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Abstract Background The direct anterior approach (DAA) for total hip arthroplasty (THA) has gained popularity due to perceived advantages in achieving better early outcomes. However, the theoretical benefits such as precise implant positioning and accurate leg length restoration are still inconsistent. In this study, we compared implant position and leg length discrepancy (LLD) of the DAA and posterolateral approach (PLA) conducted by a single surgeon who had mastered both approaches. Methods This study retrospectively reviewed the medical records and radiographic images of 244 patients who underwent THA between 2012 and 2021 by a single experienced surgeon using either the DAA (n = 120) or PLA (n = 124). Postoperative pelvic anteroposterior radiographs at 6 months follow-up were used to assess acetabular component inclination and anteversion, as well as LLD. Mann-Whitney U tests and Chi-squared test were performed to compare outcomes between the two approaches. Results No significant differences were observed in patient demographics between the two groups. The DAA group demonstrated significantly lower postoperative LLD (0.00 mm) compared to the PLA group (5.00 mm, p

Abstract We report measurements of the e + e − → B B ¯ $$ B\overline{B} $$ , B B ¯ ∗ $$ B{\overline{B}}^{\ast } $$ , and B ∗ B ¯ ∗ $$ {B}^{\ast }{\overline{B}}^{\ast } $$ cross sections at four energies, 10653, 10701, 10746 and 10805 MeV, using data collected by the Belle II experiment. We reconstruct one B meson in a large number of hadronic final states and use its momentum to identify the production process. In the first 2 – 5 MeV above B ∗ B ¯ ∗ $$ {B}^{\ast }{\overline{B}}^{\ast } $$ threshold, the e + e − → B ∗ B ¯ ∗ $$ {B}^{\ast }{\overline{B}}^{\ast } $$ cross section increases rapidly. This may indicate the presence of a pole close to the threshold.

Abstract Background Normal cells express functional tumor suppressor WW domain-containing oxidoreductase (WWOX), designated WWOXf. UV irradiation induces WWOXf cells to undergo bubbling cell death (BCD) — an event due to the accumulation of nuclear nitric oxide (NO) gas that forcefully pushes the nuclear and cell membranes to form one or two bubbles at room temperature (22 °C) and below. In contrast, when WWOX-deficient or -dysfunctional (WWOXd) cells are exposed to UV and/or cold shock, the cells undergo nuclear pop-out explosion death (POD). We aimed to determine the morphological and biochemical changes in WWOXf cells during BCD versus apoptosis. Methods WWOXf and WWOXd cells were exposed to UV followed by measuring BCD or POD by time-lapse microscopy and/or time-lapse holographic microscopy at 4, 22, or 37 °C to visualize morphological changes. Live cell stains were used to measure the kinetics of nitric oxide (NO) production and Ca2+ influx. Extent of cell death was measured by uptake of propidium iodide and by internucleosomal DNA fragmentation using agarose gel electrophoresis. Results WWOXf cells were exposed to UV and then cold shock, or cold shock and then UV, and cultured at 4, 10, and 22 °C, respectively. Initially, UV induced calcium influx and NO production, which led to nuclear bubbling and final death. Cold shock pretreatment completely suppressed UV-mediated bubbling at 37 °C, so the UV/cold shock-treated cells underwent apoptosis. Without cold shock, UV only induced bubbling at all temperatures, whereas the efficiency of bubbling at 37 °C was reduced by greater than 50%. Morphologically, the WWOXf cell height or thickness was significantly increased during cell division or apoptosis, but the event did not occur in BCD. In comparison, when WWOXd cancer cells received UV or UV/cold shock, these cells underwent NO-independent POD. UV/cold shock effectively downregulated the expression of many proteins such as the housekeeping α-tubulin (> 70%) and β-actin ( 70%) in WWOXf COS7 cells. UV/cold shock induced relocation of α-tubulin to the nucleus and nuclear bubbles in damaged cells. UV induced co-translocation of the WWOX/TRAF2 complex to the nuclei, in which the prosurvival TRAF2 blocked the proapoptotic WWOX via its zinc finger domain. Without WWOX, TRAF2 did not relocate to the nuclei. Cold shock caused the dissociation of the WWOX/TRAF2 complex in the nucleus needed for BCD. In contrast, the formation of the WWOX/TRAF2 complex, plus p53, was strengthened at 37 °C required for apoptosis. Conclusions The temperature-sensitive nuclear WWOX/TRAF2 complex acts as a molecular switch, whose dissociation favors BCD at low temperatures, and the association supports apoptosis at 37 °C in UV-treated WWOXf cells.

Abstract Background Air pollution may exacerbate diabetes-related indicators; however, the longitudinal associations between air pollutant concentrations and glycemic markers remain unclear. In this prospective cohort study, we examined the longitudinal associations between air pollution and glycemic indicators among older individuals with normoglycemia at baseline and determined whether these associations differed according to changes in physical activity levels. Methods Overall, 1,856 participants (mean age, 70.9 years) underwent baseline and 4-year follow-up surveys. We used linear mixed-effect models to examine the associations between previous 1-year exposures to air pollutants and glycemic indicators. We further investigated associations between previous 5-year exposures to air pollutants and glycemic indicators after the inverse probability of treatment weighting (IPTW). We explored effect modifications by the level of physical activity maintenance and changes in metabolic equivalent of task (METs) for physical activity. Results Levels of particulate matter with aerodynamic diameters ≤ 10 μm (PM10) and ≤ 2.5 μm, and nitrogen dioxide (NO2) were significantly associated with increased fasting blood glucose, Hemoglobin A1c, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) values. After IPTW, the associations remained significant for PM10 and NO2. The positive associations of NO2 with insulin and HOMA-IR remained significant in the maintained inactive group, but not in the maintained moderate-to-vigorous active group. The positive associations of PM10 or NO2 with insulin and HOMA-IR remained significant in the group with increased METs, but not in those with decreased METs. In the post-hoc analysis of non-linear relationships between an increase in METs and glycemic indicators, insulin and HOMA-IR remarkably increased in the higher PM10 and NO2 exposure group from the point of 12,000 and 13,500 METs-min/week increase, respectively. Conclusions We demonstrated longitudinal associations between air pollution exposures and increased insulin resistance in older individuals. Maintaining moderate-to-vigorous physical activity may mitigate the adverse effects of air pollution on insulin resistance. In older individuals dwelling in highly polluted areas, an increase of less than 12,000 METs-min/week may be beneficial for insulin resistance.

