bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a meta-analysis with trial sequential analysis of randomized controlled trials
Authors: Ren Ji , Wang Jinghe , Wang Yanan , Yang Dongying , Sheng Jianming , Zhu Shili , Liu Yunli , Li Xiaoqi , Liu Wei , Zhang Binbin
Published: January 2025

Background

The combination of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors with chemotherapy (CT) is currently under evaluation as a first-line treatment for advanced or recurrent endometrial cancer (EC). This study sought to assess the efficacy and safety of this therapeutic combination in patients with advanced or recurrent EC.

Methods

We performed an exhaustive review of randomized controlled trials (RCTs) up to September 25, 2024, examining the efficacy and safety of combining PD-1/PD-L1 inhibitors with CT versus CT alone (or plus placebo) in advanced or recurrent EC. Efficacy was measured by progression-free survival (PFS) and overall survival (OS), while safety was assessed by the incidence of any grade or grade ≥ 3 adverse events (AEs). We calculated hazard ratios (HRs) for PFS and OS, as well as risk ratios (RRs) for AEs, each accompanied by 95% confidence intervals (CIs). To evaluate heterogeneity, we employed Cochran’s Q test, I2 statistics, and 95% prediction intervals (PIs). Trial sequential analysis (TSA) was conducted using R Version 4.3.1, STATA Version 12.0, and TSA Version 0.9.5.10 Beta software.

Results

Our analysis incorporated 6 studies, encompassing a total of 2,954 patients. The combination of PD-1/PD-L1 inhibitors with CT significantly improved PFS (HR = 0.617, 95% CI: 0.506-0.752; 95% PI: 0.334-1.140) and OS (HR = 0.774, 95% CI: 0.664-0.902; 95% PI: 0.553-1.083) compared to CT alone (or plus placebo) in the overall population. Subgroup analysis based on mismatch repair (MMR) status revealed pronounced benefits in PFS and OS for patients with deficient MMR (dMMR) (PFS: HR = 0.344, 95% CI: 0.269-0.438; 95% PI: 0.231-0.510; OS: HR = 0.371, 95% CI: 0.245-0.562; 95% PI: 0.025-5.461) compared to those with proficient MMR (pMMR) (PFS: HR = 0.772, 95% CI: 0.627-0.950; 95% PI: 0.394-1.512; OS: HR = 0.996, 95% CI: 0.692-1.435; 95% PI: 0.021-47.662). Although there was no observed difference in the incidence of any grades AEs (RR = 0.994, 95% CI: 0.982-1.006; 95% PI: 0.978-1.009), the risk of grade ≥ 3 AEs was elevated in the group receiving PD-1/PD-L1 inhibitors in combination with CT (RR = 1.132, 95% CI: 1.023-1.252; 95% PI: 0.836-1.532).

Conclusion

The combination of PD-1/PD-L1 inhibitors with CT significantly improved PFS and OS in advanced or recurrent EC patients, with particularly pronounced benefits observed in those with dMMR. Clinicians can tailor treatment strategies according to individual patient characteristics to optimize therapeutic outcomes, while remaining alert to the possibility of AEs in clinical practice.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024595455.
Biomarker combinations from different modalities predict early disability accumulation in multiple sclerosis
Authors: Fleischer Vinzenz , Brummer Tobias , Muthuraman Muthuraman , Steffen Falk , Heldt Milena , Protopapa Maria , Schraad Muriel , Gonzalez-Escamilla Gabriel , Groppa Sergiu , Bittner Stefan , Zipp Frauke
Published: January 2025

Objective

Establishing biomarkers to predict multiple sclerosis (MS) disability accrual has been challenging using a single biomarker approach, likely due to the complex interplay of neuroinflammation and neurodegeneration. Here, we aimed to investigate the prognostic value of single and multimodal biomarker combinations to predict four-year disability progression in patients with MS.

Methods

In total, 111 MS patients were followed up for four years to track disability accumulation based on the Expanded Disability Status Scale (EDSS). Three clinically relevant modalities (MRI, OCT and blood serum) served as sources of potential predictors for disease worsening. Two key measures from each modality were determined and related to subsequent disability progression: lesion volume (LV), gray matter volume (GMV), retinal nerve fiber layer, ganglion cell-inner plexiform layer, serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein. First, receiver operator characteristic (ROC) analyses were performed to identify the discriminative power of individual biomarkers and their combinations. Second, we applied structural equation modeling (SEM) to the single biomarkers in order to determine their causal inter-relationships.

Results

Baseline GMV on its own allowed identification of subsequent EDSS progression based on ROC analysis. All other individual baseline biomarkers were unable to discriminate between progressive and non-progressive patients on their own. When comparing all possible biomarker combinations, the tripartite combination of MRI, OCT and blood biomarkers achieved the highest discriminative accuracy. Finally, predictive causal modeling identified that LV mediates significant parts of the effect of GMV and sNfL on disability progression.

