The casual relationship between autoimmune diseases and multiple myeloma: a Mendelian randomization study.

Observational studies showed possible associations between systemic lupus erythematosus and multiple myeloma. However, whether there is a casual relationship between different types of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis, and juvenile idiopathic arthritis) and multiple myeloma (MM) is not well known. We performed a two-sample Mendelian randomization (MR) study to estimate the casual relationship. Summary-level data of autoimmune diseases were gained from published genome-wide association studies while data of MM was obtained from UKBiobank. The Inverse-Variance Weighted (IVW) method was used as the primary analysis method to interpret the study results, with MR-Egger and weighted median as complementary methods of analysis. There is causal relationship between primary sclerosing cholangitis [OR = 1.00015, 95% CI 1.000048-1.000254, P = 0.004] and MM. Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MM. Considering the important role of age at recruitment and body mass index (BMI) in MM, we excluded these relevant instrument variables, and similar results were obtained. The accuracy and robustness of these findings were confirmed by sensitivity tests. Overall, MR analysis suggests that genetic liability to primary sclerosing cholangitis could be causally related to the increasing risk of MM. This finding may serve as a guide for clinical attention to patients with autoimmune diseases and their early screening for MM.

Comparison of the effects of using feedback devices for training or simulated cardiopulmonary arrest.

BACKGROUND: High-quality chest compression is essential for successful cardiac arrest resuscitation. High-quality cardiopulmonary resuscitation (CPR) can effectively improve the survival rate of patients with cardiopulmonary arrest. However, bystanders untrained in cardiopulmonary resuscitation may provide inadequate chest compressions. Previous studies have shown that the use of feedback devices in training alone or in simulated cardiopulmonary arrest alone can improve cardiopulmonary resuscitation. This study aims to determine whether using an audiovisual feedback (AVF) device during CPR training or a simulated cardiopulmonary arrest (CA) scenario would be more effective in improving the quality of chest compressions (CC). METHODS: We use a prospective, randomized, 2 × 2 factorial design trial. A total of 160 participants from Wuhan University and senior clinical medicine undergraduates who had not participated in any CPR training before and had no actual CPR experience are recruited. Each participant is randomized to 1 of 4 permutations, including AVF device vs. no AVF device during CPR training and AVF device vs. no AVF device during simulated CA. Main outcomes and measures are the depth, the percentage of CCs with correct depth (5-6 cm), the rate of CCs, and the percentage of CCs with the correct rate (100-120 cpm). RESULTS: The use of the AVF device during simulated CA resulted in improved CC quality. In CA without AVF device, the average compression depth and the percentage of adequate depth with AVF device are 5.1 cm, 5.0 cm and 55.5%, 56.3%, respectively, which are higher than those without AVF device (4.5 cm, 4.7 cm and 32.8%, 33.6%). (p = 0.011, p = 0.000, both < 0.05).Compared with CA without AVF device, the average compression rate and the percentage of adequate rate with AVF device are 112.3 cpm, 111.2 cpm and 79.4%, 83.1%, respectively. The average compression rate and the percentage of adequate rate without using the AVF device are 112.4 cpm, 110.3 cpm and 71.5%, 68.5%, respectively. (p = 0.567 > 0.05, p = 0.017 < 0.05)Although the average compression rate in group D is slightly lower than that in group C, the percentage of suitable frequency with the feedback device is still higher than that without AVF device. CONCLUSION: Using a feedback device during simulated cardiopulmonary arrest is more effective in improving cardiopulmonary resuscitation than during training.

Combination of On-Line and Off-Line Two-Dimensional Liquid Chromatography-Mass Spectrometry for Comprehensive Characterization of mAb Charge Variants and Precise Instructions for Rapid Process Development.

