bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning-based infection prediction model for newly diagnosed multiple myeloma patients
Authors: Peng Ting , Liu Leping , Liu Feiyang , Ding Liang , Liu Jing , Zhou Han , Liu Chong 
Published: January 2023

ObjectiveTo understand the infection characteristics and risk factors for infection by analyzing multicenter clinical data of newly diagnosed multiple myeloma (NDMM) patients.MethodsThis study reviewed 564 NDMM patients from 2 large tertiary hospitals from January 2018 to December 2021, of whom 395 comprised the training set and 169 comprised the validation set. Thirty-eight variables from first admission records were collected, including patient demographic characteristics, clinical scores and characteristics, laboratory indicators, complications, and medication history, and key variables were screened using the Lasso method. Multiple machine learning algorithms were compared, and the best performing algorithm was used to build a machine learning prediction model. The model performance was evaluated using the AUC, accuracy, and Youden’s index. Finally, the SHAP package was used to assess two cases and demonstrate the application of the model.ResultsIn this study, 15 important key variables were selected, namely, age, ECOG, osteolytic disruption, VCD, neutrophils, lymphocytes, monocytes, hemoglobin, platelets, albumin, creatinine, lactate dehydrogenase, affected globulin, β2 microglobulin, and preventive medicine. The predictive performance of the XGBoost model was significantly better than that of the other models (AUROC: 0.8664), and it also performed well for the expected dataset (accuracy: 68.64%).ConclusionA machine learning algorithm was used to establish an infection prediction model for NDMM patients that was simple, convenient, validated, and performed well in reducing the incidence of infection and improving the prognosis of patients.
Combined neuromuscular electrical stimulation and transcutaneous spinal direct current stimulation increases motor cortical plasticity in healthy humans
Authors: Koseki Tadaki , Kudo Daisuke , Yoshida Kaito , Nito Mitsuhiro , Takano Keita , Jin Masafumi , Tanabe Shigeo , Sato Toshiaki , Katoh Hiroshi , Yamaguchi Tomofumi 
Published: January 2023

IntroductionNeuromuscular electrical stimulation (NMES) induces neural plasticity of the central nervous system (CNS) and improves motor function in patients with CNS lesions. However, the extended stimulus duration of NMES reduces its clinical applicability. Transcutaneous spinal direct current stimulation (tsDCS), which increases afferent input, may enhance the effects and reduce the stimulus duration of NMES. This study investigated the excitability of the motor cortex, somatosensory cortex, and spinal motor neurons after the combined stimulation of NMES and tsDCS.MethodsAmong the 55 participants in this study, 24 were allocated to experiment 1, 15 to experiment 2, and 16 to experiment 3. They received intervention for 20 min on different days: (1) NMES combined with tsDCS (NMES + tsDCS), (2) NMES combined with sham tsDCS (NMES + sham tsDCS), and (3) sham NMES combined with tsDCS (sham NMES + tsDCS). NMES was delivered to the right common peroneal nerve at 25 Hz with the intensity at 120% of the motor threshold. For tsDCS, the cathodal electrode was positioned on the thoracic 10th–12th vertebral levels, and the anodal electrode was located on the right shoulder. The stimulus intensity was 2.5 mA. In experiment 1, motor evoked potentials (MEPs) and short-latency intracortical inhibition (SICI) were measured by transcranial magnetic stimulation up to 60 min after stimulation. The spinal motor neurons’ excitability was assessed by recording the posterior root muscle reflex (PRMR) induced via transcutaneous spinal cord stimulation in experiment 2, and the primary somatosensory cortex excitability was evaluated by recording the somatosensory evoked potentials (SEPs) in experiment 3 up to 15 min after stimulation.ResultsCompared to before the stimulation, NMES + tsDCS significantly increased MEP for 60 min or more, and significantly decreased SICI immediately after. Conversely contrast, the PRMR significantly decreased immediately after, and SEPs were unchanged.DiscussionThese results suggest that simultaneous afferent inputs from different stimulus positions critically induce primary motor cortex plasticity. The combined stimulation of NMES with tsDCS may facilitate the development of a new neurorehabilitation technique.
Coherence based graph convolution network for motor imagery-induced EEG after spinal cord injury
Authors: Li Han , Liu Ming , Yu Xin , Zhu JianQun , Wang Chongfeng , Chen Xinyi , Feng Chao , Leng Jiancai , Zhang Yang , Xu Fangzhou 
Published: January 2023