Conclusion

Multimodal biomarkers, i.e. different major surrogates for pathology derived from MRI, OCT and blood, inform about different parts of the disease pathology leading to clinical progression.
Exploring the role of ubiquitination modifications in migraine headaches
Authors: Zhu Qian , Yang Jin , Shi Lei , Zhang Jieying , Zhang Peng , Li Junlong , Song Xiaoli
Published: January 2025

Migraine is a complex neurovascular disorder whose pathogenesis involves activation of the trigeminal vascular system, central and peripheral sensitization, and neuroinflammation. Calcitonin gene-related peptide (CGRP) plays a dominant role and activation of MAPK and NF-κB signaling pathways regulates neuropeptide release, glial cell activation, and amplification of nociceptive signals. Aberrant activation of these pathways drives migraine onset and chronicity. The ubiquitin-proteasome system (UPS) is involved in neurological and inflammatory disorders. ubiquitination in the UPS is achieved through a cascade of enzymes, including Ub-activating enzyme (E1), Ub-coupling enzyme (E2), and Ub-ligase (E3). The aim of this review is to systematically explore the role of ubiquitination in the regulation of MAPK and NF-κB signaling pathways, with a focus on the mechanisms of ubiquitinating enzymes in neuroinflammation and pain signal amplification, and to explore their potential as diagnostics, biomarkers, predictors of response to therapy, and monitoring of chronicity in migraine disease.
Stemness-related gene signatures as a predictive tool for breast cancer radiosensitivity
Authors: Lai Jinzhi , Huang Rongfu , Huang Jingshan
Published: January 2025

Background

Understanding the role of cancer stemness in predicting breast cancer (BRCA) response to radiotherapy is crucial for optimizing treatment outcomes. This study developed a stemness-based signature to identify BRCA patients who are likely to benefit from radiotherapy.

Methods

Gene expression data for BRCA patients were obtained from the TCGA and METABRIC databases, including 920 TCGA-BRCA and 1980 METABRIC-BRCA patients. Univariate and multivariate Cox regression analyses were used to construct a radiosensitivity signature. Immune cell infiltration and pathway enrichment analyses were conducted using ESTIMATE and GSVA methods. The TIDE algorithm and the pRRophetic platform were employed to predict responses to radiotherapy. Radioresistant BRCA cells were examined using a colony formation assay. Key genes identified in the radiosensitivity signature were validated in vitro by qRT-PCR.

Results

By analyzing gene expression data from 920 BRCA samples, we identified a set of 267 stemness-related genes between high and low mRNAsi groups. Based on these genes, a radiosensitivity signature comprising two stemness-related genes (EMILIN1 and CYP4Z1) was constructed, stratifying patients into radiosensitive (RS) and radioresistant (RR) groups. Radiotherapy within the RS group significantly improved prognosis compared to non-radiotherapy patients. This signature was further validated in the METABRIC dataset. Notably, patients in the RS group also exhibited a significantly better response to immunotherapy compared to the RR group. We established a radioresistant BRCA cell line using the MCF-7 breast cancer cell line. A radioresistant breast cancer cell line (MCF-7/IR) was established by progressive exposure to increasing radiation doses. Comparative clonogenic and CCK8 assays demonstrated a radioresistant phenotype in the MCF-7/IR compared to MCF-7. In vitro studies utilizing both the MCF-7/IR and MCF-7 cell lines validated the expression of two radiosensitivity genes.

Conclusion

This study identified a stemness-related gene signature predictive of radiosensitivity in breast cancer. This signature may guide personalized treatment strategies and inform the development of novel radiosensitizing agents.
Hepatic encephalopathy and spontaneous bacterial peritonitis are associated with increased liver-related readmissions in cirrhosis
Authors: Wang Shan , Zhang Lin , Li Jin , Feng Jiajun , Gao Jie , Huang Rui
Published: January 2025

Introduction

Liver disease remains a significant global health concern. In China, the number of patients with liver cirrhosis is estimated to reach 7 million. In addition to the high risk of death, cirrhosis leads to several severe complications. Patients with cirrhosis have significantly longer hospital stays and higher total hospital costs than those without cirrhosis. We aimed to investigate the predictors of readmission among patients with cirrhosis in China.

Materials and methods

We conducted a retrospective study to evaluate adult patients with cirrhosis. Data on various sociodemographic, clinical, and hospitalization characteristics were collected. We defined the primary endpoint as the first liver-related readmission occurring within 30–90 days of initial hospitalization. Adult patients with cirrhosis admitted to our hospital between January 2009 and December 2022 were included. Differences between groups were analyzed using Student’s t-test and chi-square test. Logistic and multiple linear regression analyses were performed to identify predictors associated with readmission and the length of the first hospitalization.

Results

In total, 1,285 patients were diagnosed with cirrhosis. Among these patients, 767 (59.7%) were males, and the mean age was 58.9 ± 12.3 years. Seventy-two (5.6%) and 154 (12.0%) patients were readmitted within 30 and 90 days, respectively. Compared with those who were not readmitted, patients readmitted at 30-day and 90-day had a higher proportion of males, ascites, spontaneous bacterial peritonitis, electrolyte abnormalities, higher Child-Pugh–Turcotte scores, longer initial hospital stays, and higher initial hospitalization costs. Logistic regression analysis indicated that hepatic encephalopathy, spontaneous bacterial peritonitis, diabetes, and ascites were predictors of 30- and 90-day readmission. Hypertension and spontaneous bacterial peritonitis were significant predictors of the length of the first hospitalization.

