Cost-effectiveness analysis of cell-based versus egg-based quadrivalent influenza vaccines in the pediatric population in Taiwan.

Cell-based influenza vaccines avoid egg-adaptive mutations, potentially improving vaccine effectiveness. We assessed the one-season cost-effectiveness of cell-based quadrivalent influenza vaccine (QIVc) against that of egg-derived quadrivalent influenza vaccines (QIVe) in children (6 months to 17 years of age) from payer and societal perspectives in Taiwan using an age-stratified static model. Base case and high egg adaptation scenarios were assessed. Deterministic and probabilistic sensitivity analyses were performed. The incremental cost-effectiveness ratio (ICER) threshold in Taiwan was assumed to be USD 99 177/quality-adjusted life year (QALY). Compared to QIVe, QIVc would prevent 15 665 influenza cases, 2244 complicated cases, and 259 hospitalizations per year. The base case ICER was USD 68 298/QALY and USD 40 085/QALY from the payer and societal perspective, respectively. In the high egg adaptation scenario, the ICER was USD 45 782/QALY from the payer's perspective and USD 17 489/QALY from the societal perspective. Deterministic sensitivity analyses indicated that infection incidence rate, vaccination coverage, and prevalence of the A/H3N2 strain were the main drivers of ICER. In conclusion, switching the immunization strategy from QIVe to QIVc is predicted to reduce the influenza-associated disease burden and be cost-effective for the pediatric population in Taiwan. The potential benefits of QIVc would be even higher during influenza seasons with high levels of egg adaptation.

Mucinous cystadenocarcinoma of the breast harbours TRPS1 expressions and PIK3CA alterations.

AIMS: Breast mucinous cystadenocarcinoma (BMCA) is a rare tumour recently recognised as a distinct entity by the World Health Organisation Tumour Classification Series. BMCA is a triple-negative tumour that lacks specific immunohistochemical markers; therefore, distinguishing it from mimickers such as ovarian and pancreatic cystadenocarcinomas requires careful clinicopathological correlation. Due to its rarity, little is known about the molecular alterations that underlie BMCA. METHODS AND RESULTS: In this study, we used immunohistochemical staining methods to investigate TRPS1 (trichorhinophalangeal syndrome type 1) expression in BMCA and compare it to expression in ovarian and pancreatic mucinous cystadenocarcinomas. We also collected tumour samples from three BMCA patients for molecular analysis by MALDI-TOF mass spectrometry, real-time polymerase chain reaction, whole exome sequencing and fluorescence in-situ hybridisation. TRPS1 immunoreactivity was found only in BMCA tumour cells and not in the ovarian and pancreatic counterparts. One of the three BMCA tumours also showed a PIK3CA hot-spot mutation, which was confirmed by whole genome next-generation sequencing (NGS). No KRAS, NRAS, BRAF or AKT mutations were found. CONCLUSIONS: To our knowledge, this is the first demonstration of TRPS1 expression in BMCA patients and the first identification of a PIK3CA hotspot mutation in these tumours. These findings provide insights into the molecular mechanisms underlying BMCA tumorigenesis and suggest a potential drug target for this rare and poorly understood cancer.

Monitoring trends in the absolute lymphocyte count and the neutrophil-to-lymphocyte ratio in patients with breast cancer receiving eribulin.

