bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of blood urea nitrogen-to-creatinine ratio and in-hospital mortality in acute ischemic stroke patients with atrial fibrillation: data from the MIMIC-IV database
Authors: Li Bowen , Li Juan , Meng Xin , Yang Shu , Tian Furong , Song Xiang , Liu Junjie
Published: August 2024

Objective

This research aimed to investigate the association between the blood urea nitrogen-to-creatinine (BUN/Cr) ratio and the rate of in-hospital mortality in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF), who are also receiving care in intensive care unit (ICU).

Methods

A retrospective study was conducted using the MIMIC-IV database. We collected data on BUN/Cr levels at admission for patients with AIS and concurrent AF. To assess the association between BUN/Cr and in-hospital mortality rate, statistical analysis was conducted employing multivariable logistic regression models and restricted cubic spline models. These models were utilized to investigate the potential relationship and provide insights into the impact of BUN/Cr on the likelihood of in-hospital mortality. Interaction and subgroup analyses were performed to evaluate the consistency of the correlation.

Results

There were a total of 856 patients (age ≥ 18 years) with a median age of 78.0 years, of which 466 (54.4%) were female. Out of 856 patients, 182 (21.26%) died in the hospital. Upon controlling for confounding factors, the multivariable logistic regression analysis elucidated that patients falling within the third trisection (Q3 > 22.41 mg/dL) exhibited a noticeably increased susceptibility to in-hospital mortality when contrasted with their counterparts positioned in the second trisection (Q2: 17.2–22.41 mg/dL) (OR = 2.02, 95% CI: 1.26–3.26, p = 0.004). A non-linear J-shaped relationship was observed between BUN/Cr at ICU admission and in-hospital mortality rate (p = 0.027), with a turning point at 19.63 mg/dL. In the threshold analysis, there was a 4% rise in in-hospital mortality for each 1 mg/dL increase in BUN/Cr (OR: 1.04, 95% CI: 1.01–1.06, p = 0.012).

Conclusion

In patients with AIS complicated by AF, BUN/Cr at admission shows a J-shaped correlation with in-hospital mortality rate. When BUN/Cr exceeds 19.63 mg/dL, the in-hospital mortality rate increases.
Role of inflammatory biomarkers in mediating the effect of lipids on spontaneous intracerebral hemorrhage: a two-step, two-sample Mendelian randomization study
Authors: Huang Mingsheng , Liu Yiheng , Cheng Yuan , Dai Weiran
Published: August 2024

Background

Spontaneous intracerebral hemorrhage (sICH) is a form of stroke with high mortality rates and significant neurological implications for patients. Abnormalities in lipid metabolism have been implicated in various cardiovascular diseases, yet their relationship with sICH remains insufficiently explored, particularly concerning their association with inflammatory factors.

Methods

Employing a two-sample, two-step Mendelian Randomization approach, combined with data from GWAS datasets, to investigate the causal relationship between plasma lipid levels and sICH. Additionally, the role of inflammatory factors in this relationship was examined, and sensitivity analyses were conducted to ensure the robustness of the results.

Results

The results indicate a significant causal relationship between 19 plasma lipid metabolites and sICH. Furthermore, mediation analysis revealed that three distinct lipids, namely Sterol ester (27:1/20:2), Phosphatidylcholine (16:0_20:4), and Sphingomyelin (d34:1), exert their influence on sICH through inflammatory factors. TRAIL (OR: 1.078, 95% CI: 1.016–1.144, p = 0.013) and HGF (OR: 1.131, 95% CI: 1.001–1.279, p = 0.049) were identified as significant mediators.

Conclusion

This study provides new evidence linking abnormalities in lipid metabolism with sICH and elucidates the role of inflammatory factors as mediators. These findings contribute to a better understanding of the pathogenesis of sICH and offer novel insights and therapeutic strategies for its prevention and treatment.
Inflammo-immune perspective on the association of eight migraine risk factors with migraine: a multi-omics Mendelian randomization study
Authors: Zhao Jiaxi , Chen Rong , Luo Mengqi , Gong Hongping , Li Kaixin , Zhao Qian
Published: August 2024

Background

Migraine risk factors are associated with migraine susceptibility, yet their mechanisms are unclear. Evidence suggests a role for inflammatory proteins and immune cells in migraine pathogenesis. This study aimed to examine the inflammo-immune association between eight migraine risk factors and the disorder.

Methods

This study utilized inverse variance weighted (IVW) method and colocalization analysis to explore potential causal relationships between eight migraine risk factors, migraine, 731 immune cells, and 91 circulating inflammatory proteins. Mediation Mendelian randomization (MR) was further used to confirm the mediating role of circulating inflammatory proteins and immune cells between the eight migraine risk factors and migraine.

Results

Migraine risk factors are linked to 276 immune cells and inflammatory proteins, with cigarettes smoked per day strongly co-localized with CD33-HLA DR+ cells. Despite no co-localization, 23 immune cells/inflammatory proteins relate to migraine. Depression, all anxiety disorders, and sleep apnea are correlated with migraine, and all anxiety disorders are supported by strong co-localization evidence. However, the mediating effect of inflammatory proteins and immune cells between eight migraine risk factors and migraine has not been confirmed.

