bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of the risk of mortality in older patients with coronavirus disease 2019 using blood markers and machine learning
Authors: Zhu Linchao , Yao Yimin
Published: November 2024

Introduction

The mortality rate among older people infected with severe acute respiratory syndrome coronavirus 2 is alarmingly high. This study aimed to explore the predictive value of a novel model for assessing the risk of death in this vulnerable cohort.

Methods

We enrolled 199 older patients with coronavirus disease 2019 (COVID-19) from Zhejiang Provincial Hospital of Chinese Medicine (Hubin) between 16 December 2022 and 17 January 2023. Additionally, 90 patients from two other centers (Qiantang and Xixi) formed an external independent testing cohort. Univariate and multivariate analyses were used to identify the risk factors for mortality. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to select variables associated with COVID-19 mortality. Nine machine-learning algorithms were used to predict mortality risk in older patients, and their performance was assessed using receiver operating characteristic curves, area under the curve (AUC), calibration curve analysis, and decision curve analysis.

Results

Neutrophil–monocyte ratio, neutrophil–lymphocyte ratio, C‐ reactive protein, interleukin 6, and D-dimer were considered to be relevant factors associated with the death risk of COVID-19-related death by LASSO regression. The Gaussian naive Bayes model was the best-performing model. In the validation cohort, the model had an AUC of 0.901, whereas in the testing cohort, the model had an AUC of 0.952. The calibration curve showed a good correlation between the actual and predicted probabilities, and the decision curve indicated a strong clinical benefit. Furthermore, the model had an AUC of 0.873 in an external independent testing cohort.

Discussion

In this study, a predictive machine-learning model was developed with an online prediction tool designed to assist clinicians in evaluating mortality risk factors and devising targeted and effective treatments for older patients with COVID-19, potentially reducing the mortality rates.
Clinical immunotherapy in glioma: current concepts, challenges, and future perspectives
Authors: Liu Jun , Peng Jingjian , Jiang Jian , Liu Yanhui
Published: November 2024

Glioma is one of the common tumors in the central nervous system, and its treatment methods (surgery, radiotherapy, and chemotherapy) lack specificity and have a poor prognosis. With the development of immunology, cell biology, and genomics, tumor immunotherapy has ushered in a new era of tumor therapy, achieving significant results in other invasive cancers such as advanced melanoma and advanced non-small cell lung cancer. Currently, the clinical trials of immunotherapy in glioma are also progressing rapidly. Here, this review summarizes promising immunotherapy methods in recent years, reviews the current status of clinical trials, and discusses the challenges and prospects of glioma immunotherapy.
NFIL3/Tim3 axis regulates effector Th1 inflammation in COPD mice
Authors: Ke Junyi , Huang Shu , He Zhixiong , Lei Siyu , Lin Shiya , Li Yinying , Li Qiuming , Huang Hui , Huang Hongchun , Qin Huajiao , Duan Minchao
Published: November 2024

Background

IFN-γ+CD4+ cells (type 1 helper T cells, Th1) represent a critical component of the inflammatory environment in the lungs of chronic obstructive pulmonary disease (COPD). Identifying influencing factors related to COPD-associated Th1 cells will enhance our understanding of the inflammatory mechanisms involved and facilitate the development of targeted interventions.

Method

We describe T-cell immunoglobulin and mucin-domain containing-3 (Tim3) as a key gene regulating COPD-associated Th1 cells through single-cell sequencing, flow cytometry and knockout mice.

Results

Our findings indicate that Havcr2 expression gradually increases during CD4+ T cell activation in COPD mice, with Tim3 being highly expressed on both CD4+ T cells and Th1 cells. Notably, the knockout of HAVCR2 further promotes the infiltration of CD4+ T cells and the expression of IFN-γ in the lungs, resulting in a more severe emphysema phenotype, although it does not significantly affect TNF-α expression. Additionally, NFIL3, an upstream regulator of Tim3, is also highly expressed in the CD4+ T cells of COPD mice. Mice with NFIL3 knockout exhibit phenotypes similar to those of HAVCR2 knockout mice, along with a significant downregulation of Tim3 expression. In vitro, we simulated the activation process by polarizing primary CD4+ Tn cells from COPD mice and observed that NFIL3/Tim3 expression was significantly upregulated following Th1 polarization.

Conclusion

Our study demonstrates that the NFIL3/Tim3 axis plays a role in Th1 imbalance in the lungs of COPD by inhibiting Th1 differentiation.
Control of myeloid-derived suppressor cell dynamics potentiates vaccine protection in multiple mouse models of Trypanosoma cruzi infection
Authors: Borgna Eliana , Prochetto Estefanía , Gamba Juan Cruz , Vermeulen Elba Mónica , Poncini Carolina Verónica , Cribb Pamela , Pérez Ana Rosa , Marcipar Iván , González Florencia Belén , Cabrera Gabriel
Published: November 2024

