bluuebunny/crossref_metadata_2025 huggingface dataset:
Surrogate-based worst-case analysis of a knee joint model using Genetic Algorithm
Authors: Ciszkiewicz Adam , Dumas Raphael
Published: July 2024

Verification, validation, and uncertainty quantification is generally recognized as a standard for assessing the credibility of mechanical models. This is especially evident in biomechanics, with intricate models, such as knee joint models, and highly subjective acquisition of parameters. Propagation of uncertainty is numerically expensive but required to evaluate the model reliability. An alternative to this is to analyze the worst-case models obtained within the specific bounds set on the parameters. The main idea of the paper is to search for two models with the greatest different response in terms of displacement-load curve. Real-Coded Genetic Algorithm is employed to effectively explore the high-dimensional space of uncertain parameters of a 2D dynamic knee model, while Radial Basis Function surrogates reduce the computation by orders of magnitude to near real-time, with negligible impact on the quality. It is expected that the studied knee joint model is very sensitive to uncertainty in the geometrical parameters. The obtained worst-case knee models showcase unrealistic behavior with one of them unable to fully extend, and the other largely overextending. Their relative difference in extension is up to 35% under ±1 mm bound set on the geometry. This unrealistic behavior of knee joint model is confirmed by the large standard deviation obtained from a classical sampling-based sensitivity analysis. The results confirm the viability of the method in assessing the reliability of biomechanical models. The proposed approach is general and could be applied to other mechanical systems as well.
Rationale and design of the multi organ inflammation with serial testing study: a comprehensive assessment of functional and structural abnormalities in patients with recovered COVID-19
Authors: Paterson D. Ian , White James A. , Beaulieu Christian , Sherrington Rachel , Prado Carla M. , Tandon Puneeta , Halloran Kieran , Smith Stephanie , McCombe Jennifer A. , Ritchie Bruce , Pituskin Edith , Haykowsky Mark J. , Coulden Richard , Emery Derek , Tsui Albert K. , Wu Kai Y. , Oudit Gavin Y. , Ezekowitz Justin A. , Thompson Richard B.
Published: July 2024

Introduction

Short-term clinical outcomes from SARS-CoV-2 infection are generally favorable. However, 15–20% of patients report persistent symptoms of at least 12 weeks duration, often referred to as long COVID. Population studies have also demonstrated an increased risk of incident diabetes and cardiovascular disease at 12 months following infection. While imaging studies have identified multi-organ injury patterns in patients with recovered COVID-19, their respective contributions to the disability and morbidity of long COVID is unclear.

Methods

A multicenter, observational study of 215 vaccine-naïve patients with clinically recovered COVID-19, studied at 3–6 months following infection, and 133 healthy volunteers without prior SARS-CoV-2 infection. Patients with recovered COVID-19 were screened for long COVID related symptoms and their impact on daily living. Multi-organ, multi-parametric magnetic resonance imaging (MRI) and circulating biomarkers were acquired to document sub-clinical organ pathology. All participants underwent pulmonary function, aerobic endurance (6 min walk test), cognition testing and olfaction assessment. Clinical outcomes were collected up to 1 year from infection. The primary objective of this study is to identify associations between organ injury and disability in patients with long-COVID symptoms in comparison to controls. As a secondary objective, imaging and circulating biomarkers with the potential to exacerbate cardiovascular health were characterized.

Discussion

Long-term sequelae of COVID-19 are common and can result in significant disability and cardiometabolic disease. The overall goal of this project is to identify novel targets for the treatment of long COVID including mitigating the risk of incident cardiovascular disease.

Study registration

clinicaltrials.gov (MOIST late cross-sectional study; NCT04525404).
Surgical outcomes of sacrospinous hysteropexy and hysteropreservation for pelvic organ prolapse: a systematic review of randomized controlled trials
Authors: Xiao Xinyu , Yu Xia , Yin Litong , Zhang Ling , Feng Dan , Zhang Lushuang , Gong Zhaolin , Zhang Qiang , Lin Yonghong , He Li
Published: July 2024

Objective

In several randomized controlled trials (RCTs), sacrospinous hysteropexy and other forms of hysteropreservation have been compared. Nevertheless, there is no definitively best treatment. This study summarized RCT evidence for various uterine preservation surgical procedures.

Methods

From each database inception to August 2023, we searched PubMed, Embase, Cochrane Library, and Web of Science for eligible RCTs. A comparison was made between sacrospinous hysteropexy and other hysteropreservation, including vaginal and abdominal surgery. For categorical and continuous variables, relative risks (RRs) and mean differences (MDs) were calculated using random-effects models.