BackgroundSpinal cord injury (SCI) may lead to impaired motor function, autonomic nervous system dysfunction, and other dysfunctions. Brain-computer Interface (BCI) system based on motor imagery (MI) can provide more scientific and effective treatment solutions for SCI patients.MethodsAccording to the interaction between brain regions, a coherence-based graph convolutional network (C-GCN) method is proposed to extract the temporal-frequency-spatial features and functional connectivity information of EEG signals. The proposed algorithm constructs multi-channel EEG features based on coherence networks as graphical signals and then classifies MI tasks. Different from the traditional graphical convolutional neural network (GCN), the C-GCN method uses the coherence network of EEG signals to determine MI-related functional connections, which are used to represent the intrinsic connections between EEG channels in different rhythms and different MI tasks. EEG data of SCI patients and healthy subjects have been analyzed, where healthy subjects served as the control group.ResultsThe experimental results show that the C-GCN method can achieve the best classification performance with certain reliability and stability, the highest classification accuracy is 96.85%.ConclusionThe proposed framework can provide an effective theoretical basis for the rehabilitation treatment of SCI patients.
Identification of a tumor immune-inflammation signature predicting prognosis and immune status in breast cancer
Authors: Liu Yajing , Ouyang Wenhao , Huang Hong , Tan Yujie , Zhang Zebang , Yu Yunfang , Yao Herui 
Published: January 2023

BackgroundBreast cancer has become the malignancy with the highest mortality rate in female patients worldwide. The limited efficacy of immunotherapy as a breast cancer treatment has fueled the development of research on the tumor immune microenvironment.MethodsIn this study, data on breast cancer patients were collected from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. Differential gene expression analysis, univariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed to select overall survival (OS)-related, tumor tissue highly expressed, and immune- and inflammation-related genes. A tumor immune-inflammation signature (TIIS) consisting of 18 genes was finally screened out in the LASSO Cox regression model. Model performance was assessed by time-dependent receiver operating characteristic (ROC) curves. In addition, the CIBERSORT algorithm and abundant expression of immune checkpoints were utilized to clarify the correlation between the risk signature and immune landscape in breast cancer. Furthermore, the association of IL27 with the immune signature was analyzed in pan-cancer and the effect of IL27 on the migration of breast cancer cells was investigated since the regression coefficient of IL27 was the highest.ResultsA TIIS based on 18 genes was constructed via LASSO Cox regression analysis. In the TCGA-BRCA training cohort, 10-year AUC reached 0.89, and prediction performance of this signature was also validated in the METABRIC set. The high-risk group was significantly correlated with less infiltration of tumor-killing immune cells and the lower expression level of the immune checkpoint. Furthermore, we recommended some small-molecule drugs as novel targeted drugs for new breast cancer types. Finally, the relationship between IL27, a significant prognostic immune and inflammation cytokine, and immune status was analyzed in pan-cancer. Expression of IL27 was significantly correlated with immune regulatory gene expression and immune cell infiltration in pan-cancer. Furthermore, IL27 treatment improved breast cancer cell migration.ConclusionThe TIIS represents a promising prognostic tool for estimating OS in patients with breast cancer and is correlated with immune status.
Chidamide-based 3-drug combination regimen reverses molecular relapse post transplantation in AML1-ETO–positive acute myeloid leukemia
Authors: Xi Yang , Chenglong Li , Rong Zhang , Wen Wang , Yu Wang , Jiao Chen , Juan Huang , Feifei Che , Rong Xiao , Tao Jiang , Hui Li , Xiaobing Huang 
Published: January 2023