To date, there is no licensed vaccine against the protozoan parasite Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas Disease. T. cruzi has evolved numerous mechanisms to evade and manipulate the host immune system. Among the subversive strategies employed by the parasite, marked increases in CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in several organs have been described. We have reported that CD11b+ Gr-1+ cells are involved not only during infection but also after immunization with a trans-sialidase fragment (TSf) adjuvanted with a cage-like particle adjuvant (ISPA). Thus, the aim of this work was to gain control over the involvement of MDSCs during immunization to potentiate a vaccine candidate with protective capacity in multiple mouse models of T. cruzi infection. Here, we show that the Gr-1+ cells that increase during TSf-ISPA immunization have suppressive capacity over bone marrow-derived dendritic cells and CD4+ lymphocytes. Protocols using one or two doses of 5-fluorouracil (5FU) were employed to deplete and control MDSC dynamics during immunization. The protocol based on two doses of 5FU (double 5FU TSf-ISPA) was more successful in controlling MDSCs during immunization and triggered a higher immune effector response, as evidenced by increased numbers of CD4+, CD4+CD44+, CD8+, CD8+CD44+, CD11c+, and CD11c+CD8α+ cells in the spleen and lymph nodes of double 5FU TSf-ISPA mice as compared to 5FU-TSf-ISPA mice. In line with these results, the protective capacity of the double 5FU TSf-ISPA protocol was higher compared to the 5FU-TSf-ISPA protocol against high lethal doses of intraperitoneal infection with the Tulahuen T. cruzi strain. When cross-protective capacity was analyzed, the optimized protocol based on double 5FU TSf-ISPA conferred protection in several preclinical models using different discrete typing units (DTU VI and DTU I), different mouse strains (BALB/c and C57BL/6), different parasite doses (1000 to 20000), and routes of administration (intraperitoneal and intradermal). Developing vaccines that are currently lacking may require new strategies to further potentiate vaccine candidates. Results reported herein provide evidence that rational control of cells from the regulatory arm of the immune system could enhance a vaccine candidate with cross-protective capacity in multiple mouse models of T. cruzi infection.
Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in the treatment of advanced colorectal cancer: a systematic review and meta-analysis
Authors: Song Dandan , Hou Shufu , Ma Ning , Yan Bing , Gao Jing
Published: November 2024

Background

The efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in the treatment of advanced colorectal cancer is controversial. This meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors for advanced colorectal cancer.

Methods

PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for relevant studies. Outcomes including median progression-free survival (mPFS), median overall survival (mOS), overall response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs) and ≥grade 3 TRAEs were extracted for further analysis. The risk of bias was assessed by subgroup analysis.

Results

12 articles with 566 patients were identified and subjected to meta-analysis. With regard to survival analysis, the pooled mOS and mPFS were 6.66 months (95%CI 4.85-9.16) and 2.92 months (95%CI 2.23-3.83), respectively. In terms of tumor response, the pooled ORR and DCR were 21% (95%CI 6%-41%) and 49% (95%CI 27%-71%), respectively. The pooled AEs rate and ≥ grade 3 AEs rate were 94% (95%CI 86%-99%) and 44% (95%CI 30%-58%).

Conclusion

PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors have shown promising clinical responses in the treatment of colorectal cancer (CRC). Although the incidence of adverse reactions is high, they are generally tolerable.

Systematic review registration

https://inplasy.com/, identifier INPLASY202480030.
MiR-130c-5p targets the SHVV n gene and upregulates immune cytokines (IL-6, IL-22, IL-1β) to inhibit viral replication
Authors: Wei Jin , Ji Yan , Bai Yaqian , Cheng Rui , Zhang Jiaqi , Hu Xianqin , Zhang Chi
Published: November 2024

Background

Snakehead vesiculovirus (SHVV) has led to huge economic losses in snakehead aquaculture, and its pathogenic mechanisms is still not fully understood. MicroRNAs (miRNAs), as an important class of non-coding RNAs, play a key regulatory role in the process of viral infection.

Methods

We examined the effect of SHVV infection on the expression of miR-130c-5p and the effect of overexpression of miR-130c-5p on the proliferation of SHVV. Cotransfection of viral N protein and miR-130c-5p, and the effect of miR-130c-5p on the expression of N protein was detected. Meanwhile, the effect of overexpression of miR-130c-5p on the expression of various immune factors in the case of viral infection were also tested.

Results

In this study, SHVV infection significantly upregulated the expression of miR-130c-5p in channel catfish ovary (CCO) cells in a time- and dose-dependent manner. The further research revealed that miR-130c-5p mimic significantly inhibited, while its inhibitors promoted SHVV replication. In addition, miR-130c-5p could directly target the viral mRNA of n gene, and overexpression of miR-130c-5p could significantly decrease, and conversely, downregulation of miR-130c-5p could increase the mRNA and protein expression of the viral n gene. Meanwhile, overexpression of miR-130c-5p also upregulated the expression of immune-related genes, such as nucleotide-oligomerization domain (NOD)-like receptor subfamily C3 (NLRC3), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), interleukin-22 (IL-22), and interleukin-1beta (IL-1β) in host cells.

