Uncovering the health implications of abandoned mines through protein profiling of local residents.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

Discovery and validation of metabolite markers in bloodstains for bloodstain age estimation.

Bloodstain age estimation involves measuring time-dependent changes in the levels of biomolecules in bloodstains. Although several studies have identified bloodstain metabolites as markers for estimating bloodstain age, none have considered sex, age-related metabolomic differences, or long-time bloodstain age. Therefore, we aimed to identify metabolite markers for estimating the age of bloodstains at weekly intervals within 28 days and validate them through multiple reaction monitoring. Adenosine 5'-monophosphate, choline, and pyroglutamic acid were selected as markers. Seven metabolites were validated, including five previously reported metabolites, ergothioneine, hypoxanthine, L-isoleucine, L-tryptophan, and pyroglutamic acid. Choline and hypoxanthine can be used to differentiate bloodstains between days 0 and 14 after deposition at weekly intervals, whereas L-isoleucine and L-tryptophan can help distinguish bloodstains between 7 days before and 14 days after deposition. Evaluation of the changes in metabolite levels according to sex and age revealed that the average levels of all seven metabolites were higher in women on day 0. Moreover, the level of ergothioneine was significantly higher in elderly individuals than in young individuals at all time points. In this study, we confirmed the potential effectiveness of metabolites in bloodstains as forensic markers and provided a new perspective on metabolomic approaches linked to forensic science.

Effect of environmental conditions on bloodstain metabolite analysis.

Establishing a correlation between environmental variables and chemical change can significantly improve the quality of research in multiple fields. Among various environmental variables, temperature and humidity are closely related to the rate of chemical reactions. This study aimed to confirm changes in metabolite markers that were previously discovered in other temperature and humidity environment conditions and to confirm the possibility that they could act as markers. After blood collection from the subjects and bloodstain preparation, the quantitative values of the bloodstain metabolites were confirmed (when the age of the bloodstain was within a month) under eight environmental conditions (4 °C/30%, 4 °C/60%, 25 °C/30%, 25 °C/60%, 25 °C/90%, 40 °C/30%, 40 °C/60%, and 40 °C/90%). Age-of-bloodstain estimation models were constructed to confirm the applicability of bloodstain metabolites as markers for bloodstain age in various environments. The average concentration of metabolite markers exhibited a decreasing trend with the age of the bloodstain, which transformed into an increasing trend from day 7 onwards. In terms of temperature and humidity, 25 °C and 90%, respectively, showed the most dissimilar metabolite change pattern compared to other conditions. The age-of-bloodstain estimation models developed here have an R-square value of up to 0.92 for each condition and an R-square value of 0.71 when all environmental conditions were combined. The findings herein highlight the immense potential of blood metabolites for field application, confirming the possibility of predicting metabolite changes from the rates of their chemical reactions and validating the importance of metabolites as age-of-bloodstain markers under various environmental conditions.

Potential Biomarkers to Distinguish Type 1 Myocardial Infarction in Troponin-Elevated Diseases.

Classifying myocardial infarction by subtype is crucial for appropriate patient management. Although troponin is currently the most commonly used biomarker, it is not a specific marker for myocardial infarction and cannot distinguish subtypes. Furthermore, previous studies have confirmed that proteins known as myocardial infarction markers could function to distinguish the type of myocardial infarction. Therefore, we identify a marker that can distinguish type 1 myocardial infarction from other diseases with elevated troponin. We used mass spectrometry to compare type 1 myocardial infarction with other conditions characterized by troponin elevation and identified new candidate markers for disease classification. We then verified these markers, along with those already known to be associated with cardiovascular disease and plaque rupture. We identified α-1 acid glycoprotein 2, corticosteroid-binding globulin, and serotransferrin as potential distinguishing markers. The presence of these markers and other parameters, such as chest pain, electrocardiogram, and troponin levels from the complementary diagnostic processes, could provide valuable information to specifically diagnose type 1 myocardial infarction.

The Effect of Virtual Presence and Self-Efficacy on Nursing Students' Evaluation of Virtual Simulation Training.

