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The European Society for Radiotherapy and Oncology (ESTRO) recently defined delineation guidelines for the clinical target volume for postmastectomy radiation therapy (PMRT) after immediate implant-based reconstruction for early-stage breast cancer. We analyzed the three-dimensional location and pattern of local recurrence in accordance with the reconstruction type and ESTRO-target volume.This retrospective study involved patients who had undergone mastectomy with implant reconstruction between 2010 and 2019 and who had local recurrence as the first event. For mapping analysis, one subpectoral and one prepectoral implant patient were selected. All recurrence lesions were contoured and mapped in a representative case.A total of 1327 patients with breast cancer who underwent mastectomy and implant-based breast reconstruction were identified; 51 were enrolled with a total of 65 lesions. In subpectoral implant patients, 93% of recurrences were located in the ESTRO-target volume. No recurrence occurred in the implant pocket, but 7% of the recurrent tumors developed in the pectoralis major and deep thoracic muscle. In prepectoral implant patients, all recurrent tumors occurred within the ESTRO-target volume.The ESTRO-target volume in PMRT after reconstruction encompassed most local recurrences in patients who underwent mastectomy with immediate implant reconstruction. Our results support the application of the ESTRO Advisory Committee for Radiation Oncology Practice consensus guideline for target volume of PMRT after immediate implant-based reconstruction for early-stage breast cancer.

Purpose This study aimed to investigate the impact of postoperative radiotherapy (PORT) in de novo metastatic breast cancer (dnMBC) patients undergoing planned primary tumor resection (PTR) and to identify the subgroup of patients who would most benefit from PORT.Materials and Methods This study enrolled 426 patients with dnMBC administered PTR alone or with PORT. The primary and secondary outcomes were overall and progression-free survival (OS and PFS), respectively.Results The median follow-up time was 53.7 months (range, 3.1 to 194.4). The 5-year OS and PFS rates were 73.2% and 32.0%, respectively. For OS, clinical T3/4 category, triple-negative breast cancer (TNBC), postoperative chemotherapy alone were significantly poor prognostic factors, and administration of PORT failed to show its significance. Regarding PFS, PORT was a favorable prognostic factor (hazard ratio, 0.64; 95% confidence interval, 0.50 to 0.82; p < 0.001), in addition to T1/2 category, ≤ 5 metastases, and non-TNBC. According to the multivariate analyses of OS in the PORT group, we divided the patients into three groups (group 1, T1/2 and non-TNBC [n=193]; group 2, T3/4 and non-TNBC [n=171]; and group 3, TNBC [n=49]), and evaluated the effect of PORT. Although PORT had no significance for OS in all subgroups, it was a significant factor for good prognosis regarding PFS in groups 1 and 2, not in group 3.Conclusion PORT was associated with a significantly better PFS in patients with dnMBC who underwent PTR. Patients with clinical T1/2 category and non-TNBC benefited most from PORT, while those with TNBC showed little benefit.

This study aimed to propose a protocol to demonstrate the efficacy of Codonopsis lanceolata water extract for the improvement of skeletal muscle mass (SMM) and function (muscle strength or performance function) and its safety compared to a placebo in adults with reduced muscle strength.A randomized double-blind placebo-controlled clinical trial was conducted. Participants will be recruited from the Korean Medicine Hospital in South Korea. One hundred and four adults with reduced muscle strength will be randomly assigned a 1:1 ratio to either the experimental or placebo comparator groups. The participants will consume the product corresponding to their assigned group for the following 12 weeks, and efficacy and safety tests will be conducted. This is the first clinical trial of C lanceolata water extract in adults with reduced muscle strength. The results of this study would provide a clinical basis for the efficacy and safety of C lanceolata water extract in patients with sarcopenia.This trial was approved by the Institutional Review Board (IRB) of Kyung Hee University Korean Medicine Hospital at Gangdong on July 15, 2021 (amendment number: MLB_DDE_H01 [ver. 01]). When a change was made in the clinical trial plan, the IRB reviewed and approved the revised clinical trial plan. The study was registered on the Clinical Research Information Service website on December 3, 2021 (registration number: PRE20211203-003; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=20841status=1seq_group=20841search_page=M). The results of this clinical trial will be reported in the future. Every document related to the clinical trial, such as the electronic case report form, will be recorded and classified by the subject identification code and not by the subject name.