Conclusion

We elucidate the potential causal relationships between eight migraine risk factors, migraine, immune cells, and inflammatory proteins, enhancing our understanding of the molecular etiology of migraine pathogenesis from an inflammatory-immune perspective.
Fascia as a regulatory system in health and disease
Authors: Slater Alison M. , Barclay S. Jade , Granfar Rouha M. S. , Pratt Rebecca L.
Published: August 2024

Neurology and connective tissue are intimately interdependent systems and are critical in regulating many of the body’s systems. Unlocking their multifaceted relationship can transform clinical understanding of the mechanisms involved in multisystemic regulation and dysregulation. The fascial system is highly innervated and rich with blood vessels, lymphatics, and hormonal and neurotransmitter receptors. Given its ubiquity, fascia may serve as a “watchman,” receiving and processing information on whole body health. This paper reviews what constitutes fascia, why it is clinically important, and its contiguous and interdependent relationship with the nervous system. Unquestionably, fascial integrity is paramount to human locomotion, interaction with our environment, bodily sense, and general physical and emotional wellbeing, so an understanding of the fascial dysregulation that defines a range of pathological states, including hypermobility syndromes, autonomic dysregulation, mast cell activation, and acquired connective tissue disorders is critical in ensuring recognition, research, and appropriate management of these conditions, to the satisfaction of the patient as well as the treating practitioner.
Alpha oscillation mediates the interaction between suicide risk and symptom severity in Major Depressive Disorder
Authors: Zhang Haoran , Liu Xinyu , Su Ziyao , Wang Yingtan , Chen Bingxu , Zhang Zhizhen , Wang Bin , Zhou Jia , Zhang Ling , Zhao Xixi
Published: August 2024

Objective

The aim of our study was to explore the relationship between changes in neural oscillatory power in the EEG, the severity of depressive-anxiety symptoms, and the risk of suicide in MDD.

Methods

350 MDD patients’ demographic and clinical data were collected, and their depressive and anxious symptoms were evaluated using HDRS-17 and HAMA-14, along with a suicide risk assessment using the Nurses’ Global Assessment of Suicide Risk (NGASR). EEG data were captured, processed, and analyzed to study brain activity patterns related to MDD. The participants were divided based on suicide risk levels, and statistical analyses, including chi-square, t-tests, Pearson’s correlations were used to explore the associations between brain activity, symptom severity, and suicide risk. Closely related variables were identified and ultimately the optimal model was screened using stepwise regression analysis with a forward strategy, and mediation effects were further used to determine the possible interactions between the variables in the regression model.

Results

The regression model showed a significant effect of HDRS-17 and alpha power of Medial Occipital Cortex (MOC) on suicide risk, with elevated HDRS-17 increasing suicide risk and elevated alpha power decreasing suicide risk. Mediation effect analyses showed that MOC alpha power partially mediated the effect of depression level on suicide risk, and that an increase in depression severity may lead to a decrease in MOC alpha power, while a decrease in MOC alpha power may lead to an increase in suicide risk.

Conclusion

The severity of depression directly increases suicide risk, whereas higher alpha power in the MOC serves as a protective factor, reducing this risk. Notably, MOC alpha power not only directly impacts suicide risk but also mediates the effects of both depression severity and anxiety levels on this risk.

Limitations

The relatively small sample size of this study may limit the representativeness of the overall MDD patient population and the detailed analysis of different subgroups. This study did not delve into the relationship between the severity of cognitive symptoms in MDD patients and suicide risk.
Evaluation and analysis of visual perception using attention-enhanced computation in multimedia affective computing
Authors: Wang Jingyi
Published: August 2024

Facial expression recognition (FER) plays a crucial role in affective computing, enhancing human-computer interaction by enabling machines to understand and respond to human emotions. Despite advancements in deep learning, current FER systems often struggle with challenges such as occlusions, head pose variations, and motion blur in natural environments. These challenges highlight the need for more robust FER solutions. To address these issues, we propose the Attention-Enhanced Multi-Layer Transformer (AEMT) model, which integrates a dual-branch Convolutional Neural Network (CNN), an Attentional Selective Fusion (ASF) module, and a Multi-Layer Transformer Encoder (MTE) with transfer learning. The dual-branch CNN captures detailed texture and color information by processing RGB and Local Binary Pattern (LBP) features separately. The ASF module selectively enhances relevant features by applying global and local attention mechanisms to the extracted features. The MTE captures long-range dependencies and models the complex relationships between features, collectively improving feature representation and classification accuracy. Our model was evaluated on the RAF-DB and AffectNet datasets. Experimental results demonstrate that the AEMT model achieved an accuracy of 81.45% on RAF-DB and 71.23% on AffectNet, significantly outperforming existing state-of-the-art methods. These results indicate that our model effectively addresses the challenges of FER in natural environments, providing a more robust and accurate solution. The AEMT model significantly advances the field of FER by improving the robustness and accuracy of emotion recognition in complex real-world scenarios. This work not only enhances the capabilities of affective computing systems but also opens new avenues for future research in improving model efficiency and expanding multimodal data integration.
Prenatal low-dose Bisphenol A exposure impacts cortical development via cAMP-PKA-CREB pathway in offspring
Authors: Jiang Chu , Guan Jun , Tang Xiangrong , Zhang Yichun , Li Xiangyu , Li Yuting , Chen Zhiheng , Zhang Jing , Li Jia-Da
Published: August 2024