Conclusion

Patients with cirrhosis presenting with hepatic encephalopathy, ascites, and spontaneous bacterial peritonitis may have a higher risk of rehospitalization.
Untargeted metabolomic analysis uncovers metabolic variability of four Bifidobacterial strains for probiotic development
Authors: Liu Kailong , Yao Guoqiang , Yang Zhan , Huang Tian , Kwok Lai-Yu , Zhang Heping
Published: January 2025

Bifidobacterium species are essential members of the human gut microbiota, playing crucial roles in host health. Variations in the metabolic functions of different Bifidobacterium strains can have distinct health effects, making it essential to understand their metabolic characteristics for the development of targeted probiotic formulations. In this study, we cultivated four selected Bifidobacterium strains from three species: Bifidobacterium animalis subsp. lactis BB-69, Bbm-19, Bifidobacterium brevis BX-18, and Bifidobacterium longum subsp. infantis B8762. We conducted an untargeted comparative metabolomic analysis to investigate the intracellular metabolic profile and functional activities of these strains. A total of 1,340 metabolites were identified, revealing significant variations in their metabolomic profiles. Notably, Bifidobacterium animalis subsp. lactis Bbm-19 showed higher activity in amino acid biosynthesis, while Bifidobacterium animalis subsp. lactis BB-69 exhibited increased activity in secondary bile acid biosynthesis and alpha-linolenic acid metabolism. Bifidobacterium longum subsp. infantis B8762 demonstrated enhanced activity in polycyclic aromatic hydrocarbon degradation, vitamin digestion and absorption, and galactose metabolism. Bifidobacterium breve BX-18 was more active in tryptophan metabolism and pentose and glucuronate interconversions. Targeted analyses of specific metabolites further revealed strain-specific metabolic pathways. This study systematically elucidates the metabolic profile differences among the four investigated Bifidobacterium strains at the untargeted metabolomic level, providing valuable insights into their metabolic characteristics and potential applications in probiotic development.
Preparation and application evaluation of monoclonal antibodies against Monkeypox virus A29 protein
Authors: Xiangjun Ai , Xinlan Zhang , Ye Xu , Chufan Tan , Chen Duan , Nami Liao , Junxi Liu , Yilan Qiu , Defu Hou , Qinglin Wang , Rushi Liu
Published: January 2025

Monkeypox virus (MPXV) is a DNA virus belonging to the Orthopoxvirus genus of the Poxviridae family. It causes symptoms similar to Smallpox virus and is a zoonotic virus with widespread prevalence. Antigen detection is a fast and effective detection method. The MPXV A29 protein not only plays an important role in the virus lifecycle but also serves as a promising target for developing specific antibodies, which have significant potential for application in the diagnosis of MPXV. The coding sequences of the MPXV A29 protein, Cowpox virus (CPXV) 163 protein homolog and Vaccinia virus (VACV) A27 protein homolog were chemically synthesized, and all three recombinant proteins were expressed in Escherichia coli (BL21 Star). Then, the recombinant A29 protein was used as an antigen to immunize BALB/c mice, and a total of 4 monoclonal antibodies against A29 protein were obtained. Using two homologous proteins as reverse screening systems, a specific monoclonal antibody, mAb-25, against the A29 protein was screened. Then, the mAb-25 was used as a coating antibody to pair with other monoclonal antibodies, leading to the identification of a well-matched antibody pair. A chemiluminescence enzyme immunoassay (CLEIA) and immunochromatographic gold assay were subsequently established using the optimal antibody pair. The experimental results indicate that monoclonal antibodies against the A29 protein hold significant potential for application in the diagnosis of MPXV.
Improved jet lag recovery is associated with a weaker molecular biological clock response around the time of expected activity onset
Authors: Boutrin Marie-Claire , Richardson Melissa E. S. , Oriola Feyikemi , Bolo Samira
Published: January 2025

Introduction

Properly timed environmental light input to the suprachiasmatic nucleus (SCN) in the brain is crucial in maintaining the 24-hour biological rhythm (circadian rhythm). However, light exposure at the wrong time of the day-night cycle is disruptive to circadian-regulated behaviors such as the sleep-wake cycle and memory. While factors such as jet lag, variations in day length, and light at night are known disruptors to the timing of activity onset following rest, the molecular consequence of the intersection of multiple disruptions is less understood.

Methods

Here, we expose mice to a jet lag paradigm under two light-dark (LD) conditions (12:12 LD and 8:16 LD) coupled with additional light exposure at night during the recovery period (known as negative masking), previously demonstrated to improve jet lag-related memory loss in mice.

Results

Our results show that jet lag exposure in both LD cycles (to a greater extent in 8:16 LD) increased the fold-change of circadian gene expression in the SCN relative to the dark onset. The further addition of light during the jet lag recovery period reduced typical changes in circadian gene expression in the SCN to minimal levels under both LD cycles.

Discussion

This study uncovers a novel explanation for the impact of multiple disruptive light exposures on gene expression of the molecular SCN clock in the brain.
Enhancing sleep quality in synucleinopathies through physical exercise
Authors: Canonichesi Jacopo , Bellingacci Laura , Rivelli Francesco , Tozzi Alessandro
Published: January 2025

During sleep, several crucial processes for brain homeostasis occur, including the rearrangement of synaptic connections, which is essential for memory formation and updating. Sleep also facilitates the removal of neurotoxic waste products, the accumulation of which plays a key role in neurodegeneration. Various neural components and environmental factors regulate and influence the physiological transition between wakefulness and sleep. Disruptions in this complex system form the basis of sleep disorders, as commonly observed in synucleinopathies. Synucleinopathies are neurodegenerative disorders characterized by abnormal build-up of α-synuclein protein aggregates in the brain. This accumulation in different brain regions leads to a spectrum of clinical manifestations, including hypokinesia, cognitive impairment, psychiatric symptoms, and neurovegetative disturbances. Sleep disorders are highly prevalent in individuals with synucleinopathies, and they not only affect the overall well-being of patients but also directly contribute to disease severity and progression. Therefore, it is crucial to develop effective therapeutic strategies to improve sleep quality in these patients. Adequate sleep is vital for brain health, and the role of synucleinopathies in disrupting sleep patterns must be taken into account. In this context, it is essential to explore the role of physical exercise as a potential non-pharmacological intervention to manage sleep disorders in individuals with synucleinopathies. The current evidence on the efficacy of exercise programs to enhance sleep quality in this patient population is discussed.
EEG electrode setup optimization using feature extraction techniques for neonatal sleep state classification
Authors: Siddiqa Hafza Ayesha , Qureshi Muhammad Farrukh , Khurshid Arsalan , Xu Yan , Wang Laishuan , Abbasi Saadullah Farooq , Chen Chen , Chen Wei
Published: January 2025

