bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune surveillance and humoral immune responses in kidney transplantation – A look back at T follicular helper cells
Authors: Subburayalu Julien
Published: July 2023

T follicular helper cells comprise a specialized, heterogeneous subset of immune-competent T helper cells capable of influencing B cell responses in lymphoid tissues. In physiology, for example in response to microbial challenges or vaccination, this interaction chiefly results in the production of protecting antibodies and humoral memory. In the context of kidney transplantation, however, immune surveillance provided by T follicular helper cells can take a life of its own despite matching of human leukocyte antigens and employing the latest immunosuppressive regiments. This puts kidney transplant recipients at risk of subclinical and clinical rejection episodes with a potential risk for allograft loss. In this review, the current understanding of immune surveillance provided by T follicular helper cells is briefly described in physiological responses to contrast those pathological responses observed after kidney transplantation. Sensitization of T follicular helper cells with the subsequent emergence of detectable donor-specific human leukocyte antigen antibodies, non-human leukocyte antigen antibodies their implication for kidney transplantation and lessons learnt from other transplantation “settings” with special attention to antibody-mediated rejection will be addressed.
Identification of aging-related biomarkers and immune infiltration characteristics in osteoarthritis based on bioinformatics analysis and machine learning
Authors: Zhou JiangFei , Huang Jian , Li ZhiWu , Song QiHe , Yang ZhenYu , Wang Lu , Meng QingQi
Published: July 2023

Background

Osteoarthritis (OA) is a degenerative disease closely related to aging. Nevertheless, the role and mechanisms of aging in osteoarthritis remain unclear. This study aims to identify potential aging-related biomarkers in OA and to explore the role and mechanisms of aging-related genes and the immune microenvironment in OA synovial tissue.

Methods

Normal and OA synovial gene expression profile microarrays were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) from the Human Aging Genomic Resources database (HAGR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), and Gene set variation analysis (GSVA) enrichment analysis were used to uncover the underlying mechanisms. To identify Hub ARDEGs with highly correlated OA features (Hub OA-ARDEGs), Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning methods were used. Furthermore, we created diagnostic nomograms and receiver operating characteristic curves (ROC) to assess Hub OA-ARDEGs’ ability to diagnose OA and predict which miRNAs and TFs they might act on. The Single sample gene set enrichment analysis (ssGSEA) algorithm was applied to look at the immune infiltration characteristics of OA and their relationship with Hub OA-ARDEGs.

Results

We discovered 87 ARDEGs in normal and OA synovium samples. According to functional enrichment, ARDEGs are primarily associated with inflammatory regulation, cellular stress response, cell cycle regulation, and transcriptional regulation. Hub OA-ARDEGs with excellent OA diagnostic ability were identified as MCL1, SIK1, JUND, NFKBIA, and JUN. Wilcox test showed that Hub OA-ARDEGs were all significantly downregulated in OA and were validated in the validation set and by qRT-PCR. Using the ssGSEA algorithm, we discovered that 15 types of immune cell infiltration and six types of immune cell activation were significantly increased in OA synovial samples and well correlated with Hub OA-ARDEGs.

Conclusion

Synovial aging may promote the progression of OA by inducing immune inflammation. MCL1, SIK1, JUND, NFKBIA, and JUN can be used as novel diagnostic biomolecular markers and potential therapeutic targets for OA.
Implication of metabolism in the polarization of tumor-associated-macrophages: the mass spectrometry-based point of view
Authors: De Simone Giulia , Soldani Cristiana , Morabito Aurelia , Franceschini Barbara , Ferlan Fabrizio , Costa Guido , Pastorelli Roberta , Donadon Matteo , Brunelli Laura
Published: July 2023

Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. TAMs showed different activation states that can be represent by the two extremes of the complex profile of macrophages biology, the M1-like phenotype (pro-inflammatory activity) and the M2-like phenotype (anti-inflammatory activity). Based on the tumor type, and grades, TAMs can acquire different functions and properties; usually, the M1-like phenotype is typical of early tumor stages and is associated to an anti-tumor activity, while M2-like phenotype has a pro-inflammatory activity and is related to a poor patients’ prognosis. The classification of macrophages into M1/M2 groups based on well-defined stimuli does not model the infinitely more complex tissue milieu where macrophages (potentially of different origin) would be exposed to multiple signals in different sequential order. This review aims to summarize the recent mass spectrometry-based (MS-based) metabolomics findings about the modifications of metabolism in TAMs polarization in different tumors. The published data shows that MS-based metabolomics is a promising tool to help better understanding TAMs metabolic phenotypes, although it is still poorly applied for TAMs metabolism. The knowledge of key metabolic alterations in TAMs is an essential step for discovering TAMs polarization novel biomarkers and developing novel therapeutic approaches targeting TAM metabolism to repolarize TAMs towards their anti-tumor phenotype.
Serum DKK-1 level in ankylosing spondylitis: insights from meta-analysis and Mendelian randomization
Authors: Fang Xi , Chen Cong , Wang Zhi-Xin , Zhao Yan , Jiang Ling-Qiong , Fang Yang , Zhang Ruo-Di , Pan Hai-Feng , Tao Sha-Sha
Published: July 2023

Objective

The purpose of this study was to precisely evaluate the serum Dickkopf-1 (DKK-1) level in patients with ankylosing spondylitis (AS) relative to that in normal controls and to test the causal relationship between DKK-1 and the risk of AS.

