bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunosuppressive microvesicles-mimetic derived from tolerant dendritic cells to target T-lymphocytes for inflammation diseases therapy
Authors: Lin Minghao , Lei Siyun , Chai Yingqian , Xu Jianghua , Wang Youchao , Wu Chenghu , Jiang Hongyi , Yuan Shanshan , Wang Jilong , Lyu Jie , Lu Mingqin , Deng Junjie
Published: April 2024

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.
A reduced exposure heated tobacco product was introduced then abruptly taken off United States shelves: results from a tobacco harm reduction natural experiment
Authors: Noggle Brendan , Ball Kevin M. , Vansickel Andrea Rae
Published: April 2024

Background

A heated tobacco product (HTP) authorized for purchase in the United States by the Food and Drug Administration as a reduced harm product was removed from the market after about 2 years of sales. Adults who used the HTP were surveyed to determine the impact of the introduction and removal of the HTP on past and current tobacco behaviors.

Methods

Adults who were using the HTP before its United States market removal (n = 502) completed a cross-sectional online survey to determine their tobacco use behaviors at three timepoints: prior to HTP initiation, just before HTP market removal, and at the time of the survey which was administered approximately 10 months post-removal. Descriptive statistics summarized outcome variables and paired bivariate testing was used to compare percent change between timepoints. Multivariable logistic regression and general linear models estimated associations of tobacco use behaviors and cigarette consumption.

Results

Overall, significantly fewer adults consumed cigarettes while using HTP than before they tried the product (63.0% vs. 89.9%, p value < 0.0001) and the number of cigarettes consumed per week (CPW) decreased (106.3–39.0, p value < 0.0001). After HTP removal, the percent of adults who consumed cigarettes increased non-significantly (63.0–67.5%, p value = 0.0544) while CPW increased significantly (39.0–76.6 CPW, p value < 0.0001). At the time of the survey, over 25% of the sample continued to use the HTP and 7.2% reported use of no tobacco products. Electronic nicotine delivery system use had increased significantly from the prior period (27.4% increase, p value < 0.0001).

Conclusion

This study demonstrates reduction or elimination of combustible cigarette smoking while adults were using HTPs and some increased smoking after market removal, albeit at lower levels. If unable to find satisfying alternatives, adults who smoke and transition to reduced harm products may return to smoking or purchase products illicitly if their preferred products are removed from the regulated market.
Community-level group sports participation and all-cause, cardiovascular disease, and cancer mortality: a 7-year longitudinal study
Authors: Tsuji Taishi , Okada Eisaku , Saito Masashige , Kanamori Satoru , Miyaguni Yasuhiro , Hanazato Masamichi , Kondo Katsunori , Ojima Toshiyuki
Published: April 2024

Background

Community-level group sports participation is a structural aspect of social capital that can potentially impact individual health in a contextual manner. This study aimed to investigate contextual relationship between the community-level prevalence of group sports participation and the risk of all-cause, cardiovascular disease (CVD), and cancer mortality in older adults.

Methods

In this 7-year longitudinal cohort study, data from the Japan Gerontological Evaluation Study, a nationwide survey encompassing 43,088 functionally independent older adults residing in 311 communities, were used. Cause of death data were derived from the Japanese governmental agency, The Ministry of Health, Labour and Welfare, for secondary use. “Participation” was defined as engaging in group sports for one or more days per month. To analyze the data, a two-level survival analysis was employed, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Results

Among the participants, 5,711 (13.3%) deaths were identified, with 1,311 related to CVD and 2,349 to cancer. The average group sports participation rate was 28.3% (range, 10.0–52.7%). After adjusting for individual-level group sports participation and potential confounders, a higher community-level group sports participation rate was found to be significantly associated with a lower risk of both all-cause mortality (HR: 0.89, 95% CI: 0.83–0.95) and cancer mortality (HR: 0.89, 95% CI: 0.81–0.98) for every 10% point increase in the participation rate. For CVD mortality, the association became less significant in the model adjusted for all covariates (HR: 0.94, 95% CI: 0.82–1.09).

Conclusions

Our findings support the existence of a preventive relationship between community-level group sports participation and the occurrence of all-cause and cancer mortality among older individuals. Promoting group sports within communities holds promise as an effective population-based strategy for extending life expectancy, regardless of individual participation in these groups.
Plant cultural indicators of forest resources from the Himalayan high mountains: implications for improving agricultural resilience, subsistence, and forest restoration
Authors: Haq Shiekh Marifatul , Khoja Aadil Abdullah , Waheed Muhammad , Pieroni Andrea , Siddiqui Manzer H. , Bussmann Rainer W.
Published: April 2024

Aim

Biocultural legacy practices are intricately tied to forestry resources, ethnic identity, and social cohesiveness. This study aims to determine the plant cultural values of forest resources and identify plant cultural indicators in each ethnic group, which can aid in long-term natural resource management plans in the current debate on socio-environmental and ecological transitions.