An optimal arrangement of electrodes during data collection is essential for gaining a deeper understanding of neonatal sleep and assessing cognitive health in order to reduce technical complexity and reduce skin irritation risks. Using electroencephalography (EEG) data, a long-short-term memory (LSTM) classifier categorizes neonatal sleep states. An 16,803 30-second segment was collected from 64 infants between 36 and 43 weeks of age at Fudan University Children's Hospital to train and test the proposed model. To enhance the performance of an LSTM-based classification model, 94 linear and nonlinear features in the time and frequency domains with three novel features (Detrended Fluctuation Analysis (DFA), Lyapunov exponent, and multiscale fluctuation entropy) are extracted. An imbalance between classes is solved using the SMOTE technique. In addition, the most significant features are identified and prioritized using principal component analysis (PCA). In comparison to other single channels, the C3 channel has an accuracy value of 80.75% ± 0.82%, with a kappa value of 0.76. Classification accuracy for four left-side electrodes is higher (82.71% ± 0.88%) than for four right-side electrodes (81.14% ± 0.77%), while kappa values are respectively 0.78 and 0.76. Study results suggest that specific EEG channels play an important role in determining sleep stage classification, as well as suggesting optimal electrode configuration. Moreover, this research can be used to improve neonatal care by monitoring sleep, which can allow early detection of sleep disorders. As a result, this study captures information effectively using a single channel, reducing computing load and maintaining performance at the same time. With the incorporation of time and frequency-domain linear and nonlinear features into sleep staging, newborn sleep dynamics and irregularities can be better understood.
Successful treatment of generalized myasthenia gravis with telitacicept: a Chinese case series and literature review
Authors: Song Xiaodong , He Yang , Jiang Hong , Yu Yao , Sun Yue , Zhang Zhaoxu
Published: January 2025

Background

Despite existing treatments of generalized myasthenia gravis (gMG), there remains a need for more effective therapies with fewer side effects. Telitacicept, targeting B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), emerges as a potential novel therapy for gMG.

Case presentation

In our study, four patients with gMG to standard treatments underwent an 8-week course of telitacicept monotherapy. Post-treatment, all patients exhibited satisfactory improvements. The Myasthenia Gravis Foundation of America Quantitative Myasthenia Gravis (MGFA-QMG) scores, 15-item Myasthenia Gravis Quality of Life (MGQOL-15) scores, and MG-associated Activities of Daily Living (MG-ADL) scores showed a marked reduction, indicating decreased disease severity and enhanced quality of life. Additionally, immunological assessments revealed a decrease in CD19+B lymphocyte counts and acetylcholine receptor (AChR) antibodies. Only one patient reported a mild, transient injection reaction.

Conclusion

Favorable clinical improvement and mild adverse events for gMG in treated with telitacicept were observed. However, larger-scale and longer-term studies are necessary to confirm these results and fully establish the role of telitacicept in the treatment of gMG.
Linear association between high-sensitivity C-reactive protein and postoperative delirium after general anesthesia: a cross-sectional study
Authors: Qin Xiao , Ren Junming , Xing Chunping , Chen Lijiao , Wang Renjie , Tian Shouyuan
Published: January 2025

Objective

To investigate the association between high-sensitivity C-reactive protein (Hs-CRP) levels and the risk of postoperative delirium (POD) following general anesthesia.

Methods

This retrospective cross-sectional study included 644 patients who underwent general anesthesia. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between Hs-CRP and POD, with subgroup analyses used to assess stratified associations. Receiver operator characteristic (ROC) curve analysis was employed to assess the predictive efficacy of Hs-CRP for POD. Restricted cubic spline (RCS) analysis was conducted to explore the linear relationship between the log-transformed Hs-CRP (Log10Hs-CRP) and POD risk.

Results

The total population consisted of 644 individuals with a mean age of 64.02 ± 13.20 years, 506 (78.60%) of whom were male, and 114 patients (17.7%) had POD. Compared to the lower Hs-CRP group, patients in the higher Hs-CRP group exhibited higher age, heart rate, white blood cell count, blood urea nitrogen, creatinine, uric acid, fasting glucose, hemoglobin A1c, fibrinogen, D-dimer, and a higher prevalence of CKD, but lower hemoglobin, high-density lipoprotein cholesterol, albumin and estimated glomerular filtration rate. Additionally, the prevalence of POD was higher in the higher Hs-CRP group (24.7% vs. 9.5%, p < 0.001). Multivariate logistic regression confirmed that elevated Hs-CRP and its forms (Log10Hs-CRP, standardized Hs-CRP, and higher Hs-CRP group) consistently increased the risk of POD across all adjusted models (p < 0.05). Stratified analyses further highlighted significant associations between Hs-CRP and POD in specific subgroups, notably in patients aged ≥65 years, female patients, and those with or without hypertension, diabetes, or stroke history, and without chronic kidney disease (p < 0.05). ROC curve analysis demonstrated that Hs-CRP had a significant predictive ability for POD in the overall population (AUC = 0.646), as well as in male (AUC = 0.644) and female patients (AUC = 0.654). Additionally, RCS analysis indicated a linear positive association between Log10Hs-CRP and POD risk (p = 0.003, nonlinear p = 0.896).