Methods

Embase, PubMed, Web of Science, WANFANG DATA, VIP, and China National Knowledge Infrastructure (CNKI) were comprehensively searched until July 2022 for pertinent studies. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated by the fixed or random-effect model. In Mendelian randomization (MR) analysis on the causal relationship between serum DKK-1 level and AS risk, the inverse variance weighting method (IVW), MR-Egger regression, weighted median method, and weighted pattern method were applied. Sensitivity analyses, including the horizontal pleiotropy test, heterogeneity test, and leave-one-out test, were also performed.

Results

The meta-analysis of 40 studies containing 2,371 AS patients and 1,633 healthy controls showed that there was no significant difference in DKK-1 serum level between AS patients and normal controls (pooled SMD=0.207, 95% CI =−0.418-0.832, P=0.516). The subgroup analysis of the CRP ≤ 10 mg/L group showed that AS patients had higher serum DKK-1 concentration than the healthy controls (SMD=2.267, 95% CI = 0.102-4.432, P=0.040). Similarly, MR analysis also demonstrated no significant association between DKK-1 serum level and AS (IVW OR=0.999, 95% CI = 0.989-1.008, P=0.800). All sensitivity analyses revealed consistent results.

Conclusions

There was no significant change in serum DKK-1 concentration between AS patients and healthy controls. In addition, no causal relationship exists between serum DKK-1 levels and AS risk.
Gut colonization with an obesity-associated enteropathogenic microbe modulates the premetastatic niches to promote breast cancer lung and liver metastasis
Authors: Parida Sheetal , Siddharth Sumit , Gatla Himavanth R. , Wu Shaoguang , Wang Guannan , Gabrielson Kathleen , Sears Cynthia L. , Ladle Brian H. , Sharma Dipali
Published: July 2023

Introduction

Obesity, an independent risk factor for breast cancer growth and metastatic progression, is also closely intertwined with gut dysbiosis; and both obese state and dysbiosis promote each other. Enteric abundance of Bacteroides fragilis is strongly linked with obesity, and we recently discovered the presence of B. fragilis in malignant breast cancer. Given that enterotoxigenic B. fragilis or ETBF, which secretes B. fragilis toxin (BFT), has been identified as a procarcinogenic microbe in breast cancer, it is necessary to examine its impact on distant metastasis and underlying systemic and localized alterations promoting metastatic progression of breast cancer.

Methods

We used syngeneic mammary intraductal (MIND) model harboring gut colonization with ETBF to query distant metastasis of breast cancer cells. Alterations in the immune network and cytokines/chemokines in the tumor microenvironment and distant metastatic sites were examined using flow cytometry, immunohistochemistry, and multiplex arrays.

Results

ETBF infection initiates a systemic inflammation aiding in the establishment of the premetastatic niche formation in vital organs via increased proinflammatory and protumorigenic cytokines like IL17A, IL17E, IL27p28, IL17A/F, IL6, and IL10 in addition to creating a prometastatic immunosuppressive environment in the liver and lungs rich in myeloid cells, macrophages, and T regulatory cells. It induces remodeling of the tumor microenvironment via immune cell and stroma infiltration, increased vasculogenesis, and an EMT-like response, thereby encouraging early metastatic dissemination ready to colonize the conducive environment in liver and lungs of the breast tumor-bearing mice.

Discussion

In this study, we show that enteric ETBF infection concomitantly induces systemic inflammation, reshapes the tumor immune microenvironment, and creates conducive metastatic niches to potentiate early dissemination and seeding of metastases to liver and lung tissues in agreement with the “seed and soil hypothesis.” Our results also support the ETBF-induced “parallel model” of metastasis that advocates for an early dissemination of tumor cells that form metastatic lesions independent of the primary tumor load.
Evidence for a causal relationship between psoriasis and cutaneous melanoma: a bidirectional two-sample Mendelian randomized study
Authors: Zhao Nana , Guo Pengsen , Tang Mei , Yang Fan , Zhang Tongtong , Mao Rui
Published: July 2023

Background and objective

Existing cross-sectional and retrospective studies were unable to establish a causal relationship between psoriasis and cutaneous melanoma (CM). We sought to evaluate the causal role between psoriasis and CM.

Methods

We performed a bidirectional two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of psoriasis and CM among individuals of predominantly European ancestry. Mendelian randomization–Egger regression, inverse variance weighting, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, weighted mode, and weighted median were used to examine the causal effect between psoriasis and CM.

Results

Genetically predicted psoriasis was a significant risk factor for CM (odds ratio, 1.69; 95% confidence interval, 1.15–2.48; P = 0.025). In contrast, no association was observed between genetically predicted CM and psoriasis.

