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This paper presents a novel method for designing event-triggered dissipative observer-based control for discrete-time Takagi-Sugeno fuzzy singular systems, addressing admissibility, dissipativity, observer-based control, and event-triggered data challenges simultaneously. The distinctive strength of our method lies in its one-step design framework, capable of concurrently designing both fuzzy observer and controller gains without requiring any iterative search algorithms. Moreover, our proposed method not only offers flexibility by allowing for the adjustment of the fuzzy event weighting matrix in conjunction with other variables but also contributes to the enhancement of control system performance through the utilization of a fuzzy Lyapunov function. In contrast to other event-triggered output-feedback control techniques, our method stands out as it constructs the event generation function based on actual system outputs rather than estimated states, thereby ensuring that estimation errors do not influence the event-triggered mechanism. [ABSTRACT FROM AUTHOR]

Background: Several guidelines exist for minimally invasive pancreatoduodenectomy (MIPD) regarding its prerequisites and learning curve. However, these guidelines are based on the experience of the pioneers of MIPD; minimal data exist on the experience of the next generation of surgeons. The aim of this study was to compare the two surgeon types (veteran and junior) for MIPD in terms of immediate postoperative outcomes. Methods: The postoperative outcomes of 22 patients who underwent robot‐assisted pancreatoduodenectomy (RAPD) by a junior surgeon from July 2021 to December 2022 were retrospectively reviewed. The outcomes were compared with the initial postoperative outcomes and the contemporary postoperative outcomes of RAPD by a veteran surgeon. Results: In comparing the initial outcomes between the two surgeon types, the veteran surgeons showed a shorter operation time (junior surgeon vs. veteran surgeon: 606 ± 89 vs. 467 ± 77 min, p < 0.001). However, there was no significant difference in terms of postoperative outcomes, such as blood loss (300 [200–600] ml. vs. 200 [100–500] ml, p = 0.208), major complications (≥CDC IIIa: 4 (18.2%) vs. 4 (18.2%), p = 1.000), postoperative pancreatic fistula (POPF; ≥ISGPF Grade B: 2 (9.1%) vs. 3 (13.6%), p > 0.999), and length of hospital stay (18.0 ± 8.9 days vs. 18.3 ± 7.9 days, p = 0.915), between the two surgeon types. In addition, in a comparison of the contemporary outcomes, there was no significant difference in terms of postoperative outcome (complications: 4 (18.2%) vs 11 (11.1%), p = 0.580; POPF: 2 (9.1%) vs. 3 (3.0%), p = 0.484; length of hospital stay: 18.0 ± 8.9 vs. 15.0 ± 6.5 days, p = 0.065). Conclusion: The initial outcomes of MIPD by a well‐trained junior surgeon were found to be comparable to those of MIPD by a veteran surgeon. [ABSTRACT FROM AUTHOR]

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients. [ABSTRACT FROM AUTHOR]

The relationship between schizophrenia (SCZ) and cancer development remains controversial. Based on the disease-gene association platform, it has been revealed that tumor necrosis factor receptor (TNFR) could be an important mediatory factor in both cancer and SCZ development. TNF-α also increases the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) in the development of SCZ and tumor, but the role of TNFR in mediating the association between the two diseases remains unclear. We studied the vital roles of TNFR2 in the progression of tumor and SCZ-like behavior using A549 lung cancer cell xenografted TNFR2 knockout mice. TNFR2 knockout mice showed significantly decreased tumor size and weight as well as schizophrenia-like behaviors compared to wild-type mice. Consistent with the reduced tumor growth and SCZ-like behaviors, the levels of TrkB and BDNF expression were significantly decreased in the lung tumor tissues and pre-frontal cortex of TNFR2 knockout mice. However, intravenous injection of BDNF (160 μg/kg) to TNFR2 knockout mice for 4 weeks increased tumor growth and SCZ-like behaviors as well as TrkB expression. In in vitro study, significantly decreased cell growth and expression of TrkB and BDNF by siTNFR2 transfection were found in A549 lung cancer cells. However, the addition of BDNF (100 ng/ml) into TNFR2 siRNA transfected A549 lung cancer cells recovered cell growth and the expression of TrkB. These results suggest that TNFR2 could be an important factor in mediating the comorbidity between lung tumor growth and SCZ development through increased TrkB-dependent BDNF levels. [ABSTRACT FROM AUTHOR]

Background: Although many formulas for predicting postoperative pancreatic fistula (POPF) have been introduced, POPF is generally predicted during pancreatic surgery due to pancreatic texture. This study was designed to verify the correlation between Hounsfield units (HU) and pancreatic texture and to suggest a fistula risk score (FRS) that can be used before surgery. Methods: Data from 545 patients who underwent pancreatoduodenectomy for malignant disease between January 2008 and December 2019 were retrospectively reviewed. The HU level of the pancreas was measured, and odds ratio (OR) of the HU for POPF was analyzed. Additionally, the assessed HU was compared with the pancreatic texture (soft vs. hard) and calculated cutoff level. Finally, the preoperatively chosen pancreatic texture according to HU level was applied to the FRS formula (preoperative-FRS: p-FRS), and the results were compared with a previously reported FRS formula (updated alternative-FRS: ua-FRS). Results: The Hounsfield unit levels were correlated with clinically relevant POPF (CR-POPF) (odds ratio [OR]: 1.04 (1.01–1.07), p = 0.015). In the receiver operating characteristic curve, the HU showed significant prediction potential for pancreatic texture (area under the curve [AUC]: 0.744, p < 0.001). The p-FRS also showed acceptable results in predicting CR-POPF (AUC = 0.702, p < 0.001). There was no statistically significant difference in the DeLong's test compared with the ua-FRS (p = 0.314). In the Hosmer–Lemeshow test, observed probabilities were correlated with predicted probabilities (p = 0.596). Conclusions: The HU level on preoperative computed tomography (CT) is a predictive factor for POPF and could represent for pancreatic texture. [ABSTRACT FROM AUTHOR]

