bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic study of pre-eclampsia and macrophage-associated molecular networks: bioinformatics insights from multiple datasets
Authors: Cao Jinfeng , Jiang Wenxin , Yin Zhe , Li Na , Tong Chao , Qi Hongbo
Published: May 2024

Background

Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the molecular mechanism of macrophages in pre-eclampsia is not well understood.

Methods

In this study, the key biomarkers during the development of pre-eclampsia were identified using bioinformatics analysis. The GSE75010 and GSE74341 datasets from the GEO database were obtained and merged for differential analysis. A weighted gene co-expression network analysis (WGCNA) was constructed based on macrophage content, and machine learning methods were employed to identify key genes. Immunoinfiltration analysis completed by the CIBERSORT method, R package “ClusterProfiler” to explore functional enrichment of these intersection genes, and potential drug predictions were conducted using the CMap database. Lastly, independent analysis of protein levels, localization, and quantitative analysis was performed on placental tissues collected from both preeclampsia patients and healthy control groups.

Results

We identified 70 differentially expressed NETs genes and found 367 macrophage-related genes through WGCNA analysis. Machine learning identified three key genes: FNBP1L, NMUR1, and PP14571. These three key genes were significantly associated with immune cell content and enriched in multiple signaling pathways. Specifically, these genes were upregulated in PE patients. These findings establish the expression patterns of three key genes associated with M2 macrophage infiltration, providing potential targets for understanding the pathogenesis and treatment of PE. Additionally, CMap results suggested four potential drugs, including Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin, which may have the potential to reverse pre-eclampsia.

Conclusion

Studying the expression levels of three key genes in pre-eclampsia provides valuable insights into the prevention and treatment of this condition. We propose that these genes play a crucial role in regulating the maternal-fetal immune microenvironment in PE patients, and the pathways associated with these genes offer potential avenues for exploring the molecular mechanisms underlying preeclampsia and identifying therapeutic targets. Additionally, by utilizing the Connectivity Map database, we identified drug targets like Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin as potential clinical treatments for preeclampsia.
Reassessing granzyme B: unveiling perforin-independent versatility in immune responses and therapeutic potentials
Authors: Thompson Raylynn , Cao Xuefang
Published: May 2024

The pivotal role of Granzyme B (GzmB) in immune responses, initially tied to cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, has extended across diverse cell types and disease models. A number of studies have challenged conventional notions, revealing GzmB activity beyond apoptosis, impacting autoimmune diseases, inflammatory disorders, cancer, and neurotoxicity. Notably, the diverse functions of GzmB unfold through Perforin-dependent and Perforin-independent mechanisms, offering clinical implications and therapeutic insights. This review underscores the multifaceted roles of GzmB, spanning immunological and pathological contexts, which call for further investigations to pave the way for innovative targeted therapies.
Current landscape of exosomes in tuberculosis development, diagnosis, and treatment applications
Authors: Sun Xuezhi , Li Wei , Zhao Li , Fan Ke , Qin Fenfen , Shi Liwen , Gao Feng , Zheng Chunlan
Published: May 2024

Tuberculosis (TB), caused by the bacterial pathogen Mycobacterium tuberculosis (MTB), remains one of the most prevalent and deadly infectious diseases worldwide. Currently, there are complex interactions between host cells and pathogens in TB. The onset, progression, and regression of TB are correlated not only with the virulence of MTB but also with the immunity of TB patients. Exosomes are cell-secreted membrane-bound nanovesicles with lipid bilayers that contain a variety of biomolecules, such as metabolites, lipids, proteins, and nucleic acids. Exosome-mediated cell−cell communication and interactions with the microenvironment represent crucial mechanisms through which exosomes exert their functional effects. Exosomes harbor a wide range of regulatory roles in physiological and pathological conditions, including MTB infection. Exosomes can regulate the immune response, metabolism, and cellular death to remodel the progression of MTB infection. During MTB infection, exosomes display distinctive profiles and quantities that may act as diagnostic biomarkers, suggesting that exosomes provide a revealing glimpse into the evolving landscape of MTB infections. Furthermore, exosomes derived from MTB and mesenchymal stem cells can be harnessed as vaccine platforms and drug delivery vehicles for the precise targeting and treatment of TB. In this review, we highlight the functions and mechanisms through which exosomes influence the progression of TB. Additionally, we unravel the critical significance of exosomal constituents in the diagnosis and therapeutic applications of TB, aiming to offer novel perspectives and strategies for combating TB.
Disease severity, treatment patterns, and quality of life in patients with moderate-to-severe psoriasis routinely managed with systemic treatment: results of the CRYSTAL observational study in Central and Eastern European countries
Authors: Raam Liisi , Hartmane Ilona , Valiukevičienė Skaidra , Karamova Arfenya E. , Telegdy Eniko , Botev Ivan , Marina Diana , Rubant Simone , Albuquerque Teotonio , Constantin Maria Magdalena
Published: May 2024