Charge variants, as an important quality attribute of mAbs, must be comprehensively characterized and monitored during development. However, due to their complex structure, the characterization of charge variants is challenging, labor-intensive, and time-consuming when using traditional approaches. This work combines on-line and off-line 2D-LC-MS to comprehensively characterize mAb charge variants and quickly offer precise instructions for process development. Six charge variant peaks of mAb 1 were identified using the developed platform. Off-line 2D-LC-MS analysis at the peptide level showed that the acidic peak P1 and the basic peaks P4 and P5 were caused by the deamidation of asparagine, the oxidation of methionine, and incomplete C-terminal K loss, respectively. On-line 2D-LC-MS at the intact protein level was used to identify the root causes, and it was found that the acidic peak P2 and the basic peak P6 were due to the glutathionylation of cysteine and succinimidation of aspartic acid, respectively, which were not found in off-line 2D-LC-MS because of the loss occurring during pre-treatment. These results suggest that process development could focus on cell culture for adjustment of glutathionylation. In this paper, we propose the concept of precision process development based on on-line 2D-LC-MS, which could quickly offer useful data with only 0.6 mg mAb within 6 h for precise instructions for process development. Overall, the combination of on-line and off-line 2D-LC-MS can characterize mAb charge variants more comprehensively, precisely, and quickly than other approaches. This is a very effective platform with routine operations that provides precise instructions for process development within hours, and will help to accelerate the development of innovative therapeutics.

Probiotics Alleviate Chemotherapy-Associated Intestinal Mucosal Injury via the TLR4-NFκB Signaling Pathway.

Introduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ. Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1ß, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKß, IκBα, and P65 with their phosphorylation in jejunum were measured. Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos-IKKß and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group. Conclusion: LGG inhibits the activation of the TLR4-NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.

Exploration of acupuncture therapy in the treatment of MCI patients with the ApoE ε4 gene based on the brain-gut axis theory.

BACKGROUND: Mild cognitive impairment (MCI) is the predementia phase of Alzheimer's disease (AD). The intestinal microbiome is altered in MCI and AD, and apolipoprotein E (ApoE) ε4 gene polymorphism is a risk factor for the progression of MCI to AD. This study aims to investigate the improvement in cognitive function of MCI patients with and without ApoE ε4 due to acupuncture and the changes in gut microbiota community composition and abundance in MCI. METHODS: This randomized assessor-blind controlled study will enrol MCI patients with and without the ApoE ε4 gene (n = 60/60). Sixty subjects with the ApoE ε4 gene and 60 subjects without the ApoE ε4 gene will be randomly allocated into treatment and control groups in a 1:1 ratio. Intestinal microbiome profiles will be evaluated by 16 S rRNA sequencing of faecal samples and compared between the groups. RESULTS/CONCLUSIONS: Acupuncture is an effective method to improve cognitive function in MCI. This study will provide data on the relationship between the gut microbiota and the effectiveness of acupuncture in patients with MCI from a new angle. This study will also provide data on the relationship between the gut microbiota and an AD susceptibility gene by integrating microbiologic and molecular approaches. TRIAL REGISTRATION: www.chictr.org.cn , ID: ChiCTR2100043017, recorded on 4 February 2021.

AFM-based spherical indentation of a brush-coated soft material: modeling the bottom effect.

It is a common practice in the atomic force microscopy (AFM)-based studies of living cells to differentiate them by values of the elastic (Young's) modulus, which is supposed to be an effective characteristic of the mechanical properties of a cell as a heterogeneous matter. The elastic response of a cell to AFM indentation is known to be affected by a relative distance from an AFM probe to a solid support on to which the cell is cultured. Besides this so-called bottom effect, AFM measurements may carry significant information regarding the effect of molecular brushes covering living cells. Here, we develop a mathematical model for determining the intrinsic effective Young's modulus of a single brush-coated cell from the force-indentation curve with the bottom effect taken into account. The mathematical model is illustrated with the example of AFM data on testing of an eukaryotic cell taken from the literature.

Short-term environmental nitrogen dioxide exposure and neurology clinic visits for headaches, a time-series study in Wuhan, China.

BACKGROUND: Previous studies showed the adverse impacts of air pollution on headache attacks in developed countries. However, evidence is limited to the impact of exposure to air pollutants on headache attacks. In this study, we aimed to explore the impact of nitrogen dioxide (NO2) exposure on neurology clinic visits (NCVs) for headache onsets. METHODS: Records of NCVs for headaches, concentrations of ambient NO2, and meteorological variables were collected in Wuhan, China, from January 1st, 2017, to November 30th, 2019. A time-series study was conducted to investigate the short-term effects of NO2 exposure on daily NCVs for headaches. Stratified analyses were also computed according to season, age, and sex, and the exposure-response (E-R) curve was then plotted. RESULTS: A total of 11,436 records of NCVs for headaches were enrolled in our study during the period. A 10-µg/m3 increase of ambient NO2 corresponded to a 3.64% elevation of daily NCVs for headaches (95%CI: 1.02%, 6.32%, P = 0.006). Moreover, females aged less than 50 years of age were more susceptible compared to males (4.10% vs. 2.97%, P = 0.007). The short-term effects of NO2 exposure on daily NCVs for headaches were stronger in cool seasons than in warm seasons (6.31% vs. 0.79%, P = 0.0009). CONCLUSION: Our findings highlight that short-term exposure to ambient NO2 positively correlated with NCVs for headaches in Wuhan, China, and the adverse effects varied by season, age, and sex.

