parameters (waveform, frequency, intensity, epidural electrode array configuration, and transcutaneous electrode locations in the lumbosacral region) were optimised to elevate cardiovascular responses (CV-SCS). A sham condition (SHAM-SCS) served as a comparison. Participants performed arm-crank exercise to exhaustion at a fixed workload corresponding to above ventilatory threshold, on separate days, with CV-SCS or SHAM-SCS. At rest, CV-SCS increased BP and predicted left ventricular cardiac contractility and total peripheral resistance. During exercise, CV-SCS increased time to exhaustion and peak oxygen pulse (a surrogate for stroke volume), relative to SHAM-SCS. Ratings of perceived exertion also tended to be lower with CV-SCS than SHAM-SCS. Comparable improvements in time to exhaustion with ESCS and TSCS suggest that both approaches could be promising ergogenic aids to support exercise performance or rehabilitation, along with reducing fatigue during activities of daily living in individuals with SCI.
Characterization of cortical volume and whole-brain functional connectivity in Parkinson’s disease patients: a MRI study combined with physiological aging brain changes
Authors: Wang Shuaiwen , Chen Xiaoli , Zhang Yanli , Gao Yulin , Gou Lubin , Lei Junqiang
Published: August 2024

This study employed multiple MRI features to comprehensively evaluate the abnormalities in morphology, and functionality associated with Parkinson’s disease (PD) and distinguish them from normal physiological changes. For investigation purposes, three groups: 32 patients with PD, 42 age-matched healthy controls (HCg1), and 33 young and middle-aged controls (HCg2) were designed. The aim of the current study was to differentiate pathological cortical changes in PD from age-related physiological cortical volume changes. Integrating these findings with functional MRI changes to characterize the effects of PD on whole-brain networks. Cortical volumes in the bilateral temporal lobe, frontal lobe, and cerebellum were significantly reduced in HCg1 compared to HCg2. Although no significant differences in cortical volume were observed between PD patients and HCg1, the PD group exhibited pronounced abnormalities with significantly lower mean connectivity values compared to HCg1. Conversely, physiological functional changes in HCg1 showed markedly higher mean connectivity values than in HCg2. By integrating morphological and functional assessments, as well as network characterization of physiological aging, this study further delineates the distinct characteristics of pathological changes in PD.
Neuron and astrocyte specific 5mC and 5hmC signatures of BDNF’s receptor, TrkB
Authors: Wei Xiaoran , Browning Jack L. , Olsen Michelle L.
Published: August 2024

Brain derived neurotrophic factor (BDNF) is the most studied trophic factor in the central nervous system (CNS), and its role in the maturation of neurons, including synapse development and maintenance has been investigated intensely for over three decades. The primary receptor for BDNF is the tropomyosin receptor kinase B (TrkB), which is broadly expressed as two primary isoforms in the brain; the full length TrkB (TrkB.FL) receptor, expressed mainly in neurons and the truncated TrkB (TrkB.T1) receptor. We recently demonstrated that TrkB.T1 is predominately expressed in astrocytes, and appears critical for astrocyte morphological maturation. Given the critical role of BDNF/TrkB pathway in healthy brain development and mature CNS function, we aimed to identify molecular underpinnings of cell-type specific expression of each TrkB isoform. Using Nanopore sequencing which enables direct, long read sequencing of native DNA, we profiled DNA methylation patterns of the entire TrkB gene, Ntrk2, in both neurons and astrocytes. Here, we identified robust differences in cell-type specific isoform expression associated with significantly different methylation patterns of the Ntrk2 gene in each cell type. Notably, astrocytes demonstrated lower 5mC methylation, and higher 5hmC across the entire gene when compared to neurons, including differentially methylated sites (DMSs) found in regions flanking the unique TrkB.T1 protein coding sequence (CDS). These data suggest DNA methylation patterns may provide instruction for isoform specific TrkB expression across unique CNS cell types.
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

Introduction

Despite 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.

Methods

We 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.

Results

In 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.

Conclusion

β-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

Introduction

Esophagectomy 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.

Methods

We 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.

Results

A 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<0.001), longer hospital stay (P<0.001), and higher associated costs (P<0.001). Multivariable analysis showed that hybrid/open esophagectomy (OR=4.366, 95% CI=2.142 to 8.897, P<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<0.001) were independently associated with UIA.

Conclusions

We 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.