Psoriasis is a common, life-long skin disease with a significant negative health and societal impact. Data on rates of disease control and treatment strategies are lacking in Central and Eastern European countries. We aimed to describe the real-world disease severity, control, and treatment strategies for psoriasis in patients from Central and Eastern European countries. CRYSTAL (EUPAS36459) was a cross-sectional, retrospective study in adults (18–75 years) from Bulgaria, Estonia, Hungary, Latvia, Lithuania, Romania, and Russia. We enrolled patients with moderate-to-severe psoriasis receiving continuous systemic treatment for ≥24 weeks. We used the Psoriasis Area and Severity Index (PASI) to describe disease severity and the Dermatology Life Quality Index (DLQI) to assess quality of life (QoL) and collected other outcomes [psoriasis work productivity and activity impairment (WPAI-PSO), patient satisfaction] at enrollment. Analyses were descriptive. A total of 690 patients were included in the analyses. Median disease duration was 11.8 years. Current treatment was monotherapy for most patients (95.8%) with either biological (BIO group; 88.4%) or conventional (NON-BIO group; 7.4%) agents. Mean (± standard deviation) absolute PASI scores were 3.5 ± 5.7, 3.1 ± 5.3, and 6.6 ± 7.4 in the overall population, the BIO group, and the NON-BIO group, respectively. Among patients treated with monotherapy, absolute PASI scores ≤1, ≤3, and ≤5 were observed for 44.1%, 72.0%, and 82.6% of BIO patients and 21.6%, 33.3%, and 49.0% of NON-BIO patients. Mean DLQI total score was 3.3 ± 5.1; higher scores were noted for higher absolute PASI. The most impacted WPAI-PSO domain was presenteeism; for all domains, impact increased with increased absolute PASI. A total of 91.8% of BIO patients and 74.5% of NON-BIO patients were satisfied with the current treatment. We observed a better disease control in BIO than NON-BIO patients. However, around half of BIO patients did not reach clear skin status and reported an impact on QoL. An improvement in treatment strategies is still needed in Central and Eastern European countries to optimize outcomes of moderate-to-severe psoriasis.
Effect of nutrient reductions on dissolved oxygen and pH: a case study of Narragansett bay
Authors: Wang Hongjie , Codiga Daniel L. , Stoffel Heather , Oviatt Candace , Huizenga Kristin , Grear Jason
Published: May 2024

To assess the consequences of nutrient reduction strategies on water quality under climate change, we investigated the long-term dynamics of dissolved oxygen (DO) and pH in Narragansett Bay (NB), a warming urbanized estuary in Rhode Island, where nitrogen loads have declined due to extensive wastewater treatment plant upgrades. We use 15 years (January 2005-December 2019) of measurements from the Narragansett Bay Fixed Site Monitoring network. Nutrient-enhanced phytoplankton growth can increase DO in the upper water column while subsequent respiration can reduce water column DO and enhance bottom water acidification, and vice-versa. We observed significant decreases in surface DO levels, concurrent with a significant increase in bottom DO, associated with the nitrogen load reduction. Surface DO decline was primarily attributed to reduced intensity of primary productivity, supported by a concurrent decrease in surface chlorophyll concentrations. Meanwhile, the influence of reduced organic matter respiration led to the increase of bottom DO levels by 9 µmol kg-1 (approximately 0.2 mg L-1 for typical summer temperature and salinity) over a 15-year period, which overcame the opposite influence of oxygen reduction from solubility decreases due to warming temperatures. In contrast, long-term changes in surface pH have not exhibited discernible trends beyond natural variability, likely due to the complex and sometimes opposing influences of biological activity and changing river flow conditions. We observed a slight increase in bottom pH, associated with the increase in DO in bottom water. Notably, future variations in freshwater discharge, particularly linked to extreme precipitation events, may further influence water carbonate chemistry and thereby impact pH dynamics. This study highlights the necessity of long-term time series measurements in helping understand the impacts of environmental management practices in improving water quality in coastal regions during a changing climate.
The spatiotemporal characteristics and driving mechanisms of subsurface marine heatwaves in the Xisha Region
Authors: Gao Feng , Liu Cong , Zhai Fangguo , Song Jinbao , Li Peiliang , Gu Yanzhen
Published: May 2024