BACKGROUND: Studies have shown that the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR) are related to the outcomes in patients with breast cancer receiving specific chemotherapies. However, the reports have focussed on the initial blood test and there is a lack of evidence or data to support that dynamic changes of ALC or NLR are associated with the patients' survival outcomes. METHODS: We retrospectively reviewed electronic medical records from patients with breast cancer treated with eribulin from 2015 to 2019 at our institution. Blood test data were available prior to starting eribulin (baseline), and at 1, 3 and 6 months after initiating eribulin. We classified the patients into ALC and NLR high and low groups using the following cut-offs: 1000/µl for ALC and 3 for NLR. We defined ALC and NLR trends as increasing or decreasing compared with the initial data. We assessed the associations between the ALC and NLR with progression-free survival and overall survival. RESULTS: There were 136 patients with breast cancer treated with eribulin. Of these patients, 60 had complete blood tests and follow-up data. Neither a high ALC nor a low baseline NLR was associated with the survival outcome. One month after initiating eribulin treatment, a high ALC and a low NLR were significantly associated with longer progression-free survival (p = 0.044 for each). Three months after initiating eribulin, a high ALC was significantly associated with better overall survival (p = 0.006). A high NLR at 3 or 6 months after initiating eribulin was associated with worse overall survival (p = 0.017 and p = 0.001, respectively). The ALC and NLR trends across times were not associated with survivals. CONCLUSION: We showed that 1, 3 and 6 months after initiating eribulin, a high ALC and a low NLR may be related to the patients' survival outcomes. The ALC and NLR trends were not associated with survival. Accordingly, we believe patients who maintain a high ALC and a low NLR may have better clinical outcomes after initiating eribulin.

Clinical practice consensus for the diagnosis and management of melanoma in Taiwan.

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Mammographic Density Reduction is Associated to the Prognosis in Asian Breast Cancer Patients Receiving Hormone Therapy.

INTRODUCTION: Using mammographic density as a significant biomarker for predicting prognosis in adjuvant hormone therapy patients is controversial due to the conflicting results of recent studies. This study aimed to evaluate hormone therapy-induced mammographic density reduction and its association with prognosis in Taiwanese patients. METHODS: In this retrospective study, 1941 patients with breast cancer were screened, and 399 patients with estrogen receptor-positive breast cancer who received adjuvant hormone therapy were enrolled. The mammographic density was measured using a fully automatic estimation procedure based on full-field digital mammography. The prognosis included relapse and metastasis during treatment follow-up. The Kaplan-Meier method and Cox proportional hazards model were used for disease-free survival analysis. RESULTS: A mammographic density reduction rate >20.8%, measured preoperatively and after receiving hormone therapy from 12-18 months, was a significant threshold for predicting prognosis in patients with breast cancer. The disease-free survival rate was significantly higher in patients whose mammographic density reduction rate was >20.8% (P = .048). CONCLUSION: This study's findings could help estimate the prognosis for patients with breast cancer and may improve the quality of adjuvant hormone therapy after enlarging the study cohort in the future.

Does the Timing of Eribulin Treatment for Advanced or Metastatic Breast Cancer Matter? Evidence from a Real-World Setting.

BACKGROUND: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients. METHODS: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed. RESULTS: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%). CONCLUSIONS: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.

Secreted frizzled-related protein 4 induces gastric cancer progression and resistance to cisplatin and oxaliplatin via ß-catenin dysregulation.

