bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of skin manifestations in patients with COVID-19: a systematic review and meta-analysis
Authors: Aguiar Beatriz Regina Lima de , Ferreira Elaine Barros , De Luca Canto Graziela , Guerra Eliete Neves Silva , Reis Paula Elaine Diniz dos
Published: August 2024

Background

COVID-19 presents extrapulmonary manifestations that can aid in the diagnosis. Skin manifestations have been reported but their characteristics are not yet clear. Health professionals need information about its prevalence and main characteristics.

Methods

This systematic review followed the PRISMA criteria. The protocol was registered in the PROSPERO (number CRD42020193173). Seven electronic databases and the gray literature were searched independently by two researchers. Observational analytical studies that presented data on the prevalence of skin manifestations in patients aged 19 or older with COVID-19 were included. Prevalence estimates were synthesized through a meta-analysis using random-effects models. Association meta-analysis and comparisons were performed for individual characteristics.

Results

We included 31 studies with 10,934 patients, of which 10,121 tested positive for COVID-19. The general prevalence of skin manifestations was 29% (95% CI: 17.0–43.0; I2: 99%), the most in Africa, with a mean duration between 7 and 9 days and the most frequently affecting feet+hands (75%) and the trunk (71%). Patients with mild/moderate COVID-19 had more of chilblain-like+pernio-like lesions (97%) and inflammatory lesions (86%) than patients with severe or critical COVID-19. Manifestations of vascular origin were only in elderly patients and were significant with the severity of COVID-19 (p = 0).

Conclusion

The global prevalence of skin manifestations is similar to other signs and symptoms of COVID-19. Skin assessment should be considered when investigating and diagnosing COVID-19 in adult and elderly patients.

Systematic review registration: PROSPERO, identifier CRD42020193173, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193173.
The common link between sleep apnea syndrome and osteoarthritis: a literature review
Authors: Weng Lian , Luo Yuxi , Luo Xiongjunjie , Yao Kaitao , Zhang Qian , Tan Junjie , Yin Yiran
Published: August 2024

Patients with Osteoarthritis (OA) often also suffer from Sleep Apnea Syndrome (SAS), and many scholars have started to notice this link, although the relationship between the two is still unclear. In this review, we aim to summarize the current literature on these two diseases, integrate evidence of the OA and OSA connection, explore and discuss their potential common mechanisms, and thus identify effective treatment methods for patients with both OA and SAS. Some shared characteristics of the two conditions have been identified, notably aging and obesity as mutual risk factors. Both diseases are associated with various biological processes or molecular pathways, including mitochondrial dysfunction, reactive oxygen species production, the NF-kB pathway, HIF, IL-6, and IL-8. SAS serves as a risk factor for OA, and conversely, OA may influence the progression of SAS. The effects of OA on SAS are underreported in the literature and require more investigation. To effectively manage these patients, timely intervention for SAS is necessary while treating OA, with weight reduction being a primary requirement, alongside combined treatments such as Continuous positive airway pressure (CPAP) and medications. Additionally, numerous studies in drug development are now aimed at inhibiting or clearing certain molecular pathways, including ROS, NF-KB, IL-6, and IL-8. Improving mitochondrial function might represent a viable new strategy, with further research into mitochondrial updates or transplants being essential.
Is there a duration-characteristic relationship for trypsin exposure on tendon? A study on anterior cruciate ligament reconstruction in a rabbit model
Authors: Ma Rongxing , Gao Xiaokang , Jin Yangyang , Wang Xiaolong , Li Ruifeng , Qiao Ruiqi , Wang Xinliang , Liu Dayong , Xie Zhitao , Wang Limin , Zhang Jingyu , Xu Weiguo , Hu Yongcheng
Published: August 2024

Background

Decellularized allograft tendons are highly regarded for their accessibility and the reduced risk of immune rejection, making them a promising choice for grafting due to their favorable characteristics. However, effectively integrating reconstructed tendons with host bone remains a significant clinical challenge.

Purpose

This study aims to investigate the relationship between the duration of tendon exposure to trypsin and its impact on tendon biomechanical properties and healing capacity.

Methods

Morphological assessments and biochemical quantifications were conducted. Allograft tendons underwent heterotopic transplantation into the anterior cruciate ligament (ACL) in a rabbit model, with specimens harvested 6 weeks post-surgery for a comparative analysis of cell adhesion strength and mechanical performance. Duration-response curves were constructed using maximum stress and cell adhesion quantity as primary indicators.

Results

The trypsin treatment enhanced cell adhesion on the tendon surface. Adhesion rates in the control group vs. the experimental groups were as follows: 3.10 ± 0.56% vs. 4.59 ± 1.51%, 5.36 ± 1.24%, 6.12 ± 1.98%, and 8.27 ± 2.34% (F = 6.755, p = 0.001). However, increasing treatment duration led to a decline in mechanical properties, with the ultimate load (N) in the control vs. experimental groups reported as 103.30 ± 10.51 vs. 99.59 ± 4.37, 93.15 ± 12.38, 90.42 ± 7.87, and 82.68 ± 6.89, F = 4.125 (p = 0.013).