Under the background of global climate change, Subsurface Marine Heatwaves (SSMHWs) have become a ‘hot-spot’ research due to their significant impacts on marine ecosystems. Temperature data from the ECCO2 for the years 1992 to 2021 is used to research the spatiotemporal characteristics of SSMHWs in the upper 500 m over the Xisha region (110°E to 113°E, 15°N to 18°N). This study indicates that SSMHWs of high intensity occur in the Xisha area, with the vertical maximum intensity at approximately 100 m. These events exhibit significant seasonal variations, with the highest intensity occurring in May. The intensity of SSMHW in the analysis region varies interannually. SSMHWs have intensified at a rate of 1.53°C·Days/Year and tend to shift to deeper water over the past three decades. A block-based method for SSMHW identification is proposed, in order to take the vertical extent of the event in consideration. By analyzing the eight most intense events based on spatial cumulative intensity, it suggested that warm mesoscale eddies may play an important role on the spatial distribution of the SSMHWs. Statistical analysis shows that the intensity and coverage of the warm mesoscale eddy in the Xisha zone may influence the intensity and evolution of the SSMHWs. Additionally, only 18.27% of SSMHW events occur with apparent surface marine heatwave signals. These findings are vital for uncovering SSMHW dynamics in the Xisha area, and are important for future monitoring, early warnings and marine conservation.
Response of early diagenesis to methane leakage in the inner shelf of the East China Sea
Authors: Wang Chenpei , Su Jianfeng , Song Lei , Qiao Peijun , Fan Daidu
Published: May 2024

Shelf seas are experiencing a rise in shallow gas leaks, primarily methane, raising concerns due to their environmental impact. However, the effect of the leaks on early diagenesis remains poorly understood. This study analyzes sediment lithology, organic geochemistry and porewater geochemistry of two short cores collected nearby the pockmarks in the muddy inner shelf of the East China Sea. Our findings clearly demonstrate the impact of methane leakage on early diagenesis, evidenced by the shallower position of the SMTZ (sulfate-methane transition zone), higher concentrations of uranium (U), vanadium (V), and manganese (Mn) in the porewater near and above the SMTZ, and downcore decrease in Mg2+, Ca2+, and Sr2+ concentrations versus increase in Mg2+/Ca2+ and Sr2+/Ca2+ ratios. Their profile variations and the difference between two cores are determined by the intensity of methane leakage. The estimated methane diffusive flux of 619 mmol m-2 yr-1 at YEC7–2 is roughly 8.5 times that at YEC7–1 (73 mmol m-2 yr-1), consistent with a shorter distance of YEC7–2 to the pockmark with active methane leakage. A schematic model is summarized to demonstrate the response of early diagenesis processes to the increasing methane leakages in response to changing sedimentation regimes from accretion to severe erosion. This study undoubtedly improves our understanding mutual promotion effect between seafloor erosion and gas leakage, and their impact on early diagenesis processes and resultant porewater geochemical changes and authigenic mineral records.
Proof-of-concept for an automatable mortality prediction scoring in hospitalised older adults
Authors: Ho Vanda W. T. , Ling Natalie M. W. , Anbarasan Denishkrshna , Chan Yiong Huak , Merchant Reshma Aziz
Published: May 2024

Introduction

It is challenging to prognosticate hospitalised older adults. Delayed recognition of end-of-life leads to failure in delivering appropriate palliative care and increases healthcare utilisation. Most mortality prediction tools specific for older adults require additional manual input, resulting in poor uptake. By leveraging on electronic health records, we aim to create an automatable mortality prediction tool for hospitalised older adults.

Methods

We retrospectively reviewed electronic records of general medicine patients ≥75 years at a tertiary hospital between April–September 2021. Demographics, comorbidities, ICD-codes, age-adjusted Charlson Comorbidity Index (CCI), Hospital Frailty Risk Score, mortality and resource utilization were collected. We defined early deaths, late deaths and survivors as patients who died within 30 days, 1 year, and lived beyond 1 year of admission, respectively. Multivariate logistic regression analyses were adjusted for age, gender, race, frailty, and CCI. The final prediction model was created using a stepwise logistic regression.

Results

Of 1,224 patients, 168 (13.7%) died early and 370 (30.2%) died late. From adjusted multivariate regression, risk of early death was significantly associated with ≥85 years, intermediate or high frail risk, CCI > 6, cardiovascular risk factors, AMI and pneumonia. For late death, risk factors included ≥85 years, intermediate frail risk, CCI >6, delirium, diabetes, AMI and pneumonia. Our mortality prediction tool which scores 1 point each for age, pneumonia and AMI had an AUC of 0.752 for early death and 0.691 for late death.

Conclusion

Our mortality prediction model is a proof-of-concept demonstrating the potential for automated medical alerts to guide physicians towards personalised care for hospitalised older adults.
LCASPMDA: a computational model for predicting potential microbe-drug associations based on learnable graph convolutional attention networks and self-paced iterative sampling ensemble
Authors: Yang Zinuo , Wang Lei , Zhang Xiangrui , Zeng Bin , Zhang Zhen , Liu Xin
Published: May 2024

Introduction

Numerous studies show that microbes in the human body are very closely linked to the human host and can affect the human host by modulating the efficacy and toxicity of drugs. However, discovering potential microbe-drug associations through traditional wet labs is expensive and time-consuming, hence, it is important and necessary to develop effective computational models to detect possible microbe-drug associations.