Introduction Indications for therapeutic plasma exchange (TPE) have expanded over the years, and the number of procedures is expected to have been increased. Apheresis registries can be difficult to sustain due to workload and privacy issues. This study aimed to analyze national claims data to characterize the use of TPE. Materials and methods Patients who underwent TPE were retrospectively identified between January 2008 and December 2017 from the Korean Health Insurance Review and Assessment Service database. Data of patients' characteristics, primary diagnosis, hospitalization, treatment, and procedures were analyzed. Results A total of 9944 patients underwent 62 606 TPE procedures. The median number of TPE procedures performed per patient was 5 (interquartile range, 3-7). Fresh frozen plasma (71.4%) was most commonly used as the replacement fluid. The most common indication was renal diseases (36.8%), followed by hepato-biliary (17.6%) and hematological (15.2%) diseases. Increased frequency of renal diseases was the most remarkable change, which increased from 529 (21.2%) procedures in 2008 to 4107 (44.5%) procedures in 2017, reflecting the widespread implementation of ABO-incompatible kidney transplantation. The top five hospitals conducted 59.6% of the procedures, which showed a centralized distribution. Conclusions The most common indication was renal diseases. The number of TPE procedures performed annually increased by approximately 3.7 times from 2008 to 2017. This study shows that other than a registry, claims data can be successfully used to analyze various aspects of TPE procedures on a nationwide scale. This approach could be used by other countries, especially those that have national health insurance.

This study aimed to fabricate a heterogeneous phantom replicating the commercial Rando phantom by mixing plaster powder and polylactic acid (PLA) powder. Producing a heterogeneous phantom using Plaster and PLA is cheaper because it can be easily obtained in the commercial market. Additionally, patient-specific Quality Assurance can be easily performed because the phantom can be produced based on the patient’s CT image. PLA has been well studied in the field of radiation therapy and was found to be safe and effective. To match the mean Hounsfield unit (HU) values of the Rando phantom, the bone tissue was changed using plaster and 0–35% PLA powder until an appropriate HU value was obtained, and soft tissue was changed using the PLA infill value until an appropriate HU value was obtained. Bone tissue (200 HU or higher), soft issue (− 500 to 200 HU), and air cavity (less than − 500 HU) were modeled based on the HU values on the computed tomography (CT) image. The bone tissue was modeled as a cavity, and after three-dimensional (3D) printing, a solution containing a mixture of plaster and PLA powder was poured. To evaluate the bone implementation of the phantom obtained by the mixture of plaster and PLA powder, the HU profile of the CT images of the 3D-printed phantom using only PLA and the Rando phantom printed using only PLA was evaluated. The mean HU value for soft tissue in the Rando phantom (− 22.5 HU) showed the greatest similarity to the result obtained with an infill value of 82% (− 20 HU). The mean HU value for bone tissue (669 HU) showed the greatest similarity to the value obtained with 15% PLA powder (680 HU). Thus, for the phantom composed of plaster mixed with PLA powder, soft tissue was fabricated using a 3D printer with an infill value of 82%, and bone tissue was fabricated with a mixture containing 15% PLA powder. In the HU profile, this phantom showed a mean difference of 61 HU for soft tissue and 109 HU for bone tissue in comparison with the Rando phantom. The ratio of PLA powder and plaster can be adjusted to achieve an HU value similar to bone tissue. A simple combination of PLA powder and plaster enabled the creation of a custom phantom that showed similarities to the Rando phantom in both soft tissue and bone tissue.