Bisphenol A (BPA) is a widely used plasticizer known to cause various disorders. Despite a global reduction in the use of BPA-containing products, prenatal exposure to low-dose BPA, even those below established safety limits, has been linked to neurological and behavioral deficits in childhood. The precise mechanisms underlying these effects remain unclear. In the present study, we observed a significant increase in the number of cortical neurons in offspring born to dams exposed to low-dose BPA during pregnancy. We also found that this prenatal exposure to low-dose BPA led to increased proliferation but reduced migration of cortical neurons. Transcriptomic analysis via RNA sequencing revealed an aberrant activation of the cAMP-PKA-CREB pathway in offspring exposed to BPA. The use of H89, a selective PKA inhibitor, effectively rescued the deficits in both proliferation and migration of cortical neurons. Furthermore, offspring from dams exposed to low-dose BPA exhibited manic-like behaviors, including hyperactivity, anti-depressant-like responses, and reduced anxiety. While H89 normalized hyperactivity, it didn't affect the other behavioral changes. These results suggest that the overactivation of PKA plays a causative role in BPA-induced changes in neuronal development. Our data also indicate that manic-like behaviors induced by prenatal low-dose BPA exposure may be influenced by both altered neuronal development and abnormal PKA signaling in adulthood.
Variability and error in measurement of infant formula powder and water: an experimental study
Authors: Rosenkranz Richard R. , Gonzalez-Alvarez Ana , Acosta Chris , Hooyman Andrew , Hidalgo Jose R. , Ballesteros-Paniagua CindyRomina , Rosenkranz Sara K.
Published: August 2024

Introduction

Formula feeding is the only viable nutrition alternative for infants 0–6mos who cannot breastfeed. Among the drawbacks of formula feeding, however, is potential dilution or concentration errors in the formula during preparation that may lead to infant health issues. The present study aimed to investigate the accuracy of caregiver measurements as they prepared infant formula under multiple conditions, compared with manufacturer specifications.

Methods

A diverse sample of caregivers (N = 84) participated in this cross-over experimental study. Participants hand-scooped infant formula powder and poured water to prepare 4oz. and 7oz. feedings, using both a standardized set of infant formula products and participants’ own products. Linear mixed effects models were used to estimate fixed effects of target amount (4oz. versus 7oz) and products (participant versus researcher) on mean absolute percent error (MAPE) of measurement.

Results

Across all conditions MAPE was significantly greater for measuring powder than for water (9.0% vs. 4.4%; p < 0.001) with a combined powder and water MAPE at 13.0%. Greater measurement error was associated with the odd-sized 7oz. preparation and participants’ own products.

Discussion

We observed considerable variability and substantial error during infant formula preparation, particularly for hand-scooping of powder, which tended toward higher values than the theoretical gold standard.
Association between coffee intake and skeletal muscle mass among U.S. adults: a population-based study
Authors: Yin Huangyi , Zhu Wei , Guo Liuqing , Li Weishan , Liang Min
Published: August 2024

Background

A limited number of studies have reported that the possible effects of coffee intake on skeletal muscle mass, but the results have been inconsistently conclusive and there are no large sample studies concerning the U.S. population. Therefore, the purpose of our study was to explore the connection between coffee consumption and skeletal muscle mass in U.S. adults.

Methods

The population for this cross-sectional study was drawn from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Appendicular lean mass was accurately obtained from DXA, and skeletal muscle mass was assessed using appendicular skeletal muscle mass adjusted for body mass index (ASMBMI). Coffee and caffeine consumptions were obtained on a 24-h dietary recall questionnaire. Furthermore, the associations between coffee and caffeine intake and skeletal muscle mass were evaluated using three multiple linear regression models and smoothed curve fitting. Subgroup analyses based on age, gender, ethnicity and body mass index (BMI) were performed to assess the robustness of these relationships.

Results

This cross-sectional survey included a total of 8,333 participants. After adjusting for all covariates, higher intake of coffee, caffeinated coffee, and caffeine was associated with elevated ASMBMI (coffee: β = 0.01, 95% CI: 0.01, 0.02, P-value < 0.001; caffeinated coffee: β = 0.01, 95% CI: 0.01, 0.02, P-value < 0.001; caffeine: β = 0.02, 95% CI: 0.01, 0.04, P-value < 0.001). Meanwhile, smoothed curve fitting showed that coffee, caffeinated coffee, and caffeine intake were linearly and positively associated with ASMBMI. After further stratification by sex, age, and ethnicity, the positive relationships between coffee (especially caffeinated coffee) and caffeine intake and ASMBMI were not modified (P for interaction > 0.05). However, these relationships disappeared when the BMI over 30 kg/m2.