Results

We reviewed a total 1,398 studies and ultimately included five RCTs that met all inclusion criteria. These five studies included a total of 1,372 uterine POP cases all of whom received transvaginal surgery and had a follow-up period for assessment of recurrence from 12 months to 5 years. There were no significant differences between sacrospinous hysteropexy and other hysteropreservation for the incidences of recurrence (RR,1.24; 95% CI, 0.58 to 2.63; p = 0.58) or hematoma (RR,0.70; 95% CI, 0.17 to 2.92; p = 0.62). Moreover, neither sacrospinous hysteropexy nor hysteropreservation had any significant effect on the risk of mesh exposure (RR,0.34; 95% CI, 0.03 to 4.31; p = 0.41), dyspareunia (RR,0.45; 95% CI, 0.13 to1.6; p = 0.22), urinary tract infection (RR,0.66; 95% CI, 0.38 to 1.15; p = 0.15), bothersome bulge symptoms (RR,0.03; 95% CI, −0.02 to 0.08; p = 0.24), operative time (MD, −4.53; 95% CI, −12.08 to 3.01; p = 0.24), and blood loss (MD, −25.69; 95% CI, −62.28 to 10.91; p = 0.17). However, sacrospinous hysteropexy was associated with a lower probability of pain (RR,4.8; 95% CI, 0.79 to 29.26; p = 0.09) compared with other hysteropreservation.

Conclusion

There was no difference between sacrospinous hysteropexy and hysteropreservation in terms of recurrence, hematoma, mesh exposure, dyspareunia, urinary tract infection, bothersome bulge symptoms, operative time, pain, and blood loss.

Systematic Review Registration

PROSPERO [CRD42023470025].
Is fluorometric sentinel lymph node biopsy in endometrial cancer necessary?
Authors: Huang Liqiong , Cheng Wei , He Chenghui , Li Xin , Huang Lu , Zhang Jiajia , Song Liwen , Zhou Yifan , Wang Chenchen , Gan Xiaoqin , Qiu Jin
Published: July 2024

Objective

In this study, we collected perioperative and postoperative follow-up data from patients with endometrial cancer (EC) at different stages to evaluate the role of sentinel lymph node biopsy (SLNB) in endometrial cancer surgery.

Methods

A total of 186 endometrial cancer patients undergoing radical hysterectomy from January 2018 to April 2022 were retrospectively analyzed. Patients were classified into four groups. Group A comprised patients diagnosed with stage IA grade 1 and 2 endometrioid EC who underwent SLNB. Group B comprised patients with stage IA grade 1 and 2 endometrioid EC who did not undergo SLNB. Group C comprised patients with higher-grade endometrioid EC, wherein systematic lymph node dissection was performed based on SLNB results. Group D comprised patients with higher-grade endometrioid EC who did not undergo SLNB and instead underwent direct systematic lymph node dissection. Clinical, pathological data, and follow-up information for all patients were collected.

Results

In Group A and B, SLNB was performed on 36 out of 67 patients with IA stage 1 and 2 endometrial cancer, yielding a SLN positivity rate of 5.6%. There were no significant differences observed between the two groups regarding perioperative outcomes and postoperative follow-up. Conversely, among 119 patients with higher-grade endometrial cancer, 52 underwent SLNB, with 20 patients exhibiting SLN positivity, resulting in a SLN positivity rate of 38.4%. However, the decision to undergo SLNB did not yield significant differences in perioperative outcomes and postoperative follow-up among these patients.

Conclusion

For stage IA grade 1 and 2 endometrioid EC, the incidence of lymph node positivity is low, omitting SLNB in this subpopulation is a feasible option. In other stages of endometrioid EC, there is no significant difference in perioperative and postoperative follow-up data between patients undergoing routine systematic lymphadenectomy and those undergoing systematic lymphadenectomy based on SLNB results. Therefore, if SLNB is not available, the standard procedure of PLND remains an option to obtain information about lymph node status, despite the surgical complications associated with this procedure.
The impact of simultaneous inoculation with Torulaspora delbrueckii and Hanseniaspora uvarum combined with Saccharomyces cerevisiae on chemical and sensory quality of Sauvignon blanc wines
Authors: Li Linbo , Yuan Chenyang , Zhang Lei , Chu Ruichao , Yu Qingquan , Cai Jian , Yang Tianyou , Zhang Mingxia
Published: July 2024

Non-Saccharomyces yeasts have great potential in improving wine quality, showing personality characteristics, and highlighting the terroir of wine. In this study, we evaluated the impact of simultaneous inoculation with the non-Saccharomyces yeasts Torulaspora delbrueckii or (and) Hanseniaspora uvarum in combination with Saccharomyces cerevisiae (EC1118 or VL3) on the aromatic compounds and sensory quality of Sauvignon blanc wines. The growth of yeast groups in the alcoholic fermentation process was tracked using fluorescence in situ hybridization. The presence of non-Saccharomyces yeast notably impacted the distribution of S. cerevisiae and was related to the species of yeast. The co-fermentation of H. uvarum and S. cerevisiae improved the content of total esters, especially acetate esters. Simultaneous inoculation of T. delbrueckii or (and) H. uvarum significantly increased the content of total terpenes, especially linalool. Similar results were found for some higher alcohols and organic acids. Sensory evaluation showed that the wines mixed fermentation with H. uvarum had significantly tropical fruit aroma characteristics. Citrus and mineral notes, typical aroma characteristics of Sauvignon blanc wine, were enhanced by mixed fermentation strategies with T. delbrueckii or (and) H. uvarum and different S. cerevisiae. Hence, co-fermentation by T. delbrueckii or H. uvarum combined with S. cerevisiae could significantly improve the sensory quality of Sauvignon blanc wine.
The role of actin cytoskeleton CFL1 and ADF/cofilin superfamily in inflammatory response
Authors: Xing Jianxiao , Wang Ying , Peng Aihong , Li Junqin , Niu Xuping , Zhang Kaiming
Published: July 2024