Conclusion

Elevated Hs-CRP levels are significantly associated with an increased risk of POD following general anesthesia.
Electromyographic correlates of effortful listening in the vestigial auriculomotor system
Authors: Schroeer Andreas , Corona-Strauss Farah I. , Hannemann Ronny , Hackley Steven A. , Strauss Daniel J.
Published: January 2025

Recently, electromyographic (EMG) signals of auricular muscles have been shown to be an indicator of spatial auditory attention in humans, based on a vestigial pinna-orienting system. Because spatial auditory attention in a competing speaker task is closely related to the more generalized concept of attentional effort in listening, the current study investigated the possibility that the EMG activity of auricular muscles could also reflect correlates of effortful listening in general. Twenty participants were recruited. EMG signals from the left and right superior and posterior auricular muscles (SAM, PAM) were recorded while participants attended a target podcast in a competing speaker paradigm. Three different conditions, each more difficult and requiring a higher amount of effortful listening, were generated by varying the number and pitch of distractor streams, as well as the signal-to-noise ratio. All audio streams were either presented from a loudspeaker placed in front of the participants (0°), or in the back (180°). Overall, averaged PAM activity was not affected by different levels of effortful listening, but was significantly larger when stimuli were presented from the back, as opposed to the front. Averaged SAM activity, however, was significantly larger in the most difficult condition, which required the largest amount of effort, compared to the easier conditions, but was not affected by stimulus direction. We interpret the increased SAM activity to be the response of the vestigial pinna–orienting system to an effortful stream segregation task.
Development and validation of a food and nutrition literacy questionnaire for Chinese parents of children with functional constipation (FNLQ-p)
Authors: Yang Jie , Wang Hui , Shen Yanchi , Yang Hui , Huang Yan , Cao Jinjin
Published: January 2025

Objectives

Childhood functional constipation is a widespread condition with a global prevalence. Dietary interventions play a crucial role in the management of childhood constipation. Hence, the development and validation of a specialized food and nutrition literacy assessment tool for parents of school-aged children with functional constipation is of paramount significance.

Methods

On the basis of literature review, the first draft was formed, and the results of expert correspondence and pre survey were combined to delete and modify the first draft. In the second stage, 459 parents of school-age children with constipation were invited to fill out the questionnaire. Item analysis, exploratory factor analysis, and confirmatory factor analysis were then conducted to assess the questionnaire's reliability and validity.

Results

The final scale comprises 4 dimensions and 25 items. Exploratory factor analysis extracted four common factors (nutrition knowledge, nutrition skills, nutrition interaction, nutrition evaluation), and the cumulative variance contribution rate was 64. 532%. The content validity index (I-CVI) of each item level is 0.86–1, the content validity index (S-CVI) at the scale level is 0.96. The overall Cronbach'sα coefficient was 0.85. Confirmatory factor analysis supported the four-factor structure derived from exploratory analysis, with all relevant fit indices meeting standard criteria.

Conclusions

The food and nutrition literacy questionnaire developed in our study had good validity and reliability, making it a useful tool for assessing the food and nutrition literacy among parents of school-aged children diagnosed with functional constipation.
Risk factors for pelvic lymph node metastasis in cervical cancer: a retrospective analysis of 186 patients
Authors: Sun Xingyu , He Lijuan , Wang Shaohua
Published: January 2025

Background

Pelvic lymph node metastasis is a critical factor influencing prognosis and treatment strategies in cervical cancer patients. This study aimed to identify significant clinical and pathological risk factors associated with pelvic lymph node metastasis in patients with cervical cancer.

Methods

We conducted a retrospective analysis of 186 cervical cancer patients treated at the Affiliated Hospital, Southwest Medical University from January 2010 to December 2020. Patients were divided into two groups: those with pelvic lymph node metastasis (n=40) and those without (n=146). Data on demographics, clinical characteristics, pathological features, and treatment modalities were collected. Statistical analysis included t-tests, chi-square tests, and logistic regression to evaluate potential risk factors for lymph node metastasis.

Results

Patients with pelvic lymph node metastasis were significantly older (mean age 52.5 ± 8.3 years) than those without metastasis (mean age 48.7 ± 10.2 years; p=0.023). High-risk HPV positivity was significantly associated with lymph node metastasis (75% vs. 41%, p=0.001). Lymphovascular invasion was observed in 75% of the metastatic group compared to 24.7% in the non-metastatic group (p<0.001). Tumor size >4 cm was more frequent in patients with metastasis (50% vs. 12.3%, p<0.001). Multivariate logistic regression analysis identified high-risk HPV infection (OR 4.13, 95% CI: 2.09-8.17, p<0.001), lymphovascular invasion (OR 7.87, 95% CI: 4.05-15.29, p<0.001), and tumor size >4 cm (OR 6.24, 95% CI: 3.24-12.02, p<0.001) as independent risk factors for pelvic lymph node metastasis.