The study aims to determine the effect of virtual simulation practice in nursing students using the Virtual Patient Learning System Evaluation (VPLSE) tool. The study uses descriptive research, centering on correlation and regression analysis. 295 nursing students in Grades 3 and 4 who have experienced virtual simulation practice within the past year were included. The main variables of VPLSE comprise four sub-domains: nursing knowledge improvement, clinical competency development, confidence in nursing performance, and nursing care plan application. In addition to the VPLSE, two other tools, measuring virtual presence and self-efficacy, were utilized. The VPLSE was significantly positively correlated with virtual presence and self-efficacy, respectively. The VPLSE subdomain of "clinical competency development" had a strong positive correlation with virtual presence. To increase the effect of virtual simulation education, it is necessary to maintain the advantages of virtual simulation practice, such as freedom from space and time, repeated learning, psychological stability and application of nursing plans.

Bloodstain Metabolite Markers: Discovery and Validation for Estimating Age of Bloodstain within 7 Days.

Metabolomic research using analytical chemistry methods has been carried out in a wide range of research fields. However, research combining forensic science and metabolomics is rare. Determining the age of bloodstains could provide key information regarding when a crime was committed. Currently, validated methods for estimating the age of bloodstains are unavailable. Metabolites are intermediate and final products of chemical reactions. Therefore, they are less likely to be degraded than other components of blood under field conditions. In this study, metabolites in bloodstains were analyzed using liquid chromatography-mass spectrometry to discover and validate metabolic markers for determining the age of bloodstains within a week post-bleeding. Nontargeted analysis of bloodstain metabolites revealed statistically significant differences over time. Quantitative analysis of identified candidates via multiple reaction monitoring confirmed the statistical significance according to the age of bloodstain. Pyroglutamic acid, l-glutamine, acetylcarnitine, and adenosine 5'-monophosphate were selected as the final markers. The content of each marker exhibited a statistically significant and consistent tendency to decrease with the age of bloodstain. Furthermore, the effect of hemolysis was considered according to the blood fraction spots of the four markers. This study is the first to identify and validate metabolite markers that may help determine the age of bloodstains within a week post-bleeding. If applied to crime scenes as indicators of the age of bloodstains, they can be used as innovative and important tools for reconstructing crime scenes, suggesting initial investigative direction. This study highlights the forensic utility of blood metabolites ex vivo.

Discovery of donor age markers from bloodstain by LC-MS/MS using a metabolic approach.

Bloodstains are frequently encountered at crime scenes and they provide important evidence about the incident, such as information about the victim or suspect and the time of death or other events. Efforts have been made to identify the age of the bloodstain's donor through genomic approaches, but there are some limitations, such as the availability of databases and the quality dependence of DNA. There is a need for the development of a tool that can obtain information at once from a small blood sample. The aim of this study is to identify bloodstain metabolite candidates that can be used to determine donor age. We prepared bloodstain samples and analyzed metabolites using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eighteen molecular features (MFs) were selected as candidates using volcano plots and multivariate analysis. Based on the MS/MS spectrum of the MFs, the following nine metabolites were identified from the METaboliteLINk database: Δ2-cis eicosenoic acid, ergothioneine, adenosine 5'-monophosphate, benzaldehyde, phenacylamine, myristic acid ethyl ester, p-coumaric acid, niacinamide, and N-arachidonoyl-L-alanine. These nine age markers at high or low abundances could be used to estimate the age of a bloodstain's donor. This study was the first to develop metabolite age markers that can be used to analyze crime scene bloodstains.

Effectiveness of hydraulic pressure-assisted sinus augmentation in a rabbit sinus model: a preclinical study.