Conclusion

The findings reveal an increasing trend in adhesion effectiveness with prolonged exposure duration, while mechanical strength declines. The selection of the optimal processing duration should involve careful consideration of the benefits derived from both outcomes.
Deep learning model shows pathologist-level detection of sentinel node metastasis of melanoma and intra-nodal nevi on whole slide images
Authors: Siarov Jan , Siarov Angelica , Kumar Darshan , Paoli John , Mölne Johan , Neittaanmäki Noora
Published: August 2024

Introduction

Nodal metastasis (NM) in sentinel node biopsies (SNB) is crucial for melanoma staging. However, an intra-nodal nevus (INN) may often be misclassified as NM, leading to potential misdiagnosis and incorrect staging. There is high discordance among pathologists in assessing SNB positivity, which may lead to false staging. Digital whole slide imaging offers the potential for implementing artificial intelligence (AI) in digital pathology. In this study, we assessed the capability of AI to detect NM and INN in SNBs.

Methods

A total of 485 hematoxylin and eosin whole slide images (WSIs), including NM and INN from 196 SNBs, were collected and divided into training (279 WSIs), validation (89 WSIs), and test sets (117 WSIs). A deep learning model was trained with 5,956 manual pixel-wise annotations. The AI and three blinded dermatopathologists assessed the test set, with immunohistochemistry serving as the reference standard.

Results

The AI model showed excellent performance with an area under the curve receiver operating characteristic (AUC) of 0.965 for detecting NM. In comparison, the AUC for NM detection among dermatopathologists ranged between 0.94 and 0.98. For the detection of INN, the AUC was lower for both AI (0.781) and dermatopathologists (range of 0.63–0.79).

Discussion

In conclusion, the deep learning AI model showed excellent accuracy in detecting NM, achieving dermatopathologist-level performance in detecting both NM and INN. Importantly, the AI model showed the potential to differentiate between these two entities. However, further validation is warranted.
Effectiveness and safety of acupuncture modalities for overweight and obesity treatment: a systematic review and network meta-analysis of RCTs
Authors: Kim Youngjin , Park Ha-im , Chu Hongmin , Jin Hanbit , Leem Jungtae
Published: August 2024

Introduction

The effectiveness and safety of acupuncture in the treatment of obesity have not been assessed. This poses a challenge for clinicians who choose to use acupuncture in the treatment of obesity, as they are unable to prioritize this approach based on outcome variables.

Methods

In May 2024, a literature search of five databases was conducted. Only randomized controlled trials evaluating body weight (BW), body mass index, waist circumference (WC), and adverse events in patients with a body mass index (BMI) of 25 or higher for various acupuncture modalities were included. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials, version 2. Pairwise meta-analysis (PMA) and Bayesian network meta-analysis (NMA) were performed using a random effects model for quantitative synthesis.

Results

Fourteen studies (n = 868) were included. The included studies evaluated the following acupuncture modalities: electroacupuncture (EA) (N = 6), laser acupuncture (LA) (N = 2), auricular acupuncture (AA) (N = 5), and manual acupuncture (MA) (N = 3). The PMA found that adding EA to usual care (UC), compared to UC alone, reduced BW (MD = 2.46, 95% CI = 1.12 to 3.80, I2 = 58%, REM, N = 3, n = 157). The NMA of BW showed the following effect sizes for UC alone versus each acupuncture modality combined with UC: LA (MD = 2.09, 95% CI = 0.04 to 3.86), EA (MD = 2.04, 95% CI = 0.88 to 3.50), AA (MD = 1.69, 95% CI = −0.11 to 3.58), and MA (MD = 1.02, 95% CI = −0.82 to 2.94). The probability of each modality being the optimal treatment was evaluated using the surface under the cumulative ranking curve. EA was the most efficacious for BW and BMI, while LA was the most efficacious for WC.

Discussion

EA and LA can effectively complement clinical obesity management. The number of included studies was limited, and publication bias may have occurred, necessitating a cautious interpretation of the results. Furthermore, most studies lasted between six and 12 weeks. Future clinical studies of acupuncture for obesity should include longer follow-up periods.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=387788, identifier CRD42023387788.
Unraveling the roles of IFIT3 gene and immune-metabolic pathways in psoriasis: a bioinformatics exploration for diagnostic markers and therapeutic targets
Authors: Chen Guangshan , Chen Xi , Duan Xingwu , Zhang Runtian , Bai Chunxiao
Published: August 2024

Background

The functions and related signal pathways of the IFIT3 gene in the skin lesions of patients with psoriasis were explored through bioinformatics methods to determine the potential specific molecular markers of psoriasis.

Methods

The “limma” R package was used to analyze three datasets from the Gene Expression Omnibus database (GSE13355, GSE30999 and GSE106992), and the differential genes were screened. The STRING database was used for gene ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, and protein–protein interaction network integration. Then, the IFIT3 subnetwork was extracted and analyzed by gene set enrichment analysis (GSEA) using the Metascape database to verify the effectiveness of gene differentiation and disease tissue identification.

Results

In this study, 426 differential genes were obtained, of which 322 were significantly upregulated and 104 were significantly downregulated. GO enrichment analysis showed that the differential genes were mainly involved in immunity and metabolism; the KEGG pathway enrichment analysis mainly included the chemokine signal pathway, PPAR signal pathway, and IL-17 signal pathway, among others. Based on the IFIT3 subnetwork analysis, it was found that IFIT3 was mainly involved in the biological processes of viruses, bacteria, and other microorganisms. The pathways obtained by GSEA were mainly related to immunity, metabolism, and antiviral activities. IFIT3 was highly expressed in psoriatic lesions and may thus be helpful in the diagnosis of psoriasis.