Purpose Concurrent chemoradiotherapy (CCRT) is recommended as the standard treatment for locally advanced cervical cancer (LACC). However, the synergistic effect of hyperthermia (HT) with CCRT remains unclear. Therefore, we performed a meta-analysis to evaluate the effect of HT with CCRT on LACC patients. Methods and materials A systematic literature search was conducted on the MEDLINE, PubMed, Embase, Cochrane library and SCOPUS databases for articles that compared CCRT with HT and CCRT alone as treatments for LACC. Hazard ratios (HRs) and risk ratios (RRs) were used to compare five-year overall survival (OS), local relapse-free survival (LRFS) and incidence of acute and chronic toxicity between the two treatments. Results Two articles out of 2860 were finally selected for analysis. A total of 536 patients were evaluated (CCRT with HT group: 268, CCRT group: 268). FIGO stages I–II and III–IV were found in 295 (55.0%) and 241 patients (45.0%), respectively. The CCRT with HT group had significantly better five-year OS than the CCRT group (HR 0.67, 95% confidence interval [CI] 0.47–0.96, p = 0.03). LRFS of patients was superior in the CCRT with HT group than in the CCRT group, but without significance (HR 0.74, 95% CI 0.49–1.12; p = 0.16). Moreover, there was no difference between the two groups regarding acute and chronic toxicity. Conclusion This systematic review and meta-analysis showed that CCRT with HT significantly improved OS in LACC patients without increasing acute and chronic toxicity. Therefore, tri-modality treatment could be a feasible approach for patients with LACC.

Various applications of head-tilting techniques in whole-brain radiotherapy (WBRT) have been introduced. However, a study on the setup uncertainties and margins in head-tilting techniques has not been reported. This study evaluated the setup uncertainties and determined the appropriate planning target volume (PTV) margins for patients treated in the head-tilted supine (ht-SP) and conventional supine position (c-SP) in WBRT. Thirty patients who received WBRT at our institution between October 2020 and May 2021 in the c-SP and ht-SP were investigated. The DUON head mask (60124, Orfit Industries, Wijnegem, Belgium) was used in the c-SP, and a thermoplastic U-Frame Mask (R420U, Klarity Medical & Equipment Co. Ltd., Lan Yu, China) was used in the ht-SP. Daily setup verification using planning computed tomography (CT) and cone-beam CT was corrected for translational (lateral, longitudinal, and vertical) and rotational (yaw) errors. In the c-SP, the means of systematic errors were -0.80, 0.79, and 0.37 mm and random errors were 0.27, 0.54, and 0.39 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. Whereas, for the ht-SP, the means of systematic errors were -0.07, 0.73, and -0.63 mm, and random errors were 0.75, 1.39, 1.02 mm in the lateral, longitudinal, and vertical translational dimensions, respectively. The PTV margins were calculated using Stroom et al.’s [2Σ+0.7σ] and van Herk et al.’s recipe [2.5Σ+0.7σ]. Appropriate PTV margins with van Herk et al.’s recipe in WBRT were

Background Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a standard treatment modality for locally-advanced esophageal cancer. However, patients who achieve clinical complete response (cCR) after nCRT have been reported to have better prognosis. Further, the role of surgery in these patients is controversial. Thus, this meta-analysis aimed to evaluate whether surgery is still useful in patients with cCR after nCRT. Methods We systematically reviewed the MEDLINE, PubMed, Embase, Cochrane library, and Scopus databases for studies on surgical efficacy in complete responders after concurrent chemoradiotherapy for esophageal cancer. The publication date was set to January 1, 2010–January 31, 2020. The hazard ratio (HR) and risk ratio were used to compare the 2-year overall survival (OS), disease-free survival (DFS), incidence of locoregional failure, distant metastasis, and treatment mortality between the nCRT and nCRT plus surgery groups. Results Six articles involving 609 patients were included. There was a significant benefit of nCRT for OS (HR = 0.80, 95% confidence interval [CI] 0.64–0.99, p = 0.04), but not for DFS (HR = 1.55, 95% CI 0.35–6.86, p = 0.56). The nCRT group tended to have lower mortality than the nCRT plus surgery group (risk ratio = 0.15, 95% CI 0.02–1.18, p = 0.07). Conclusion Omitting surgery provides better OS in complete responders after nCRT. Adding surgery could increase the morbidity and mortality and decrease the quality of life. Thus, nCRT alone could be a feasible approach for patients with cCR.