Abstract Background Bone grafts are extensively used for repairing bone defects and voids in orthopedics and dentistry. Moldable bone grafts offer a promising solution for treating irregular bone defects, which are often difficult to fill with traditional rigid grafts. However, practical applications have been limited by insufficient mechanical strength and rapid degradation. Methods This study developed a ceramic composite bone graft composed of calcium sulfate (CS), β-tricalcium phosphate (β-TCP) with/without graphene oxide (GO) nano-particles. The biomechanical properties, degradation rate, and in-vitro cellular responses were investigated. In addition, the graft was implanted in-vivo in a critical-sized calvarial defect model. Results The results showed that the compressive strength significantly improved by 135% and the degradation rate slowed by 25.5% in comparison to the control model. The addition of GO nanoparticles also improved cell compatibility and promoted osteogenic differentiation in the in-vitro cell culture study and was found to be effective at promoting bone repair in the in-vivo animal model. Conclusions The mixed ceramic composites presented in this study can be considered as a promising alternative for bone graft applications.

Background: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. Methods: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. Results: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P

Abstract We present a study of Ξ c 0 → Ξ 0 π 0 $$ {\Xi}_c^0\to {\Xi}^0{\pi}^0 $$ , Ξ c 0 → Ξ 0 η $$ {\Xi}_c^0\to {\Xi}^0\eta $$ , and Ξ c 0 → Ξ 0 η ′ $$ {\Xi}_c^0\to {\Xi}^0{\eta}^{\prime } $$ decays using the Belle and Belle II data samples, which have integrated luminosities of 980 fb −1 and 426 fb −1, respectively. We measure the following relative branching fractions B Ξ c 0 → Ξ 0 π 0 / B Ξ c 0 → Ξ − π + = 0.48 ± 0.02 stat ± 0.03 syst , B Ξ c 0 → Ξ 0 η / B Ξ c 0 → Ξ − π + = 0.11 ± 0.01 stat ± 0.01 syst , B Ξ c 0 → Ξ 0 η ′ / B Ξ c 0 → Ξ − π + = 0.08 ± 0.02 stat ± 0.01 syst $$ {\displaystyle \begin{array}{c}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.48\pm 0.02\left(\textrm{stat}\right)\pm 0.03\left(\textrm{syst}\right),\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0\eta \right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.11\pm 0.01\left(\textrm{stat}\right)\pm 0.01\left(\textrm{syst}\right),\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\eta}^{\prime}\right)/\mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right)=0.08\pm 0.02\left(\textrm{stat}\right)\pm 0.01\left(\textrm{syst}\right)\end{array}} $$ for the first time, where the uncertainties are statistical (stat) and systematic (syst). By multiplying by the branching fraction of the normalization mode, B Ξ c 0 → Ξ − π + $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right) $$ , we obtain the following absolute branching fraction results B Ξ c 0 → Ξ 0 π 0 = 6.9 ± 0.3 stat ± 0.5 syst ± 1.3 norm × 10 − 3 , B Ξ c 0 → Ξ 0 η = 1.6 ± 0.2 stat ± 0.2 syst ± 0.3 norm × 10 − 3 , B Ξ c 0 → Ξ 0 η ′ = 1.2 ± 0.3 stat ± 0.1 syst ± 0.2 norm × 10 − 3 , $$ {\displaystyle \begin{array}{c}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)=\left(6.9\pm 0.3\left(\textrm{stat}\right)\pm 0.5\left(\textrm{syst}\right)\pm 1.3\left(\operatorname{norm}\right)\right)\times {10}^{-3},\\ {}\mathcal{B}\left({\Xi}_c^0\to {\Xi}^0\eta \right)=\left(1.6\pm 0.2\left(\textrm{stat}\right)\pm 0.2\left(\textrm{syst}\right)\pm 0.3\left(\operatorname{norm}\right)\right)\times {10}^{-3},\\ {}\mathcal{B}\left({\varXi}_c^0\to {\Xi}^0{\eta}^{\prime}\right)=\left(1.2\pm 0.3\left(\textrm{stat}\right)\pm 0.1\left(\textrm{syst}\right)\pm 0.2\left(\operatorname{norm}\right)\right)\times {10}^{-3},\end{array}} $$ where the third uncertainties are from B Ξ c 0 → Ξ − π + $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+}\right) $$ . The asymmetry parameter for Ξ c 0 → Ξ 0 π 0 $$ {\Xi}_c^0\to {\Xi}^0{\pi}^0 $$ is measured to be α Ξ c 0 → Ξ 0 π 0 = − 0.90 ± 0.15 stat ± 0.23 syst $$ \alpha \left({\Xi}_c^0\to {\Xi}^0{\pi}^0\right)=-0.90\pm 0.15\left(\textrm{stat}\right)\pm 0.23\left(\textrm{syst}\right) $$ .

Abstract Low muscle mass is a risk factor for mortality in patients with chronic kidney disease (CKD). However, it is not clear to what extent low muscle mass contributes to this risk, either independently or in combination with metabolic abnormalities and frailty. This study used data from the National Health and Nutrition Examination Survey 1999–2006 and 2011–2018. Low muscle mass was defined as Appendicular Skeletal Mass Index

Pasteurella spp. can cause fatal zoonotic infections in humans. We performed a multicenter study to investigate the prevalence and clinical features of Pasteurella infections in South Korea during 2018‒2022. We also conducted a collaborative systematic review and meta-analysis of the global burden of Pasteurella bacteremia. The study included 283 cases found an increasing trend in Pasteurella infections. Blood cultures were positive in 8/35 (22.9%) cases sampled, for overall bacteremia-associated rate of 2.8% (8/283). Aging was a significant risk factor for bacteremia (odds ratio 1.05 [95% CI 1.01–1.10]), according to multivariate analyses. For the meta-analysis, we included a total of 2,012 cases from 10 studies. The pooled prevalence of bacteremia was 12.4% (95% CI 7.3%–18.6%) and of mortality 8.4% (95% CI 2.7%–16.5%). Our findings reflect the need for greater understanding of the increase in Pasteurella infections and the global burden of Pasteurella bacteremia to determine appropriate case management.