Conclusion

Our findings corroborated the existence of genetically predicted psoriasis increases risk of CM. Enhanced early screening of cutaneous melanoma in patients with psoriasis may improve clinical burden. However, we did not find evidence for a causal link from CM to psoriasis, so further studies are required to elucidate the effect of CM activity on psoriasis.
HPV16 E6/E7 -based mRNA vaccine is therapeutic in mice bearing aggressive HPV-positive lesions
Authors: Zhou Kun , Yuzhakov Olga , Behloul Nouredine , Wang Dehua , Bhagat Lakshmi , Chu Dafeng , Zhang Xinyue , Cheng Xinwei , Fan Lusheng , Huang Xinyu , Mirabella Teodelinda
Published: July 2023

HPV (Human papillomavirus) affects 600,000 people worldwide each year. Almost all cervical cancers are associated with a past HPV infection. In particular, the positivity to the high-risk type HPV16 is detected in most of the invasive cervical cancers. FDA has approved prophylactic vaccines that protect against new HPV16 infections, but do not induce immunity in those patients with established infections or neoplasms. To date, no therapeutic vaccine targeting HPV16-associated lesions has been authorized. We have developed an mRNA-based vaccine against the HPV16 late oncoproteins E6 and E7, which are abundantly and exclusively expressed in high-grade squamous intraepithelial lesions (HSILs), a stage of the cervical disease that precedes the progression to carcinoma. Our in vitro and in vivo studies demonstrated that the translated mRNA is functional and elicits an antigen-specific adaptive immune response. Upon immunization with the vaccine, mice with HPV16+ lesions exhibited tumor growth inhibition, extension of lifespan, and development of a protective immune memory. In light of these results and the remarkable clinical success of mRNA vaccines against SARS-CoV2, we believe that our mRNA-based therapeutic vaccine has the potential to offer a non-invasive treatment alternative to the current standard of care for HPV16+ HSILs.
Case Report: Biological treatment of epidermolysis bullosa acquisita: report on four cases and literature review
Authors: Szymański Konrad , Kowalewski Cezary , Pietrzyk Ewelina , Woźniak Katarzyna
Published: July 2023

Epidermolysis bullosa acquisita (EBA) is a chronic, recurrent autoimmune subepidermal bullous disease characterized by the presence of autoantibodies targeting type VII collagen -- basement membrane zone antigen. Standard therapy for EBA includes a combination of systemic corticosteroids and dapsone; however, severe cases may require advanced treatment. The current article reports on four EBA cases in which biologics: infliximab, rituximab (Rtx), and intravenous immunoglobulin (IVIG) were applied. All patients fulfilled the clinical and immunological criteria of EBA: they presented tense blisters healing with atrophic scars on the skin on traumatized areas and in mucous membranes. The diagnosis of EBA was established using numerous techniques: direct and indirect immunofluorescence, salt split skin, ELISA, Fluorescence Overlay Antigen Mapping using Laser Scanning Confocal Microscopy. Since all the patients did not achieve long-term remission on standard treatment (prednisone, dapsone) due to ineffectiveness or side effects of drugs, they eventually were treated with biologics leading to extraordinary skin improvement and stopping the disease for 1-3 years. Biologics in all patients were tolerated very well. No side effects were observed during application as well as multi-month follow-up. The presented cases provide a premise that biological drugs can be a valuable component of EBA therapy.
Design and redesign of a bottom trawl survey in Chesapeake Bay, USA
Authors: Latour Robert J. , Gartland James , Bonzek Christopher F.
Published: July 2023

Fisheries-independent surveys that reliably sample a broad size range of exploited and ecologically important species provide valuable data in support of fisheries management and ecosystem science. The operational consistency of surveys over time and space is fundamental to the interpretation of data in the contexts of population dynamics processes, community interactions, policy impacts, and environmental forcing. However, the need to maintain historic sampling protocols over extended time periods limits the utilization of new technologies that could lead to improved data collection. Survey vessel replacements also become inevitable as the maturity of sampling programs becomes multidecadal. This case study describes the motivational origin, initial design, and redesign of a bottom trawl survey operating in Chesapeake Bay, the largest estuary in the United States. Regional aspirations to consider ecosystem principles in fisheries management aided initial development of the survey, and the need to collect specific data types to support that endeavor impacted several early design elements. Following the beginning years of full-scale survey operations, a consistently evolving awareness of potential areas of improvement for the survey grew from formal efforts to engage with scientific and industry partners on trawl gear design, leverage the program for additional survey opportunities, utilize gear testing technology, and analyze extant data. When the delivery of a new, state-of-the-art research vessel forced the transfer of survey operations to a new platform, all potential changes were incorporated simultaneously. A subsequent paired-tow experiment was conducted to build a calibration database that successfully provided estimates of relative selectivity for routinely sampled taxa. This experience yielded several lessons learned that are intended to aid investigators faced with adopting structural changes to fisheries-independent surveys in the future.
Image quality and evaluation ability of magnetic resonance imaging techniques for thyroid-associated ophthalmopathy: Dixon fat-suppression technique vs. spectral attenuated inversion recovery
Authors: Huang Kai , Lin Xiaoxin , Luo Yaosheng , Hu Qiugen , Guo Baoliang , Ouyang Fusheng , Ouyang Yufeng , Song Cheng , Chen Haixiong
Published: July 2023

Purpose

We aimed to compare two magnetic resonance imaging (MRI) techniques, Dixon and spectral attenuated inversion recovery (SPAIR) fat-suppression, in terms of image quality and suitability for evaluating thyroid-associated ophthalmopathy (TAO) lesion characteristics.