OBJECTIVES: To investigate the effectiveness of hydraulic pressure-assisted sinus augmentation (SA) in a rabbit sinus model in terms of radiographical and histological healing. MATERIALS AND METHODS: Bilateral SA was performed in 12 rabbits. Each sinus was randomly assigned to either a hydraulic pressure-assisted SA (test) or a conventional SA (control) group. Healing periods of 2 and 4 weeks were applied (n = 6 for each week). Healing pattern including newly formed bone (NB) and residual bone substitute material (RM) was analyzed with microcomputed tomographically, histologically, and histomorphometrically. RESULTS: No sinus membrane perforation was detected in either group. In the microcomputed tomographic analysis, the test group exhibited higher apico-coronal spread of RM compared to the control group (p < 0.05). Particularly, the test group exhibited several masses of NB out of the cluster of RM. Histologically, the test group showed an elongated shape of the augmented space, whereas the control group generally presented a dome shape. Histomorphometrically, the total augmented area and the area of NB (1.32 ± 0.56 vs. 0.84 ± 0.40 mm2 at 2 weeks, 2.24 ± 1.09 vs. 2.22 ± 0.85 mm2 at 4 weeks) were not significantly different between the test and the control groups at both healing periods (p > 0.05). CONCLUSION: Hydraulic pressure-assisted SA led to new bone formation in the distant areas from the bony access hole, but similar histological healing pattern to conventional SA. CLINICAL RELEVANCE: Hydraulic pressure-assisted SA is a promising option for treating pneumatized posterior maxilla.

Validation of the Metabolite Ergothioneine as a Forensic Marker in Bloodstains.

Ergothioneine, which is a naturally occurring metabolite, generally accumulates in tissues and cells subjected to oxidative stress, owing to its structural stability at physiological pH; therefore, it has been attracting attention in various biomedical fields. Ergothioneine has also been suggested as a potential forensic marker, but its applicability has not yet been quantitatively validated. In this study, quantitative analysis of ergothioneine in bloodstains was conducted to estimate the age of bloodstains and that of bloodstain donors. Blood from youth and elderly participants was used to generate bloodstains. After extracting metabolites from the bloodstains under prevalent age conditions, ergothioneine levels were quantified by mass spectrometry via multiple reaction monitoring. The concentration of ergothioneine in day 0 bloodstains (fresh blood), was significantly higher in the elderly group than in the youth group, but it did not differ by sex. Statistically significant differences were observed between the samples from the two age groups on days 0, 5 and 7, and on days 2 and 3 compared with day 0. The findings suggest that ergothioneine can be used to estimate the age of bloodstains and of the donor; it could be useful as a potential marker in reconstructing crime scenes.

ZNF746/PARIS promotes the occurrence of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer to cause liver cancer related deaths worldwide. Zinc finger protein 746 (ZNF746), initially identified as a Parkin-interacting substrate (PARIS), acts as a transcriptional repressor of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in Parkinson's disease. As recent studies reported that PARIS is associated with cancer onset, we investigated whether PARIS is associated with HCC. We found an increase in insoluble parkin and PARIS accumulation in the liver of diethylnitrosamine (DEN)-injected mice, leading to the downregulation of PGC-1α and nuclear respiratory factor 1 (NRF1). Interestingly, the occurrence of DEN-induced tumors was significantly alleviated in the livers of DEN-injected PARIS knockout mice compared to DEN-injected wild-type mice, suggesting that PARIS is involved in DEN-induced hepatocellular tumorigenesis. Moreover, H2O2-treated Chang liver cells showed accumulation of PARIS and downregulation of PGC-1α and NRF1. Thus, these results suggest that PARIS upregulation by oncogenic stresses can promote cancer progression by suppressing the transcriptional level of PGC-1α, and the modulation of PARIS can be a promising therapeutic target for HCC.

Hollow adrenal gland sign on dual-phase contrast-enhanced CT in critically ill patients with sepsis.