The triage process in emergency departments (EDs) relies on the subjective assessment of medical practitioners, making it unreliable in certain aspects. There is a need for a more accurate and objective algorithm to determine the urgency of patients. This paper explores the application of advanced data-synthesis algorithms, machine learning (ML) algorithms, and ensemble models to predict patient mortality. Patients predicted to be at risk of mortality are in a highly critical condition, signifying an urgent need for immediate medical intervention. This paper aims to determine the most effective method for predicting mortality by enhancing the F1 score while maintaining high area under the receiver operating characteristic curve (AUC) score. This study used a dataset of 7325 patients who visited the Yonsei Severance Hospital's ED, located in Seoul, South Korea. The patients were divided into two groups: patients who deceased in the ED and patients who didn't. Various data-synthesis techniques, such as SMOTE, ADASYN, CTGAN, TVAE, CopulaGAN, and Gaussian Copula, were deployed to generate synthetic patient data. Twenty two ML models were then utilized, including tree-based algorithms like Decision tree, AdaBoost, LightGBM, CatBoost, XGBoost, NGBoost, TabNet, which are deep neural network algorithms, and statistical algorithms such as Support Vector Machine, Logistic Regression, Random Forest, k-nearest neighbors, and Gaussian Naive Bayes, as well as Ensemble Models which use the results from the ML models. Based on 21 patient information features used in the pandemic influenza triage algorithm (PITA), the models explained previously were applied to aim for the prediction of patient mortality. In evaluating ML algorithms using an imbalanced medical dataset, conventional metrics like accuracy scores or AUC can be misleading. This paper emphasizes the importance of using the F1 score as the primary performance measure, focusing on recall and specificity in detecting patient mortality. The highest-ranked model for predicting mortality utilized the Gaussian Copula data-synthesis technique and the CatBoost classifier, achieving an AUC of 0.9731 and an F1 score of 0.7059. These findings highlight the effectiveness of machine learning algorithms and data-synthesis techniques in improving the prediction performance of mortality in EDs. [ABSTRACT FROM AUTHOR]

This paper aims to investigate the problem of local nonquadratic stabilization and disturbance attenuation for Takagi–Sugeno (T–S) fuzzy systems under the limited operating region of premise variables. To derive less conservative local stabilization conditions, this paper first proposes a parameterized linear matrix inequality (PLMI) formulation method that enables both the nonquadratic Lyapunov function and the non-parallel distributed compensation control scheme. Specifically, in the PLMI formulation process, the time derivatives of fuzzy basis functions are addressed without any boundary assumptions and by avoiding excessive use of inequality constraints and slack variables. Moreover, an effective relaxation technique is proposed to obtain a finite set of LMIs from PLMIs in a less conservative way without extra slack variables. Finally, three examples are provided to illustrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

The relevant study of transcriptome-wide variations and neurological disorders in the evolved field of genomic data science is on the rise. Deep learning has been highlighted utilizing algorithms on massive amounts of data in a human-like manner, and is expected to predict the dependency or druggability of hidden mutations within the genome. Enormous mutational variants in coding and noncoding transcripts have been discovered along the genome by far, despite of the fine-tuned genetic proofreading machinery. These variants could be capable of inducing various pathological conditions, including neurological disorders, which require lifelong care. Several limitations and questions emerge, including the use of conventional processes via limited patient-driven sequence acquisitions and decoding-based inferences as well as how rare variants can be deduced as a population-specific etiology. These puzzles require harnessing of advanced systems for precise disease prediction, drug development and drug applications. In this review, we summarize the pathophysiological discoveries of pathogenic variants in both coding and noncoding transcripts in neurological disorders, and the current advantage of deep learning applications. In addition, we discuss the challenges encountered and how to outperform them with advancing interpretation. [ABSTRACT FROM AUTHOR]

Indoor fungi obtain carbon sources from natural sources and even recalcitrant biodegradable materials, such as plastics and synthetic dye. Their vigorous activity may have negative consequences, such as structural damage to building materials or the destruction of precious cultural materials. The animal specimen room of the Seoul National University stocked 36,000 animal resources that had been well-maintained for over 80 years. Due to abandonment without the management of temperature and humidity during the rainy summer season, many stuffed animal specimens had been heavily colonized by fungi. To investigate the fungal species responsible for the destruction of the historical specimens, we isolated fungi from the stuffed animal specimens and identified them at the species level based on morphology and molecular analysis of the β-tubulin (BenA) gene. A total of 365 strains were isolated and identified as 26 species in Aspergillus (10 spp.), Penicillium (14 spp.), and Talaromyces (2 spp.). Penicillium brocae and Aspergillus sydowii were isolated from most sections of the animal specimens and have damaged the feathers and beaks of valuable specimens. Our findings indicate that within a week of mismanagement, it takes only a few fungal species to wipe out the decades of history of animal diversity. The important lesson here is to prevent this catastrophe from occurring again through a continued interest, not to put all previous efforts to waste. [ABSTRACT FROM AUTHOR]