Conclusion

The differential genes, biological processes, and signal pathways of psoriasis, especially information related to and diagnostic efficiency of the IFIT3 gene, were obtained by bioinformatics analysis. These results are expected to provide the theoretical basis and new directions for exploring the pathogenesis of psoriasis, in addition to helping with finding diagnostic markers and developing drug treatment targets.
Comprehensive analysis of hypoxia-related genes in diagnosis and immune infiltration in acute myocardial infarction: based on bulk and single-cell RNA sequencing data
Authors: Liu Guoqing , Liao Wang , Lv Xiangwen , Zhu Miaomiao , Long Xingqing , Xie Jian
Published: August 2024

Background

Hypoxia has been found to cause cellular dysfunction and cell death, which are essential mechanisms in the development of acute myocardial infarction (AMI). However, the impact of hypoxia-related genes (HRGs) on AMI remains uncertain.

Methods

The training dataset GSE66360, validation dataset GSE48060, and scRNA dataset GSE163956 were downloaded from the GEO database. We identified hub HRGs in AMI using machine learning methods. A prediction model for AMI occurrence was constructed and validated based on the identified hub HRGs. Correlations between hub HRGs and immune cells were explored using ssGSEA analysis. Unsupervised consensus clustering analysis was used to identify robust molecular clusters associated with hypoxia. Single-cell analysis was used to determine the distribution of hub HRGs in cell populations. RT-qPCR verified the expression levels of hub HRGs in the human cardiomyocyte model of AMI by oxygen-glucose deprivation (OGD) treatment in AC16 cells.

Results

Fourteen candidate HRGs were identified by differential analysis, and the RF model and the nomogram based on 8 hub HRGs (IRS2, ZFP36, NFIL3, TNFAIP3, SLC2A3, IER3, MAFF, and PLAUR) were constructed, and the ROC curves verified its good prediction effect in training and validation datasets (AUC = 0.9339 and 0.8141, respectively). In addition, the interaction between hub HRGs and smooth muscle cells, immune cells was elucidated by scRNA analysis. Subsequently, the HRG pattern was constructed by consensus clustering, and the HRG gene pattern verified the accuracy of its grouping. Patients with AMI could be categorized into three HRG subclusters, and cluster A was significantly associated with immune infiltration. The RT-qPCR results showed that the hub HRGs in the OGD group were significantly overexpressed.

Conclusion

A predictive model of AMI based on HRGs was developed and strongly associated with immune cell infiltration. Characterizing patients for hypoxia could help identify populations with specific molecular profiles and provide precise treatment.
Old innovations and shifted paradigms in cellular neuroscience
Authors: Fesce Riccardo
Published: August 2024

Once upon a time the statistics of quantal release were fashionable: “n” available vesicles (fusion sites), each with probability “p” of releasing a quantum. The story was not so simple, a nice paradigm to be abandoned. Biophysicists, experimenting with “black films,” explained the astonishing rapidity of spike-induced release: calcium can trigger the fusion of lipidic vesicles with a lipid bilayer, by masking the negative charges of the membranes. The idea passed away, buried by the discovery of NSF, SNAPs, SNARE proteins and synaptotagmin, Munc, RIM, complexin. Electrophysiology used to be a field for few adepts. Then came patch clamp, and multielectrode arrays and everybody became electrophysiologists. Now, optogenetics have blossomed, and the whole field has changed again. Nice surprise for me, when Alvarez de Toledo demonstrated that release of transmitters could occur through the transient opening of a pore between the vesicle and the plasma-membrane, no collapse of the vesicle in the membrane needed: my mentor Bruno Ceccarelli had cherished this idea (“kiss and run”) and tried to prove it for 20 years. The most impressive developments have probably regarded IT, computers and all their applications; machine learning, AI, and the truly spectacular innovations in brain imaging, especially functional ones, have transformed cognitive neurosciences into a new extraordinarily prolific field, and certainly let us imagine that we may finally understand what is going on in our brains. Cellular neuroscience, on the other hand, though the large public has been much less aware of the incredible amount of information the scientific community has acquired on the cellular aspects of neuronal function, may indeed help us to eventually understand the mechanistic detail of how the brain work. But this is no more in the past, this is the future.
Association between systemic immune-inflammation index and serum neurofilament light chain: a population-based study from the NHANES (2013–2014)
Authors: Liu Xinyu , Yang Yue , Lu Qiutong , Yang Jianshu , Yuan Jing , Hu Jun , Tu Yue
Published: August 2024

Background

The systemic immune-inflammation index (SII) is a novel inflammatory marker used to assess the immune-inflammatory status of the human body. The systemic immune inflammation has an interplay and mutual relationship with neurological disorders. Serum neurofilament light chain (sNfL) is widely regarded as a potential biomarker for various neurological diseases. The study aimed to examine the association between SII and sNfL.

Methods

This cross-sectional investigation was conducted in a population with complete data on SII and sNfL from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). The SII was calculated by dividing the product of platelet count and neutrophil count by the lymphocyte count. Multivariate linear regression models and smooth curves were used to explore the linear connection between SII and sNfL. Sensitivity analyses, interaction tests, and diabetes subgroup smoothing curve fitting were also performed.