OBJECTIVE: We aimed to describe the clinical manifestations of patients with sepsis who had the hollow adrenal gland sign (HAGS) during the acute phase of resuscitation and evaluated its value in predicting in-hospital mortality. METHODS: We performed a single-center, retrospective study of patients with sepsis who visited the emergency department (ED) from November 2015 to December 2018. The patients were categorized into the positive HAGS (pHAGS) and negative HAGS (nHAGS) groups, based on its presence in initial dual-phase contrast-enhanced abdominal computed tomography (CT). The primary outcome was in-hospital mortality. A multiple logistic regression model was developed to assess variables related to in-hospital mortality. RESULTS: In all, 156 patients were included, and 36.5% (n = 57) was assigned to the pHAGS group. Both the maximal Sequential Organ Failure Assessment score within 24 h after ED arrival (10, interquartile range [IQR] 7-13 vs. 8, IQR 6-10, p < 0.01) and APACHE II score (24, IQR 20-31 vs. 20, IQR 17-25, p < 0.01) were significantly higher in the pHAGS than in the nHAGS group; the former group received significantly more interventions including vasopressors, renal replacement therapy, mechanical ventilation, and transfusions; in-hospital mortality was significantly higher in the former than in the latter group (29.8% vs. 10.1%, p < 0.01). pHAGS was an independent predictor of in-hospital mortality (adjusted odds ratio, 2.89; 95% confidence interval, 1.08-7.78; p = 0.04). CONCLUSIONS: Patients with sepsis who showed the HAGS had more severe illness than those who did not, and had an increased need for organ-supportive interventions. Presence of the HAGS was independently associated with in-hospital mortality.

FOPR test: a virtual reality-based technique to assess field of perception and field of regard in hemispatial neglect.

BACKGROUND: We previously proposed a novel virtual reality-based method to assess human field of perception (FOP) and field of regard (FOR), termed the FOPR test. This study assessed the diagnostic validity of the FOPR test for hemispatial neglect (HSN). METHODS: We included 19 stroke patients with a lesion in the right hemisphere and with HSN (HSN+SS), 22 stroke patients with a lesion in the right hemisphere and without HSN (HSN-SS), and 22 healthy controls aged 19-65 years. The success rate (SR) and response time (RT) in the FOPR test for both FOP and FOR were assessed (FOP-SR, FOR-SR, FOP-RT, and FOR-RT, respectively). Using a Bland-Altman plot, agreements between the FOPR test and conventional tests were confirmed, and the FOPR test accuracy was verified using the support vector machine (SVM). Measured values were analysed using ANOVA and Kruskall-Wallis tests for group comparison. RESULTS: The Bland-Altman plot showed good agreement between FOPR test and conventional tests; individuals within 95% agreement limits were within the range of 94.8-100.0%. The SVM classification accuracy, using FOP and FOR variables from the left hemispace, ranged from 83.3 to 100.0% in a binary classification (HSN vs non-HSN). The FOPR test demonstrated differences in SR and RT for both FOP and FOR across the groups. CONCLUSION: The FOPR test was valid for the HSN diagnosis and provided quantitative and intuitive information regarding visuospatial function. Furthermore, it might enhance our understanding of visuospatial function including HSN by applying the time relative component and concepts of perception and exploration, FOP and FOR. TRIAL REGISTRATION: NCT03463122. Registered 13 March 2018, retrospectively registered.

α-Synuclein A53T Binds to Transcriptional Adapter 2-Alpha and Blocks Histone H3 Acetylation.

α-Synuclein (α-syn) is a hallmark amyloidogenic protein component of Lewy bodies in dopaminergic neurons affected by Parkinson's disease (PD). Despite the multi-faceted gene regulation of α-syn in the nucleus, the mechanism underlying α-syn crosstalk in chromatin remodeling in PD pathogenesis remains elusive. Here, we identified transcriptional adapter 2-alpha (TADA2a) as a novel binding partner of α-syn using the BioID system. TADA2a is a component of the p300/CBP-associated factor and is related to histone H3/H4 acetylation. We found that α-syn A53T was more preferentially localized in the nucleus than the α-syn wild-type (WT), leading to a stronger disturbance of TADA2a. Indeed, α-syn A53T significantly reduced the level of histone H3 acetylation in SH-SY5Y cells; its reduction was also evident in the striatum (STR) and substantia nigra (SN) of mice that were stereotaxically injected with α-syn preformed fibrils (PFFs). Interestingly, α-syn PFF injection resulted in a decrease in TADA2a in the STR and SN of α-syn PFF-injected mice. Furthermore, the levels of TADA2a and acetylated histone H3 were significantly decreased in the SN of patients with PD. Therefore, histone modification through α-syn A53T-TADA2a interaction may be associated with α-syn-mediated neurotoxicity in PD pathology.

