bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of four nuclei in the human brainstem: Individual differences, left-right asymmetry, species differences
Authors: Baizer Joan S. , Witelson Sandra F. 
Published: February 2023

IntroductionIt is commonly thought that while the organization of the cerebral cortex changes dramatically over evolution, the organization of the brainstem is conserved across species. It is further assumed that, as in other species, brainstem organization is similar from one human to the next. We will review our data on four human brainstem nuclei that suggest that both ideas may need modification.MethodsWe have studied the neuroanatomical and neurochemical organization of the nucleus paramedianus dorsalis (PMD), the principal nucleus of the inferior olive (IOpr), the arcuate nucleus of the medulla (Arc) and the dorsal cochlear nucleus (DC). We compared these human brainstem nuclei to nuclei in other mammals including chimpanzees, monkeys, cats and rodents. We studied human cases from the Witelson Normal Brain collection using Nissl and immunostained sections, and examined archival Nissl and immunostained sections from other species.ResultsWe found significant individual variability in the size and shape of brainstem structures among humans. There is left-right asymmetry in the size and appearance of nuclei, dramatically so in the IOpr and Arc. In humans there are nuclei, e.g., the PMD and the Arc, not seen in several other species. In addition, there are brainstem structures that are conserved across species but show major expansion in humans, e.g., the IOpr. Finally, there are nuclei, e.g. the DC, that show major differences in structure among species.DiscussionOverall, the results suggest several principles of human brainstem organization that distinguish humans from other species. Studying the functional correlates of, and the genetic contributions to, these brainstem characteristics are important future research directions.
Prognostic role of dynamic neutrophil-to-lymphocyte ratio in acute ischemic stroke after reperfusion therapy: A meta-analysis
Authors: Wu Bing , Liu Fang , Sun Guiyan , Wang Shuang 
Published: February 2023

BackgroundThe prognostic role of the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, in acute ischemic stroke (AIS) after reperfusion therapy remains controversial. Therefore, this meta-analysis sought to assess the correlation between the dynamic NLR and the clinical outcomes of patients with AIS after reperfusion therapy.MethodsPubMed, Web of Science, and Embase databases were searched to identify relevant literature from their inception to 27 October 2022. The clinical outcomes of interest included poor functional outcome (PFO) at 3 months, symptomatic intracerebral hemorrhage (sICH), and 3-month mortality. The NLR on admission (pre-treatment) and post-treatment was collected. The PFO was defined as a modified Rankin scale (mRS) of &gt;2.ResultsA total of 17,232 patients in 52 studies were included in the meta-analysis. The admission NLR was higher in the 3-month PFO (standardized mean difference [SMD] = 0.46, 95% confidence interval [CI] = 0.35–0.57), sICH (SMD = 0.57, 95% CI = 0.30–0.85), and mortality at 3 months (SMD = 0.60, 95% CI = 0.34–0.87). An elevated admission NLR was associated with an increased risk of 3-month PFO (odds ratio [OR] = 1.13, 95% CI = 1.09–1.17), sICH (OR = 1.11, 95% CI = 1.06–1.16), and mortality at 3 months (OR = 1.13, 95% CI = 1.07–1.20). The post-treatment NLR was significantly higher in the 3-month PFO (SMD = 0.80, 95% CI = 0.62–0.99), sICH (SMD = 1.54, 95% CI = 0.97–2.10), and mortality at 3 months (SMD = 1.00, 95% CI = 0.31–1.69). An elevated post-treatment NLR was significantly associated with an increased risk of 3-month PFO (OR = 1.25, 95% CI = 1.16–1.35), sICH (OR = 1.14, 95% CI = 1.01–1.29), and mortality at 3 months (OR = 1.28, 95% CI = 1.09–1.50).ConclusionThe admission and post-treatment NLR can be used as cost-effective and easily available biomarkers to predict the 3-month PFO, sICH, and mortality at 3 months in patients with AIS treated with reperfusion therapy. The post-treatment NLR provides better predictive power than the admission NLR.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022366394.
Comparison of Yizhiqingxin formula extraction methods and their pharmacodynamic differences
Authors: Wei Wei , Pei Hui , Ma Li-Na , Zheng Rui , Huang Qiao-Yi , Chang Su-rui , Cao Yu , Li Hao 
Published: February 2023