Results

A total of 2,025 participants were included in our present research. SII showed a significant positive association with the natural logarithm-transformed sNfL (ln-sNfL) in crude model [0.17 (0.07, 0.28)], partially adjusted model [0.13 (0.03, 0.22)], and fully adjusted model [0.12 (0.02, 0.22)]. In all participants, the positive association between SII and ln-sNfL served as a linear relationship, as indicated by a smooth curve. Interaction tests showed that age, gender, BMI, hypertension, and diabetes did not have a significant impact on this positive association (p for interaction >0.05). The subgroup analysis of diabetes was conducted using smooth curve fitting. It was found that compared to the group without diabetes and the group in a pre-diabetic state, the effect was more pronounced in the group with diabetes.

Conclusion

Our findings suggest that there is a positive association between SII and sNfL. Furthermore, in comparison to individuals without diabetes and those in a pre-diabetic state, the positive association between SII and sNfL was more pronounced in individuals with diabetes. Further large-scale prospective studies are needed to confirm the association between SII and sNfL.
Efficacy and safety of different doses of vamorolone in boys with Duchenne muscular dystrophy: a systematic review and network meta-analysis
Authors: Wang Qin , Zeng Yaqing , Jiao Linna , He Jianli , Li Baoyi , Guo Yihua , Song Zhibin
Published: August 2024

Background and objectives

Several recent clinical studies have indicated that vamorolone is comparable in effectiveness to glucocorticosteroids for treating Duchenne muscular dystrophy (DMD). However, there is a lack of extensive data regarding the efficacy and safety of various doses of vamorolone. We conducted a study to evaluate the efficacy of different doses of vamorolone in boys with DMD, and compare the safety of vamorolone vs. glucocorticosteroids, prednisone or deflazacort in boys with DMD.

Methods

We performed systematic searches of the PubMed, Embase, and Cochrane Library databases for vamorolone, glucocorticosteroids, prednisone or deflazacort in boys with DMD. We assessed statistical heterogeneity across trials based on the Newcastle Ottawa scale (NOS) tool test and I2 values, and mean differences were pooled using the random-effects model. We used traditional meta-analysis to evaluate efficacy and safety of vamorolone 6.0 mg/kg/d vs. vamorolone 2.0 mg/kg/d and vamorolone vs. prednisone. A network meta-analysis was applied to estimated the safety of vamorolone in comparison to glucocorticosteroids, prednisone and deflazacort. Our meta-analysis were performed using Revman 5.4 software, and our network meta-analysis were performed using Stata/MP 18.0.

Results

In the meta-analysis, a total of 193 patients were analyzed across four clinical trials (97 patients receiving vamorolone 2 mg/kg per day; 96 patients receiving vamorolone 2 mg/kg per day). We observed that there were statistically significant differences in boys with DMD between vamorolone 6.0 mg/kg/d and vamorolone 2.0 mg/kg/d in TTSTANDV (MD = 0.03, 95%CI = 0.00–0.06, p = 0.04), TTRWV (MD = 0.13, 95%CI = 0.08–0.19, p < 0.01), 6MWT (MD = 24.54, 95%CI = 4.46–44.82, p = 0.02), TTCLIMBV (MD = 0.04, 95%CI = 0.01–0.06, p = 0.009), no significant difference in BMI z score (MD = 0.09, 95%CI = −0.03–0.20, p = 0.13). Indirect comparisons derived from network meta-analysis did not show significant differences among vamorolone, glucocorticosteroids, prednisone and deflazacort in BMI z score.

Conclusion

Our findings implied that boys with DMD who took vamorolone 6 mg/kg daily instead of 2 mg/kg daily may be safer and have superior motor function. However, more large sample randomized controlled trials are needed to confirm our results.

Systematic Review Registration

This systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration number: CRD42024562916).
Association between osteoarthritis with Parkinson’s disease in the US (NHANES 2011–2020)
Authors: Liu Yang , Zhou Xue , Chen Chunhai , Li Xuefeng , Pan Ting , Liu Ziqi , Wu Dalong , Chen Xinhua
Published: August 2024

Objected

To evaluate the association between osteoarthritis (OA) and Parkinson’s disease (PD) in adults in the United States.

Methods

Using 2011–2020 NHANES data, a cross-sectional study of 11,117 adults over the age of 40 was conducted. Univariate logistic regression and multivariate logistic regression were used to analyze the relationship between arthritis and PD. In addition, stratified analysis was used to examine whether the relationship between arthritis and PD was interactive with age, gender, race, education, BMI.

Results

In this study, a total of 11,117 participants were included, and we found that osteoarthritis was positively correlated with the development of PD compared with non-arthritis patients [1.95 (1.44 ~ 2.62)] (p < 0.001). After adjusting the covariates, the results are still stable.