Biomarker Discovery of Acute Coronary Syndrome Using Proteomic Approach.

Acute coronary syndrome (ACS) is a condition in which the coronary artery supplying blood to the heart is infarcted via formation of a plaque and thrombus, resulting in abnormal blood supply and high mortality and morbidity. Therefore, the prompt and efficient diagnosis of ACS and the need for new ACS diagnostic biomarkers are important. In this study, we aimed to identify new ACS diagnostic biomarkers with high sensitivity and specificity using a proteomic approach. A discovery set with samples from 20 patients with ACS and 20 healthy controls was analyzed using mass spectrometry. Among the proteins identified, those showing a significant difference between each group were selected. Functional analysis of these proteins was conducted to confirm their association with functions in the diseased state. To determine ACS diagnostic biomarkers, standard peptides of the selected protein candidates from the discovery set were quantified, and these protein candidates were validated in a validation set consisting of the sera of 50 patients with ACS and 50 healthy controls. We showed that hemopexin, leucine-rich α-2-glycoprotein, and vitronectin levels were upregulated, whereas fibronectin level was downregulated, in patients with ACS. Thus, the use of these biomarkers may increase the accuracy of ACS diagnosis.

Metabolomic profiling of bloodstains on various absorbent and non-absorbent surfaces.

Bloodstains found at crime scenes contain immense information about the crime; thus, studies involving analysis of small molecules in bloodstains have been conducted. However, most of these studies have not accounted for the difference in the results of small molecule analysis due to the surface of bloodstains. To evaluate the "surface effect," we prepared bloodstains on seven surfaces, including both absorbent and non-absorbent surfaces, and performed global small molecule analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). We used three indicators: (1) count recovery rate (%) of molecular features (MFs), (2) the number of MFs extracted from the surface without bloodstains, and (3) difference in abundance recovery rate (%) of MFs, to determine the ranking of the seven surfaces in the order of their similarity with blood. We also confirmed the correlation between each surface and blood through multivariate analysis. We found that the non-absorbent surfaces ranked better than the absorbent surfaces; wooden flooring was ranked as the most efficient surface, followed by stainless, vinyl flooring, glass, tile, filter paper, and mixed cotton. This study will help in the selection of the most efficient surface for collection of bloodstains for small molecule analysis from a crime scene. This is the first study to identify the effects of surface on extraction of global small molecules from bloodstains; it will help forensic scientists in obtaining more accurate information from small molecules present in the bloodstains collected at the field. Graphical abstract.

Histogram analysis of apparent diffusion coefficients for predicting pelvic lymph node metastasis in patients with uterine cervical cancer.

OBJECTIVE: To investigate the value of apparent diffusion coefficient (ADC) histogram analysis in predicting pelvic lymph node (LN) metastasis in patients with cervical cancer undergoing surgery. MATERIALS AND METHODS: A total of 162 cervical cancer patients who underwent radical abdominal hysterectomy with pelvic LN dissection performed with pelvic 3 T-MRI including diffusion-weighted imaging were enrolled in this study. The ADC histogram variables (minimum, mean, median, 97.5th percentile [ADC97.5], and maximum) of the tumors were developed using in-house software. For predicting pelvic LN metastasis, clinical and imaging variables were evaluated using logistic regression and receiver-operating characteristic (ROC) analyses. RESULTS: Pelvic LN metastasis was identified histopathologically in 50 patients (30.9%). In patients with LN metastasis, all ADC histogram variables were significantly different from those without LN metastasis (all p < 0.01). Univariate analysis demonstrated that long- and short-axis diameter of LN, MRI T-stage, squamous cell carcinoma antigen, tumor size, and the ADC97.5 were significantly associated with pelvic LN metastasis (all p < 0.05). However, multivariate analysis demonstrated that the ADC97.5 was the only independent predictor of pelvic LN metastasis (odds ratio, 0.996; p = 0.001). The area under the ROC curve of ADC97.5 was 0.782, which was the greatest among all variables. Interobserver agreement of all ADC histogram variables was fair to good. DISCUSSION: The ADC97.5 from histogram analysis may be a useful marker for the prediction of pelvic LN metastasis in patients with cervical cancer.