Conclusions

In general, consumption of coffee and caffeine is positively associated with skeletal muscle mass. Therefore, an appropriate increase in coffee and caffeine intake may be advocated in populations at high risk for low skeletal muscle mass.
Breeding in bread-making wheat varieties for Mediterranean climate: the need to get resilient varieties
Authors: Maçãs Benvindo , Costa Rita , Gomes Conceição , Bagulho Ana Sofia , Pinheiro Nuno , Moreira José , Costa Armindo , Patanita Manuel , Dores José , Rodrigo Sara
Published: August 2024

Introduction

Being one of the “big three” most cultivated cereals in the world, wheat plays a crucial role in ensuring global food/nutrition security, supplying close to 20% of the global needs for calories and proteins. However, the increasingly large fluctuations between years in temperatures and precipitation due to climate change cause important variations in wheat production worldwide. This fact makes wheat breeding programs a tool that, far from going out of fashion, is becoming the most important solution to develop varieties that can provide humanity with the sufficient amount of food it demands without forgetting the objective of quality.

Material and methods

The National Institute of Agricultural and Veterinary Research in Portugal has carried out a long-term experiment (9 years) in different locations to test four different bread-making wheat cultivars, each representing important variations in germplasm. Wheat yield and quality traits obtained by official methods were recorded in 18 different environments regarding temperature and precipitation.

Results and discussion

According to the ANOVA and PCA, protein content, wet gluten, dough tenacity, and extensibility were found to be highly affected by the environment. Paiva cultivar presented a higher yield in almost all the tested environments, but its quality traits varied enormously. Contrary behavior was recorded for Valbona cultivar. Antequera cultivar, with a production ranging between 4.7 and 9.3 tons/ha and a protein content between 11 and 16.8%, seems to be the most resilient cultivar regarding both productivity and quality of the flour with reference to changes in the main climate traits. The most ancient cultivar, Roxo, released in 1996, showed the worst results in this experiment, supporting the need to continue working in wheat breeding to meet the unavoidable changes in the environment.
Characteristics of stachyose-induced effects on gut microbiota and microbial metabolites in vitro associated with obesity in children
Authors: Pi Xionge , Du Zhi , Teng Weilin , Fu Hao , Hu Lidan , Li Jiabin , Ding Jieying , Yang Xiaoxia , Zhang Yinjun
Published: August 2024

Childhood obesity presents a serious health concern associated with gut microbiota alterations. Dietary interventions targeting the gut microbiota have emerged as promising strategies for managing obesity in children. This study aimed to elucidate the impact of stachyose (STS) supplementation on the gut microbiota composition and metabolic processes in obese children. Fecal samples were collected from 40 obese children (20 boys and 20 girls) aged between 6 and 15 and in vitro fermentation was conducted with or without the addition of STS, respectively, followed by 16S rRNA amplicon sequencing and analysis of short-chain fatty acids (SCFAs) and gases. Notably, our results revealed that STS supplementation led to significant alterations in gut microbiota composition, including an increase in the abundance of beneficial bacteria such as Bifidobacterium and Faecalibacterium, and a decrease in harmful bacteria including Escherichia-Shigella, Parabacteroides, Eggerthella, and Flavonifractor. Moreover, STS supplementation resulted in changes in SCFAs production, with significant increases in acetate levels and reductions in propionate and propionate, while simultaneously reducing the generation of gases such as H2S, H2, and NH3. The Area Under the Curve (AUC)-Random Forest algorithm and PICRUSt 2 were employed to identify valuable biomarkers and predict associations between the gut microbiota, metabolites, and metabolic pathways. The results not only contribute to the elucidation of STS’s modulatory effects on gut microbiota but also underscore its potential in shaping metabolic activities within the gastrointestinal environment. Furthermore, our study underscores the significance of personalized nutrition interventions, particularly utilizing STS supplementation, in the management of childhood obesity through targeted modulation of gut microbial ecology and metabolic function.
Platycodon grandiflorum exhibits anti-neuroinflammatory potential against beta-amyloid-induced toxicity in microglia cells
Authors: Ji Yun-Jeong , Kang Min Hye , Kim Geum-Soog , Kim Hyung Don , Jang Gwi Yeong
Published: August 2024

Background/objectives

Platycodon grandiflorum (PG) is used in traditional oriental medicine to treat several ailments.

Methods

The study investigated the anti-inflammatory and neuroprotective effects of PGW (P. grandiflorum) extract in Aβ25-35-induced inflammation in BV2 microglia cells.

Result

PGW demonstrated significant inhibition of nitric oxide (NO) production, with reductions of 30.4, 36.7, and 61.2% at concentrations of 50, 100, and 200 μg/mL, respectively. Moreover, PGW effectively suppressed the production of pro-inflammatory cytokines IL-1β and IL-6 and exhibited significant inhibitory activity against TNF-α at 200 μg/mL. Furthermore, PGW treatment mitigated apoptosis in Aβ-induced BV2 cells by modulating the mitochondrial apoptosis pathway, regulating Bcl-2 family protein synthesis, and inhibiting caspase activation. Mechanistically, PGW attenuated the activation of the MAPK (JNK, ERK, p38) pathway induced by Aβ, showing a concentration-dependent decrease in phosphorylation levels of these proteins. Additionally, PGW inhibited the NF-κB pathway activation by reducing the phosphorylation levels of p65 and IκBα in a concentration-dependent manner.

