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Objective: Anterior cranial fossa (ACF) dural arteriovenous fistulas (DAVFs) are notoriously malignant vascular abnormalities, and their drainage into the cortical vein poses a high risk of intracranial hemorrhage (ICH). Stereotactic radiosurgery (SRS) is increasingly seen as an alternative to microsurgery or embolization for the treatment of DAVFs; however, researchers have yet to report on its applicability to ACF DAVFs. This paper summarizes the authors' experience in the use of SRS for ACF DAVFs. The authors' objective was to gain a preliminary overview of SRS outcomes in the treatment of ACF DAVFs., Methods: This retrospective study examined all patients who underwent SRS for ACF DAVFs at a single academic medical center between November 2000 and November 2023. Demographic data, DAVF characteristics, and clinical outcomes were obtained from medical records., Results: A total of 12 patients diagnosed with ACF DAVFs were treated using SRS. One patient was lost to follow-up. The mean age was 54.8 years and men comprised 82% of the cohort. The most common presenting symptoms included headache (n = 5), ocular symptoms (n = 3), seizure (n = 2), anosmia (n = 1), and tinnitus (n = 1). Two patients were asymptomatic. Four patients (36%) initially presented with ICH. Nine patients exhibited DAVF Cognard type IV, and 2 patients exhibited Cognard type III. DAVF obliteration in 7 of the 11 patients (64%) was confirmed by brain MR angiography (n = 4) or digital subtraction angiography (n = 3). No post-SRS episodes of ICH were reported. Most of the patients (10 of 11) reported improvements in clinical symptoms., Conclusions: SRS appears to be a viable alternative treatment for ACF DAVFs, particularly for patients who are not suitable candidates for surgery or those with an unfavorable angioarchitecture.

Purpose: Conventional minimally invasive surgery requires mini-laparotomy to extract the pathological specimen. However, by using a natural orifice as the delivery route, natural orifice specimen extraction (NOSE) surgery avoids the need for a large incision. This study analyzed the short-term outcome of NOSE compared with conventional mini-laparotomy (CL) for colorectal cancer surgery., Methods: We conducted a retrospective analysis of 1,189 patients who underwent surgery for primary colorectal cancer between the cecum and upper rectum. Propensity score analyses were applied to the NOSE and CL groups in a 1:1 matched cohort., Results: After propensity score matching, each group included 201 patients. The NOSE group and CL group did not differ significantly in terms of baseline characteristics. Postoperative morbidity and mortality rates were comparable. Compared with the CL group, the NOSE group experienced a shorter time to first flatus (1.6 ± 0.8 vs. 2.0 ± 1.2 days, p < 0.001), first stool (2.7 ± 1.5 vs. 4.1 ± 1.9, p < 0.001), liquid diet (2.3 ± 1.3 vs. 3.6 ± 1.8 days, p < 0.001), soft diet (3.9 ± 2.0 vs. 5.2 ± 1.9 days, p < 0.001) and a shorter hospital stay (5.1 ± 3.5 vs. 7.4 ± 4.8 days, p < 0.001). The NOSE group exhibited lower mean pain intensity and lower highest pain intensity on postoperative days 1, 2, and 3., Conclusion: NOSE has several advantages over conventional mini-laparotomy following minimally invasive surgery for colon cancer. These advantages include reduced time to oral intake, shorter hospital stays, and less postoperative pain. NOSE can be adopted and applied to highly selective patients without additional risk of short-term complications., (© 2024. The Author(s).)

Purpose: To evaluate the association between contrast sensitivity (CS), vessel density (VD), and functional parameters in patients with glaucoma of varying severity., Methods: Ninety-four eyes of 94 patients (57 men and 37 women, aged 56.52 ± 11.28 years) were divided into mild and moderate to advanced glaucoma groups. The mild glaucoma group was further subdivided based on the presence of central visual field defect (CVFD). Pearson's correlations were used to evaluate the associations between area under the log CS function (AULCSF), best-corrected visual acuity (BCVA), 10 - 2 visual field (VF), and structural parameters, including VD. The area under the receiver operating characteristic (AUROC) curve was calculated to detect abnormal CS (AULCSF < 1.2)., Results: In mild glaucoma without CVFD, AULCSF was associated with radial peripapillary capillary VD (γ = 0.597, P = 0.001), with an AUROC of 0.840 (P = 0.006) for detecting abnormal CS. In mild glaucoma with CVFD, AULCSF worsened and was associated with superficial parafoveal VD (γ = 0.569, P = 0.017) and macular whole image VD (γ = 0.632, P = 0.007), with AUROCs of 0.833 (P = 0.021) and 0.792 (P = 0.043), respectively. In moderate to advanced glaucoma, the relationship between AULCSF and the mean deviation of 10 - 2 VF and BCVA was more robust than that observed in structural measures., Conclusions: Decreased VD is linked to early CS impairment. Radial peripapillary capillary and macular VD can serve as indicators of CS function in the early stages of glaucoma. KEY  MESSAGES: What is known Contrast sensitivity loss has been reported in glaucoma patients but its relationship with glaucoma-related structural and functional changes in different glaucoma severity and central visual field defect (CVFD) remains elusive. What is new Decline in RPC peripapillary vessel density was associated with early impairment of contrast sensitivity in mild glaucoma without CVFD. Decline in macular vessel density and central 16 points of 10-2 visual field damage were associated with contrast sensitivity reduction in mild glaucoma with CVFD. Microvasculature change can serve as an indicator for abnormal contrast sensitivity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Medication-related problem is a concerning issue in older adults with multimorbidity due to complexity of disease conditions and polypharmacy, and may lead to increase in risk for adverse health outcomes. This study aims to investigate the prevalence and associated factors of potentially inappropriate medication use among the growing population of older adults with multimorbidity in Taiwan., Method: The study population was composed of patients who were aged 65 years or older with multimorbidity (two or more chronic diseases) and had at least one outpatient clinic visit with drug prescription in 2018 identified from the Taiwan National Health Insurance Research Database. Potentially inappropriate medication use was defined using the 2019 Beers criteria for drugs to be avoided for older adults. Multiple logistic regression model was conducted to examine patient-related and prescriber-related factors associated with PIM use., Results: A total of 2 432 416 patients (69.7% of the entire older adult population) had multimorbidity and received at least one drug prescription at the outpatient clinic in Taiwan in 2018. The prevalence of having at least one PIM in this population was found to be 85.6%. Patient-related factors (age, sex, specific chronic diseases, frequency of outpatient visits) and prescriber-related factors (physician characteristics, healthcare setting, total number of medications, prior PIM use) were found to be associated with use of PIM., Conclusion: High prevalence of PIM use was found in older patients with multimorbidity in Taiwan. Both patient-related and prescriber-related factors had been found to be predictors of PIM use, and should be addressed when trying to improve the medication quality in this population., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: We introduced an adapted Lyman normal-tissue complication probability (NTCP) model, incorporating clinical risk factors and censored time-to-event data, to estimate the risk of major adverse cardiac events (MACE) following left breast cancer radiotherapy (RT)., Materials and Methods: Clinical characteristics and MACE data of 1100 women with left-side breast cancer receiving postoperative RT from 2005 to 2017 were retrospectively collected. A modified generalized Lyman NTCP model based on the individual left ventricle (LV) equivalent uniform dose (EUD), accounting for clinical risk factors and censored data, was developed using maximum likelihood estimation. Subgroup analysis was performed for low-comorbidity and high-comorbidity groups., Results: Over a median follow-up 7.8 years, 64 patients experienced MACE, with higher mean LV dose in affected individuals (4.1 Gy vs. 2.9 Gy). The full model accounting for clinical factors identified D 50  = 43.3 Gy, m = 0.59, and n = 0.78 as the best-fit parameters. The threshold dose causing a 50 % probability of MACE was lower in the high-comorbidity group (D 50  = 30 Gy) compared to the low-comorbidity group (D 50  = 45 Gy). Predictions indicated that restricting LV EUD below 5 Gy yielded a 10-year relative MACE risk less than 1.3 and 1.5 for high-comorbidity and low-comorbidity groups, respectively., Conclusion: Patients with comorbidities are more susceptible to cardiac events following breast RT. The proposed modified generalized Lyman model considers nondosimetric risk factors and addresses incomplete follow-up for late complications, offering comprehensive and individualized MACE risk estimates post-RT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of electronic cigarettes (e-cigarettes) is on the rise among young adults, with higher public acceptance than traditional tobacco. A study in Taiwan employed concept mapping to explore risk and benefit perceptions of e-cigarette use among college students. The study involved 100 college students from 11 Taiwanese universities, with 50 being e-cigarette users and 50 non-users. Data collection and analysis were done with the GroupWisdom™ platform. Participants engaged in brainstorming, rating and sorting their perceptions, which were analyzed using multidimensional scaling and hierarchical cluster analyses. The participants' mean age was 19.24 years, and 55% were male. This process resulted in the identification of 10 clusters encompassing 64 statements, with 3 clusters focused on risk perceptions, 6 on benefit perceptions, and 1 dealing with e-cigarette regulations. Notably, risk perceptions were rated higher than benefit perceptions. Non-users held significantly higher risk perceptions and lower benefit perceptions across the nine clusters related to e-cigarette use. Concept mapping proved to be an effective tool for understanding college students' perceptions. These findings can assist health educators in comprehending college students' viewpoints on e-cigarette use and in developing targeted interventions. Additionally, exploring benefit perceptions may enhance students' critical thinking skills regarding e-cigarette advertising., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Scope: Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with muscle mass. The effect of KMP on C2C12 myoblast differentiation and the mechanisms that might underlie that effect are studied., Methods and Results: This study finds that KMP (1, 10 µM) increases the migration and differentiation of C2C12 myoblasts in vitro. Studying the possible mechanism underlying its effect on migration, the study finds that KMP activates Integrin Subunit Beta 1 (ITGB1) in C2C12 myoblasts, increasing p-FAK (Tyr398) and its downstream cell division cycle 42 (CDC42), a protein previously associated with cell migration. Regarding differentiation, KMP upregulates the expression of myosin heavy chain (MHC) and activates IGF1/AKT/mTOR/P70S6K. Interestingly, pretreatment with an AKT inhibitor (LY294002) and siRNA knockdown of IGF1R leads to a decrease in cell differentiation, suggesting that IGF1/AKT activation is required for KMP to induce C2C12 myoblast differentiation., Conclusion: Together, the findings suggest that KMP enhances the migration and differentiation of C2C12 myoblasts through the ITG1B/FAK/paxillin and IGF1R/AKT/mTOR pathways. Thus, KMP supplementation might potentially be used to prevent or delay age-related loss of muscle mass and help maintain muscle health., (© 2024 Wiley‐VCH GmbH.)

