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Abstract Background Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are found in 1% of gliomas across children and adults. TRK inhibitors are promising therapeutic agents for NTRK-fused gliomas because they are tissue agnostic and cross the blood–brain barrier (BBB). Methods We investigated twelve NGS-verified NTRK-fused gliomas from a single institute, Seoul National University Hospital. Results The patient cohort included six children (aged 1–15 years) and six adults (aged 27–72 years). NTRK2 fusions were found in ten cerebral diffuse low-grade and high-grade gliomas (DLGGs and DHGGs, respectively), and NTRK1 fusions were found in one cerebral desmoplastic infantile ganglioglioma and one spinal DHGG. In this series, the fusion partners of NTRK2 were HOOK3, KIF5A, GKAP1, LHFPL3, SLMAP, ZBTB43, SPECC1L, FKBP15, KANK1, and BCR, while the NTRK1 fusion partners were TPR and TPM3. DLGGs tended to harbour only an NTRK fusion, while DHGGs exhibited further genetic alterations, such as TERT promoter/TP53/PTEN mutation, CDKN2A/2B homozygous deletion, PDGFRA/KIT/MDM4/AKT3 amplification, or multiple chromosomal copy number aberrations. Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). The treatment outcomes for patients receiving TRK inhibitors varied: one child who received larotrectinib for residual DLGG maintained stable disease. In contrast, another child with DHGG in the spinal cord experienced multiple instances of tumour recurrence. Despite treatment with larotrectinib, ultimately, the child died as a result of tumour progression. An adult patient with glioblastoma (GBM) treated with entrectinib also experienced tumour progression and eventually died. However, there was a successful outcome for a paediatric patient with DHGG who, after a second gross total tumour removal followed by repotrectinib treatment, showed no evidence of disease. This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions.

Background/Aims Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P

Traditional 3D projection models, such as perspective and orthographic projection, are limited to two types of projective ray fields: rays passing through a single point and parallel rays. In this paper, we introduce an ellipsoidal-based 3D projection model to overcome the sparsity of 3D projections. Our ellipsoidal 3D projection model comprises an ellipsoid and an axis-aligned geometry such as a line or a plane. By linearly mapping these two geometries along their principal axes, our model enables us to explore the continuous domain of projective ray fields while taking advantage of the anisotropy in ellipsoids. We introduce the intrinsic characteristic of our projection field, called the ellipse property, that enables testing isomorphism with other projection models. We prove the difference between ours and the catadioptric projection model employing an elliptic mirror. Besides, we propose a perspectivity metric for the intuitive control over the parameter space. We present both forward and backward projections of our model, demonstrating its applicability across several visual applications, ranging from image synthesis to scene reconstruction.

Abstract Local recurrences in patients with grade 4 adult-type diffuse gliomas mostly occur within residual non-enhancing T2 hyperintensity areas after surgical resection. Unfortunately, it is challenging to distinguish non-enhancing tumors from edema in the non-enhancing T2 hyperintensity areas using conventional MRI alone. Quantitative DCE MRI parameters such as Ktrans and Ve convey permeability information of glioblastomas that cannot be provided by conventional MRI. We used the publicly available nnU-Net to train a deep learning model that incorporated both conventional and DCE MRI to detect the subtle difference in vessel leakiness due to neoangiogenesis between the non-recurrence area and the local recurrence area, which contains a higher proportion of high-grade glioma cells. We found that the addition of Ve doubled the sensitivity while nonsignificantly decreasing the specificity for prediction of local recurrence in glioblastomas, which implies that the combined model may result in fewer missed cases of local recurrence. The deep learning model predictive of local recurrence may enable risk-adapted radiotherapy planning in patients with grade 4 adult-type diffuse gliomas.