Methods

In this manuscript, we proposed a new prediction model named LCASPMDA by combining the learnable graph convolutional attention network and the self-paced iterative sampling ensemble strategy to infer latent microbe-drug associations. In LCASPMDA, we first constructed a heterogeneous network based on newly downloaded known microbe-drug associations. Then, we adopted the learnable graph convolutional attention network to learn the hidden features of nodes in the heterogeneous network. After that, we utilized the self-paced iterative sampling ensemble strategy to select the most informative negative samples to train the Multi-Layer Perceptron classifier and put the newly-extracted hidden features into the trained MLP classifier to infer possible microbe-drug associations.

Results and discussion

Intensive experimental results on two different public databases including the MDAD and the aBiofilm showed that LCASPMDA could achieve better performance than state-of-the-art baseline methods in microbe-drug association prediction.
Discovery of Epichloë as novel endophytes of Psathyrostachys lanuginosa in China and their alkaloid profiling
Authors: Chen Taixiang , Wang Tian , Du Mingxiang , Malik Kamran , Li Chunjie , Bao Gensheng
Published: May 2024

The Epichloë genus represents a significant group of above-ground endophytes extensively researched for their potential applications in agriculture and ecology. Additionally, Epichloë species synthesize bioactive alkaloids, which generally cause health problems in livestock and have detrimental effects on the performance of insect herbivores. Psathyrostachys lanuginosa serves as a valuable forage grass for livestock owing to its high nutritional value and resilience in adverse environmental conditions. Nevertheless, to date, no reports have documented Epichloë as endophytes of P. lanuginosa. In this study, four strains (PF5, PF9, QG2, and QG4) were isolated and identified through morphological, molecular, and phylogenetic analyses as endophytes of P. lanuginosa. Morphological analysis indicated colony characteristics and conidia features consistent with symbiotic Epichloë, with no significant differences observed in growth rates or conidia dimensions among the four strains. Phylogenetic analysis confirmed all strains as E. bromicola. Additionally, alkaloid biosynthetic genes were detected, revealing differences in the potential synthesis of peramine and indole diterpenoid alkaloids among strains from different geographic origins. However, all four E. bromicola strains exhibited similar potential for synthesizing ergot alkaloids, but not loline alkaloids. Overall, this study identified P. lanuginosa as a novel host for E. bromicola and provided insights into the alkaloid profiles of these strains, laying a solid foundation for the scientific and rational utilization of Epichloë resources.
Performance evaluation of a SARS-CoV-2 and influenza A/B combo rapid antigen test
Authors: Rosenblatt Kevin P. , Romeu Hugo , Romeu Camille , Granger Elder
Published: May 2024

Introduction: The global COVID-19 pandemic and seasonal influenza outbreaks have drawn attention to the critical need for accurate and efficient diagnostic tools.

Methods: The performance of the InstaView COVID-19/Flu Ag Combo Test, which was designed to simultaneously detect the SARS-CoV-2, influenza A, and influenza B viruses, was analytically and clinically evaluated.

Results: The InstaView COVID-19/Flu Ag Combo Test exhibited robust detection capabilities, accurately identifying SARS-CoV-2, influenza A, and influenza B viruses over a wide concentration range (1.41 × 103 to 7.05 × 104 TCID50/mL). Extensive testing against potential cross-reactants and interferences yielded no false-positive results, indicating the high specificity of the test. Clinical evaluation further confirmed the kit’s reliability, with sensitivity ranging from 95.1% to 98.2% for SARS-CoV-2, 88.9%–95.2% for influenza A, and 91.7%–100% for influenza B depending on the sample type. The specificity was consistently 100% for all of the targeted viruses.

Discussion: The InstaView COVID-19/Flu Ag Combo Test thus demonstrated high performance, ease of use, rapid results, and the ability to precisely detect SARS-CoV-2 and influenza A/B infections, making it an effective tool in streamlining diagnostic workflows, optimizing resource allocation, and improving patient outcomes.
Unveiling the domino effect: a nine-year follow-up on pentalogy of central nervous system induced by a large unruptured cerebral arteriovenous malformation: a case report and literature review
Authors: He Yunsen , Tao Ye , Tian Jing , Bao Mingbin , Zhang Mengjun , Huang Qinjiang , Li Hongliang , Chang Xinxin , Li Kun , Liu Ping , Guo Lili , Qin Xiaohong , Huang Caiquan , Wu Bo
Published: May 2024

Background

The disruption of intracranial fluid dynamics due to large unruptured cerebral arteriovenous malformation (AVM) commonly triggers a domino effect within the central nervous system. This phenomenon is frequently overlooked in prior clinic and may lead to catastrophic misdiagnoses. Our team has documented the world’s first case of so-called AVM Pentalogy (AVMP) induced by a AVM.

Clinical presentation and result

A 30-year-old female was first seen 9 years ago with an occasional fainting, at which time a huge unruptured AVM was discovered. Subsequently, due to progressive symptoms, she sought consultations from several prestigious neurosurgical departments in China, where all consulting neurosurgeons opted for conservation treatment due to perceived surgical risks. During the follow-up period, the patient gradually presented with hydrocephalus, empty sella, secondary Chiari malformation, syringomyelia, and scoliosis (we called as AVMP). When treated in our department, she already displayed numerous symptoms, including severe intracranial hypertension. Our team deduced that the hydrocephalus was the primary driver of her AVMP symptoms, representing the most favorable risk profile for intervention. As expected, a ventriculoperitoneal shunt successfully mitigated all symptoms of AVMP at 21-months post-surgical review.