Conclusion

PD patients were positively correlated with OA. Among people with OA, there was a 95% increased risk of PD compared to people without arthritis. Therefore, when treating OA, attention should be paid to the increased risk of PD. In the meantime, further studies are needed to explore the link between OA and PD patients.
Neural oscillation in bipolar disorder: a systematic review of resting-state electroencephalography studies
Authors: Su Ziyao , Zhang Haoran , Wang Yingtan , Chen Bingxu , Zhang Zhizhen , Wang Bin , Liu Jun , Shi Yuwei , Zhao Xixi
Published: August 2024

Bipolar disorder (BD) is a severe psychiatric disease with high rates of misdiagnosis and underdiagnosis, resulting in a significant disease burden on both individuals and society. Abnormal neural oscillations have garnered significant attention as potential neurobiological markers of BD. However, untangling the mechanisms that subserve these baseline alternations requires measurement of their electrophysiological underpinnings. This systematic review investigates consistent abnormal resting-state EEG power of BD and conducted an initial exploration into how methodological approaches might impact the study outcomes. This review was conducted in Pubmed-Medline and Web-of-Science in March 2024 to summarize the oscillation changes in resting-state EEG (rsEEG) of BD. We focusing on rsEEG to report spectral power in different frequency bands. We identified 10 studies, in which neural oscillations was compared with healthy individuals (HCs). We found that BD patients had abnormal oscillations in delta, theta, beta, and gamma bands, predominantly characterized by increased power, indicating potential widespread neural dysfunction, involving multiple neural networks and cognitive processes. However, the outcomes regarding alpha oscillation in BD were more heterogeneous, which is thought to be potentially influenced by the disease severity and the diversity of samples. Furthermore, we conducted an initial exploration into how demographic and methodological elements might impact the study outcomes, underlining the importance of implementing standardized data collection methods. Key aspects we took into account included gender, age, medication usage, medical history, the method of frequency band segmentation, and situation of eye open/eye close during the recordings. Therefore, in the face of abnormal multiple oscillations in BD, we need to adopt a comprehensive research approach, consider the multidimensional attributes of the disease and the heterogeneity of samples, and pay attention to the standardized experimental design to improve the reliability and reproducibility of the research results.
Proteomics analysis of periplaque and chronic inactive multiple sclerosis lesions
Authors: Wilkins Jordan M. , Mangalaparthi Kiran K. , Netzel Brian C. , Sherman William A. , Guo Yong , Kalinowska-Lyszczarz Alicja , Pandey Akhilesh , Lucchinetti Claudia F.
Published: August 2024

Background

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by increased inflammation and immune responses, oxidative injury, mitochondrial dysfunction, and iron dyshomeostasis leading to demyelination and axonal damage. In MS, incomplete remyelination results in chronically demyelinated axons and degeneration coinciding with disability. This suggests a failure in the ability to remyelinate in MS, however, the precise underlying mechanisms remain unclear. We aimed to identify proteins whose expression was altered in chronic inactive white matter lesions and periplaque white matter in MS tissue to reveal potential pathophysiological mechanisms.

Methods

Laser capture microdissection coupled to proteomics was used to interrogate spatially altered changes in formalin-fixed paraffin-embedded brain tissue from three chronic MS individuals and three controls with no apparent neurological complications. Histopathological maps guided the capture of inactive lesions, periplaque white matter, and cortex from chronic MS individuals along with corresponding white matter and cortex from control tissue. Label free quantitation by liquid chromatography tandem mass spectrometry was used to discover differentially expressed proteins between the various brain regions.

Results

In addition to confirming loss of several myelin-associated proteins known to be affected in MS, proteomics analysis of chronic inactive MS lesions revealed alterations in myelin assembly, metabolism, and cytoskeletal organization. The top altered proteins in MS inactive lesions compared to control white matter consisted of PPP1R14A, ERMN, SIRT2, CARNS1, and MBLAC2.

Conclusion

Our findings highlight proteome changes in chronic inactive MS white matter lesions and periplaque white matter, which may be crucial for proper myelinogenesis, bioenergetics, focal adhesions, and cellular function. This study highlights the importance and feasibility of spatial approaches such as laser capture microdissection-based proteomics analysis of pathologically distinct regions of MS brain tissue. Identification of spatially resolved changes in the proteome of MS brain tissue should aid in the understanding of pathophysiological mechanisms and the development of novel therapies.
Efficacy and safety of PD-1 inhibitors plus anti-angiogenesis tyrosine kinase inhibitors with or without transarterial chemo(embolization) for unresectable hepatocellular carcinoma: a meta-analysis
Authors: Chen Yue , Jia Luyao , Li Yu , Cui Wenhao , Wang Jukun , Zhang Chao , Bian Chunjing , Luo Tao
Published: August 2024

Background

The triple combination of programmed cell death protein–1 (PD-1) inhibitors plus anti-angiogenesis tyrosine kinase inhibitors (TKIs) with or without transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) enhance the effect of treatment for unresectable hepatocellular carcinoma (uHCC). The present study compared the efficacy and safety of PD-1 plus TKI with or without transarterial chemo(embolization) for uHCC.

Methods

The meta-analysis was conducted using data acquired from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials.gov from the inception date to December 2023. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were used to measure the pooled effect. In addition, subgroup analysis was conducted to determine the specific patient population that benefited.

Results

The OS (HR = 0.47; 95% CI: 0.39–0.56, P <  0.05), PFS (HR = 0.52; 95% CI: 0.45–0.60, P < 0.05), and ORR (RR = 1.94; 95% CI: 1.60–2.35, P < 0.05) were significantly better in TACE/HAIC+TKI+PD-1(TACE/HAIC TP) group than TKI+PD-1(TP) group. The incidence of AEs was acceptable.

Conclusion

The triple therapy of TACE/HAIC TP had better efficacy for uHCC than TP, with acceptable security.