Methods

This cross-sectional, retrospective study involved 70 patients with TAO (140 eyes) who underwent orbital coronal MRI examinations, including Dixon-transverse relaxation (T2)-weighted imaging (T2WI) and SPAIR-T2WI, between 2020 and 2022. We compared the fat-suppression quality and artifacts, noise (N), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal intensity ratio (SIR) of extraocular muscles (SIR-EOM) and lacrimal glands (SIR-LG), and TAO activity evaluation efficiency.

Results

Dixon-T2WI showed a higher frequency of better subjective image quality and suitability for evaluating the characteristics of TAO lesions (65.7% vs. 14.3%) than SPAIR-T2WI. Fat-suppression quality and artifact scores were lower for Dixon-T2WI than for SPAIR-T2WI (p < 0.001). The N, SNR, and CNR values, EOM-SIR, and LG-SIR were higher for orbital coronal Dixon-T2WI than for SPAIR-T2WI (all p < 0.001). Clinical activity scores (CASs) showed positive correlations with SIR. The correlation between EOM-SIR and LG-SIR of orbital coronal Dixon-T2WI with CAS was higher than that of SPAIR-T2WI (0.590 vs. 0.493, all p < 0.001; 0.340 vs. 0.295, all p < 0.01). EOM-SIR and LG-SIR of Dixon-T2WI yielded a higher area under the curve than SPAIR-T2WI for evaluating TAO activity (0.865 vs. 0.760, p < 0.001; 0.695 vs. 0.617, p = 0.017).

Conclusion

Dixon-T2WI yields higher image quality than SPAIR-T2WI. Furthermore, it has a stronger ability to evaluate TAO inflammation than SPAIR, with higher sensitivity and specificity in active TAO staging.
Evaluating the design of the Integrated Care for Older People: a theory of change approach
Authors: Gutiérrez-Barreto Samuel E. , Sosa-Tinoco Eduardo , Rojas-Calixto Oscar , Deniss-Navarro Zayda , Avila-Avila Arturo , Gutierrez Juan Pablo
Published: July 2023

Introduction

Given the progressive aging of the population, there is an urgent need at the health system level to implement effective models to care for older people (OP). Healthy aging is imperative to reach the Sustainable Development Goals. The World Health Organization (WHO) developed the Integrated Care for Older People (ICOPE) strategy to address this challenge. Implementing ICOPE requires its adaption to a specific context. We propose a pathway for such adaptation through an evaluation of the design of ICOPE; thus, we aim to describe the Theory of Change (ToC) of ICOPE and evaluate it for its implementation in Mexico City.

Methods

Based on the WHO and published literature documentation, we drafted an initial ToC for ICOPE. Then, we validated the ToC with experts in ICOPE, after which we evaluated and refined it by discussing the causal pathway, intervention required to activate it, rationale, and assumptions in consecutive workshops with 91 stakeholders and healthcare workers, using the nominal group technique to reach a consensus.

Results

The resulting ToC has the potential to contribute to healthy aging by three expected impacts: (1) prevention, reversal, or delaying of the decline of intrinsic capacity (IC) in OP; (2) improvement of the quality of life of OP; and (3) increase of disability-free life expectancy. The ICOPE causal pathway had ten preconditions, including the availability of resources, identifying at-risk individuals, available treatments, and evaluating results.

Discussion

We adapted ICOPE to a specific implementation context by evaluating its ToC in a participatory process that allows us to identify challenges and address them, at least in terms of the guidelines to operate the strategy. As ICOPE is an approach for a primary healthcare system, its adoption in a community healthcare program is promising and feasible. Evaluation as a tool could contribute to the design of effective interventions. The evaluation of the design of ICOPE for its implementation contributes to the strength of its potential to improve care for OP. This design for implementing ICOPE has the potential to be applied to similar contexts, for example, in other lower-middle-income countries.
Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients
Authors: Liu Jiaping , Shao Tianyu , Chen Hanwen , Ma Chenyang , Lu Xiaohui , Yang Xiaoming , Song Kang , Wang Lu , Lei Shu , Wang Dafen
Published: July 2023

Aim

The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies.

Method

A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48 h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores.

Results

Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p < 0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p < 0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO2 before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647–0.782) better than heart rate (AUC 0.618; 95% CI 0.545–0.690), PaO2 (AUC 0.59; 95% CI 0.515–0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p = 0.05). And the SCHE concentration was strongly correlated with the patient’s weaning difficulties (p < 0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman’s correlation analysis (p < 0.01).

