bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrahigh-resolution 7-Tesla anatomic magnetic resonance imaging and diffusion tensor imaging of ex vivo formalin-fixed human brainstem-cerebellum complex
Authors: Hanalioglu Sahin , Bahadir Siyar , Ozak Ahmet C. , Yangi Kivanc , Mignucci-Jiménez Giancarlo , Gurses Muhammet Enes , Fuentes Alberto , Mathew Ethan , Graham Dakota T. , Altug Muhammed Yakup , Gok Egemen , Turner Gregory H. , Lawton Michael T. , Preul Mark C. 
Published: November 2024

IntroductionBrain cross-sectional images, tractography, and segmentation are valuable resources for neuroanatomical education and research but are also crucial for neurosurgical planning that may improve outcomes in cerebellar and brainstem interventions. Although ultrahigh-resolution 7-Tesla (7T) magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) reveal such structural brain details in living or fresh unpreserved brain tissue, imaging standard formalin-preserved cadaveric brain specimens often used for neurosurgical anatomic studies has proven difficult. This study sought to develop a practical protocol to provide anatomic information and tractography results of an ex vivo human brainstem-cerebellum specimen.Materials and methodsA protocol was developed for specimen preparation and 7T MRI with image postprocessing on a combined brainstem-cerebellum specimen obtained from an 85-year-old male cadaver with a postmortem interval of 1 week that was stored in formalin for 6 months. Anatomic image series were acquired for detailed views and diffusion tractography to map neural pathways and segment major anatomic structures within the brainstem and cerebellum.ResultsComplex white matter tracts were visualized with high-precision segmentation of crucial brainstem structures, delineating the brainstem-cerebellum and mesencephalic-dentate connectivity, including the Guillain-Mollaret triangle. Tractography and fractional anisotropy mapping revealed the complexities of white matter fiber pathways, including the superior, middle, and inferior cerebellar peduncles and visible decussating fibers. 3-dimensional (3D) reconstruction and quantitative and qualitative analyses verified the anatomical precision of the imaging relative to a standard brain space.DiscussionThis novel imaging protocol successfully captured the intricate 3D architecture of the brainstem-cerebellum network. The protocol, unique in several respects (including tissue preservation and rehydration times, choice of solutions, preferred sequences, voxel sizes, and diffusion directions) aimed to balance high resolution and practical scan times. This approach provided detailed neuroanatomical imaging while avoiding impractically long scan times. The extended postmortem and fixation intervals did not compromise the diffusion imaging quality. Moreover, the combination of time efficiency and ultrahigh-resolution imaging results makes this protocol a strong candidate for optimal use in detailed neuroanatomical studies, particularly in presurgical trajectory planning.
A randomized, double-blind, placebo-controlled clinical trial to evaluate pregabalin efficacy in the treatment of behavioral and psychological symptoms of dementia in patients with Alzheimer’s disease
Authors: Maleki Leyla , Mohammadian Fatemeh , Panahishokouh Mahsa , Mohebbi Niayesh 
Published: November 2024

BackgroundBehavioral and Psychological Symptoms of Dementia (BPSD) are common during Alzheimer’s disease and cause severe problems for patients and their caregivers.ObjectivesTo assess the therapeutic efficacy of Pregabalin in comparison with a placebo in treating BPSD in patients with Alzheimer’s disease (AD) visiting the memory and cognition clinic of Roozbeh Psychiatric Hospital in Tehran, Iran.MethodsA 12-week double-blind, randomized comparison of Pregabalin and placebo treatments was conducted in 53 patients with DSM-V diagnosis of dementia of Alzheimer’s type. They were randomly assigned to receive Pregabalin (doses: 50 titrated up to 300 mg/day) or a placebo. Clinical response was evaluated using the Neuropsychiatric Inventory (NPI), and the Behavioral Pathology in AD Rating Scale (BEHAVE-AD) scores compared with baseline. Side effects were also recorded carefully.ResultsPatients receiving Pregabalin had better outcomes in comparison with patients receiving a placebo regarding both NPI and BEHAVE-AD scores after 12 weeks (p-value = 0.009 for NPI and p-value = 0.003 for BEHAVE-AD). There was also a statistically significant decrease in the treatment group depression sub-score regarding NPI and BEHAVE-AD (respectively, p-value =0.000, 0.003). The caregiver burden sub-score of the NPI test was also lower in patients receiving pregabalin (p-value = 0.000). There was no statistically significant difference between the occurrence of adverse effects between the two groups (p-value = 1.00).ConclusionPregabalin at a dose of 300 mg/day was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms in patients with AD. Pregabalin could be considered a favorable choice for treating BPSD in adults with mild to moderate stages of Alzheimer ‘s-type dementia, considering its befitting safety profile.Clinical trial registrationhttps://www.irct.ir/trial/52750, identifier IRCT20201201049553N1
The causal effects of dietary component intake and blood metabolites on risk of delirium: a Mendelian randomization study
Authors: Zhu Qian , Liu Yingjian , Li Xiaona , Wang Chao , Xie Zhenyan , Guo Gongjie , Gu Wenqing , Hu Yongzhen , Wei Xiaobing , Wen Yiqi , Jing Yingchao , Zhong Shilong , Lin Li , Li Xuesong 
Published: November 2024