Conclusion

This study identifies several independent risk factors for pelvic lymph node metastasis in cervical cancer, including high-risk HPV infection, lymphovascular invasion, and tumor size greater than 4 cm. These findings can help guide clinical decision-making and individualized treatment planning, improving outcomes for patients with cervical cancer. Further prospective studies are warranted to validate these findings.
A narrative review of the literature on the pediatric orthopedic management of fibrous dysplasia
Authors: Paris Elio , De Marco Giacomo , Vazquez Oscar , Steiger Christina , Boudabbous Sana , Dayer Romain , Ceroni Dimitri
Published: January 2025

Fibrous dysplasia is a congenital, non-inherited, benign intramedullary bone lesion in which the normal bone marrow is replaced by abnormal fibro-osseous tissue. The disorder can be monostotic (involving a single bone) or polyostotic (involving multiple bones). As the abnormal fibro-osseous tissue compromises the mechanical strength of bone, it can result in pain, deformity, fractures, or abnormalities in bone mechanics with inappropriate bone alignment. This narrative review attempts to summarize more than 20 years of observations of patients with FD to help pediatric orthopedists establish a care framework that can improve its identification, understand the impact that endocrinopathies can have on its clinical presentation, and optimize the management of bone disorders. Our focus is specifically on orthopedic manifestations of FD and modern management alternatives. The past 20 years have provided major advances in understanding of fibrous dysplasia (FD), and it is clear that the pediatric orthopedist's role remains highly relevant in the management of all types of FD. Surgical treatment remains appropriate when pain is unresponsive to other medical treatments, when a pathological fracture is impending or has happened, when a deformity is worsening or has formed, or when there is a suspicion of malignant transformation. The pediatric orthopedist must be aware, therefore, of the particularities of the different bones on which they may be called to intervene, and they should give very careful consideration to their operative strategy, which must be adjusted to the biological and static characteristics of the bone.
Mechanism of mTOR/RILP-regulated autophagic flux in increased susceptibility to myocardial ischemia-reperfusion in diabetic mice
Authors: Zhao Jiyao , Shi Wei , Zheng Yan , Wang Junjie , Yuan Muzhao , Anwar Yultuz , He Yuxuan , Ma Haiping , Wu Jianjiang
Published: January 2025

Background

The increased myocardial vulnerability that occurs in diabetic patients following an ischemia-reperfusion injury (I/RI) represents a significant perioperative safety risk. A comprehensive understanding of the intrinsic mechanisms underlying this phenomenon is therefore of paramount importance.

Purposes

The objective of this study is to investigate the potential mechanism of action between impaired autophagic flux and increased vulnerability in diabetic myocardium. This will provide a foundation for the clinical search for effective preventive and curative measures.

Methods

The transcriptomic alterations in autophagy-related genes following myocardial exposure to I/RI were analyzed by single-cell sequencing. This was followed by the validation of potential mechanisms of action between impaired autophagic flux and increased susceptibility at the cellular and animal levels, respectively.

Results

After I/RI in diabetic myocardium, there was a significant increase in the number of CM1 subgroups and a specific downregulation of 239 autophagy-related genes led by RILP. HE staining revealed that myocardial injury was exacerbated in diabetic mice subjected to I/RI. Transmission electron microscopy revealed that the accumulation of autophagic vesicles in cardiomyocytes of diabetic mice resulted in impaired autophagic flux. qRT-PCR revealed that the expression of RILP was significantly reduced in diabetic mice subjected to I/RI. WB showed that P62 was significantly increased and RILP was significantly decreased in diabetic mice subjected to I/RI compared to healthy mice. Inhibition of mTOR during hypoxia/reoxygenation (H/R) injury restored RILP expression and attenuated cellular injury in cardiomyocytes cultured with high glucose.

Conclusion

Following I/RI in diabetic myocardium, an increase in the CM1 subpopulation and a reduction in RILP expression result in impaired autophagic flux. Regulation of the mTOR/RILP pathway can restore impaired autophagic flux and improve myocardial vulnerability, thereby exerting cardioprotective effects.
Targeted ErbB4 receptor activation prevents D-galactose-induced neuronal senescence via inhibiting ferroptosis pathway
Authors: Dao Ji-Ji , Zhang Wei , Liu Chong , Li Qian , Qiao Chen-Meng , Cui Chun , Shen Yan-Qin , Chen Shuang-Xi , Zhao Wei-Jiang
Published: January 2025

Background

Neuronal senescence is a common pathological feature of various neurodegenerative diseases, with ferroptosis playing a significant role. This study aims to investigate the role of ErbB4 receptor activation in preventing D-Galactose (D-gal)-induced neuronal senescence.

Methods

Mice subjected to D-gal-induced aging were administered a small molecule ErbB4 receptor agonist (E4A), identified via virtual screening, melatonin, or a combination of both. Behavioral assessments were conducted to evaluate therapeutic efficacy in memory and cognitive functions. Immunofluorescence staining, western blot, and biochemical assays were primarily employed to assess changes in both senescence- and ferroptosis-related molecules in mouse hippocampal tissues in response to each treatment. Additionally, mouse hippocampal HT22 neuronal cell cultures were utilized to corroborate the in vivo findings.

