bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and immunological characterization of cuproptosis-related molecular clusters in Alzheimer's disease
Authors: Lai Yongxing , Lin Chunjin , Lin Xing , Wu Lijuan , Zhao Yinan , Lin Fan 
Published: July 2022

IntroductionAlzheimer's disease is the most common dementia with clinical and pathological heterogeneity. Cuproptosis is a recently reported form of cell death, which appears to result in the progression of various diseases. Therefore, our study aimed to explore cuproptosis-related molecular clusters in Alzheimer's disease and construct a prediction model.MethodsBased on the GSE33000 dataset, we analyzed the expression profiles of cuproptosis regulators and immune characteristics in Alzheimer's disease. Using 310 Alzheimer's disease samples, we explored the molecular clusters based on cuproptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were identified using the WGCNA algorithm. Subsequently, the optimal machine model was chosen by comparing the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting. Nomogram, calibration curve, decision curve analysis, and three external datasets were applied for validating the predictive efficiency.ResultsThe dysregulated cuproptosis-related genes and activated immune responses were determined between Alzheimer's disease and non-Alzheimer's disease controls. Two cuproptosis-related molecular clusters were defined in Alzheimer's disease. Analysis of immune infiltration suggested the significant heterogeneity of immunity between distinct clusters. Cluster2 was characterized by elevated immune scores and relatively higher levels of immune infiltration. Functional analysis showed that cluster-specific differentially expressed genes in Cluster2 were closely related to various immune responses. The Random forest machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.9829). A final 5-gene-based random forest model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.8529 and 0.8333). The nomogram, calibration curve, and decision curve analysis also demonstrated the accuracy to predict Alzheimer's disease subtypes. Further analysis revealed that these five model-related genes were significantly associated with the Aβ-42 levels and β-secretase activity.ConclusionOur study systematically illustrated the complicated relationship between cuproptosis and Alzheimer's disease, and developed a promising prediction model to evaluate the risk of cuproptosis subtypes and the pathological outcome of Alzheimer's disease patients.
Efficacy of electroacupuncture with different frequencies in the treatment of chemotherapy-induced peripheral neuropathy: A study protocol for a randomized controlled trial
Authors: Lu Chao , Bao Wenlong , Deng Dehou , Li Rongrong , Li Guangliang , Zou Shanlin , Wang Yan 
Published: July 2022

IntroductionChemotherapy-induced peripheral neuropathy (CIPN) is a common complication in patients with cancer during chemotherapy. It mainly leads to severe numbness of the hands and feet and causes great pain in patients. Electroacupuncture (EA) is considered to be beneficial in improving peripheral neuropathy and relieving numbness of the hands and feet. This trial aims to evaluate the therapeutic effect of different frequencies of EA on CIPN in patients with cancer.Methods and analysisThis study is a randomized controlled trial. In total, 160 eligible CIPN patients are randomly assigned to the 2 Hz EA group, 100 Hz EA group, 2/100 Hz EA group, and control group in the ratio of 1:1:1:1. All patients in the EA treatment groups receive treatment with EA three times a week for 4 weeks and following up for 4 weeks. The patients in the control group are given Mecobalamin (MeCbl) tablets orally, one tablet at a time, three times a day, for 4 weeks, and following up for 4 weeks. The primary outcome measures are the participant neurotoxicity questionnaire (PNQ) and the peripheral neurotoxicity assessment rating (NCI CTCAE V5.0). Secondary outcomes are the quality of life scale (EORTC QLQ-C30) and the measurement of peripheral nerve conduction velocity (NCV). The results are evaluated at baseline, post-treatment phase, and following up for 4 weeks. All major analyses are based on the intention to treat principle.Ethics/disseminationThis protocol was approved by the Medical Ethics Committee of the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) on 7 December 2021. The license number is IRB-2021-458. This study provides clinical efficacy data of different frequencies of EA in the treatment of CIPN. The results help to prove whether EA is an effective therapy for CIPN and optimize the frequency of EA for CIPN. The results of this study are shared with health care professionals, the public, and relevant organizations through the publication of manuscripts and conference reports.Trial registration numberChiCTR2100054458.
The endogenous neuropeptide calcitonin gene-related peptide after spontaneous subarachnoid hemorrhage–A potential psychoactive prognostic serum biomarker of pain-associated neuropsychological symptoms
Authors: Bründl Elisabeth , Proescholdt Martin , Störr Eva-Maria , Schödel Petra , Bele Sylvia , Zeman Florian , Hohenberger Christoph , Kieninger Martin , Schmidt Nils Ole , Schebesch Karl-Michael 
Published: July 2022