Background/aim: Ixazomib, lenalidomide, and dexamethasone (IRd) have proven efficacy and an excellent safety profile in relapsed and/or refractory multiple myeloma (RRMM). However, there are limited reports on the real-world safety and effectiveness of IRd regimens in Asian patients with RRMM. Patients and methods: This was a retrospective study of 60 patients with RRMM who were treated with IRd. Results: The median patient age was 68 years. Forty percent of patients did not meet the eligibility criteria for the TOURMALINE-MM1 trial. Patients received a median of one prior line of therapy. Non-hematologic adverse events (AEs) were more common than hematologic AEs. The most common AE was skin rash, followed by gastrointestinal toxicities. Most grade 3 or higher AEs were observed in less than 5% of the patients, except for skin rashes and infections. IRd therapy did not aggravate peripheral neuropathy (PN) in 20 of the 24 patients with pre-existing peripheral neuropathy. The overall response rate was 85%. After a median follow-up of 26.3 months, the median progression-free survival was 25.9 months and overall survival was not reached. Conclusion: Ixazomib and Rd combination therapy had a comparable toxicity profile and effectiveness in real-world RRMM patients. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive pancreaticoduodenectomy (MIPD) is a challenging procedure. Laparoscopic pancreaticoduodenectomy (LPD) is feasible and safe. Since the development of robotic platforms, the number of reports on robot-assisted pancreatic surgery has increased. We compared the technical feasibility and safety between LPD and robot-assisted LPD (RALPD). Methods: From September 2012 to August 2020, 257 patients who underwent MIPD for periampullary tumors were enrolled. Of these, 207 underwent LPD and 50 underwent RALPD. We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographics and surgical outcomes. Results: After PSM analysis, no difference was noted in demographics. Operation times and estimated blood loss were similar, as was the incidence of complications (p > 0.05). In subgroup analysis in patients with soft pancreas with pancreatic duct ≤ 2 mm, no significant between-group difference was noted regarding short-term surgical outcomes, including clinically relevant POPF (CR-POPF) (p > 0.05). In multivariable analysis, the only soft pancreatic texture was a predictive factor (HR 3.887, 95% confidence interval 1.121–13.480, p = 0.032). Conclusion: RALPD and LPD are safe and effective for MIPD and can compensate each other to achieve the goal of minimally invasive surgery. [ABSTRACT FROM AUTHOR]

Plastic waste has a negative impact on marine ecosystems and the quantity of this source of anthropogenic pollution continues to increase. Several studies have investigated plastic biodegradation using various microorganisms. In this study, we isolated fungi from polyethylene terephthalate (PET) waste on Korean seacoasts and evaluated their ability to degrade plastic by comparing the diameters of the clear zones they formed on polycaprolactone (PCL) agar. We isolated 262 strains from 47 plastic waste sources and identified 108 fungal species via molecular methods. The PCL agar assay revealed that 87 species presented with varying degrees of PCL degradation capacity. Among them, certain fungal species were strong PCL degraders. The present study demonstrated the possibility that some fungi inhabiting plastic could potentially degrade it in the marine environment. We believe that the discoveries made herein lay theoretical and practical foundations for the development of novel bioremediation systems for marine plastispheres and help mitigate the environmental pollution issues related to plastic wastes. [ABSTRACT FROM AUTHOR]

The International Myeloma Working Group has recently revised the diagnostic criteria for primary plasma cell leukemia (PCL) to circulating plasma cells (CPCs) ≥ 5% in a peripheral blood smear. The present study validated new criteria in patients with multiple myeloma or PCL diagnosed using the previous diagnostic criteria, who were administered immunomodulatory drugs or proteasome inhibitors as induction therapy. We analyzed the medical records of 1357 patients from eight hospitals in South Korea. The median age of the all patients was 64 years, and 187 (13.8%) had CPCs at diagnosis. Only 79 (5.8%) of the patients had ≥ 5% CPCs. The median overall survival (OS) of patients with CPCs ≥ 5% and ≥ 20% was similar, but had significantly inferior median progression-free survival (PFS) and median OS than those with CPCs < 5% (13.1 vs. 21.5 months, P < 0.001, and 21.5 vs. 60.9 months, P < 0.001, respectively). Primary PCL diagnosed using the revised criteria presented with higher total calcium levels and serum creatinine levels, lower platelet counts and frequent organomegaly and plasmacytoma at diagnosis. Univariate and multivariate analyses demonstrated that the presence of plasmacytoma and elevated serum β2-microglobulin were significantly associated with OS in primary PCL. In conclusion, the revised criterion of CPCs ≥ 5% in a peripheral blood smear is appropriate for PCL diagnosis. [ABSTRACT FROM AUTHOR]