Conclusion

During the monitoring of unruptured AVM, it is crucial to remain vigilant for the development or progression of AVMP. When any component of AVMP is identified, thorough etiological studies and analysis of cascade reactions are imperative to avert misdiagnosis. When direct AVM intervention is not viable, strategically addressing hydrocephalus as part of the AVMP may serve as the critical therapeutic focus.
Mechanisms and recent advances in the diagnosis and treatment of nitrous oxide-induced peripheral neuropathy: a narrative review
Authors: Zou Xiaodi , Yi Fangyu , Zhou Weijie , Dong Yanzhao , Alhaskawi Ahmad , Zhou Haiying , Ezzi Sohaib Hasan Abdullah , Kota Vishnu Goutham , Abdulla Mohamed Hasan Abdulla Hasan , Alenikova Olga , Abdalbary Sahar Ahmed , Lu Hui , Wang Changxin
Published: May 2024

Under standard conditions, nitrous oxide (N2O) manifests as a colorless, odorless gas with a mildly sweet taste. The compound finds applications in various fields, including its use as an aerosol propellants, an accelerant in motor racing, and an anesthetic in surgical procedures and dentistry. Unfortunately, the recreational misuse of N2O has become prevalent among young individuals due to its euphoric and hallucinogenic effects. Compounding this issue is the fact that nitrous oxide can be easily obtained from over-the-counter household items, facilitating its non-medical use. The global community has witnessed a surge in the recreational utilization of nitrous oxide gas in recent years. Despite the widespread non-medical abuse of N2O, there remains inadequate understanding of the potential adverse effects resulting from exposure to it. This paper provides an overview of management findings, laboratory and electrodiagnostic characteristics, as well as clinical presentations associated with neurological disorders induced by nitrous oxide usage.
Association of body mass index with rapid eye movement sleep behavior disorder in Parkinson’s disease
Authors: Gu Si-Chun , Yuan Xiao-Lei , Yin Ping , Li Yuan-Yuan , Wang Chang-De , Gu Min-Jue , Xu Li-Min , Gao Chen , Wu You , Hu Yu-Qing , Yuan Can-Xing , Cao Yang , Ye Qing
Published: May 2024

Background

The association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson’s disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients.

Methods

In this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson’s Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models.

Results

We identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results.

Conclusion

The current study found a significant dose–response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.
Predictive value of red cell distribution width for overlap syndrome in obstructive sleep apnea
Authors: Akyol Gurses Asli , Akyildiz Utku Ogan
Published: May 2024

Purpose

Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) are prevalent disorders, and the concurrence so-called overlap syndrome (OVS) is not rare either. Early recognition of OVS is essential because this group is more prone to cardiovascular morbidities and requires effective multidisciplinary follow-up. This study aimed to evaluate RDW in patients with severe OSAS and investigate whether it can predict OVS.

Patients and methods

96 patients were retrospectively analyzed, of whom 66 were found to have severe OSAS alone and 30 OVS during diagnostic workups. Demographic, polysomnographic, and laboratory results, including RDW, were compared between groups. Multivariate logistic regression was used to determine independent associates of OVS.

Results

Gender and body mass index (BMI) were similar, however, the mean age and RDW were higher in the OVS group (p:0.008, p:0.002). The increase in RDW remained significant after adjustment for age, BMI, and cardiovascular risk factors. An RDW value of >13.65% was shown to have a 78.3% sensitivity and 60% specificity for predicting OVS in severe OSAS (p:0.004).

Conclusion

The results suggest that RDW can be a reliable indicator for diagnosing OVS in OSAS. It can help in identifying the subset of patients who would benefit from proper consultations and multidisciplinary follow-up, leading to appropriate treatment of each disease component and effective monitoring to prevent adverse cardiovascular outcomes.
Research application of session-RPE in monitoring the training load of elite endurance athletes
Authors: Yang Shengjie , Yin Yiquan , Qiu Zhaoyi , Meng Qingjun
Published: May 2024

Purpose

TRIMP and sRPE are both representative indicators of training load(TL), and the correlation between two has been widely demonstrated across various sports. The aim of this study was to investigate the reliability of sRPE-TRIMP correlation across different intensities/duration of training in cross-country skiing, and whether sRPE can serve as an validity supplement to TRIMP data in cases of lost heart rate data.

Method

10 athletes were used as the experimental objects. The intensity, duration and RPE of 273 different types of training sessions were collected, and statistical methods were used for data analysis.