BackgroundThe pronociceptive neuromediator calcitonin gene-related peptide (CGRP) is associated with pain transmission and modulation. After spontaneous subarachnoid hemorrhage (sSAH), the vasodilatory CGRP is excessively released into cerebrospinal fluid (CSF) and serum and modulates psycho-behavioral function. In CSF, the hypersecretion of CGRP subacutely after good-grade sSAH was significantly correlated with an impaired health-related quality of life (hrQoL). Now, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into serum after good-grade sSAH and its impact on hrQoL.MethodsTwenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out n = 5): n = 9 underwent endovascular aneurysm occlusion, n = 6 microsurgery, and n = 6 patients with perimesencephalic SAH received standardized intensive medical care. Plasma was drawn daily from day 1 to 10, at 3 weeks, and at the 6-month follow-up (FU). CGRP levels were determined with competitive enzyme immunoassay in duplicate serum samples. All patients underwent neuropsychological self-report assessment after the onset of sSAH (t1: day 11–35) and at the FU (t2).ResultsDuring the first 10 days, the mean CGRP levels in serum (0.470 ± 0.10 ng/ml) were significantly lower than the previously analyzed mean CGRP values in CSF (0.662 ± 0.173; p = 0.0001). The mean serum CGRP levels within the first 10 days did not differ significantly from the values at 3 weeks (p = 0.304). At 6 months, the mean serum CGRP value (0.429 ± 0.121 ng/ml) was significantly lower compared to 3 weeks (p = 0.010) and compared to the first 10 days (p = 0.026). Higher mean serum CGRP levels at 3 weeks (p = 0.001) and at 6 months (p = 0.005) correlated with a significantly poorer performance in the item pain, and, at 3 weeks, with a higher symptom burden regarding somatoform syndrome (p = 0.001) at t2.ConclusionOur study reveals the first insight into the serum levels of endogenous CGRP in good-grade sSAH patients with regard to hrQoL. In serum, upregulated CGRP levels at 3 weeks and 6 months seem to be associated with a poorer mid-term hrQoL in terms of pain. In migraineurs, CGRP receptor antagonists have proven clinical efficacy. Our findings corroborate the potential capacity of CGRP in pain processing.
The relationship between red blood cell distribution width at admission and post-stroke fatigue in the acute phase of acute ischemic stroke
Authors: Peng Meidi , Chen Yupei , Chen Yan , Feng Koulan , Shen Haiyan , Huang Hongtao , Zhao Wenxuan , Zou Hua , Ji Jianan 
Published: July 2022

IntroductionPost-stroke fatigue (PSF) is a common complication in the patients with acute ischemic stroke (AIS). This prospective study aimed to investigate the relationship between red blood cell distribution width (RDW) at admission and PSF in the acute phase.MethodsThe AIS patients were enrolled in Nantong Third People's Hospital, consecutively. PSF in the acute phase was scored according to the Fatigue Severity Scale. Levels of RDW were measured at admission. The associations were analyzed using multivariate regression and restricted cubic splines (RCS).ResultsFrom April 2021 to March 2022, a total of 206 AIS patients (mean age, 69.3 ± 10.7 years; 52.9% men) were recruited. After the adjustment for potential confounding factors, RDW at admission remained the independent associated factor with PSF in the acute phase (OR [odds ratio], 1.635; 95% CI [confidence interval], 1.153–2.318; P = 0.006). The linear dose-response associations of RDW with PSF in the acute phase were found, based on the RCS model (P for non-linearity = 0.372; P for linearity = 0.037). These results remained significant in other models.ConclusionsRDW at admission could serve as a novel biomarker of PSF in the acute phase of AIS.
Insulin resistance is associated with an unfavorable outcome among non-diabetic patients with isolated moderate-to-severe traumatic brain injury – A propensity score-matched study
Authors: Cao Cheng , Wang Huxu , Gao Heng , Wu Wei 
Published: July 2022