Systematic review registration

PROSPERO, identifier CRD42023475953.
Metabolic profiles in gestational diabetes mellitus can reveal novel biomarkers for prediction of adverse neonatal outcomes
Authors: Yin Xiaoxiao , Yu Tingting , Jiang Dongmei , Shan Chunjian , Xia Jiaai , Su Min , Zhang Min , Chen Ling , Zhong Hong , Cui Xianwei , Ji Chenbo
Published: August 2024

Background

Gestational diabetes mellitus (GDM) significantly affects the fetal metabolic environment, elevating risks of neonatal hypoglycemia and macrosomia. Metabolomics offers promising avenues for early prediction and diagnosis of GDM and associated adverse offspring outcomes.

Methods

This study analyzed serum samples from pregnant women diagnosed with GDM at 24 to 28 weeks of gestation using untargeted metabolomics. We monitored the health outcomes of their offspring to explore the correlation between initial serum metabolite profiles and subsequent health outcomes, to uncover the predictive markers for hypoglycemia and macrosomia in these offspring.

Results

Out of 200 participants, 154 had normal newborns, 33 had offspring with hypoglycemia, and 19 had offspring with macrosomia. From 448 identified metabolites, 66 showed significant differences in cases of hypoglycemia, and 45 in macrosomia. A panel of serum metabolite biomarkers achieved Area Under the Curve (AUC) values of 0.8712 for predicting hypoglycemia and 0.9434 for macrosomia.

Conclusion

The study delineated metabolic disruptions in GDM during 24–28 weeks of gestation and pinpointed biomarkers capable of forecasting adverse neonatal outcomes. These findings could inform GDM management strategies and minimize the incidence of such outcomes.
Caplacizumab as an add-on therapy in a 7-year-old girl with exacerbated immune-mediated thrombotic thrombocytopenic purpura, a case report and literature review
Authors: Chavaz Lara , Cimasoni Laurent , Kremer Hovinga Johanna A. , Coppo Paul , Ansari Marc
Published: August 2024

The cornerstone treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) in children is a combination of therapeutic plasma exchange (TPE), corticosteroids, and rituximab. Caplacizumab is an anti-von Willebrand factor (VWF) NANOBODY molecule approved as a frontline therapy of iTTP for adults and children aged ≥12 years. Using caplacizumab in children aged <12 years remains a gray area based on recommendations but with no marketing authorization. We report the first case of a pediatric patient with iTTP successfully treated with a caplacizumab dose adjustment of 5 mg daily based on ADAMTS13 activity. We also review all published cases of iTTP in children aged <12 years treated with caplacizumab. This is a 7-year-old girl with clinical thrombotic microangiopathy, in the absence of diarrhea and kidney injury. With a French score of 2 and a PLASMIC score of 7 (high risk), the diagnosis of TTP was suspected and later confirmed by severely low ADAMTS13 activity (<5%). Immune-mediated TTP was distinguished from the congenital one due to the presence of a functional ADAMTS13 inhibitor. Daily TPE and intravenous corticosteroids were started on day 0 (D0). Rituximab was added on D4, and due to refractoriness under daily TPE, we considered off-label administration of caplacizumab from D12. A clinical answer, with a significant increase in the platelet count, was observed within 48 h. A complete ADAMTS13 recovery was reached on D62. No major adverse events were observed during the treatment. She was discharged from the hospital over 3 months ago with a platelet count still within normal ranges. In the literature, we identified a total of four case reports describing five iTTP patients aged <12 years treated with caplacizumab, with a 100% success and tolerability rate. These published data attest to the efficacy and safety of the systematic use of caplacizumab and rituximab as frontline therapy in pediatric iTTP under 12 years of age. Therefore, prospective data are needed to support commercial authorization of caplacizumab in this subpopulation. Close monitoring of ADAMTS13 activity is particularly of interest among children to limit the number of caplacizumab injections.
Chlorogenic acid compounds from sweetpotato (Ipomoea batatas L.) leaves facilitate megakaryocyte differentiation and thrombocytopoiesis via PI3K/AKT pathway
Authors: Zhang Yi , Zhao Lu , Wang Liping , Yue Ruixue , Zhu Hong , Zhang Wenting , Sun Jian , Zhang Zifeng , Ma Daifu
Published: August 2024

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, thrombocytopenia, and bleeding, however, its treatment options are limited. In this study, a kind of active component, chlorogenic acid compounds (CGAs) from sweetpotato leaves was extracted out to explore its medicinal value and provide novel therapeutic strategies for the treatment of ITP. CGAs was isolated by ionic liquids-ultrasound (IL-UAE), which contains six isomers of chlorogenic acid with total purity of 95.69%. The thrombopoietic effect and mechanism of CGAs were investigated using in silico prediction and experimental validation. The changes of HEL cells morphology in volume and the increase in the total cell percentage of polyploid cells indicated that CGAs could promote megakaryocyte differentiation. Meanwhile, CGAs could promote platelet formation in a murine model of ITP, which was established by injection of antiplatelet antibody. Further quantitative proteomics analysis and Western blot verification revealed that CGAs could activate PI3K/AKT signaling pathway, which confirmed the mechanism prediction. It suggested that CGAs may provide a novel therapeutic strategy that relies on the PI3K/AKT pathway to facilitate megakaryocyte differentiation and platelet production.
In silico and in vivo evaluations of multistage antiplasmodial potency and toxicity profiling of n-Hexadecanoic acid derived from Vernonia amygdalina
Authors: Afolayan F. I. D. , Odeyemi R. A. , Salaam R. A.
Published: August 2024

Background

Despite the widely reported potentials of n-Hexadecanoic acid (HA) as a bioactive, its multi-stage antiplasmodial activity and toxicity profiles remain largely unknown.