ObjectivesThis study compared different extraction methods of Yizhiqingxin formula (YQF) and its neuroprotective effects based on pharmacodynamic indices such as learning and memory ability, brain tissue histopathology and morphology, and inflammatory factor expression in a mouse model of Alzheimer’s disease (AD).MethodsThe pharmaceutical components of YQF were extracted using three extraction processes, and the components were analyzed by high performance liquid chromatography. Donepezil hydrochloride was used as a positive control drug. Fifty 7–8-month-old 3 × Tg AD mice were randomly divided into three YQF groups (YQF-1, YQF-2, and YQF-3), a donepezil group, and a model group. Ten age-matched C57/BL6 mice were used as normal controls. YQF and Donepezil were administered by gavage at a clinically equivalent dose of 2.6 and 1.3 mg⋅kg–1⋅d–1, respectively, with a gavage volume of 0.1 ml/10 g. Control and model groups received equal volumes of distilled water by gavage. After 2 months, the efficacy was evaluated using behavioral experiments, histopathology, immunohistochemistry, and serum assays.ResultsThe main components in YQF are ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, epiberberine, coptisine chloride, palmatine, berberine, and ferulic acid. YQF-3 (alcohol extraction) has the highest content of active compounds, followed by YQF-2 (water extraction and alcohol precipitation method). Compared to the model group, the three YQF groups showed alleviated histopathological changes and improved spatial learning and memory, with the effect in YQF-2 being the most significant. YQF showed protection of hippocampal neurons, most significantly in the YQF-1 group. YQF significantly reduced Aβ pathology and tau hyperphosphorylation, decreased expressions of serum pro-inflammatory factors interleukin-2 and interleukin-6 as well as serum chemokines MCP-1 and MIG.ConclusionYQF prepared by three different processes showed differences in pharmacodynamics in an AD mouse model. YQF-2 was significantly better than the other extraction processes in improving memory.
Alteration of brain network centrality in CTN patients after a single triggering pain
Authors: Ge Xiuhong , Wang Luoyu , Wang Mengze , Pan Lei , Ye Haiqi , Zhu Xiaofen , Fan Sandra , Feng Qi , Du Quan , Wenhua Yu , Ding Zhongxiang 
Published: February 2023

ObjectiveThe central nervous system may also be involved in the pathogenesis of classical trigeminal neuralgia (CTN). The present study aimed to explore the characteristics of static degree centrality (sDC) and dynamic degree centrality (dDC) at multiple time points after a single triggering pain in CTN patients.Materials and methodsA total of 43 CTN patients underwent resting-state function magnetic resonance imaging (rs-fMRI) before triggering pain (baseline), within 5 s after triggering pain (triggering-5 s), and 30 min after triggering pain (triggering-30 min). Voxel-based degree centrality (DC) was used to assess the alteration of functional connection at different time points.ResultsThe sDC values of the right caudate nucleus, fusiform gyrus, middle temporal gyrus, middle frontal gyrus, and orbital part were decreased in triggering-5 s and increased in triggering-30 min. The sDC value of the bilateral superior frontal gyrus were increased in triggering-5 s and decreased in triggering-30 min. The dDC value of the right lingual gyrus was gradually increased in triggering-5 s and triggering-30 min.ConclusionBoth the sDC and dDC values were changed after triggering pain, and the brain regions were different between the two parameters, which supplemented each other. The brain regions which the sDC and dDC values were changing reflect the global brain function of CTN patients, and provides a basis for further exploration of the central mechanism of CTN.
Brain activation of the PFC during dual-task walking in stroke patients: A systematic review and meta-analysis of functional near-infrared spectroscopy studies
Authors: Wang Qinglei , Dai Wenjun , Xu Sheng , Zhu Shizhe , Sui Youxin , Kan Chaojie , Shen Ying , Zhu Yi , Guo Chuan , Wang Tong 
Published: February 2023