Results

1. There was a significant correlation between sRPE and TRIMP (r = 0.68, p < 0.05), but the correlation differs among the LIT, MIT and HIT groups (r = 0.70, 0.46, r = 0.31, p < 0.05) 2. sRPE-TRIMP correlation among three different time duration in the LIT group (0-60 min, 60-120 min and 120-180 min), are all highly significant (r = 0.70, 0.67, 0.69, p < 0.05) and the LRsRPE-TRIMP of 3 duration have no significant differences (chow test, p > 0.05). 3. The difference in actual training duration between samples was the main reason for the difference in the application effect of sRPE, because the actual training duration ratio of LIT was 89.7 ± 16.4%; MIT, 98.5 ± 6.2%; and HIT, 94.4 ± 13.5%.

Conclusion

1. The linear relationship between sRPE and TRIMP (LRsRPE-TRIMP) is more significant in LIT compared to that in MIT and HIT. 2. Variations in the duration of LIT sessions do not affect the consistency of the relationship between sRPE and TRIMP. 3. Discrepancies between actual and planned training durations directly impact the significance of the LRsRPE-TRIMP.
Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention
Authors: Lu Qiuyi , Yu Anqi , Pu Juncai , Chen Dawei , Zhong Yujie , Bai Dingqun , Yang Lining
Published: May 2024

Post-stroke cognitive impairment (PSCI) is a major stroke consequence that has a severe impact on patients’ quality of life and survival rate. For this reason, it is especially crucial to identify and intervene early in high-risk groups during the acute phase of stroke. Currently, there are no reliable and efficient techniques for the early diagnosis, appropriate evaluation, or prognostication of PSCI. Instead, plenty of biomarkers in stroke patients have progressively been linked to cognitive impairment in recent years. High-throughput omics techniques that generate large amounts of data and process it to a high quality have been used to screen and identify biomarkers of PSCI in order to investigate the molecular mechanisms of the disease. These techniques include metabolomics, which explores dynamic changes in the organism, gut microbiomics, which studies host–microbe interactions, genomics, which elucidates deeper disease mechanisms, transcriptomics and proteomics, which describe gene expression and regulation. We looked through electronic databases like PubMed, the Cochrane Library, Embase, Web of Science, and common databases for each omics to find biomarkers that might be connected to the pathophysiology of PSCI. As all, we found 34 studies: 14 in the field of metabolomics, 5 in the field of gut microbiomics, 5 in the field of genomics, 4 in the field of transcriptomics, and 7 in the field of proteomics. We discovered that neuroinflammation, oxidative stress, and atherosclerosis may be the primary causes of PSCI development, and that metabolomics may play a role in the molecular mechanisms of PSCI. In this study, we summarized the existing issues across omics technologies and discuss the latest discoveries of PSCI biomarkers in the context of omics, with the goal of investigating the molecular causes of post-stroke cognitive impairment. We also discuss the potential therapeutic utility of omics platforms for PSCI mechanisms, diagnosis, and intervention in order to promote the area’s advancement towards precision PSCI treatment.
The long noncoding RNA SUMO1P3 as urinary biomarker for monitoring bladder cancer progression
Authors: Galbiati Silvia , Bettiga Arianna , Colciago Giorgia , Senti Chiara , Trevisani Francesco , Villa Giulia , Marzinotto Ilaria , Ghidini Michele , Passalacqua Rodolfo , Montorsi Francesco , Salonia Andrea , Vago Riccardo
Published: May 2024

Introduction

Urothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients’ workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression.

Methods

This study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls.

Results

SUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application.

Discussion

We have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a.
Exploiting tertiary lymphoid structures gene signature to evaluate tumor microenvironment infiltration and immunotherapy response in colorectal cancer
Authors: Xu Zhu , Wang Qin , Zhang Yiyao , Li Xiaolan , Wang Mei , Zhang Yuhong , Pei Yaxin , Li Kezhen , Yang Man , Luo Liping , Wu Chuan , Wang Weidong
Published: May 2024

Background

Tertiary lymphoid structures (TLS) is a particular component of tumor microenvironment (TME). However, its biological mechanisms in colorectal cancer (CRC) have not yet been understood. We desired to reveal the TLS gene signature in CRC and evaluate its role in prognosis and immunotherapy response.

Methods

The data was sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Based on TLS-related genes (TRGs), the TLS related subclusters were identified through unsupervised clustering. The TME between subclusters were evaluated by CIBERSORT and xCell. Subsequently, developing a risk model and conducting external validation. Integrating risk score and clinical characteristics to create a comprehensive nomogram. Further analyses were conducted to screen TLS-related hub genes and explore the relationship between hub genes, TME, and biological processes, using random forest analysis, enrichment and variation analysis, and competing endogenous RNA (ceRNA) network analysis. Multiple immunofluorescence (mIF) and immunohistochemistry (IHC) were employed to characterize the existence of TLS and the expression of hub gene.