Objective: We aimed to explore a new method to reverse early relapse in patients with AML1-ETO–positive acute myeloid cell transplantation.Methods: A chidamide-based 3-drug combination regimen was used in our center to treat patients with AML1-ETO–positive AML post transplantation but negative flow cytometry results. A retrospective analysis was performed of the survival rate and possible influencing factors of patients with relapse treated with this regimen in our center from January 2018 to January 2022.Results: The overall response rate was 95.8% (23/24), and the median number of treatment courses was 4 (range, 3–12 courses). The total molecular complete response (MCR) was 79.1% (19/24) after all treatments, and the molecular complete response was 37.5% (9/24) after one cycle of treatment but reached 58.3% (14/24) after four cycles; overall, the proportion of MCR increased gradually with the increase in treatment cycles. The projected 5-year overall survival rate was 73.9%. The projected 5-year leukemia-free survival rate was 64.8%, and the projected 1-year cumulative relapse rate was 35.5%. The incidence of grade II–IV graft-versus-host diseases (GVHD) was 29.2% (7/24), and that of grade III–IV GVHD was 20.8% (5/24), which could be effectively controlled by glucocorticoid therapy combined with calcineurin inhibitors The total incidence of chronic GVHD was 29.2% (7/24), and all cases were localized chronic GVHD. The total infection rate was 33.3% (8/24), mainly involving bacterial and fungal infections, and the incidence of life-threatening infections was 4.17% (1/24). The treatment-related mortality rate was 0%; and the total mortality rate was 20.8% (5/24). Nausea and vomiting, thrombocytopenia, and neutropenia were common adverse reactions, all of which were Common Terminology Criteria for Adverse Events grade 2–3 events and reversible after drug withdrawal. In terms of immunity, Th1 cell counts gradually increased, Th17 cell counts gradually decreased, and the Th1/Th17 ratio gradually increased after treatment. The CD8+ T lymphocyte count increased gradually, while the CD4+ T lymphocyte count did not change significantly.Conclusion: Our chidamide-based 3-drug combination regimen led to a high remission rate and tolerable adverse reactions in patients with AML1-ETO–positive post-transplant relapse, and most patients can achieve long-term survival with this regimen.
Development and validation of two bioanalysis methods for the determination of etimicin in human serum and urine by liquid chromatography-tandem mass spectrometry: Applications to a human pharmacokinetic and breakpoint study
Authors: Cui Xinge , Zheng Xin , Ren Jianwei , Liu Hongzhong , Jia Yuan , Wu Aiguo , Han Xiaohong 
Published: January 2023

Etimicin is a fourth-generation aminoglycoside antibiotic. It has potent activity and low toxicity when employed for the treatment of Gram-negative and Gram-positive bacterial infections. The pharmacokinetics of etimicin in humans have not been elucidated completely. Two liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical methods, without the use of any ion-pairing reagents, were developed and validated for the quantification of etimicin in human samples of serum and urine. Using a deuterated reagent as the internal standard, analytes in serum and urine samples were extracted by protein precipitation and dilution before LC-MS/MS analysis, respectively. For the two methods, chromatographic separations were undertaken under isocratic elution of water–ammonia solution–acetic acid (96:3.6:0.2, v/v/v) and methanol at 50%:50% and a flow rate of 0.35 ml/min within 5 min. A Waters XTerra MS C18 column (2.1 × 150 mm, 3.5 μm) and a column temperature of 40°C were chosen. A Sciex Qtrap 5500 mass spectrometer equipped with an electrospray ion source was used in both methods under multiple-reaction monitoring in positive-ion mode. The two methods showed good linearity, accuracy, and precision with high recovery and a minimal matrix effect in the range of 50.0–20000 ng/ml for serum samples and 50.0–10000 ng/ml for urine samples, respectively. Carry-over effects were not observed. Etimicin remained stable in human samples of serum or urine under the storage, preparation, and analytical conditions of the two methods. These two simple and reliable methods were applied successfully to a dose-escalation, phase I clinical trial of etimicin in Chinese healthy volunteers after intravenous administration of single and multiple doses. Based on these two methods we ascertained, for the first time, the comprehensive pharmacokinetics of etimicin in humans, which will be used for the exploration of the breakpoint research further.
Naringenin protects against acute pancreatitis-associated intestinal injury by inhibiting NLRP3 inflammasome activation via AhR signaling
Authors: Yan Xu , Lin Tianjiao , Zhu Qingyun , Zhang Yushi , Song Zhimin , Pan Xinting 
Published: January 2023