BackgroundDual-task walking is a good paradigm to measure the walking ability of stroke patients in daily life. It allows for a better observation of brain activation under dual-task walking to assess the impact of the different tasks on the patient when combining with functional near-infrared spectroscopy (fNIRS). This review aims to summarize the cortical change of the prefrontal cortex (PFC) detected in single-task and dual-task walking in stroke patients.MethodsSix databases (Medline, Embase, PubMed, Web of Science, CINAHL, and Cochrane Library) were systematically searched for relevant studies, from inception to August 2022. Studies that measured the brain activation of single-task and dual-task walking in stroke patients were included. The main outcome of the study was PFC activity measured using fNIRS. In addition, a subgroup analysis was also performed for study characteristics based on HbO to analyze the different effects of disease duration and the type of dual task.ResultsTen articles were included in the final review, and nine articles were included in the quantitative meta-analysis. The primary analysis showed more significant PFC activation in stroke patients performing dual-task walking than single-task walking (SMD = 0.340, P = 0.02, I2 = 7.853%, 95% CI = 0.054–0.626). The secondary analysis showed a significant difference in PFC activation when performing dual-task walking and single-task walking in chronic patients (SMD = 0.369, P = 0.038, I2 = 13.692%, 95% CI = 0.020–0.717), but not in subacute patients (SMD = 0.203, P = 0.419, I2 = 0%, 95% CI = −0.289–0.696). In addition, performing walking combining serial subtraction (SMD = 0.516, P &lt; 0.001, I2 = 0%, 95% CI = 0.239–0.794), obstacle crossing (SMD = 0.564, P = 0.002, I2 = 0%, 95% CI = 0.205–0.903), or a verbal task (SMD = 0.654, P = 0.009, I2 = 0%, 95% CI = 0.164–1.137) had more PFC activation than single-task walking, while performing the n-back task did not show significant differentiation (SMD = 0.203, P = 0.419, I2 = 0%, 95% CI = −0.289–0.696).ConclusionsDifferent dual-task paradigms produce different levels of dual-task interference in stroke patients with different disease durations, and it is important to choose the matching dual-task type in relation to the walking ability and cognitive ability of the patient, in order to better improve the assessment and training effects.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42022356699.
Regional citrate anticoagulation for replacement therapy in patients with liver failure: A systematic review and meta-analysis
Authors: Peng Bo , Lu Jiaqi , Guo Hebing , Liu Jingyuan , Li Ang 
Published: February 2023

BackgroundCitrate refers to an anticoagulant agent commonly used in extracorporeal organ support. Its application is limited in patients with liver failure (LF) due to the increased risk of citrate accumulation induced by liver metabolic dysfunction. This systematic review aims to assess the efficacy and safety of regional citrate anticoagulation in extracorporeal circulation for patients with liver failure.MethodsPubMed, Web of Science, Embase, and Cochrane Library were searched. Studies regarding extracorporeal organ support therapy for LF were included to assess the efficacy and safety of regional citrate anticoagulation. Methodological quality of included studies were assessed using the Methodological Index for Non-randomized Studies (MINORS). Meta-analysis was performed using R software (version 4.2.0).ResultsThere were 19 eligible studies included, involving 1026 participants. Random-effect model showed an in-hospital mortality of 42.2% [95%CI (27.2, 57.9)] in LF patients receiving extracorporeal organ support. The during-treatment incidence of filter coagulation, citrate accumulation, and bleeding were 4.4% [95%CI (1.6-8.3)], 6.7% [95%CI (1.5-14.4)], and 5.0% [95%CI (1.9-9.3)], respectively. The total bilirubin(TBIL), alanine transaminase (ALT), aspartate transaminase(AST), serum creatinine(SCr), blood urea nitrogen(BUN), and lactate(LA) decreased, compared with those before the treatment, and the total calcium/ionized calcium ratio, platelet(PLT), activated partial thromboplastin time(APTT), serum potential of hydrogen(pH), buffer base(BB), and base excess(BE) increased.ConclusionRegional citrate anticoagulation might be effective and safe in LF extracorporeal organ support. Closely monitoring and timely adjusting during the process could reduce the risk for complications. More prospective clinical trials of considerable quality are needed to further support our findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022337767.
The prognostic nutritional index represents a novel inflammation-nutrition-based prognostic factor for nasopharyngeal carcinoma
Authors: Jiang Yan-Ming , Huang Shi-Ting , Pan Xin-Bin , Ma Jia-Lin , Zhu Xiao-Dong 
Published: February 2023