Methods

Semi-structured interviews, focus group discussions, and field observations were employed to collect data for a comprehensive and systematic ethnobotanical survey from February 2018 to October 2022.

Results

A total of 330 informants reported 154 plant species from 65 families. Asteraceae was the most prominent botanical family, with herbaceous plant groups outnumbering trees and shrubs. The Gujjar and Pahari groups exhibited the highest level of overlap, followed by significant overlaps between the Gujjar and Kashmiri communities. The close affinity observed between the Gujjar and Pahari groups suggests the horizontal pattern of local plant knowledge between these communities, influenced by their sociocultural interactions and intermarriages. Notably, the Pahari community displayed a rich understanding of medicinal plants and shared unique uses for the reported taxa. This study affirms that both ecological factors and sociocultural influences have played significant roles in shaping local plant knowledge. A total of 31 plant species have been identified as plant cultural markers among all four ethnic groups. We observed a positive correlation between plant cultural values and plant use with the Gujjar and Kashmiri ethnic groups. Artemisia absinthium reported the highest use value of (0.57) with use reports of (189). Adonis aestivalis, Cynoglossum nervosum, Geum elatum, Geranium himalayense, Juncus inflexus, Oxalis acetosella, Polygonatum biflorum, and Salvia hians from the Himalayan region are among the plant taxa whose ethnomedicinal applications are described here for the first time.

Conclusion

Our data show that local and indigenous forest knowledge and practices could significantly contribute to forest conservation and ecological transition. This may happen if stakeholders generate clear frameworks and biocultural conservation strategies aimed at both dynamically preserve natural habitats and ways of traditional management of local natural resources.
Guidelines for conscientious objection in Spain: a proposal involving prerequisites and protocolized procedure
Authors: Herreros Benjamín , Ramnath Venktesh R. , Santiago-Saez Andrés , Velasco Sanz Tamara Raquel , Pinto Pastor Pilar
Published: April 2024

Healthcare professionals often face ethical conflicts and challenges related to decision-making that have necessitated consideration of the use of conscientious objection (CO). No current guidelines exist within Spain’s healthcare system regarding acceptable rationales for CO, the appropriate application of CO, or practical means to support healthcare professionals who wish to become conscientious objectors. As such, a procedural framework is needed that not only assures the appropriate use of CO by healthcare professionals but also demonstrates its ethical validity, legislative compliance through protection of moral freedoms and patients’ rights to receive health care. Our proposal consists of prerequisites of eligibility for CO (individual reference, specific clinical context, ethical justification, assurance of non-discrimination, professional consistency, attitude of mutual respect, assurance of patient rights and safety) and a procedural process (notification and preparation, documentation and confidentiality, evaluation of prerequisites, non-abandonment, transparency, allowance for unforeseen objection, compensatory responsibilities, access to guidance and/or consultative advice, and organizational guarantee of professional substitution). We illustrate the real-world utility of the proposed framework through a case discussion in which our guidelines are applied.
Positive buttress reduction in femoral neck fractures: a literature review
Authors: Han Shun , Zhang Ze-Yang , Zhou Ke , Yin Gui-Kun , Liu Yu-Chen , Wang Ben-jie , Wen Zhun
Published: April 2024

Background

Femoral neck fractures (FNFs) in young adults are usually caused by high-energy trauma, and their treatment remains a challenging issue for orthopedic surgeons. The quality of reduction is considered an important factor in improving the poor prognosis of patients with FNFs. In recent years, positive buttress closed reduction technique has received widespread attention in the treatment of FNFs. This comprehensive literature review is designed to encapsulate the impacts of both non-anatomic and anatomic reduction on the biomechanical stability, clinical outcomes, and postoperative complications in the management of FNFs, conjecture the efficacy of positively braced reduction techniques and provide a thorough summarization of the clinical outcomes.

Methods

In this literature review, we have examined all clinical and biomechanical studies related to the treatment of FNFs using non-anatomical reduction or positive and negative buttress reduction. PubMed, Web of Science, Google Scholar and Embase Library databases were searched systematically for studies published before September 1, 2023. Published literature on fracture reduction techniques for treating FNFs was reviewed. In addition, we evaluated the included literature using the MINORs tool.

Results

Although the “arch bridge” structure formed by the positive buttress reduction technique improved the support to the cortical bone and provided a more stable biomechanical structure, no significant differences were noted in the clinical efficacy and incidence of postoperative complications between the positive buttress reduction and anatomical reduction.