BackgroundsGrowing evidence has indicated that the nutritional quality of dietary intake and alterations in blood metabolites were related to human brain activity. This study aims to investigate the causal relationship between dietary component intake, blood metabolites, and delirium risks.MethodsWe performed Mendelian randomization (MR) analysis using genetic variants as instrumental variables for dietary component intake, blood metabolites, and delirium. Inverse variance weighting, maximum likelihood, weighted median, weighted mode, and MR-Egger methods were used for statistical analyses.ResultsWe found that genetic prediction of salt added to food (odds ratio [OR] 1.715, 95% confidence interval [CI] 1.239–2.374, p = 0.001) significantly increased the risks of delirium, while low-fat polyunsaturated margarine used in cooking (OR 0.044, 95%CI 0.004–0.432, p = 0.007), cheese intake (OR 0.691, 95%CI 0.500–0.955, p = 0.025) and coffee intake (OR 0.595, 95%CI 0.370–0.956, p = 0.032) was suggestively associated with decreased risks of delirium. Moreover, increased blood 1-stearoylglycerol levels (OR 0.187, 95%CI 0.080–0.435, p = 9.97E-05) significantly contributed to reducing the risks of delirium. 3-methoxytyrosine (OR 0.359, 95%CI 0.154–0.841, p = 0.018) also has the potential to decrease the risk of delirium.ConclusionOur study highlights the potential causal effect relationships of dietary component intake and blood metabolites on the risk of delirium, which potentially provides novel insights into targeted dietary prevention strategies or biomarkers for delirium.
The burden of acute malnutrition among children under five in conflict-afflicted Gaza strip: prevalence and associated factors
Authors: Albelbeisi Ahmed , Zinszer Kate , El Bilbeisi Abdel Hamid , Abuzerr Samer 
Published: November 2024

BackgroundThis study aims to assess the prevalence and associated factors of Severe Acute Malnutrition (SAM) and Moderate Acute Malnutrition (MAM) among children in this region during a period of conflict.MethodsA cross-sectional study was conducted with a sample of 1,200 children under 5 years old, selected through stratified random sampling from three governorates in the Gaza Strip. Data were collected using structured interviews and physical examinations, including Mid-Upper Arm Circumference (MUAC) measurements to determine nutritional status based on established cut-off points. Statistical analyses were performed using IBM-SPSS, version 26.ResultsAmong the 1,200 children screened, 605 (50.8%) were males and 595 (49.2%) were females. The age distribution of the children screened showed that 48.4% (n = 581) fall within the range of 6 months to &lt;24 months category and 51.6% (n = 619) fall within the range of 24–60 months. Overall, 58.3% of children live in schools, 26.6% live in houses, and 15.1% reside in tents. The overall prevalence of malnutrition across all regions was 16.6%, including 6.7% with SAM and 9.7% with MAM. The prevalence of SAM is highest in North Gaza and South Gaza (both at 6.8%) and slightly lower in the Middle Zone (6.5%). For MAM, the highest prevalence is in South Gaza (11.5%), with Middle Zone showing the lowest rate (7.3%). Logistic regression analysis indicated that children living in houses had a higher likelihood of SAM (OR = 2.36; 95% CI = 1.39–3.99) and MAM (OR = 1.44; 95% CI = 1.13–1.84), and children living in schools had a higher likelihood of SAM (OR = 2.79; 95% CI = 1.35–5.74) and MAM (OR = 2.08; 95% CI = 1.14–3.80) compared to those in tents. Notably, children residing in North Gaza were significantly more likely to experience SAM (OR = 13.2; 95% CI = 6.23–27.95) and MAM (OR = 10.51; 95% CI = 5.74–19.3) compared to those in South Gaza.ConclusionThe study highlights a high prevalence of malnutrition among children under five in the Gaza Strip, particularly among those living in houses, shelters and in the North Gaza governorate. These findings underscore the urgent need for targeted nutritional interventions and support for affected families in conflict zones.
Impact of the Coronavirus disease pandemic on early breast cancer
Authors: Li Yong , Lu Xiao-ju , Xu Bo , Li Wei-wen 
Published: November 2024