INTRODUCTION: Gastric cancer is the 5th most common cancer and 3rd leading cause of cancer-related death worldwide. There are three main ways to treat gastric cancer: surgical resection, radiation therapy, and drug therapy. Furthermore, combinations of two to three regimens can improve survival. However, the survival outcomes of chemotherapy in advanced gastric cancer patients are still unsatisfactory. Unfortunately, no widely useful biomarkers have been verified to predict the efficacy of chemotherapy for locally advanced gastric cancer. METHODS: An MTT assay was used to determine the cell viability after cisplatin or oxaliplatin treatment. Western blotting and immunohistochemistry were utilized to examine the sFRP4 level and associated signaling pathways. Immunofluorescence staining was utilized to analyze the location of ß-catenin. Colony formation and Transwell assays were used to analyze the functions related with cisplatin, oxaliplatin and sFRP4. RESULTS: We have found that gastric cancer patients treated with combinations of 5-fluorouracil (5-FU) and cisplatin regimens have better survival rates than those treated with 5-FU-based chemotherapy alone. Secreted frizzled-related protein 4 (sFRP4) was selected as a potential target from stringent analysis and intersection of 5-FU and cisplatin resistance-related gene sets. sFRP4 was shown to be overexpressed in clinical gastric tumor tissues and positively correlated with a worse survival rate. In addition, sFRP4 and ß-catenin were upregulated in cisplatin-resistant and oxaliplatin-resistant gastric cancer cells compared to parental cells. Immunofluorescence staining and nuclear fractionation showed that ß-catenin translocated from the cytosol into the nucleus. Moreover, sFRP4 was detected in the conditioned medium of these resistant cells, which indicates that sFRP4 might have an extracellular role in chemotherapy resistance. Increased migration capacity and dysregulation of epithelial-mesenchymal transition-related markers, which might result from the dysregulation of sFRP4, were observed in cisplatin-resistant and oxaliplatin-resistant gastric cancer cells. DISCUSSION/CONCLUSION: In summary, sFRP4 might play a critical role in resistance to cisplatin and oxaliplatin, cell metastasis and poor prognosis in gastric cancer via the Wnt-ß-catenin pathway. Investigations of the molecular mechanism underlying sFRP4-modulated cancer progression and chemotherapeutic outcomes can provide additional therapeutic strategies for gastric cancer.

Dataset for pathology reporting of ductal carcinoma in situ, variants of lobular carcinoma in situ and low-grade lesions: recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: To describe a new international dataset for pathology reporting of ductal carcinoma in situ (DCIS), variants of lobular carcinoma in situ (LCIS) and low-grade lesions (encapsulated papillary carcinoma, solid papillary carcinoma in situ, Paget's disease) produced by the International Collaboration on Cancer Reporting (ICCR). METHODS AND RESULTS: The ICCR, a global alliance of pathology bodies, uses a rigorous and efficient process for the development of evidence-based, structured datasets for pathology reporting of common cancers. Their aim is to support quality pathology reporting and engender understanding between the breast surgeon, pathologist, and oncologist for optimal and uniform patient management globally. Here we describe the dataset for DCIS, some variants of LCIS (namely the pleomorphic and the florid variants), and low-grade lesions by a multidisciplinary panel of internationally recognized experts. The agreed dataset comprises 12 core (required) and five noncore (recommended) elements suitable for both developed and low-income jurisdictions, derived from a review of current evidence. Areas of contention were addressed using a pragmatic approach in the absence of evidence. Use of all core elements is the minimum reporting standard for any individual case. Commentary is provided, explaining each element's clinical relevance, definitions to be applied where appropriate for the agreed list of value options and the rationale for considering the element as core or noncore. CONCLUSION: This first internationally agreed dataset for DCIS, variants of LCIS, and low-grade lesions reporting will enable their standardization of pathology reporting and enhance clinicopathological communication leading to improved patient outcomes. Widespread adoption will also facilitate international comparisons, multinational clinical trials, and help to improve the management of breast disease globally.

A para-aortic malignant melanotic nerve sheath tumor mimicking a gastrointestinal stromal tumor: a rare case report and review of literature.