Conclusion

Positive buttress reduction is an effective treatment method for young patients with FNFs. When facing difficult-to-reduce FNF, positive buttress reduction should be considered first, followed by anatomical reduction. However, negative buttress reduction should be avoided.
Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer’s disease
Authors: Vandermeulen Lina , Geric Ivana , Fumagalli Laura , Kreir Mohamed , Lu Ashley , Nonneman Annelies , Premereur Jessie , Wolfs Leen , Policarpo Rafaela , Fattorelli Nicola , De Bondt An , Van Den Wyngaert Ilse , Asselbergh Bob , Fiers Mark , De Strooper Bart , d’Ydewalle Constantin , Mancuso Renzo
Published: April 2024

Background

Microglia play important roles in maintaining brain homeostasis and neurodegeneration. The discovery of genetic variants in genes predominately or exclusively expressed in myeloid cells, such as Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2), as the strongest risk factors for Alzheimer’s disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of several microglial proteins are poorly conserved across species, which has hampered the development of strategies aiming to modulate the expression of specific microglial genes. One way to target APOE and TREM2 is to modulate their expression using antisense oligonucleotides (ASOs).

Methods

In this study, we identified, produced, and tested novel, selective and potent ASOs for human APOE and TREM2. We used a combination of in vitro iPSC-microglia models, as well as microglial xenotransplanted mice to provide proof of activity in human microglial in vivo.

Results

We proved their efficacy in human iPSC microglia in vitro, as well as their pharmacological activity in vivo in a xenografted microglia model. We demonstrate ASOs targeting human microglia can modify their transcriptional profile and their response to amyloid-β plaques in vivo in a model of AD.

Conclusions

This study is the first proof-of-concept that human microglial can be modulated using ASOs in a dose-dependent manner to manipulate microglia phenotypes and response to neurodegeneration in vivo.
Quantitative characterization of breast lesions and normal fibroglandular tissue using compartmentalized diffusion-weighted model: comparison of intravoxel incoherent motion and restriction spectrum imaging
Authors: He Litong , Qin Yanjin , Hu Qilan , Liu Zhiqiang , Zhang Yunfei , Ai Tao
Published: April 2024

Background

To compare the compartmentalized diffusion-weighted models, intravoxel incoherent motion (IVIM) and restriction spectrum imaging (RSI), in characterizing breast lesions and normal fibroglandular tissue.

Methods

This prospective study enrolled 152 patients with 157 histopathologically verified breast lesions (41 benign and 116 malignant). All patients underwent a full-protocol preoperative breast MRI, including a multi-b-value DWI sequence. The diffusion parameters derived from the mono-exponential model (ADC), IVIM model (Dt, Dp, f), and RSI model (C1, C2, C3, C1C2, F1, F2, F3, F1F2) were quantitatively measured and then compared among malignant lesions, benign lesions and normal fibroglandular tissues using Kruskal-Wallis test. The Mann-Whitney U-test was used for the pairwise comparisons. Diagnostic models were built by logistic regression analysis. The ROC analysis was performed using five-fold cross-validation and the mean AUC values were calculated and compared to evaluate the discriminative ability of each parameter or model.

Results

Almost all quantitative diffusion parameters showed significant differences in distinguishing malignant breast lesions from both benign lesions (other than C2) and normal fibroglandular tissue (all parameters) (all P < 0.0167). In terms of the comparisons of benign lesions and normal fibroglandular tissues, the parameters derived from IVIM (Dp, f) and RSI (C1, C2, C1C2, F1, F2, F3) showed significant differences (all P < 0.005). When using individual parameters, RSI-derived parameters-F1, C1C2, and C2 values yielded the highest AUCs for the comparisons of malignant vs. benign, malignant vs. normal tissue and benign vs. normal tissue (AUCs = 0.871, 0.982, and 0.863, respectively). Furthermore, the combined diagnostic model (IVIM + RSI) exhibited the highest diagnostic efficacy for the pairwise discriminations (AUCs = 0.893, 0.991, and 0.928, respectively).

Conclusions

Quantitative parameters derived from the three-compartment RSI model have great promise as imaging indicators for the differential diagnosis of breast lesions compared with the bi-exponential IVIM model. Additionally, the combined model of IVIM and RSI achieves superior diagnostic performance in characterizing breast lesions.
OTUD5 promotes the growth of hepatocellular carcinoma by deubiquitinating and stabilizing SLC38A1
Authors: Yang Yingnan , Jia Siying , Zhu Ning , Xiao Xuelian , Ma Ying , Tu Kangsheng , Guo Yong , Xu Qiuran
Published: April 2024

Background

Deubiquitinating enzymes (DUBs) cleave ubiquitin on substrate molecules to maintain protein stability. DUBs reportedly participate in the tumorigenesis and tumour progression of hepatocellular carcinoma (HCC). OTU deubiquitinase 5 (OTUD5), a DUB family member, has been recognized as a critical regulator in bladder cancer, breast cancer and HCC. However, the expression and biological function of OTUD5 in HCC are still controversial.