Actin remodeling proteins are important in immune diseases and regulate cell cytoskeletal responses. These responses play a pivotal role in maintaining the delicate balance of biological events, protecting against acute or chronic inflammation in a range of diseases. Cofilin (CFL) and actin depolymerization factor (ADF) are potent actin-binding proteins that cut and depolymerize actin filaments to generate actin cytoskeleton dynamics. Although the molecular mechanism by which actin induces actin cytoskeletal reconstitution has been studied for decades, the regulation of actin in the inflammatory process has only recently become apparent. In this paper, the functions of the actin cytoskeleton and ADF/cofilin superfamily members are briefly introduced, and then focus on the role of CFL1 in inflammatory response.
Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer’s disease
Authors: Han Sang-Won , Lee Sang-Hwa , Kim Jong Ho , Lee Jae-Jun , Park Young Ho , Kim SangYun , Nho Kwangsik , Sohn Jong-Hee
Published: July 2024

Background

Alzheimer’s disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition.

Methods

We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer’s Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations.

Results

Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the APOE ε4 carrier group in the Alzheimer’s Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group.

Conclusion

This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.
Importance of serum albumin in machine learning-based prediction of cognitive function in the elderly using a basic blood test
Authors: Karako Kenji , Hata Takeo , Inoue Atsushi , Oyama Katsunori , Ueda Eiichiro , Sakatani Kaoru
Published: July 2024

Introduction

In this study, we investigated the correlation between serum albumin levels and cognitive function, and examined the impact of including serum albumin values in the input layer on the prediction accuracy when forecasting cognitive function using deep learning and other machine learning models.

Methods

We analyzed the electronic health record data from Osaka Medical and Pharmaceutical University Hospital between 2014 and 2021. The study included patients who underwent cognitive function tests during this period; however, patients from whom blood test data was not obtained up to 30 days before the cognitive function tests and those with values due to measurement error in blood test results were excluded. The Mini-Mental State Examination (MMSE) was used as the cognitive function test, and albumin levels were examined as the explanatory variable. Furthermore, we estimated MMSE scores from blood test data using deep learning models (DLM), linear regression models, support vector machines (SVM), decision trees, random forests, extreme gradient boosting (XGBoost), and light gradient boosting machines (LightGBM).

Results

Out of 5,017 patients who underwent cognitive function tests, 3,663 patients from whom blood test data had not been obtained recently and two patients with values due to measurement error were excluded. The final study population included 1,352 patients, with 114 patients (8.4%) aged below 65 and 1,238 patients (91.6%) aged 65 and above. In patients aged 65 and above, the age and male sex showed significant associations with MMSE scores of less than 24, while albumin and potassium levels showed negative associations with MMSE scores of less than 24. Comparing MMSE estimation performance, in those aged below 65, the mean squared error (MSE) of DLM was improved with the inclusion of albumin. Similarly, the MSE improved when using SVM, random forest and XGBoost. In those aged 65 and above, the MSE improved in all models.

Discussion

Our study results indicated a positive correlation between serum albumin levels and cognitive function, suggesting a positive correlation between nutritional status and cognitive function in the elderly. Serum albumin levels were shown to be an important explanatory variable in the estimation of cognitive function for individuals aged 65 and above.
Association between caffeine intake from foods and beverages in the diet and hearing loss in United States adults
Authors: Xia Fei , Ren Yuanyuan
Published: July 2024

Background

Hearing loss (HL) is the third most prevalent condition, significantly affecting individuals and society. Recent research has explored the potential impact of nutrition, particularly caffeine intake, on HL. While some studies focus on coffee, caffeine intake should be assessed across all dietary sources. This study examines the association between dietary caffeine intake and HL.

Methods

Our cross-sectional study included 6,082 participants from the National Health and Nutrition Examination Survey (NHANES). Participants were divided into two groups based on their median caffeine intake: low and high. The study investigated two types of HL: speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL). Binary logistic regression analyzed the correlation between caffeine intake and HL, and a restricted cubic spline (RCS) model assessed potential non-linear associations. Subgroup analyses were also conducted.

Results

High caffeine intake was associated with significantly higher rates of SFHL and HFHL compared to low intake (SFHL: 15.4% vs. 10%, HFHL: 30.5% vs. 20.6%, both p < 0.001). Unadjusted logistic regression showed a higher likelihood of SFHL (OR[95%CI] = 1.65[1.41–1.92]) and HFHL (OR[95%CI] = 1.69[1.50–1.90]) in high caffeine consumers. After adjusting for confounders, high caffeine intake remained significantly associated with SFHL (OR[95%CI] = 1.35[1.09–1.66]) but not HFHL (OR[95%CI] = 1.14[0.96–1.35]). The RCS model indicated a linear increase in the risk of SFHL and HFHL with higher caffeine intake (non-linear p = 0.229 for SFHL, p = 0.894 for HFHL). Subgroup analysis revealed that increased caffeine intake was linked to higher SFHL and HFHL risks in participants under 65 years but not in those 65 years and older (SFHL: p for interaction = 0.002; HFHL: p for interaction <0.001).