BackgroundHyperglycemia is an independent risk factor for the poor prognosis in patients with traumatic brain injury (TBI), and stress-induced impaired insulin function is the major factor of hyperglycemia in non-diabetic patients with TBI. Several types of research suggested that insulin resistance (IR) is related to the poor prognosis of neurocritical ill patients; here we focused on the role of IR in non-diabetic patients after TBI.MethodsWe performed a prospective observational study with the approval of the Ethics Committee of our institute. IR was accessed via the update Homeostasis Model Assessment (HOMA2) of IR, a computer-calculated index by glucose and insulin level. HOMA2 ≥ 1.4 was considered as the threshold of IR according to the previous studies. The glycemic variability (GV) indices were calculated by fingertip blood glucose concentration at an interval of 2 h within 24 h to explore the relationship between IR and GV. The outcome was the 6-month neurological outcome evaluated with the Glasgow outcome scale.ResultsA total of 85 patients with isolated moderate-to-severe TBI (admission GCS ≤ 12) were finally included in our study, 34 (40%) were diagnosed with IR with HOMA2 ≥ 1.4. After propensity score matching (PSM), 22 patients in IR group were matched to 34 patients in non-IR group. Patients with IR suffered increased systemic glycemic variation after isolated moderate-to-severe TBI. IR was a significant factor for the poor prognosis after TBI (OR = 3.25, 95% CI 1.03–10.31, p = 0.041).ConclusionsThe IR estimated by HOMA2 was associated with greater GV and an unfavorable outcome after isolated moderate-to-severe TBI. Ameliorating impaired insulin sensitivity may be a potential therapeutic strategy for the management of TBI patients.
Preliminary psychometric properties of a standard vocabulary test administered using a non-invasive brain-computer interface
Authors: Warschausky Seth , Huggins Jane E. , Alcaide-Aguirre Ramses Eduardo , Aref Abdulrahman W. 
Published: July 2022

ObjectiveTo examine measurement agreement between a vocabulary test that is administered in the standardized manner and a version that is administered with a brain-computer interface (BCI).MethodThe sample was comprised of 21 participants, ages 9–27, mean age 16.7 (5.4) years, 61.9% male, including 10 with congenital spastic cerebral palsy (CP), and 11 comparison peers. Participants completed both standard and BCI-facilitated alternate versions of the Peabody Picture Vocabulary Test - 4 (PPVT™-4). The BCI-facilitated PPVT-4 uses items identical to the unmodified PPVT-4, but each quadrant forced-choice item is presented on a computer screen for use with the BCI.ResultsMeasurement agreement between instruments was excellent, including an intra-class correlation coefficient of 0.98, and Bland-Altman plots and tests indicating adequate limits of agreement and no systematic test version bias. The mean standard score difference between test versions was 2.0 points (SD 6.3).ConclusionThese results demonstrate that BCI-facilitated quadrant forced-choice vocabulary testing has the potential to measure aspects of language without requiring any overt physical or communicative response. Thus, it may be possible to identify the language capabilities and needs of many individuals who have not had access to standardized clinical and research instruments.
The CX-DZ-II intelligent electronic stimulator for neck pain caused by cervical spondylosis: A two-center, randomized, controlled, and non-inferiority trial
Authors: Chen Liping , Li Dehua , Xu Jing , Liang Hao , Zhang Ya , Ren Yulan , Liang Fanrong 
Published: July 2022