Background/purpose: Understanding the relationship between maxillary sinus and posterior root apices is critical in preventing dental treatment complications. This study aimed to analyze and showcase the relationship between the posterior root apices and the maxillary sinus floor, the distance to the buccal cortical bone, and their correlation with age, gender, and sides. Materials and methods: Cone-beam computed tomography images were collected from 94 patients with a total of 478 maxillary posterior teeth and 997 roots. The shortest distance from root apices to the closest border of maxillary sinus and the outer buccal cortical bone margin were measured and grouped for statistical analysis for the differences (P

Background: The mainstay of treatment for melasma is topical hydroquinone or preparations containing hydroquinone. In recent years, cysteamine cream has gained popularity in the treatment of hyperpigmentation disorders. Objectives: This study aimed to compare the efficacy of combined hydroquinone/betamethasone to cysteamine in the treatment of melasma. Methods: Eighteen patients had completed this open-label controlled trial. Subjects received either 5% cysteamine cream or a combination of 4% hydroquinone cream and 0.06% betamethasone valerate for 12 weeks according to standardized protocols. Patients were assessed at recruitment, 4 weeks, and 12 weeks after treatment for Melasma Area and Severity Index (MASI) scores. Other parameters relating to skin complexions and patient satisfaction were also assessed. Results: Patients treated with hydroquinone (n = 7) and cysteamine (n = 11) both showed significant decreases in MASI score at week 12: 33.1% (P = 0.009) and 37.9% (P = 0.009), respectively. There was no statistically significant difference between the two treatment groups (P = 0.236). Melanin content at week 12 decreased by 8.8% (P = 0.016) in the hydroquinone group and 11.5% (P = 0.046) in the cysteamine group, with no significant difference between the groups (P = 0.253). No significant differences were observed between the groups for other parameters or patient satisfaction. Conclusion: Cysteamine cream may provide an alternative treatment option for individuals with melasma, offering fewer side effects while delivering comparable results.

Abstract Many insects utilise optical information in linearly polarised light for navigation, with the degree of linear polarisation (DoLP) determining whether the ‘visibility’ of such optical information is available to them. However, changes in degree of linear polarisation in response to increased atmospheric levels of fine particulate matter (PM2.5) are poorly understood. We present analyses based on both ground-based monitoring and particulate matter modelling, establishing a quantitative relationship between PM2.5 mass concentration and the DoLP. We apply this relationship to a global PM2.5 projection for 2050 and estimate the increase in number and spatial extent of low visibility days for honeybees. We find an increase by up to 20% in the geographical extent of low visibility days in 2050, with an augmented frequency of low visibility days across an area exceeding 0.75 million km2 in India and 2 million km2 in China. More frequent and widespread low visibility conditions can reduce the ability of insects to navigate, especially in hotspot regions.

Abstract Ferritin, comprising heavy (FTH1) and light (FTL) chains, is the main iron storage protein, and pancreatic cancer patients exhibit elevated serum ferritin levels. Specifically, higher ferritin levels are correlated with poorer pancreatic ductal adenocarcinoma (PDAC) prognosis; however, the underlying mechanism and metabolic programming of ferritin involved in KRAS-mutant PDAC progression remain unclear. Here, we observed a direct correlation between FTH1 expression and cell viability and clonogenicity in KRAS-mutant PDAC cell lines as well as with in vivo tumor growth through the control of proline metabolism. Our investigation highlights the intricate relationship between FTH1 and pyrroline-5-carboxylate reductase 1 (PYCR1), a crucial mitochondrial enzyme facilitating the glutamate-to-proline conversion, underscoring its impact on proline metabolic imbalance in KRAS-mutant PDAC. This regulation is further reversed by miR-5000-3p, whose dysregulation results in the disruption of proline metabolism, thereby accentuating the progression of KRAS-mutant PDAC. Additionally, our study demonstrated that deferasirox, an oral iron chelator, significantly diminishes cell viability and tumor growth in KRAS-mutant PDAC by targeting FTH1-mediated pathways and altering the PYCR1/PRODH expression ratio. These findings underscore the novel role of FTH1 in proline metabolism and its potential as a target for PDAC therapy development.

Abstract Background Viral neutralization (NT) assays can be used to determine the immune status of patients or assess the potency of candidate vaccines or therapeutic monoclonal antibodies (mAbs). Focus reduction neutralization test (FRNT) is a conventional neutralization test (cVNT) with superior specificity for measurement of neutralizing antibodies against a specific virus. Unfortunately, the application of FRNT to the chikungunya virus (CHIKV) involves a highly pathogenic bio-agent requiring biosafety level 3 (BSL3) facilities, which inevitably imposes high costs and limits accessibility. In this study, we evaluated a safe surrogate virus neutralization test (sVNT) that uses novel CHIKV replicon particles (VRPs) expressing eGFP and luciferase (Luc) to enable the rapid detection and quantification of neutralizing activity in clinical human serum samples. Methods This unmatched case-control validation study used serum samples from laboratory-confirmed cases of CHIKV (n = 19), dengue virus (DENV; n = 9), Japanese encephalitis virus (JEV; n = 5), and normal individuals (n = 20). We evaluated the effectiveness of sVNT, based on mosquito cell-derived CHIK VRPs (mos-CHIK VRPs), in detecting (eGFP) and quantifying (Luc) neutralizing activity, considering specificity, sensitivity, and reproducibility. We conducted correlation analysis between the proposed rapid method (20 h) versus FRNT assay (72 h). We also investigated the correlation between sVNT and FRNT in NT titrations in terms of Pearson’s correlation coefficient (r) and sigmoidal curve fitting. Results In NT screening assays, sVNT-eGFP screening achieved sensitivity and specificity of 100%. In quantitative neutralization assays, we observed a Pearson’s correlation coefficient of 0.83 for NT50 values between sVNT-Luc and FRNT. Conclusions Facile VRP-based sVNT within 24 h proved highly reliable in the identification and quantification of neutralizing activity against CHIKV in clinical serum samples.