Conclusion

Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO2 were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients.
Risk factors for BK virus infection in DCD donor kidney transplant recipients
Authors: Liu Yiting , Kong Chenyang , Hu Haochong , Zhang Yalong , Wang Tianyu , Qiu Tao , Zhou Jiangqiao
Published: July 2023

Background

BK virus infection after kidney transplantation can negatively impact the prognosis of patients. However, current risk factor analyses primarily focus on BK virus nephropathy, while BK viruria and BK viruria progressing to BK viremia receive less attention. This study aims to analyze the risk factors associated with BK viruria and BK viruria progressing to BK viremia in recipients of donation after cardiac death (DCD), with the goal of facilitating early intervention.

Methods

Donor characteristics and clinical data of recipients before and after transplantation were evaluated, and logistic univariate and multivariate analyses were performed to determine the risk factors associated with BK viruria and the progression of BK viruria to BK viremia. Additionally, machine learning techniques were employed to identify the top five features associated with BK viruria evolving into BK viremia.

Results

During a median follow-up time of 1,072 days (range 739–1,418), 69 transplant recipients (15.6% incidence rate) developed BK viruria after transplantation, with 49.3% of cases occurring within 6 months post-transplantation. Moreover, 19 patients progressed to BK viremia. Donor age [OR: 1.022 (1.000, 1.045), p = 0.047] and donor procalcitonin (PCT) levels [0.5–10 ng/ml; OR: 0.482 (0.280, 0.828), p = 0.008] were identified as independent risk factors for BK viruria. High BK viruria [OR: 11.641 (1.745, 77.678), p = 0.011], recipient age [OR: 1.106 (1.017, 1.202), p = 0.018], and immunoinduction regimen [ATG; OR: 0.063 (0.006, 0.683), p = 0.023] were independent risk factors for BK viruria progressing to BK viremia. Machine learning analysis confirmed the importance of high BK viruria, recipient age, and immunoinduction regimen (ATG) in predicting the progression of BK viruria to BK viremia.

Conclusion

The development and progression of BK virus in DCD kidney transplant recipients is influenced by multiple factors. Early intervention and treatment could potentially extend the lifespan of the transplanted organ.
The glycoside hydrolase gene family profile and microbial function of Debaryomyces hansenii Y4 during South-road dark tea fermentation
Authors: Zou Yao , Liu Minqiang , Lai Yuqing , Liu Xuyi , Li Xian , Li Yimiao , Tang Qian , Xu Wei
Published: July 2023

Microbes are crucial to the quality formation of Sichuan South-road Dark Tea (SSDT) during pile-fermentation, but their mechanism of action has not yet been elucidated. Here, the glycoside hydrolase (GH) gene family and microbial function of Debaryomyces hansenii Y4 during solid-state fermentation were analyzed, and the results showed that many GH genes being distributed in comparatively abundant GH17, GH18, GH76, GH31, GH47, and GH2 were discovered in D. hansenii. They encoded beta-galactosidase, alpha-D-galactoside galactohydrolase, alpha-xylosidase, mannosidase, etc., and most of the GHs were located in the exocellular space and participated in the degradation of polysaccharides and oligosaccharides. D. hansenii Y4 could develop the mellow mouthfeel and “reddish brown” factors of SSDT via increasing the levels of water extracts, soluble sugars and amino acids but decreasing the tea polyphenols and caffeine levels, combined with altering the levels of thearubiins and brown index. It may facilitate the isomerization between epicatechin gallate and catechin gallate. Moreover, the expression levels of DEHA2G24860g (Beta-galactosidase gene) and DEHA2G08602g (Mannan endo-1,6-alpha-mannosidase DFG5 gene) were sharply up-regulated in fermentative anaphase, and they were significantly and negatively correlated with epicatechin content, especially, the expression of DEHA2G08602g was significantly and negatively correlated with catechin gallate level. It was hypothesized that D. hansenii Y4 is likely to be an important functional microbe targeting carbohydrate destruction and catechin transformation during SSDT pile-fermentation, with DEHA2G08602g as a key thermotolerant functional gene.
The advantages of artificial intelligence-based gait assessment in detecting, predicting, and managing Parkinson’s disease
Authors: Wu Peng , Cao Biwei , Liang Zhendong , Wu Miao
Published: July 2023

Background

Parkinson’s disease is a neurological disorder that can cause gait disturbance, leading to mobility issues and falls. Early diagnosis and prediction of freeze episodes are essential for mitigating symptoms and monitoring the disease.

Objective

This review aims to evaluate the use of artificial intelligence (AI)-based gait evaluation in diagnosing and managing Parkinson’s disease, and to explore the potential benefits of this technology for clinical decision-making and treatment support.

Methods

A thorough review of published literature was conducted to identify studies, articles, and research related to AI-based gait evaluation in Parkinson’s disease.

Results

AI-based gait evaluation has shown promise in preventing freeze episodes, improving diagnosis, and increasing motor independence in patients with Parkinson’s disease. Its advantages include higher diagnostic accuracy, continuous monitoring, and personalized therapeutic interventions.