Attitudes and willingness toward out-of-hospital CPR and AED: A questionnaire study among Chinese middle school students.

Objectives: This study's purpose was to assess the attitudes and willingness of middle school students to perform cardiopulmonary resuscitation (CPR) and to use automated external defibrillator (AED) in emergencies, and to evaluate the overall effects of first aid training. Results: Middle school students demonstrated a high willingness to learn CPR (95.87%) and AED (77.90%). However, the rate of CPR (9.87%) and AED (3.51%) training was relatively low. These trainings could improve their confidence while facing emergencies. Their main concerns were "Lack of first aid knowledge", "Lack of confidence in rescue skills" and "Fear of hurting the patient". Conclusions: Chinese middle school students are willing to learn CPR and AED skills, but relative trainings are insufficient and should be reinforced.

Acute effects of ambient air pollution on daily neurology clinic visits for vertigo: a time-series study in Wuhan, China.

This study aimed to disclose the relationship between ambient air pollution and neurology clinic visits (NCVs) for vertigo. A time-series study was conducted to examine relationships between six different criteria air pollutants (SO2, NO2, PM2.5, PM10, CO, and O3) and daily NCVs for vertigo in Wuhan, China, from January 1st, 2017 to November 30th, 2019. Stratified analyses were computed according to gender, age, and season. A total of 14,749 records of NCVs for vertigo were enrolled in this study. Data showed that the increase in daily NCVs for vertigo corresponding to 10 µg/m3 increase of respective pollutants are: SO2 (- 7.60%; 95% CI: - 14.25 to - 0.44%), NO2 (3.14%; 95% CI: 0.23 to 6.13%), PM2.5 (0.53%; 95% CI: - 0.66 to 1.74%), PM10 (1.32%; 95% CI: - 0.36 to 3.06%), CO (0.00%; 95% CI: - 0.12 to 0.13%), and O3 (0.90%; 95% CI: - 0.01% to 1.83%). Males were more susceptible to acute exposure to SO2 and NO2, compared to females (SO2: - 11.91% vs. - 4.16%; NO2: 3.95% vs. 2.92%), whereas the acute effect of O3 exposure was more significantly obvious in females than males (0.94% vs. 0.87%). Moreover, correlations between daily NCVs for vertigo and acute exposure to SO2, NO2, and O3 were all stronger in individuals under 50 years old (SO2: - 12.75% vs. - 4.41%; NO2: 4.55% vs. 2.75%; O3: 1.27% vs. 0.70%). Short-term exposure to PM2.5 was more significantly associated with daily NCVs for vertigo in cool seasons (1.62% vs. - 0.68%), while the correlation between CO exposure and daily NCVs for vertigo was stronger in warm seasons (0.21% vs. - 0.03%). Our study demonstrated acute exposure to ambient NO2 and O3 positively associated with daily NCVs for vertigo. Acute effects of air pollution on daily NCVs for vertigo varied according to gender, age, and season.

[Development and application of an smart emergency respirator with open airway].

To solve the problems of insufficient airway opening, insufficient or excessive ventilation, ventilation interruption, and the rescuer's physical strength during the process of cardiopulmonary resuscitation (CPR) outside the hospital and in the hospital, and to ensure the accuracy of ventilation frequency rate and tidal volume. Zhongnan Hospital and School of Nursing, Wuhan University, jointly designed and developed a smart emergency respirator with open airway function, that has been granted National Utility Model Patent of China (ZL 2021 2 1557989.8). The device is structured of pillow, pneumatic booster pump and mask. It can be used simply by plugging the pillow under the patient's head and shoulder, turning on the power supply and wearing the mask. The smart emergency respirator can quickly and effectively open the patient's airway and give accurate ventilation with adjustable ventilation parameters. The default settings are 10 times/min in respiratory rate and 500 mL in tidal volume. The whole operation does not require the operator have professional operation ability, which can be independently applied used in any cases without oxygen source or power supply, therefore, the application scenario has no limit. The device has the advantages of small size, simple operation and low production cost, which can reduce human source, save physical strength and significantly improve the quality of CPR. The device is suitable for respiratory support in multiple scenes outside and inside the hospital, and can significantly improve the success rate of treatment.