Conclusion

Our study indicates a strong correlation between dietary caffeine intake and the risk of HL in American adults, particularly those under 65. High caffeine intake was linked to an increased risk of SFHL, but not HFHL, after adjusting for relevant variables.
Experiencing anesthesia and surgery early in life impairs cognitive and behavioral development
Authors: Jia Xuqin , Tan Siyou , Qin Yinying , Wei Yi , Jiang Yage , Pan Sining , Li Chunlai , Chen Jing , Liu Tianxiao , Xie Yubo
Published: July 2024

Background

The impact of anesthesia and surgery on neurocognitive and behavioral development in infants and children remains inadequately understood.

Objective

To investigate the impact of early-life exposure to general anesthesia and surgery on cognitive and behavioral development.

Methods and materials

Children aged 0–3 years who underwent general anesthesia and surgical procedures between 2012 and 2015 were included. The cognitive and behavioral development of these children at ages 4–6 years was assessed. Age-, race-, and gender-matched children from the same geographic region, who did not undergo general anesthesia or surgery, served as the control group. The Wechsler Preschool Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to evaluate children’s total intelligence quotient (FSIQ) and specific cognitive domains. The Gesell Development Schedules (GSCH) and Child Behavior Checklist (CBCL) were employed to assess behavioral and personality development. Additionally, the study analyzed the effects of various factors including anesthesia drugs, surgery duration, number of surgeries, age, weight, ethnicity, and gender on postoperative neurocognitive and behavioral outcomes.

Results

The study included 447 children with anesthesia/surgical exposure (AS) and 459 children in the control group. Analysis of cognitive and behavioral development showed a significant difference in the working memory index (WMI) between the AS and control groups (p < 0.05). Exploratory findings indicated that children administered remifentanil exhibited lower developmental quotient (DQ) values, whereas those given fentanyl showed higher (worse) Child Behavior Checklist (CBCL) total scores. Moreover, increased anesthesia/surgical exposures, younger age and lower body weight at exposure, and longer surgery durations were associated with cognitive and behavioral developmental challenges.

Conclusion

This study examined the impact of early-life exposure to surgery and anesthesia on postoperative cognitive and behavioral development. Findings indicate that higher frequency of exposure to surgery and anesthesia, younger age, and lower body weight at exposure could negatively influence cognitive and behavioral development. Furthermore, variations in the effects of different anesthetics on behavior and cognition were observed. Caution is advised regarding the use of opioid analgesics such as remifentanil and fentanyl for more rigorous clinical applications.
The correlation between urinary iodine levels and gallstone risk: elevated iodine intake linked to gallstone occurrence
Authors: Li Yunfan , Wang Minchen , Du Wenyi , Qi Liuyao , Liu Xiaopeng , Fan Xin
Published: July 2024

Background

Essential trace elements are vital for human growth and development. Nevertheless, excessive intake can pose risks. As of yet, no research has looked at the possibility of a relationship between the prevalence of gallstones and urinary concentrations of nickel, molybdenum, and iodine.

Objectives

The purpose of this study was to examine the correlation between urinary levels of iodine, molybdenum, and nickel and the occurrence of gallstones in a U.S. population and to verify whether excessive iodine intake is associated with the occurrence of gallstones.

Methods

Data from 2,734 participants that were gathered between 2017 and 2020 were examined. Employing inductively coupled plasma mass spectrometry (ICP-MS), the levels of nickel (Ni), iodine (I), and molybdenum (Mo) in the urine were determined. Gallstones presence was determined using a standardized questionnaire. Restricted cubic spline analysis, subgroup analysis, and logistic regression analysis were used to evaluate the relationship between the occurrence of gallstones and urinary essential trace elements.

Results

The logistic regression analysis indicated an increased risk of gallstone development in Quartiles 2, Quartiles 3, and Quartiles 4 groups in comparison to the Quartiles 1 group, based on urinary iodine levels (OR = 1.69, 95% CI: 1.11–2.56; OR = 1.68, 95% CI: 1.10–2.55; OR = 1.65, 95% CI: 1.09–2.51). Urinary iodine levels were nonlinearly positively linked with the development of gallstones, according to restricted cubic spline analysis (P-Nonlinear = 0.032). Subgroup analyses showed that high levels of urinary iodine were associated with a high risk of gallstones in different populations, and were more pronounced in adults aged 60 years and older, in women, with a BMI ≥ 25, and in diabetic patients.

Conclusion

Our research revealed a correlation between an increased risk of gallstones and increasing urinary iodine levels. Urinary iodine levels serve as indicators of the body’s iodine status, thus suggesting that excessive iodine intake may be linked to an elevated risk of gallstone formation.
Identification and validation of metastasis-related gene ZG16 in the prognosis and progression in colorectal cancer
Authors: Liu Yulun , Yang Jie , Han Wei , Gu Tingting , Yao Liqian , Wang Yongqiang , Chen Hua
Published: July 2024

Background

Metastasis remains the leading cause of mortality among colorectal cancer (CRC) patients. Identification of new metastasis-related genes are critical to improve colorectal cancer prognosis.