Background: As ChatGPT becomes a primary information source for college students, its performance in providing dietary advice is under scrutiny. This study assessed ChatGPT's performance in providing nutritional guidance to college students., Methods: ChatGPT's performance on dietary advice was evaluated by 30 experienced dietitians and assessed using an objective nutrition literacy (NL) test. The dietitians were recruited to assess the quality of ChatGPT's dietary advice, including its NL achievement and response quality., Results: The results indicate that ChatGPT's performance varies across scenarios and is suboptimal for achieving NL with full achievement rates from 7.50% to 37.56%. While the responses excelled in readability, they lacked understandability, practicality, and completeness. In the NL test, ChatGPT showed an 84.38% accuracy rate, surpassing the NL level of Taiwanese college students. The top concern among the dietitians, cited 52 times in 242 feedback entries, was that the "response information lacks thoroughness or rigor, leading to misunderstandings or misuse". Despite the potential of ChatGPT as a supplementary educational tool, significant gaps must be addressed, especially in detailed dietary inquiries., Conclusion: This study highlights the need for improved AI educational approaches and suggests the potential for developing ChatGPT teaching guides or usage instructions to train college students and support dietitians.

Background and Aims: Niche differentiation is a crucial issue in speciation. Although it has a well-known role in adaptive processes of hybrid angiosperms, it is less understood in hybrid ferns. Here, we investigate whether an intermediate ecological niche of a fern hybrid is a novel adaptation that provides insights into fern hybrid speciation., Methods: Pteris fauriei (Pteridaceae) is a natural hybrid fern, occurring in environments between its parent species. The maternal Pteris minor is found in sunny areas, but the habitat of the paternal Pteris latipinna is shady. We combined data from morphology, leaf anatomy and photosynthetic traits to explore adaptation and differentiation, along with measuring the environmental features of their niches. We also performed experiments in a common garden to understand ecological plasticity., Key Results: The hybrid P. fauriei was intermediate between the parent species in stomatal density, leaf anatomical features and photosynthetic characteristics in both natural habitats and a common garden. Interestingly, the maternal P. minor showed significant environmental plasticity and was more similar to the hybrid P. fauriei in the common garden, suggesting that the maternal species experiences stress in its natural habitats but thrives in environments similar to those of the hybrid., Conclusions: Based on the similar niche preferences of the hybrid and parents, we propose hybrid superiority. Our results indicate that the hybrid P. fauriei exhibits greater fitness and can compete with and occupy the initial niches of the maternal P. minor. Consequently, we suggest that the maternal P. minor has experienced a niche shift, elucidating the pattern of niche differentiation in this hybrid group. These findings offer a potential explanation for the frequent occurrence of hybridization in ferns and provide new insights into fern hybrid speciation, enhancing our understanding of fern diversity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background : Cardiorespiratory fitness positively correlates with longevity and immune health. Regular exercise may provide health benefits by reducing systemic inflammation. In chronic disease conditions, such as chronic heart failure and chronic fatigue syndrome, mechanistic links have been postulated between inflammation, muscle weakness, frailty, catabolic/anabolic imbalance, and aberrant chronic activation of immunity with monocyte upregulation. We hypothesize that (1) temporal changes in transcriptome profiles of peripheral blood mononuclear cells during strenuous acute bouts of exercise using cardiopulmonary exercise testing are present in adult subjects, (2) these temporal dynamic changes are different between healthy persons and heart failure patients and correlate with clinical exercise-parameters and (3) they portend prognostic information. Methods : In total, 16 Heart Failure (HF) patients and 4 healthy volunteers (HV) were included in our proof-of-concept study. All participants underwent upright bicycle cardiopulmonary exercise testing. Blood samples were collected at three time points (TP) (TP1: 30 min before, TP2: peak exercise, TP3: 1 h after peak exercise). We divided 20 participants into 3 clinically relevant groups of cardiorespiratory fitness, defined by peak VO 2 : HV ( n = 4, VO 2 ≥ 22 mL/kg/min), mild HF (HF1) ( n = 7, 14 < VO 2 < 22 mL/kg/min), and severe HF (HF2) ( n = 9, VO 2 ≤ 14 mL/kg/min). Results : Based on the statistical analysis with 20-100% restriction, FDR correction ( p -value 0.05) and 2.0-fold change across the three time points (TP1, TP2, TP3) criteria, we obtained 11 differentially expressed genes (DEG). Out of these 11 genes, the median Gene Expression Profile value decreased from TP1 to TP2 in 10 genes. The only gene that did not follow this pattern was CCDC181 . By performing 1-way ANOVA, we identified 8/11 genes in each of the two groups (HV versus HF) while 5 of the genes ( TTC34 , TMEM119 , C19orf33 , ID1 , TKTL2 ) overlapped between the two groups. We found 265 genes which are differentially expressed between those who survived and those who died. Conclusions : From our proof-of-concept heart failure study, we conclude that gene expression correlates with VO 2 peak in both healthy individuals and HF patients, potentially by regulating various physiological processes involved in oxygen uptake and utilization during exercise. Multi-omics profiling may help identify novel biomarkers for assessing exercise capacity and prognosis in HF patients, as well as potential targets for therapeutic intervention to improve VO 2 peak and quality of life. We anticipate that our results will provide a novel metric for classifying immune health.