Plasma cell leukemia (PCL) is clinically and genetically distinct from multiple myeloma (MM), despite controversies regarding the disease definition. To determine the distinct features of PCL, the genetic property of primary PCL (pPCL) was compared with that of secondary PCL (sPCL) and MM. In patients with pPCL, Eighty-nine non-synonymous mutations were observed in 68 genes. The most frequently mutated genes were

Background In the coronavirus disease 2019 (COVID-19) pandemic era, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus (Flu), and respiratory syncytial virus (RSV) is important in the rapid differential diagnosis in patients with respiratory symptoms. Three multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assays have been recently developed commercially in Korea: PowerChek™ SARS-CoV-2, Influenza A&B Multiplex Real-time PCR Kit (PowerChek; KogeneBiotech); STANDARD™ M Flu/SARS-CoV-2 Real-time Detection Kit (STANDARD M; SD BioSensor); and Allplex™ SARS-CoV-2/FluA/FluB/RSV Assay (Allplex; Seegene). We evaluated the analytical and clinical performances of these kits. Methods A limit of detection tests were performed and cross-reactivity analysis was executed using clinical respiratory samples. Ninety-seven SARS-CoV-2-positive, 201 SARS-CoV-2-negative, 71 influenza A-positive, 50 influenza B-positive, 78 RSV-positive, and 207 other respiratory virus-positive nasopharyngeal swabs were tested using the three assays. The AdvanSure™ respiratory viruses rRT-PCR assay (AdvanSure; LG Life Sciences) was used as a comparator assay for RSV. Results Except in influenza B, in SARS-CoV-2 and influenza A, there were no significant differences in detecting specific genes of the viruses among the three assays. All three kits did not cross-react with common respiratory viruses. All three kits had greater than 92% positive percent agreement and negative percent agreement and ≥ 0.95 kappa value in the detection of SARS-CoV-2 and flu A/B. Allplex detected RSV more sensitively than AdvanSure. Conclusion The overall performance of three multiplex rRT-PCR assays for the concurrent detection of SARS-CoV-2, influenza A/B, and RSV was comparable. These kits will promote prompt differential diagnosis of COVID-19, influenza, and RSV infection in the COVID-19 pandemic era., Graphical Abstract

Exercise intensity of exoskeleton-assisted walking in patients with spinal cord injury (SCI) has been reported as moderate. However, the cardiorespiratory responses to long-term exoskeleton-assisted walking have not been sufficiently investigated. We investigated the cardiorespiratory responses to 10 weeks of exoskeleton-assisted walking training in patients with SCI. Chronic nonambulatory patients with SCI were recruited from an outpatient clinic. Walking training with an exoskeleton was conducted three times per week for 10 weeks. Oxygen consumption and heart rate (HR) were measured during a 6-min walking test at pre-, mid-, and post-training. Exercise intensity was determined according to the metabolic equivalent of tasks (METs) for SCI and HR relative to the HR reserve (%HRR). Walking efficiency was calculated as oxygen consumption divided by walking speed. The exercise intensity according to the METs (both peak and average) corresponded to moderate physical activity and did not change after training. The %HRR demonstrated a moderate (peak %HRR) and light (average %HRR) exercise intensity level, and the average %HRR significantly decreased at post-training compared with mid-training (31.6 ± 8.9% to 24.3 ± 7.3%, p = 0.013). Walking efficiency progressively improved after training. Walking with an exoskeleton for 10 weeks may affect the cardiorespiratory system in chronic patients with SCI.

In managing patients with coronavirus disease 2019 (COVID‐19), early identification of those at high risk and real‐time monitoring of disease progression to severe COVID‐19 is a major challenge. We aimed to identify potential early prognostic protein markers and to expand understanding of proteome dynamics during clinical progression of the disease. We performed in‐depth proteome profiling on 137 sera, longitudinally collected from 25 patients with COVID‐19 (non‐severe patients, n = 13; patients who progressed to severe COVID‐19, n = 12). We identified 11 potential biomarkers, including the novel markers IGLV3‐19 and BNC2, as early potential prognostic indicators of severe COVID‐19. These potential biomarkers are mainly involved in biological processes associated with humoral immune response, interferon signalling, acute phase response, lipid metabolism, and platelet degranulation. We further revealed that the longitudinal changes of 40 proteins persistently increased or decreased as the disease progressed to severe COVID‐19. These 40 potential biomarkers could effectively reflect the clinical progression of the disease. Our findings provide some new insights into host response to SARS‐CoV‐2 infection, which are valuable for understanding of COVID‐19 disease progression. This study also identified potential biomarkers that could be further validated, which may support better predicting and monitoring progression to severe COVID‐19.