Methods

Data on mRNA expression in metastatic and primary CRC was obtained from the Gene Expression Omnibus (GEO) database, including GSE81986, GSE41568, GSE71222, GSE21510, and GSE14333. Additionally, data concerning mRNA expression in colon cancer (COAD) and adjacent normal tissues were acquired from The Cancer Genome Atlas (TCGA) database. Hub genes were identified by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Moreover, we assessed the impact of hub gene expression on both overall survival (OS) and disease-free survival (DFS) in patients and identified ZG16 as a potential target. We generated CRC cell lines transfected with lentivirus OE-ZG16 to investigate proliferation, invasion, and migration in vitro. To further elucidate the involvement of ZG16, we utilized gene set enrichment analysis (GSEA) to identify enriched pathways, which were subsequently validated via Western blot analysis.

Results

Five datasets containing primary and metastatic CRC samples from GEO database and CRC samples from TCGA database were included in this study and 29 hub genes were identified by WGCNA and differentially expressed gene (DEG) analysis. Low expression of the hub genes (CLCA1 and ZG16) was associated with poor DFS and OS. We confirmed the low expression of ZG16 in CRC using external database and IHC analysis at both transcriptional and protein levels. In addition, the expression of ZG16 was notably elevated in NCM460 cells in comparison to CRC cell lines. The overexpression of ZG16 in CRC cells has been shown to inhibit the proliferation, invasion, and migration of CRC cells. Furthermore, the overexpression of ZG16 has been found to suppress the activation of the epithelial-mesenchymal transition (EMT) and Wnt/β-catenin signaling pathways in CRC.

Conclusion

ZG16 may serve as a promising therapeutic target for metastatic CRC treatment.
CT morphological features and histogram parameters to predict micropapillary or solid components in stage IA lung adenocarcinoma
Authors: Chen Qin , Lin Kaihe , Zhang Baoteng , Jiang Youqin , Wu Suying , Lin Jiajun
Published: July 2024

Objectives

This study aimed to construct prediction models based on computerized tomography (CT) signs, histogram and morphology features for the diagnosis of micropapillary or solid (MIP/SOL) components of stage IA lung adenocarcinoma (LUAC) and to evaluate the models’ performance.

Methods

This clinical retrospective study included image data of 376 patients with stage IA LUAC based on postoperative pathology, admitted to Putian First Hospital from January 2019 to June 2023. According to the presence of MIP/SOL components in postoperative pathology, patients were divided into MIP/SOL+ and MIP/SOL- groups. Cases with tumors ≤ 3 cm and ≤ 2 cm were separately analyzed. Each subgroup of patients was then randomly divided into a training set and a test set in a ratio of 7:3. The training set was used to build the prediction model, and the test set was used for internal validation.

Results

For tumors ≤ 3 cm, ground-glass opacity (GGO) [odds ratio (OR) = 0.244; 95% confidence interval (CI): 0.103–0.569; p = 0.001], entropy (OR = 1.748; 95% CI: 1.213–2.577; p = 0.004), average CT value (OR = 1.002; 95% CI: 1.000–1.004; p = 0.002), and kurtosis (OR = 1.240; 95% CI: 1.023–1.513; p = 0.030) were independent predictors of MIP/SOL components of stage IA LUAC. The area under the ROC curve (AUC) of the nomogram prediction model for predicting MIP/SOL components was 0.816 (95% CI: 0.756–0.877) in the training set and 0.789 (95% CI: 0.689–0.889) in the test set. In contrast, for tumors ≤ 2 cm, kurtosis was no longer an independent predictor. The nomogram prediction model had an AUC of 0.811 (95% CI: 0.731–0.891) in the training set and 0.833 (95% CI: 0.733–0.932) in the test set.

Conclusion

For tumors ≤ 3 cm and ≤ 2 cm, GGO, average CT value, and entropy were the same independent influencing factors in predicting MIP/SOL components of stage IA LUAC. The nomogram prediction models have potential diagnostic value for identifying MIP/SOL components of early-stage LUAC.
Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid
Authors: Wang Xinyu , Lu Yanhong , Chen Feng , Ruan Linan , Gu Lingtong , Wang Ting , Dong Heting , Wang Yuqing , Hao Chuangli , Huang Li , Yan Yongdong , Sun Huiming , Chen Zhengrong
Published: July 2024

Background

This study aimed to investigate the clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia (CAP) and concomitant cytomegalovirus (CMV) infection.

Methods

This cross-sectional study enrolled consecutive pediatric patients admitted with CAP who tested positive for CMV DNA in bronchoalveolar lavage fluid (BALF). Flexible fiberoptic bronchoscopy was performed when routine treatment for CAP proved ineffective. The study participants were further stratified into two groups based on CMV serological test results: recent CMV infection group and CMV replication group. Clinical characteristics were compared between these two groups.

