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Kun-Ming Chan,1 Yin Lai,1 Hao-Chien Hung,1 Jin-Chiao Lee,1 Chih-Hsien Cheng,1 Yu-Chao Wang,1 Tsung-Han Wu,1 Chen-Fang Lee,1 Ting-Jung Wu,1 Hong-Shiue Chou,1 Ching-Ting Wang,2 Pei-Mei Chai,2 Hsin-Yi Lien,3 Wei-Chen Lee1 1Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Nursing, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan; 3Graduate School of Education, Ming Chuan University, Taoyuan, TaiwanCorrespondence: Kun-Ming Chan, Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, No. 5 Fu-Hsing Street, Gui-Shan District, Taoyuan City, 33305, Taiwan, Tel +886-3-3281200 Ext 3366, Fax +886-3-3285818, Email chankunming@cgmh.org.twBackground: Tyrosine kinase inhibitors (TKIs) remain the primary therapeutic option for patients with advanced-stage hepatocellular carcinoma (HCC). However, the selection of a suitable TKI is an issue in real-world clinical practice. Thus, this study aimed to identify patients most likely to benefit from lenvatinib treatment.Methods: A retrospective review of 143 patients with unresectable advanced-stage HCC treated with lenvatinib between January 2020 and December 2021 was performed. Outcomes related to lenvatinib treatment were measured, and the clinical parameters affecting prognosis were analyzed.Results: Overall, the median time of progression-free survival (PFS) and overall survival (OS) were 7.1 months and 17.7 months, respectively. Prognostic analyses found that Child-Pugh score > 5 (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 1.55– 3.80, p = 0.001) was a significant factor affecting the PFS of HCC after lenvatinib treatment. Child-Pugh score > 5 (HR = 2.12, 95% CI = 1.20– 3.74, p = 0.009), body weight ≥ 60 kg (HR = 0.54, 95% CI = 0.32– 0.90, p = 0.020), and additional trans-arterial chemoembolization (TACE) treatment (HR = 0.38, 95% CI = 0.21– 0.70, p = 0.003) were significant prognostic factors for OS. However, early α-fetoprotein reduction was not significantly correlated with patient outcomes. Additionally, patients with pre-treatment neutrophil-lymphocyte ratio > 4.07 showed a significant worse PFS and OS than other patients.Conclusion: The outcome of patients with advanced-stage HCC remains poor. However, the host condition, including good physical status and better functional liver preservation, largely affected the outcome of patients receiving lenvatinib treatment. Moreover, additional locoregional therapy for intrahepatic HCC, other than TKI treatment, can be considered in certain patients to achieve a favorable outcome.Keywords: hepatocellular carcinoma, advanced-stage, tyrosine kinase inhibitor, lenvatinib, outcome

Chien-Feng Lee,1,* Yunn-Jy Chen,2,* Wen-Chi Huang,3 Jen-Wen Hou,4 Yu-Ting Liu,5 Tiffany Ting-Fang Shih,6 Pei-Lin Lee,7– 10 Chong-Jen Yu1,8,9 1Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; 2Department of Dentistry, School of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan; 4Graduate Institute of Electronics Engineering, National Taiwan University, Taipei, Taiwan; 5MediaTek Inc., Hsinchu, Taiwan; 6Department of Radiology and Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; 7Center of Sleep Disorder, National Taiwan University Hospital, Taipei, Taiwan; 8Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 9School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 10Center for Electronics Technology Integration, National Taiwan University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Pei-Lin Lee, Tel +886-2-2356-2755, Fax +886-2-2358-2867, Email leepeilin@ntu.edu.twObjective: Both continuous positive airway pressure (CPAP) pressure and polysomnographic phenotypes have been associated with mandibular advancement device (MAD) treatment response, but the precise relationship has not been fully elucidated. We hypothesized that utilizing CPAP pressure would predict the MAD response in treatment-naïve patients with moderate-severe obstructive sleep apnea (OSA), and the MAD response would be associated with two polysomnographic phenotypes, including sleep stage dependency and positional dependency.Methods: OSA treatment-naïve patients with an apnea-hypopnea index (AHI) ≥ 15/h who declined CPAP treatment and received MAD treatment for 3– 6 months were enrolled. The MAD treatment response was defined as 1) residual AHI under MAD (AHIMAD) < 5/h and 2) AHIMAD < 10/h. Logistic regression was applied to identify the association between CPAP pressure and MAD treatment responders. The predictability of the MAD responder status utilizing CPAP pressure was assessed with the area under the receiver operating characteristic (AUROC).Results: A total of 128 enrolled patients (AHI ≥ 30/h in 74.2%) were recruited, of whom 119 patients and 80 patients were included for analysis of sleep stage and positional dependency, respectively. REM-predominant OSA had