Short-term effects of ambient air pollution on emergency department visits for urolithiasis: A time-series study in Wuhan, China.

Background: Previous studies have explored the correlation between short-term exposure to air pollution and urinary system diseases, but lack of evidence on the correlation between air pollution and urolithiasis. Methods: Daily data of emergency department visits (EDVs), concentrations of six air pollutants (SO2, NO2, PM2.5, PM10, CO, and O3) and meteorological variables were collected in Wuhan, China, from 2016 to 2018. And a time-series study was conducted to investigate short-term effects of air pollutants on urolithiasis EDVs. In addition, stratified analyses by season, age and gender were also conducted. Results: A total of 7,483 urolithiasis EDVs were included during the study period. A 10-µg/m3 increase of SO2, NO2, PM2.5, CO, PM10, and O3 corresponded to 15.02% (95% confidence interval [CI]: 1.69%, 30.11%), 1.96% (95% CI: 0.19%, 3.76%), 1.09% (95% CI:-0.24%, 2.43%), 0.14% (95% CI: 0.02%, 0.26%), 0.72% (95% CI: 0.02%, 1.43%), and 1.17% (95% CI: 0.40%, 1.94%) increases in daily urolithiasis EDVs. Significant positive correlations were observed between SO2, NO2, CO, and O3 and urolithiasis EDVs. The correlations were mainly among females (especially PM2.5 and CO) and younger people (especially SO2, NO2, and PM10) but the effect of CO was more obvious in elders. Furthermore, the effects of SO2 and CO were stronger in warm seasons, while the effects of NO2 were stronger in cool seasons. Conclusion: Our time-series study indicates that short-term exposure to air pollution (especially SO2, NO2, CO, and O3) was positively correlated with EDVs for urolithiasis in Wuhan, China, and the effects varied by season, age and gender.

Effects of Electroacupuncture for Opioid-Induced Constipation in Patients With Cancer in China: A Randomized Clinical Trial.

Importance: Opioid-induced constipation (OIC) is prevalent among patients treated with opioids for cancer pain. Safe and effective therapies for OIC in patients with cancer remain an unmet need. Objective: To determine the efficacy of electroacupuncture (EA) for OIC in patients with cancer. Design, Setting, and Participants: This randomized clinical trial was conducted at 6 tertiary hospitals in China among 100 adult patients with cancer who were screened for OIC and enrolled between May 1, 2019, and December 11, 2021. Interventions: Patients were randomized to receive 24 sessions of EA or sham electroacupuncture (SA) over 8 weeks and then were followed up for 8 weeks after treatment. Main Outcomes and Measures: The primary outcome was the proportion of overall responders, defined as patients who had at least 3 spontaneous bowel movements (SBMs) per week and an increase of at least 1 SBM from baseline in the same week for at least 6 of the 8 weeks of the treatment period. All statistical analyses were based on the intention-to-treat principle. Results: A total of 100 patients (mean [SD] age, 64.4 [10.5] years; 56 men [56.0%]) underwent randomization; 50 were randomly assigned to each group. Among them, 44 of 50 patients (88.0%) in the EA group and 42 of 50 patients (84.0%) in the SA group received at least 20 (≥83.3%) sessions of treatment. The proportion of overall responders at week 8 was 40.1% (95% CI, 26.1%-54.1%) in the EA group and 9.0% (95% CI, 0.5%-17.4%) in the SA group (difference between groups, 31.1 percentage points [95% CI, 14.8-47.6 percentage points]; P < .001). Compared with SA, EA provided greater relief for most OIC symptoms and improved quality of life among patients with OIC. Electroacupuncture had no effects on cancer pain and its opioid treatment dosage. Electroacupuncture-related adverse events were rare, and, if any, all were mild and transient. Conclusions and Relevance: This randomized clinical trial found that 8-week EA treatment could increase weekly SBMs with a good safety profile and improve quality of life for the treatment of OIC. Electroacupuncture thus provided an alternative option for OIC in adult patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03797586.