ObjectiveTo assess the impact of the COVID-19 pandemic on the presentation, treatment, and survival of patients with early breast cancer (Stage I–III).MethodsThis study utilized data from the Surveillance, Epidemiology, and End Results database from January 1, 2018, to December 31, 2020. Patients diagnosed with primary breast cancer in 2020 were compared to those diagnosed in 2018 or 2019. The primary outcomes were stage distribution and changes in the treatment modalities for early breast cancer. The secondary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS).ResultsWe analyzed 142,038 patients. There has been a decrease in breast cancer diagnoses in 2020, as well as the smaller number of surgeries. The distribution of breast cancer stages among patients exhibited a notable shift in 2020, with a decrease in the proportion of Stage 0-I and an increase in advanced-stage. Additionally, there was a significant decrease in the proportion of breast-conserving surgery (BCS) performed in 2020. The proportion of patients undergoing radiation decreased, while that of chemotherapy cases increased significantly in 2020. Patients showed a shorter treatment delay in 2020 than in 2018 or 2019 (2018: hazard ratio [HR] = 0.969, 95% confidence interval [CI] = 0.956–0.982, p &lt; 0.001; 2019: HR=0.959, 95% CI = 0.946–0.972, p &lt; 0.001). Diagnosis in 2020 showed a significant correlation with worse OS than diagnosis in 2018 (HR = 0.861, 95% CI = 0.743-0.996, p = 0.045).ConclusionWe observed a shift to advanced-stage and a change of treatment modalities of early breast cancer in 2020. The OS of patients with breast cancer was worse during the pandemic than before the pandemic. The findings could provide empirical basis for optimizing cancer prevention and control strategies in future public health emergencies.
Optimized FDG-PET/MRI protocol reveals metabolic predictors of long-term survival in pancreatic cancer patients
Authors: Juengling Freimut D. , Valenta-Schindler Ines , Chirindel Alin 
Published: November 2024

PurposeTo optimize and assess an abbreviated dual time-point 18-Fluor-Deoxyglucose (FDG)-Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) protocol for predicting patient outcomes in pancreatic cancer.Methods70 patients (47 pancreatic cancer, 23 chronic pancreatitis) underwent hybrid PET/MRI with dual time-point PET/CT at 60 and 84 minutes post-injection. Metabolic indices (MI) were calculated from Standardized Uptake Value (SUV) changes (SUVmin, SUVmean and SUVmax). Multivariate analysis was performed on PET, MRI, laboratory, and histologic data. Top predictors were used for survival analysis.ResultsMI SUVmax, thresholded at 11%, was the best outcome predictor, distinguishing high-risk (2year (2y)-Overall Survival (OAS) 32%, 5y-OAS 14%, 10y-OAS 8%) and low-risk groups (2y-OAS 76%, 5y-OAS 32%, 10y-OAS 23%). Tumor size, CBD obstruction, and infiltrative disease had lower predictive value.ConclusionsMetabolic indices from abbreviated dual time-point FDG-PET/MRI can differentiate pancreatic malignancy from pancreatitis and predict outcomes, outperforming other indices. This protocol offers a valuable diagnostic tool for characterizing pancreatic lesions and predicting outcomes based on imaging criteria.
Construction of a risk prediction model for postoperative deep vein thrombosis in colorectal cancer patients based on machine learning algorithms
Authors: Liu Xin , Shu Xingming , Zhou Yejiang , Jiang Yifan 
Published: November 2024