Background: In this study, we examined the functions and mechanisms by which naringenin protects against SAP (severe acute pancreatitis)-related intestinal injury by modulating the AhR/NLRP3 signaling pathway.Material and methods: Fifteen healthy male C57BL/6 mice were randomly divided into SAP (n = 12) and normal (n = 3) groups. Mice in the SAP group received caerulein and lipopolysaccharide intraperitoneal injections and were then randomly assigned to the SAP, NAR, CH223191, and Dexamethasone (DEX) groups. Pathological changes in the pancreatic and intestinal mucosa were observed by Hematoxylin &amp; Eosin (H&amp;E) staining. In vitro, RAW264.7 cells were exposed to lipopolysaccharide and treated with naringenin. The levels of NLRP3, AhR, IL-1β, TNF, and IL-6 in the SAP model and RAW264.7 cells were evaluated by enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. The nuclear translocation of AhR was shown by immunofluorescence. AutoDockTools was used to predict the conformations of naringenin-AhR binding, and PyMol 2.4 was used to visualize the conformations.Results: Mouse pancreatic and intestinal injury was alleviated by treatment with naringenin. Naringenin inhibited the activation of the NLRP3 inflammasome and inhibited damage to intestinal tight junctions. Moreover, naringenin increased AhR nuclear translocation and activated the AhR pathway.Conclusion: Naringenin can reduce SAP-associated intestinal injury by inhibiting the activation of the NLRP3 inflammasome via the AhR signaling pathway.
Effect of increased protein intake and exogenous ketosis on body composition, energy expenditure and exercise capacity during a hypocaloric diet in recreational female athletes
Authors: Hiroux Charlotte , Schouten Moniek , de Glisezinski Isabelle , Simon Chantal , Crampes François , Hespel Peter , Koppo Katrien 
Published: January 2023

Introduction:Since low body weight is an important determinant of success in many sports such as gymnastics, martial arts and figure skating, athletes can benefit from effective weight loss strategies that preserve muscle mass and athletic performance. The present study investigates the effects of increased protein intake and exogenous ketosis on body composition, energy expenditure, exercise capacity, and perceptions of appetite and well-being during a hypocaloric diet in females.Methods:Thirty-two female recreational athletes (age: 22.2 ± .5 years; body weight: 58.3 ± .8 kg; BMI: 20.8 ± .2 kg·m−2) underwent 4 weeks of 30% caloric restriction and were randomized to receive either an increased daily amount of dietary protein (PROT, ∼2.0–2.2 g protein·kg−1·day−1), 3 × 20 g·day−1of a ketone ester (KE), or an isocaloric placebo (PLA). Body composition was measured by DXA, resting energy expenditure (REE) by indirect calorimetry, exercise capacity during a VO2max test, appetite hormones were measured in serum, and perceptions of general well-being were evaluatedviaquestionnaires.Results:The hypocaloric diet reduced body weight by 3.8 ± .3 kg in PLA, 3.2 ± .3 kg in KE and 2.4 ± .2 kg in PROT (Ptime&lt;.0001). The drop in fat mass was similar between treatments (average: 2.6 ± .1 kg, Ptime&lt;.0001), while muscle mass was only reduced in PLA and KE (average: .8 ± .2 kg, Ptime&lt;.05), and remained preserved in PROT (Pinteraction&lt;.01). REE [adjusted for lean mass] was reduced after caloric restriction in PLA (pre: 32.7 ± .5, post: 28.5 ± .6 kcal·day−1·kg−1) and PROT (pre: 32.9 ± 1.0, post: 28.4 ± 1.0 kcal·day−1·kg−1), but not in KE (pre: 31.8 ± .9, post: 30.4 ± .8 kcal·day−1·kg−1) (Pinteraction&lt;.005). Furthermore, time to exhaustion during the VO2max test decreased in PLA (by 2.5 ± .7%,p&lt; .05) but not in KE and PROT (Pinteraction&lt;.05). Lastly, the perception of overall stress increased in PLA and PROT (p&lt; .05), but not in KE (Pinteraction&lt;.05).Conclusion:Increased protein intake effectively prevented muscle wasting and maintained exercise capacity during a period of caloric restriction in female recreational athletes. Furthermore, exogenous ketosis did not affect body composition, but showed its potential in weight management by preserving a drop in exercise capacity and REE and by improving overall stress parameters during a period of caloric restriction.
Characteristics of menstrual cycle disorder and saliva metabolomics of young women in a high-temperature environment
Authors: Wei MengFan , An GaiHong , Fan LiJun , Chen XueWei , Li Chao , Chen JiaJun , Ma Qiang , Yang DanFeng , Wang Jing 
Published: January 2023