lower AHI than stage-independent OSA, while the supine-predominant phenotype had lower anthropometrics than the nonpositional-dependent phenotype. The response rates for AHIMAD < 5/h and AHIMAD < 10/h were 25.8% and 48.4%, respectively. Lower anthropometrics, baseline AHI, and supine predominance were associated with the responder status, while CPAP pressure was an independent predictor. The AUROCs for the prediction of AHIMAD < 5/h and AHIMAD < 10/h responders were 0.635 and 0.664, respectively. Utilizing a CPAP level > 14 cmH2O as the cutoff to predict criterion 1 and 2 nonresponders, the sensitivity was 93.9% and 95.2%, respectively.Conclusion: In treatment-naïve patients with moderate-severe OSA, the supine-predominant phenotype and lower CPAP pressure were associated with the MAD response, while the sleep stage dependency phenotype was not. Utilization of a CPAP level > 14 cmH2O could be a sensitive measure to identify nonresponders.Keywords: continuous positive airway pressure, mandibular advancement device, polysomnography, phenotype, sleep apnea, obstructive

Kun-Ming Chan, Chih-Hsien Cheng, Tsung-Han Wu, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou, Wei-Chen LeeDepartment of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, TaiwanBackground: The scarcity of deceased donor organ donation has led to increasing utilization of living donor liver transplantation (LDLT), which is an optimal treatment for cirrhosis associated with hepatocellular carcinoma (HCC). The study thus aims to analyze prognostic factors and beneficial effects of LDLT for patients with HCC.Methods: All patients who underwent LDLT for HCC were included in this study. A multivariate analysis of patients’ clinicopathologic parameters was performed to determine prognostic factors. Subsequently, the type of LDLT was further analyzed and compared based on the result of multivariate analysis.Results: Overall, 36 (11.9%) of 303 patients were identified as having HCC recurrence after LDLT. Salvage LDLT (sLDLT) defined by liver transplantation for those patients with recurrent HCC after primary liver resection (LR) was identified as the major prognostic factor of HCC recurrence following the transplantation (HR=2.49 [1.12–5.54], p=0.025). The HCC recurrence incidence and recurrence-free survival after LDLT were significantly inferior in the salvage group than the other group. The pre-transplantation factors were further evaluated and resulted in only maximum tumour size ≥5 cm at primary LR(HR=10.79 [2.10–55.43], p=0.004) affecting post-transplantation HCC recurrence in those patients who had been performed sLDLT. However, patients receiving salvage LDLT had 5- and 10-year overall survival of 86.7% and 52.9%, respectively, measured from the time of initial HCC diagnosis.Conclusion: Overall, LDLT achieves a satisfactory result with low incidence of HCC recurrence based on certain transplantation criteria. Despite the higher incidence of HCC recurrence after sLDLT, it remains a promising strategy to improve long-term outcomes.Keywords: hepatocellular carcinoma, living donor liver transplantation, salvage, recurrence, prognosis

Kun-Ming Chan, Tsung-Han Wu, Chih-Hsien Cheng, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou, Wei-Chen Lee Department of General Surgery and Department of Organs Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan Background: Sorafenib is the first regimen listed in the treatment algorithm for hepatocellular carcinoma (HCC) worldwide. This study aimed to assess the efficacy of sorafenib treatment for advanced HCC in a clinical practice using a nationwide population study. Methods: All patients registered with a diagnosis of primary HCC and identified as having been prescribed sorafenib between August 2012 and December 2015 were selected from a national database and retrospectively reviewed. Outcomes related to prescription of sorafenib for these patients were further assessed. Results: A total of 9,738 patients were enrolled and analyzed. As a result, 32.33% of patients had an initial treatment response and were eligible for the prescribed second term (240 tablets/term) of sorafenib and 8.91% of patients received more than three terms of sorafenib. Meanwhile, the duration of sorafenib usage beyond 6 months was noted in 15.49% of patients, including 10.59% of patients with a period of usage between 6 and 12 months and 4.9% of patients with more than 12 months usage. Survival analysis showed that patients who received locoregional therapy plus sorafenib had significantly better survival rates than those who underwent only sorafenib treatment. Certain patients who underwent hepatectomy (n=12) or liver transplantation (n=13) were subsequently free of HCC. Conclusion: The disease control rate of sorafenib in advanced HCC patients in this study seemed similarly poorer as what has been previously reported by clinical trials. The combination of sorafenib and additional treatments could perhaps provide survival benefits and possibly cure disease in combination with surgical management. Keywords: sorafenib, hepatocellular carcinoma, hepatectomy, liver transplantation, locoregional therapy, outcome