Virtual reality(VR) applications are typically developed within their own immersive digital worlds; therefore, virtual spaces are usually treated as discrete from the physical space where augmented and mixed reality users exist, which makes it difficult to combine these heterogeneous realities into an integrated extended reality(XR) environment. Along these lines, we propose a method that enables a user to geometrically register the virtual space within a VR application to a real space using a commodity camera in a workspace as an anchor point. We first investigate the mathematical aspect of the computational model for connecting the virtual space to the physical world. Then, we present a computational procedure that implements our proposed method with numerical accuracy and stability. As an application, we demonstrate that users of two VR systems from different vendors may collaborate within a shared real workspace while interacting with each other physically. The presented method provides a key mechanism for enabling XR users to leverage these immersive technologies by effectively using different realities within an integrated environment.

Abstract Background We examined the incidence and predictors of clinical outcomes in metabolic dysfunction‐associated fatty liver disease (MAFLD), focusing on anthropometric parameters. Methods Adult patients with MAFLD were identified in nationwide databases and a hospital cohort. Primary endpoints were atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis. Logistic and Cox regression analyses were used to analyse the association between anthropometric parameters and endpoints. Results In total, 4407 of 15 256 (28.9%) and 6274 of 25 784 subjects (24.3%) had MAFLD in the nationwide database; of these, 403 (9.2%) and 437 (7.0%) subjects were of lean/normal weight, respectively. Compared to the overweight/obese group, the lean/normal weight group had a significantly lower muscle mass (15.0 vs. 18.9 kg) and handgrip strength (31.9 vs. 35.1 kg) and had a higher ASCVD risk (9.0% vs. 6.3% and 15.9% vs. 8.5%; Ps

Abstract Adult-type diffuse glioma (grade 4) has infiltrating nature, and therefore local progression is likely to occur within surrounding non-enhancing T2 hyperintense areas even after gross total resection of contrast-enhancing lesions. Cerebral blood volume (CBV) obtained from dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) is a parameter that is well-known to be a surrogate marker of both histologic and angiographic vascularity in tumors. We built two nnU-Net deep learning models for prediction of early local progression in adult-type diffuse glioma (grade 4), one using conventional MRI alone and one using multiparametric MRI, including conventional MRI and DSC-PWI. Local progression areas were annotated in a non-enhancing T2 hyperintense lesion on preoperative T2 FLAIR images, using the follow-up contrast-enhanced (CE) T1-weighted (T1W) images as the reference standard. The sensitivity was doubled with the addition of nCBV (80% vs. 40%, P = 0.02) while the specificity was decreased nonsignificantly (29% vs. 48%, P = 0.39), suggesting that fewer cases of early local progression would be missed with the addition of nCBV. While the diagnostic performance of CBV model is still poor and needs improving, the multiparametric deep learning model, which presumably learned from the subtle difference in vascularity between early local progression and non-progression voxels within perilesional T2 hyperintensity, may facilitate risk-adapted radiotherapy planning in adult-type diffuse glioma (grade 4) patients.

Abstract Background/Aims Regression of liver fibrosis during antiviral therapy in chronic hepatitis B (CHB) patients has been demonstrated, but data on the influence of long-term treatment with tenofovir disoproxil fumarate (TDF) on liver stiffness (LS) measured by transient elastography are scarce. We aimed to investigate the changes in LS values during the 144-week TDF therapy in treatment-naïve CHB patients. Methods This prospective observational study was conducted from April 2015 to July 2020 at CHA Bundang Medical Center. Laboratory tests and LS measurements were performed at baseline and repeated at weeks 12, 24, 48, 96, and 144. A significant decline in LS was defined as ≥ 30% decrease in LS value at week 96 from baseline. Results A total of 48 treatment-naïve CHB patients initiating TDF therapy were screened, and 36 patients were included in the final analysis (median age, 46 [interquartile range, 34.5–55.8] years; 19 men [52.8%]). During TDF therapy, the median LS values decreased from 13.8 kPa at baseline to 8.7 kPa, 6.5 kPa, and 6.4 kPa at weeks 48, 96, and 144, respectively (all P

Abstract Background The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. Methods Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups. Results We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression. Conclusions This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies.