Conclusion

miR-130c-5p was upregulated in the host during SHVV infection, and the upregulated miR-130c-5p directly inhibited viral replication by targeting the n gene of SHVV and promoting viral nucleoprotein degradation. The up-regulated miR-130c-5p also activated the expression of immune-related genes such as NLRC3, MyD88, NF-κB, IL-6, IL-22, and IL-1β, which were involved in the regulation of the signaling pathways including NF-κB, MyD88, Toll-like receptor (TLR), NLR, and janus tyrosine kinase-signal converter and activator of transcription (JAK-STAT), to enhance the host's antiviral immune response, and thus indirectly inhibited the viral proliferation.
Macrophages in tumor cell migration and metastasis
Authors: Friedman-DeLuca Madeline , Karagiannis George S. , Condeelis John S. , Oktay Maja H. , Entenberg David
Published: November 2024

Tumor-associated macrophages (TAMs) are a phenotypically diverse, highly plastic population of cells in the tumor microenvironment (TME) that have long been known to promote cancer progression. In this review, we summarize TAM ontogeny and polarization, and then explore how TAMs enhance tumor cell migration through the TME, thus facilitating metastasis. We also discuss how chemotherapy and host factors including diet, obesity, and race, impact TAM phenotype and cancer progression. In brief, TAMs induce epithelial-mesenchymal transition (EMT) in tumor cells, giving them a migratory phenotype. They promote extracellular matrix (ECM) remodeling, allowing tumor cells to migrate more easily. TAMs also provide chemotactic signals that promote tumor cell directional migration towards blood vessels, and then participate in the signaling cascade at the blood vessel that allows tumor cells to intravasate and disseminate throughout the body. Furthermore, while chemotherapy can repolarize TAMs to induce an anti-tumor response, these cytotoxic drugs can also lead to macrophage-mediated tumor relapse and metastasis. Patient response to chemotherapy may be dependent on patient-specific factors such as diet, obesity, and race, as these factors have been shown to alter macrophage phenotype and affect cancer-related outcomes. More research on how chemotherapy and patient-specific factors impact TAMs and cancer progression is needed to refine treatment strategies for cancer patients.
PCV13 vaccine prevents pneumococcal biofilms without affecting Staphylococcus aureus population within the polymicrobial biofilm
Authors: Sempere Julio , Yuste José , Domenech Mirian
Published: November 2024

In respiratory pathogens such as Streptococcus pneumoniae, biofilm formation is associated with the colonization of the nasopharynx and chronic respiratory infection. Previous data have shown that pneumococcal conjugate vaccines (PCVs) had an impact on S. pneumoniae colonization and a potential replacement by other respiratory pathogens such as Staphylococcus aureus. The objective of this work was to evaluate the evasion of the immune system by monospecific biofilms and by S. aureus-S. pneumoniae mixed biofilms. We performed opsonophagocytosis assays (OPA) using human HL-60 against previously disaggregated monospecific biofilms of MSSA, MRSA and S. aureus-S. pneumoniae mixed biofilms. We used pre-immune and post-immune serum from immunocompetent adult patients vaccinated with PCV13. Immune sera had a clear effect in reducing pneumococcal biofilms of serotypes 3, 14, 18C, 19F and 19A, whereas had no effect in non-PCV13 serotypes such as 8, 11A and 24F. Our study confirmed that serum from vaccinated patients with PCV13 did not have any effect in reducing S. aureus population in monospecific biofilms, regardless the methicillin resistance phenotype. Moreover, immunized sera from vaccinated patients with PCV13 did not have any effect in S. aureus population in the mixed biofilm, whereas significantly reduced the population of pneumococcal serotype 19A strain in the mixed biofilm which is of great interest because this serotype is included in PCV13, and it is associated with vaccine failures.
Optimization of entrainment and interfacial flow patterns in countercurrent air-water two-phase flow in vertical pipes
Authors: Wang Yongzhi , Luo Feng , Zhu Zichen , Li Ruijie , Sina Mohammad
Published: November 2024

This study investigates countercurrent air-water two-phase flow in vertical pipes with inner diameters of 26 mm and 44 mm and a height of 2000 mm, under controlled conditions to eliminate heat and mass transfer. Cutting-edge techniques were employed to measure the liquid film thickness (δ) and entrainment (e) within the annular flow pattern. The methodology involved a systematic comparative analysis of experimental results against established models, identifying the most accurate methods for predicting flow behavior. Specifically, the Schubring et al. correlation was found to most accurately predict e in 26 mm pipes, while the Wallis correlation was more accurate for 44 mm pipes. Additionally, interfacial shear stress was analyzed, confirming the high precision of the δ and e parameters. This research enhances the understanding of countercurrent air-water two-phase flow by providing reliable estimation methods for different pipe diameters and emphasizes the significance of accurately determining interfacial shear stress. Key findings include the identification of the most accurate models for different pipe sizes and addressing challenges in measuring δ and e under controlled conditions. The study’s novelty lies in its comprehensive comparative analysis of existing models, leading to improved predictions of flow dynamics in vertical pipes, thereby contributing valuable insights into two-phase flow behavior in geosciences and environmental engineering.
Uremic sarcopenia: the role of intramuscular adipose tissue as a potential early identifier
Authors: Noce Annalisa , Ceravolo Maria Josè , Gualtieri Paola , Marrone Giulia , Romano Lorenzo , Shoshi Amir , Di Lauro Manuela , De Lorenzo Antonino
Published: November 2024

Introduction

Sarcopenia is a chronic pathological condition, first defined in 2010 and revised in 2018. The most recent definition of sarcopenia focuses mostly on “low muscle strength.” A secondary form of sarcopenia is represented by uremic sarcopenia (US), a condition that characterizes end-stage kidney disease (ESKD) patients. The intramuscular adipose tissue (IMAT) seems to impact negatively on muscle strength, as it would seem to replace muscle fibers with a non-contractile component. The study aims to compare body composition parameters—both standardized and innovative—related to the diagnosis of US in hemodialysis (HD) patients, stratified by sarcopenia diagnosis. Furthermore, the different indices of sarcopenia are compared in order to evaluate their predictive capacity.