Results

Among 124 patients aged 1–11 months included in this study, 80 (64.5%) patients were categorized as having recent CMV infection, and 44 (35.5%) tested positive for CMV replication. Co-infection with other pathogens was detected more frequently in the CMV replication group (n = 29, 65.9%) than in the recent CMV infection group (n = 35, 43.7%; P = 0.018). Patients with recent CMV infection were younger and exhibited higher levels of alanine transaminase (ALT) and aspartate aminotransferase compared to those with CMV replication (all P < 0.05). Multivariable regression analysis showed age was independently associated with recent CMV infection (odds ratio [OR], 0.707; 95% confidence interval [CI], 0.586–0.853; P < 0.001). Notably, receiver operating characteristic curve analysis showed that a CMV PCR level of 3,840 copies/ml in blood samples had a sensitivity of 34.7% and specificity of 90.0% for diagnosis of recent CMV infection with an area under the curve (AUC) of 0.625 (95% CI: 0.513–0.736, P = 0.048). A CMV PCR level of 6,375 copies/ml in urine samples had a sensitivity of 77.1% and specificity of 61.5% for diagnosis of recent CMV infection with an AUC of 0.695 (95% CI: 0.531–0.858, P = 0.04). Furthermore, multivariate linear regression analysis revealed that the blood CMV DNA copy number was associated with ALT (B = 0.001; P < 0.001).

Conclusions

The CMV DNA copy numbers in blood and urine could serve as discriminatory markers between recent CMV infection and CMV replication. Measuring CMV DNA levels in blood may be an effective method for monitoring liver function impairment in pediatric patients presenting with CAP and concurrent CMV infection.
Combined non-targeted and targeted metabolomics reveals the mechanism of delaying aging of Ginseng fibrous root
Authors: Yang Xiang , Yang Xiang , Li Bo , Zhang Jianyun , Yan Zhuyun
Published: July 2024

Background: The fibrous root of ginseng (GFR) is the dried thin branch root or whisker root of Ginseng (Panax ginseng C. A. Mey). It is known for its properties such as tonifying qi, producing body fluid, and quenching thirst. Clinically, it is used to treat conditions such as cough, hemoptysis, thirst, stomach deficiency, and vomiting. While GFR and Ginseng share similar metabolites, they differ in their metabolites ratios and efficacy. Furthermore, the specific role of GFR in protecting the body remains unclear.

Methods: We employed ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to examine alterations in brain neurotransmitters and elucidate the impact of GFR on the central nervous system. Additionally, we analyzed the serum and brain metabolic profiles of rats using ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry to discern the effect and underlying mechanism of GFR in delaying aging in naturally aged rats.

Results: The findings of the serum biochemical indicators indicate that the intervention of GFR can enhance cardiovascular, oxidative stress, and energy metabolism related indicators in naturally aging rats. Research on brain neurotransmitters suggests that GFR can augment physiological functions such as learning and memory, while also inhibiting central nervous system excitation to a certain degree by maintaining the equilibrium of central neurotransmitters in aged individuals. Twenty-four abnormal metabolites in serum and seventeen abnormal metabolites in brain could be used as potential biomarkers and were involved in multiple metabolic pathways. Among them, in the brain metabolic pathways, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, histidine metabolism, and tyrosine metabolism were closely related to central neurotransmitters. Butanoate metabolism improves energy supply for life activities in the aging body. Cysteine and methionine metabolism contributes to the production of glutathione and taurine and played an antioxidant role. In serum, the regulation of glycerophospholipid metabolism pathway and proline metabolism demonstrated the antioxidant capacity of GFR decoction.

Conclution: In summary, GFR plays a role in delaying aging by regulating central neurotransmitters, cardiovascular function, oxidative stress, energy metabolism, and other aspects of the aging body, which lays a foundation for the application of GFR.
Treatment of an accident of imidacloprid poisoning
Authors: Zeng Mei , Shi Mengdi , Jian Xiangdong , Dong Laidong
Published: July 2024

Objective: Accidental oral imidacloprid poisoning occurred in a family in Shandong, China, in May 2023. This study aimed to analyze the clinical characteristics of this imidacloprid poisoning event and investigated the detection of toxicants.

Methods: Clinical data of four patients with oral imidacloprid poisoning were collected and retrospectively analyzed. The relevant literature was then reviewed.

Results: Four patients from the same family received different oral doses of imidacloprid. The main clinical manifestations were digestive and neurological symptoms, including nausea, vomiting, and varying degrees of consciousness. Laboratory tests showed an increased white blood cell count, neutrophil proportion, and mild elevation of transaminase and urea nitrogen levels in some patients. Following comprehensive treatment, which included hemoperfusion, gastric lavage, total gastrointestinal decontamination, and drug symptomatic treatment, the patient’s symptoms were quickly relieved, and the concentration of imidacloprid in the blood rapidly decreased.