Abstract By analyzing e + e − annihilation data corresponding to an integrated luminosity of 2.93 fb −1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the semileptonic decays D 0 → K S 0 π − π 0 e + ν e $$ {D}^0\to {K}_S^0{\pi}^{-}{\pi}^0{e}^{+}{\nu}_e $$ and D + → K S 0 π + π − e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^{+}{\pi}^{-}{e}^{+}{\nu}_e $$ is reported. In the hypothesis that all events correspond to K 1(1270) decays, the branching fractions are measured to be B D 0 → K 1 1270 − → K S 0 π − π 0 e + ν e = 1.69 − 0.46 + 0.53 ± 0.15 × 10 − 4 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}\left(\to {K}_S^0{\pi}^{-}{\pi}^0\right){e}^{+}{\nu}_e\right)=\left({1.69}_{-0.46}^{+0.53}\pm 0.15\right)\times {10}^{-4} $$ and B D + → K ¯ 1 1270 0 → K S 0 π + π − e + ν e = 1.47 − 0.40 + 0.45 ± 0.14 × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0\left(\to {K}_S^0{\pi}^{+}{\pi}^{-}\right){e}^{+}{\nu}^e\right)=\left({1.47}_{-0.40}^{+0.45}\pm 0.14\right)\times {10}^{-4} $$ with statistical significance of 5.4σ and 5.6σ, respectively. When combined with measurements of the K 1(1270) → K + π − π decays, the absolute branching fractions are determined to be B D 0 → K 1 1270 − e + ν e = 1.08 − 0.13 − 0.10 + 0.14 + 0.08 ± 0.21 × 10 − 3 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}{e}^{+}{\nu}_e\right)=\left({1.08}_{-0.13-0.10}^{+0.14+0.08}\pm 0.21\right)\times {10}^{-3} $$ and B D + → K ¯ 1 1270 0 e + ν e = 1.70 − 0.23 + 0.26 ± 0.13 ± 0.35 × 10 − 3 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0{e}^{+}{\nu}_e\right)=\left({1.70}_{-0.23}^{+0.26}\pm 0.13\pm 0.35\right)\times {10}^{-3} $$ . The first and second uncertainties are statistical and systematic, respectively, and the third uncertainties originate from the assumed branching fractions of the K 1(1270) → Kππ decays.

Abstract Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04–7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN.

Abstract Programmable RNA editing is harnessed for modifying mRNA. Besides mRNA, miRNA also regulates numerous biological activities, but current RNA editors have yet to be exploited for miRNA manipulation. To engineer primary miRNA (pri-miRNA), the miRNA precursor, we present a customizable editor REPRESS (RNA Editing of Pri-miRNA for Efficient Suppression of miRNA) and characterize critical parameters. The optimized REPRESS is distinct from other mRNA editing tools in design rationale, hence enabling editing of pri-miRNAs that are not editable by other RNA editing systems. We edit various pri-miRNAs in different cells including adipose-derived stem cells (ASCs), hence attenuating mature miRNA levels without disturbing host gene expression. We further develop an improved REPRESS (iREPRESS) that enhances and prolongs pri-miR-21 editing for at least 10 days, with minimal perturbation of transcriptome and miRNAome. iREPRESS reprograms ASCs differentiation, promotes in vitro cartilage formation and augments calvarial bone regeneration in rats, thus implicating its potentials for engineering miRNA and applications such as stem cell reprogramming and tissue regeneration.

Abstract We present the result of a search for the charged-lepton-flavor violating decay τ − → μ − μ + μ − using a 424 fb −1 sample of data recorded by the Belle II experiment at the SuperKEKB e + e − collider. The selection of e + e − → τ + τ − events is based on an inclusive reconstruction of the non-signal tau decay, and on a boosted decision tree to suppress background. We observe one signal candidate, which is compatible with the expectation from background processes. We set a 90% confidence level upper limit of 1.9 × 10 −8 on the branching fraction of the τ − → μ − μ + μ − decay, which is the most stringent bound to date.

Background/Aims: Bile duct invasion (BDI) is rarely observed in patients with advanced hepatocellular carcinoma (HCC), leading to hyperbilirubinemia. However, the efficacy of pretreatment biliary drainage for HCC patients with BDI and obstructive jaundice is currently unclear. Thus, the aim of this study was to assess the effect of biliary drainage on the prognosis of these patients. Methods: We retrospectively enrolled a total of 200 HCC patients with BDI from multicenter cohorts. Patients without obstructive jaundice (n=99) and those who did not undergo HCC treatment (n=37) were excluded from further analysis. Finally, 64 patients with obstructive jaundice (43 subjected to drainage and 21 not subjected to drainage) were included. Propensity score matching was then conducted. Results: The biliary drainage group showed longer overall survival (median 10.13 months vs 4.43 months, p=0.004) and progression-free survival durations (median 7.00 months vs 1.97 months, p

The WHO (World Health Organization) conducted an elimination of cervical cancer program using triple pillar intervention strategy to target 90%-70%-90% of women before the year 2030, including (1) a full vaccination of HPV (human papillomavirus) vaccine to 90% of girls

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m2+triweekly cisplatin 40 mg/m2), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m2) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC.

Background: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. Methods: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. Results: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432–5p and miRNA-382–3p were upregulated in patients with abnormal SSS. Conclusion: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.

Background: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. Methods: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Abstract Investigate the impact of remnant cholesterol (RC) levels on carotid artery intima thickness (CIT) in type 2 diabetes mellitus (T2DM) patients. From September 2021 to September 2023, a prospective multicenter study involved 158 T2DM patients. They were divided into a higher RC group (n = 80) and a lower RC group (n = 78) based on median RC levels. Additionally, 92 healthy volunteers served as the control group. CIT, carotid media thickness (CMT), and carotid intima-media thickness (CIMT) were measured. General clinical data, lab results, CIMT, CIT, and CMT differences among the three groups were compared. Multiple regression analysis explored CIT factors in T2DM patients. 1. No significant sex, age, BMI, high-density lipoprotein cholesterol (HDL-C), T2DM duration, fasting blood glucose, or glycated hemoglobin differences were found among the groups (p > 0.05). 2. CIMT and CIT were significantly higher in T2DM than the control group (p 0.05). Multiple linear regression analysis showed RC as an influencing CIT factor in T2DM patients (β = 0.473, p = 0.005). CIT is significantly thicker in T2DM patients with higher RC than in those with lower RC, and RC is the influence factor of CIT, which suggests that more attention should be paid to the detection of RC in T2DM patients.