In the phase 3 IKEMA study (NCT03275285), isatuximab (Isa) plus carfilzomib (K) and dexamethasone (d) significantly improved progression-free survival (PFS) in relapsed multiple myeloma (MM), compared with Kd. This IKEMA subgroup analysis evaluated efficacy and safety of Isa-Kd versus Kd among East Asian patients. Eligible patients had 1–3 prior lines of therapy and were stratified by number of prior lines and revised International Staging System. The primary endpoint was PFS. Key secondary endpoints included overall response, very good partial response or better (≥VGPR), minimal residual disease (MRD) negativity, and complete response (CR) rate. Forty-six East Asian patients (19 Japanese, 27 South Korean) were randomized to Isa-Kd (n = 25) or Kd (n = 21). Isa-Kd improved PFS (HR 0.64; 95% CI 0.23–1.76), ≥VGPR (80.0% vs 52.4%), MRD negativity rate (44.0% vs 9.5%), and CR (44.0% vs 23.8%). The rate of grade ≥ 3 treatment-emergent adverse events (TEAEs) was 79% for Isa-Kd versus 55% for Kd. The rate of serious TEAEs was 46% versus 50%, and the rate of TEAEs leading to treatment discontinuation was 4% versus 10%. Overall, Isa-Kd improved efficacy and safety versus Kd in East Asian patients with relapsed MM, consistent with the overall IKEMA population. [ABSTRACT FROM AUTHOR]

Objectives: To develop and evaluate a deep learning (DL)–based system for measuring leg length on full leg radiographs of diverse patients, including those with orthopedic hardware implanted for surgical treatment. Methods: This study retrospectively assessed 2767 X-ray scanograms of 2767 patients who did or did not have orthopedic hardware implanted between January 2016 and December 2019. A cascaded DL model was developed to localize the relevant landmarks on the pelvis, knees, and ankles required for measuring leg length. Statistical analysis was performed using the correlation coefficient analysis and Bland–Altman plots to assess the agreement between the reference standard and DL-calculated lengths. Results: Testing data comprised 400 radiographs from 400 patients. Of these radiographs, 100 were from patients with orthopedic hardware implanted in their pelvis, knees, or ankles. For all testing data, leg lengths derived from the DL-based measurement system, with or without internal fixation devices, showed excellent agreement with the reference standard (femoral length, r = 0.99 (P <.001); root mean square error (RMSE) = 0.17 cm; mean difference, − 0.01 ± 0.17 cm; 95% limit of agreement (LoA), − 0.35 to 0.34; tibial length, r = 0.99 (P <.001); RMSE = 0.17 cm; mean difference, − 0.02 ± 0.17 cm, 95% LoA, − 0.34 to 0.31; and full leg length, r = 1.0 (P <.001); RMSE = 0.19 cm; mean difference, 0.05 ± 0.18 cm; 95% LoA, − 0.31 to 0.40). The mean time for leg length measurement for each patient using the DL-based system was 8.68 ± 0.18 s. Conclusion: The DL-based leg length measurement system could provide similar performance to radiologists in terms of accuracy and reliability for a diverse group of patients. [ABSTRACT FROM AUTHOR]

This study was aimed at enhancing surface plasmon resonance through a combination of Ag nanoparticles (NPs) and an asymmetric crater structure capable of concentrating light. The crater structure was fabricated via wet-chemical etching of a GaAs(100) wafer, after which an Ag film was deposited inside, and subjected to rapid thermal annealing to form NPs. The results were analysed in terms of the magnitude of the Raman intensity, from which an optimal combination of annealing temperature and film thickness was determined. Ag nanowires (NWs) were also spray-coated onto the AgNPs to elucidate the effect of coupling the NPs with the NWs. The Raman intensity was 22 times higher inside the crater with AgNPs and NWs than on a flat area without NPs; however, further increases in the amount of AgNWs resulted in greater coverage of the AgNPs, which reduced the Raman intensity. We expect the proposed method for Raman signal enhancement to promote further development and applications of surface-enhanced Raman scattering (SERS) spectroscopy. [ABSTRACT FROM AUTHOR]

DNA cyclization assay together with single-molecule FRET was employed to monitor protein-mediated bending of a short dsDNA (~ 100 bp). This method provides a simple and easy way to monitor the structural change of DNA in real-time without necessitating prior knowledge of the molecular structures for the optimal dye-labeling. This assay was applied to study how Anabaena sensory rhodopsin transducer (ASRT) facilitates loop formation of DNA as a possible mechanism for gene regulation. The ASRT-induced DNA looping was maximized at 50 mM of Na+, while Mg2+ also played an essential role in the loop formation. [ABSTRACT FROM AUTHOR]

We examined the feasibility of explainable computer-aided detection of cardiomegaly in routine clinical practice using segmentation-based methods. Overall, 793 retrospectively acquired posterior–anterior (PA) chest X-ray images (CXRs) of 793 patients were used to train deep learning (DL) models for lung and heart segmentation. The training dataset included PA CXRs from two public datasets and in-house PA CXRs. Two fully automated segmentation-based methods using state-of-the-art DL models for lung and heart segmentation were developed. The diagnostic performance was assessed and the reliability of the automatic cardiothoracic ratio (CTR) calculation was determined using the mean absolute error and paired t-test. The effects of thoracic pathological conditions on performance were assessed using subgroup analysis. One thousand PA CXRs of 1000 patients (480 men, 520 women; mean age 63 ± 23 years) were included. The CTR values derived from the DL models and diagnostic performance exhibited excellent agreement with reference standards for the whole test dataset. Performance of segmentation-based methods differed based on thoracic conditions. When tested using CXRs with lesions obscuring heart borders, the performance was lower than that for other thoracic pathological findings. Thus, segmentation-based methods using DL could detect cardiomegaly; however, the feasibility of computer-aided detection of cardiomegaly without human intervention was limited. [ABSTRACT FROM AUTHOR]

Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM. [ABSTRACT FROM AUTHOR]

Introduction: Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS).Methods: Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated.Results: Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03-63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603-5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had ≥ 1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications.Conclusion: The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5 years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13.Trial Registration: ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015). [ABSTRACT FROM AUTHOR]

Fueled by ATP hydrolysis in N-ethylmaleimide sensitive factor (NSF), the 20S complex disassembles rigid SNARE (soluble NSF attachment protein receptor) complexes in single unraveling step. This global disassembly distinguishes NSF from other molecular motors that make incremental and processive motions, but the molecular underpinnings of its remarkable energy efficiency remain largely unknown. Using multiple single-molecule methods, we found remarkable cooperativity in mechanical connection between NSF and the SNARE complex, which prevents dysfunctional 20S complexes that consume ATP without productive disassembly. We also constructed ATP hydrolysis cycle of the 20S complex, in which NSF largely shows randomness in ATP binding but switches to perfect ATP hydrolysis synchronization to induce global SNARE disassembly, minimizing ATP hydrolysis by non-20S complex-forming NSF molecules. These two mechanisms work in concert to concentrate ATP consumption into functional 20S complexes, suggesting evolutionary adaptations by the 20S complex to the energetically expensive mechanical task of SNARE complex disassembly. Fueled by ATP hydrolysis in N-ethylmaleimide sensitive factor (NSF), the 20S complex disassembles SNARE complexes in a single unravelling step. Here authors use single-molecule methods to show cooperativity between the NSF and SNARE complex, which prevents ATP consumption without productive disassembly. [ABSTRACT FROM AUTHOR]

Background: Complications are important indicators of immediate postoperative outcomes. The Clavien–Dindo classification (CDC) is a widely used index for the classification of surgical complications. More recently, the comprehensive complication index (CCI) has also been introduced for classifying postoperative complications. The aim of this study was to compare the relationship of CCI and CDC with clinical or economic parameters. Methods: The study prospectively enrolled patients from April 2015 to October 2016. Two hundred and twenty-two patients underwent pancreatectomy during the enrolled period. Complications were ranked according to CDC and CCI indices. After analyzing the correlation between CCI and CDC, the correlations of length of stay (LOS) and cost with CCI and CDC were compared. Finally, differences between the correlation coefficients of CDC and CCI parameters were calculated. Results: Complications occurred in 211 patients (95.0%). The correlation between CDC and CCI was r = 0.938. (p < 0.001) Compared to the CDC, CCI showed significantly stronger correlations with LOS and cost of complications (LOS: CCI vs. CDC, r = 0.725 vs. r = 0.630, p < 0.001; cost: CCI vs. CDC, r = 0.774 vs. r = 0.723, p < 0.001). Conclusion: CCI is a more accurate classification index, compared to CDC, for evaluating the risk of postoperative complications. [ABSTRACT FROM AUTHOR]

In construction machinery, attachments, such as buckets and breakers, that are mounted on the equipment convert the fluid energy of the construction machine into impact energy, vibration energy, etc., depending on the purpose. To ensure the reliability of such attachments under repeated or excessive stress, the fatigue life of the structure must be evaluated in terms of strength and rigidity. The present study focused on symmetric structures. A functional analysis was performed on the field data obtained from the construction machine with an attached vibration hammer, and the fatigue life of the symmetric bracket was assessed. The results were used to develop an accelerated fatigue-life test algorithm for the prediction and health management. Residual-useful-life prognostics of basic data in the prediction of life and failure of attachments used in construction machinery as well as the integrity management of their symmetric structures. [ABSTRACT FROM AUTHOR]

This study aimed to compare gait analysis and balance function measurements, such as the Berg balance scale (BBS) score to seek specific measurements that can represent the balance functions of patients with brain lesions. Additionally, we also compared other different gait function scale scores with gait analysis measurements. This study included 77 patients with brain lesions admitted to our institution between January 2017 and August 2020. Their gait analysis parameters and clinical data, including personal data; clinical diagnosis; duration of the disease; cognition, ambulation, and stair-climbing sub-scores of the modified Barthel index (MBI); manual muscle test (MMT) findings of both lower extremities; functional ambulation category (FAC); and BBS score, were retrospectively analyzed. A multiple linear regression analysis was performed to identify the gait analysis parameters that would significantly correlate with the balance function and other physical performances. In the results, the BBS scores were significantly correlated with the gait speed and step width/height2. However, the other gait function measurements, such as the FAC and ambulation and stair-climbing sub-scores of the MBI, were correlated only with the gait speed. Additionally, both the summations of the lower extremity MMT findings and anti-gravity lower extremity MMT findings were correlated with the average swing phase time. Therefore, in the gait analysis, the gait speed may be an important factor in determining the balance and gait functions of the patients with brain lesions. Moreover, the step width/height2 may be a significant factor in determining their balance function. However, further studies with larger sample sizes should be performed to confirm this relationship. [ABSTRACT FROM AUTHOR]

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival. [ABSTRACT FROM AUTHOR]