Background: Colorectal cancer (CRC) presents with varying prognoses, and identifying factors for predicting metastasis and outcomes is crucial. Perineural invasion (PNI) is a debated prognostic factor for CRC, particularly in stage I-III patients, but its role in guiding adjuvant chemotherapy for node-positive colon cancer remains uncertain., Methods: We conducted a single-center study using data from the Colorectal Section Tumor Registry Database at Chang Gung Memorial Hospital, Taiwan. This prospective study involved 3,327 CRC patients, 1,536 of whom were eligible after application of the exclusion criteria, to investigate the prognostic value of PNI in stage I-III patients and its predictive value for node-positive/negative cancer patients receiving adjuvant chemotherapy. Propensity score matching (PSM) was used to minimize selection bias, and follow-up was performed with standardized procedures., Results: PNI-positive (PNI+) tumors were associated with higher preoperative CEA levels and more frequent adjuvant chemotherapy. After PSM, PNI + tumors were associated with marginally significantly lower 5-year disease-free survival (DFS) and significantly lower overall survival (OS) rates in stages III CRC. However, no significant differences were observed in stages I and II. Subgroup analysis showed that among PNI + tumors, only poorly differentiated tumors had higher odds of recurrence. PNI did not predict outcomes in node-negative colon cancer. Adjuvant chemotherapy benefited PNI + patients with node-positive but not those with node-negative disease., Conclusions: Our study indicates that PNI is an independent poor prognostic factor in stage III colon cancer but does not predict outcomes in node-negative disease. Given the potential adverse effects of adjuvant chemotherapy, our findings discourage its use in node-negative colon cancer when PNI is present., (© 2024. The Author(s).)

Global warming has a significant impact on the dairy farming industry, as heat stress causes reproductive endocrine imbalances and leads to substantial economic losses, particularly in tropical-subtropical regions. The Holstein breed, which is widely used for dairy production, is highly susceptible to heat stress, resulting in a dramatic reduction in milk production during hot seasons. However, previous studies have shown that cells of cows produced from reconstructed embryos containing cytoplasm (o) from Taiwan yellow cattle (Y) have improved thermotolerance despite their nuclei (n) being derived from heat-sensitive Holstein cattle (H). Using spindle transfer (ST) technology, we successfully produced ST-Yo-Hn cattle and proved that the thermotolerance of their ear fibroblasts is similar to that of Y and significantly better than that of H ( p < 0.05). Despite these findings, the genes and molecules responsible for the different sensitivities of cells derived from ST-Yo-Hn and H cattle have not been extensively investigated. In the present study, ear fibroblasts from ST-Yo-Hn and H cattle were isolated, and differentially expressed protein and gene profiles were compared with or without heat stress (hs) (42 °C for 12 h). The results revealed that the relative protein expression levels of pro-apoptotic factors, including Caspase-3, -8, and -9, in the ear fibroblasts from the ST-Yo-Hn-hs group were significantly lower ( p < 0.05) than those from the H-hs group. Conversely, the relative expression levels of anti-apoptotic factors, including GNA14 protein and the CRELD2 and PRKCQ genes, were significantly higher ( p < 0.05) in the ear fibroblasts from the ST-Yo-Hn-hs group compared to those from the H-hs group. Analysis of oxidative phosphorylation-related factors revealed that the relative expression levels of the GPX1 gene and Complex-I, Complex-IV, CAT, and PGLS proteins were significantly higher ( p < 0.05) in the ear fibroblasts from the ST-Yo-Hn-hs group compared to those from the H-hs group. Taken together, these findings suggest that ear fibroblasts from ST-Yo-Hn cattle have superior thermotolerance compared to those from H cattle due to their lower expression of pro-apoptotic factors and higher expression of oxidative phosphorylation and antioxidant factors. Moreover, this improved thermotolerance is attributed, at least partially, to the cytoplasm derived from more heat-tolerant Y cattle. Hence, using ST technology to produce more heat-tolerant H cattle containing Y cytoplasm could be a feasible approach to alleviate the negative impacts of heat stress on dairy cattle in tropical-subtropical regions.

Background: Previous research on the factors associated with surgical dose-response in strabismus surgery for exotropia has yielded inconsistent results. This study determined the factors influencing surgical dose-response in exotropia patients who underwent recession and resection (R&R)., Methods: Exotropia patients who underwent unilateral R&R at the National Taiwan University Hospital between 2006 and 2021 were evaluated. Deviation-angle differences in prism diopters (PD) were measured preoperatively and at 1 month postoperatively. Surgical dose-response (PD/mm) was defined as the difference in deviation angle (in PD) divided by the surgical dose in millimeters. Linear and non-linear regression models were used to evaluate the influence of variables including age, sex, axial length, and preoperative deviation on surgical dose-response., Results: Overall, 295 patients (162 children; 133 adults) were included. Average surgical dose-response in the pediatric and adult groups was 2.82 ± 0.60 PD/mm and 3.02 ± 0.62 PD/mm, respectively. Male sex was negatively correlated with surgical dose-response in children. The surgical dose-response was larger in adults with longer axial length (>25.64 mm) and patients with larger preoperative deviation (>42.6 PD and >38.7 PD in pediatric and adult groups, respectively). Surgical dose-responses peaked at 35.1 years., Conclusion: Age, axial length, and preoperative deviation have a nonlinear effect on surgical dose-responses in exotropia patients undergoing R&R. Surgical dose-responses were larger in patients in young adulthood, with longer axial length and larger preoperative deviation angle. A table with fitted values for surgical dose-response based on age, axial length, and preoperative deviation was established for clinical reference., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