Background/Aims The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. Methods We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. Results The study included 232 patients. ‘Gout concern overall’ scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and ‘well-being during attack’ scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the ‘well-being during attack’ and ‘gout concern during attack’ scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the ‘gout concern overall’ and ‘gout concern during attack’ scores (p = 0.04 and p = 0.002, respectively). Conclusions Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

The aberrant fibrillization of huntingtin exon 1 (Httex1) characterized by an expanded polyglutamine (polyQ) tract is a defining feature of Huntington's disease, a neurodegenerative disorder. Recent investigations underscore the involvement of a small EDRK-rich factor 1a (SERF1a) in promoting Httex1 fibrillization through interactions with its N terminus. By establishing an integrated approach with size-exclusion-column-based small- and wide-angle X-ray scattering (SEC-SWAXS), NMR, and molecular simulations using Rosetta, the analysis here reveals a tight binding of two NT17 fragments of Httex1 (comprising the initial 17 amino acids at the N terminus) to the N-terminal region of SERF1a. In contrast, examination of the complex structure of SERF1a with a coiled NT17-polyQ peptide (33 amino acids in total) indicates sparse contacts of the NT17 and polyQ segments with the N-terminal side of SERF1a. Furthermore, the integrated SEC-SWAXS and molecular-simulation analysis suggests that the coiled NT17 segment can transform into a helical conformation when associated with a polyQ segment exhibiting high helical content. Intriguingly, NT17-polyQ peptides with enhanced secondary structures display diminished interactions with SERF1a. This insight into the conformation-dependent binding of NT17 provides clues to a catalytic association mechanism underlying SERF1a's facilitation of Httext1 fibrillization.

Rapid growth in industrial sectors such as automotive and shipbuilding has highlighted the significance of strip casting technology to produce lightweight alloys, particularly aluminum alloys widely used in both industrial production and daily life. Twin-roll casting (TRC), as an economically and environmentally friendly method for slab/strip production and processing, has attracted significant interest from researchers. However, the development of TRC aluminum alloys faces many challenges due to limited understanding of microstructural characteristics and control mechanisms. To further enhance comprehension of TRC aluminum alloys, this article reviews the influencing parameters, control methods, and existing issues related to TRC sub-rapid solidification (SRS) microstructure. It firstly summarizes TRC equipment types and their solidification characteristics, followed by a detailed analysis on key parameters affecting the evolution of TRC microstructure including rolling speed, roll separation force (RSF), and heat transfer coefficient (HTC). Finally, solutions to TRC defects are summarized and evaluated alongside their underlying mechanisms. This article provides a comprehensive review of the characteristics and control mechanisms of TRC microstructure while offering valuable insights for the future production of high-quality TRC aluminum strips.

Objectives: The World Health Organization named Stenotrophomonas maltophilia (SM) a critical multi-drug resistant threat, necessitating rapid diagnostic strategies. Traditional culturing methods require up to 96 h, including 72 h for bacterial growth, identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) through protein profile analysis, and 24 h for antibiotic susceptibility testing. In this study, we aimed at developing an artificial intelligence-clinical decision support system (AI-CDSS) by integrating MALDI-TOF MS and machine learning to quickly identify levofloxacin and trimethoprim/sulfamethoxazole resistance in SM, optimizing treatment decisions. Methods: We selected 8,662 SM from 165,299 MALDI-TOF MS-analysed bacterial specimens, collected from a major medical centre and four secondary hospitals. We exported mass-to-charge values and intensity spectral profiles from MALDI-TOF MS .mzML files to predict antibiotic susceptibility testing results, obtained with the VITEK-2 system using machine learning algorithms. We optimized the models with GridSearchCV and 5-fold cross-validation. Results: We identified distinct spectral differences between resistant and susceptible SM strains, demonstrating crucial resistance features. The machine learning models, including random forest, light-gradient boosting machine, and XGBoost, exhibited high accuracy. We established an AI-CDSS to offer healthcare professionals swift, data-driven advice on antibiotic use. Conclusions: MALDI-TOF MS and machine learning integration into an AI-CDSS significantly improved rapid SM resistance detection. This system reduced the identification time of resistant strains from 24 h to minutes after MALDI-TOF MS identification, providing timely and data-driven guidance. Combining MALDI-TOF MS with machine learning could enhance clinical decision-making and improve SM infection treatment outcomes.

Microglia mediated neuronal inflammation has been reported to be responsible for neurodegenerative disease. Isoquercitrin (IQC), widely found in fruits, vegetables and foods, has high bioavailability and offers many benefits of humans. Although IQC has been shown to possess pleiotropic biological activities, but its anti-inflammatory mechanism in microglia at molecular level remains largely unclear. Therefore, this study aimed to investigate IQC’s inhibition on inflammation within BV2 microglia cells induced by lipopolysaccharide (LPS) and the underlying mechanism.

Abstract We present a measurement of the ratio R μ = B τ − → μ − ν ¯ μ ν τ / B τ − → e − ν ¯ e ν τ $$ {R}_{\mu }=\mathcal{B}\left({\tau}^{-}\to {\mu}^{-}{\overline{\nu}}_{\mu }{\nu}_{\tau}\right)/\mathcal{B}\left({\tau}^{-}\to {e}^{-}{\overline{\nu}}_e{\nu}_{\tau}\right) $$ of branching fractions B $$ \mathcal{B} $$ of the τ lepton decaying to muons or electrons using data collected with the Belle II detector at the SuperKEKB e + e − collider. The sample has an integrated luminosity of 362 ± 2 fb −1 at a centre-of-mass energy of 10.58 GeV. Using an optimised event selection, a binned maximum likelihood fit is performed using the momentum spectra of the electron and muon candidates. The result, R μ = 0.9675 ± 0.0007 ± 0.0036, where the first uncertainty is statistical and the second is systematic, is the most precise to date. It provides a stringent test of the light-lepton universality, translating to a ratio of the couplings of the muon and electron to the W boson in τ decays of 0.9974 ± 0.0019, in agreement with the standard model expectation of unity.