Methods

We analyzed 48 ESKD patients according to the sarcopenia diagnosis, obtained using dual-energy X-ray absorptiometry (DXA). Moreover, we assessed the presence of IMAT and calculated the sarcopenia index (SI).

Results

For the study, the enrolled population was divided according to the sarcopenia diagnosis: no sarcopenic patients had higher transferrin (p = 0.03), total proteins (p = 0.04), and azotemia pre-dialysis (p = 0.05) values. On the contrary, atherogenic indices were lower in no sarcopenic patients. Moreover, we observed an indirect correlation between the SI and parathyroid hormone (PTH) (p = 0.00138, R2 = 0.54). Finally, we calculated the prevalence of sarcopenia and sarcopenia adjusted for IMAT. We showed a different prevalence between sarcopenia diagnosed with a standard index and an index adjusted for IMAT (p = 0.043). In conclusion, we believe that the most important result obtained is the indirect correlation between SI and PTH. These data corroborate the theories, in which PTH seems to play a central role in the cachexia genesis. Moreover, the SI adjusted for IMAT seems to be a more reliable parameter for the early identification of subjects at risk of developing US, allowing timely implementation of targeted therapeutic strategies.
Diagnostic accuracy of lung ultrasound to predict weaning outcome: a systematic review and meta-analysis
Authors: Zhang Zhiyang , Guo Li , Wang Huawei , Zhang Ze , Shen Limin , Zhao Heling
Published: November 2024

Background

This systematic review and meta-analysis aim to systematically assess the diagnostic accuracy of lung ultrasound in predicting weaning failure from mechanical ventilation in critically ill patients.

Methods

We searched the relevant literature up to January 2024 in the databases Web of Science, Cochrane Library, Embase, and PubMed. Two researchers independently screened eligible studies and extracted data; disagreements, if any, were resolved through discussion or consultation with a third-party expert. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Statistical analyses were performed using Review Manager version 5.3 and Stata version 18.0, applying bivariate random-effects models to estimate sensitivity, specificity, diagnostic odds ratios, and their 95% confidence intervals, as well as to summarize receiver operating characteristic curves. Inter-study heterogeneity was assessed using the I-squared statistic, and potential sources of heterogeneity were explored by meta-regression analysis. The study follows the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses in reporting.

Results

Fourteen studies were included in the systematic review, of which 13 studies (totaling 988 patients) were included in the meta-analysis. The meta-analysis revealed an overall sensitivity of 0.86 (95% confidence interval: 0.77–0.91) and a specificity of 0.75 (95% confidence interval: 0.66–0.83) for lung ultrasound in predicting extubation failure. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval: 0.84–0.89). Meta-regression analysis identified lung ultrasound thresholds, reference standards (extubation outcomes), and study flow and time bias as significant factors influencing diagnostic accuracy.

Conclusion

This systematic review and meta-analysis demonstrated that lung ultrasound has high diagnostic accuracy in predicting extubation failure in mechanically ventilated critically ill patients. Despite some study heterogeneity, lung ultrasound proved to be a reliable predictive tool for extubation failure. Future research should focus on standardizing the definition of extubation failure, exploring the impact of different thresholds on the predictive ability of lung ultrasound, and validating its application in various clinical settings to enhance its utility and accuracy in clinical practice.

Systematic review registration

This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42024555909). The study adhered to the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Details of the PROSPERO protocol can be found in Supplementary Table 1.
IL-18 biology in severe asthma
Authors: Thawanaphong Sarita , Nair Aswathi , Volfson Emily , Nair Parameswaran , Mukherjee Manali
Published: November 2024

The role of interleukin-18 (IL-18) and inflammasomes in chronic inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), has garnered significant attention in recent years. This review aims to provide an overview of the current understanding of IL-18 biology, the associated signaling pathways, and the involvement of inflammasome complexes in airway diseases. We explore the multifaceted role of IL-18 in asthma pathophysiology, including its interactions with other cytokines and contributions to both T2 and non-T2 inflammation. Importantly, emerging evidence highlights IL-18 as a critical player in severe asthma, contributing to chronic airway inflammation, airway hyperresponsiveness (AHR), and mucus impaction. Furthermore, we discuss the emerging evidence of IL-18’s involvement in autoimmunity and highlight potential therapeutic targets within the IL-18 and inflammasome pathways in severe asthma patients with evidence of infections and airway autoimmune responses. By synthesizing recent advancements and ongoing research, this review underscores the importance of IL-18 as a potential novel therapeutic target in the treatment of severe asthma and other related conditions.
Altitude shapes gut microbiome composition accounting for diet, thyroid hormone levels, and host genetics in a subterranean blind mole rat
Authors: Solak Halil Mert , Kreisinger Jakub , Čížková Dagmar , Sezgin Efe , Schmiedová Lucie , Murtskhvaladze Marine , Henning Yoshiyuki , Çolak Faruk , Matur Ferhat , Yanchukov Alexey
Published: November 2024