BACKGROUND: Malignant melanotic nerve sheath tumor (MMNST), formerly called melanotic schwannoma, is a rare tumor of neural crest derivation which most frequently arises from the region of spinal or autonomic nerves near the midline. Recent studies have reported malignant behavior of MMNST, and there still has no standard management guidelines. Intra-abdominal MMNST, which has never been reviewed as an entity, is even rarer. In this study, we present a rare case of a cystic MMNST arising from the para-aortic region and mimicking an intra-abdominal gastrointestinal stromal tumor (GIST), and review the literature regarding MMNSTs located in the abdominal cavity. CASE PRESENTATION: A 59-year-old female was incidentally found a tumor located in the left para-aortic area by non-contrast computed tomography. A Magnetic Resonance Imaging showed a cystic mass originated from the inferior mesenteric artery (IMA) territory. A GIST was initially diagnosed. The tumor was resected en bloc by laparoscopic surgery and was found between mesocolon and Gerota's fascia with blood supply of IMA. Grossly, dark brown materials were noted at the inner surface of the cystic wall. Microscopically, the tumor cells were melanin-containing, and no psammomatous bodies were present. Immunohistochemically, the tumor showed positivity for MART1, HMB45, collagen IV, and SOX10, and negativity for AE1/AE3. MMNST was favored over malignant melanoma, since the tumor was located near ganglia and had cells with less atypical cytology and a low mitotic rate, and subsequent adjuvant radiotherapy was performed. The patient was alive with no evidence of recurrent or metastatic disease 11 months after radiotherapy. CONCLUSIONS: Our review of abdominal MMNST cases showed a female predominance, with an average age of 54.8 years, and a trend toward being a larger tumor showing cystic or necrotic changes. Local recurrence and metastasis rate were reviewed, and both showed a low rate. Diagnosis of MMNST should combine all the available findings, and complete excision of the tumor should be performed, followed by long-term patient monitoring.

Galangin Reverses H2O2-Induced Dermal Fibroblast Senescence via SIRT1-PGC-1α/Nrf2 Signaling.

UV radiation and H2O2 are the primary factors that cause skin aging. Both trigger oxidative stress and cellular aging. It has been reported that deacetylase silent information regulator 1 (SIRT1), a longevity gene, enhances activation of NF-E2-related factor-2 (Nrf2), as well as its downstream key antioxidant gene hemeoxygenase-1 (HO-1), to protect cells against oxidative damage by deacetylating the transcription coactivator PPARγ coactivator-1α (PGC-1α). Galangin, a flavonoid, possesses anti-oxidative and anti-inflammatory potential. In the present study, we applied Ultraviolet B/H2O2-induced human dermal fibroblast damage as an in vitro model and UVB-induced photoaging of C57BL/6J nude mice as an in vivo model to investigate the underlying dermo-protective mechanisms of galangin. Our results indicated that galangin treatment attenuates H2O2/UVB-induced cell viability reduction, dermal aging, and SIRT1/PGC-1α/Nrf2 signaling activation. Furthermore, galangin treatment enhanced Nrf2 activation and nuclear accumulation, in addition to inhibiting Nrf2 degradation. Interestingly, upregulation of antioxidant response element luciferase activity following galangin treatment indicated the transcriptional activation of Nrf2. However, knockdown of SIRT1, PGC-1α, or Nrf2 by siRNA reversed the antioxidant and anti-aging effects of galangin. In vivo evidence further showed that galangin treatment, at doses of 12 and 24 mg/kg on the dorsal skin cells of nude mice resulted in considerably reduced UVB-induced epidermal hyperplasia and skin senescence, and promoted SIRT1/PGC-1α/Nrf2 signaling. Furthermore, enhanced nuclear localization of Nrf2 was observed in galangin-treated mice following UVB irradiation. In conclusion, our data indicated that galangin exerts anti-photoaging and antioxidant effects by promoting SIRT1/PGC-1α/Nrf2 signaling. Therefore, galangin is a potentially promising agent for cosmetic skin care products against UV-induced skin aging.

In Silico Prediction and Validation of CB2 Allosteric Binding Sites to Aid the Design of Allosteric Modulators.

Although the 3D structures of active and inactive cannabinoid receptors type 2 (CB2) are available, neither the X-ray crystal nor the cryo-EM structure of CB2-orthosteric ligand-modulator has been resolved, prohibiting the drug discovery and development of CB2 allosteric modulators (AMs). In the present work, we mainly focused on investigating the potential allosteric binding site(s) of CB2. We applied different algorithms or tools to predict the potential allosteric binding sites of CB2 with the existing agonists. Seven potential allosteric sites can be observed for either CB2-CP55940 or CB2-WIN 55,212-2 complex, among which sites B, C, G and K are supported by the reported 3D structures of Class A GPCRs coupled with AMs. Applying our novel algorithm toolset-MCCS, we docked three known AMs of CB2 including Ec2la (C-2), trans-ß-caryophyllene (TBC) and cannabidiol (CBD) to each site for further comparisons and quantified the potential binding residues in each allosteric binding site. Sequentially, we selected the most promising binding pose of C-2 in five allosteric sites to conduct the molecular dynamics (MD) simulations. Based on the results of docking studies and MD simulations, we suggest that site H is the most promising allosteric binding site. We plan to conduct bio-assay validations in the future.