Results

We determined that the expression of OTUD5 was significantly upregulated in HCC tissues. High levels of OTUD5 were also detected in most HCC cell lines. TCGA data analysis demonstrated that high OTUD5 expression indicated poorer overall survival in HCC patients. OTUD5 silencing prominently suppressed HCC cell proliferation, while its overexpression markedly enhanced the proliferation of HCC cells. Mass spectrometry analysis revealed solute carrier family 38 member 1 (SLC38A1) as a candidate downstream target protein of OTUD5. Coimmunoprecipitation analysis confirmed the interaction between OTUD5 and SLC38A1. OTUD5 knockdown reduced and OTUD5 overexpression increased SLC38A1 protein levels in HCC cells. However, OTUD5 alteration had no effect on SLC38A1 mRNA expression. OTUD5 maintained SLC38A1 stability by preventing its ubiquitin-mediated proteasomal degradation. SLC38A1 silencing prominently attenuated the OTUD5-induced increase in HCC cell proliferation. Finally, OTUD5 knockdown markedly suppressed the growth of HCC cells in vivo.

Conclusions

OTUD5 is an oncogene in HCC. OTUD5 contributes to HCC cell proliferation by deubiquitinating and stabilizing SLC38A1. These results may provide a theoretical basis for the development of new anti-HCC drugs.
INSaFLU-TELEVIR: an open web-based bioinformatics suite for viral metagenomic detection and routine genomic surveillance
Authors: Santos João Dourado , Sobral Daniel , Pinheiro Miguel , Isidro Joana , Bogaardt Carlijn , Pinto Miguel , Eusébio Rodrigo , Santos André , Mamede Rafael , Horton Daniel L. , Gomes João Paulo ,   TELEVIR Consortium, Bigarré Laurent , Fernández-Pinero Jovita , Pais Ricardo J. , Marcacci Maurilia , Moreno Ana , Lilja Tobias , Øines Øivind , Rzeżutka Artur , Mathijs Elisabeth , Van Borm Steven , Rasmussen Morten , Spiess Katja , Borges Vítor
Published: April 2024

Background

Implementation of clinical metagenomics and pathogen genomic surveillance can be particularly challenging due to the lack of bioinformatics tools and/or expertise. In order to face this challenge, we have previously developed INSaFLU, a free web-based bioinformatics platform for virus next-generation sequencing data analysis. Here, we considerably expanded its genomic surveillance component and developed a new module (TELEVIR) for metagenomic virus identification.

Results

The routine genomic surveillance component was strengthened with new workflows and functionalities, including (i) a reference-based genome assembly pipeline for Oxford Nanopore technologies (ONT) data; (ii) automated SARS-CoV-2 lineage classification; (iii) Nextclade analysis; (iv) Nextstrain phylogeographic and temporal analysis (SARS-CoV-2, human and avian influenza, monkeypox, respiratory syncytial virus (RSV A/B), as well as a “generic” build for other viruses); and (v)algn2phenofor screening mutations of interest. Both INSaFLU pipelines for reference-based consensus generation (Illumina and ONT) were benchmarked against commonly used command line bioinformatics workflows for SARS-CoV-2, and an INSaFLU snakemake version was released. In parallel, a new module (TELEVIR) for virus detection was developed, after extensive benchmarking of state-of-the-art metagenomics software and following up-to-date recommendations and practices in the field. TELEVIR allows running complex workflows, covering several combinations of steps (e.g., with/without viral enrichment or host depletion), classification software (e.g., Kaiju, Kraken2, Centrifuge, FastViromeExplorer), and databases (RefSeq viral genome, Virosaurus, etc.), while culminating in user- and diagnosis-oriented reports. Finally, to potentiate real-time virus detection during ONT runs, we developedfindONTime, a tool aimed at reducing costs and the time between sample reception and diagnosis.

Conclusions

The accessibility, versatility, and functionality of INSaFLU-TELEVIR are expected to supply public and animal health laboratories and researchers with a user-oriented and pan-viral bioinformatics framework that promotes a strengthened and timely viral metagenomic detection and routine genomics surveillance. INSaFLU-TELEVIR is compatible with Illumina, Ion Torrent, and ONT data and is freely available athttps://insaflu.insa.pt/(online tool) andhttps://github.com/INSaFLU(code).
The effect of extracorporeal shock-wave therapy on pain in patients with various tendinopathies: a systematic review and meta-analysis of randomized control trials
Authors: Majidi Lobat , Khateri Sorour , Nikbakht Nikta , Moradi Yousef , Nikoo Mohammad Reza
Published: April 2024

Objectives

Tendinopathy is a common condition that affects the body’s tendon structures, causing discomfort, restricted movement, and reduced functionality. In this study, we looked at how extracorporeal shock wave therapy (ESWT) affected pain levels in individuals with various forms of tendinopathy around the world.