Conclusion

PGW demonstrated anti-inflammatory and neuroprotective effects in Aβ-induced neuronal cells, suggesting its potential as a therapeutic agent for neuroinflammatory associated with neurodegenerative diseases.
Association of US county-level social vulnerability index with breast, colorectal, and lung cancer screening, incidence, and mortality rates across US counties
Authors: Mehta Akhil , Jeon Won Jin , Nagaraj Gayathri
Published: August 2024

Background

Despite being the second leading cause of death in the United States, cancer disproportionately affects underserved communities due to multiple social factors like economic instability and limited healthcare access, leading to worse survival outcomes. This cross-sectional database study involves real-world data to explore the relationship between the Social Vulnerability Index (SVI), a measure of community resilience to disasters, and disparities in screening, incidence, and mortality rates of breast, colorectal, and lung cancer. The SVI encompasses four themes: socioeconomic status, household composition & disability, minority status & language, and housing type & transportation.

Materials and methods

Using county-level data, this study compared cancer metrics in U.S. counties and the impact of high and low SVI. Two-sided statistical analysis was performed to compare SVI tertiles and cancer screening, incidence, and mortality rates. The outcomes were analyzed with logistic regression to determine the odds ratio of SVI counties having cancer metrics at or above the median.

Results

Our study encompassed 3,132 United States counties. From publicly available SVI data, we demonstrated that high SVI scores correlate with low breast and colorectal cancer screening rates, along with high incidence and mortality rates for all three types of cancers. County level SVI has impact on incidence rates of cancers; breast cancer rates were lowest in high SVI counties, while colorectal and lung cancer rates were highest in the same counties. Age-adjusted mortality rates for all three cancers increased across SVI tertiles. After risk adjustment, a 10-point SVI increase correlated with lower screening and higher mortality rates.

Conclusion

In conclusion, our study establishes a significant correlation between SVI and cancer metrics, highlighting the potential to identify marginalized communities with health disparities for targeted healthcare initiatives. It underscores the need for further longitudinal studies on bridging the gap in overall cancer care in the United States.
Construction of nomogram based on clinical factors for the risk prediction of postoperative complications in children with choledochal cyst
Authors: Lin Yang , Xu Xinru , Chen Shan , Zhang Ling , Wang Jianbin , Qiu Xinyi , Li Lizhi
Published: August 2024

Objective

The aim of the study was to develop a prediction nomogram based on clinical factors to assess the risk of postoperative complications in children with congenital choledochal cyst.

Methods

The clinical data from 131 children who underwent choledochal cyst resection and Roux-en-Y hepaticojejunostomy in our hospital between January 2016 and December 2022 were retrospectively analyzed. The general information, clinical symptoms, procedure, biochemical indicators, and imaging data were recorded. A prolonged hospital stay induced by postoperative complications or a follow-up over 6 months was assessed as the event outcome. A logistics regression analysis was performed to screen for risk factors with statistical significance in inducing postoperative complications. Then, with the dataset split into the training group and internal validation group, the nomogram for the prediction of postoperative complications was developed based on a computer algorithm. In addition, the receiver operating characteristic (ROC) curve and calibration curve were performed for nomogram verification.

Results

Of 131 children, the multivariate logistics regression analysis suggested that age ≤2 years [odds ratio (OR) 0.93; 95% confidence interval (CI) 0.15–5.65; p = 0.938], Todani classification type 1 (OR 36.58; 95% CI 4.14–871.74; p = 0.005), cyst wall thickness >0.4 cm (OR 10.82; 95% CI 2.88–49.13; p < 0.001), with chronic cholecystitis (OR 7.01; 95% CI 1.62–38.52; p = 0.014), and choledochal cyst diameter (OR 1.01; 95% CI 0.99–1.03; p = 0.370) were predictors associated with the postoperative complications of choledochal cysts. The data were randomly divided into the training group (n = 92) and internal validation group (n = 39) to build the prediction nomogram including the appeal factors. The accuracy and discrimination of the model were evaluated using a ROC curve and calibration curve. The results showed that the nomogram area under the ROC curve [area under the curve (AUC) = 0.894; 95% CI 0.822–0.966; p < 0.001], validation (AUC = 0.844; 95% CI 0.804–0.952; p < 0.001), and Brier = 0.120 (95% CI 0.077–0.163p; p < 0.001) were indicative of the good stability and calibration of the predictive nomogram.