BackgroundElectroacupuncture (EA) has been commonly used for the management of neck pain caused by cervical spondylosis (NPCS); however, current electrical instruments have limitations on intelligence, digitalization, and visualization. The intelligent electronic stimulator (CX-DZ-II) is a digital device with an evidence-based diagnosis and treatment system. This study aimed to investigate the efficacy and safety of the CX-DZ-II intelligent EA instrument for NPCS.Materials and MethodsA total of 164 patients with NPCS [mean age (SD), 49.48 (13.47) years] were randomly assigned to receive 8 sessions (over 2 weeks) EA of the intelligent electronic stimulator (CX-DZ-II) or the regular electronic stimulator (SDZ-II). The primary outcome was the change of the visual analog scale (VAS) from baseline to 2 weeks of treatment. Secondary outcomes included mean scores of the VAS after each treatment in 1 week, responder rate, drug-usage rate of non-steroidal antipyretic analgesics (NSAAs), the occurrence rate of adverse events (AEs), proportions of apparatus with defect during treatment, and excellent rate of apparatus.ResultsThe intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) for changes from baseline in the VAS [3.36 vs. 3.23, with a difference of 0.17 (95% CI, −0.36 to 0.69), P &lt; 0.025 for non-inferiority]. No between-group differences were found in outcomes of VAS in 1 week, overall responders, and drug-usage rate of NSAAs. The defect rate and excellent rate of the instrument were similar in the CX-DZ-II and SDZ-II groups. Adverse events occurred in 9 (10.84%) patients in the CX-DZ-II group and 4 (5.00%) patients in the SDZ-II group.ConclusionThe intelligent electronic stimulator (CX-DZ-II) was non-inferior to the regular electronic stimulator (SDZ-II) in relieving neck pain. The intelligent electronic stimulator (CX-DZ-II) is a promising non-inferior alternative instrument for NPCS.Clinical Trial Registration[https://clinicaltrials.gov/], identifier [NCT030 05301].
Automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging of rat brain
Authors: Bao Zhiguo , Zhang Tianhao , Pan Tingting , Zhang Wei , Zhao Shilun , Liu Hua , Nie Binbin 
Published: July 2022

AimsTo construct an automatic method for individual parcellation of manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain with high accuracy, which could preserve the inherent voxel intensity and Regions of interest (ROI) morphological characteristics simultaneously.Methods and resultsThe transformation relationship from standardized space to individual space was obtained by firstly normalizing individual image to the Paxinos space and then inversely transformed. On the other hand, all the regions defined in the atlas image were separated and resaved as binary mask images. Then, transforming the mask images into individual space via the inverse transformations and reslicing using the 4th B-spline interpolation algorithm. The boundary of these transformed regions was further refined by image erosion and expansion operator, and finally combined together to generate the individual parcellations. Moreover, two groups of MEMRI images were used for evaluation. We found that the individual parcellations were satisfied, and the inherent image intensity was preserved. The statistical significance of case-control comparisons was further optimized.ConclusionsWe have constructed a new automatic method for individual parcellation of rat brain MEMRI images, which could preserve the inherent voxel intensity and further be beneficial in case-control statistical analyses. This method could also be extended to other imaging modalities, even other experiments species. It would facilitate the accuracy and significance of ROI-based imaging analyses.
Improved Brain Pathology and Progressive Peripheral Neuropathy in a 15 Year Old Survivor of Infantile Krabbe Disease Treated With Umbilical Cord Transplantation
Authors: Kofler Julia , Beltran-Quintero Maria L. , Rugari Anne , Zuccoli Giulio , Klotz Sarah , Escolar Maria L. 
Published: July 2022

ObjectiveKrabbe disease is a fatal leukodystrophy caused by deficiency in galactocerebrosidase enzyme activity. The only currently available therapy is hematopoietic stem cell transplantation with bone marrow or umbilical cord blood (UCBT), which leads to increased lifespan and functional abilities when performed in the preclinical stage. While stabilization of white matter disease has been seen on serial MRI studies, neuropathological changes following transplantation have not been documented so far.Materials and MethodsWe report the first postmortem examination of a 15-year-old female patient with infantile Krabbe disease after UCBT in infancy.ResultsIn contrast to an untreated Krabbe disease brain, which showed severe myelin and oligodendrocyte loss with occasional globoid cells, the transplanted brain displayed markedly improved myelin preservation, but not reaching normal myelination levels. Consistent with the transplanted patient’s clinical presentation of pronounced deficits in gross motor skills, corticospinal tracts were most severely affected. No globoid cells or evidence of active demyelination were observed in the central nervous system, indicative of at least partially successful functional restoration. This was corroborated by the identification of male donor-derived cells in the brain by in situ hybridization. Unlike the observed disease stabilization in the central nervous system, the patient experienced progressive peripheral neuropathy. While diminished macrophage infiltration was seen postmortem, peripheral nerves exhibited edema, myelin and axon loss and persistent Schwann cell ultrastructural inclusions.ConclusionUmbilical cord blood transplantation was able to alter the natural disease progression in the central but less so in the peripheral nervous system, possibly due to limited cross-correction of Schwann cells.
Home enteral nutrition for patients with esophageal cancer undergoing esophagectomy: A systematic review and meta-analysis
Authors: Zhang Chi , Hu Li-Wen , Qiang Yong , Cong Zhuang-Zhuang , Zheng Chao , Gu Wen-Feng , Luo Chao , Xie Kai , Shen Yi 
Published: July 2022