This study aimed to assess the performance of a tongue-positioning device in interfractional tongue position reproducibility by cone-beam computed tomography (CBCT). Fifty-two patients treated with radiation therapy (RT) while using a tongue positioning device were included in the study. All patients were treated with 28 or 30 fractions using the volumetric modulated arc therapy technique. CBCT images were acquired at the 1st, 7th, 11th, 15th, 19th, 23th, and 27th fractions. Tongues on planning computed tomography (pCT) and CBCT images were contoured in the treatment planning system. Geometric differences in the tongue between pCT and CBCT were assessed by the Dice similarity coefficient (DSC) and averaged Hausdorff distance (AHD). Two-dimensional in vivo measurements using radiochromic films were performed in 13 patients once a week during sessions. The planned dose distributions were compared with the measured dose distributions using gamma analysis with criteria of 3%/3 mm. In all patients, the mean DSC at the 1st fraction (pCT versus 1st CBCT) was 0.80 while the mean DSC at the 27th fraction (pCT versus 27th CBCT) was 0.77 with statistical significance (p-value = 0.015). There was no statistically significant difference in DSC between the 1st fraction and any other fraction, except for the 27th fraction. There was statistically significant difference in AHD between the 1st fraction and the 19th, 23th, and 27th fractions (p-value < 0.05). In vivo measurements showed an average gamma passing rate of 90.54%. There was no significant difference between measurements at the 1st week and those at other weeks. The tongue geometry during RT was compared between pCT and CBCT. In conclusion, the novel tongue-positioning device was found to minimize interfractional variations in position and shape of the tongue.

Abstract Background The purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor. Methods A retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54 Gy (range 48–60 Gy), and the median fraction number was 4 (range 4–6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort. Results The 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%, P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity. Conclusions The local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable.

IntroductionThe dosimetric factors of radiotherapy have an acute impact on the host immune system during chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, even after CRT, a substantial number of patients remain immunosuppressed with delayed lymphopenia. Therefore, we aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia after CRT in locally advanced NSCLC.Materials and methodsWe retrospectively reviewed 272 patients with locally advanced NSCLC who received definitive CRT from January 2012 to August 2020. Differential blood count data, including serum albumin values, were obtained at baseline, during and at first follow up after CRT. Acute and delayed lymphopenia events were defined as grade III/IV lymphopenia developed during or 4-12 weeks after CRT completion, which accounted for 84% and 10% of cases, respectively. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated.ResultsMultivariate analysis revealed that patients with delayed lymphopenia were associated with inferior overall survival (HR 2.53, P = 0.001) and progression-free survival (HR 1.98, P = 0.006). However, there was no significant survival difference between groups stratified by acute lymphopenia. On multivariable logistic regression models, lung V5, baseline ALC, during-CRT ALC, and albumin nadir were significant predictors for delayed lymphopenia. Furthermore, the nomogram for delayed lymphopenia based on these variables had good discrimination (area under the curve, 0.905).ConclusionsIn this study, we investigated the prognostic significance of delayed lymphopenia and identified clinico-dosimetric parameters to predict delayed lymphopenia.

PurposeWe aimed to compare the outcomes of adjuvant radiotherapy (ART) and surveillance in patients with grade 2 meningiomas (MNG2) who underwent surgical resection.Materials and MethodsData from four hospitals, in which patients aged ≥18 years underwent Simpson grade 1−4 surgical resection for newly diagnosed MNG2 between 1998 and 2018, were examined in this multicenter retrospective cohort study. Patients receiving ART with conventional fractionation were compared with those undergoing surveillance. Progression-free survival (PFS), progression/recurrence (P/R) were evaluated.ResultsThis study included 518 patients, 158 of whom received ART. The median follow-up duration was 64.9 months. In the total cohort, ART was independently associated with significantly improved PFS (HR, 0.35; 95% CI, 0.23–0.55; P

Abstract Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903–1.000) for local recurrence; 0.864 (0.726–0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or “radiomic risk score”, increased risk of recurrence/progression (hazard ratio, 1.61; p = 0.03) in multivariate Cox regression on progression-free survival.