Background/aims This study aimed to assess adherence to physical activity guidelines in cancer survivors and to investigate related factors. Methods The cross-sectional data of 39,845 community-dwelling participants aged ≥ 20 years (1,254 cancer survivors) in the Korea National Health and Nutrition Examination Survey were analyzed. The age- and sex-stratified prevalence for meeting exercise guidelines was obtained. The correlates of meeting exercise recommendations were evaluated by using complex-sample logistic regression models. Results Overall, 36.2% and 20.5% of cancer survivors met the recommendations for aerobic and resistance exercises, respectively. Cancer survivors and noncancer controls had similar low adherence to exercise recommendations in most age and sex groups, except young female cancer survivors (20 to 49 years old) who showed higher engagement in aerobic exercise than female noncancer controls in the same age group. Old cancer survivors (≥ 65 years) were less likely to engage in recommended levels of aerobic exercise than young cancer survivors (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.24 to 0.79). Female cancer survivors were less likely to meet resistance exercise guidelines than male cancer survivors (OR, 0.32; 95% CI, 0.21 to 0.50). In addition, cancer survivors with current smoking status and cardiovascular disease were less likely to meet aerobic exercise recommendations. Conclusions The prevalence of meeting exercise guidelines are low in Korean cancer survivors and varied by age and sex. Old age is associated with an insufficient level of aerobic exercise, and female sex is associated with low participation in resistance exercise.

Inter-joint coordination and gait variability in knee osteoarthritis (KOA) has not been well investigated. Hip-knee cyclograms can visualize the relationship between the hip and knee joint simultaneously. The aim of this study was to elucidate differences in inter-joint coordination and gait variability with respect to KOA severity using hip-knee cyclograms. Fifty participants with KOA (early KOA, n = 20; advanced KOA, n = 30) and 26 participants (≥ 50 years) without KOA were recruited. We analyzed inter-joint coordination by hip-knee cyclogram parameters including range of motion (RoM), center of mass (CoM), perimeter, and area. Gait variability was assessed by the coefficient of variance (CV) of hip-knee cyclogram parameters. Knee RoM was significantly reduced and total perimeter tended to be decreased with KOA progression. KOA patients (both early and advanced) had reduced stance phase perimeter, swing phase area, and total area than controls. Reduced knee CoM and swing phase perimeter were observed only in advanced KOA. Both KOA groups had a greater CV for CoM, knee RoM, perimeter (stance phase, swing phase and total) and swing phase area than the controls. Increased CV of hip RoM was only observed in advanced KOA. These results demonstrate that hip-knee cyclograms can provide insights into KOA patient gait.

The objective of this study was to analyze the difference in residual setup errors between 6D ExacTrac and 3D cone-beam computed tomography (CBCT) image-guided systems in spinal stereotactic body radiation therapy (SBRT). We investigated 76 patients with spinal tumors who received SBRT using Novalis Tx at our institution between January 2013 and September 2020. A Vac-lok (EZ-FIX®, Arlico Medical Company, South Korea) fixture and an assistive device, based on the region involved, were used to immobilize patients and to increase the inter-fractional setup reproducibility. The difference in the root mean square (RMS) between the 6D ExacTrac and 3D CBCT was -0.75 mm, 0.45 mm, 0.16 mm, and -0.03°; the RMS value was 1.31 mm, 1.06 mm, 0.87 mm, and 0.64°; and the standard deviation was 0.80 mm, 0.72 mm, 0.62 mm, and 0.44° for lateral, longitudinal, vertical, and yaw directions, respectively. The difference in the average RMS between ExacTrac and CBCT was