Clinical significance and molecular annotation of cellular morphometric subtypes in lower-grade gliomas discovered by machine learning.

BACKGROUND: Lower-grade gliomas (LGG) are heterogeneous diseases by clinical, histological, and molecular criteria. We aimed to personalize the diagnosis and therapy of LGG patients by developing and validating robust cellular morphometric subtypes (CMS) and to uncover the molecular signatures underlying these subtypes. METHODS: Cellular morphometric biomarkers (CMBs) were identified with artificial intelligence technique from TCGA-LGG cohort. Consensus clustering was used to define CMS. Survival analysis was performed to assess the clinical impact of CMBs and CMS. A nomogram was constructed to predict 3- and 5-year overall survival (OS) of LGG patients. Tumor mutational burden (TMB) and immune cell infiltration between subtypes were analyzed using the Mann-Whitney U test. The double-blinded validation for important immunotherapy-related biomarkers was executed using immunohistochemistry (IHC). RESULTS: We developed a machine learning (ML) pipeline to extract CMBs from whole-slide images of tissue histology; identifying and externally validating robust CMS of LGGs in multicenter cohorts. The subtypes had independent predicted OS across all three independent cohorts. In the TCGA-LGG cohort, patients within the poor-prognosis subtype responded poorly to primary and follow-up therapies. LGGs within the poor-prognosis subtype were characterized by high mutational burden, high frequencies of copy number alterations, and high levels of tumor-infiltrating lymphocytes and immune checkpoint genes. Higher levels of PD-1/PD-L1/CTLA-4 were confirmed by IHC staining. In addition, the subtypes learned from LGG demonstrate translational impact on glioblastoma (GBM). CONCLUSIONS: We developed and validated a framework (CMS-ML) for CMS discovery in LGG associated with specific molecular alterations, immune microenvironment, prognosis, and treatment response.

Combination treatment of acupoint therapy and conventional medication for motor function of Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Combination treatment with acupoint therapy and conventional medication (CM) has been proposed as a strategy that could improve motor dysfunction in Parkinson's disease (PD). We performed this systematic review and meta-analysis to assess the effects of this combination treatment on motor function in patients with PD. METHODS: We searched randomized controlled trials (RCTs) from eight databases, comparing combined acupoint therapy and CM and CM (alone or with sham interventions). The quality of the trials was evaluated according to the Cochrane risk of bias. Subgroup and sensitivity analyses were performed on different types of acupoint interventions. RESULTS: Forty-seven trials of 2929 participants were included, with 45 studies used for the meta-analyses. Combination treatment yielded an improved reduction in United Parkinson's disease rating scale (UPDRS) III of -3.85 [95% CI, -4.83 to -2.86] and Webster scale score of -3.17 [95% CI, -4.07 to -2.27]. Further analyses demonstrated that real (compared with sham) intervention was linked to a decreased UPDRS III of -2.02 ([95% CI, -3.60 to -0.44], I2 = 40%), and beneficial effects were observed when combination intervention was used for patients with Hoehn-Yahr (H-Y) stages >3 with mild to moderate stimulation for 4-12-week treatment. CONCLUSIONS: Acupoint therapy and CM treatment may improve motor function of patients with PD. Patients with H-Y stage >3 could tolerate real acupoint intervention with mild to moderate stimulation for 4-12-week treatment and showed improvement. However, this was demonstrated with low to moderate levels of evidence in statistical description.

Establishment and validation of PTE prediction model in patients with cerebral contusion.