The animal gut microbiome acts as a crucial link between the host and its environment, playing a vital role in digestion, metabolism, physiology, and fitness. Using 16S rRNA metabarcoding, we investigated the effect of altitude on the microbiome composition of Anatolian Blind Mole Rats (Nannospalax xanthodon) across six locations and three altitudinal groups. We also factored in the host diet, as well as host microsatellite genotypes and thyroid hormone levels. The altitude had a major effect on microbiome composition, with notable differences in the relative abundance of several bacterial taxa across elevations. Contrary to prior research, we found no significant difference in strictly anaerobic bacteria abundance among altitudinal groups, though facultatively anaerobic bacteria were more prevalent at higher altitudes. Microbiome alpha diversity peaked at mid-altitude, comprising elements from both low and high elevations. The beta diversity showed significant association with the altitude. Altitude had a significant effect on the diet composition but not on its alpha diversity. No distinct altitude-related genetic structure was evident among the host populations, and no correlation was revealed between the host genetic relatedness and microbiome composition nor between the host microbiome and the diet. Free thyroxine (FT4) levels increased almost linearly with the altitude but none of the bacterial ASVs were found to be specifically associated with hormone levels. Total thyroxine (TT4) levels correlated positively with microbiome diversity. Although we detected correlation between certain components of the thyroid hormone levels and the microbiome beta diversity, the pattern of their relationship remains inconclusive.
Anhydrous microwave synthesis as efficient method for obtaining model advanced glycation end-products
Authors: Bronowicka-Szydełko Agnieszka , Madziarska Katarzyna , Kuzan Aleksandra , Lewandowski Łukasz , Adamiec-Mroczek Joanna , Pietkiewicz Jadwiga , Tota Maciej , Ziomek Maciej , Stach Wojciech , Trocha Tymoteusz , Piersiak Marcin , Pachana Maciej , Galińska Zuzanna , Korpacki Andrzej , Dróżdż Olgierd , Matuszyk Janusz , Mitkiewicz Małgorzata , Gamian Andrzej , Gostomska-Pampuch Kinga
Published: November 2024

Introduction

Advanced glycation end-products (AGEs) are capable of stimulating oxidative stress and inflammation. This study investigates the synthesis of medium crosslinked AGEs (the most optimal form of AGEs because of soluble in water, used in many assays as markers) and their biochemical properties.

Methods

One of model protein–myoglobin from horse heart muscle (MB) and a chosen respective glycation factor – D-melibiose (mel), acrolein (ACR), D-glucose (glc), 4-hydroksynonenal (4HNE), trans-2-nonenal (T2N), methylglyoxal (MGO) – were subjected to high temperature water synthesis (HTWS) and high temperature microwave synthesis in anhydrous conditions (HTMS). The syntheses were deliberately carried out in two different conditions to check whether adding an additional energy source (microwaves) while lowering the temperature and shortening the reaction time would allow for more effective obtaining of medium-cross-linked AGEs, monitored with SDS-PAGE. Products were analyzed using fluorescence measurements, Enzyme-Linked Immunosorbent Assay (ELISA) and immunoblotting tests and electrophoretic mobility shift assay to evaluate their ability to activate nuclear factor kappa-light-chain-enhancer (NF-κB).

Results

Medium cross-linked AGEs were more efficiently obtained in HTMS. Fluorescence was high for MB-ACR, MB-T2N and MB-glc products. Anti-MAGE antibodies showed reactivity towards MB-mels of HTMS and HTWS, and the MB-4HNEs from HTMS. HTWS products, apart from MB-ACR, did not activate NF-κB, whereas MB-ACR, MB-4HNE, MB-mel, and MB-T2N products of HTMS strongly activated this factor that indicates their strong pro-inflammatory properties.

Conclusion

HTMS is a fast and efficient method of synthesizing medium cross-linked AGEs.
Exploring motor imagery as a therapeutic intervention for Parkinson’s disease patients: a scoping review
Authors: Michel Maxime , Terragno Elena , Bereau Matthieu , Magnin Eloi , Gueugneau Nicolas , Soares Antonio Vinicius , Sagawa Yoshimasa
Published: November 2024

Background

Motor imagery (MI) has emerged as a promising therapeutic approach for Parkinson’s disease (PD). MI entails mentally rehearsing motor actions without executing them. This cognitive process has garnered attention due to its potential benefits in aiding motor function recovery in patients. The purpose of this review was to highlight the findings observed in motor symptoms, balance, gait, and quality of life.

Methods

A literature search was carried out in Medline, Embase, Cochrane, and Physiotherapy Evidence Database (PEDro), from the first publication to February 2024. Studies with at least one keyword to PD and MI in the title were included.

Results

The analysis included 53 studies out of the 262 identified. These comprised 12 randomized controlled trials (RCTs) with an average PEDro score of 6.6 out of 10, as well as 41 non-RCT studies. Notably, the majority of the RCTs focused on balance, gait, and lower limb exercises. The experimental group found an 85.2% improvement on the Timed Up and Go (TUG) with a cognitive task (p < 0.02), 5.8% improvement on the TUG (p < 0.05), and 5.1% improvement in walking speed (p < 0.05). Other variables did not show significant improvement. In descriptive and non-RCT studies, there were various tasks and outcomes for the lower and upper limbs. It has been demonstrated that there was no difference in execution time in MI between patients and healthy subjects (HS), whereas motor execution was slower in patients. Several tasks were analyzed for the upper limb, including thumb opposition, joystick movements, and writing tasks with variable results. RCTs were more focused on balance, lower limbs, and walking. There was no specific outcome regarding the upper limb or speech. Additionally, the heterogeneity of tasks and outcomes across studies is also a limitation.