Conclusion: Toxicant detection is an important criterion for the differential diagnosis of poisoning and is helpful for disease assessment, treatment plan formulation, and in determining patient prognosis.
Protective signature of xanthohumol on cognitive function of APP/PS1 mice: a urine metabolomics approach by age
Authors: Liu Wei , Chen Xiao , Zhao Jing , Yang Chen , Huang Guanqin , Zhang Zhen , Liu Jianjun
Published: July 2024

Alzheimer’s disease (AD) has an increasing prevalence, complicated pathogenesis and no effective cure. Emerging evidences show that flavonoid compounds such as xanthohumol (Xn) could play an important role as a dietary supplement or traditional Chinese herbal medicine in the management of diseases such as AD. This study aims to analyze the target molecules of Xn in the prevention and treatment of AD, and its potential mechanism from the perspective of metabolites. APP/PS1 mice 2- and 6-months old were treated with Xn for 3 months, respectively, the younger animals to test for AD-like brain disease prevention and the older animals to address therapeutic effects on the disease. Memantine (Mem) was selected as positive control. Behavioral tests were performed to assess the course of cognitive function. Urine samples were collected and analyzed by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) coupled with online Compound Discoverer software. Morris Water Maze (MWM) tests showed that Xn, like Mem, had a therapeutic but not a preventive effect on cognitive impairment. The expression levels of urinary metabolites appeared to show an opposite trend at different stages of Xn treatment, downregulated in the prevention phase while upregulated in the therapy phase. In addition, the metabolic mechanisms of Xn during preventive treatment were also different from that during therapeutic treatment. The signaling pathways metabolites nordiazepam and genistein were specifically regulated by Xn but not by Mem in the disease prevention stage. The signaling pathway metabolite ascorbic acid was specifically regulated by Xn in the therapeutic stage. In conclusion, dietary treatment with Xn altered the urinary metabolite profile at different stages of administration in APP/PS1 mice. The identified potential endogenous metabolic biomarkers and signal pathways open new avenues to investigate the pathogenesis and treatment of AD.
Crotoxin induces cytotoxic effects in human malignant melanoma cells in both native and detoxified forms
Authors: Almeida Tamires Cunha , Giannotti Karina Cristina , Ribeiro Silva Lorena Morais , Marques-Porto Rafael , DeOcesano-Pereira Carlos , Camargo Lauren , Chudzinski-Tavassi Ana Marisa , Reid Paul , Picolo Gisele
Published: July 2024

Introduction: Melanoma, a highly aggressive skin cancer originating in melanocytes, poses a significant threat due to its metastatic potential. While progress has been made in treating melanoma with targeted therapies and immunotherapies, challenges persist. Crotoxin (CTX), the principal toxin in Crotalus durissus terrificus snake venom, exhibits various biological activities, including anti-tumoral effects across multiple cancers. However, its clinical use is limited by toxicity. Thus, exploring alternatives to mitigate adverse effects is crucial.

Methods and Results: This study investigates the antitumoral potential of CTX in its native and in a detoxified form, in melanoma cells. Firstly, we demonstrated that detoxified CTX presented reduced phospholipase activity. Both forms proved to be more cytotoxic to SK-MEL-28 and MeWo melanoma cells than non-tumoral cells. In SK-MEL-28 cells, where cytotoxic effects were more pronounced, native and detoxified CTX induced increased necrosis and apoptosis rates. We also confirmed the apoptosis death demonstrated by the activation of caspase-3 and 7, and the formation of apoptotic bodies. Furthermore, both CTX caused cell cycle arrest at the G2/M phase, interfering with melanoma cell proliferation. Cell migration and invasion were also suppressed by both CTX. These results confirm the antitumoral potential of CTX.

Discussion: The maintenance of the antiproliferative effects in the detoxified version, with reduced enzymatic activity often liked to harm effects, supports further studies to identify active parts of the molecule responsible for the interesting effects without causing substantial toxic events, contributing to the future use of CTX-derived drugs with safety and efficacy.
Dynamic phenotypic shifts and M2 receptor downregulation in bladder smooth muscle cells induced by mirabegron
Authors: Muderrisoglu A. E. , Ciotkowska A. , Rutz B. , Hu S. , Qian S. , Tamalunas A. , Stief C. G. , Hennenberg M.
Published: July 2024

Introduction

Mirabegron is available for treatment of overactive bladder (OAB). However, mechanisms underlying symptom improvements and long-term effects on bladder smooth muscle cells are uncertain. Contractility and growth of bladder smooth muscle contribute to OAB, and depend on smooth muscle phenotypes, and on muscarinic receptor expression. Here, we examined prolonged exposure to mirabegron (20–48 h) on phenotype markers, muscarinic receptor expression, and phenotype-dependent functions in human bladder smooth muscle cells (hBSMC).

Methods

Expression of markers for contractile (calponin, MYH11) and proliferative (MYH10, vimentin) phenotypes, proliferation (Ki-67), and of muscarinic receptors were assessed by RT-PCR. Proliferation, viability, actin organization and contractions in cultured hBSMC were examined by EdU, CCK-8, phalloidin staining and matrix contraction assays.