The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling.

Background and Objectives: PNU-74654, a Wnt/ß-catenin inhibitor, has reported antitumor activities; however, the therapeutic potential of PNU-74654 in hepatocellular carcinoma (HCC) has not been investigated in detail. The aim of this study was to clarify the cytotoxic effects of PNU-74654 against HCC and to uncover its molecular mechanism. Materials and Methods: HepG2 and Huh7 liver cancer cell lines were selected to determine the antitumor properties of PNU-74654. Survival of the liver cancer cells in response to PNU-74654 was assessed by cell viability assays, and the apoptosis effect of PNU-74654 was analyzed by flow cytometry and visualized by Hoechst staining. An oncology array was used to explore the underlying molecular routes of PNU-74654 action in the cells. The migration properties were examined with a wound healing assay, and western blotting was conducted to evaluate protein expression. Results: Treatment with PNU-74654 decreased cell viability and inhibited cell migration. The cell cycle analysis and Hoechst staining revealed an increase in the population of cells at the sub-G1 stage and apoptotic morphological changes in the nucleus. The oncology array identified 84 oncology-related proteins and a suppressed expression of Bcl-xL and survivin. Western blotting showed that PNU-74654 could interfere with cell cycle-related proteins through the NF-κB pathway. Conclusions: PNU-74654 shows antiproliferative and antimigration effects against HepG2 and Huh7 cells, and its antitumor activity may be attributable to its interference in cell cycle regulation and the NF-κB pathway.

Combination treatment of Src inhibitor Saracatinib with GMI, a Ganoderma microsporum immunomodulatory protein, induce synthetic lethality via autophagy and apoptosis in lung cancer cells.

Saracatinib is an oral Src-kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed-resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase-7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B-II in A400 cells. ATG5 silencing abolished the caspase-7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.

Distinguishing lupus lymphadenitis from Kikuchi disease based on clinicopathological features and C4d immunohistochemistry.

OBJECTIVES: Distinguishing Kikuchi disease (KD) from lupus lymphadenitis (LL) histologically is nearly impossible. We applied C4d immunohistochemical (IHC) stain to develop diagnostic tools. METHODS: We retrospectively investigated clinicopathological features and C4d IHC staining in an LL-enriched development cohort (19 LL and 81 KD specimens), proposed risk stratification criteria and trained machine learning models, and validated them in an external cohort (2 LL and 55 KD specimens). RESULTS: Clinically, we observed that LL was associated with an older average age (33 vs 25 years; P=0.005), higher proportion of biopsy sites other than the neck [4/19 (21%) vs 1/81 (1%); P=0.004], and higher proportion of generalized lymphadenopathy compared with KD [9/16 (56%) vs 7/31 (23%); P=0.028]. Histologically, LL involved a larger tissue area than KD did (P=0.006). LL specimens exhibited more frequent interfollicular pattern [5/19 (26%) vs 3/81 (4%); P=0.001] and plasma cell infiltrates (P=0.002), and less frequent histiocytic infiltrates in the necrotic area (P=0.030). Xanthomatous infiltrates were noted in 6/19 (32%) LL specimens. Immunohistochemically, C4d endothelial staining in the necrotic area [11/17 (65%) vs 2/62 (3%); P<10-7], and capillaries/venules [5/19 (26%) vs 7/81 (9%); P=0.048] and trabecular/hilar vessels [11/18 (61%) vs 8/81 (10%); P<10-4] in the viable area was more common in LL. During validation, both the risk stratification criteria and machine learning models were superior to conventional histological criteria. CONCLUSIONS: Integrating clinicopathological and C4d findings could distinguish LL from KD.