This study aimed to examine the relationship between social media use, e-health literacy, and the risk and benefit perceptions of e-cigarettes among college students in Taiwan. A cross-sectional online survey was conducted with 1,571 Taiwanese college students, which included four questionnaires to assess participants' perceptions, social media use behavior, e-health literacy, and sociodemographic factors. The data were presented in terms of means, standard deviations, and percentages. Stepwise regression was used to identify factors associated with the participants' perceptions. The study found that 75.01% of the participants were exposed to e-cigarette information on social media, with 31.26% actively searching for it and 15.95% sharing it. Participants had a high e-cigarette risk perception, indicating low benefit perception, but acceptable e-health literacy. Factors such as current e-cigarette and tobacco use, e-health literacy, academic achievement, and sex significantly predicted e-cigarette risk perception, while sharing e-cigarette related information, sex, age, academic achievement, and current e-cigarette use significantly predicted its benefit perception. Thus, implementing effective e-health literacy programs to enhance college students' e-cigarette risk perception is recommended along with a proactive approach to tackle e-cigarette advertising messages on social media, minimizing their sharing behavior to decrease their perception of associated benefits., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Breast cancer is one of the most common cancers in women, and treatment options include surgery, systemic therapies, and radiotherapy (RT). While postoperative RT plays an important role in reducing local recurrence rates and improving survival outcomes, its exact impact on patients with pathological stage IIB breast cancers remains unidentified., Methods: In this retrospective cohort study, patients with newly diagnosed pathological stage IIB breast cancer who underwent surgery and postoperative RT were included. The data were collected from medical records, and survival outcomes were assessed using the Kaplan-Meier method, log-rank tests, and Cox regression models., Results: In total, 350 patients participated in this study. Overall survival, locoregional recurrence-free survival, event-free survival, and distant metastasis-free survival rates did not significantly differ between those who received RT and those who did not. Multivariate analyses revealed that patients who received anthracycline or taxane chemotherapy had better survival outcomes., Conclusion: Our findings demonstrated that postoperative RT had no significant effect on overall survival, locoregional recurrence, event-free survival, or distant metastasis rates in patients with pathological stage IIB breast cancer. However, anthracycline- and taxane-based chemotherapies were associated with improved outcomes. These findings demonstrated the complexities of treating such patient populations with multimodal therapies. Further research is needed to ensure optimal postoperative RT in patients with pathological stage IIB breast cancer. Clinicians must consider individual patient characteristics and incorporate comprehensive treatment approaches to ensure successful outcomes in this population., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Purpose: This paper presents a deep learning model for use in the automated segmentation of metastatic brain tumors and associated perilesional edema., Methods: The model was trained using Gamma Knife surgical data (90 MRI sets from 46 patients), including the initial treatment plan and follow-up images (T1-weighted contrast-enhanced (T1cWI) and T2-weighted images (T2WI)) manually annotated by neurosurgeons to indicate the target tumor and edema regions. A mask region-based convolutional neural network was used to extract brain parenchyma, after which the DeepMedic 3D convolutional neural network was in the segmentation of tumors and edemas., Results: Five-fold cross-validation demonstrated the efficacy of the brain parenchyma extraction model, achieving a Dice similarity coefficient of 96.4%. The segmentation models used for metastatic tumors and brain edema achieved Dice similarity coefficients of 71.6% and 85.1%, respectively. This study also presents an intuitive graphical user interface to facilitate the use of these models in clinical analysis., Conclusion: This paper introduces a deep learning model for the automated segmentation and quantification of brain metastatic tumors and perilesional edema trained using only T1cWI and T2WI. This technique could facilitate further research on metastatic tumors and perilesional edema as well as other intracranial lesions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gemcitabine is frequently utilized to treat pancreatic cancer. The purpose of our study was to create a gemcitabine-resistant MIA-PaCa-2 pancreatic cancer cell line (MIA-GR100) and to evaluate the anti-pancreatic cancer efficacy of HMJ-38, a new quinazolinone analogue. Compared to their parental counterparts, MIA-PaCa-2, established MIA-GR100 cells were less sensitive to gemcitabine. MIA-GR100 cell viability was not affected by 10, 50 and 100 nM gemcitabine concentrations. HMJ-38 reduced MIA-GR100 cell growth and induced autophagy and apoptosis. When stained with monodansylcadaverine (MDC), acridine orange (AO), and terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), MIA-GR100 cells shrunk, punctured their membranes, and produced autophagy vacuoles and apoptotic bodies. Combining chloroquine (CQ) and 3-methyladenine (3-MA) with HMJ-38 dramatically reduced cell viability, indicating that autophagy function as a cytoprotective mechanism. MIA-GR100 cells treated with both z-VAD-FMK and HMJ-38 were much more viable than those treated with HMJ-38 alone. HMJ-38 promotes apoptosis in MIA-GR100 cells by activating caspases. Epidermal growth factor receptor (EGFR) is one of HMJ-38's principal targets, as determined via in silico target screening with network prediction. HMJ-38 also inhibited EGFR kinase activity and EGFR-associated signaling in MIA-GR100 cells. HMJ-38 may be an effective chemotherapeutic adjuvant for gemcitabine-resistant pancreatic cancer cells, in which it induces an antitumor response., Competing Interests: Conflict of interest: The authors declare that they have no competing interests., (© the Author(s).)

Objective: This study aimed to develop and evaluate a scenario-based nutrition literacy (NL) online programme for Taiwanese college students., Design: A randomised pilot trial design was used in this study., Setting: The study was conducted at a university in Taiwan. The intervention consisted of a five-unit web-based NL programme including videos of real-life scenario-based stories, situational analysis teaching and after-unit quizzes. Theme-related website information and smartphone apps (both iOS and Android systems) were offered for reference in every unit. The NL measure consisted of a self-rated scale, a scenario-based test and a healthy eating behaviour survey. Paired sample t-tests and ANCOVA were performed to test the effects on NL and healthy eating behaviour., Participants: Participants were ninety-eight students, with a retention rate of 98 %. The ratio of men to women was 0·2:1. Most students were freshmen (48 %)., Results: Compared with the control group, the experimental group showed significant post-intervention improvements in the NL and healthy eating behaviours after controlling for pretest scores., Conclusions: This pilot study offers preliminary evidence of the potential positive effects of implementing a scenario-based NL online programme for college students. It offers a possibly novel strategy to enhance health-promoting behaviours in Taiwanese universities. Further research with larger sample sizes and more rigorous designs is warranted to confirm and build upon these initial findings.

Background and Aims: Patients with left-sided breast cancer receive a higher mean heart dose (MHD) after radiotherapy, with subsequent risk of ischaemic heart disease. However, the optimum dosimetric predictor among cardiac substructures has not yet been determined., Methods and Results: This study retrospectively reviewed 2158 women with breast cancer receiving adjuvant radiotherapy. The primary endpoint was a major ischaemic event. The dose-volume parameters of each delineated cardiac substructure were calculated. The risk factors for major ischaemic events and the association between MHD and major ischaemic events were analysed by Cox regression. The optimum dose-volume predictors among cardiac substructures were explored in multivariable models by comparing performance metrics of each model. At a median follow-up of 7.9 years (interquartile range 5.6-10.8 years), 89 patients developed major ischaemic events. The cumulative incidence rate of major ischaemic events was significantly higher in left-sided disease (P = 0.044). Overall, MHD increased the risk of major ischaemic events by 6.2% per Gy (hazard ratio 1.062, 95% confidence interval 1.01-1.12; P = 0.012). The model containing the volume of the left ventricle receiving 25 Gy (LV V25) with the cut-point of 4% presented with the best goodness of fit and discrimination performance in left-sided breast cancer. Age, chronic kidney disease, and hyperlipidaemia were also significant risk factors., Conclusion: Risk of major ischaemic events exist in the era of modern radiotherapy. LV V25 ≥ 4% appeared to be the optimum parameter and was superior to MHD in predicting major ischaemic events. This dose constraint could aid in achieving better heart protection in breast cancer radiotherapy, though a further validation study is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.