Summary: Background/Objective: The number of gastric cancer and type II diabetes mellitus is increasing in Korea. Metabolic surgery could be extended to gastric cancer patients with type II diabetes, especially those who are expected to achieve long-term survival. This study aimed to investigate change of diabetic status in patients undergoing long-limb Roux-en-Y bypass reconstruction compared with conventional Billroth II after curative gastrectomy. In total, 130 patients from five university hospital centers underwent long-limb Roux-en Y reconstruction after radical distal gastrectomy. Methods: In the long-limb group, the length of biliopancreatic limbs was more than 80 cm, and the length of the Roux limb was more than 80 cm. The control group comprised 96 patients who underwent conventional Billroth II reconstruction after distal gastrectomy. Follow-up data at three, six, nine, and 12 months were compared between the two groups. Results: Fasting blood sugar (FBS) and hemoglobin (Hb) A1c levels decreased more significantly in the long-limb Roux-en-Y group (FBS: 28.8 mg/dL; HbA1c: 0.72%). However, decreases in body mass index, albumin, and hemoglobin did not differ significantly between the two groups. Diabetes control significantly improved in the long-limb group. In multivariate analysis, long-limb bypass reconstruction was the significant factor for glycemic outcomes. Conclusion: Roux-en-Y bypass with increased length of limbs after gastrectomy shows a favorable glycemic control for gastric cancer patients with type II diabetes without nutritional deficit and anemia. To obtain future perspectives, large-scale prospective studies with long-term outcomes are needed. Keywords: Type II DM, Gastric cancer, Long limb Roux-en Y

Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m². Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI ≥35 kg/m² and for Korean patients with BMI ≥30 kg/m² who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity.

Background/Aims Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake. Methods Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors. Results Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9–8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122–8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404–7.228; P=0.47). Conclusions Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

Laparoscopic sleeve gastrectomy has become a standard procedure in bariatric surgery owing to its efficacy and simplicity. However, this procedure can cause life-threatening complications such as a gastric staple-line leak. A 24-year-old woman was transferred to the emergency department for evaluation of epigastric pain. Nine days prior to transfer, she underwent laparoscopic sleeve gastrectomy at another institution. Abdominal computed tomography (CT) revealed fluid collection with air density along the left subphrenic space and gastrosplenic ligament area. Intravenous antibiotics and total parenteral nutrition were initiated. She underwent percutaneous catheter drainage. On postoperative day 18, an esophagogastroduodenoscopy was performed to assess the site and size of the leak, and revealed a leak at the proximal staple line just below the gastroesophageal junction. A newly designed, fully covered antimigratory esophageal stent was placed to cover the leak from the distal esophagus to gastric midbody. Follow-up abdominal CT demonstrated improvement of the fluid collection at the location of the previous gastric leak. The stent was removed 3 weeks after insertion, and a barium study confirmed no more leakage. In this case, we experienced that the newly designed esophageal stent was safe and effective for preventing migration in the management of leak after laparoscopic sleeve gastrectomy.

Portal vein thrombosis (PVT) is a form of venous thrombosis that usually presents in chronic form without any sequalae in patients with hepatocellular carcinoma (HCC) or liver cirrhosis. Accurate differential diagnosis of bland PVT from neoplastic PVT is an important step for planning treatment options, but the acute form can be challenging. Here we present a case of acute hepatic infarction caused by acute bland PVT combined with pylephlebitis, which was misdiagnosed as infiltrative hepatic malignancy with neoplastic PVT owing to the perplexing imaging results and elevated tumor markers. (Korean J Gastroenterol 2016;68:156-160)

Entecavir (BaracludeⓇ) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy. (Korean J Gastroenterol 2016;67:216-219)