Results

The targeted activation of ErbB4 receptor by E4A significantly ameliorated the behavioral deficits induced by D-gal in mice, demonstrating an effect comparable to that of melatonin, a natural inhibitor of in vivo senescence and ferroptosis. Both E4A and melatonin mitigated D-gal-induced aging in hippocampal neurons of mice. This was evidenced by the upregulation of Lamin B1 and the downregulation of P53, P21, P16, GFAP, and Iba-1 expression levels. Moreover, D-gal treatment markedly decreased the protein expression of the ferroptosis inhibitor Nrf2 while augmenting the expression of the ferroptosis promoter TFRC. These alterations were partially reversed by the individual administration of E4A and melatonin. In vitro studies further corroborated that D-gal treatment significantly and concurrently induced the expression of senescence markers and ferroptosis promoters. However, both E4A and melatonin were able to significantly reverse these changes. Additionally, E4A markedly ameliorated Erastin-induced ferroptosis in mouse hippocampal neuronal cells.

Conlusion

Our findings suggest that targeted activation of ErbB4 receptor may be a viable strategy for treating neuronal senescence by inhibiting ferroptosis, thereby offering a potential therapeutic avenue for senescence-associated neurodegenerative diseases.
Cannabinoid receptor 2 selective agonist ameliorates adjuvant-induced arthritis by modulating the balance between Treg and Th17 cells
Authors: Tian Na , Yang Cui , Du Yu , Chen Miao , Li Bin , Li Dan , Dai Sheng-Ming
Published: January 2025

Background

Adjuvant-induced arthritis (AIA) serves as a classic model for rheumatoid arthritis (RA), typified by inflammatory cell infiltration and joint damage. This study explores the therapeutic efficacy of HU-308, a CB2 receptor-specific agonist, on inflammation and immune balance in AIA.

Methods

AIA was induced in mice by CFA injection. AIA mice were treated with HU-308 or vehicle, and effects on paw swelling, spleen index, histopathology, and immune cell profiles were evaluated. Flow cytometry, in vitro differentiation assays, and Western blot analysis were performed to examine Th17 and Treg cells, as well as signaling pathways involved in their differentiation.

Results

HU-308 reduced paw swelling, lowered spleen index, and preserved joint integrity in AIA mice, mitigating inflammatory cell infiltration and bone erosion. Flow cytometry revealed that HU-308 restored the Th17/Treg imbalance in AIA, decreasing Th17 cell frequency and enhancing Treg cell infiltration. In vitro assays confirmed HU-308s role in promoting Treg differentiation and inhibiting Th17 polarization. Western blot analysis indicated that HU-308 modulated immune balance through the JAK/STAT5 and TGF-β/SMAD signaling pathways, increasing Foxp3 and TGF-β expression.

Conclusion

HU-308 demonstrates significant anti-inflammatory effects in AIA by restoring Th17/Treg balance and reducing joint damage. The findings indicate that HU-308 holds potential as an immunomodulatory agent for RA, providing valuable insights into CB2-mediated therapeutic strategies for autoimmune diseases.
Yishenyangsui granule for degenerative cervical myelopathy: a randomized, double-blind, placebo-controlled trial with long-term follow-up
Authors: Yin He , Chen Xin , Liu Zhiwei , Xu Bo , Jin Zhefeng , Liu Yan , Qi Baoyu , Tang Bin , Wang Ping , Xu Fanping , Wei Xu , Yu Jie , Zhu Liguo
Published: January 2025

Objective

This randomized controlled trial aims to evaluate the efficacy and safety of Yishenyangsui granule for treating Degenerative Cervical Myelopathy.

Materials and methods

A randomized, double-blind, placebo-controlled clinical trial was conducted with 152 participants recruited from three centers and randomly assigned to receive either Yishenyangsui granule or placebo. The Japanese Orthopaedic Association (JOA) score and Neck Disability Index (NDI) score were evaluated for 32 weeks. Patient-reported outcomes including surgical treatment data, re-treatment data, and patient-reported condition were collected for long-term follow-up. This trial was approved by the ethics committee of WangJing Hospital of China Academy of Chinese Medical Sciences (WJEC-KT-2016-004-P001) and was registered at the Chinese Clinical Trials Registry (ChiCTR-INR-16009723) on 03 November 2016 (Check out at https://www.chictr.org.cn/indexEN.html for a more comprehensive overview).

Results

The results showed that the improvement in JOA score at week 8 was significantly better in the Yishenyangsui granule group than in the placebo group (1.47 vs. 0.43; P < 0.001). Furthermore, improvements in motor function of upper/lower extremities, sensory function of upper extremities, reading ability, and recreation domain scores were also significantly superior in the Yishenyangsui granule group compared to the placebo group (P < 0.05). Long-term follow-up outcomes revealed no statistical differences between groups regarding surgical treatment data or patient-reported condition (P > 0.05). However, there was a significant difference detected in re-treatment data between groups with a lower rate observed among those receiving Yishenyangsui granule compared to those receiving placebo [25 (43.10%) vs. 40 (68.97%); P = 0.033], indicating its effectiveness for treating mild-to-moderate Degenerative Cervical Myelopathy.

Conclusion

Yishenyangsui granule was effective in treating mild to moderate Degenerative Cervical Myelopathy. The participants have improved long-term outcomes.