PurposeThis study explored the relationship between the prognostic nutritional index (PNI) and overall survival rate (OS) in patients with nasopharyngeal carcinoma (NPC), and established and validated an effective nomogram to predict clinical outcomes.MethodsThis study included 618 patients newly diagnosed with locoregionally advanced NPC. They were divided into training and validation cohorts at a ratio of 2:1 based on random numbers. The primary endpoint of this study was OS, progression-free survival (PFS) was the second endpoint. A nomogram was drawn from the results of multivariate analyses. Harrell’s concordance index (C-index), area under the receiver operator characteristic curve (AUC), and decision curve analysis (DCA) were used to evaluate the clinical usefulness and predictive ability of the nomogram and were compared to the current 8th edition of the International Union Against Cancer/American Joint Committee (UICC/AJCC) staging system.ResultsThe PNI cutoff value was 48.1. Univariate analysis revealed that age (p &lt; 0.001), T stage (p &lt; 0.001), N stage (p = 0.036), tumor stage (p &lt; 0.001), PNI (p = 0.001), lymphocyte-neutrophil ratio (NLR, p = 0.002), and lactate dehydrogenase (LDH, p = 0.009) were significantly associated with OS, age (p = 0.001), T-stage (p &lt; 0.001), tumor stage (p &lt; 0.001), N-stage (p = 0.011), PNI (p = 0.003), NLR (p = 0.051), and LDH (p = 0.03) were significantly associated with PFS. Multivariate analysis showed that age (p &lt; 0.001), T-stage (p &lt; 0.001), N-stage(p = 0.02), LDH (p = 0.032), and PNI (p = 0.006) were significantly associated with OS, age (p = 0.004), T-stage (&lt;0.001), N-stage (&lt;0.001), PNI (p = 0.022) were significantly associated with PFS. The C-index of the nomogram was 0.702 (95% confidence interval [CI]: 0.653–0.751). The Akaike information criterion (AIC) value of the nomogram for OS was 1142.538. The C-index of the TNM staging system was 0.647 (95% CI, 0.594–0.70) and the AIC was 1163.698. The C-index, DCA, and AUC of the nomogram demonstrated its clinical value and higher overall net benefit compared to the 8th edition of the TNM staging system.ConclusionThe PNI represents a new inflammation-nutrition-based prognostic factor for patients with NPC. In the proposed nomogram, PNI and LDH were present, which led to a more accurate prognostic prediction than the current staging system for patients with NPC.
Differential metabolites in cirrhotic patients with hepatitis B and muscle mass loss
Authors: Liu Xuechun , Han Lei , Bi Shenghua , Ding Xueli , Sheng Qi , Jiang Yueping , Guan Ge , Niu Qinghui , Jing Xue 
Published: February 2023

BackgroundSarcopenia leads to complications (infections, hepatic encephalopathy and ascites) and poor overall survival in patients with cirrhosis, in which the phenotypic presentation is loss of muscle mass. This study aimed to reveal the metabolic profile and identify potential biomarkers in cirrhotic patients with hepatitis B virus and muscle mass loss.MethodTwenty decompensated cirrhotic patients with HBV and muscle mass loss were designated Group S; 20 decompensated cirrhotic patients with HBV and normal muscle mass were designated Group NS; and 20 healthy people were designated Group H. Muscle mass loss was defined as the skeletal muscle mass index less than 46.96 cm2/m2 for males and less than 32.46 cm2/m2 for females. Gas chromatography–mass spectrometry was used to explore the distinct metabolites and pathways in the three groups.ResultsThirty-seven metabolic products and 25 associated metabolic pathways were significantly different in the Group S patients from Group NS patients. Strong predictive value of 11 metabolites (inosine-5′-monophosphate, phosphoglycolic acid, D-fructose-6-phosphate, N-acetylglutamate, pyrophosphate, trehalose-6-phosphate, fumaric acid, citrulline, creatinine, (r)-3-hydroxybutyric acid, and 2-ketobutyric acid) were selected as potential biomarkers in Group S patients compared with Group NS patients. Two pathways may be associated with loss of muscle mass in patients with liver cirrhosis: amino acid metabolism and central carbon metabolism in cancer.ConclusionSeventy differential metabolites were identified in patients who have liver cirrhosis and loss of muscle mass compared with patients who have cirrhosis and normal muscle mass. Certain biomarkers might distinguish between muscle mass loss and normal muscle mass in HBV-related cirrhosis patients.
Recurrence risk stratification for locally advanced cervical cancer using multi-modality transformer network
Authors: Wang Jian , Mao Yixiao , Gao Xinna , Zhang Yu 
Published: February 2023