Radiation dermatitis can develop after fluoroscopy-guided interventional procedures. Cases of fluoroscopy-induced radiation dermatitis have been reported since 1996, mostly documented in the fields of radiology, cardiology and dermatology. Since diagnosis and treatment of fluoroscopy-induced radiation dermatitis can be difficult, high grade of suspicion is required. The extent of this reaction is determined by radiation dose, duration of exposure, type of procedure, and host factors and can be aggravated by concomitant use of photosensitizers. Follow-up is important after long and complicated procedures and efforts to minimize radiation exposure time will be necessary to prevent radiation dermatitis. Herein, we report a case of a 58-year-old man with hepatocellular carcinoma presenting with subacute radiation dermatitis after prolonged fluoroscopic exposure during transarterial chemoembolization and chemoport insertion. Physicians should be aware that fluoroscopy is a potential cause of radiation dermatitis. (Korean J Gastroenterol 2016;67:112-115)

Non-alcoholic fatty liver disease (NAFLD) is defined as a pathologic accumulation of fat in the form of triglycerides (TG) in the liver (steatosis) that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis), which is referred to as non-alcoholic steatohepatitis (NASH). Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC). NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications.

Background/AimsApolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies.MethodsThis hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits.ResultsThe ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype.ConclusionsThe ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.

This paper concerns the use of synthetic data for protecting the confidentiality of business data during statistical analysis. Synthetic data sets are traditionally constructed by replacing sensitive values in a confidential data set with draws from statistical models estimated on the confidential data set. Unfortunately, the process of generating effective statistical models can be a difficult and labour-intensive task. Recently, it has been proposed to use easily-implemented methods from machine learning instead of statistical model estimation in the data synthesis task. J. Drechsler and J.P. Reiter (2011) have conducted an evaluation of four such methods, and have found that regression trees could give rise to synthetic data sets which provide reliable analysis results as well as low disclosure risks. Their conclusion was based on simulations using a subset of the 2002 Uganda census public use file. It is an interesting question whether the same conclusion applies to other types of data with different characteristics, for example business data which have quite different characteristics from population census and survey data. In particular, business data generally have few variables that are mostly categorical, and often have highly skewed distributions with outliers. In this paper we investigate the applicability of regression-tree-based methods for constructing synthetic business data. We give a detailed example comparing exploratory data analysis and linear regression results under two variants of a regression-tree-based synthetic data approach. We also include an evaluation of the analysis results with respect to the results of analysis of the original data. We further investigate the impact of different stopping criteria on performance. While it is certainly true that any method designed to protect confidentiality introduces error, and may indeed give misleading conclusions, our analysis of the results for synthesisers based on CART models has provided some evidence that this error is not random but is due to the particular characteristics of business data. We conclude that more careful analysis needs to be done in applying these methods and end users certainly need aware of possible discrepancies.

Purpose: This study aimed to evaluate the impact of facilitating target delineation of continuous positive airway pressure (CPAP) in patients undergoing stereotactic ablative radiation therapy (SABR) for lung tumors by lung expansion and respiratory motion management. Materials and Methods: We performed a prospective single-institutional trial of patients who were diagnosed with either primary lung cancer or lung metastases and received SABR with a dose of 40 to 60 Gy in 4 fractions. Four-dimensional computed tomography simulations were conducted for each patient: once without CPAP and again with CPAP. Results: Thirty-two patients with 39 tumors were analyzed, after the withdrawal of five patients due to discomfort. For 26 tumors separated from the diaphragm, CPAP significantly increased the superoinferior distance between the tumor and the diaphragm (5.96 cm vs. 8.06 cm; p < 0.001). For 13 tumors located adjacent to the diaphragm, CPAP decreased the overlap of planning target volume (PTV) with the diaphragm significantly (6.32 cm³ vs. 4.09 cm³; p = 0.002). PTV showed a significant reduction with CPAP (25.06 cm³ vs. 22.52 cm³, p = 0.017). In dosimetric analyses, CPAP expanded lung volume by 58.4% with a significant reduction in mean dose and V5 to V40. No more than grade 2 adverse events were reported. Conclusion: This trial demonstrated significant improvement of CPAP in target delineation uncertainties for lung SABR, with dosimetric benefits, a favorable safety profile and tolerability. Further investigation is warranted to explore the role of CPAP as a novel strategy for respiratory motion management. [ABSTRACT FROM AUTHOR]