Design

This study is a comprehensive review and meta-analysis of previously published randomized controlled trials. To gather relevant data, the researchers performed keyword searches in international databases, including PubMed (Medline), Scopus, Web of Sciences, Cochrane Central Register of Controlled Trials (CENTRAL), Research Registers of ongoing trials (ClinicalTrials.gov), as well as Embase. The search was conducted up until March 2023. The quality of the selected articles was assessed using the Cochrane risk-of-bias method for randomized trials (RoB2).

Results

Based on the results of the meta-analysis, which included 45 clinical studies, the use of ESWT was found to have a significant impact on reducing pain in various conditions. The standardized mean difference (SMD) in patients with plantar fasciitis (PF) was reduced by 1.63 (SMD: -1.63, 95% CI: -3.04, -0.21; I2: 77.36%; P heterogeneity: 0.0001). For lateral epicondylitis (LE), the SMD was 0.63 (SMD: -0.63, 95% CI: -1.11, -0.16; I2: 67.50%; P heterogeneity: 0.003). In the case of chronic Achilles tendinopathy, the SMD was 1.38 (SMD: -1.38, 95% CI: -1.66, -1.10; I2: 96.44%; P heterogeneity: 0.0001). Additionally, in individuals with rotator cuff tendinopathy, the SMD for pain reduction was 2.37 units (SMD: -2.37, 95% CI: -3.58, -1.15; I2: 98.46%; P heterogeneity: 0.0001).

Conclusion

This study suggests that ESWT can be a highly effective therapy option for relieving pain in people with tendinopathy. Nonetheless, it is encouraged to make additional recommendations based on high-quality clinical research and more accurate information in order to define the optimal therapeutic options for each type of tendinopathy.
Microblading reaction as a manifestation of systemic sarcoidosis: two case reports and a review of the literature
Authors: Merzel Šabović Eva Klara , Starbek Zorko Mateja , Hosta Violeta , Žgavec Borut , Bajuk Vid
Published: April 2024

Background

Sarcoidosis is a multisystemic disease characterized by granulomatous inflammation. Sarcoidosis often poses a diagnostic challenge owing to its nonspecific or mild clinical features. In 20–35% of cases, sarcoidosis initially presents on skin. However, skin lesions commonly mimic dermatological conditions. Therefore, it is important to not underestimate the skin manifestations and perform histopathological examinations to make a timely diagnosis.

Case presentation

We present two cases of 33-year-old Caucasian female patients with orange–red macules and plaques that developed in the eyebrow area 1 and 6 years after microblading, respectively. Histopathological examination confirmed a diagnosis of sarcoidosis. The lymph nodes and lungs were also affected in both patients.

Conclusion

Our two reports suggest that an esthetic procedure involving dermal or subcutaneous injection of foreign materials can trigger the development of cutaneous and systemic sarcoidosis. However, this relationship has not been described yet. Physicians should, therefore, be aware of this complication to properly evaluate and treat such patients in a timely manner.
Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy
Authors: Liu Boxin , Wei Yan , He Jingjing , Feng Baofeng , Chen Yimeng , Guo Ruiyun , Griffin Matthew D. , Hynes Seán O. , Shen Sanbing , Liu Yan , Cui Huixian , Ma Jun , O’Brien Timothy
Published: April 2024

Background

Diabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators.

Methods

A male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators.

Results

Saline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1β) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks.

Conclusion

Intravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.
GC–IMS facilitates identification of carbapenem-resistant Klebsiella pneumoniae in simulated blood cultures
Authors: Li Fuxing , Zheng Yunwei , Zhao Chuwen , Zhu Junqi , Hang Yaping , Fang Youling , Hu Longhua
Published: April 2024

This study aimed to identify carbapenem-resistant Klebsiella pneumoniae (CRKP) based on changes in levels of its volatile organic compounds (VOCs) in simulated blood cultures (BCs) using the gas chromatography–ion mobility spectrometry (GC–IMS) technique. A comprehensive analysis of volatile metabolites produced by Klebsiella pneumoniae (K. pneumoniae) in BC bottles was conducted using GC–IMS. Subsequently, the released VOCs were analyzed to examine differences in VOC release between CRKP and carbapenem-susceptible Klebsiella pneumoniae (CSKP). A total of 54 VOCs were detected, of which 18 (6 VOCs found in both monomer and dimer forms) were successfully identified. The VOCs produced by K. pneumoniae in BC bottles (BacT/ALERT® SA) were primarily composed of organic acids, alcohols, esters, and ketones. The content of certain VOCs was significantly different between CRKP and CSKP after the addition of imipenem (IPM). Moreover, the inclusion of carbapenemase inhibitors facilitated the identification of carbapenemase-producing K. pneumoniae based on the variations in VOCs. This study demonstrates the utility of GC–IMS technology in identifying CRKP, and reveals that changes in VOCs are closely related to the growth and metabolism of K. pneumoniae, indicating that they can be leveraged to promote early identification of CRKP bacteremia. However, further in-depth studies and experiments are needed to validate our findings.
The impact of resource limitation on the pest-natural enemy ecosystem with anti-predator behavior and fear effect
Authors: Qin Wenjie , Dong Zhengjun
Published: April 2024