Results

Calponin-1 mRNA decreased with 100 nM and 150 nM mirabegron applied for 20 h (0.56–0.6 fold of controls). Decreases were resistant to the β3-AR antagonist L-748,337 (0.34–0.55 fold, 100–150 nM, 20 h). After 40 h, decreases occured in the presence of L-748,337, but not without L-748,337. MYH11 mRNA increased with 150 nM mirabegron (40 h, 1.9 fold). This was partly preserved with L-748,337, but not observed after 20 h mirabegron exposure. Vimentin mRNA reduced with 150 nM mirabegron after 20 h, but not after 40 h, with and without L-748,337 (0.71–0.63 fold). MYH10 mRNA expression remained unaffected by mirabegron. Exposure to 150 nM mirabegron increased Ki-67 mRNA after 20 h in the presence of, but not without L-748,337, and after 40 h without, but not with L-748,337. Proliferation rates and actin organization were stable with 50–150 nM mirabegron (24 h, 48 h). Viability increased significantly after mirabegron exposure for 20 h, and by trend after 40 h, which was fully sensitive to L-748,337. M2 mRNA was reduced by 20 h mirabegron, which was resistant to L-748,337. Carbachol (3 µM) enhanced time-dependent contractions of hBSMC, which was inhibited by mirabegron (150 nM) in late phases (24 h), but not in early phases of contractions.

Conclusion: Mirabegron induces dynamic phenotype alterations and M2 downregulation in hBSMC, which is paralleled by time-shifted anticontractile effects. Phenotype transitions may be involved in improvements of storage symptoms in OAB by mirabegron.
Mitigating citrus fruit cracking: the efficacy of chelated calcium or silicon foliar fertilizers in ‘Okitsu no. 58’ citrus fruit
Authors: Wang Tie , Tan Liping , Chen Zhaofang , Yang Youting , Yuan Ya , Zheng Zhendong , Deng Lijun , Zhang Mingfei , Sun Guochao , He Siya , Wang Jun , Xiong Bo , Wang Zhihui
Published: July 2024

The ‘Okitsu No. 58’ citrus variety is highly prone to fruit cracking, which jeopardizes yield and results in economic losses. In this study, we investigated the impacts of spraying 5 distinct concentrations (0.1, 0.2, 0.3, 0.4, and 0.5 g/L) of chelated calcium (Ca) or silicon (Si) fertilizers at the young fruit stage (60-90 days after flowering, DAF) on fruit cracking and quality in the citrus variety ‘Okitsu No. 58’. The results showed either Ca or Si fertilizer treatments reduced fruit cracking. We found that all Ca and partial Si treatments (0.4 and 0.5 g/L) significantly promoted the accumulation of Ca content in the peel. Notably, Ca or Si treatments significantly reduced polygalacturonase (PG) activity and inhibited the production of water-soluble pectin (WSP) in the peel. Additionally, Ca or Si treatments elevated the superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content of the peels. Changes in these parameters likely contributed to strengthening the durability of peel cell wall constituents, thus enhancing the fruit’s resistance to fruit cracking. Overall, except for the C3 (0.3 g/L of Ca), Ca or Si fertilizers contributed to fruit conventional quality, mainly in terms of higher soluble sugars (SS) and SS/TA (titratable acid). Therefore, our findings will provide a reference for the prevention and control of citrus fruit cracking and the development of new fertilizers.
Variable response of eastern filbert blight resistance sources in New Jersey
Authors: Jacobs Daniel C. , Revord Ronald S. , Capik John M. , Mehlenbacher Shawn A. , Molnar Thomas J.
Published: July 2024

Eastern filbert blight (EFB), caused by Anisogramma anomala, is the primary limiting factor for hazelnut (Corylus sp.) production in the United States. In this study, 82 cultivars and selections shown to be resistant or tolerant to EFB in Oregon were field planted in New Jersey in 2017 and 2019 and evaluated for their EFB response under high disease pressure. The trees carry known single resistance (R) genes with most mapped to their respective linkage groups (LG), including LG2, LG6, and LG7, or they express quantitative resistance (QR, horizontal resistance). Disease incidence and severity was documented, stem cankers counted and measured, and the proportion of diseased wood calculated. The EFB disease response of some cultivars/selections varied considerably between New Jersey and Oregon while others were consistent. Trends were observed in relation to resistance source origin and LGs, which provide insight into durability and usefulness of resistance. In striking contrast to Oregon, nearly all selections with R-genes mapped to LG6, including those carrying the ‘Gasaway’ resistance allele, exhibited severe EFB infections (232 of 266 [87%]). This finding is of consequence since the U.S. hazelnut industry currently relies solely on LG6 resistance for EFB resistance. Further, for the first time, EFB was observed on several selections carrying LG7 resistance, specifically offspring of ‘Ratoli’ from Spain. Interestingly, selections carrying LG7 resistance from origins other than ‘Ratoli’ remained free of EFB, with one exception, all selections carrying LG2 (n=9) resistance also remained free from EFB. Interestingly, the EFB responses of selections expressing QR (n=26) more closely resembled the disease phenotypes they exhibited in Oregon. Overall, the divergence in EFB response between Oregon and New Jersey, where pathogen populations differ, supports the presence of pathogenic variation in A. anomala and highlights potential limitations of using single R-genes to manage the disease. Results also suggest trees expressing QR may be more stable across pathogenic populations.