A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key ...immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (S
) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from S
-immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.
Plate-related complications are major long-term complications in mandible reconstruction. There are controversies regarding the use of a reconstruction plate versus miniplates and a bone flap versus ...a soft tissue flap with a bridging plate. Direct comparisons of a fibula flap and an anterolateral thigh flap, the applicability between a reconstruction plate and miniplate, and the correlation between plate-related complications and quality of life remain unclarified. Therefore, this study aimed to the explore complications of different flaps and plates and how they impact the patients' quality of life.
We retrospectively reviewed the medical records of a total of 205 patients aged >18 years who underwent segmental mandibulectomy and reconstruction using fibula flap with reconstruction plate (FR; n = 86), fibula flap with miniplate (FM; n = 61), and anterolateral thigh flap with reconstruction plate (AR; n = 58) due to cancer ablation, osteoradionecrosis, or benign tumor excision between August 2010 and December 2019. Data on characteristics, complications, and health-related quality of life were collected and analyzed.
The plate-related complication rate was the highest in the AR group (37.9%), then in the FR group (25.6%), and was the lowest in the FM group (13.1%; p = 0.0079). The plate exposure rate was the highest in the AR group (24.1%), then in the FR group (15.7%), and was the lowest in the FM group (4.9%; p = 0.0128). The plate fracture and dislodge rates for the AR group were both higher than those for the FR and FM groups (24.1% versus 9.3% versus 9.8%, respectively; p = 0.023). The AR group had worse complication-free survival (hazard ratio HR: 3.61, 95% CI: 1.99-6.56, and p < 0.0001) than the FR and FM groups. Osteoradionecrosis (HR: 6.19, 95% CI: 2.11-18.21, and p = 0.0009) and postoperative radiotherapy (HR: 2.87, 95% CI: 1.34-6.12, and p = 0.0402) were both independent adverse factors for complication-free survival, whereas patient treated primarily (HR: 0.35, 95% CI: 0.17-0.73, and p = 0.0048) was an independent protective factor. Plate-related complication negatively impacted the quality of life based on pain scores (β: -0.56, SE: 0.26, and p = 0.034).
Using a fibular flap fixed with miniplates and avoiding the use of a reconstruction plate may yield a reduced plate exposure rate and better health-related quality of life, particularly for patients with osteoradionecrosis or those who need postoperative radiotherapy.
Background
Basal cell carcinoma (BCC), the most common skin cancer in humans, requires early detection. Dermoscopy enhances diagnostic accuracy through a noninvasive approach. Pigmented BCC (pBCC) is ...characterized by distinctive dermoscopic features, including the presence of pigmented globules or nests. While dermoscopic features of large pBCC (size >6 mm) have been extensively studied, limited data are available on small pBCC (size ≤6 mm) and its relationship with tumor progression.
Methods
Dermoscopic images of histologically proven pBCCs were collected between 2014 and 2022 at Hualien Tzu Chi Hospital. Each image was analyzed for patterns of pigmentation, vasculature, and epidermal and dermal structures. Statistical analysis was performed to compare the differences according to the size and the trend during tumor progression.
Results
In total, 135 pBCCs (48 small and 87 large) were included. Pigment structures were present in all cases. Short fine telangiectasia and small erosions constituted over 85% of the cases, showing no significant distinction between small and large pBCCs, nor any specific pattern correlating with tumor enlargement. The number of arborizing vessels, ulcerations, and shiny white structures showed an increasing trend associated with size progression. Arborizing vessels appeared when tumor size exceeded 6 mm.
Conclusions
This study provides a dynamic interpretation of the dermoscopic features of pBCC according to size enlargement. Short fine telangiectasia and small erosions are highly important features for the early diagnosis of small pBCCs. Arborizing vessels, ulceration, and shiny white structures are more frequent in large pBCCs, and they increase in association with tumor progression.
We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and ...hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti‐HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 μm in diameter PM2.5, nitrogen dioxide NO2, ozone O3 and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio OR, 3.13; 95% confidence interval CI, 2.05–4.77; p < 0.001), smoking (OR, 1.79; 95% CI, 1.16–2.74; p = 0.01), age (OR, 1.04; 95% CI, 1.02–1.05; p < 0.001) and PM2.5 (OR, 1.10; 95% CI, 1.05–1.16; p < 0.001). Linear regression analysis revealed that LSM was independently correlated with PM2.5 (β: 0.134; 95% CI: 0.025, 0.243; p = 0.02). There was a dose‐dependent relationship between different fibrotic stages and the PM2.5 level (the PM2.5 level in patients with fibrotic stages 0, 1–2 and 3–4: 27.9, 28.4, and 29.3 μg/m3, respectively; trend p < 0.001). Exposure to PM2.5, as well as HBV and HCV infections, is associated with advanced liver fibrosis in patients with MAFLD. There was a dose‐dependent correlation between PM2.5 levels and the severity of hepatic fibrosis.
Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing ...guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.