Research on agricultural pest control data indicates that the actual effectiveness of insecticides may exhibit slight variations, influenced by factors such as the type and quantity of pests. Additionally, the development of resistance by pests, as a result of adaptation to the environment, can impact the precision of pest control strategies. Hence we suggest implementing a nonlinear pulse state-dependent feedback control system, considering resource limitations, to investigate the influence of varying pesticide fatality rates on pest outbreaks. This paper takes into account the fear effect and anti-predator behavior to accurately portray the farmland ecosystem. We assessed the phase set and Poincaré map under the conditions for the existence of order-k (where $k=1,2,3$
k
=
1
,
2
,
3
) periodic solutions and examined their stability behavior. Remarkably, the system exhibited diverse bifurcation phenomena associated with pesticide-related parameters. Furthermore, the system demonstrated a multistability phenomenon involving the coexistence of the order-1 periodic solution and the limit cycle. This suggests that altering control strategies can disturb the initial coexistence status of pests and natural enemies. It also underscores that resource limitations can indeed impact the outbreak patterns and frequencies of pests. In addition to the variability in pesticide fatality rates, the inclusion of natural enemy releases in the nonlinear pulse strategy contributes to the model exhibiting complex dynamic characteristics. All these findings are substantiated by numerical simulations.
Quantum mechanical analysis of yttrium-stabilized zirconia and alumina: implications for mechanical performance of esthetic crowns
Authors: Saini Ravinder S. , Alshadidi Abdulkhaliq Ali F. , Gurumurthy Vishwanath , Okshah Abdulmajeed , Vaddamanu Sunil Kumar , Binduhayyim Rayan Ibrahim H. , Chaturvedi Saurabh , Bavabeedu Shashit Shetty , Heboyan Artak
Published: April 2024

Background

Yttrium-stabilized zirconia (YSZ) and alumina are the most commonly used dental esthetic crown materials. This study aimed to provide detailed information on the comparison between yttrium-stabilized zirconia (YSZ) and alumina, the two materials most often used for esthetic crowns in dentistry.

Methodology

The ground-state energy of the materials was calculated using the Cambridge Serial Total Energy Package (CASTEP) code, which employs a first-principles method based on density functional theory (DFT). The electronic exchange–correlation energy was evaluated using the generalized gradient approximation (GGA) within the Perdew (Burke) Ernzerhof scheme.

Results

Optimization of the geometries and investigation of the optical properties, dynamic stability, band structures, refractive indices, and mechanical properties of these materials contribute to a holistic understanding of these materials. Geometric optimization of YSZ provides important insights into its dynamic stability based on observations of its crystal structure and polyhedral geometry, which show stable configurations. Alumina exhibits a distinctive charge, kinetic, and potential (CKP) geometry, which contributes to its interesting structural framework and molecular-level stability. The optical properties of alumina were evaluated using pseudo-atomic computations, demonstrating its responsiveness to external stimuli. The refractive indices, reflectance, and dielectric functions indicate that the transmission of light by alumina depends on numerous factors that are essential for the optical performance of alumina as a material for esthetic crowns. The band structures of both the materials were explored, and the band gap of alumina was determined to be 5.853 eV. In addition, the band structure describes electronic transitions that influence the conductivity and optical properties of a material. The stability of alumina can be deduced from its bandgap, an essential property that determines its use as a dental material. Refractive indices are vital optical properties of esthetic crown materials. Therefore, the ability to understand their refractive-index graphs explains their transparency and color distortion through how the material responds to light..The regulated absorption characteristics exhibited by YSZ render it a highly attractive option for the development of esthetic crowns, as it guarantees minimal color distortion.

Conclusion

The acceptability of materials for esthetic crowns is strongly determined by mechanical properties such as elastic stiffness constants, Young's modulus, and shear modulus. YSZ is a highly durable material for dental applications, owing to its superior mechanical strength.
Prioritization of therapeutic targets for cancers using integrative multi-omics analysis
Authors: Jin Xin , Mei Yunyun , Yang Puyu , Huang Runze , Zhang Haifeng , Wu Yibin , Wang Miao , He Xigan , Jiang Ziting , Zhu Weiping , Wang Lu
Published: April 2024

Background

The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers’ development and progression.