Conclusion

The prognosis of congenital choledochal cysts was associated with multiple aspects of clinical factors. Combined with the internal validation, the novel prediction nomogram was suitable for evaluating the individualized risk of postoperative complications of choledochal cysts. The prediction nomogram could provide a more accurate strategy of procedure and postoperative follow-up for children with choledochal cysts.
Rhabdomyosarcoma of the biliary tract in a child: a case report
Authors: Ran Tang , Gong Chen , Rui Dong , Shan Zheng
Published: August 2024

Pediatric rhabdomyosarcoma of the biliary tract (BRMS) is extremely rare. Here, we present a case of a 2-year-old child who was initially misdiagnosed with choledocholithiasis upon admission. The diagnosis was later confirmed as BRMS through endoscopic retrograde cholangiopancreatography (ERCP). The patient was cured through surgery followed by chemotherapy. Due to the lack of specific early symptoms and the challenges in imaging differentiation, particularly in pediatric patients, clinical awareness of this condition needs to be heightened. Our findings indicate that ERCP is currently the optimal diagnostic tool for this disease, and a combination of surgery and chemotherapy can yield better therapeutic outcomes.
Exploring stevioside binding affinity with various proteins and receptors actively involved in the signaling pathway and a future candidate for diabetic patients
Authors: Khan Salman , Ahmad Nisar , Fazal Hina , Saleh Ibrahim A. , Abdel-Maksoud Mostafa A. , Malik Abdul , AbdElgayed Gehad , Jalal Arshad , Rauf Kamran , Ali Liaqat , Ullah Sami , Niqabullah  , Ahmad Sajjad
Published: August 2024

Introduction and Background: Diabetes is a chronic metabolic disease characterized by elevated blood glucose levels and is one of the main global health concerns. Synthetic sugar substrate has many side effects such as leukemia, bladder cancer, hepatotoxicity, breast cancer, headache, and brain toxicity. The WHO and FDA has recently banned some of the synthetic sugar alternatives due to their carcinogenic effects.

Objective and Methodology: Therefore, the main objective of the current study was to investigate the safety and binding affinity of Stevioside with Glucose Transpoter-4 (GLUT-4), Akt, Insulin Receptor (IR) and Insulin Receptor Substrate-1 (IRS-1) to confirmed that Stevioside is one the potent natural sweetener/drug for diabetes. This study delves into the molecular interaction between Stevioside and key diabetic proteins: GLUT-4, Akt, IR and IRS-1. A precise molecular docking approach was used to simulate the binding affinity of Stevioside to these proteins. The pharmacokinetic properties of the molecule should be taken into consideration as important variables throughout the virtual screening process.

Results: The result of active site analysis of GLUT-4, Akt, IR and IRS-1 showed a zone of 2158.359 Ǻ2, 579.259 Ǻ2, 762.651 Ǻ2, and 152.167 Ǻ2 and a volume of 2765.094 Ǻ³, 355.567 Ǻ³, 686.806 Ǻ³, and 116.874 Ǻ³, respectively. Docking analysis of the Stevioside compound showed the highest docking energy with scores of −9.9 with GLUT-4, −6.7 with Akt, −8.0 with IR and −8.8 with IRS-1. Studies indicated that it remains undigested by stomach acids and enzymes and is not absorbed in the upper small intestine. Further, tests revealed no hepatotoxicity, AMES toxicity, or skin sensitivity, making it a promising candidate for safe consumption as drug metabolism.

Conclusion and Recommendations: Instead of other sugar alternatives, Stevioside will help diabetic patients with a lower chance of infections, lowered blood pressure/blood sugar, and increased glucose uptake in diabetic muscles. Stevioside is a natural sweetener, and the current study recommends its usage in various dietary products for diabetic patients.
CKD-497 inhibits NF-kB signaling and ameliorates inflammation and pulmonary fibrosis in ovalbumin-induced asthma and particulate matter-induced airway inflammatory diseases
Authors: Kim Hyejeong , Choi Jihye , Seo Jaeok , Lim Hyungjoon , Kang Sung Kwon
Published: August 2024

Introduction: Air pollution, allergens, and bacterial infections are major contributors to pathological respiratory disorders worldwide. CKD-497, derived from the rhizome of Atractylodes japonica and the fruits of Schisandra chinensis, is known for its ability to relieve cough and facilitate phlegm expectoration. However, its protective action against allergic asthma and fine dust-induced lung inflammation, along with its underlying mechanisms, have not been thoroughly investigated.

Methods: In this study, we established mouse models of ovalbumin (OVA)-induced asthma and particulate matter (PM)-induced pulmonary inflammation to evaluate the effects of CKD-497. Mice were administered CKD-497 orally, and various parameters such as airway inflammation, mucus production, and proinflammatory cytokine levels (IL-1β, IL-6, TNF-α) were measured. Additionally, the macrophage cell line RAW264.7 was pretreated with CKD-497 and stimulated with lipopolysaccharide (LPS) to assess inflammation via the NF-kB signaling pathway.

Results: Oral administration of CKD-497 effectively attenuated airway inflammation and mucus production in both OVA-induced asthma and PM-induced lung inflammation models. It also significantly decreased the production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. CKD-497 alleviated leukocyte infiltration, including neutrophils, and reduced fibrillary collagen deposition in PM10-treated mice. In vitro, CKD-497 pretreatment inhibited LPS-induced inflammation in RAW264.7 cells through the suppression of the NF-kB signaling pathway.