Objective: To investigate the maternal−neonatal outcomes of obstetric deliveries performed in negative pressure isolated delivery rooms (NPIDRs) during the coronavirus disease 2019 (COVID-19) omicron ...variant pandemic period in a single tertiary center in northern Taiwan. Methods: Confirmed positive and suspected-positive COVID-19 cases delivered in NPIDRs and COVID-19-negative mothers delivered in conventional delivery rooms (CDRs) in the period of 1 May 2022 to 31 May 2022 during the COVID-19 omicron variant pandemic stage were reviewed. The maternal−neonatal outcomes between the two groups of mothers were analyzed. All deliveries were performed following the obstetric and neonatologic protocols conforming to the epidemic prevention regulations promulgated by the Taiwan Centers for Disease Control (T-CDC). Multiple gestations, deliveries at gestational age below 34 weeks, and major fetal anomalies were excluded from this study. Results: A total of 213 obstetric deliveries were included. Forty-five deliveries were performed in NPIDRs due to a positive COVID-19 polymerase chain reaction (PCR) test (n = 41) or suspected COVID-19 positive status (n = 4). One hundred and sixty-eight deliveries with negative COVID-19 PCR tests were performed in CDRs. There was no statistical difference in maternal characteristics between the two groups of pregnant women. All COVID-19-confirmed cases either presented with mild upper-airway symptoms (78%) or were asymptomatic (22%); none of these cases developed severe acute respiratory syndrome. The total rate of cesarean section was not statistically different between obstetric deliveries in NPIDRs and in CDRs (38.1% vs. 40.0%, p = 0.82, respectively). Regardless of delivery modes, poorer short-term perinatal outcomes were observed in obstetric deliveries in NPIDRs: there were significant higher rates of neonatal respiratory distress (37.8% vs. 10.7%, p < 0.001, respectively), meconium-stained amniotic fluid (22.2% vs. 4.2%, p < 0.001, respectively) and newborn intensive care unit admission (55.6% vs. 8.3%, p < 0.001, respectively) in obstetric deliveries performed in NPIDRs than in CDRs. Maternal surgical outcomes were not significantly different between the two groups of patients. There was no vertical transmission or nosocomial infection observed in COVID-19 confirmed cases in this study period. Conclusions: Our study demonstrates that obstetric deliveries for positive and suspected COVID-19 omicron-variant cases performed in NPIDRs are associated with poorer short-term perinatal outcomes. Reasonable use of personal protective equipment in NPIDRs could effectively prevent nosocomial infection during obstetric deliveries for pregnant women infected with the COVID-19 omicron variant.
Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial ...morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO) cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology.
Temozolomide (TMZ)-induced side effects and drug tolerance to human gliomas are still challenging issues now. Our previous studies showed that honokiol, a major bioactive constituent of Magnolia ...officinalis (Houpo), is safe for normal brain cells and can kill human glioma cells. This study was further aimed to evaluate the improved effects of honokiol and TMZ on drug-sensitive and -resistant glioma cells and the possible mechanisms.
TMZ-sensitive human U87-MG and murine GL261 glioma cells and TMZ-resistant human U87-MR-R9 glioma cells were exposed to honokiol and TMZ, and cell viability and LC50 of honokiol were assayed. To determine the death mechanisms, caspase-3 activity, DNA fragmentation, apoptotic cells, necrotic cells, cell cycle, and autophagic cells. The glioma cells were pretreated with 3-methyladenine (3-MA) and chloroquine (CLQ), two inhibitors of autophagy, and then exposed to honokiol or TMZ.
Exposure of human U87-MG glioma cells to honokiol caused cell death and significantly enhanced TMZ-induced insults. As to the mechanism, combined treatment of human U87-MG cells with honokiol and TMZ induced greater caspase-3 activation, DNA fragmentation, cell apoptosis, and cell-cycle arrest at the G
phase but did not affect cell necrosis. The improved effects of honokiol on TMZ-induced cell insults were further verified in mouse GL261 glioma cells. Moreover, exposure of drug-tolerant human U87-MG-R9 cells to honokiol induced autophagy and consequent apoptosis. Pretreatments with 3-MA and CLQ caused significant attenuations in honokiol- and TMZ-induced cell autophagy and apoptosis in human TMZ-sensitive and -tolerant glioma cells.
Taken together, this study demonstrated the improved effects of honokiol with TMZ on autophagy and subsequent apoptosis of drug-sensitive and -tolerant glioma cells. Thus, honokiol has the potential to be a drug candidate for treating human gliomas.
Background
Pangenotypic direct‐acting antiviral agents (DAAs) glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL) are effective against all hepatitis C virus (HCV) genotype ...infections. However, data on pangenotypic DAA treatment for mixed genotype HCV infection are sparse.
Methods
This is a retrospective, single site cohort study analyzing all patients with mixed HCV genotype infections treated with GLE/PIB or SOF/VEL from August 2018 to August 2020 in Chiayi Chang Gung Memorial Hospital, Taiwan. The primary study endpoint was sustained virologic response (SVR) 12 weeks after treatment cessation. We also reported adverse events (AEs).
Results
A total of 108 patients with mixed infections of any two or three genotypes of 1a, 1b, 2, 3, and 6 received pangenotypic DAAs during the study period. A total of 67 patients received GLE/PIB and 41 received SOF/VEL. The evaluable population analysis revealed SVR rates of 94% (63/67) and 95.1% (39/41) for GLE/PIB and SOF/VEL therapy, respectively, and the per‐protocol analysis revealed an SVR of 100% for both regimens. Four patients in the GLE/PIB group and two patients in the SOF/VEL were lost to follow‐up. The most common AEs for GLE/PIB versus SOF/VEL therapy included pruritus (14.9% vs 2.4%), fatigue (6.0% vs 7.3%), abdominal discomfort (4.5% vs 7.3%), and acid reflux (3.0% vs 4.9%). DAA‐related significant laboratory abnormalities occurred in three patients with > 1.5 × elevated bilirubin level in the GLE/PIB group. None of the above AEs resulted in DAA discontinuation.
Conclusions
Pangenotypic DAAs are well tolerated by and yield high SVR rates in patients with mixed genotype HCV infection.
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