Nitidine chloride (NC) was recently reported to exhibit a wide range of pharmacological properties for several diseases, including cancer. Here we report for the first time that NC is a potential therapeutic agent for mucoepidermoid carcinoma (MEC) occurring in the head and neck because it suppresses X chromosome-linked inhibitor of apoptosis protein (XIAP) in human MEC in vitro and in vivo. The antitumor effects of NC were evaluated by trypan blue exclusion assay, western blotting, live/dead assay, 4',6-diamidino-2-phenylindole (DAPI) staining, human apoptosis antibody array, immunofluorescence staining, immunohistochemistry, small interfering RNA assay, transient transfection of XIAP overexpression vector, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and histopathological examination of organs. NC inhibited cell viability and induced caspase-dependent apoptosis in vitro. A human apoptosis antibody array assay showed that XIAP is suppressed by NC treatment. XIAP was overexpressed in oral squamous cell carcinoma (OSCC) tissues that arose from the head and neck, and high XIAP expression was correlated with poor prognosis in OSCC patients. XIAP depletion significantly increased apoptosis, and ectopic XIAP overexpression attenuated the apoptosis induced by NC treatment. NC suppressed tumor growth in vivo at a dosage of 5 mg/kg/day. The number of TUNEL-positive cells increased and the protein expression of XIAP was consistently downregulated in NC-treated tumor tissues. In addition, NC caused no histopathological changes in the liver or kidney. These findings provide new insights into the mechanism of action underlying the anticancer effects of NC and demonstrate that NC is a promising therapeutic agent for the treatment of human MEC of the head and neck. Key messages: • Nitidine chloride induces caspase-dependent apoptosis in MEC of the head and neck. • High XIAP expression correlates with poor prognosis of OSCC patients. • Nitidine chloride suppresses tumor growth in vivo without any systemic toxicities. • Targeting XIAP is a novel chemotherapeutic strategy for MEC of the head and neck. [ABSTRACT FROM AUTHOR]

Accurate quantification of pulmonary nodules can greatly assist the early diagnosis of lung cancer, enhancing patient survival possibilities. A number of nodule segmentation techniques, which either rely on a radiologist-provided 3-D volume of interest (VOI) or use the constant region of interests (ROIs) for all the slices, are proposed; however, these techniques can only investigate the presence of nodule voxels within the given VOI. Such approaches restrain the solutions to freely investigate the nodule presence outside the given VOI and also include the redundant structures (non-nodule) into VOI, which limits the segmentation accuracy. In this work, a novel semi-automated approach for 3-D segmentation of lung nodule in computerized tomography scans, has been proposed. The technique is segregated into two stages. In the first stage, a 2-D ROI containing the nodule is provided as an input to perform a patch-wise exploration along the axial axis using a novel adaptive ROI algorithm. This strategy enables the dynamic selection of the ROI in the surrounding slices to investigate the presence of nodules using a Deep Residual U-Net architecture. This stage provides the initial estimation of the nodule utilized to extract the VOI. In the second stage, the extracted VOI is further explored along the coronal and sagittal axes, in patchwise fashion, with Residual U-Nets. All the estimated masks are then fed into a consensus module to produce a final volumetric segmentation of the nodule. The algorithm is rigorously evaluated on LIDC–IDRI dataset, which is the largest publicly available dataset. The proposed approach achieved the average dice score of 87.5%, which is significantly higher than the existing state-of-the-art techniques. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) is not frequently performed for elderly patients multiple myeloma (MM) in Korea, despite its being a standardized approach for young patients. Medical records of 150 patients from 15 Korean institutions who received ASCT at age ≥ 64 years were analyzed retrospectively. Patients included had symptomatic MM, and had received their first ASCT at age ≥ 64 following induction chemotherapy. The main outcome was the response after ASCT. Overall survival (OS) and progression-free survival (PFS) were also analyzed. Median time to ASCT was 6.3 months. Complete response plus stringent complete response rate increased from 36 (24.0%) to 105 (70.0%) after ASCT, and high-quality response (≥ very good partial response) increased from 96 (64.0%) to 125 (83.3%). With a median follow-up of 32.6 months after ASCT, 5-year OS and PFS were 59.7% and 22.8%, respectively. Febrile neutropenia occurred in 43.5%, and nausea (21.3%) and stomatitis (13.2%) were common grade 3-4 non-hematologic adverse events. Of 44 deaths, disease progression (n = 23) was the most common cause of mortality, followed by infection (n = 13). Treatment-related death occurred in four cases (2.7%). ASCT is an effective and safe option for elderly MM patients and is associated with superior clinical outcomes. [ABSTRACT FROM AUTHOR]

This paper investigates the problem of designing a dissipative controller for interval type-2 nonhomogeneous Markovian jump fuzzy systems (MJFSs) with incomplete transition descriptions. To explore a generalized model for MJFSs under realistic situations, the coexistence of incompletely known transition rates and mismatched membership functions is considered in MJFS models, and the corresponding stabilization conditions are derived in terms of multi-parameterized linear matrix inequalities (M-PLMIs). In addition, to handle the problem of M-PLMIs, two novel relaxation techniques are additionally proposed such that the use of redundant constraints on multiple time-varying parameters can be significantly reduced. Finally, the validity of the proposed method is demonstrated via two illustrative examples. [ABSTRACT FROM AUTHOR]