Abstract We present measurements of the branching fractions of eight B ¯ 0 $$ {\overline{B}}^0 $$ → D (*)+ K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ , B − → D (*)0 K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ decay channels. The results are based on data from SuperKEKB electron-positron collisions at the Υ(4S) resonance collected with the Belle II detector, corresponding to an integrated luminosity of 362 fb −1. The event yields are extracted from fits to the distributions of the difference between expected and observed B meson energy, and are efficiency-corrected as a function of m(K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ ) and m(D (*) K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ ) in order to avoid dependence on the decay model. These results include the first observation of B ¯ 0 $$ {\overline{B}}^0 $$ → D + K − K S 0 $$ {K}_S^0 $$ , B − → D* 0 K − K S 0 $$ {K}_S^0 $$ , and B ¯ 0 $$ {\overline{B}}^0 $$ → D* + K − K S 0 $$ {K}_S^0 $$ decays and a significant improvement in the precision of the other channels compared to previous measurements. The helicity-angle distributions and the invariant mass distributions of the K − K S ∗ 0 $$ {K}_{(S)}^{\left(\ast \right)0} $$ systems are compatible with quasi-two-body decays via a resonant transition with spin-parity J P = 1− for the K − K S 0 $$ {K}_S^0 $$ systems and J P = 1+ for the K − K* 0 systems. We also present measurements of the branching fractions of four B ¯ 0 $$ {\overline{B}}^0 $$ → D (*)+ D s − $$ {D}_s^{-} $$ , B − → D (*)0 D s − $$ {D}_s^{-} $$ decay channels with a precision compatible to the current world averages.

Abstract MRI-guided targeted biopsy (MRGB) was recommended as part of biopsy paradigm of prostate cancers by current guidelines. This study aimed to analyze the diagnostic efficacy of MRGB and systemic biopsy (SB), and to compare diagnostic capabilities within subgroups of MRGB: MRI-cognitive biopsy (MRCB) and MRI-fusion biopsy (MRFB). We retrospectively enrolled patients who underwent MRGB for suspicious malignant lesion(s) identified on MRI in a single tertiary center, sample size was 74 patients. An mpMRI was performed prior to biopsy and reviewed by an experienced radiologist specialized in prostate cancer. Per-person results of MRGB and each concomitant SB were analyzed as independent biopsies for its positive biopsy rate and positive core percentage. Per-lesion results of MRFB and MRCB were compared for the detection rate. Variables of interest were analyzed with t-test, chi-squared test, and logistic regression analysis. Statistical analyses were performed with IBM Statistical Product and Service Solutions (SPSS), Version 23 (IBM, Armonk, New York). Total of 74 patients fulfilled the inclusion criteria and were enrolled. MRFB had higher PCa detection rate comparing to both MRCB and SB (56.1%, 30.3%, and 33.9% respectively, p value = 0.036); clinically significant prostate cancer (csPCa) detection rate was also significantly higher in MRFB group (43.9%, 24.2%, and 16.9% in each group respectively, p value = 0.011). In per-lesion analysis, MRCB and MRFB had no significant difference in PCa and csPCa detection rate (41.0% vs. 26.2% and 29.5% vs. 16.7% respectively, p value = 0.090 and 0.103). In the lesion ≦ 1.3 cm group, MRFB could achieve higher PCa detection rate, comparing to MRCB (36.4% vs. 14.3%, p value = 0.047); there were also higher positive rates for PCa and csPCa per biopsied cores (22.1% vs. 6.8% and 15.6% vs. 2.7%, p value = 0.029 and 0.028, respectively). Further logistic regression of multi-variate analysis in subgroup of lesion ≦ 1.3 cm revealed that PIRADS score and biopsy method were significant predictors of positive biopsy result for PCa (p value = 0.045 and 0.026, respectively) and for csPCa (p value = 0.043 and 0.025, respectively). In patients receiving trans-perineal prostate biopsy, MRFB had higher cancer detection rate than MRCB and SB. In per lesion comparison, MRFB and MRCB had similar diagnostic accuracy. However, in lesions with diameter less than 1.3 cm, MRFB can provided better diagnose value for PCa and csPCa than MRCB.

Abstract Background and Objectives Nintedanib, a tyrosine kinase inhibitor, is integral in slowing pulmonary fibrosis progression in chronic fibrotic interstitial lung disease (ILD). However, the occurrence of adverse drug reactions (ADRs) often limits its use, leading to treatment discontinuation, typically within 3–12 months. Discontinuation adversely affects patient outcomes. The study investigated whether aggressive ADR management can prolong nintedanib therapy and improve patient outcomes. Methods This retrospective, single-center study enrolled Taiwanese patients with chronic fibrotic ILD who were treated with nintedanib from January 2016 to December 2022 in Kaohsiung Chang Gung Memorial Hospital. Patients were categorized into those who discontinued treatment within 180 days and those continuing beyond. Management of ADRs was identified through concurrent prescriptions for symptoms such as nausea, vomiting, diarrhea, or hepatic dysfunction. Baseline demographics, comorbidities, pulmonary function tests, and instances of acute exacerbation were analyzed. Results The study enrolled 94 patients, with 71 (75.5%) experiencing ADRs. Among these, 41 (43.6%) discontinued nintedanib within 180 days. The administration of medications for managing nausea/vomiting [17 (41.5%) versus 36 (67.9%), p = 0.0103] and diarrhea [12 (29.3%) versus 33 (62.3%), p = 0.0015] was less frequent in the discontinued group compared with the continued group. Additionally, a higher incidence of acute exacerbation was observed in the discontinued group (34.1% versus 20.8%, p = 0.016). Conclusion Aggressive management of ADRs may enhance patient tolerance to nintedanib, potentially prolonging treatment duration and improving outcomes in chronic fibrotic ILD.

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5’s tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA’s regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.

Abstract Background Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation. Methods PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs. Results The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I 2 = 49.6%). The subgroup dose–response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400–1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I 2 = 55.7%, number needed to treat [NNT]: 36), trials duration

Abstract This study introduces a novel microwave applicator and optimized processing conditions to enhance the stability of Polyacrylonitrile (PAN)-based precursor fiber (PF). The innovative microwave applicator facilitates the propagation of the electromagnetic (EM) field akin to a quasi-traveling wave, thus circumventing standing wave nodes. This ensures a uniform thermal distribution and broadens the heating zone. Utilizing this applicator, the PF undergoes thermal stabilization in a streamlined two-step process, completing in just 13 min, a significant improvement over the conventional 90-min process. This not only saves manufacturing time, promoting energy efficient manufacturing but also aligns with the global trend towards green energy and lightweight carbon fiber-reinforced polymer matrix composites, potentially catalyzing rapid economic growth. Fiber characterization through Raman spectroscopy (RS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and complex permittivity measurements reveals that the microwave-processed fiber meets the standard of commercial stabilization fiber (SF).

Abstract Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan–Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 ± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25–201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (≤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I–III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (≤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.

Abstract Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials.