Discussion: CKD-497 shows potent anti-inflammatory effects in mouse models of asthma and PM-induced lung inflammation, potentially mediated by the inhibition of the NF-kB pathway. These findings suggest that CKD-497 could serve as a functional supplement to protect against respiratory diseases by mitigating pulmonary and airway inflammation induced by allergens and air pollution.
The first-in-class pro-apoptotic peptide PEP-010 is effective in monotherapy and in combination with paclitaxel on resistant ovarian adenocarcinoma cell models
Authors: Lacroix Aline , Farhat Rayan , Robert Aude , Brenner Catherine , Wiels Joëlle , Germini Diego
Published: August 2024

Ovarian adenocarcinoma is the gynecological malignancy with the worst prognosis and the highest mortality rate. In the first stages of treatment, chemotherapy results effective, but its prolonged use and high doses lead to the appearance of resistance to treatments and relapse in most patients, representing a major challenge for clinicians. We developed PEP-010, a cell penetrating proapoptotic peptide disrupting the protein-protein interaction between caspase-9 and protein phosphatase 2A, thereby leading to the recovery of their activity in the apoptotic pathway. MTT assay or Annexin-V/Propidium Iodide staining and flow cytometry analysis were used to assess sensitivity to chemotherapies and apoptosis after treatment with PEP-010 in monotherapy or in combination with paclitaxel in ovarian carcinoma cell lines. DNA damage was assessed by immunofluorescence using γH2AX marker. We show here that PEP-010 effectively induces cell death in monotherapy on in up to 55% of cells from ovarian adenocarcinoma cell models resistant to different chemotherapies. Moreover, when used in combination with paclitaxel, one of the therapeutic options for recurrent ovarian carcinoma, PEP-010 showed a beneficial effect leading to the reduction of the IC50 of paclitaxel of 2.2 times and to apoptosis in 87% of cells. The described results suggest the potential therapeutic interest for PEP-010 and lead to the choice of ovarian adenocarcinoma as one of the major indications of the ongoing clinical trial.
DaiTongXiao improves gout nephropathy by inhibiting inflammatory response through the TLR4/MyD88/NF-κB pathway
Authors: Liu Feifan , Bai Yuanmei , Wan Yan , Luo Shifang , Zhang Linao , Wu Xue , Chen Rong , Yin Zili , Xie Yuhuan , Guo Peixin
Published: August 2024

Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties.

Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression.

Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and β2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type Ⅳ (COL-Ⅳ). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) −18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and IL-1β in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue.

Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/ NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression.
Genome-wide analysis and identification of the TBL gene family in Eucalyptus grandis
Authors: Tang Jiye , Ling Tenghong , Li Huiling , Fan Chunjie
Published: August 2024

The TRICHOME BIREFRINGENCE-LIKE (TBL) gene encodes a class of proteins related to xylan acetylation, which has been shown to play an important role in plant response to environmental stresses. This gene family has been meticulously investigated in Arabidopsis thaliana, whereas there have been no related reports in Eucalyptus grandis. In this study, we identified 49 TBL genes in E. grandis. A conserved amino acid motif was identified, which plays an important role in the execution of the function of TBL gene family members. The expression of TBL genes was generally upregulated in jasmonic acid-treated experiments, whereas it has been found that jasmonic acid activates the expression of genes involved in the defense functions of the plant body, suggesting that TBL genes play an important function in the response of the plant to stress. The principle of the action of TBL genes is supported by the finding that the xylan acetylation process increases the rigidity of the cell wall of the plant body and thus improves the plant’s resistance to stress. The results of this study provide new information about the TBL gene family in E. grandis and will help in the study of the evolution, inheritance, and function of TBL genes in E. grandis, while confirming their functions.
Soil metagenomics reveals the effect of nitrogen on soil microbial communities and nitrogen-cycle functional genes in the rhizosphere of Panax ginseng
Authors: Li Kexin , Lin Hongmei , Han Mei , Yang Limin
Published: August 2024

Nitrogen (N) is the primary essential nutrient for ginseng growth, and a reasonable nitrogen application strategy is vital for maintaining the stability of soil microbial functional communities. However, how microbial-mediated functional genes involved in nitrogen cycling in the ginseng rhizosphere respond to nitrogen addition is largely unknown. In this study, metagenomic technology was used to study the effects of different nitrogen additions (N0: 0, N1: 20, N2: 40 N g/m2) on the microbial community and functional nitrogen cycling genes in the rhizosphere soil of ginseng, and soil properties related to the observed changes were evaluated. The results showed that N1 significantly increased the soil nutrient content compared to N0, and the N1 ginseng yield was the highest (29.90% and 38.05% higher than of N0 and N2, respectively). N2 significantly decreased the soil NO3–N content (17.18 mg/kg lower than N0) and pH. This resulted in a decrease in the diversity of soil microorganisms, a decrease in beneficial bacteria, an increase in the number of pathogenic microorganisms, and an significant increase in the total abundance of denitrification, assimilatory nitrogen reduction, and dissimilatory nitrogen reduction genes, as well as the abundance of nxrA and napA genes (17.70% and 65.25% higher than N0, respectively), which are functional genes involved in nitrification that promote the soil nitrogen cycling process, and reduce the yield of ginseng. The results of the correlation analysis showed that pH was correlated with changes in the soil microbial community, and the contents of soil total nitrogen (TN), ammonium nitrogen (NH4+-N), and alkaline-hydrolyzed nitrogen (AHN) were the main driving factors affecting the changes in nitrogen cycling functional genes in the rhizosphere soil of ginseng. In summary, nitrogen addition affects ginseng yield through changes in soil chemistry, nitrogen cycling processes, and functional microorganisms.
The overlooked manipulation of nucleolar functions by plant pathogen effectors
Authors: Ranty-Roby Sarah , Pontvianne Frédéric , Quentin Michaël , Favery Bruno
Published: August 2024