Background: The standard treatment for diffuse intrinsic pontine glioma (DIPG) is radiotherapy, although conventional fractionated radiotherapy (CFRT) may not be in the best interest of the patient. Instead, hypofractionated radiotherapy (HFRT) may shorten the treatment period and reduce related costs for this treatment, which is typically palliative in nature. Methods: This systematic review and meta-analysis evaluated survival outcomes among patients who received HFRT or CFRT for DIPG. The PubMed, Medline, EMBASE, Cochrane Central Register, and Scopus databases were searched to identify relevant studies. Overall survival was the primary outcome of interest and progression-free survival was the secondary outcome of interest. Results: The search identified a total of 2376 reports, although only 4 reports were ultimately included in the meta-analysis. The studies included 88 patients who underwent HFRT and 96 patients who underwent CFRT. Relative to CFRT, HFRT provided comparable outcomes in terms of overall survival (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 0.77–1.47) and progression-free survival (HR: 1.04, 95% CI: 0.75–1.45). Conclusions: The results of this meta-analysis suggest that CFRT and HFRT provide similar survival outcomes for patients with DIPG.

Background Spinal cord injury (SCI) is a serious clinical condition that impacts a patient's physical, psychological, and socio-economic status. The aim of this pilot study was to evaluate the effects of training with a newly developed powered wearable exoskeleton (Hyundai Medical Exoskeleton [H-MEX]) on functional mobility, physiological health, and quality of life in non-ambulatory SCI patients. Methods Participants received 60 minutes of walking training with a powered exoskeleton 3 times per week for 10 weeks (total 30 sessions). The 6-minute walking test (6MWT) and timed-up-and-go test (TUGT) were performed to assess ambulatory function. The physiological outcomes of interest after exoskeleton-assisted walking training were spasticity, pulmonary function, bone mineral density, colon transit time, and serum inflammatory markers. Effects of walking training on subjective outcomes were estimated by the Korean version of the Falls Efficacy Scale—International and the 36-Item Short-Form Health Survey version 2. Results Ten participants finished 30 sessions of training and could ambulate independently. No severe adverse events were reported during the study. After training, the mean distance walked in the 6MWT (49.13 m) was significantly enhanced compared with baseline (20.65 m). The results of the TUGT also indicated a statistically significant improvement in the times required to stand up, walk 3 m and sit down. Although not statistically significant, clinically meaningful changes in some secondary physiological outcomes and/or quality of life were reported in some participants. Conclusion In conclusion, this study demonstrated that the newly developed wearable exoskeleton, H-MEX is safe and feasible for non-ambulatory SCI patients, and may have potential to improve quality of life of patients by assisting bipedal ambulation. These results suggest that the H-MEX can be considered a beneficial device for chronic non-ambulatory SCI patients. Trial Registration ClinicalTrials.gov Identifier: NCT04055610, Graphical Abstract

Aim This study aimed to evaluate the prevalence and associated factors of radiographic hip osteoarthritis (OA) in the Korean community-dwelling population. Methods This study included 11 814 individuals (5025 men and 6789 women) ≥50 years of age from the Korea National Health and Nutrition Examination Surveys. Radiographic hip OA was defined as having a Kellgren-Lawrence grading scale score ≥2. Painful hip OA was defined as radiographic hip OA with the presence of hip pain. The prevalence of radiographic hip OA was evaluated with respect to age group, sex and presence of hip pain. The associations of sociodemographic and clinical variables with hip OA and hip pain were assessed using multivariable logistic regression analyses. Results The weighted prevalence of radiographic hip OA and painful hip OA was 1.1% and 0.2%, respectively, in Korea. Older age (≥75 years) and male sex were independently associated with radiographic hip OA and painless hip OA. Comorbid musculoskeletal pain (knee pain) was independently associated with painful hip OA. The difference between painful and painless hip OA was the presence of comorbid musculoskeletal pain (knee pain and low back pain). Although hip pain was more common in women than in men, it was associated with the severity of hip OA only in men. Conclusions Radiographic hip OA is rare in Korean middle-aged and elderly people. Furthermore, hip pain is infrequent in radiographic hip OA. Geriatr Gerontol Int 2021; 21: 20-26.