Abstract Purpose This study explores integrating clinical features with radiomic and dosiomic characteristics into AI models to enhance the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT). Materials and methods This study involved a retrospective analysis of 120 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital from 2018 to 2023. Patient data included CT images, radiation doses, Dose-Volume Histogram (DVH) data, and clinical information. Using a Treatment Planning System (TPS), we segmented CT images into Regions of Interest (ROIs) to extract radiomic and dosiomic features, focusing on intensity, shape, texture, and dose distribution characteristics. Features significantly associated with the development of RD were identified using ANOVA and LASSO regression (p-value

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count 200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Introduction: COVID-19 poses risks and leads to complications for vulnerable populations, including children. Unreported cases of COVID-19 among children hinder our understanding of the true disease burden. In this study, we aimed to investigate the proportion of children who report no prior infection to SARS-CoV-2 but who nevertheless exhibit serological evidence of prior infection. Methods: Between November 2022 and February 2023, we recruited children and adolescents under 19 years of age who lacked a prior history of SARS-CoV-2 infection. Participants underwent SARS-CoV-2 antibody testing to assess the presence of IgG antibodies specific to nucleocapsid (N) and spike (S) proteins. Demographic and contact information were also collected. Results: Among 260 COVID-19-free children, the overall anti-N antibody positivity rate, which varied across age groups (4%–25%), was 9.2% (24/260). Contact with individuals who were positive for COVID-19, particularly the children's mothers, significantly increased the likelihood of antibody positivity. The median age of the 34 children who remained unvaccinated against COVID-19 was lower than that of the children who were vaccinated (6.5 vs. 9 years; p

Bladder cancer poses a significant challenge to chemotherapy due to its resistance to cisplatin, especially at advanced stages. Understanding the mechanisms behind cisplatin resistance is crucial for improving cancer therapy. The enzyme glutathione S‐transferase omega class 1 (GSTO1) is known to be involved in cisplatin resistance in colon cancer. This study focused on its role in cisplatin resistance in bladder cancer. Our analysis of protein expression in bladder cancer cells stimulated by secretions from tumor‐associated macrophages (TAMs) showed a significant increase in GSTO1. This prompted further investigation into the role of GSTO1 in bladder cancer. We found a strong correlation between GSTO1 expression and cisplatin resistance. Mechanistically, GSTO1 triggered the release of large extracellular vesicles (EVs) that promoted cisplatin efflux, thereby reducing cisplatin–DNA adduct formation and enhancing cisplatin resistance. Inhibition of EV release effectively counteracted the cisplatin resistance associated with GSTO1. In conclusion, GSTO1‐mediated EV release may contribute to cisplatin resistance caused by TAMs in bladder cancer. Strategies to target GSTO1 could potentially improve the efficacy of cisplatin in treating bladder cancer.

Objective: Whether pregnancy is associated with severe injuries from motor vehicle crashes (MVCs) remains unclear. This study aimed to investigate the potential relationship between pregnancy and severity of injuries from MVCs. Methods: We identified a total of 23,559 pregnant women victims who encountered MVCs during pregnancy as well as 94,236 age- and calendar year-at MVC matched non-pregnant women victims that are also involved in MVCs. Injury severity was assessed using the Maximum Abbreviated Injury Scale (MAIS) based on the diagnosis of medical claims after MVCs. Multinomial logistic regression models were used to estimate the odds ratio and corresponding 95 % CI of injury severity levels associated with pregnancy. Results: Pregnant women had a significantly higher risk of both severe (adjusted odds ratio, aOR = 1.79, 95 % CI = 1.54–2.08) and mild injuries (aOR = 8.63, 95 % CI = 8.21–9.07) following MVCs as compared to non-pregnant women victims. Particularly, pregnant women who were riding scooters had an increased risk of severe injury (aOR = 4.25, 95 % CI = 3.58–5.04). In addition, pregnant women who experienced MVC but without any injury were more likely to visit a clinic than non-pregnant MVC victims. Conclusion: Pregnant women victims, particularly those who were riding scooters involved in MVCs suffered from a higher risk of severe injury as compared to their non-pregnant counterparts. Our findings suggest that women should consider avoiding riding a scooter and must use restrictive devices during pregnancy, which would help reduce the severity of injuries sustained following an MVC.

Background: Lorlatinib is a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-positive metastatic non-small cell lung cancer (NSCLC). In a global phase II study, patients who experience disease progression despite prior treatment with ALK tyrosine kinase inhibitors (TKIs) was assessed. Herein, we report real-world clinical outcomes of lorlatinib-treated patients with ALK-positive advanced NSCLC who were heavily pretreated and progressed on first- and second-generation ALK-TKIs, in a Taiwanese population under the lorlatinib expanded access program (EAP). Methods: This multicenter observational study examined the effectiveness and safety of ALK-positive advanced NSCLC patients that progressed from previous second-generation ALK-TKI therapy and received lorlatinib treatment subsequently. Patients who received lorlatinib treatment under EAP between Jul 2017 and Sep 2019 were eligible. Patients were followed for at least one year from the first lorlatinib treatment until study completion. Results: Sixty-three patients were eligible for safety analysis (male: 46.0 %; median age: 52.8 [27.5–78.3] years; brain metastases: 81.0 %). Fifty-four patients with more than one-month lorlatinib treatment were included in the effectiveness analysis. Prior to lorlatinib treatment, 10 patients (18.5 %) received one ALK-TKI, 27 (50.0 %) received two ALK-TKIs, and 17 (31.5 %) received three or more ALK-TKIs. The overall median rwPFS was 9.2 months (95 % confidence interval: 5.3–21.1). The best overall response rate (n = 51) was 13.7 %, with a disease control rate of 80.4 %. Conclusion: Lorlatinib exhibits substantial activity and tolerability when used clinically in a later-line setting in a Taiwanese population with ALK-positive advanced NSCLC.