Conclusion

AI-based gait evaluation systems hold great promise for managing Parkinson’s disease and improving patient outcomes. They offer the potential to transform clinical decision-making and inform personalized therapies, but further research is needed to determine their effectiveness and refine their use.
An EEG-based attention recognition method: fusion of time domain, frequency domain, and non-linear dynamics features
Authors: Chen Di , Huang Haiyun , Bao Xiaoyu , Pan Jiahui , Li Yuanqing
Published: July 2023

Introduction

Attention is a complex cognitive function of human brain that plays a vital role in our daily lives. Electroencephalogram (EEG) is used to measure and analyze attention due to its high temporal resolution. Although several attention recognition brain-computer interfaces (BCIs) have been proposed, there is a scarcity of studies with a sufficient number of subjects, valid paradigms, and reliable recognition analysis across subjects.

Methods

In this study, we proposed a novel attention paradigm and feature fusion method to extract features, which fused time domain features, frequency domain features and nonlinear dynamics features. We then constructed an attention recognition framework for 85 subjects.

Results and discussion

We achieved an intra-subject average classification accuracy of 85.05% ± 6.87% and an inter-subject average classification accuracy of 81.60% ± 9.93%, respectively. We further explored the neural patterns in attention recognition, where attention states showed less activation than non-attention states in the prefrontal and occipital areas in α, β and θ bands. The research explores, for the first time, the fusion of time domain features, frequency domain features and nonlinear dynamics features for attention recognition, providing a new understanding of attention recognition.
Weight, insulin resistance, blood lipids, and diet quality changes associated with ketogenic and ultra low-fat dietary patterns: a secondary analysis of the DIETFITS randomized clinical trial
Authors: Aronica Lucia , Landry Matthew J. , Rigdon Joseph , Gardner Christopher D.
Published: July 2023

Background

The DIETFITS trial reported no significant difference in 12-month weight loss between a healthy low-fat and healthy low-carbohydrate diet. Participants were instructed to restrict fat or carbohydrates to levels consistent with a ketogenic or ultra low-fat diet for 2  months and to subsequently increase intakes until they achieved a comfortable maintenance level.

Objective

To compare 3- and 12-month changes in body weight and cardiometabolic risk factors between a subsample of participants who reported 3-month fat or carbohydrates intakes consistent with either a ketogenic-like diet (KLD) or ultra low-fat diet (ULF).

Design

3-month and 12-month weight and risk factor outcomes were compared between KLD (n = 18) and ULF (n = 21) sub-groups of DIETFITS participants (selected from n = 609, healthy overweight/obese, aged 18–50  years).

Results

Less than 10% of DIETFITS participants met KLD or ULF criteria at 3-months. Both groups achieved similar weight loss and insulin resistance improvements at 3-months and maintained them at 12- months. Significant differences at 3-months included a transient ~12% increase in LDL cholesterol (LDL-C) for KLD with a concomitant greater reduction in log(TG/HDL), a measure of LDL-C’s atherogenic potential. The latter was maintained at 12-months, despite substantial diet recidivism for both groups, whereas LDL-C levels were similar for ULF at baseline and 12-months. KLD participants achieved and maintained the greatest reductions in added sugars and refined grains at 3- months and 12-months, whereas ULF participants reported a 50% increase in refined grains intake from baseline to 12-months.

Conclusion

Among the ~10% of study participants that achieved the most extreme restriction of dietary fat vs. carbohydrate after 3  months, weight loss and improvement in insulin sensitivity were substantial and similar between groups. At 12  months, after considerable dietary recidivism, the few significant differences in diet quality and blood lipid parameters tended to favor KLD over ULF.
Glioblastoma-on-a-chip construction and therapeutic applications
Authors: Xie Zuorun , Chen Maosong , Lian Jiangfang , Wang Hongcai , Ma Jingyun
Published: July 2023

Glioblastoma (GBM) is the most malignant type of primary intracranial tumor with a median overall survival of only 14 months, a very poor prognosis and a recurrence rate of 90%. It is difficult to reflect the complex structure and function of the GBM microenvironment in vivo using traditional in vitro models. GBM-on-a-chip platforms can integrate biological or chemical functional units of a tumor into a chip, mimicking in vivo functions of GBM cells. This technology has shown great potential for applications in personalized precision medicine and GBM immunotherapy. In recent years, there have been efforts to construct GBM-on-a-chip models based on microfluidics and bioprinting. A number of research teams have begun to use GBM-on-a-chip models for the investigation of GBM progression mechanisms, drug candidates, and therapeutic approaches. This review first briefly discusses the use of microfluidics and bioprinting technologies for GBM-on-a-chip construction. Second, we classify non-surgical treatments for GBM in pre-clinical research into three categories (chemotherapy, immunotherapy and other therapies) and focus on the use of GBM-on-a-chip in research for each category. Last, we demonstrate that organ-on-a-chip technology in therapeutic field is still in its initial stage and provide future perspectives for research directions in the field.
Photodynamic therapy induced cell cycle arrest and cancer cell synchronization: review
Authors: Moloudi Kave , Abrahamse Heidi , George Blassan P.
Published: July 2023