Aims: To compare methods to measure time outdoor and light levels, two possible predictors of myopia, in Singapore children.Methods: Outdoor time from a diary and portable light meter over a 1-week period was compared in 117 Singapore children aged 6-12 years with and without myopia. All children wore a (HOBO Pendant temp/light Part # UA-002-64) light meter for 1 week and the parents filled the 7-day outdoor diary to track the outdoor activity.Results: Mean outdoor time from diary and time with light levels was 5.44 hours per week and 7.91 hours per week, respectively, during school term and school holidays. Time spent with light levels of >1000 Lux from the light meter were 7.08 h per week and 9.81 h per week, respectively, during school term and school holidays. The intraclass correlation coefficients were 0.21 and 0.28 for outdoor time from the diary and light meter (1000 Lux cut-off) during the school term and holidays, respectively. The correlation coefficient was 0.34 (95% CI 0.05, 0.58) for a weekday during school holidays, 0.17 (-0.14, 0.45) for a weekday during school term, 0.07 (-0.16, 0.29) for a weekday during school term, and 0.25 (0.02, 0.46) for a weekend during school term.Conclusions: The agreement between the light meter and 1-week diary was poor to fair. Both instruments measure different parameters, time outdoors and light intensity, and could therefore capture different aspects of risk in future myopia studies. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: This was a population-based retrospective study. OBJECTIVE.: To fully estimate the costs of the Hong Kong scoliosis screening program through a large, population-based study. SUMMARY OF BACKGROUND DATA.: School screening for scoliosis has often been criticized for having high costs. In fact, the screening cost that has reported varied widely, from less than 1 to more than 30 US dollars (USD) per child screened. This variation is mainly due to the incomplete inclusion of cost items. METHODS.: We examined the screening and medical histories of a cohort of 115,190 screened students who were in Grade 5 in 1995/96 or 1996/97. The average costs spent on screening, diagnosing, following, and treating this cohort of students were calculated. RESULTS.: The total expenses in the screening centers increased steadily from USD 380,930 in 1995/96 to USD 2,417,824 in 2005/06. Based on the 115,190 students who were followed up until they were 19 years old or they left school, the costs of screening and diagnosing 1 student during adolescence were USD 17.94 and USD 2.08, respectively. Of the 1311 referrals who attended the specialist hospitals for diagnosis, 264 and 39 had been braced and operated on, respectively. The medical care cost averaged USD 34.61 per student screened. The cost of finding 1 student with a curvature >=20° and 1 treated case were USD 4475.67 and USD 20,768.29 respectively. CONCLUSION.: This was the largest study that has evaluated school scoliosis screening on students who were followed during their adolescence and accounted for all relevant costs. The cost per student screened in the scoliosis screening program in Hong Kong was comparable to that in Rochester, which had a similar protocol and was evaluated in a similar manner. The estimated costs can help the policy makers when they allocate healthcare resources. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the clinical effectiveness of school scoliosis screening using a large and long-term-followed cohort of students in Hong Kong. SUMMARY OF BACKGROUND DATA: School screening for adolescent idiopathic scoliosis has been criticized as resulting in over-referrals for radiography and having low predictive values. Indeed, all but one previous retrospective cohort studies had no follow-up assessments of students until their skeletal maturity, leaving any late-developed curves undetected. The one study that completed this follow-up was well conducted but had low precisions due to its small sample size. METHODS: A total of 157,444 students were eligible for a biennial scoliosis screening, and their screening results and medical records up to 19 years of age were available. Students first had forward bending test and angle of trunk rotation (ATR) performed. Those with ATR between 5 degrees and 14 degrees or signs of adolescent idiopathic scoliosis were assessed by moiré topography regularly. Students with an ATR >or=15 degrees , >or=2 moiré lines, or significant clinical signs were referred for radiography and had their Cobb angle measured. RESULTS: Of the 115,190 screened students in the cohort, 3228 (2.8%, 95% confidence interval [CI] = 2.7%-2.9%) were referred for radiography. At the final follow-up, the positive predictive values were 43.6% (41.8%-45.3%) for a Cobb angle >or=20 degrees and 9.4% (8.4%-10.5%) for needing treatment, while the sensitivities were 88.1% (86.4%-89.6%) and 80.0% (75.6%-83.9%), respectively. CONCLUSION: This is the largest study that has demonstrated that school scoliosis screening in Hong Kong is predictive and sensitive with a low referral rate. Screening should thus be continued in order to facilitate early administration of conservative treatments. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroid (ICS) is the mainstay therapy for asthma, but general adherence is low. There is a paucity of real-world inhaler prescribing and adherence data from Asia and at the population level. To address these gaps, we performed a real-world data analysis of inhaler prescribing pattern and adherence in a multi-ethnic Asian asthma cohort and evaluated the association with asthma outcomes. We performed a retrospective analysis of adult asthma patients (aged ≥18 years) treated in the primary and specialist care settings in Singapore between 2015 to 2019. Medication adherence was measured using the medication possession ratio (MPR), and categorised into good adherence (MPR 0.75-1.2), poor adherence (MPR 0.75) or medication oversupply (MPR > 1.2). All statistical analyses were performed using R Studio. 8023 patients, mean age 57 years, were evaluated between 2015 and 2019. Most patients were receiving primary care (70.4%) and on GINA step 1-3 therapies (78.2%). ICS-long-acting beta-2 agonist (ICS-LABA) users increased over the years especially in the primary care, from 33% to 52%. Correspondingly, inpatient admission and ED visit rates decreased over the years. Between 2015 and 2019, the proportion of patients with poor adherence decreased from 12.8% to 10.5% (for ICS) and from 30.0% to 26.8% (for ICS-LABA) respectively. Factors associated with poor adherence included minority ethnic groups (Odds ratio of MPR 0.75-1.2: 0.73-0.93; compared to Chinese), presence of COPD (OR 0.75, 95% CI 0.59-0.96) and GINA step 4 treatment ladder (OR 0.71, 95% CI 0.61-0.85). Factors associated with good adherence were male gender (OR 1.14, 95% CI 1.01-1.28), single site of care (OR 1.22 for primary care and OR 1.76 for specialist care), GINA step 2 treatment ladder (OR 1.28, 95% CI 1.08-1.50). Good adherence was also associated with less frequent inpatient admission (OR 0.91, 95% CI 0.84-0.98), greater SABA overdispensing (OR 1.66, 95% CI 1.47-1.87) and oral corticosteroids use (OR 1.10, 95% CI 1.05-1.14). Inhaled corticosteroid (ICS) adherence has improved generally, however, poor adherence was observed for patients receiving asthma care in both primary and specialist care, and those from the minority ethnicities., (© 2024. The Author(s).)

Background: Women with overweight (OW) and those with obesity (OB) tend to gain excessive weight during pregnancy, often resulting in adverse outcomes. The long-term effects of mobile health (mHealth) interventions on maternal and infant outcomes remain unclear., Aims: To examine the effects of an mHealth intervention on OW and OB from the course of their pregnancy to six months postpartum., Methods: A randomized controlled trial was conducted in northern Taiwan. Ninety-two pregnant women with a body mass index (BMI)of ≥25 kg/m 2 were recruited from prenatal clinics at <17 weeks of gestation. Prepregnancy weight was baseline maternal weight, with data collected subsequently at the last assessment before childbirth and six months postpartum. The intervention group (IG) received the mHealth intervention, while the control group (CG) received standard antenatal care. The trial was registered on ClinicalTrials.gov (identifier: NCT04553731) with the initial registration date of September 16, 2020., Findings: The IG tended to have a lower mean body weight than the CG at the last assessment before childbirth (82.23 kg vs 84.35 kg) and at six months postpartum (72.55 Kg vs 72.58 Kg). IG's newborn birth weight was significantly lower than CG's (3074.8 vs. 3313.6 g; p = 0.009). Regression analysis revealed that OB in IG had a significant reduction in weight before childbirth (β = -7.51, p = 0.005) compared to OB in CG. Compared to OW in CG, both OW in IG (β = -243.59, p = 0.027) and OB in IG (β = -324.59, p = 0.049) were associated with decreased newborn birth weight., Conclusions: mHealth helped women with obesity to successfully manage their GWG and body weight before childbirth and newborns' birth weight, despite this effect not persisting to reduce weight retention at six months postpartum., 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 Elsevier Ltd. All rights reserved.)