Introduction: Modified teaching strategies (MTS), asynchronous online teaching and smaller dissection groups, were applied to a gross anatomy course for dental students in the National Taiwan University in April 2020 in response to the COVID-19 pandemic. This study aimed to investigate the effects and perceptions of MTS on dental students., Materials and Methods: Scores for anatomy examinations for 2018-2019 (without MTS) and 2019-2020 (with MTS) cohorts were compared to explore the effect on academic performance. Moreover, questionnaire from the 2019-2020 cohort was analysed to determine dental students' perceptions about MTS., Results: The lecture performance in the final examination of the second semester for the 2019-2020 cohort was significantly higher than that of the first semester (pre-COVID-19) and that for the 2018-2019 cohort. However, the laboratory performance in the midterm examination of the second semester for the 2019-2020 cohort was significantly lower than that for the 2018-2019 cohort and showed no difference in the final examination of the first semester. The questionnaires revealed that the majority of students displayed positive attitudes towards MTS and agreed with the importance of peer discussion during laboratory dissection., Conclusions: Asynchronous online learning for anatomy lecture may be beneficial for dental students; however, a smaller dissection group accompanied by reduced peer discussion may temporarily exert negative effects on their laboratory performance at the beginning of the application. Furthermore, more dental students exhibited positive perceptions towards smaller dissection groups. These findings could illuminate the learning condition of dental students in anatomy education., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging., Methods: PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle-Ottawa scale was used to assess the risk of bias of the observational cohort studies., Results: This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01-5.35, I 2  = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24-3.67, I 2  = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65-4.32, I 2  = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04-3.71, I 2  = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study., Conclusions: For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin., (© 2023. The Author(s).)

Purpose: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC., Methods: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies., Results: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23-10.10; p = 0.02)., Conclusions: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status ( p = 0.003), disease-free interval < 24 months ( p = 0.041), and biologically effective dose (BED 10 ) < 100 Gy ( p = 0.006) were independently associated with inferior OS. BED 10 ≥ 100 Gy ( p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status ( p = 0.017) and EPD ( p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED 10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Euphrasia nankotaizanensis (Orobanchaceae) is a rare alpine herb that is endemic to Taiwan. Only four small populations remain in Xue, Nanhu, and Cilai Mountains of Taiwan. The distribution of alpine herbs is severely threatened by climate change, which influences genetic variation and population structure. In this study, we investigated the effects of the natural isolation of alpine habitats on the genetic diversity and geographic structure of populations of E. nankotaizanensis using chloroplast (cp) and nuclear DNA (nrDNA) markers. We found lower levels of genetic diversity in E. nankotaizanensis than in other alpine plants and little to no genetic variation within populations, which could be mainly attributed to the small population size and genetic drift. Only one nrDNA haplotype was present in each population. The lack of monophyly of the four populations in cpDNA probably resulted from lineage sorting or occasional long-distance seed dispersal. Phylogeographic analysis suggested that Nanhu Mountain was probably a refugium over the glacial maxima, agreeing with the potential refugia in central Taiwan. The STRUCTURE and AMOVA analyses revealed significant genetic differentiation in nrDNA among the mountains, which resulted from geographical isolation among these mountains. Estimates of the effective population size (Ne) and demography reflected lower Ne values and a recent population decline, probably implying a greater extinction risk for E. nankotaizanensis . We observed genetic depletion and considerable genetic differentiation among mountain populations, which should be considered in future conservation efforts for this species. In addition, this study provides important insights into the long-term potential of alpine herbs in Taiwan, which are useful for a better prediction of their responses to future climate change., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units., Competing Interests: Declaration of competing interest The concept of this work has filed an application of a United States patent with the University of Macau as the assignee. This patent application is pending with publication number US20200093415A1., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The resection of large gastric gastrointestinal stromal tumors (GISTs) by laparoscopic has been controversial. Extending from our prior study, the long-term oncological outcome of laparoscopic resection of large (5-8 cm) gastric GISTs was reported., Methods: From 2002 to 2018, a consecutive 66 patients with gastric GISTs of 5-8 cm were treated at National Taiwan University Hospital. Among them, 30 patients received open surgery, and 36 received laparoscopic surgery. The clinicopathological data, peri-operative and oncological outcomes were compared between groups., Results: The clinical demographics including sex, age, BMI, tumor locations and ratio of wedge resection were similar between groups. The mean tumor size was 6.0 ± 0.83 cm versus 6.3 ± 1.07 cm (Open vs. Laparoscopic, p = 0.3). The operation time, blood loss, and post-operative complications, were also similar. The mean hospital stay was shorter in the laparoscopic group (8.8 ± 2.5 days) than in the open group (12.0 ± 8.9 days), though not significantly different. The median follow-up time was 108 ± 58 months (97 ± 50 in laparoscopic group; 122 ± 64 in open group). All except three patients remain disease-free. One in the open group and two in the laparoscopic group had recurrence of tumor, and they were stable of disease under Imatinib treatment. Eight patients died in non-GIST causes during follow-up. The 5-year recurrence-free survival were 100% for the open and 94.2% for the laparoscopic group (p = 0.2)., Conclusion: Our data showed that laparoscopic surgery for gastric GIST between 5 and 8 cm was safe and oncologically feasible., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancers evade immune surveillance, which can be reversed through immune-checkpoint therapy in a small subset of cases. Here, we report that the MYC oncogene suppresses innate immune surveillance and drives resistance to immunotherapy. In 33 different human cancers, MYC genomic amplification and overexpression increased immune-checkpoint expression, predicted nonresponsiveness to immune-checkpoint blockade, and was associated with both Th2-like immune profile and reduced CD8 T-cell infiltration. MYC transcriptionally suppressed innate immunity and MHCI-mediated antigen presentation, which in turn impeded T-cell response. Combined, but not individual, blockade of PDL1 and CTLA4 could reverse MYC-driven immune suppression by leading to the recruitment of proinflammatory antigen-presenting macrophages with increased CD40 and MHCII expression. Depletion of macrophages abrogated the antineoplastic effects of PDL1 and CTLA4 blockade in MYC-driven hepatocellular carcinoma (HCC). Hence, MYC is a predictor of immune-checkpoint responsiveness and a key driver of immune evasion through the suppression of proinflammatory macrophages. The immune evasion induced by MYC in HCC can be overcome by combined PDL1 and CTLA4 blockade., Significance: Macrophage-mediated immune evasion is a therapeutic vulnerability of MYC-driven cancers, which has implications for prioritizing MYC-driven hepatocellular carcinoma for combination immunotherapy., (©2022 American Association for Cancer Research.)

Alzheimer's disease (AD) is characterized by the progressive degeneration of neuronal cells. With the increase in aged population, there is a prevalence of irreversible neurodegenerative changes, causing a significant mental, social, and economic burden globally. The factors contributing to AD are multidimensional, highly complex, and not completely understood. However, it is widely known that aging, neuroinflammation, and excessive production of reactive oxygen species (ROS), along with other free radicals, substantially contribute to oxidative stress and cell death, which are inextricably linked. While oxidative stress is undeniably important in AD, limiting free radicals and ROS levels is an intriguing and potential strategy for deferring the process of neurodegeneration and alleviating associated symptoms. Therapeutic compounds from natural sources have recently become increasingly accepted and have been effectively studied for AD treatment. These phytocompounds are widely available and a multitude of holistic therapeutic efficiencies for treating AD owing to their antioxidant, anti-inflammatory, and biological activities. Some of these compounds also function by stimulating cholinergic neurotransmission, facilitating the suppression of beta-site amyloid precursor protein-cleaving enzyme 1, α-synuclein, and monoamine oxidase proteins, and deterring the occurrence of AD. Additionally, various phenolic, flavonoid, and terpenoid phytocompounds have been extensively described as potential palliative agents for AD progression. Preclinical studies have shown their involvement in modulating the cellular redox balance and minimizing ROS formation, displaying them as antioxidant agents with neuroprotective abilities. This review emphasizes the mechanistic role of natural products in the treatment of AD and discusses the various pathological hypotheses proposed for AD.