Conclusion

Current research on walking disorders in PD shows promise, but further investigations are crucial, particularly with an emphasis on upper limb function and speech. Studies with larger sample sizes and more precise methodologies are needed to enhance our understanding of the potential benefits of MI within the framework of comprehensive PD rehabilitation.
Hemodynamic alterations and their clinical implications in the vertebrobasilar system among patients with isolated posterior circulation ischemic vertigo
Authors: Song Xuhua , Liang Jingwei , Tian Congzhe
Published: November 2024

Background

This research aimed to ascertain independent risk factors and the diagnostic value of vascular parameters in differentiating posterior circulation ischemic isolated vertigo (PCI-IV) from vestibular peripheral vertigo (VPV).

Methods

This study involved 247 patients with acute-onset vertigo, categorized into two groups: PCI-IV and VPV. Multivariate logistic regression was conducted to pinpoint independent risk factors for PCI-IV.

Results

The duration of vertigo, particularly episodes lasting more than a few hours, was a significant predictor of PCI-IV (OR = 2.183, p < 0.001). The presence of diabetes mellitus (OR = 1.746, p = 0.008) and hypertension (OR = 2.291, p = 0.004) also notably increased the likelihood of PCI-IV. Hemodynamic measurements such as the inner diameter and average blood flow velocity (Vmean) of the vertebral artery, as well as the resistive index (RI), were identified as significant predictive factors (p ≤ 0.033). The ROC analysis demonstrated the vertebral artery RI had the highest diagnostic accuracy with an area under the curve (AUC) of 0.78, indicating an optimal balance between sensitivity and specificity.

Conclusion

Clinical features such as the duration of vertigo, diabetes mellitus, and hypertension, along with vascular hemodynamics, are crucial in assessing the risk of PCI-IV. The RI in the vertebral artery emerged as a particularly potent diagnostic parameter. These findings advocate a multifaceted diagnostic approach, combining clinical and vascular parameters for the effective identification and management of PCI-IV.
Neural functions vary by return-to-sport status in participants with anterior cruciate ligament reconstruction: a retrospective cohort study using sub-bands of resting-state functional magnetic resonance
Authors: Song Hongyun , Zhu Sunan , Pan Zongyou , Yu XiaoJing , Xiong Bing , Dai Xuesong
Published: November 2024

Objective

This study aimed to characterize the differences in neural function among patients with different functional abilities 2 years after anterior cruciate ligament reconstruction (ACLR).

Design

Resting-state functional magnetic resonance imaging was performed to obtain blood-oxygen-level-dependent values for ACLR returned to sports coper participants (CP), non-coper participants (NP), and healthy controls (HC). The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) calculated changes in the standard frequency band (SFB) (0.01–0.08 Hz), Slow4 (0.027–0.073 Hz), and Slow5 (0.01–0.027 Hz). Clinical correlations were investigated.

Results

The right cerebellum_8 and bilateral putamen in SFB, while the right cerebellum_crus2 and left putamen in Slow5 were higher in CP than in NP. The ALLF values of the bilateral putamen in Slow4 were increased, while the right parietal lobule in Slow4 and left upper temporal pole in Slow5 were lower in CP than in HC. The ReHo values in the CP group in the right cerebellum_crus2 was higher than that in the NP group in Slow5 (voxel p < 0.05, cluster p < 0.05, Gaussian Random Field theory correction). Y-balance test was correlated with cerebellum ALFF values; Tegner was moderately correlated with putamen ALFF values (p < 0.05). Knee Injury and Osteoarthritis Outcome Score-sports, International Knee Documentation Committee Subjective Knee Evaluation Form and Tegner scores were correlated with the ReHo values of right cerebellum_crus2 (p < 0.05).

Conclusion

Subcortical function transfer was performed in patients with ACLR who returned to sports postoperatively: the function of the somatosensory brain area decreased, while that of the subcortical cerebellum and basal ganglia and cerebellum ReHo increased in CP, which was correlated with clinical function. ALFF and ReHo are consistent to some extent, and sub-band studies can reveal information on different brain functions compared to the classical band.
Farmed blue mussels (Mytilus edulis)—a nutrient-dense resource retaining nutritional value through processing
Authors: Bjerknes Hanne , Elvevoll Edel O. , Alterskjær Sundset Monica , Langdal Andreas , Eilertsen Karl-Erik
Published: November 2024

This study investigated how farmed blue mussels (Mytilus edulis) can optimize human nutrient intake. A particular focus was on assessing nutrient preservation during steaming and freeze-drying, processes that could deplete nutrients. The study compared the content of essential amino acids and fatty acids in steamed and freeze-dried blue mussels to the nutritional needs of humans and farmed Atlantic salmon (Salmo salar). Additionally, it assessed the ethyl acetate method versus the traditional, more toxic Folch method for lipid extraction from blue mussels. Both steaming and freeze-drying effectively preserved essential amino acids and fatty acids in blue mussels. A 100 g serving of steamed blue mussels contributes from 26.8 ± 0.78% (Phe) to 54.9 ± 1.66% (Thr) of the daily recommended intake of essential amino acids (EAA). For steamed freeze-dried blue mussels, over 100% of the recommended intake is met for all EAA and as much as 243% for threonine. The 100 g serving will also provide 271 mg eicosapentaenoic acid (EPA; 20:5n-3) and 220 mg docosahexaenoic acid (DHA; 22:6n-3), thus covering the required intake of n-3 long-chain polyunsaturated fatty acids for adults as well as the recommended intake for pregnant and lactating women. Mussels are non-fed filter feeders that generally provide these nutrients with significantly lower environmental footprints, measured as global warming, eutrophication, and acidification, compared to farmed Atlantic salmon. Blue mussels can also be a valuable feed ingredient for farmed Atlantic salmon. Finally, it was demonstrated that the ethyl acetate method is not suited for lipid extraction from blue mussels, as the lipid yield was only half compared to the lipid yield using the Folch method.
Prevalence, risk factors, impact and management of constipation among adults in Urumqi, China: a cross-sectional survey
Authors: Shi Lingyun , Shi Li , Wei Minghui , Zhang Mengke , Zhang Yuan , Li Jiaxue , Maimaiti Palida
Published: November 2024