Cell Population Data (CPD) provides various blood cell parameters that can be used for differential diagnosis. Data analytics using Machine Learning (ML) have been playing a pivotal role in revolutionizing medical diagnostics. This research presents a novel approach of using ML algorithms for screening hematologic malignancies using CPD. The data collection was done at Konkuk University Medical Center, Seoul. A total of (882 cases: 457 hematologic malignancy and 425 hematologic non-malignancy) were used for analysis. In our study, seven machine learning models, i.e., SGD, SVM, RF, DT, Linear model, Logistic regression, and ANN, were used. In order to measure the performance of our ML models, stratified 10-fold cross validation was performed, and metrics, such as accuracy, precision, recall, and AUC were used. We observed outstanding performance by the ANN model as compared to other ML models. The diagnostic ability of ANN achieved the highest accuracy, precision, recall, and AUC ± Standard Deviation as follows: 82.8%, 82.8%, 84.9%, and 93.5% ± 2.6 respectively. ANN algorithm based on CPD appeared to be an efficient aid for clinical laboratory screening of hematologic malignancies. Our results encourage further work of applying ML to wider field of clinical practice.

Gait disturbance is a common sequela of stroke. Conventional gait analysis has limitations in simultaneously assessing multiple joints. Therefore, we investigated the gait characteristics in stroke patients using hip-knee cyclograms, which have the advantage of simultaneously visualizing the gait kinematics of multiple joints. Stroke patients (n = 47) were categorized into two groups according to stroke severity, and healthy controls (n = 32) were recruited. An inertial measurement unit sensor-based gait analysis system, which requires placing seven sensors on the dorsum of both feet, the shafts of both tibias, the middle of both femurs, and the lower abdomen, was used for the gait analysis. Then, the hip-knee cyclogram parameters (range of motion, perimeter, and area) were obtained from the collected data. The coefficient of variance of the cyclogram parameters was obtained to evaluate gait variability. The cyclogram parameters differed between the stroke patients and healthy controls, and differences according to stroke severity were also observed. The gait variability parameters mainly differed in patients with more severe stroke, and specific visualized gait patterns of stroke patients were obtained through cyclograms. In conclusion, the hip-knee cyclograms, which show inter-joint coordination and visualized gait cycle in stroke patients, are clinically significant.

We aimed to compare the volumetric-modulated arc therapy (VMAT) plans with or without multi-criteria optimization (MCO) on commercial treatment-planning systems (Eclipse, Varian Medical System, Palo Alto, CA, USA) for patients with prostate cancer. We selected 25 plans of patients with prostate cancer who were previously treated on the basis of a VMAT plan. All plans were imported into the Eclipse Treatment Planning System version 15.6, and re-calculation and re-optimization were performed. The MCO plan was then generated. The dosimetric quality of the plans was evaluated using dosimetric parameters and dose indices that account for target coverage and sparing of the organs at risk (OARs). We defined the rectum, bladder, and bilateral femoral heads. The VMAT-MCO plan offers an improvement of gross treatment volume coverage with increased minimal dose and reduced maximal dose. In the planning treatment volume, the Dmean and better gradient, homogeneity, and conformity indexes improved despite the increasing hot and cold spots. When implemented through the MCO plan, a steeper fall off the adjacent OARs in the overlap area was achieved to obtain lower dose parameters. MCO generated better sparing of the rectum and bladder through a tradeoff of the increasing dose to the bilateral femoral heads within the tolerable dose constraints. Compared with re-optimization and re-calculation, respectively, significant dose reductions were observed in the bladder (241 cGy and 254 cGy; pp

Purpose Coplanar arcs are used with limited arc range to prevent direct beam entrance through the lens, which is challenging for satisfactory planning of hippocampal sparing in whole brain radiotherapy (HS-WBRT) with VMAT. We evaluated the dosimetric impact of applying a head-tilting technique during VMAT, which allows unrestricted use of the arc range. Methods and materials Twenty patients with multiple brain metastases who had received two computed tomography (CT)-simulation sessions between January 2016 and December 2018 were included. One session was delivered in a traditional supine position; the other was delivered with a tilting acrylic supine baseplate (MedTec, USA) to elevate the patients’ head by 40°. For each patient, a VMAT without (sVMAT) and with head-tilting (htVMAT) plan was generated. Conformity index (CI), homogeneity index (HI), and organ at risk (OAR) dose were evaluated. The Wilcoxon-signed test was used to compare the effect between two plans. Results The mean CI was 0.860±0.007 and 0.864±0.008 (p