HOTAIR is a 2.2-kb long noncoding RNA (lncRNA) whose dysregulation has been linked to oncogenesis, defects in pattern formation during early development, and irregularities during the process of epithelial-to-mesenchymal transition (EMT). However, the oncogenic transformation determined by HOTAIR in vivo and its impact on chromatin dynamics are incompletely understood. Here, we generate a transgenic mouse model with doxycycline-inducible expression of human HOTAIR in the context of the MMTV-PyMT breast cancer-prone background to systematically interrogate the cellular mechanisms by which human HOTAIR lncRNA acts to promote breast cancer progression. We show that sustained high levels of HOTAIR over time increased breast metastatic capacity and invasiveness in breast cancer cells, promoting migration and subsequent metastasis to the lung. Subsequent withdrawal of HOTAIR overexpression reverted the metastatic phenotype, indicating oncogenic lncRNA addiction. Furthermore, HOTAIR overexpression altered both the cellular transcriptome and chromatin accessibility landscape of multiple metastasis-associated genes and promoted EMT. These alterations are abrogated within several cell cycles after HOTAIR expression is reverted to basal levels, indicating an erasable lncRNA-associated epigenetic memory. These results suggest that a continual role for HOTAIR in programming a metastatic gene regulatory program. Targeting HOTAIR lncRNA may potentially serve as a therapeutic strategy to ameliorate breast cancer progression., Competing Interests: QM, LY, KT, GW, YZ, UL, QS, LZ, CY, HJ, FZ, RL, MT, JC, IL, HZ, LL No competing interests declared, HC Reviewing editor, eLife, (© 2022, Ma, Yang, Tolentino et al.)

Background: Laparoscopic radical distal gastrectomy (LDG) has been more frequently performed for locally advanced distal gastric cancer (AGC) than open distal gastrectomy (ODG). However, the benefits of LDG for elderly AGC patients (AGC-lap) remain unclear., Methods: Patients aged ≥ 70 years who underwent D2 distal gastrectomy from July 2014 to July 2021 were enrolled consecutively. Perioperative parameters, pathological features, and oncological outcomes of AGC-lap patients (n = 39) were compared with those of elderly AGC patients receiving ODG (AGC-open; n = 37) and elderly early gastric cancer patients receiving LDG (EGC-lap; n = 41) respectively., Results: The median age of all AGC patients was 77 years, and 28% of them had an Eastern Cooperative Oncology Group score ≥ 2. Most of the perioperative and pathological features (including the number of lymph nodes harvested) were similar between the AGC-lap and AGC-open groups. AGC-lap patients had longer median operative times (215 min versus 192 min) but significantly less surgical complications (10.3% versus 37.8%) and shorter median hospital stays (11 days versus 13 days) than did AGC-open patients (all p < 0.05). The 3-year recurrence-free and overall survival was 66.2% and 88.8% in the AGC-lap group and 51% and 66.3% in the AGC-open group (both p = 0.1). The perioperative features, including operative time, number of lymph nodes harvested, hospital stay, and complication rates, were similar between the AGC- and EGC-lap groups., Conclusions: LDG was safely and effectively performed in elderly AGC patients, resulting in faster recovery and a lower complication rate than ODG, without compromising oncological outcomes., (© 2022. The Author(s).)

Hyperuricemia and gout are two of the most common metabolic disorders worldwide; their incidence is increasing with changes in lifestyle, and they are correlated with many diseases, including renal and cardiovascular diseases. The majority of studies on hyperuricemia and gout have focused on the discovery of the associated genes and their functions and on the roles of monocytes and neutrophils in the development of gout. Virtually no studies investigating the epigenomics of gout disease or exploring the clinical significance of such research have been conducted. In this study, we observed that the expression of enzymes involved in RNA modifications or RNA editing was affected in uric acid (UA)- or monosodium urate (MSU)-treated cell lines. RNA alternative splicing and splicing factors were also affected by UA or MSU treatment. We used transcriptome sequencing to analyze genome-wide RNA splicing and RNA editing and found significant changes in RNA splicing and RNA editing in MSU- or UA-treated THP-1 and HEK293 cells. We further found significant changes of RNA modifications, editing, and splicing in patients with gout. The data indicate that RNA modifications, editing, and splicing play roles in gout. The findings of this study may help to understand the mechanism of RNA splicing and modifications in gout, facilitating the development of new diagnostic and therapeutic strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Chen, Lai, Chen, Huang, Tu, Lee, Yen, Lin, Liu and Chang.)

It is controversial whether patients who achieve clinical complete remission (cCR) of rectal cancer should be treated with the "watch and wait" (W&W) or radical resection (RR) strategy. Our study aimed to compare the survival outcomes and ostomy rate of the W&W and RR strategies. Between January 2008 and December 2015, we investigated 26 patients who achieved pathologic complete remission after undergoing RR and 36 patients who adopted the W&W strategy because of cCR. The tumor regrowth, salvage surgery, recurrence, disease-free, and overall survival (OS) rates were assessed. In our study, recurrences occurred in nine and two patients from the W&W and RR groups, respectively. Each patient in the RR group had a temporary or permanent ostomy, but only three (8.3%) had an ostomy in the W&W group. The 5-year recurrence rate was 25.0% in the W&W group and 7.7% in the RR group. Six patients (16.7%) had tumor regrowth in the W&W group, and all were resectable when regrowth. The 5-year OS rates between the two groups were nonsignificant. There is no specific risk factor for recurrence and OS. Under close surveillance, the W&W group achieved similar OS to the RR group and benefited from a lower ostomy rate., Competing Interests: Conflict of interest: There is no conflict of interest, use of off-label or unapproved drugs or products, and use of previously copyrighted material. None of the authors has any potential financial or non-financial conflicts of interest., (© 2022 Yu-Jen Hsu et al., published by De Gruyter.)

(1) Background: The coronavirus disease 2019 (COVID-19) pandemic had overwhelming impacts on medical services. During its initial surge, Taiwan was unique in maintaining its medical services without imposing travel restrictions, which provided an ideal environment in which to test if the fear of becoming infected with COVID-19 interfered with health-seeking behavior (HSB). We tested this hypothesis among adults with acute complicated appendicitis (ACA). (2) Methods: Adults with acute appendicitis were enrolled between 1 January and 30 June 2020 (COVID-19 period). The first two quarters of the preceding 3 years were defined as a historical control group. Outcome measures included the rate of ACA and the number of hospital stays. (3) Results: The COVID-19 era included 145 patients with acute appendicitis. Compared to the historical control (320 patients), the COVID-19 era was significantly associated with a higher length of symptom duration until presentation to the emergency room within >48 h (17.2% vs. 9.1%, p = 0.011), a higher incidence of ACA (29.7% vs. 19.4%, p = 0.014), and a longer length of hospital stays (5.0 days vs. 4.0 days, p = 0.043). The adjusted models showed that the COVID-19 period had a significant relationship with a higher rate of ACA (odds ratio (OR) = 1.87; 95% confidence interval (CI): 1.23-2.52; p = 0.008) and longer length of hospital stays (OR= 2.10; 95% CI: 0.92 to 3.31; p < 0.001). (4) Conclusions: The fear of COVID-19 may prohibit patients from seeking medical help, worsening their clinical outcomes. The surgical community should take action to provide scientific information to relive mental stress.