BackgroundColorectal cancer is a prevalent malignancy of the digestive system, with an increasing incidence. Lower extremity deep vein thrombosis (DVT) is a frequent postoperative complication, occurring in up to 40% of cases.ObjectiveThis research aims to develop and validate a machine learning model (ML) to predict the risk of lower limb deep vein thrombosis in patients with colorectal cancer, facilitating preventive and therapeutic measures to enhance recovery and ensure safety.MethodsIn this retrospective cohort study, we collected data from 429 colorectal cancer patients from January 2021 to January 2024. The medical records included age, blood test results, body mass index, underlying diseases, clinical staging, histological typing, surgical methods, and postoperative complications. We employed the Synthetic Minority Oversampling Technique to address imbalanced data and split the dataset into training and validation sets in a 7:3 ratio. Feature selection was performed using Random Forest (RF), XGBoost, and Least Absolute Shrinkage and Selection Operator algorithms (LASSO). We then trained six machine learning models: Logistic Regression (LR), Naive Bayes (NB), Gaussian Process (GP), Random Forest, XGBoost, and Multilayer Perceptron (MLP). The model’s performance was evaluated using metrics such as area under the Receiver Operating Characteristic curve, accuracy, sensitivity, specificity, F1 score, and confusion matrix. Additionally, SHAP and LIME were used to enhance the interpretability of the results.ResultsThe study combined Random Forest, XGBoost algorithms, and LASSO regression with univariate regression analysis to identify significant predictive factors, including age, preoperative prealbumin, preoperative albumin, preoperative hemoglobin, operation time, PIKVA2, CEA, and preoperative neutrophil count. The XGBoost model outperformed other ML algorithms, achieving an AUC of 0.996, an accuracy of 0.9636, a specificity of 0.9778, and an F1 score of 0.9576. Moreover, the SHAP method identified age and preoperative prealbumin as the primary determinants influencing ML model predictions. Finally, the study employed LIME for more precise prediction and interpretation of individual predictions.ConclusionThe machine learning algorithms effectively predicted postoperative lower limb deep vein thrombosis in colorectal cancer patients. The XGBoost model demonstrated strong potential for improving early detection and treatment in clinical settings.
Anti-tumor and anti-metastatic effects of RRx-001 on hepatocellular carcinoma: mechanisms of action and therapeutic potential
Authors: Yan Guohong , Zhao Shuqi , Chen Meifeng , Mo Shutian , Huang Hailian , Liao Yuan , Lu Ziyan , Liang Jiaming , Wei Shuxin , Han Chuangye , Ye Xinping 
Published: November 2024

Background1-Bromoacetyl-3,3-dinitroazetidine (RRx-001) has potent antitumor effects, indicating its promising therapeutic potential against various cancers. This research investigates RRx-001 activity against hepatocellular carcinoma (HCC) and elucidates its underlying mechanisms.MethodsHuh7, Hepa1-6, and MHCC97H cells were cultured and treated with varying RRx-001 concentrations for 24, 48, and 72 h. Cell viability was assessed using cell counting kit-8. The cells were divided into control and RRx-001 treatment groups at 0.5 × IC50, 1.0 × IC50, and 2.0 × IC50 concentrations for each cell line. Migration and invasion were evaluated using scratch and Transwell assays, and apoptosis was examined by apoptosis assays. RNA sequencing was performed on the Huh7 cells treated with RRx-001 for 24 h to identify differential gene expression. CD47 and TP53 protein levels were measured by Western blot. A xenograft mouse model was utilized to evaluate the effect of RRx-001 on HCC.ResultsRRx-001 inhibits HCC cell viability, migration, and invasion while inducing apoptosis, These effects are potentially mediated by the downregulation of CD47 and the upregulation of TP53, both of which modulate key signaling pathways. In vivo experiments demonstrated that RRx-001 effectively inhibits tumor growth.ConclusionRRx-001 reduces the viability of HCC cells and induces apoptosis. This effect may be due to the downregulation of CD47 expression and the alteration of the TP53 protein regulatory pathway.
Role of Rab10 in cocaine-induced behavioral effects is associated with GABAB receptor membrane expression in the nucleus accumbens
Authors: Yu Zhuoxuan , Fu Qiang , Qiu Tianyun , Yang Caidi , Lu Mingfen , Peng Qinghua , Yang Jianhua , Hu Zhenzhen 
Published: November 2024