Constipation, a prevalent gastrointestinal disorder, significantly impacts quality of life. This study aimed to investigate the prevalence, risk factors, and implications of constipation in Urumqi City. A cross-sectional survey was conducted from July to August 2023, involving 1,386 participants aged 20–80 years. Data were collected via a self-administered questionnaire, with constipation severity assessed using the Patient Assessment of Constipation Symptoms (PAC-SYM) scale. Key findings indicated that various factors, including residing in rural areas, outdoor work, and sleep disorders, were positively correlated with higher PAC-SYM scores. Conversely, higher daily water intake and certain dietary patterns showed negative correlations. Additionally, increased constipation severity was associated with greater physiological strain and psychosocial concerns (all p < 0.05), emphasizing the disorder’s profound effect on quality of life. These findings underscore the need for comprehensive management strategies in Urumqi, considering its diverse lifestyle and dietary factors.
Relationship between serum vitamin D levels and the atherogenic index of plasma: a study based on NHANES database 2011–2018
Authors: Hu Tingting , Zhang Ying , Chen Zhu , Su Jun
Published: November 2024

Objective

This study aims to investigate the relationship between serum vitamin D levels and the atherogenic index of plasma (AIP) in individuals aged 20 years and above, as well as analyze potential influencing factors.

Methods

A total of 9,637 participants aged 20 years and above from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018 were included in this study. The AIP was calculated using the formula log[triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C)]. Due to the skewed distribution of serum vitamin D levels in the study population, a normal transformation was performed. Weighted multivariate linear regression models were used to assess the linear relationship between the transformed serum vitamin D levels and AIP. Subgroup analysis was conducted by stratifying the data based on age, gender, and race to evaluate the stability of the relationship between serum vitamin D levels and AIP in different populations. In addition, a smooth curve fitting and generalized linear models were employed to examine the nonlinear relationship between serum vitamin D levels and AIP.

Results

After controlling for confounding factors, the multivariate linear regression analysis revealed a negative correlation between serum vitamin D levels and AIP [β = −0.0065, 95% CI: (−0.0106, −0.0024)]. This negative correlation was significant in male participants [β = −0.0077, 95% CI: (−0.0142, −0.0011)], Non-Hispanic Black participants [β = −0.0135, 95% CI: (−0.0211, −0.0059)], as well as participants aged 40–50 [β = −0.0124, 95% CI: (−0.0226, −0.0022)] and 60–70 [β = −0.0118, 95% CI: (−0.0214, −0.0023)]. Furthermore, a nonlinear relationship and saturation effect were observed between the transformed serum vitamin D levels and AIP, with a turning point at 8.5617 nmol/L.

Conclusion

Our study revealed a significant negative correlation and saturation effect between serum vitamin D levels and AIP.
Therapeutic strategies to overcome ALK-fusion and BRAF-mutation as acquired resistance mechanism in EGFR-mutated non-small cell lung cancer: two case reports
Authors: Zeng Yuan , Zeng Qiang , Yang Bin , Hu Yang
Published: November 2024

Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world. EGFR tyrosine inhibitors are the preferred first-line treatment for patients with epidermal growth factor-cell receptor mutant (EGFR mutant) advanced NSCLC. Unfortunately, drug resistance inevitably occurs leading to disease progression. Activation of the ALK and BRAF bypass signaling pathways is a rare cause of acquired drug resistance for EGFR-TKIs.We report two NSCLC-patients with EGFR- mutations, in exon 19, and exon 18, correspondingly, who were treated with EGFR-TKIs. The first case shows acquired BRAF-mutation, and the second case demonstrates acquired ALK-fusion. The overall survival of patients was significantly prolonged by drug-match therapies. As it is well-known that ALK-fusion and BRAF-mutations are described forms of acquired resistance. These two case reports contribute to the previous reports that ALK-fusion and BRAF-mutation are potential underlying mechanisms of EGFR-TKI resistance.
Exercise’s impact on lung cancer molecular mechanisms: a current overview
Authors: Mancini Annamaria , Orlandella Francesca Maria , Vitucci Daniela , Luciano Neila , Alfieri Andreina , Orrù Stefania , Salvatore Giuliana , Buono Pasqualina
Published: November 2024