Background/purpose: Endoscopic stenting at malignant distal duodenum stenosis (MDDS) is challenging because of the duodenal C-loop configuration, the acute angle of the duodenojejunal junction, and the limited length of the endoscope. Few studies have investigated the clinical outcomes of stenting at the distal duodenum. Therefore, this study aimed to investigate the clinical outcomes of treating MDDS with different types of metallic stents. Methods: From January 2012 to December 2020, fifty-six patients with MDDS who underwent duodenal stenting were enrolled for analysis. Thirty-five patients received uncovered self-expandable metallic stents (UC-SEMS), and twenty-one patients received partially covered self-expandable metallic stents (PC-SEMS). All patients were followed up till death or for 18 months. The clinical success rate, stent dysfunction rate, and stent patency were compared between the groups. Multivariate analysis was conducted to identify factors related to stent dysfunction. Results: The clinical success rates were 85.7 % in both the UC-SEMS and PC-SEMS groups. Stent dysfunction rates (UC-SEMS: 34.3 %, PC-SEMS: 38.1 %, p = 0.773) and the average stent patency (UC-SEMS: 117.2 days, PC-SEMS: 100.0 days, p = 0.576) were not statistically different between the groups. Multivariate analysis disclosed the age ≥65 years was significantly related to stent dysfunction (odds ratio: 4.78, p = 0.031). Conclusion: Both UC-SEMS and PC-SEMS are safe and effective treatment options for MDDS. However, stent dysfunction remains a significant issue to overcome, particularly in the elderly. Further research is needed to explore novel strategies that can improve the effectiveness of stent placement and reduce the risk of stent dysfunction.

Abstract Background Computed tomography (CT) body compositions reflect age‐related metabolic derangements. We aimed to develop a multi‐outcome deep learning model using CT multi‐level body composition parameters to detect metabolic syndrome (MS), osteoporosis and sarcopenia by identifying metabolic clusters simultaneously. We also investigated the prognostic value of metabolic phenotyping by CT model for long‐term mortality. Methods The derivation set (n = 516; 75% train set, 25% internal test set) was constructed using age‐ and sex‐stratified random sampling from two community‐based cohorts. Data from participants in the individual health assessment programme (n = 380) were used as the external test set 1. Semi‐automatic quantification of body compositions at multiple levels of abdominal CT scans was performed to train a multi‐layer perceptron (MLP)‐based multi‐label classification model. External test set 2 to test the prognostic value of the model output for mortality was built using data from individuals who underwent abdominal CT in a tertiary‐level institution (n = 10 141). Results The mean ages of the derivation and external sets were 62.8 and 59.7 years, respectively, without difference in sex distribution (women 50%) or body mass index (BMI; 23.9 kg/m2). Skeletal muscle density (SMD) and bone density (BD) showed a more linear decrement across age than skeletal muscle area. Alternatively, an increase in visceral fat area (VFA) was observed in both men and women. Hierarchical clustering based on multi‐level CT body composition parameters revealed three distinctive phenotype clusters: normal, MS and osteosarcopenia clusters. The L3 CT‐parameter‐based model, with or without clinical variables (age, sex and BMI), outperformed clinical model predictions of all outcomes (area under the receiver operating characteristic curve: MS, 0.76 vs. 0.55; osteoporosis, 0.90 vs. 0.79; sarcopenia, 0.85 vs. 0.81 in external test set 1; P

Abstract Aims The PIONEER‐HF and PARAGLIDE‐HF trials aimed to determine the efficacy and safety of the in‐hospital initiation of sacubitril/valsartan in patients hospitalized for AHF. However, whether the inclusion and exclusion criteria of the trials apply to patients encountered in real‐world routine care is unclear. This study aimed to investigate the applicability of the PIONEER‐HF and PARAGLIDE‐HF trials to real‐world AHF patients. Methods and results We identified 28 293 AHF hospitalized patients between August 2008 to August 2017 from the Chang Gung Research Database and classified them into four groups based on left ventricular ejection fraction (LVEF) and trial criteria. Cox proportional hazards models were used to compare the risk of HF hospitalization and cardiovascular (CV) death. We defined PIONEER‐HF eligible (n = 3683) and non‐eligible (n = 3502) patients with an LVEF ≤40%, and PARAGLIDE‐HF eligible (n = 5191) and non‐eligible (n = 5832) patients with an LVEF >40%. Over a mean follow‐up of 3.5 years, the PIONEER‐HF non‐eligible and eligible groups exhibited similar rates of HF hospitalization and CV death (41.1% vs. 41.8%, adjusted hazard ratio [aHR]: 0.95; 95% CI: 0.88–1.04). No significant difference was found in the composite outcome between PARAGLIDE‐HF non‐eligible and eligible groups (36.7% vs. 38.6%; aHR: 0.97; 95% CI: 0.90–1.04). Conclusions Using trial criteria, only 31.3% of AHF patients were eligible for sacubitril–valsartan. Yet, non‐eligible patients demonstrated similar outcomes to eligible patients, indicating a need for further evaluation of sacubitril–valsartan benefits in non‐eligible AHF patients.

Abstract Aims Heart failure with reduced ejection fraction (HFrEF) significantly impacts health‐related quality of life (HR‐QoL). Existing HR‐QoL questionnaires can show inconsistencies, potentially misrepresenting patient self‐reports. This study examines the variation in HR‐QoL measurement tools for HFrEF patients, identifying related determinants. Methods and results We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post‐Acute‐Care (HF‐PAC) programme. Participants completed the EuroQol‐5 dimension (EQ‐5D) questionnaire, the EQ‐5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ‐5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR‐QoL measurements and determinants. Average scores for EQ‐5D, MLHFQ, EQ‐5D utility, and VAS were 6.1 ± 1.6, 21.8 ± 21.3, 81.7 ± 27.0, and 59.5 ± 14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ‐5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6 min walk test; EQ‐5D VAS with chronic kidney disease; and MLHFQ with age. Conclusions This study illuminates the variance in HR‐QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient‐centred care. However, for a more precise HR‐QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ‐5D‐derived utility scores might be necessary, emphasizing the importance of patient‐specific considerations within the HF‐PAC programme.

We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.

Parkinson disease (PD) is defined by the loss of dopamine (DA). Changes in the pedunculopontine nucleus (PPN), particularly in local field potential (LFP), can be attributed to deficits in DA and DA receptor expression levels. PPN is a heterogeneous nucleus consisting of cholinergic, γ-aminobutyric acid (GABAergic), and glutamatergic neurons. However, it is unclear whether low levels of DA receptors affect the activity of different PPN neuron types. We record the neuronal activity of PPN by administering the selective dopamine D1 and D2 receptor antagonists, SCH23390 and Raclopride, respectively. This study discover that the firing rates of glutamatergic neurons could be normalized, and their firing patterns were more consistent in lesioned rats treated with raclopride. Raclopride administration could correct the increased coherence and phase locking between glutamatergic spikes and beta-band oscillatory activity in lesioned rats. Raclopride administration correct the increased coherence and phase locking between glutamatergic spikes and beta-band oscillatory activity in lesioned rats.