A comparison of the effects and usability of two exoskeletal robots with and without robotic actuation for upper extremity rehabilitation among patients with stroke: a single-blinded randomised controlled pilot study.

BACKGROUND: Robotic rehabilitation of stroke survivors with upper extremity dysfunction may yield different outcomes depending on the robot type. Considering that excessive dependence on assistive force by robotic actuators may interfere with the patient's active learning and participation, we hypothesised that the use of an active-assistive robot with robotic actuators does not lead to a more meaningful difference with respect to upper extremity rehabilitation than the use of a passive robot without robotic actuators. Accordingly, we aimed to evaluate the differences in the clinical and kinematic outcomes between active-assistive and passive robotic rehabilitation among stroke survivors. METHODS: In this single-blinded randomised controlled pilot trial, we assigned 20 stroke survivors with upper extremity dysfunction (Medical Research Council scale score, 3 or 4) to the active-assistive robotic intervention (ACT) and passive robotic intervention (PSV) groups in a 1:1 ratio and administered 20 sessions of 30-min robotic intervention (5 days/week, 4 weeks). The primary (Wolf Motor Function Test [WMFT]-score and -time: measures activity), and secondary (Fugl-Meyer Assessment [FMA] and Stroke Impact Scale [SIS] scores: measure impairment and participation, respectively; kinematic outcomes) outcome measures were determined at baseline, after 2 and 4 weeks of the intervention, and 4 weeks after the end of the intervention. Furthermore, we evaluated the usability of the robots through interviews with patients, therapists, and physiatrists. RESULTS: In both the groups, the WMFT-score and -time improved over the course of the intervention. Time had a significant effect on the WMFT-score and -time, FMA-UE, FMA-prox, and SIS-strength; group × time interaction had a significant effect on SIS-function and SIS-social participation (all, p < 0.05). The PSV group showed better improvement in participation and smoothness than the ACT group. In contrast, the ACT group exhibited better improvement in mean speed. CONCLUSIONS: There were no differences between the two groups regarding the impairment and activity domains. However, the PSV robots were more beneficial than ACT robots regarding participation and smoothness. Considering the high cost and complexity of ACT robots, PSV robots might be more suitable for rehabilitation in stroke survivors capable of voluntary movement. Trial registration The trial was registered retrospectively on 14 March 2018 at ClinicalTrials.gov (NCT03465267).

Value of blood oxygenation level-dependent MRI for predicting clinical outcomes in uterine cervical cancer treated with concurrent chemoradiotherapy.

OBJECTIVES: To investigate the value of blood oxygenation level-dependent (BOLD) MRI as a predictor of clinical outcomes in cervical cancer patients treated with concurrent chemoradiotherapy (CCRT). METHOD: Enrolled 92 patients with stage IB2-IVB cervical cancer who received CCRT underwent 3-T BOLD MRI before treatment. The R2* value (rate of spin dephasing, s-1) was measured in the tumor. Cox regression analysis was used to evaluate the associations of imaging and clinical parameters with progression-free survival (PFS) and cancer-specific survival (CSS). Inter-reader reliability for the R2* measurements was evaluated using an intraclass correlation coefficient (ICC). RESULTS: Tumor R2* values were significantly different between patients with and without disease progression (p < 0.001). Multivariate analysis demonstrated that tumor R2* value was significantly independent factor for PFS (hazard ratio [HR] = 5.746, p < 0.001) and CSS (HR = 12.878, p = 0.001). Additionally, squamous cell carcinoma antigen (HR = 1.027, p = 0.001) was significantly independent factor for PFS. Inter-reader reliability for the R2* measurements was good (ICC = 0.702). CONCLUSION: Pretreatment 3-T BOLD MRI may be useful for predicting clinical outcomes in uterine cervical cancer patients treated with CCRT, with good inter-reader reliability. KEY POINTS: • Tumor R2* values are different between patients with and without disease progression. • The R2* value is an independent factor for treatment outcomes in cervical cancer. • Inter-reader reliability for R2* measurements using BOLD MRI is good.

