Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

The real physical image of the affected limb, which is difficult to move in the traditional mirror training, can be realized easily by the rehabilitation robots. During this training, the affected limb is often in a passive state. However, with the gradual recovery of the movement ability, active mirror training becomes a better choice. Consequently, this paper took the self-developed shoulder joint rehabilitation robot with an adjustable structure as an experimental platform, and proposed a mirror training system completed by next four parts. First, the motion trajectory of the healthy limb was obtained by the Inertial Measurement Units (IMU). Then the variable universe fuzzy adaptive proportion differentiation (PD) control was adopted for inner loop, meanwhile, the muscle strength of the affected limb was estimated by the surface electromyography (sEMG). The compensation force for an assisted limb of outer loop was calculated. According to the experimental results, the control system can provide real-time assistance compensation according to the recovery of the affected limb, fully exert the training initiative of the affected limb, and make the affected limb achieve better rehabilitation training effect.
Electromyography ; Humans ; Movement ; Muscle Strength ; Robotics ; Shoulder Joint ; Stroke Rehabilitation

Objective: The aim of the study is to analyze the effects of vestibular spontaneous nystagmus(SN) on the smooth pursuit function of visual ocularmotor system. Methods: A total of 46 patients with acute unilateral peripheral vestibular syndrome with SN (26 cases of vestibular neuritis, 6 cases of Ramsay Hunt Syndrome (RHS) with vertigo, 14 cases of sudden deafness with vertigo) were included in this work. In the study group, the results of SPT and SN test with videonystagmography(VNG) were also reviewed. Taking SPT parameters, the influence of SN intensity on SPT gain, asymmetry and waveform and their correlation were analyzed.SPSS19.0 software was used for statistical analysis. Results: Among the 46 patients, there were 36 cases of SN pointing to the healthy side(SN intensity range of 2.68°/s-32.53°/s), and 10 cases of SN pointing to the affected side (SN intensity range of 2.66°/s-16.54°/s). SN intensity was divided into 3 groups, including light(0.50°/s-5.00°/s), medium(5.01°/s-10.00°/s) and strong(>10.01°/s), accounting for 14 cases(30.4%), 18 cases(39.1%) and 14 cases(30.4%), respectively. The differences of the gain of SPT to the fast phase and slow phase direction in the overall groups and light, medium and strong groups of SN intensity respectively were statistically significant(t_total=13.338, t_light=6.184, t_medium=8.436, t_strong=8.477, all of P<0.001). The difference of SPT gain in SN fast phase direction between groups with different SN intensity was statistically significant(F=9.639, P<0.001),there was no statistically significant difference in SPT gain between the groups on the SN slow phase direction(F=1.137, P=0.330).The SN intensity significantly negatively correlated with the SPT gain of the fast phase direction of SN (r=-0.433, P=0.003), that was, the SPT gain on the fast phase direction of SN decreased with the increase of SN intensity. There was no significant correlation between SN intensity and the gain of SPT on the slow phase direction of SN (r=-0.061, P=0.687). SPT waveform analysis showed that type I, type II and type III accounted for 8 cases(17.4%), 21 cases(45.6%) and 17 cases(37.0%), respectively. The corresponding mean values of SN intensity were (3.71±0.69)°/s, (7.44±1.88)°/s, (20.04±5.53)°/s, respectively, without type IV wave. The intensity of SN was positively correlated with the asymmetric value of the gain of SPT left and right(r=0.450,P=0.002). That was, with the increase of SN strength, the asymmetric value also increased, and the worse the asymmetry of the gain of SPT left and right pursuit was, the worse the SPT waveform was. Conclusion: SPT gain, asymmetry and SPT waveforms are all affected by SN, and the greater the intensity of SN, the greater the influence on the three. When SN is strong, type III waves may occur, suggesting that acute peripheral vestibular syndrome can also affect the visual ocularmotor systems.
Humans ; Nystagmus, Pathologic ; Pursuit, Smooth ; Vertigo ; Vestibular Diseases ; Vestibular Function Tests ; Vestibular Neuronitis

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

Biomarkers ; Biomarkers, Tumor ; Circulating Tumor DNA/genetics* ; Female ; Genital Neoplasms, Female/diagnosis* ; Humans ; Prognosis

Anti-HIV Agents/therapeutic use* ; China ; Consensus ; HIV ; HIV Infections/prevention & control* ; Humans ; Pre-Exposure Prophylaxis

Genetic as well as genomic study has advanced the development of precision medicine. We are marching on the road for right patients who are receiving more and more right treatment at right time. In hypertension field, precision medicine is available, actionable and affordable. First and the most practical advancement is monogenic hypertension, the disease-genes have been found for at least 17 types of monogenic hypertension. These patients can be precisely treated according to their carried gene mutation. Secondly, pharmacogenetic and pharmacogenomic guided anti-hypertensive drug selection, very promising but lack of clinic outcome data to support widely clinical application. Majority of hypertension are due to multiple genetic and environmental factors. GWAS fund some genetic variants related to primary hypertension, but these variants can only be responsible for 1-10% of blood pressure variation. We have a long way to go in exploring the real cause of primary hypertension.