Post-traumatic epilepsy (PTE) is an important cause of poor prognosis in patients with cerebral contusions. The primary purpose of this study is to evaluate the high-risk factors of PTE by summarizing and analyzing the baseline data, laboratory examination, and imaging features of patients with a cerebral contusion, and then developing a Nomogram prediction model and validating it. This study included 457 patients diagnosed with cerebral contusion who met the inclusion criteria from November 2016 to November 2019 at the Qinghai Provincial People's Hospital. All patients were assessed for seizure activity seven days after injury. Univariate analysis was used to determine the risk factors for PTE. Significant risk factors in univariate analysis were selected for binary logistic regression analysis. P < 0.05 was statistically significant. Based on the binary logistic regression analysis results, the prediction scoring system of PTE is established by Nomogram, and the line chart model is drawn. Finally, external validation was performed on 457 participants to assess its performance. Univariate and binary logistic regression analyses were performed using SPSS software, and the independent predictors significantly associated with PTE were screened as Contusion site, Chronic alcohol use, Contusion volume, Skull fracture, Subdural hematoma (SDH), Glasgow coma scale (GCS) score, and Non late post-traumatic seizure (Non-LPTS). Based on this, a Nomogram model was developed. The prediction accuracy of our scoring system was C-index = 98.29%. The confidence interval of the C-index was 97.28% ~ 99.30%. Internal validation showed that the calibration plot of this model was close to the ideal line. This study developed and verified a highly accurate Nomogram model, which can be used to individualize PTE prediction in patients with a cerebral contusion. It can identify individuals at high risk of PTE and help us pay attention to prevention in advance. The model has a low cost and is easy to be popularized in the clinic. This model still has some limitations and deficiencies, which need to be verified and improved by future large-sample and multicenter prospective studies.

Development and validation of chest CT-based imaging biomarkers for early stage COVID-19 screening.

Coronavirus Disease 2019 (COVID-19) is currently a global pandemic, and early screening is one of the key factors for COVID-19 control and treatment. Here, we developed and validated chest CT-based imaging biomarkers for COVID-19 patient screening from two independent hospitals with 419 patients. We identified the vasculature-like signals from CT images and found that, compared to healthy and community acquired pneumonia (CAP) patients, COVID-19 patients display a significantly higher abundance of these signals. Furthermore, unsupervised feature learning led to the discovery of clinical-relevant imaging biomarkers from the vasculature-like signals for accurate and sensitive COVID-19 screening that have been double-blindly validated in an independent hospital (sensitivity: 0.941, specificity: 0.920, AUC: 0.971, accuracy 0.931, F1 score: 0.929). Our findings could open a new avenue to assist screening of COVID-19 patients.

Develop a diagnostic tool for dementia using machine learning and non-imaging features.

Background: Early identification of Alzheimer's disease or mild cognitive impairment can help guide direct prevention and supportive treatments, improve outcomes, and reduce medical costs. Existing advanced diagnostic tools are mostly based on neuroimaging and suffer from certain problems in cost, reliability, repeatability, accessibility, ease of use, and clinical integration. To address these problems, we developed, evaluated, and implemented an early diagnostic tool using machine learning and non-imaging factors. Methods and results: A total of 654 participants aged 65 or older from the Nursing Home in Hangzhou, China were identified. Information collected from these patients includes dementia status and 70 demographic, cognitive, socioeconomic, and clinical features. Logistic regression, support vector machine (SVM), neural network, random forest, extreme gradient boosting (XGBoost), least absolute shrinkage and selection operator (LASSO), and best subset models were trained, tuned, and internally validated using a novel double cross validation algorithm and multiple evaluation metrics. The trained models were also compared and externally validated using a separate dataset with 1,100 participants from four communities in Zhejiang Province, China. The model with the best performance was then identified and implemented online with a friendly user interface. For the nursing dataset, the top three models are the neural network (AUROC = 0.9435), XGBoost (AUROC = 0.9398), and SVM with the polynomial kernel (AUROC = 0.9213). With the community dataset, the best three models are the random forest (AUROC = 0.9259), SVM with linear kernel (AUROC = 0.9282), and SVM with polynomial kernel (AUROC = 0.9213). The F1 scores and area under the precision-recall curve showed that the SVMs, neural network, and random forest were robust on the unbalanced community dataset. Overall the SVM with the polynomial kernel was found to be the best model. The LASSO and best subset models identified 17 features most relevant to dementia prediction, mostly from cognitive test results and socioeconomic characteristics. Conclusion: Our non-imaging-based diagnostic tool can effectively predict dementia outcomes. The tool can be conveniently incorporated into clinical practice. Its online implementation allows zero barriers to its use, which enhances the disease's diagnosis, improves the quality of care, and reduces costs.

[Efficacy prediction of acupuncture in treatment of moderate-to-severe allergic rhinitis based on miRNA expression profile].