Clinical Trials Registration

https://www.chictr.org.cn/indexEN.html, identifier ChiCTR-INR-16009723.
Consistent analyses for determination of the point-nucleon distributions by electron and proton scattering
Authors: Suzuki Toshio , Danjo Rika , Suda Toshimi , Matsuzaki Masayuki , Wakasa Tomotsugu
Published: January 2025

Electron scattering cross section, as well as proton scattering cross section, observes the point-proton and the point-neutron distributions, ρτ(r),(τ=p,n), but both cross sections are not able to determine them separately. If they are analyzed consistently with each other, there is a possibility to determine them with less ambiguity. The consistency can be examined through the moments of the charge distribution, ρc(r), which linearly depend on the moments of the point-proton and -neutron distributions, ρτ(r), (τ=p,n). The fourth moment, ⟨ r4 ⟩c, of ρc(r) in 208Pb observed in electron scattering is well-reproduced by the mean square radii, ⟨ r2 ⟩τ, of ρτ(r) obtained consistently in the non-relativistic analyses of electron and proton scattering cross sections. The regression analyses of the non-relativistic mean-field models reproduce well those values of the moments.
Cerebral microvascular density, blood-brain barrier permeability, and support for neuroinflammation indicate early aging in a Marfan syndrome mouse model
Authors: Curry-Koski Tala , Curtin Liam P. , Esfandiarei Mitra , Thomas Theresa Currier
Published: January 2025

Introduction

Marfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 (Fbn1), where a Fbn1 missense mutation (Fbn1C1039G/+) can result in systemic increases in the bioavailability and signaling of transforming growth factor-β (TGF-β). In a well-established mouse model of MFS (Fbn1C1041G/+), pre-mature aging of the aortic wall and the progression of aortic root aneurysm are observed by 6-month-of-age. TGF-β signaling has been implicated in cerebrovascular dysfunction, loss of blood-brain barrier (BBB) integrity, and age-related neuroinflammation. We have reported that pre-mature vascular aging in MFS mice could extend to cerebrovasculature, where peak blood flow velocity in the posterior cerebral artery (PCA) of 6-month-old (6M) MFS mice was reduced, similarly to 12-month-old (12M) control mice. Case studies of MFS patients have documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well as headaches and migraines, with reported incidences of pain and chronic fatigue. Despite these significant clinical observations, investigation into cerebrovascular dysfunction and neuropathology in MFS remains limited.

Methods

Using 6M-control (C57BL/6) and 6M-MFS (Fbn1C1041G/+) and healthy 12M-control male and female mice, we test the hypothesis that abnormal Fbn1 protein expression is associated with altered cerebral microvascular density, BBB permeability, and neuroinflammation in the PCA-perfused hippocampus, all indicative of a pre-mature aging brain phenotype. Glut1 immunostaining was used to quantify microvascular density, IgG staining to assess BBB permeability, and microglial counts to evaluate neuroinflammation.

Results

Using Glut1 staining, 6M-MFS mice and 12M-CTRL similarly present decreased microvascular density in the dentate gyrus (DG), cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) regions of the hippocampus. 6M-MFS mice exhibit increased BBB permeability in the DG and CA3 as evident by Immunoglobulin G (IgG) staining. No differences were detected between 6M and 12M-CTRL mice. 6M-MFS mice show a higher number of microglia in the hippocampus compared to age-matched control mice, a pattern resembling that of 12M-CTRL mice.

Discussion

This study represents the first known investigation into neuropathology in a mouse model of MFS and indicates that the pathophysiology underlying MFS leads to a systemic pre-mature aging phenotype. This study is crucial for identifying and understanding MFS-associated neurovascular and neurological abnormalities, underscoring the need for research aimed at improving the quality of life and managing pre-mature aging symptoms in MFS and related connective tissue disorders.
Effects of dribbling restrictions in small-sided games on aerobic and anaerobic fitness in youth basketball players
Authors: Li Mingbang , Tan Liang , Wu Hong , Wu Jianwei
Published: January 2025

Introduction

Imposing constraints such as limiting dribbling in smallsided games (SSGs) is known to increase physiological and locomotor demands. However, the long-term effects on physical adaptations remain unexplored. This experimental study aimed to compare the impact of free-play SSGs (freeD) and limited-dribbling SSGs (limitedD) in SSGs on the aerobic and anaerobic adaptations of youth basketball players.

Methods

Forty-five youth basketball players (aged 15.7 ± 0.6 years, with 4.2 ± 0.7 years of experience) were randomly assigned to two experimental groups (freeD and limitedD) and a control group (not exposed to SSG interventions). During the eight-week intervention, the experimental groups participated in additional SSG sessions twice a week, with session work time durations ranging from 12 to 16 min. Both experimental groups followed identical SSG formats, court dimensions, and training regimens, with the only difference being that one group participated in free play while the other group was prohibited from dribbling during progression. Aerobic capacity was assessed using the Yo-Yo Intermittent Recovery Test Level 1 (YYIRT), while the 30-second Wingate Test measured peak power output (PPO) and average power output (APO) at baseline and post-intervention. Statistical analysis was conducted using a mixed ANOVA to examine the interactions between time and group.

Results

Comparisons of YYIRT between groups at post-intervention revealed that limitedD performed significantly better than both freeD (p = 0.035; d = 1.038) and the control group (p < 0.001; d = 2.050), while freeD also showed significantly better performance (p = 0.021; d = 0.082) than the control group. Regarding PPO, limitedD was significantly better than the control group (p = 0.043; d = 0.943). Finally, for APO, limitedD was significantly better than both freeD (p = 0.043; d = 0.928) and the control group (p < 0.001; d = 1.793), while freeD also exhibited significantly better performance than the control group (p = 0.046; d = 0.036).

Conclusions

Limiting dribbling in basketball SSGs is more effective than free play. This makes it a potentially valuable strategy for designing SSGs in basketball training. Coaches may consider incorporating limited-dribbling conditions into SSGs to boost the intensity of training sessions, improve cardiovascular endurance, and enhance anaerobic power.