Cisplatin is a prevalent chemotherapeutic agent used for non-small cell lung cancer (NSCLC) that is difficult to treat by targeted therapy, but the emergence of resistance severely limits its efficacy. Thus, an effective strategy to combat cisplatin resistance is required. This study demonstrated that, at clinically achievable concentrations, the combination of selenium yeast (Se-Y) and fish oil (FO) could synergistically induce the apoptosis of cancer stem cell (CSC)-like A549 NSCLC sphere cells, accompanied by a reversal of their resistance to cisplatin. Compared to parental A549 cells, sphere cells have higher cisplatin resistance and possess elevated CSC markers (CD133 and ABCG2), epithelial-mesenchymal transition markers (anexelekto (AXL), vimentin, and N-cadherin), and cytoprotective endoplasmic reticulum (ER) stress marker (glucose-regulated protein 78) and increased oncogenic drivers, such as yes-associated protein, transcriptional coactivator with PDZ-binding motif, β-catenin, and cyclooxygenase-2. In contrast, the proapoptotic ER stress marker CCAAT/enhancer-binding protein homologous protein and AMP-activated protein kinase (AMPK) activity were reduced in sphere cells. The Se-Y and FO combination synergistically counteracted the above molecular features of A549 sphere cells and diminished their elevated CSC-like side population. AMPK inhibition by compound C restored the side population proportion diminished by this nutrient combination. The results suggest that the Se-Y and FO combination can potentially improve the outcome of cisplatin-treated NSCLC with phenotypes such as A549 cells.

Background: This multinational study was conducted to report clinical presentations and treatment strategies in patients with intracranial germinomas across selected Asian centers, including failure patterns, risk factors, and outcomes., Methods: A retrospective data collection and analysis of these patients, treated between 1995 and 2015 from eight healthcare institutions across four countries was undertaken., Results: From the results, 418 patients were analyzed, with a median follow-up of 8.9 years; 79.9% of the patients were M0, and 87.6% had β-human chorionic gonadotropin values <50 mIU/mL. The 5/10-year overall survival (OS) and recurrence-free survival (RFS) rates were 97.2%/96.2% and 89.9%/86.9%, respectively. RFS was predicted by the radiotherapy (RT) field, with focal RT having the worst outcome, whereas chemotherapy usage had no impact on survival. Among patients who received chemotherapy, response to chemotherapy did not predict survival outcomes. In M0 patients, primary basal ganglia tumors predicted a worse RFS. In patients with bifocal tumors, an extended field RT was associated with better outcomes. In multivariable analysis, only RT fields were associated with RFS. In relapsed patients, salvage rates were high at 85.7%. Additionally, patients who received salvage RT had a better outcome (91.6% vs. 66.7%)., Conclusions: Survival outcomes of patients with germinoma were excellent. Thus, the focus of treatment for intracranial germinoma should be on survivorship. Further studies are warranted to find the optimal intensity and volume of radiation, including the role of chemotherapy in the survival of patients with intracranial germinomas, considering age, primary tumor location, and extent of disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess ocular involvement in sarcoidosis and to analyze the manifestations of ocular sarcoidosis (OS) in Taiwan., Methods: A retrospective review was performed in 364 patients diagnosed as sarcoidosis at National Taiwan University Hospital from 2015 to 2019. The OS diagnosis was based on the revised criteria of International Workshop on Ocular Sarcoidosis. Demographics, clinical manifestations, treatment and effects, complications, visual outcomes and risk factors of poor vision (<20/200) were analyzed., Results: A total of 122 eyes of 66 patients (13 males and 53 females) with OS were identified. Bilateral involvement accounted for 84.8%. Thirty-five patients were diagnosed with definite OS, 14 with presumed OS and 17 with probable OS. The average age was 51.9 ± 14.1 years, with no significant difference in sex. Most patients presented with panuveitis (61 eyes, 50.0%) and posterior uveitis (52 eyes, 42.6%). Systemic steroid was the mainstay treatment, and immunosuppressants or anti-metabolic agents were supplemented. Common complications included cataract (50.8%), ocular hypertension/glaucoma (25.4%) and posterior synechiae (20.5%). Forty-three eyes (36.1%) and 74 eyes (62.2%) had a final vision of 20/20 and 20/40 or better, respectively. The causes of poor visual outcome were diverse, and generalized estimating equations analysis indicated that female and poor initial vision were risk factors., Conclusion: Uveitis is an early sign of sarcoidosis and it might result in several complications. The overall visual outcomes were good if patients received proper treatment. Both poor initial vision and females that tended to have more severe complications were associated with poor outcome., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work. No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: The appropriate management of postoperative upper alimentary tract fistula (UATF) remains uncertain. The efficacy of esophagogastroduodenoscopy (EGD) tissue glue repair in the treatment of patients with postoperative UATF was explored. We also conducted a systematic review of the literature regarding the inpatient management of UATF., Methods: Totally 24 patients received EGD tissue glue repair for postoperative UATF at our institute from April 2014 to April 2020. Independent characteristics of size of fistula, location of the UATF, complications, and recurrences were analyzed. PubMed and Cochrane Library databases were reviewed. A pooled analysis was performed, and subgroup analysis was conducted separately for different anatomic locations and techniques., Results: With a mean follow-up of 40 months, the fistula failed to close with EGD tissue glue repair in 2 of 24 patients (8.3%). Eight patients required repeated EGD tissue glue repair, which was more frequent in oral or thoracic UATF (p = 0.053), but all achieved a successful seal in the EGD tissue after glue repair alone (n = 22). The fistula size was correlated with the demand for repeated EGD tissue glue repair (p = 0.017). Besides, a total of 30 studies regarding 2356 cases of postoperative UATF between 2010 and 2021 were retrieved and analyzed. Several non-operative methods were generally accepted as the initial approach, with a non-inferior success rate compared to operative techniques., Conclusion: The results suggest that no single approach toward UATF is superior in terms of success rate and healing time. The potential advantages of EGD tissue glue repair after drainage were more suitable for patients with postoperative UATF and multiple comorbidities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models in which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous Qk/Trp53/Pten (QPP) triple-knockout model of human GBM, comparing the immune microenvironment of QPP mice with that of patient-derived tumors to determine whether this model provides opportunity for gaining insights into tumor physiopathology and preclinical evaluation of therapeutic agents. Immune profiling analyses and single-cell sequencing of implanted and spontaneous tumors from QPP mice and from patients with glioma revealed intratumoral immune components that were predominantly myeloid cells (e.g., monocytes, macrophages, and microglia), with minor populations of T, B, and NK cells. When comparing spontaneous and implanted mouse samples, we found more neutrophils and T and NK cells in the implanted model. Neutrophils and T and NK cells were increased in abundance in samples derived from human high-grade glioma compared with those derived from low-grade glioma. Overall, our data demonstrate that our implanted and spontaneous QPP models recapitulate the immunosuppressive myeloid-dominant nature of the tumor microenvironment of human gliomas. Our model provides a suitable tool for investigating the complex immune compartment of gliomas.