Results

Two subclusters that enriched or depleted in TLS were identified. The two subclusters had distinct prognoses, clinical characteristics, and tumor immune infiltration. We established a TLS-related prognostic risk model including 14 genes and validated its predictive power in two external datasets. The model’s AUC values for 1-, 3-, and 5-year overall survival (OS) were 0.704, 0.737, and 0.746. The low-risk group had a superior survival rate, more abundant infiltration of immune cells, lower tumor immune dysfunction and exclusion (TIDE) score, and exhibited better immunotherapy efficacy. In addition, we selected the top important features within the model: VSIG4, SELL and PRRX1. Enrichment analysis showed that the hub genes significantly affected signaling pathways related to TLS and tumor progression. The ceRNA network: PRRX1-miRNA (hsa-miR-20a-5p, hsa-miR-485–5p) -lncRNA has been discovered. Finally, IHC and mIF results confirmed that the expression level of PRRX1 was markedly elevated in the TLS- CRC group.

Conclusion

We conducted a study to thoroughly describe TLS gene signature in CRC. The TLS-related risk model was applicable for prognostic prediction and assessment of immunotherapy efficacy. The TLS-hub gene PRRX1, which had the potential to function as an immunomodulatory factor of TLS, could be a therapeutic target for CRC.
Optical diagnosis in still images of colorectal polyps: comparison between expert endoscopists and PolyDeep, a Computer-Aided Diagnosis system
Authors: Davila-Piñón Pedro , Nogueira-Rodríguez Alba , Díez-Martín Astrid Irene , Codesido Laura , Herrero Jesús , Puga Manuel , Rivas Laura , Sánchez Eloy , Fdez-Riverola Florentino , Glez-Peña Daniel , Reboiro-Jato Miguel , López-Fernández Hugo , Cubiella Joaquín
Published: May 2024

Background

PolyDeep is a computer-aided detection and classification (CADe/x) system trained to detect and classify polyps. During colonoscopy, CADe/x systems help endoscopists to predict the histology of colonic lesions.

Objective

To compare the diagnostic performance of PolyDeep and expert endoscopists for the optical diagnosis of colorectal polyps on still images.

Methods

PolyDeep Image Classification (PIC) is an in vitro diagnostic test study. The PIC database contains NBI images of 491 colorectal polyps with histological diagnosis. We evaluated the diagnostic performance of PolyDeep and four expert endoscopists for neoplasia (adenoma, sessile serrated lesion, traditional serrated adenoma) and adenoma characterization and compared them with the McNemar test. Receiver operating characteristic curves were constructed to assess the overall discriminatory ability, comparing the area under the curve of endoscopists and PolyDeep with the chi- square homogeneity areas test.

Results

The diagnostic performance of the endoscopists and PolyDeep in the characterization of neoplasia is similar in terms of sensitivity (PolyDeep: 89.05%; E1: 91.23%, p=0.5; E2: 96.11%, p<0.001; E3: 86.65%, p=0.3; E4: 91.26% p=0.3) and specificity (PolyDeep: 35.53%; E1: 33.80%, p=0.8; E2: 34.72%, p=1; E3: 39.24%, p=0.8; E4: 46.84%, p=0.2). The overall discriminative ability also showed no statistically significant differences (PolyDeep: 0.623; E1: 0.625, p=0.8; E2: 0.654, p=0.2; E3: 0.629, p=0.9; E4: 0.690, p=0.09). In the optical diagnosis of adenomatous polyps, we found that PolyDeep had a significantly higher sensitivity and a significantly lower specificity. The overall discriminative ability of adenomatous lesions by expert endoscopists is significantly higher than PolyDeep (PolyDeep: 0.582; E1: 0.685, p < 0.001; E2: 0.677, p < 0.0001; E3: 0.658, p < 0.01; E4: 0.694, p < 0.0001).

Conclusion

PolyDeep and endoscopists have similar diagnostic performance in the optical diagnosis of neoplastic lesions. However, endoscopists have a better global discriminatory ability than PolyDeep in the optical diagnosis of adenomatous polyps.
Research gaps in the neurodevelopmental assessment of children with complex congenital heart defects: a scoping review
Authors: Hofer Johannes , Blum Marina , Wiltsche Regina , Deluggi Nikoletta , Holzinger Daniel , Fellinger Johannes , Tulzer Gerald , Blum Gina , Oberhuber Raphael
Published: May 2024

Background

Children with congenital heart defects (CHD) are at risk for a range of developmental disabilities that challenge cognition, executive functioning, self-regulation, communication, social-emotional functioning, and motor skills. Ongoing developmental surveillance is therefore key to maximizing neurodevelopmental outcome opportunities. It is crucial that the measures used cover the spectrum of neurodevelopmental domains relevant to capturing possible predictors and malleable factors of child development.

Objectives

This work aimed to synthesize the literature on neurodevelopmental measures and the corresponding developmental domains assessed in children aged 1−8 years with complex CHD.

Methods

PubMed was searched for terms relating to psycho-social, cognitive and linguistic-communicative outcomes in children with CHD. 1,380 papers with a focus on complex CHD that reported neurodevelopmental assessments were identified; ultimately, data from 78 articles that used standardized neurodevelopmental assessment tools were extracted.