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To develop and evaluate a deep learning (DL)–based system for measuring leg length on full leg radiographs of diverse patients, including those with orthopedic hardware implanted for surgical treatment. Methods: This study retrospectively assessed 2767 X-ray scanograms of 2767 patients who did or did not have orthopedic hardware implanted between January 2016 and December 2019. A cascaded DL model was developed to localize the relevant landmarks on the pelvis, knees, and ankles required for measuring leg length. Statistical analysis was performed using the correlation coefficient analysis and Bland–Altman plots to assess the agreement between the reference standard and DL-calculated lengths. Results: Testing data comprised 400 radiographs from 400 patients. Of these radiographs, 100 were from patients with orthopedic hardware implanted in their pelvis, knees, or ankles. For all testing data, leg lengths derived from the DL-based measurement system, with or without internal fixation devices, showed excellent agreement with the reference standard (femoral length, r = 0.99 (P <.001); root mean square error (RMSE) = 0.17 cm; mean difference, − 0.01 ± 0.17 cm; 95% limit of agreement (LoA), − 0.35 to 0.34; tibial length, r = 0.99 (P <.001); RMSE = 0.17 cm; mean difference, − 0.02 ± 0.17 cm, 95% LoA, − 0.34 to 0.31; and full leg length, r = 1.0 (P <.001); RMSE = 0.19 cm; mean difference, 0.05 ± 0.18 cm; 95% LoA, − 0.31 to 0.40). The mean time for leg length measurement for each patient using the DL-based system was 8.68 ± 0.18 s. Conclusion: The DL-based leg length measurement system could provide similar performance to radiologists in terms of accuracy and reliability for a diverse group of patients. [ABSTRACT FROM AUTHOR]

The Glasgow Prognostic Score (GPS) serves a prognostic role in several lymphomas. The objectives of the present study were to determine whether GPS predicts clinical outcomes and to compare the utility of four prognostic scores, including GPS, in patients diagnosed with peripheral T-cell lymphoma (PTCL). We selected for this retrospective study 96 patients consecutively diagnosed with PTCL according to the World Health Organization classification from January 2002 to February 2013 and followed up in five different institutions. Low GPS was a good prognostic biomarker of progression-free survival (PFS, P = 0.030) and overall survival (OS, P = 0.013). Estimated 3-year OS rates (low-risk vs. intermediate- or high-risk) by the International Prognostic Index (IPI), the Prognostic Index for T-cell lymphoma (PIT), the International Peripheral T-cell Lymphoma Project (IPTCLP) score, and GPS were 83% vs. 44% (P < 0.001), 68% vs. 37% (P = 0.004), 71% vs. 26% (P < 0.001) and 68% vs. 51% (P = 0.031), respectively. These results indicate that GPS has prognostic value for PTCL. In addition, all four prognostic scores demonstrate their usefulness in assessing PTCL outcomes. [ABSTRACT FROM AUTHOR]

This paper deals with the problem of asynchronous mode-dependent dissipative control synthesis for a class of nonhomogeneous discrete-time Markovian jump fuzzy systems. By exploring the asynchronous phenomenon between plant and control operation modes characterized by nonhomogeneous Markov chains, a more realistic situation is reflected in the relaxation problem of multi-parameterized matrix inequalities. Further, via the proposed relaxation method, (1) the strict range constraints are imposed on multiple time-varying parameters and (2) the conditional relation between asynchronous Markov chains is definitely exploited to achieve less conservative results. Finally, two examples are given to illustrate the validity of the proposed approach. [ABSTRACT FROM AUTHOR]

Purpose: ABT-263 is a potent BH3 mimetic that possesses anticancer potential against various types of cancer. In general, this potential is due to its high binding affinity to anti-apoptotic proteins in the Bcl-2 family that disrupt sequestration of pro-apoptotic proteins. In the present study, we sought to identify an alternative regulatory mechanism responsible for ABT-263-mediated anticancer activity in human oral cancer. Methods: We investigated the in vitro anti-cancer effects of ABT-263 using a trypan blue exclusion assay, Western blotting, DAPI staining, immunofluorescence staining, a live/dead assay, microarray-based expression profiling, and quantitative real-time PCR. In vivo anti-tumorigenic effects of ABT-263 were examined using a nude mouse tumor xenograft model, a TUNEL assay, and immunohistochemistry. Results: We found that ABT-263 suppressed viability and induced apoptosis in human oral cancer-derived cell lines HSC-3 and HSC-4. Subsequent microarray-based gene expression profiling revealed 55 differentially expressed genes in the ABT-263-treatead group, including 12 genes associated with "endoplasmic reticulum stress and apoptosis." Consistent with the microarray results, the mRNA expression levels of the top four genes (CHOP, TRB3, ASNS, and STC2) were found to be significantly increased. In addition, we found that ABT-263 considerably enhanced the expression levels of the C/EBP-homologous protein (CHOP) and its mRNA, resulting in apoptosis induction in four other human oral cancer-derived cell lines (MC-3, YD-15, HN22, and Ca9.22). Extending our in vitro findings, we found that ABT-263 reduced the growth of HSC-4 cells in vivo at a dosage of 100 mg/kg/day without any change in body weight. TUNEL-positive cells were also found to be increased in tumors of ABT-263-treated mice without any apparent histopathological changes in liver or kidney tissues. Conclusions: These results provide evidence that ABT-263 may serve as an effective therapeutic agent for the treatment of human oral cancer. [ABSTRACT FROM AUTHOR]