Background: Cigarette smoking remains a leading cause of mortality worldwide. Streptococcus pneumoniae, also known as pneumococcus, is one of the most common pathogens that colonizes the human respiratory tract, causing life-threatening infections. Several studies have reported that cigarette smoke (CS) exposure promotes pneumococcal infectivity; however, the underlying mechanisms remain to be illustrated., Methods: In this study, we prepared cigarette smoke extract (CSE) from tobacco containing nicotine (0.8 mg/cigarette) and tar (10 mg/cigarette) to investigate the effects of CSE on innate immune response using murine macrophage models., Results: The results from the cytokine array showed that the production of C-C Motif Chemokine Ligand 2 (CCL2), CCL4, CCL3, C-X-C Motif Chemokine Ligand 2 (CXCL2), and CXCL-10, in pneumococcus-infected cells was reduced upon 5 % CSE treatment. Our results further demonstrated that 5 % CSE exposure, followed by pneumococcal challenge, significantly decreased CCL2 and type I interferon (IFN) production in macrophages by inhibiting nuclear factor (NF)-κB and IFN regulatory factor 3 (IRF3) signaling pathways. Moreover, CSE disrupts macrophage polarization and impedes innate immune signaling to suppress pneumococcal phagocytosis by macrophages., Conclusion: Our results provide evidence that CS manipulates the signaling molecules to subvert macrophage functions, thereby hindering the innate response against pneumococcal infection., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Four previously described species of Argopistes are recognized and redescribed from Japan and Taiwan: A.biplagiatus Motschulsky, 1860, A.rufus Chen, 1934, A.tsekooni Chen, 1934, and A.unicolor Jacoby, 1885. Three new species from Taiwan, A.jungchani sp. nov. , A.tsoui sp. nov. , and A.yuae sp. nov. , are described. Descriptions of species include illustrations of aedeagi, antennae, gonocoxae, abdominal ventrite VIII, and spermathecae. Argopistesrufus Chen, 1934, stat. nov. is raised to species status from a variety of A.biplagiatus Motschulsky, 1860. Argopistescoccinelliformis Csiki, 1940, syn. nov. and A.ryukyuensis Shigetoh & Suenaga, 2022, syn. nov. are proposed as junior synonyms of A.rufus Chen, 1934 Lectotypes are designated for A.undecimmaculata Jacoby, 1885, A.unicolor Jacoby, 1885, and A.biplagiatusvar.rufus Chen, 1934., Competing Interests: The authors have declared that no competing interests exist., (Chi-Feng Lee, Ming-Yao Chiang, Haruki Suenaga.)

During meiosis, the parental chromosomes are drawn together to enable exchange of genetic information. Chromosomes are aligned through the assembly of a conserved interface, the synaptonemal complex, composed of a central region that forms between two parallel chromosomal backbones called axes. Here we identify the axis-central region interface in C. elegans , containing a conserved positive patch on the axis component HIM-3 and the C-terminus of the central region protein SYP-5. Crucially, the canonical ultrastructure of the synaptonemal complex is altered upon weakening this interface. We developed a thermodynamic model that recapitulates our experimental observations, indicating that the liquid-like central region can assemble by wetting the axes without active energy consumption. More broadly, our data show that condensation drives tightly regulated nuclear reorganization during sexual reproduction., Competing Interests: Declaration of interests The authors declare no competing interests.

The Vicsek simulation model of flocking together with its theoretical treatment by Toner and Tu in 1995 were two foundational cornerstones of active matter physics. However, despite the field's tremendous progress, the actual universality class (UC) governing the scaling behavior of Viscek's "flocking" phase remains elusive. Here, we use nonperturbative, functional renormalization group methods to analyze, numerically and analytically, a simplified version of the Toner-Tu model, and uncover a novel UC with scaling exponents that agree remarkably well with the values obtained in a recent simulation study by Mahault et al. [Phys. Rev. Lett. 123, 218001 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.218001], in both two and three spatial dimensions. We therefore believe that there is strong evidence that the UC uncovered here describes Vicsek's flocking phase.