Lung cancer is the major cause of cancer-related deaths worldwide with an estimated 1.8 million deaths and 2.4 million new cases in 2022. Poor cardiorespiratory fitness, dyspnea and fatigue are the common features in lung cancer patients, partially limiting the exercise prescription. Exercise improves cardiorespiratory and muscular fitness and reduces the risk of some types of cancer, including lung cancer. Recently, the American Society of Clinical Oncology has encouraged preoperative exercise for lung cancer patients. Nonetheless, only limited data, mostly obtained from mouse models of lung cancer, are available on the molecular effects of exercise in lung cancer. Thus, the present minireview aims to shed light on the molecular mechanisms induced by different type of exercise in lung cancer. In particular, the role of the exercise in tumor microenvironment remodeling, angiogenesis, gene expression, apoptosis and intermediate metabolism will be examined.
Prevalence of cancer-related fatigue, associated factors and adult cancer patients’ experiences at Hawassa University Comprehensive Specialized Hospital in Ethiopia: a mixed methods study
Authors: Asefa Tseganesh , Bitew Gedamnesh , Tezera Hiwot , Tesfaye Winta
Published: November 2024

Purpose

Cancer-related fatigue is a prevalent issue affecting 50–90% of cancer patients who experience fatigue at diagnosis, during therapy, and often for months or years after the completion of therapy. This study aimed to explore the prevalence of cancer-related fatigue, associated factors, and adult cancer patients’ experiences at Hawassa University Comprehensive Specialized Hospital in Ethiopia.

Methods

A mixed-method study was conducted from February 25 to May 15, 2023, via cross-sectional descriptive and phenomenological approaches. The validated Amharic Brief Fatigue Inventory scale and semistructured interview guide were used. The data were processed via Epi-data version 4.4.3.1 and SPSS version 24, with logistic regression analysis. The interview records and field notes were transcribed and translated from Amharic to English and then analysed thematically.

Results

All participants (100%) completed the study, with 77.4% reporting significant fatigue. Fatigue was strongly associated with uninsured medical expenses (P = 0.008, OR = 3.22), late-stage cancer (P = 0.000, OR = 6.11), anaemia (P = 0.009, OR = 3.71), and comorbidities (P = 0.000, OR = 7.22). From the in-depth interviews with 16 participants, two main themes emerged: financial strain (giving up basics, and inability to work) and disease progression (intensified symptoms, increased treatment side effects, and managing multiple conditions).

Conclusion

This study revealed that 77.4% of cancer patients experience significant fatigue, which is linked to a lack of medical insurance, late-stage cancer, anaemia, and comorbid conditions. Financial strain limits access to care, whereas disease progression and managing multiple conditions intensify fatigue. Early intervention, financial support, and integrated care are crucial for reducing fatigue and improving quality of life. Future research should focus on multicentre and longitudinal studies to improve generalizability and track fatigue progression over time.
Development of a prognostic model incorporating a cuproptosis-related signature and CNN3 as a predictor in childhood acute myelocytic leukemia
Authors: Cao Jiafan , Xie Mengyun , Sun Kexin , Zhao Yijun , Zheng Jiayin , Wang Ying , Zheng Yucan , Liu Sixi , Yu Uet
Published: November 2024

Background

Childhood acute myeloid leukemia (cAML) is the second most common pediatric blood cancer, with high heterogeneity and poor prognosis. Recent studies have highlighted cuproptosis, a newly discovered form of programmed cell death triggered by the accumulation of intracellular copper ions, as a critical mechanism influencing cancer survival and resistance. Given its emerging role in cancer biology, we investigated cuproptosis-related genes (CRGs) in cAML to explore their potential in prognostic prediction and therapeutic targeting.

Methods

Gene expression data from publicly available sources were analyzed to identify differentially expressed CRGs. Samples were categorized based on their expression profiles, followed by the development of a prognostic risk model using multivariable Cox regression, LASSO, and univariable analyses. The model’s performance was evaluated through Kaplan-Meier survival analysis and ROC analysis. Immune infiltration in the tumor microenvironment was assessed using ssGSEA, validated by CIBERSORT. Drug sensitivity correlations were analyzed, and functional validation experiments were conducted on THP-1 and MOLM13 cell lines to assess the role of CNN3.

Results

A set of 12 differential CRGs was used to build a robust prognostic risk model, with high accuracy in predicting patient outcomes (P < 0.001). Significant differences in immune cell composition were identified between risk groups, particularly in T cells, B cells, monocytes, and dendritic cells. Drug sensitivity analysis revealed altered IC50 values for drugs like 5-fluorouracil and bortezomib. Knockdown of CNN3 in leukemia cell lines led to reduced cell proliferation.

Conclusion

Our CRGs-based prognostic model shows potential for guiding personalized treatment strategies in cAML. The differences in immune cell infiltration between risk groups suggest that immune modulation is key in cAML progression. CNN3 and LGR4 were identified as modulators of cAML progression, making them potential therapeutic targets. Future studies with larger cohorts are essential to validate these findings and further explore CRGs-targeted therapies.
The “Pocket book of primary health care for children and adolescents”: WHO standards for improving paediatric and adolescent primary care in Europe, Central Asia and worldwide
Authors: Krüger Carsten , Huss Gottfried , Yasmin Farzana , Weigel Ralf
Published: November 2024

Paediatric primary care is more frequently provided both by physicians other than specialised paediatricians as well as non-physician cadres in Europe and globally. The quality of paediatric primary care including a focus on preventive measures is rather variable and often does not comply with agreed international standards. WHO Europe developed standards for paediatric primary care applicable to the WHO Europe region and globally to improve the provision and outcome of paediatric primary care across all settings. These standards were published in an open-access pocketbook and in an open-access app, both accessible free-of-charge. Although originally intended for use in the WHO Europe region, the pocketbook provides valuable information for all settings of paediatric primary care worldwide.