In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

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

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

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

OBJECTIVETo obtain monoclonal antibodies (McAbs) against severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) nucleocapsid (N) protein to develop diagnostic test for SARS and study the pathogenesis of the disease.

METHODSBALB/c mice were immunized with purified N protein of SARS-CoV. Hybridoma cell lines secreting monoclonal antibodies against SARS-associated coronavirus nucleocapsid were established after cell fusion with mouse splenic cells and SP2/0 cells. The specificity of the McAbs obtained was examined by Western blot and indirect fluorescence assay. Epitopes reacted with the McAbs were preliminarily located through Western blot by expressing truncated N proteins.

RESULTSAfter cell fusion and three rounds of cell cloning, six hybridoma cell lines secreting monoclonal antibodies specifically against SARS-CoV nucleocapsid were obtained. Western blot and indirect fluorescence assay showed that the McAbs reacted specifically with nucleocapsid protein and SARS-CoV. Among the six McAbs, three recognize the epitopes located in the N-terminus of the protein, whereas the others reacted with those located in the C-terminus.

CONCLUSIONThe anti-SARS-CoV nucleocapsid McAbs were developed and these McAbs may be useful in the development of diagnosis assays and basic research of SARS.

Animals ; Antibodies, Monoclonal ; biosynthesis ; immunology ; Antibodies, Viral ; biosynthesis ; immunology ; Antibody Specificity ; Female ; Hybridomas ; secretion ; Mice ; Mice, Inbred BALB C ; Nucleocapsid Proteins ; immunology ; isolation & purification ; SARS Virus ; chemistry ; immunology

This study was conducted to investigate the supplementary effects of Suwon 464 developed by Rural Development Administration, which has over two times of dietary fiber content compared with normal rice (Ilpum), on lipid metabolism in diabetic mice. We supplied 5 kinds of experimental diets (corn starch diet as a control (CO), Ilpum polished rice diet (IP), Ilpum brown rice diet (IB), polished rice diet (SP) and brown rice diet (SB) of Suwon 464) to diabetic mice for 8 weeks, after analyzing dietary fiber contents of 5 experimental diets. Diet intake, body weight, organ weights, and lipids levels of serum, liver and feces were measured. The dietary fiber contents in CO, IP, IB, SP, and SB diets were 1.0, 1.2, 1.4, 1.4, and 2.0% respectively. Body weight and liver and epididymal fat pad weights were lower in SB group than the other groups though there was no significant difference in diet intake among experimental groups. The concentrations of serum triglyceride was lower in SP and SB groups than CO and IP groups. The levels of hepatic total lipid and total cholesterol were significantly lower in SP and SB groups than CO group, and the level of hepatic triglyceride was lower in IB, SP and SB groups than CO group. The levels of total lipid and triglyceride excreted in feces were higher in IB, SP and SB, and the level of total cholesterol in feces was higher in SP and SB groups than CO group. These results suggested that the high dietary fiber rice (Suwon 464) decrease the triglyceride or total cholesterol concentrations of serum and liver by increasing of fecal lipid excretion in diabetic mice.
Adipose Tissue ; Animals ; Body Weight ; Cholesterol ; Diet ; Dietary Fiber* ; Feces ; Gyeonggi-do ; Lipid Metabolism* ; Liver ; Mice* ; Organ Size ; Social Planning ; Starch ; Triglycerides ; Weights and Measures

OBJECTIVETo obtain monoclonal antibodies (McAbs) which can be widely used to detect mammalian prions (PrP) and to develop diagnostic tests for screening transmissile spongiform encephalopathies (TSE) as well as for studying pathogenesis of prion-related diseases.

METHODSBALB/c mice were immunized separately with bovine PrP peptide 29-48 (BoP1) and 89-108 (BoP2) coupled to keyhole limpt hemocyan. Two hybridoma cell lines secreting monoclonal antibodies against these peptides were established by cell fusion and 2 to 3 rounds of cell cloning. The reactions of the McAbs to the recombinant bovine (Bo)PrP(25-242), human (Hu)PrP(23-231) and hamster (Ha) PrP (23?231) were tested separately by Western blotting.

RESULTSThrough cell fusion, two hybridoma cell lines secreting McAbs against BoP1 and BoP2, designated D11 and D8 accordingly, were identified by ELISA and cell cloning. The McAbs produced by these cell lines reacted well with the recombinant PrP proteins; (Bo) PrP (25-242), (Hu) PrP (23-231), and (Ha) PrP (23-231), respectively.

CONCLUSIONSTwo McAbs reacting with bovine, human and hamster PrPs were successfully generated, they are potential to be used to detect PrPs in mammals and to study the mechanism of pathogenesis of TSE.

Animals ; Antibodies, Monoclonal ; biosynthesis ; Antibodies, Viral ; biosynthesis ; immunology ; Antibody Specificity ; Cattle ; Cricetinae ; Cross Reactions ; Encephalopathy, Bovine Spongiform ; prevention & control ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hybridomas ; secretion ; Male ; Mice ; Mice, Inbred BALB C ; PrPSc Proteins ; immunology ; Prion Diseases ; prevention & control ; Prions ; immunology ; Recombinant Fusion Proteins ; biosynthesis ; immunology

Finite element analyses were performed to study effects on stress distribution generated in jaw bone for various shapes of dental implants: plateau type, plateau with small radius of curvature, triangular thread screw type in accordance with ISO regulations and square thread screw filleted with small radius partially. It was found that square thread screw filleted with small radius was more effective on stress distribution than other dental implants used in analyses. Additional analyses were performed on the implant with square thread screw filleted with small radius for verying design parameters, such as the width of thread end, the height of the thread of the implant and load direction, to determine the optimum dimensions of the implant. The highest stress concentration occurred at the region in jaw bone adjacent to the first thread of the implant. The maximum effective stress induced by a 15 degree oblique load of 100 N was twice as high as the maximum effective stress caused by an equal amount of vertical load. Stress distribution was more effective in the case when the width of thread end and the height of thread were p/2 and 0.46p, respectively, where p is the pitch of thread. At last, using tensile force calculated from the possible insert torque without breading bone thread, finite element analysis was performed on the implant to calculate pre-stress when the primary fixation of the implant was operated in jaw bone. The maximum effective stress was 136.8 MPa which proven to be safe.
Bread ; Dental Implants ; Finite Element Analysis ; Jaw ; Radius ; Social Control, Formal ; Torque