Effects of virtual reality-based planar motion exercises on upper extremity function, range of motion, and health-related quality of life: a multicenter, single-blinded, randomized, controlled pilot study.

BACKGROUND: Virtual reality (VR)-based rehabilitation is considered a beneficial therapeutic option for stroke rehabilitation. This pilot study assessed the clinical feasibility of a newly developed VR-based planar motion exercise apparatus (Rapael Smart Board™ [SB]; Neofect Inc., Yong-in, Korea) for the upper extremities as an intervention and assessment tool. METHODS: This single-blinded, randomized, controlled trial included 26 stroke survivors. Patients were randomized to the intervention group (SB group) or control (CON) group. During one session, patients in the SB group completed 30 min of intervention using the SB and an additional 30 min of standard occupational therapy; however, those in the CON group completed the same amount of conventional occupational therapy. The primary outcome was the change in the Fugl-Meyer assessment (FMA) score, and the secondary outcomes were changes in the Wolf motor function test (WMFT) score, active range of motion (AROM) of the proximal upper extremities, modified Barthel index (MBI), and Stroke Impact Scale (SIS) score. A within-group analysis was performed using the Wilcoxon signed-rank test, and a between-group analysis was performed using a repeated measures analysis of covariance. Additionally, correlations between SB assessment data and clinical scale scores were analyzed by repeated measures correlation. Assessments were performed three times (baseline, immediately after intervention, and 1 month after intervention). RESULTS: All functional outcome measures (FMA, WMFT, and MBI) showed significant improvements (p < 0.05) in the SB and CON groups. AROM showed greater improvements in the SB group, especially regarding shoulder abduction and internal rotation. There was a significant effect of time × group interactions for the SIS overall score (p = 0.038). Some parameters of the SB assessment, such as the explored area ratio, mean reaching distance, and smoothness, were significantly associated with clinical upper limb functional measurements with moderate correlation coefficients. CONCLUSIONS: The SB was available for improving upper limb function and health-related quality of life and useful for assessing upper limb ability in stroke survivors. TRIAL REGISTRATION: The study was registered with the clinical research information service (CRIS) ( KCT0003783 , registered 15 April 2019; retrospectively registered).

Proteomics Approach for the Discovery of Rheumatoid Arthritis Biomarkers Using Mass Spectrometry.

Rheumatoid arthritis is an autoimmune disease that causes serious functional loss in patients. Early and accurate diagnosis of rheumatoid arthritis may attenuate its severity. Despite a diagnosis guideline in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis, the practical difficulties in its diagnosis highlight the need of developing new methods for diagnosing rheumatoid arthritis. The current study aimed to identify rheumatoid arthritis diagnostic biomarkers by using a proteomics approach. Serum protein profiling was conducted using mass spectrometry, and five distinguishable biomarkers were identified therefrom. In the validation study, the five biomarkers were quantitatively verified by multiple reaction monitoring (MRM) analysis. Two proteins, namely serum amyloid A4 and vitamin D binding protein, showed high performance in distinguishing patients with rheumatoid arthritis from healthy controls. Logistic analysis was conducted to evaluate how accurately the two biomarkers distinguish patients with rheumatoid arthritis from healthy controls. The classification accuracy was 86.0% and 81.4% in patients with rheumatoid arthritis and in healthy controls, respectively. Serum amyloid A4 and vitamin D binding protein could be potential biomarkers related to the inflammatory response and joint destruction that accompany rheumatoid arthritis.