Methods

Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis   to investigate metabolic pathways related to cancers.

Results

Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors.

Conclusions

A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.
Sleep and mental health among Chinese adolescents: the chain-mediating role of physical health perception and school adjustment
Authors: Li Liangliang , Zhang Yueying , Fan Mingyue , Cao Bing
Published: April 2024

Objective

Sleep problems and their detrimental effects on adolescents’ physical and mental health have received substantial attention. Prior studies have focused mainly on the direct association between sleep and mental health; however, little is known about the underlying mediating mechanism. To address this gap, the present study constructed a chain mediation model to examine the association between sleep deficiency and mental health status in adolescents, by introducing two mediating variables-physical health perception and school adjustment.

Methods

A sample of 7530 senior high school students completed a battery of self-report questionnaires measuring their sleep duration, mental health status, physical health perception, and school adjustment. Data were collected from the Database of Youth Health at Shandong University. All the measures showed good reliability and validity in the present study. Data were analyzed using SPSS 25.0 and the SPSS PROCESS.

Results

The results were as follows: (1) Sleep duration was significantly associated with physical health perception and mental health. (2) Physical health perception partially mediated the association between sleep and mental health. (3) Physical health perception and school adjustment played a chain mediating role between sleep and mental health. In conclusion, sleep not only directly associated with mental health among adolescents, but also influences mental health by the chain mediating effect of perception of physical health and school adjustment.

Conclusion

These findings in the present study contribute to understanding the mechanisms underlying the association between sleep and mental health and have important implications for interventions aimed at improving mental health status among adolescents in China. Our results indicated that promoting adequate sleep duration and improving sleep quality are possible key mental health promotion strategies for adolescents.
Numerical study on the three-dimensional temperature distribution according to laser conditions in photothermal therapy of peri-implantitis
Authors: Paik Jeeyong , Kim Donghyuk , Kim Hyunjung , Kim Hee-Sun
Published: April 2024

Purpose

Dental implants have been successfully implemented as a treatment for tooth loss. However, peri-implantitis, an inflammatory reaction owing to microbial deposition around the implant, can lead to implant failure. So, it is necessary to treat peri-implantitis. Therefore, this numerical study is aimed at investigating conditions for treating peri-implantitis.

Methods

Photothermal therapy, a laser treatment method, utilizes photothermal effect, in which light is converted to heat. This technique has advantage of selectively curing inflamed tissues by increasing their temperature. Accordingly, herein, photothermal effect on peri-implantitis is studied through numerical analysis with using Arrhenius damage integral and Arrhenius thermal damage ratio.

Results

Through numerical analysis on peri-implantitis treatment, we explored temperature changes under varied laser settings (laser power, radius, irradiation time). We obtained the temperature distribution on interface of artificial tooth root and inflammation and determined whether temperature exceeds or does not exceed 47℃ to know which laser power affects alveolar bone indirectly. We defined the Arrhenius thermal damage ratio as a variable and determined that the maximum laser power that does not exceed 47℃ at the AA’ line is 1.0 W. Additionally, we found that the value of the Arrhenius thermal damage ratio is 0.26 for a laser irradiation time of 100 s and 0.50 for 500 s.

Conclusion

The result of this numerical study indicates that the Arrhenius thermal damage ratio can be used as a standard for determining the treatment conditions to help assisted laser treatment for peri-implantitis in each numerical analysis scenario.
Intrinsic conformal order revealed in geometrically confined long-range repulsive particles
Authors: Yao Zhenwei
Published: April 2024

Elucidating long-range interaction guided organization of matter is a fundamental question in physical systems covering multiple length scales. Here, based on the hexagonal disk model, we analyze the characteristic inhomogeneity created by long-range repulsions, and reveal the intrinsic conformal order in particle packings in mechanical equilibrium. Specifically, we highlight the delicate angle-preserved bending of the lattice to match the inhomogeneity condition. The revealed conformal order is found to be protected by the surrounding topological defects. These results advance our understanding on long-range interacting systems, and open the promising possibilities of using long-range forces to create particle packings not accessible by short-range forces, which may have practical consequences.
Design and optimization of soft colonoscopy robot with variable cross section
Authors: Chen Gang , Yu Weiren , Wu Yutong , Zheng Jianxiao
Published: April 2024