Cell cycle arrest (CCA) is seen as a prime candidate for effective cancer therapy. This mechanism can help researchers to create new treatments to target cancer cells at particular stages of the cell cycle (CC). The CCA is a characteristic of various therapeutic modalities, including radiation (RT) and chemotherapy (CT), which synchronizes the cells and facilitates the standardization of radio-chemotherapy protocols. Although it was discovered that photodynamic treatment (PDT) had a biological effect on CCA in cancer cells, the mechanism remains unclear. Furthermore, besides conventional forms of cell death such as apoptosis, autophagy, and necrosis, various unconventional types of cell death including pyroptosis, mitotic catastrophe, paraptosis, ferroptosis, necroptosis, and parthanatos after PDT have been reported. Thus, a variety of elements, such as oxygen, the tumor’s microenvironment, the characteristics of light, and photosensitizer (PS), influence the effectiveness of the PDT treatment, which have not yet been studied clearly. This review focuses on CCA induced by PDT for a variety of PSs agents on various cell lines. The CCA by PDT can be viewed as a remarkable effect and instructive for the management of the PDT protocol. Regarding the relationship between the quantity of reactive oxygen species (ROS) and its biological consequences, we have proposed two mathematical models in PDT. Finally, we have gathered recent in vitro and in vivo studies about CCA post-PDT at various stages and made suggestions about how it can standardize, potentiate, and customize the PDT methodology.
Early bile drainage improves native liver survival in biliary atresia without cholangitis
Authors: Liu Fei , Xu Xiaogang , Liang Zijian , Tao Boyuan , Lan Menglong , Zeng Jixiao
Published: July 2023

Objectives

To explore the outcomes and related factors in children without cholangitis after Kasai portoenterostomy (KPE).

Methods

We retrospectively analyzed the data of infants with type III BA who underwent KPE from June 2016 to December 2021. We compared and analyzed the difference in native liver survival (NLS) rates in different types of cholangitis. We also investigated the relationship between the absence of cholangitis and the effect of early bile drainage (EBD) as well as the related factors affecting EBD efficacy.

Results

A total of 145 children were included in this study. Among these children, 82 (56.6%, 82/145) had cholangitis, including 40 (48.8%, 40/82) with early cholangitis and 33 (40.2%, 33/82) with recurrent cholangitis. The median follow-up period was 29 months (range, 2–75 months). The NLS rates were 67.6%, 51.7%, 45.5% and 43.4% at 6 months, 1 year, 2 years and 5 years following KPE, while the NLS rates for infants without cholangitis after KPE were 68.3%, 50.8%, 46.0% and 46.0%, respectively. Higher gamma-glutamyl transferase (γ- GT) and total bile acid (TBA) before KPE were risk factors for cholangitis (P < 0.05). The NLS rate in recurrent cholangitis was significantly lower than that in occasional cholangitis (P < 0.01). Compared with the EBD-poor group, the NLS rate in the EBD-good group of infants was significantly increased (P < 0.001). EBD was significantly correlated with the occurrence and frequency of cholangitis (P < 0.05).

Conclusions

Recurrent cholangitis was an important factor affecting NLS. For children without cholangitis after KPE, early bile drainage was better, and the NLS was longer.
Comparing the efficacy of vaginal micronized progesterone gel and capsule for prevention of preterm birth in singleton pregnancies with short cervical length at midtrimester: an indirect comparison meta-analysis
Authors: Kabiri Doron , Hamou Yael , Gordon Gali , Ezra Yosef , Matok Ilan
Published: July 2023

Objective: To evaluate the effectiveness of vaginal progesterone in preventing preterm birth in women with a singleton gestation and short cervical length and to determine which of the two formulations, micronized progesterone vaginal capsule versus vaginal gel containing micronized progesterone, is more effective for preventing preterm birth.

Data sources: A systematic search was performed in the following databases: EMBASE, PubMed (MEDLINE), The Cochrane Library, and the Clinical Trials Registry (clinicaltrials.gov).

Study eligibility criteria: Randomized controlled trials (RCTs), prospective and retrospective observational studies were included. We searched for progesterone administration to prevent preterm birth in asymptomatic women with a shortened cervix (<25 mm) measured by ultrasound in the second trimester of singleton pregnancy.

Study appraisal and synthesis methods: Assessments of the risk of bias of RCTs were performed by applying the Cochrane Collaboration’s Risk of Bias Tool; non-randomized control trials were evaluated with the Newcastle–Ottawa Scale (NOS). The primary outcome was preterm birth ≤33 weeks of gestation. Pooled relative risks (RR) and 95% CI’s were calculated for dichotomous outcomes. Heterogeneity of treatment effect was assessed with the I2 statistic. We pooled results of the primary outcome for individual studies using a random-effect model. We then performed a network meta-analysis to pool indirect comparisons between the two formulations (gel vs capsule). This analysis was performed using the network meta-analysis package within the R environment.

Results: Five studies met the inclusion criteria (4 RCTs, one cohort study) including 1,048 women. The meta-analysis demonstrated that vaginal micronized progesterone significantly reduces preterm birth risk, Risk Ratio = 0.63; 95% CI, 0.48–0.82; p = 0.0006; with no heterogeneity between the studies: I2 = 0%. In the network meta-analysis, no significant difference was demonstrated (OR = 0.85; 95% CI, 0.43–1.69) between the effect of the two formulations of vaginal micronized progesterone (vaginal gel versus vaginal capsules) on the risk of PTB.