Autophagy is an essential process for maintaining cellular homeostasis, a critical process in all cell types. Because neurons are post-mitotic cells, maintaining cellular and functional homeostasis is more important in neurons than in other types of cells. Synapses are fundamental units needed for neural communication, and synapses with consistent protein quality are essential for neural functionality. Dysregulation of autophagy in neurons has been shown to be related to neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. This review describes the role of autophagy in the maintenance of synaptic functionality and the association between synaptic autophagy and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

This paper investigates the robust control synthesis problem of nonhomogeneous Markovian jump systems with actuator saturation and uncertainties. First of all, to make a comprehensive mode-transition description, three separate mode sets are established according to the property of transition rates. And then, to improve the numerical solvability of inequality conditions dependent on time-varying transition rates, two useful relaxation methods are developed on the basis of the mode sets. Especially, by taking advantage of a new zero-sum constraint, the relaxation process is further evolved such that the conservatism arising from incomplete knowledge of transition rates can be reduced. Lastly, this paper provides the LMI-based conditions capable of estimating the attraction domain as well as of designing a mode-dependent robust control. [ABSTRACT FROM AUTHOR]

Blinatumomab, a bispecific T cell-engaging antibody, has demonstrated efficacy for relapsed or refractory acute lymphoblastic leukemia (ALL). In this study, we evaluated the efficacy and toxicity of blinatumomab in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. A total of 50 patients received blinatumomab treatment between June 2016 and August 2017 in Korea. The median number of prior therapy was one (range, 1-4). Among the 49 evaluable patients, 22 (44.9%) achieved complete response (CR) or CR with incomplete blood count recovery, and 16 of whom subsequently underwent allogenic stem cell transplantation. Although no statistically significant differences were observed, patients with extramedullary disease and poor performance status had lower responses to blinatumomab treatment. In addition, the use of high-dose dexamethasone prior to blinatumomab treatment did not affect the response to blinatumomab. The median event-free survival and overall survival of the responders were 7.5 and 8.1 months, respectively. For non-hematologic toxicities, the most common toxicity was infection. The incidences of severe cytokine release syndrome and neurologic toxicity each was 4%. In conclusion, blinatumomab was an effective and tolerable therapy in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. [ABSTRACT FROM AUTHOR]

Bone homeostasis is achieved through coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. When the balance is skewed in favor of osteoclasts due to hormonal or inflammatory issues, pathologic bone loss occurs leading to conditions such as osteoporosis, rheumatoid arthritis, and periodontitis. Bortezomib is the first in-class of proteasome inhibitors used as an anti-myeloma agent. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor κB ligand (RANKL)-dependent osteoclast differentiation of mouse bone marrow macrophages. Bortezomib significantly reduced the induction of osteoclast marker genes and proteins including nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1). The intraperitoneal injection of bortezomib reduced ovariectomy-induced osteoclastogenesis and protected the mice from bone loss. These data propose novel use of bortezomib as a potential anti-resorptive agent. [ABSTRACT FROM AUTHOR]

Abstract: Unsupported MoS2 catalysts were prepared for the methanation reaction by varying the pressure and temperature in the hydrothermal reaction by using ammonium tetrathiomolybdate (ATTM). The physical and chemical characteristics of the catalysts were analyzed by using XRD, SEM, TEM, BET, XPS, H2-TPR, and CO-TPD techniques. The catalyst particles were formed in the bent fringe shape by stacking the (0 0 2) planes, and consisted mostly of MoS2, with some Mo2S5 and MoS3. It was found that the BET surface and active sites such as surface Mo4+ and sulfur vacancies increased with increasing preparation pressure, which could contribute to the improvement of MoS2 catalytic activity. The increase in preparation temperature not only favored the decomposition of ATTM into MoS2, but also lowered the number of active sites accessible for the reaction. Thus, it was suggested that the preparation temperature should be controlled at 350 °C to improve the catalytic activity.Graphical Abstract: [ABSTRACT FROM AUTHOR]

The present study attempted to build a single nucleotide polymorphism (SNP)-based risk model for predicting overall survival (OS) and event-free survival (EFS) in patients with core binding factor acute myeloid leukemia (CBF-AML). Adopting genome-wide SNP array using Affymetrix SNP array 6.0, we analyzed 868,157 SNPs with respect to OS and EFS in 104 patients with CBF-AML. Significant SNPs were identified from single SNP analysis. The risk model was constructed with incorporation of six SNPs and three clinical factors (age, c-kit exon 17 mutation, and LDH) for OS and six SNPs and three clinical factors (age, WBC, and LDH) for EFS. The model was further defined into low- and high-risk groups based on risk scores. The median age was 39 years, and the subgroup of t(8;21) and inv(16) or t(16;16) was assessed in 68 (65.4%) and 36 patients (34.6%). Finally, six SNPs per each OS (rs4353685, rs4908185, rs7709207, rs12034, rs1554844, and rs17241868) and EFS (rs13385610, rs11210617, rs11169282, rs7709207, rs4438401, and rs16894846) were incorporated into the risk model. OS was significantly different in favor of the low risk group (80.4 ± 8.4%) compared to the high-risk group (22.0 ± 7.3% at 3 years; p = 8.75 × 10- 13; HR 8.67). For EFS, there was also a significant difference between the low- (75.0 ± 5.8%) versus high-risk group (17.1 ± 6.3% at 3 years; p = 5.95 × 10- 13; HR 7.67). A genome-wide SNP-based risk model can stratify CBF-AML patients according to their OS and EFS in 104 patients. [ABSTRACT FROM AUTHOR]