Background Colonoscopy is the best choice for detecting bowel cancer; its effectiveness and early screening can significantly reduce the incidence rate of bowel cancer. However, the existing colonoscopy procedure is very technically demanding for doctors and painful for patients due to the difficult maneuver of long and slender colonoscope inside human colon. This paper will be focused on designing flexible robots with high dexterity to improve the performance of current colonoscopy. Methods This article optimizes and simulates the shape and layout of the driving cavity of the soft robot, as well as the multi-stage structure. This paper presents a design scheme of the soft robot with variable cross-section. The robot comprises two cross-sections in serial connection, with the outer diameter of the upper section 14mm and the outer diameter of the lower part 16mm. The bending angle and direction of the soft robot can be controlled by adjusting the pressure of the cavity. The soft robot is placed at the end of the traditional colonoscopy, replacing the standard manual operation for guidance during colonoscopy surgery. The relationship between the end position of the actuator and air pressure is calculated by the piecewise constant curvature (PCC) method and verified by subsequent experiments. At the same time, the motion trajectory of the soft robot is further simulated by finite element analysis. Results Experimental verification shows that the bending performance of the newly designed soft robot has significantly improved compared to the old design. Conclusion An improvement was made to address the design shortcomings of traditional actuators, and a new actuator was obtained. The performance of the latest and old actuators was compared through experiments, and it was ultimately known that the new actuator had significantly improved performance compared to the old actuator.
Unveiling the Variances: Myelodysplastic Syndrome (MDS) Patient Admissions in Teaching vs Nonteaching Hospitals
Authors: Javaid Saad , Aziz Nouman , Frasier Kelly
Published: April 2024

Background We have carried out an analysis to evaluate the influence of hospital teaching status on the outcomes of individuals hospitalized with MDS. Methods The National Inpatient Sample (NIS) dataset for the years 2019-2020 was employed to identify individuals who were hospitalized with a primary diagnosis of MDS. These patients were then categorized into two groups: those who were hospitalized in teaching hospitals and those who were hospitalized in non-teaching hospitals. Multivariate regression analysis was performed to calculate the primary and secondary outcomes. Results In the years 2019 and 2020, a total of 17,000 patients were hospitalized with myelodysplastic syndromes (MDS). Among these, 24.05% (4,080) were admitted to non-teaching hospitals, while 75.94% (12,920) were admitted to teaching hospitals. Patients admitted to teaching hospitals had a higher likelihood of mortality (OR 1.84, 95% CI 1.03-3.27, P=0.037), as well as increased lengths of stay (+3.58 Days, 95% CI 2.82-4.34, P<0.001)and total hospitalization costs (+USD 66818, 95% CI 50528-83108, P<0.001). Additionally, patients in teaching hospitals had a higher incidence of acute respiratory failure (6.81% vs 4.4%), acute kidney injury (23.89% vs 17.72%), hematopoietic stem cell transplantation (14.36% vs 0.61%), and febrile neutropenia (11.03% vs 5.86%). However, patients in teaching hospitals had a lower incidence of anemia (41.86% vs 48.53%) and blood transfusions (38.8% vs 55.37%). Conclusion Individuals who were admitted to teaching hospitals with Myelodysplastic Syndromes (MDS) exhibited a notably higher mortality rate, as well as an extended length of stay and a corresponding increase in the total cost of hospitalization. Patients in teaching hospitals were also at risk for acute kidney injury, acute respiratory failure and febrile neutropenia.
Changes in prevalence and patterns of consanguinity in Bradford, UK – evidence from two cohort studies
Authors: Small Neil , Kelly Brian , Wright John
Published: April 2024

Background Research undertaken using the Born in Bradford cohort study identified consanguinity as a major risk factor for congenital anomalies and also reported longer term adverse health outcomes associated with consanguinity. Methods We report the prevalence of consanguinity from two cohort studies in the same geographical area with a nine year gap: Born in Bradford (BiB) and Born in Bradford’s Better Start (BiBBS). We examine and compare rates of consanguinity and the characteristics of the consanguineous in each study population to examine if and how these have changed in the years between the recruitment periods of 2007–2010 (BiB) and 2016–2019 (BiBBS). Results There had been a substantial decrease in consanguineous unions in women of Pakistani heritage, the proportion of women who were first cousins with the father of their baby fell from 39.3% to 27.0%, and those who were other blood relations fell from 23.1% to 19.3%. Only 37.6% of Pakistani heritage women were unrelated to the father of their baby in BiB, but 53.7% were unrelated in BiBBS. All but one White British respondent was unrelated to their baby’s father in both cohorts, and around 90% of the ‘Other ethnicities’ group (i.e., not White British or Pakistani heritage) were unrelated to the baby’s father in both cohorts. The reduction was most marked in women of Pakistani heritage who were born in the UK, in those educated to A level or higher and in women under age 25. Conclusions An appreciation of changing rates of consanguinity and linked health needs will be valuable to those who commission and provide antenatal, paediatric and genetic services in Bradford and in other areas where consanguinity is likely to be a major risk factor. Falling rates in this city may reflect wider changes in partner choices in similar populations.