Retrospective Seroepidemiology study of dengue virus infection in Taiwan.

BACKGROUND: Dengue virus infection has been an important and serious public health concern in Taiwan, where local outbreaks of dengue fever occurred almost every year. To our knowledge, no nationwide investigation has been carried out to determine the actual extent of infection in the general population. METHODS: A total of 1308 random serum samples were collected from the general population in Taiwan in 2010. The antibody-captured enzyme-linked immunosorbent assays were used to detect DENV-specific IgM and IgG. Demographics data were used for risk analysis. RESULTS: The weighted overall seroprevalence was 1.96% for anti-DENV IgM, and 3.4% for anti-DENV IgG, respectively. A significant rise of DENV IgG seropositive rate had been noted since late adulthood stage, from 1.1% at the age group of 50-59 years to 7.6% at the age group of 60-69 years. For people aged over 70 years, the seropositive rate reached 19%. Age, nationality, and regions of residency were associated with the IgG seropositivity. There was no statistically significant difference in seroprevalence of anti-Dengue IgM, indicating recent infection, among univariate predictors we proposed, including gender, age, residency, nationality, and household size. CONCLUSIONS: Our results indicated that the majority of population in Taiwan born after 1940 is naive to dengue virus and the prevalence of IgG antibody against dengue virus rises with age. Nationality, and regions of residency are associated with the exposure of population to infection by dengue viruses. Further studies are needed to realize the current situation of seroprevalence of dengue fever in Taiwan.

Cutaneous Pseudolymphoma With Langerhans Cell Hyperplasia-A Rare Case With Clinical Presentation Mimicking Malignancy and Potential Diagnostic Pitfall.

ABSTRACT: We describe a rare case of cutaneous pseudolymphoma with Langerhans cell hyperplasia. An 84-year-old female patient presented with erythematous and pernicious-looking plaques on her scalp that had been present for months. Histologically, lymphoid follicles consisting of mixed-type lymphocytes and Langerhans cells were aggregated focally. The diagnosis was verified by several immunohistochemical stains and by clinical evaluation. Skin lesions were steadily resolved with low-dose corticosteroid and hydroxychloroquine.

Calcifying fibrous tumour: An IgG4-related disease or not?

Calcifying fibrous tumour (CFT) has some of the histopathological features, such as abundant plasma cells and stromal fibrosis, that are exhibited by IgG4-related diseases (IgG4-RD). The possible role of IgG4-positive plasma cells in calcifying fibrous tumour was investigated. The aim of this study was to determine any potential relationship between IgG4-RD and CFT. Thirteen cases with a total of 16 CFTs were reviewed. Lesion samples were immunostained with anti-IgG4 and anti-IgG antibodies. The number of IgG4-positive and IgG-positive plasma cells (IgG + PC) and their ratios were estimated. Plasma cells were found in all tumours. IgG4-positive plasma cells ranged from 0 to 71 per high-power field (HPF; mean 17.8/HPF), and IgG + PC ranged from 2 to 93/HPF (mean 42.6/HPF). The IgG4/IgG ratio ranged from 0% to 80% (mean 29%). There were seven tumours with the ratio of IgG4/IgG + PC that exceeded 40%. Various degrees of stromal fibrosis were present in eight tumours. All tumours have variable calcification. The histopathological features of CFT were found to be similar to those of IgG4-RD. Some CFT also showed a high number of IgG4-positive plasma cells, and the ratio of IgG4/IgG + PC exceeded 40%, most notably in patients with concomitant inflammatory or autoimmune disease. The long-term follow-up showed no evidence of IgG4-RD in any of these patients. Our findings suggest that while CFT overlaps morphologically with IgG4-RD, it probably should not be classified as an IgG4-RD.