Major parts of anthropogenic and natural aerosols are hygroscopic and deliquesce at high humidity, particularly when depositing to leaf surfaces close to transpiring stomata. Deliquescence and subsequent salt creep may establish thin, extraordinary pathways into the stomata, which foster stomatal uptake of nutrients and water but may also cause stomatal liquid water loss by wicking. Such additional water loss is not accompanied by a wider stomatal aperture with a larger CO 2 influx and hypothetically reduces water use efficiency (WUE). Here, the possible direct impacts of aerosols on physical and physiological parameters of camphor ( Cinnamomum camphora ) were studied (i) in a greenhouse experiment using aerosol exclusion and (ii) in a field study in Taiwan, comparing trees at two sites with different aerosol regimes. Scanning electron microscopy (SEM) images showed that leaves grown under aerosol exclusion in filtered air (FA) were lacking the amorphous, flat areas that were abundant on leaves grown in ambient air (AA), suggesting salt crusts formed from deliquescent aerosols. Increasing vapor pressure deficit (VPD) resulted in half the Ball-Berry slope and double WUE for AA compared to FA leaves. This apparent contradiction to the wicking hypothesis may be due to the independent, overcompensating effect of stomatal closure in response to VPD, which affects AA more than FA stomata. Compared to leaves in a more polluted region in the Taiwanese Southwest, NaCl aerosols dominated the leaf surface conditions on mature camphor trees in Eastern Taiwan, while the considerably lower contact angles and the 2.5 times higher minimum epidermal conductances might have come from organic surfactants. Interpretations of SEM images from leaf surface microstructures should consider amorphous areas as possible indicators of aerosol deposition and other hygroscopic material. The amount and type of the material determine the resulting impacts on plant water relations, together with the surrounding atmosphere and ecophysiological traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chi, Zinsmeister, Lai, Chang, Kuo and Burkhardt.)

Large-area surface-enhanced Raman spectroscopy (SERS) sensing platforms displaying ultrahigh sensitivity and signal uniformity have potentially enormous sensing applicability, but they are still challenging to prepare in a scalable manner. In this study, silver nanopaste (AgNPA) was employed to prepare a wafer-scale, ultrasensitive SERS substrate. The self-generated, high-density Ag nanocracks (NCKs) with small gaps could be created on Si wafers via a spin-coating process, and provided extremely abundant hotspots for SERS analyses with ultrahigh sensitivity-down to the level of single molecules (enhancement factor: ca. 10 10 ; detection limit: ca. 10 -18  M)-and great signal reproducibility (variation: ca. 3.6%). Moreover, the Ag NCK arrays demonstrated broad applicability and practicability for on-site detection when combined with a portable 785 Raman spectrometer. This method allowed the highly sensitive detection of a diverse range of analytes (benzo[a]pyrene, di-2-ethylhexyl phthalate, aflatoxins B1, zearalenone, ractopamine, salbutamol, sildenafil, thiram, dimethoate, and methamidophos). In particular, pesticides are used extensively in agricultural production. Unfortunately, they can affect the environment and human health as a result of acute toxicity. Therefore, the simultaneous label-free detection of three different pesticides was demonstrated. Finally, the SERS substrates are fabricated through a simple, efficient, and scalable process that offers new opportunities for mass production., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The complete mitogenome of an endemic silkmoth in Taiwan, Antheraea formosana , was determined using Illumina next-generation sequencing. The mitogenome is 15,318 bp in length and consists of 13 protein-coding genes (PCGs), two rRNAs, 22 tRNAs, and one non-coding control region. The overall base composition of the mitogenome showed a high A + T bias, and the A + T content (80.2%) was significantly higher than the G + C content (19.8%). All PCGs use the typical ATN as the initiation codon, with the exception of cox2 , which begins with GTG, respectively. The complete mitogenome was used to reconstruct a phylogenetic tree, indicating that A. formosana is more closely related to Antheraea assamensis than other Antheraea species, with 93.19% nucleotide similarity., Competing Interests: No potential conflict of interest was reported by the authors., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

This study's purpose was to describe changes in symptom distress and fatigue characteristics identifying which symptoms significantly impacted fatigue characteristics of patients with Gastric Cancer (GC) within 1 month after gastrectomy. A prospective longitudinal study was conducted. Patients with GC who were scheduled for gastrectomy were recruited from surgical outpatient clinics and surgery wards in northern Taiwan. Data were collected using a set of questionnaires before (T0) and 7 (T1) and 28 days (T2) after gastrectomy. Over all, 86 patients experienced mild levels of fatigue and symptom distress. The changes in worst fatigue and fatigue interference were greatest at T1. Anxiety had a significant negative effect on both worst fatigue and fatigue interference. Dry mouth, pain, and body image had significant deleterious effects on worst fatigue. The co-occurring symptoms affecting fatigue for patients with GC in the acute phase after gastrectomy should be actively assessed to ensure optimal fatigue management.

Purpose: To demonstrate the changes in the retinal nerve fiber layer (RNFL) after orbital decompression for thyroid eye disease (TED)., Methods: We retrospectively enrolled 52 surgical TED patients, 30 nonsurgical TED patients, and 30 control subjects. Five surgical TED eyes with disc edema were excluded. The surgical TED patients were classified into the "dysthyroid optic neuropathy (DON)" group (16 eyes) and the "non-DON" group (83 eyes). Optical coherence tomography (OCT) and visual field (VF) examinations were performed preoperatively and 6 months later. The control subjects and nonsurgical TED patients received two OCT examinations at 6-month intervals. The postoperative changes in the RNFL thickness were compared between groups. Three cases with severe postoperative vision loss were presented additionally., Results: The changes in the RNFL thickness of the controls (0.5 ± 3.4  μ m) and the nonsurgical TED patients (0.3 ± 2.8  μ m) were significantly smaller than the surgical TED patients ( P < 0.001). The DON group (-9.2 ± 9.2  μ m) had greater RNFL thickness reduction than the non-DON group (-3.9 ± 5.4  μ m) ( P = 0.002). Bone removal decompression was associated with decreased RNFL in the non-DON ( P = 0.025; β = -2.49) and DON ( P = 0.042; β = -9.43) groups. Three cases who were hard to operate due to extensive fibrosis experienced severe vision loss postoperatively due to anterior ischemic optic neuropathy, posterior ischemic optic neuropathy, and posterior ciliary artery occlusion, respectively., Conclusions: TED patients experienced subclinical optic nerve injury and significant RNFL loss after the orbital decompression surgery. Aggressive manipulation during decompression surgery may lead to dreadful vision loss. Tailored surgical plans and delicate manipulation are warranted., Competing Interests: No conflicting relationship exists for any author., (Copyright © 2022 Yun Hsia et al.)

Purpose: To determine the relationship of intraocular pressure (IOP) control with subsequent retinal nerve fiber layer (RNFL) thinning in patients with primary angle closure disease (PACD)., Design: Prospective cohort study., Methods: The study monitored 517 treated PACD eyes from 280 Chinese patients at least 24 months. IOP was measured every 3 months using Goldmann applanation tonometry, and RNFLs were measured by spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering) every 6 months. IOP mean and fluctuation were calculated as the average and the coefficient of variation of IOP measurements during the first 18 months of the study period. The relationship between IOP and subsequent RNFL changes over time were examined using multivariable linear mixed models. Intraclass correlations at the patient and eye levels were also controlled using nested random intercepts in the models., Results: IOP mean (β = -1.20 µm/y per 1 mm Hg, P < .001) and IOP fluctuation (β = -3.10 µm/y per 10% unit change in the coefficient of variation, P < .001) were independently negatively associated with subsequent progressive global RNFL changes, after adjustment for age, sex, and baseline RNFL thickness. In the sectoral analysis, both higher mean IOP and IOP fluctuation predicted progressive RNFL thinning in the inferotemporal, superotemporal, superonasal, and temporal sectors in the order of strength of association. In the subgroup analysis by disease category, IOP fluctuation showed greater association with global RNFL thinning in eyes with primary angle closure glaucoma (P = .010) than in eyes without glaucomatous changes (P = .07)., Conclusions: In treated PACD eyes, large IOP fluctuation is an independent predictor for subsequent progressive RNFL thinning in addition to high mean IOP during follow-up., (Copyright © 2021 Elsevier Inc. All rights reserved.)