Methodology

Thus, this study uses a combination of in silico approaches and in vivo studies to assess the inhibitory activities of HA at different stages of the Plasmodium lifecycle, antiplasmodial performance, and toxicity profiles. The HA was retrieved from the PubChem database, while antiplasmodial target proteins from different stages of the Plasmodium falciparum life cycle were collated from the Protein Databank (PDB). Molecular Docking and Visualization were conducted between the compound and target proteins using AutoVina PyRx software and Biovia Discovery Studio, respectively. Also, the AdmetLab 3.0 algorithm was used to predict the absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles of HA. Based on a 4-day suppressive test, the antiplasmodial activity against the Plasmodium berghei ANKA strain in mice was evaluated. Furthermore, subacute toxicity and micronucleus assays were used for further toxicity assessment.

Results

The molecular docking analysis indicates multi-stage, multi-target potentials of HA with favourable ligand-receptor complexes across the four Plasmodium falciparum stages. Meanwhile, the mice administered with 100 mg/kg, 50 mg/kg, and 10 mg/kg of HA demonstrated considerable chemosuppression in a dose-dependent manner of 89.74%, 83.80%, and 71.58% percentage chemosuppression, respectively, at p < 0.05. The ADMET prediction, histopathological tests, and micronucleus assays show that HA is safer at a lower dose.

Conclusion

This study showed that n-Hexadecanoic acid is a potential drug candidate for malaria. Hence, it is recommended for further molecular and biochemical investigations.
The impact of sucralose and neotame on the safety of metal precipitation in electronic cigarettes
Authors: Yan Xinyang , Chen Zheng , Rong Xianfang , Chen Zhichao , Wu Guanlin , Dong Zeyi , Fu Yao , Hai Tao
Published: August 2024

This study investigated the impact of sweeteners on the release of heavy metals during the heating and atomization processes in electronic cigarettes. Based on a PG/VG base e-liquid with the addition of 2% and 5% neotame or sucralose, we quantitatively analyzed the impact of sweetener content on the levels of heavy metals such as Ni, Cr, and Fe in the e-liquid and aerosol after heating and atomization. Additionally, the heated e-liquid samples were used to culture SH-SY-5Y and Beas-2B cells, and their cytotoxic effects were assessed using the CCK-8 assay. The results indicated that the e-liquid with 5% sucralose had the highest average levels of heavy metals after heating and atomization, particularly nickel (13.36 ± 2.50 mg/kg in the e-liquid and 12,109 ± 3,229 ng/200 puffs in the aerosol), whereas the e-liquid with neotame had significantly lower average heavy metal content in comparison. Additionally, it was measured that the chloride ion concentration in the e-liquid with 5% sucralose reached 191 mg/kg after heating at 200°C for 1 h, indicating that heating sucralose generated chloride ions, Which might corrode metal parts components leading to heavy metal release. Cytotoxicity tests revealed that the base e-liquid without sweeteners exhibited the highest average cell viability after heating, at 64.80% ± 2.84% in SH-SY-5Y cells and 63.24% ± 0.86% in Beas-2B cells. Conversely, the e-liquid variant with 5% sucralose showed a significant reduction in average cell viability, reducing it to 50.74% ± 0.88% in SH-SY-5Y cells and 53.03% ± 0.76% in Beas-2B cells, highlighting its more pronounced cytotoxic effects compared to other tested e-liquids. In conclusion, sucralose in e-liquids should be limited preferably less than 2%, or replaced with neotame, a safer alternative, to minimize health risks.
MCMV-infected maize attracts its insect vector Frankliniella occidentalis by inducing β-myrcene
Authors: Huang Weiling , Wei Shujun , Zhou Tao , Fan Zaifeng , Cao Lijun , Li Zhihong , Guo Shaokun
Published: August 2024

Maize lethal necrosis is attributed to the accumulation of maize chlorotic mottle virus (MCMV), an invasive virus transmitted by insect vectors. The western flower thrips (WFT) can shift host to maize, thus promoting the spread of MCMV. However, our understanding of the characteristics and interactions involved in the transmission of MCMV is still limited. This study finds that non-viruliferous WFTs showed a 57.56% higher preference for MCMV-infected maize plants compared to healthy maize plants, while viruliferous WFTs showed a 53.70% higher preference for healthy maize plants compared to MCMV-infected maize plants. We also show for the first time that both adults and larvae of WFT could successfully acquire MCMV after 1 min of acquisition access period (AAP), and after 48 h of AAP, WFT could transmit MCMV in an inoculation access period of 1 h without a latent period. Both adults and larvae of WFT can transmit MCMV for up to 2 days. Furthermore, the decreasing number of viruliferous WFTs and transmission rates as time progressed, together with the transcriptomic evidence, collectively suggest that WFTs transmit MCMV in a semi-persistent method, a mode of transmission requiring minutes to several hours for acquisition access and having a retention time of several hours to a few days. Additionally, β-myrcene can attract WFTs significantly and is detected in Nicotiana benthamiana plants transiently expressing MCMV CP (coat protein), which is consistent with results in MCMV-infected maize plants through the metabolomic profiling and the preference analyses of WFT. Therefore, this study demonstrates the indirect interaction between MCMV and WFT by inducing maize to synthesize β-myrcene to attract insect vectors. The exploration of specific interactions between MCMV and WFT could help to expand the mechanism studies of virus–vector–host plant interaction and put forward a new insight for the combined control of MCMV and WFT through the manipulation of plant volatiles and key insect genes.
Study on chemical constituents and antioxidant activities of Dianthus caryophyllus L.
Authors: Wang Miaomiao , Shen Qiuyu , Pang Jianyu , Mao Yu , Li Xiaofei , Tao Yanxia , Tang Wenru , Sun Ruifen , Zhou Xuhong
Published: August 2024