Detection and phylogeny of Staphylococcus aureus sequence type 398 in Taiwan.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) ST398 is a livestock associated-bacterium that is most prevalent in Europe. Human-adapted MRSA ST398 was recently reported from China, but there is no data available yet for Taiwan. METHODS: To identify S. aureus ST398 isolates, we examined 6413 S. aureus isolates (5632 MRSA and 781 susceptible strains) that were collected in Taiwan between 1995 and 2017. If isolates could not be typed by pulsed-field gel electrophoresis upon Sma I digestion, we performed further characterization and complete genome sequencing. RESULTS: We identified 18 ST398 S. aureus isolates from 16 subjects (0.28%), including 6 sensitive and 12 resistant strains. Of these, 14 were colonizing isolates, 3 were clinical (infecting) isolates and one isolate was from a pork specimen. All 3 infecting isolates were MSSA strains identified in 2015 from two children with recurrent otitis media or sinusitis. The other 3 MSSA isolates were identified from workers handling pork (2) or pork meat (1) in 2015. The first 5 MRSA colonizing isolates were identified from residents in two nursing homes in 2012. Six MRSA isolates were identified from residents and foreign employees at a nursing home in 2016 and one MRSA from a foreign worker in 2017. Phylogenetic analysis of genome sequences indicated that all 12 local ST398 MRSA strains cluster together, human-adapted and phylogenetically related to a human MRSA strain identified in China in 2002. Two local MSSA isolates could be linked to isolates from livestock. The toxin profiles were similar for the MRSA and MSSA isolates. CONCLUSIONS: Our results demonstrate that S. aureus ST398 was present in Taiwan in 2012 and potentially earlier. Although some isolates could be linked to livestock, most ST398 S. aureus isolates identified in Taiwan, particularly MRSA, represent human-adapted strains. Local transmission of human-adapted MRSA ST398 strains has occurred in nursing homes in Taiwan, possibly after import from China. Further surveillance is needed.

Plasmonic hot electrons for sensing, photodetection, and solar energy applications: A perspective.

In plasmonic metals, surface plasmon resonance decays and generates hot electrons and hot holes through non-radiative Landau damping. These hot carriers are highly energetic, which can be modulated by the plasmonic material, size, shape, and surrounding dielectric medium. A plasmonic metal nanostructure, which can absorb incident light in an extended spectral range and transfer the absorbed light energy to adjacent molecules or semiconductors, functions as a "plasmonic photosensitizer." This article deals with the generation, emission, transfer, and energetics of plasmonic hot carriers. It also describes the mechanisms of hot electron transfer from the plasmonic metal to the surface adsorbates or to the adjacent semiconductors. In addition, this article highlights the applications of plasmonic hot electrons in photodetectors, photocatalysts, photoelectrochemical cells, photovoltaics, biosensors, and chemical sensors. It discusses the applications and the design principles of plasmonic materials and devices.

Protective effects of galangin against H2 O2 -induced aging via the IGF-1 signaling pathway in human dermal fibroblasts.

Galangin, a natural flavonol, has anti-inflammatory and antioxidative potential. However, the cytoprotective effects of galangin against oxidative-induced aging in human fibroblasts have not been well studied. IGF-1 signaling pathway is associated with the control of aging and longevity in human. The goal of this study was to investigate the effects of galangin on human skin fibroblast HS68 cells under H2 O2 exposure to induce aging. In this study, we demonstrate that galangin could decrease the levels of pro-inflammatory proteins and enhanced collagen formation through promoting the IGF-1R pathway. Furthermore, aging markers such as senescence-associated ß-galactosidase p53, p21Cip1/WAF1 , and p16INK4A were upregulated under H2 O2 exposure and galangin could reverse its effects. Taken together, these data indicated that anti-inflammatory and antiaging activities of galangin may be mediated through the IGF-1R signaling pathway. These findings may provide the evidence for galangin to develop as an antiwrinkle product on human skin.