Conclusion: Vaginal progesterone is associated with a decreased risk of premature birth in women with a shortened cervix in the second trimester of pregnancy. No differences were found between vaginal micronized progesterone in gel or capsule formulations.

Systematic Review Registration: PROSPERO, identifier CRD42020165198.
Major adverse cardiovascular events associated with testosterone treatment: a pharmacovigilance study of the FAERS database
Authors: Zhao Hui , Li Jun-Min , Li Zi-Ran , Zhang Qian , Zhong Ming-Kang , Yan Ming-Ming , Qiu Xiao-Yan
Published: July 2023

Background and purpose: Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website. The data mining protocol including the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) was applied to analyze overreporting caused by risk factors and MACEs, including TRT, morbidities, and ages. The ROR and the BCPNN were also applied to investigate the annually developing trend of pharmacovigilance (PV) signals in the real world, retrospectively.

Results: A total of 3,057 cases referring to MACEs, with a median age of 57 years old (yo), were identified from 28,921 cases of testosterone users. MACEs related to PV signals have emerged since 2014, including cardiac death, non-fatal myocardial infarction, and non-fatal stroke. Myocardial infarction (MI) (ROR: 9.46; IC025: 3.08), acute myocardial infarction (AMI) (ROR: 16.20; IC025: 3.72), ischemic cardiomyopathy (ROR: 11.63; IC025: 2.20), and cardiomyopathy (ROR: 5.98; IC025: 1.96) were the most significant signals generated, and weaker signals included cardiac failure acute (ROR: 4.01; IC025: 0.71), cardiac arrest (ROR: 1.88; IC025: 0.56), and ventricular fibrillation (VF) (ROR: 2.38; IC025: 0.38). The time-to-onset (TTO) of MACEs was calculated with a median of 246 days for AMI.

Conclusion: For myocardial infarction and cardiomyopathy, TRT statistically tended to increase the risk of MACEs, while for cardiac arrhythmia, cardiac failure, and stroke, TRT demonstrated beneficial effects among the population with morbidities, such as testosterone deficiency (TD), diabetes mellitus (DM), and hypertension. MACEs were rare but led to serious outcomes including significant increase in death and disability. Since 2018, and before 2014, reports referring to TRT associated with MACEs were relatively scarce, which indicated that there might be a considerable number of cases that went unrecorded, due to neglection. Health workers and testosterone users might pay more attention to testosterone-induced MACEs.
The localised density of H2O2 in the effluent of a cold atmospheric pressure plasma jet determined by continuous-wave cavity ring-down spectroscopy
Authors: Klose S.-J. , Krös L. , van Helden J. H.
Published: July 2023

Although the research on cold atmospheric pressure plasma jets and their applications is steadily growing, several questions remain open regarding fundamental aspects of how reactive species, such as hydrogen peroxide (H2O2), are generated in cold atmospheric pressure plasma jets, and how the composition of reactive species can be tailored for a specific purpose. Accordingly, absolute and spatially resolved distributions of the densities of reactive species in the effluent of cold atmospheric pressure plasma jets are required. In this work, a time efficient way to determine the local distribution of gas phase H2O2 in the effluent of a cold atmospheric-pressure plasma jet using continuous-wave cavity ring-down spectroscopy at a wavelength of 8.12 μm is presented. By a combination of an axial scan and of several radial distributions, the localised density distribution of H2O2 in the effluent of the kINPen-sci plasma jet was obtained. Therefore, the effective absorption length was determined from the evolution of the radial distributions as a function of the distance from the nozzle, which was 1.6 mm close to the nozzle of the plasma jet, and increased to approximately 5 mm at a distance of 10 mm from the nozzle. The maximum density of approximately 2 ⋅ 1014 cm−3 was found in the centre of the effluent close to the nozzle. From the presented localised density distribution, it can be concluded that H2O2 is significantly generated within the plasma zone of the plasma jet. This work presents an important step towards the understanding of formation and consumption mechanisms of biomedically relevant species in the plasma zone and the effluent of a cold atmospheric pressure plasma jet.
Role of oxidative stress in the relationship between periodontitis and systemic diseases
Authors: Shang Jiaxin , Liu Haifeng , Zheng Youli , Zhang Zheng
Published: July 2023

Periodontitis is a common inflammatory disease. It is characterized by destruction of the supporting structures of the teeth and could lead to tooth loss and systemic inflammation. Bacteria in inflamed gingival tissue and virulence factors are capable of entering the bloodstream to induce systemic inflammatory response, thus influencing the pathological process of many diseases, such as cardiovascular diseases, diabetes, chronic kidney disease, as well as liver injury. An increasing body of evidence show the complex interplay between oxidative stress and inflammation in disease pathogenesis. When periodontitis occurs, increased reactive oxygen species accumulation leads to oxidative stress. Oxidative stress contributes to major cellular components damage, including DNA, proteins, and lipids. In this article, the focus will be on oxidative stress in periodontal disease, the relationship between periodontitis and systemic inflammation, and the impact of periodontal therapy on oxidative stress parameters.