OBJECTIVE: To investigate the differential characteristics of plasma mircoRNA (miRNA) expression profile in the patients of moderate-to-severe allergic rhinitis treated with acupuncture so as to provide an index for screening the potential biomarkers of acupuncture efficacy. METHODS: Of 33 patients of moderate-to-severe allergic rhinitis underwent acupuncture, the superior efficacy patients (superior efficacy group, 3 cases) and the inferior efficacy patients (inferior efficacy group, 3 cases) were selected. Using human miRNA microarray technology, the differences in plasma miRNA expression before and after treatment were analyzed in the patients of two groups. Besides, 10 cases of superior efficacy and 10 cases of inferior one were selected respectively among the patients of moderate-to-severe allergic rhinitis treated with same acupuncture regimen; and the real-time PCR was used to validate miRNAs of differential expression determined by microarray technology. The bioinformatics analysis was performed for miRNAs of significant differences in expression so as to predict the potential functional target genes, and then, the predicted target genes were annotated in reference with the databases of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). RESULTS: Before treatment, there were 51 miRNAs of differential expression between two groups, of which, the expression levels of 26 miRNAs were up-regulated and those of 25 miRNAs were down-regulated. Compared with before treatment, 33 miRNAs presented differential expression in the superior efficacy group after treatment. The results of real-time PCR showed that the expression levels of hsa-miR-126-3p, hsa-miR-15a-5p, hsa-miR-494-3p and hsa-miR-574-5p were consistent with the results of microarray analysis in tendency. GO/KEGG analysis indicated that miRNAs with significant differences of expression between two groups were involved in regulating various biological processes, molecular functions and signaling pathways. CONCLUSION: Plasma miRNA-mediated biological processes may be associated with the efficacy response of acupuncture in treatment of moderate-to-severe allergic rhinitis. Plasma miRNAs of differential expression may be the potential non-invasive biomarkers to predict the effectiveness of acupuncture on moderate-to-severe allergic rhinitis.

Feasibility and positive effects of scalp acupuncture for modulating motor and cerebral activity in Parkinson's disease: A pilot study.

BACKGROUND: A variety of acupuncture therapies have shown efficacy in Parkinson's disease (PD). OBJECTIVE: To evaluate scalp acupuncture (SA) effects on motor and cerebral activity by using gait equipment and resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twelve patients with PD received SA. They underwent the first functional-imaging scan after tactile stimulation and the second scan following needle removal. Gait test and local sensation assessment were performed immediately after each functional scan. Gait parameter differences between pre- and post-SA were analyzed using a paired t-test and altered brain areas in degree centrality (DC) and fractional amplitude of low-frequency fluctuation (fALFF) were identified between the two scans. RESULTS: Eight patients completed the experiment. Stride length, maximum ankle height, maximum ankle horizontal displacement, gait speed, and range of shank motion significantly increased post-treatment (P < 0.05). fALFF in left middle frontal gyrus and DC in left cerebellum (corrected) increased, while fALFF in left inferior parietal lobule (corrected) during SA decreased, compared with those in tactile stimulation. A positive correlation was observed between right limb swings and both fALFF areas. CONCLUSIONS: Differences in gait and brain analyses presented modulation to motor and brain activity in PD, thus, providing preliminary evidence for SA efficacy.

Transcriptome-Wide N6-Methyladenosine Methylome Alteration in the Rat Spinal Cord After Acute Traumatic Spinal Cord Injury.

Recent studies showed that RNA N6-methyladenosine (m6A) plays an important role in neurological diseases. We used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) technology to generate the m6A modification map after traumatic spinal cord injury (TSCI). A total of 2,609 differential m6A peaks were identified after TSCI. Our RNA sequencing results after TSCI showed 4,206 genes with significantly altered expression. Cross-link analysis of m6A sequencing results and RNA sequencing results showed that 141 hyper-methylated genes were upregulated, 53 hyper-methylated genes were downregulated, 57 hypo-methylated genes were upregulated, and 197 hypo-methylated genes were downregulated. Among these, the important inflammatory response factor Tlr4 and the important member of the neurotrophin family Ngf were both upregulated and hyper-methylated after TSCI. This study provides that in the future, the epigenetic modifications of the genes could be used as an indicator of TSCI.