Objective: Menstrual disorders induced by high-temperature environments, can seriously damage women’s reproductive health and workability. The regulation mechanism underlying it is not yet to be elucidated. Saliva is an information-rich biological fluid that can reflect systemic diseases. Here, we investigated the characteristics of menstrual cycle disorders and saliva metabolomics to provide a deeper insight of the regulation mechanism of young women in high-temperature environments.Methods: Women from high and normal temperature areas of China were selected and divided into two groups—high-temperature (H group) and control (C group). A questionnaire survey was conducted in summer (July) to investigate the incidence rate of menstrual disorders, characteristics of the disorders, and factors influencing the risk of these disorders in different regions. Metabolomics was applied to analyze the characteristics of the salivary metabolites and neurotransmitters in the two groups of women with menstrual disorders.Results: The incidence rate of menstrual disorders was significantly higher in the H group than that in the C group (p &lt; 0.05). High-temperature environment, stress, and sleep quality were identified as critical factors associated with menstrual disorders. Non-targeted saliva metabolomics identified 64 significantly different metabolites between two groups, which mainly enriched in metabolic pathways such as carbohydrate metabolism, membrane transport, digestive system, and nucleotide metabolism (p &lt; 0.05). N-acetylneuraminic acid, MYO, and tyramine may be candidate markers for early diagnosis of menstrual disorders in high temperature environments. Metabolites may be involving in the acute-phase response during an inflammatory process, to affecting the reproductive system by influencing the HPA axis loop. Regulations about oocyte membrane production and the luteal functions would be exerted in menstrual disorders. Targeted metabolomics of neurotransmitters revealed increased expression of histamine (HA) and glutamine and decreased expression of 5-hydroxyindole acetic acid (5-HIAA) (p &lt; 0.05).Conclusion: Menstrual disorder characteristics induced by high temperature environments were specific. Anxiety, sleep quality and temperature feeling were the key factors to the menstrual disorder. endocrine regulation mechanism and inflammatory reactions might contribute to the development of menstrual disorders through influencing the formation of the follicular cell membrane.
Full-length huntingtin is palmitoylated at multiple sites and post-translationally myristoylated following caspase-cleavage
Authors: Lemarié Fanny L. , Sanders Shaun S. , Nguyen Yen , Martin Dale D. O. , Hayden Michael R. 
Published: January 2023

Introduction: Huntington disease is an autosomal dominant neurodegenerative disorder which is caused by a CAG repeat expansion in the HTT gene that codes for an elongated polyglutamine tract in the huntingtin (HTT) protein. Huntingtin is subjected to multiple post-translational modifications which regulate its cellular functions and degradation. We have previously identified a palmitoylation site at cysteine 214 (C214), catalyzed by the enzymes ZDHHC17 and ZDHHC13. Reduced palmitoylation level of mutant huntingtin is linked to toxicity and loss of function. Moreover, we have described N-terminal myristoylation by the N-myristoyltransferases of a short fragment of huntingtin (HTT553-586) at glycine 553 (G553) following proteolysis at aspartate 552 (D552).Results: Here, we show that huntingtin is palmitoylated at numerous cysteines: C105, C433, C3134 and C3144. In addition, we confirm that full-length huntingtin is cleaved at D552 and post-translationally myristoylated at G553. Importantly, blocking caspase cleavage at the critical and pathogenic aspartate 586 (D586) significantly increases posttranslational myristoylation of huntingtin. In turn, myristoylation of huntingtin promotes the co-interaction between C-terminal and N-terminal huntingtin fragments, which is also protective.Discussion: This suggests that the protective effect of inhibiting caspase-cleavage at D586 may be mediated through post-translational myristoylation of huntingtin at G553.