Objective

Carnation is a plant that holds high value in terms of its edibility, medicinal properties, and ornamental appeal. Creating no sense he aim of this study was to evaluate the antioxidant and antitumor properties of extracts derived from various parts of the carnation plant. Metabolomics technology was employed to identify the primary chemical constituents.

Methods

Initially, we measured the total phenolic and total flavonoid contents in carnation roots, stems, leaves, and flowers, followed by assessing the antioxidant and anti-tumor capabilities of each component using diverse experimental methods. Subsequently, UPLC-MS/MS was employed to identify metabolites in different parts of carnation and investigate their roles in antioxidant and anti-tumor activities.

Results

Mention numerical value- for better underatnding- Results of the study indicated that the methanol extract obtained from carnation flowers and roots exhibited superior antioxidant capacity compared to that from the stems and leaves. This disparity may be attributed to the abundance of polyphenols, flavonoids, and antioxidants present in the flowers, including methyl ferulate and luteolin-4’-O-glucoside. Furthermore, the significant presence of the anthraquinone compound rhein-8-O-glucoside in carnation roots may contribute to their enhanced antioxidant properties. Ten distinct compounds were isolated and recognized in carnation flowers, with Isoorientin 2”-O-rhamnoside and Kurarinone demonstrating notable antioxidant activity and binding affinity to SOD1 and SOD3, as validated through antioxidant screening and molecular docking.

Conclusion

Overall, the findings from this study have expanded our knowledge of the phytochemical composition across different anatomical regions of the carnation plant, providing valuable insights for its holistic utilization.
Transcriptome analysis reveals the promoting effects of exogenous melatonin on the selenium uptake in grape under selenium stress
Authors: Wang Jin , Lu Yuhang , Xing Shanshan , Yang Jinman , Liu Lei , Huang Kewen , Liang Dong , Xia Hui , Zhang Xiaoli , Lv Xiulan , Lin Lijin
Published: August 2024

Introduction

Exogenous melatonin (MT) can promote horticultural crops growth under stress conditions.

Methods

In this study, the effects of exogenous MT on the accumulation of selenium (Se) in grape were studied under Se stress.

Results and discussion

Under Se stress, exogenous MT increased the biomass, content of photosynthetic pigments and antioxidant enzyme activity of grapevines. Compared with Se treatment, MT increased the root biomass, shoot biomass, chlorophyll a content, chlorophyll b content, carotenoids, superoxide dismutase activity, and peroxidase activity by 18.11%, 7.71%, 25.70%, 25.00%, 25.93%, 5.73%, and 9.41%, respectively. Additionally, MT increased the contents of gibberellin, auxin, and MT in grapevines under Se stress, while it decreased the content of abscisic acid. MT increased the contents of total Se, organic Se and inorganic Se in grapevines. Compared with Se treatment, MT increased the contents of total Se in the roots and shoots by 48.82% and 135.66%, respectively. A transcriptome sequencing analysis revealed that MT primarily regulated the cellular, metabolic, and bioregulatory processes of grapevine under Se stress, and the differentially expressed genes (DEGs) were primarily enriched in pathways, such as aminoacyl-tRNA biosynthesis, spliceosome, and flavonoid biosynthesis. These involved nine DEGs and nine metabolic pathways in total. Moreover, a field experiment showed that MT increased the content of Se in grapes and improved their quality. Therefore, MT can alleviate the stress of Se in grapevines and promote their growth and the accumulation of Se.
The influence of home environment on 2-year-old Chinese children's language development: the mediating effect of executive function and the moderating effect of temperament
Authors: Qiu Siyao , Wang Zhidan
Published: August 2024

Prior research highlighted the effect of home environment on the language development of young children. Recent research has mainly discussed the moderating effect of personality traits like temperament. Nevertheless, the precise mechanism about the relationship between home environments to children's language development remains incompletely understood. This study explored how home environment impacts the language development of 2-year-old toddlers and the role of temperament and executive function in this relationship. We used the Chinese Child Adaptive Behavior Scale, the Temperament Scale for 1–3 years old of toddlers and the Home Environment Scale for Infants' and Toddlers' families to assess children's language development, temperament, and home environment. Simultaneously, the research used the Stroop-like day-night task and the multiple location search task to evaluate children's executive function. A total of 117 2-year-old children as well as their parents were involved in the study. The results revealed that home environment significantly predicts children's language ability with executive function as a mediating role. Temperament dimensions including extraversion, independence, reactivity, and social inhibition play a moderating role between home environment and executive function. The findings contributed to the improved implementation of home education tailored to children with different temperament traits, offering effective support for the cognitive and language development of young children.