IntroductionHome enteral nutrition (HEN) is a relatively new nutritional intervention that provides patients with EN support at home through jejunostomy or nasogastric feeding tubes. We conducted this systematic review and meta-analysis to explore the safety and effect of HEN compared with normal oral diet (NOD) in postoperative patients with esophageal cancer (EC).MethodsEMBASE, Medline, Web of Science, and the Cochrane Library were used to search articles in English-language journals. The intervention effect was expressed using risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcome measures, with 95% confidence intervals (95% CIs). The chi-square test and I-square test were used to test heterogeneity among studies.ResultsFour studies were eventually included in this meta-analysis. Compared with NOD, HEN has a favorable impact on postoperative body mass index (BMI) (weighted mean difference [WMD] = 0.70, 95% CI: 0.09–1.30, P = 0.02), lean body mass (LBM) (WMD = 0.76, 95% CI: 0.04–1.48, P = 0.04), and appendicular skeletal muscle mass index (ASMI) (WMD = 0.30, 95% CI: 0.02–0.58, P = 0.03). Physical function (WMD = 9.26, 95% CI: 8.00–10.53, P &lt; 0.001), role function (WMD = 9.96, 95% CI: 8.11–11.82, P &lt; 0.001), and social function (WMD = 8.51, 95% CI: 3.48–13.54, P = 0.001) of the HEN group were better than those of the NOD group at 3 months, and HEN could reduce the fatigue of patients (WMD = −12.73, 95% CI: −14.8 to −10.66, P &lt; 0.001) and the incidence of postoperative pneumonia (RR = 0.53, 95% CI: 0.34–0.81, P = 0.004). There was no significant difference in albumin between HEN and NOD groups (WMD = 0.05, 95% CI: −0.03 to 0.13, P = 0.20).ConclusionHEN improved nutritional status and quality of life (QOL) in postoperative patients with EC and reduced fatigue and the incidence of postoperative pneumonia. All in all, the results of our meta-analysis support the use of HEN after esophagectomy.
A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC
Authors: Rao Zuqin , Li Heng , Yao Wenchao , Wang Qiang , Ma Biao , Xue Dongbo , Meng Xianzhi 
Published: July 2022

Decaprenyl diphosphate synthase subunit 1 (PDSS1) is closely related to a variety of human diseases, but its expression pattern and biological function in HCC have not been studied to date.MethodsThe expression level of PDSS1 was analyzed using the TCGA and GEO databases. The relationships between PDSS1 and patient clinicopathological characteristics were verified based on TCGA clinical data. Additionally, the co-expressed genes of PDSS1were investigated and Gene Set Enrichment Analysis (GSEA) was conducted using LinkedOmics. Next, the association between PDSS1 and immune infiltration was determined using version 1.34.0 of the GSVA package. EdU assay, colony-formation assay, transwell assay, wound-healing assay, and flow cytometry analysis were used to assess the effect of PDSS1 on the cell phenotype.ResultsPDSS1 was upregulated in HCC compared with adjacent tissues. High PDSS1 in HCC was associated with poor overall survival, disease-specific survival, and progress-free interval. Results suggested that PDSS1 may activate multiple oncogenic pathways in HCC, especially those involved in the cell cycle. The expression of PDSS1 was significantly related to Th2 cells, TFH, T helper cells, NK CD56bright cells, cytotoxic cells, DC, CD8 T cells, and neutrophils. PDSS1 knockdown inhibited cell proliferation, cell cycle, migration and invasion. Furthermore, PDSS1 acted as an oncogene through the STAT3 signaling pathway.ConclusionOur study reveals that a high level of PDSS1 is significantly correlated with poor patient prognosis and immune cell infiltration in HCC. PDSS1 may be a novel biomarker and potential therapeutic target for HCC.