Pathogens need to manipulate plant functions to facilitate the invasion of their hosts. They do this by secreting a cocktail of molecules called effectors. Studies of these molecules have mostly focused on the mechanisms underlying their recognition and the subsequent transcriptional reprogramming of cells, particularly in the case of R gene-dependent resistance. However, the roles of these effectors are complex, as they target all cell compartments and their plant targets remain largely uncharacterized. An understanding of the mechanisms involved would be a considerable asset for plant breeding. The nucleolus is the site of many key cellular functions, such as ribosome biogenesis, cellular stress regulation and many other functions that could be targets for pathogenicity. However, little attention has been paid to effectors targeting nucleolar functions. In this review, we aim to fill this gap by providing recent findings on pathogen effectors that target and manipulate nucleolar functions and dynamics to promote infection. In particular, we look at how some effectors hijack ribosome biogenesis, the modulation of transcription or alternative splicing, all key functions occurring at least partially in the nucleolus. By shedding light on the role of the plant nucleolus in pathogen interactions, this review highlights the importance of understanding nucleolar biology in the context of plant immunity and the mechanisms manipulated by plant pathogens.
Complete mitochondrial genome of Hippophae tibetana: insights into adaptation to high-altitude environments
Authors: Zeng Zhefei , Zhang Zhengyan , Tso Norzin , Zhang Shutong , Chen Yan , Shu Qi , Li Junru , Liang Ziyi , Wang Ruoqiu , Wang Junwei , Qiong La
Published: August 2024

Hippophae tibetana, belonging to the Elaeagnaceae family, is an endemic plant species of the Qinghai–Tibet Plateau, valued for its remarkable ecological restoration capabilities, as well as medicinal and edible properties. Despite being acknowledged as a useful species, its mitochondrial genome data and those of other species of the Elaeagnaceae family are lacking to date. In this study, we, for the first time, successfully assembled the mitochondrial genome of H. tibetana, which is 464,208 bp long and comprises 31 tRNA genes, 3 rRNA genes, 37 protein-coding genes, and 3 pseudogenes. Analysis of the genome revealed a high copy number of the trnM-CAT gene and a high prevalence of repetitive sequences, both of which likely contribute to genome rearrangement and adaptive evolution. Through nucleotide diversity and codon usage bias analyses, we identified specific genes that are crucial for adaptation to high-altitude conditions. Notably, genes such as atp6, ccmB, nad4L, and nad7 exhibited signs of positive selection, indicating the presence of unique adaptive traits for survival in extreme environments. Phylogenetic analysis confirmed the close relationship between the Elaeagnaceae family and other related families, whereas intergenomic sequence transfer analysis revealed a substantial presence of homologous fragments among the mitochondrial, chloroplast, and whole genomes, which may be linked to the high-altitude adaptation mechanisms of H. tibetana. The findings of this study not only enrich our knowledge of H. tibetana molecular biology but also advance our understanding of the adaptive evolution of plants on the Qinghai–Tibet Plateau. This study provides a solid scientific foundation for the molecular breeding, conservation, and utilization of H. tibetana genetic resources.
Religion, personality, or none of them? Exploratory evidence on their correlations with economic preference parameters
Authors: Bessey Donata
Published: August 2024

Introduction

Previous empirical research in the social sciences suggests sizable differences across religious denominations for various outcomes of interest, such as educational attainment, marital stability, wealth, or fertility. A small body of previous experimental literature has investigated possible differences in economic preference parameters (including time preference and risk attitude) between religious denominations that might explain those differences.

Methods

This research adds to the extant literature on religion and preferences by including information on subjects’ Big Five personality traits and analyzing potential correlations with loss aversion. It combines experimental data from incentivized choices with information on religious affiliation during high school and Big Five personality traits to test for possible correlations of religious denomination with risk attitude, time preference, and loss aversion, using Bayesian analysis of variance (ANOVA) and Bayesian regression analysis.

Results

Bayesian ANOVA results suggest no preference differences between the religions analyzed in this research. When controlling for Big Five personality traits and a host of other background variables, Bayesian regression results suggest no effects of either religious affiliation or Big Five personality traits measures on the three economic preference parameters analyzed here.

Discussion

These findings highlight the complexity of the relationship between religion, personality traits, and economic preference parameters, suggesting that previously observed differences may be influenced by the preference measures used or other unobserved factors.