Background Radiculopathies caused by spinal stenosis in the upper lumbar spinal canal (L1/2, L2/3, L3/4) have not been comprehensively investigated. Methods This retrospective study reviewed 14 patients from a tertiary hospital outpatient clinic. The inclusion criteria were upper lumbar stenosis seen on MRI and radiculopathies with active denervation confirmed on electromyography. Patients with any other conditions that could explain the clinical or electrophysiological manifestations were excluded. Results Neurogenic findings were predominantly observed in L5 or S1 myotomes on electromyography. Abnormal spontaneous activity was observed in distal muscles in all patients and in proximal muscles in eight patients. Axonal involvement was bilateral in 10 patients and unilaterally in 4 patients. MRI showed redundant nerve roots in 13 patients with chronic reinnervation on electromyography. Conclusions Upper lumbar spinal stenosis usually causes L5 or S1 radiculopathies with diverse patterns. This discrepancy may cause diagnostic confusion.

Park, JH, Seo, KS, and Lee, S-U. Effect of superimposed electromyostimulation on back extensor strengthening: a pilot study. J Strength Cond Res 30(9): 2470-2475, 2016-Electromyostimulation (EMS) superimposed on voluntary contraction (VC) can increase muscle strength. However, no study has examined the effect of superimposing EMS on back extensor strengthening. The purpose of this study was to determine the effect of superimposed EMS on back extensor strengthening in healthy adults. Twenty healthy men, 20-29 years of age, without low-back pain were recruited. In the EMS group, electrodes were attached to bilateral L2 and L4 paraspinal muscles. Stimulation intensity was set for maximally tolerable intensity. With VC, EMS was superimposed for 10 seconds followed by a 20-second rest period. The same protocol was used in the sham stimulation (SS) group, except that the stimulation intensity was set at the lowest intensity (5 mA). All subjects performed back extension exercise using a Swiss ball, with 10 repetitions per set, 2 sets each day, 5 times a week for 2 weeks. The primary outcome measure was the change in isokinetic strength of the back extensor using an isokinetic dynamometer. Additionally, endurance was measured using the Sorensen test. After 2 weeks of back extension exercise, the peak torque and endurance increased significantly in both groups (p ≤ 0.05). Effect size between the EMS group and the SS group was medium in strength and endurance. However, there was no statistically significant difference between 2 groups. In conclusion, 2 weeks of back extensor strengthening exercise was effective for strength and endurance. Superimposing EMS on back extensor strengthening exercise could provide an additional effect on increasing strength.

Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012 , 341 , 90 ), which was selected for advanced preclinical characterization based on its favorable properties.

In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic template with potent activity against the NS5B polymerase, a critical enzyme on the life cycle of HCV. In continuation of our exploration to improve the stilbene series, the 3,5,6,8-tetrasubstituted quinoline core was identified as replacement of the stilbene moiety. 6-Methoxy-2(1H)-pyridone was identified among several heterocyclic headgroups to have the best potency. Solubility of the template was improved by replacing a planar aryl linker with a saturated pyrrolidine. Profiling of the most promising compounds led to the identification of quinoline 41 (RG7109), which was selected for advancement to clinical development.

The splicing of pre-mRNA is a critical process in normal cells and is deregulated in cancer. Compounds that modulate this process have recently been shown to target a specific vulnerability in tumors. We have developed a novel cell-based assay that specifically activates luciferase in cells exposed to SF3B1 targeted compounds, such as sudemycin D6. This assay was used to screen a combined collection of approved drugs and bioactive compounds. This screening approach identified several active hits, the most potent of which were CGP-74514A and aminopurvalanol A, both have been reported to be cyclin-dependent kinases (CDKs) inhibitors. We found that these compounds, and their analogs, show significant cdc2-like kinase (CLK) inhibition and clear structure-activity relationships (SAR) at CLKs. We prepared a set of analogs and were able to ‘dial out’ the CDK activity and simultaneously developed CLK inhibitors with low nanomolar activity. Thus, we have demonstrated the utility of our exon-skipping assay and identified new molecules that exhibit potency and selectivity for CLK, as well as some structurally related dual CLK/CDK inhibitors.

The development of a new series of p38α inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38α, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.