Results

Thirty-nine (50%) of these excluded children with syndromes, and 9 (12%) excluded children with disorders of intellectual development. 10% of the studies were longitudinal. The neurodevelopmental domains addressed by the methods used were: 53% cognition, 16% psychosocial functioning, 18% language/communication/speech production, and 13% motor development-associated constructs.

Conclusions

Data on social communication, expressive and receptive language, speech motor, and motor function are underrepresented. There is a lack of research into everyday use of language and into measures assessing language and communication early in life. Overall, longitudinal studies are required that include communication measures and their interrelations with other developmental domains.
A detailed overview of quercetin: implications for cell death and liver fibrosis mechanisms
Authors: Xiong Fei , Zhang Yichen , Li Ting , Tang Yiping , Song Si-Yuan , Zhou Qiao , Wang Yi
Published: May 2024

Background

Quercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential.

Purpose

This review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis.

Methods

A comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employed were “quercetin”, “natural sources of quercetin”, “quercetin extraction methods”, “bioavailability of quercetin”, “pharmacokinetics of quercetin”, “cell death pathways”, “apoptosis”, “autophagy”, “pyroptosis”, “necroptosis”, “ferroptosis”, “cuproptosis”, “liver fibrosis”, and “hepatic stellate cells”. These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis.

Results

This review details quercetin’s involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin’s effects on liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin’s structure and its potential for specific actions in the liver.

Conclusion

The paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential.
Activation of GABA type A receptor is involved in the anti-insomnia effect of Huanglian Wendan Decoction
Authors: Li Liang , Wu Xiaorong , Gong Jili , Wang Zhuqiang , Dai Weibo , Qiu Li , Zuo Hongyuan , Yi Mengqin , Yuan Hui , Hu Mei , Gao Zhaobing , Tian Fuyun
Published: May 2024

Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) prescribed to patients diagnosed with insomnia, which can achieve excellent therapeutic outcomes. As positively modulating the γ-aminobutyric acid (GABA) type A receptors (GABAARs) is the most effective strategy to manage insomnia, this study aimed to investigate whether the activation of GABAARs is involved in the anti-insomnia effect of HWD. We assessed the metabolites of HWD using LC/MS and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and tested the pharmacological activity in vitro and in vivo using whole-cell patch clamp and insomnia zebrafish model. In HEK293 cells expressing α1β3γ2L GABAARs, HWD effectively increased the GABA-induced currents and could induce GABAAR-mediated currents independent of the application of GABA. In the LC-MS (QToF) assay, 31 metabolites were discovered in negative ion modes and 37 metabolites were found in positive ion modes, but neither three selected active metabolites, Danshensu, Coptisine, or Dihydromyricetin, showed potentiating effects on GABA currents. 62 active metabolites of the seven botanical drugs were collected based on the TCMSP database and 19 of them were selected for patch-clamp verification according to the virtual docking simulations and other parameters. At a concentration of 100 μM, GABA-induced currents were increased by (+)-Cuparene (278.80% ± 19.13%), Ethyl glucoside (225.40% ± 21.77%), and β-Caryophyllene (290.11% ± 17.71%). In addition, (+)-Cuparene, Ethyl glucoside, and β-Caryophyllene could also serve as positive allosteric modulators (PAMs) and shifted the GABA dose-response curve (DRC) leftward significantly. In the PCPA-induced zebrafish model, Ethyl glucoside showed anti-insomnia effects at concentrations of 100 μM. In this research, we demonstrated that the activation of GABAARs was involved in the anti-insomnia effect of HWD, and Ethyl glucoside might be a key metabolite in treating insomnia.
Computational drug discovery approaches identify mebendazole as a candidate treatment for autosomal dominant polycystic kidney disease
Authors: Brownjohn Philip W. , Zoufir Azedine , O’Donovan Daniel J. , Sudhahar Saatviga , Syme Alexander , Huckvale Rosemary , Porter John R. , Bange Hester , Brennan Jane , Thompson Neil T.
Published: May 2024

Autosomal dominant polycystic kidney disease (ADPKD) is a rare genetic disorder characterised by numerous renal cysts, the progressive expansion of which can impact kidney function and lead eventually to renal failure. Tolvaptan is the only disease-modifying drug approved for the treatment of ADPKD, however its poor side effect and safety profile necessitates the need for the development of new therapeutics in this area. Using a combination of transcriptomic and machine learning computational drug discovery tools, we predicted that a number of existing drugs could have utility in the treatment of ADPKD, and subsequently validated several of these drug predictions in established models of disease. We determined that the anthelmintic mebendazole was a potent anti-cystic agent in human cellular and in vivo models of ADPKD, and is likely acting through the inhibition of microtubule polymerisation and protein kinase activity. These findings demonstrate the utility of combining computational approaches to identify and understand potential new treatments for traditionally underserved rare diseases.