ObjectivesRecurrence risk evaluation is clinically significant for patients with locally advanced cervical cancer (LACC). We investigated the ability of transformer network in recurrence risk stratification of LACC based on computed tomography (CT) and magnetic resonance (MR) images.MethodsA total of 104 patients with pathologically diagnosed LACC between July 2017 and December 2021 were enrolled in this study. All patients underwent CT and MR scanning, and their recurrence status was identified by the biopsy. We randomly divided patients into training cohort (48 cases, non-recurrence: recurrence = 37: 11), validation cohort (21 cases, non-recurrence: recurrence = 16: 5), and testing cohort (35 cases, non-recurrence: recurrence = 27: 8), upon which we extracted 1989, 882 and 315 patches for model's development, validation and evaluation, respectively. The transformer network consisted of three modality fusion modules to extract multi-modality and multi-scale information, and a fully-connected module to perform recurrence risk prediction. The model's prediction performance was assessed by six metrics, including the area under the receiver operating characteristic curve (AUC), accuracy, f1-score, sensitivity, specificity and precision. Univariate analysis with F-test and T-test were conducted for statistical analysis.ResultsThe proposed transformer network is superior to conventional radiomics methods and other deep learning networks in both training, validation and testing cohorts. Particularly, in testing cohort, the transformer network achieved the highest AUC of 0.819 ± 0.038, while four conventional radiomics methods and two deep learning networks got the AUCs of 0.680 ± 0.050, 0.720 ± 0.068, 0.777 ± 0.048, 0.691 ± 0.103, 0.743 ± 0.022 and 0.733 ± 0.027, respectively.ConclusionsThe multi-modality transformer network showed promising performance in recurrence risk stratification of LACC and may be used as an effective tool to help clinicians make clinical decisions.
Nonfunctional ectopic adrenocortical carcinoma in the lung: A case report and literature review
Authors: Nie Limin , Wang Shuyun , Feng Zongfeng , Sun Yuping , Wang Zhen , Dang Qi , Gao Aiqin , Lv Yajuan 
Published: February 2023

BackgroundEctopic adrenocortical tissues and neoplasms are rare and usually found in the genitourinary system and abdominal cavity. The thorax is an extremely rare ectopic site. Here, we report the first case of nonfunctional ectopic adrenocortical carcinoma (ACC) in the lung.Case presentationA 71-year-old Chinese man presented with vague left-sided chest pain and irritable cough for 1 month. Thoracic computed tomography revealed a heterogeneously enhancing 5.3 × 5.8 × 6.0-cm solitary mass in the left lung. Radiological findings suggested a benign tumor. The tumor was surgically excised upon detection. Histopathological examination using hematoxylin and eosin staining showed that the cytoplasm of the tumor cells was rich and eosinophilic. Immunohistochemical profiles (inhibin-a+, melan-A+, Syn+) indicated that the tumor had an adrenocortical origin. The patient showed no symptoms of hormonal hypersecretion. The final pathological diagnosis was non-functional ectopic ACC. The patient was disease-free for 22 months and is still under follow-up.ConclusionsNonfunctional ectopic ACC in the lung is an extremely rare neoplasm that can be easily misdiagnosed as primary lung cancer or lung metastasis, both preoperatively and on postoperative pathological examination. This report may provide clues to clinicians and pathologists regarding the diagnosis and treatment of nonfunctional ectopic ACC.
Molecular features and predictive models identify the most lethal subtype and a therapeutic target for osteosarcoma
Authors: Zheng Kun , Hou Yushan , Zhang Yiming , Wang Fei , Sun Aihua , Yang Dong 
Published: February 2023

BackgroundOsteosarcoma is the most common primary malignant bone tumor. The existing treatment regimens remained essentially unchanged over the past 30 years; hence the prognosis has plateaued at a poor level. Precise and personalized therapy is yet to be exploited.MethodsOne discovery cohort (n=98) and two validation cohorts (n=53 &amp; n=48) were collected from public data sources. We performed a non-negative matrix factorization (NMF) method on the discovery cohort to stratify osteosarcoma. Survival analysis and transcriptomic profiling characterized each subtype. Then, a drug target was screened based on subtypes’ features and hazard ratios. We also used specific siRNAs and added a cholesterol pathway inhibitor to osteosarcoma cell lines (U2OS and Saos-2) to verify the target. Moreover, PermFIT and ProMS, two support vector machine (SVM) tools, and the least absolute shrinkage and selection operator (LASSO) method, were employed to establish predictive models.ResultsWe herein divided osteosarcoma patients into four subtypes (S-I ~ S-IV). Patients of S- I were found probable to live longer. S-II was characterized by the highest immune infiltration. Cancer cells proliferated most in S-III. Notably, S-IV held the most unfavorable outcome and active cholesterol metabolism. SQLE, a rate-limiting enzyme for cholesterol biosynthesis, was identified as a potential drug target for S-IV patients. This finding was further validated in two external independent osteosarcoma cohorts. The function of SQLE to promote proliferation and migration was confirmed by cell phenotypic assays after the specific gene knockdown or addition of terbinafine, an inhibitor of SQLE. We further employed two machine learning tools based on SVM algorithms to develop a subtype diagnostic model and used the LASSO method to establish a 4-gene model for predicting prognosis. These two models were also verified in a validation cohort.ConclusionThe molecular classification enhanced our understanding of osteosarcoma; the novel predicting models served as robust prognostic biomarkers; the therapeutic target SQLE opened a new way for treatment. Our results served as valuable hints for future biological studies and clinical trials of osteosarcoma.