AimPrevious studies have demonstrated that Ras-related GTP-binding protein Rab10 (Rab10) plays a role in psychostimulant-induced behavioral effects. In this study, we showed that Rab10 in the nucleus accumbens (NAc) of male animals affects the development of cocaine-induced behavioral effects, which are associated with the plasma membrane expression of the GABAB heteroreceptor (GABABR).MethodsWe performed flow cytometry, immunoendocytosis, pHluorin activity analysis, electrophysiology analysis, and open-field testing to explore the role of Rab10 in modulating the membrane expression and function of GABABR and its regulatory effect on cocaine-induced behavioral effects.ResultsTranscriptomics analysis showed that Rab10 was elevated following acute cocaine treatment. Membrane levels of Rab10 increased within day 1 of the cocaine treatment, subsequently decreasing at later time points. Rab10 deficiency in NAc regions significantly increased cocaine-inhibited membrane GABABR levels and inhibited cocaine-induced hyperlocomotion and behavioral sensitization. In addition, GAD67+-expressing neurons from NAc regions treated with cocaine revealed a significant decrease in Rab10 membrane expression. Furthermore, NAc neuron-specific Rab10 knockout resulted in a significant increase in the cocaine-inhibited membrane expression of GABABR, along with increased miniature inhibitory postsynaptic current (mIPSC) amplitude and attenuation of baclofen-amplified Ca2+ influx.ConclusionThese results uncover a new mechanism in which Rab10-GABABR signaling may serve as a potential pathway for regulating cocaine-induced behavioral effects.
Arbuscular mycorrhizal fungi alleviate Mn phytotoxicity by altering Mn subcellular distribution and chemical forms in Lespedeza davidii
Authors: Pan Gao , Hu Jiayao , Zi Zhen , Wang Wenying , Li Xinhang , Xu Xiaoli , Liu Wensheng 
Published: November 2024

IntroductionArbuscular mycorrhizal fungi (AMF) can relieve manganese (Mn) phytotoxicity and promote plant growth under Mn stress, but their roles remain unclear.MethodsIn this study, Lespedeza davidii inoculated with or without AMF (Glomus mosseae) under different Mn concentrations (0 mmol/L, 1 mmol/L, 5 mmol/L, 10 mmol/L, and 20 mmol/L) was cultivated via a pot experiment, and plant biomass, physiological and biochemical characteristics, manganese absorption, subcellular distribution, and chemical forms of Mn were examined.ResultsThe results showed that root biomass, stem biomass, leaf biomass, and total individual biomass decreased under high Mn concentrations (above 10 mmol/L), and the inoculated plants had higher biomass than the uninoculated plants. With the increasing Mn concentration, the contents of soluble sugar, soluble protein, free proline, superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased first and then decreased, while the malondialdehyde (MDA) content increased. The contents of soluble sugar, soluble protein, free proline, SOD, POD, and CAT in the inoculated group were higher than those in the uninoculated group at the Mn concentration of 20 mmol/L. The content of MDA in the inoculated plants was lower than that in the uninoculated plants. AMF inoculation enriched most of the manganese in the root system when compared with the non-mycorrhizal treatment. Subcellular distribution of Mn indicated that most of the Mn ions were stored in the cell wall and the vacuoles (the soluble fractions), and the proportion of Mn content in the cell wall components and the vacuole components in leaves in the inoculated group was higher than that in the uninoculated group. Furthermore, the proportions of Mn extracted using ethanol and deionized water in the uninoculated group in stems and roots were higher than those in the inoculated group, which suggested that AMF could convert Mn into inactive forms.DiscussionThe present study demonstrated that AMF could improve the resistance of L. davidii to Mn toxicity by increasing the activity of antioxidant enzymes and altering the subcellular distribution and chemical forms of Mn.
Validation of the schema coping inventory for dysfunctional coping strategies
Authors: Gazzellini Simone , Pellegrini Valerio , Napoli Eleonora , Ventre Vanessa , Lettori Donatella , Castelli Enrico , Basile Barbara , Giacomantonio Mauro 
Published: November 2024

IntroductionAccording to the theoretical model of Schema Therapy, each human being has basic needs that require natural satisfaction from childhood. When these emotional needs are frustrated, early maladaptive schemas (EMS) develop, leading to coping styles that are strategies to manage the pain caused by activated EMS. The study validates and standardizes the Schema Coping Inventory in the Italian population and evaluates correlations between psychological variables and the SCI.MethodsWe analysed data from a community sample of 602 Italian adults, aged between 18 and 69 years, who endorsed a structured questionnaire, involving demographic information, the Italian version of the SCI, and an array of theoretically related psychological constructs.Results and discussionConfirmative factor analysis corroborated the tridimensional structure of the SCI (Surrender, Avoidance, Overcompensation), both in terms of the overall goodness-of-fit of the model and the single items’ factor loading in the corresponding factors. The internal consistency turned out to be satisfactory. Construct validity was assessed through convergent and divergent (positive and negative) correlations with other coping style measures and psychopathological scales. Mean values and mean standard deviations are reported for the general population, for psychopathological clinical and non-pathological samples.