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Abstract 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.

Background: A surge of encephalitis was reported in children during the early wave of the omicron epidemic in Taiwan. Information on the COVID-19-associated encephalitis, including epidemiologic features and factors of unfavorable outcomes, remained unclear. Methods: A total of 128 hospitalized Taiwanese children with laboratory-confirmed COVID-19 were enrolled between April 01, 2022, and May 31, 2022. The information on demographics and clinical features was abstracted from the medical records. Virologic lineages were determined by sequences of the spike protein. Factors associated with encephalitis and unfavorable outcomes were identified by comparisons to children without encephalitis and with favorable outcomes, respectively. Results: The leading syndromes associated with COVID-19 in hospitalized children were febrile seizure (20, 15.7%), fever as the solitary symptom (18, 14.1%), and croup syndrome (14, 10.9%). Encephalitis was diagnosed in nine (7.03%) children. When compared to the three leading syndromes, children with encephalitis were at older ages, had greater rates of hypotension, PICU admissions, use of inotropic agents (P

Key Clinical Message Invasive cribriform carcinoma (ICC) is a rare form of invasive breast carcinoma with good prognosis. To date, case reports considering skin manifestations of ICC are scarce. We herein report a case of pure ICC presenting as an erythematous papule on the nipple with mammary Paget's disease in the epidermis. We aim to bring awareness to skin manifestation of ICC.

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.

Background/Objectives: This study aimed to assess the reactogenicity and immunogenicity of various SARS-CoV-2 vaccines and compare their protective effects against COVID-19 among healthcare workers (HCWs) during the Omicron outbreak in Taiwan. Methods: Conducted from March 2021 to July 2023, this prospective observational study included healthy HCWs without prior COVID-19 immunization. Participants chose between adenovirus-vectored (AstraZeneca), mRNA (Moderna, BioNTech-Pfizer), and protein-based (Medigen, Novavax) vaccines. Blood samples were taken at multiple points to measure neutralizing antibody (nAb) titers, and adverse events (AEs) were recorded via questionnaires. Results: Of 710 HCWs, 668 (94.1%) completed three doses, and 290 (40.8%) received a fourth dose during the Omicron outbreak. AEs were more common with AstraZeneca and Moderna vaccines, while Medigen caused fewer AEs. Initial nAb titers were highest with Moderna but waned over time regardless of the vaccine. Booster doses significantly increased nAb titers, with the highest levels observed in Moderna BA1 recipients. The fourth dose significantly reduced COVID-19 incidence, with Moderna BA1 being the most effective. Conclusions: Regular booster doses, especially with mRNA and adjuvant-protein vaccines, effectively enhance nAb levels and reduce infection rates, providing critical protection for frontline HCWs during variant outbreaks.

Abstract This study proposes a method to extract the signature bands from the deep learning models of multispectral data converted from the hyperspectral data. The signature bands with two deep-learning models were further used to predict the sugar content of the Syzygium samarangense. Firstly, the hyperspectral data with the bandwidths lower than 2.5 nm were converted to the spectral data with multiple bandwidths higher than 2.5 nm to simulate the multispectral data. The convolution neural network (CNN) and the feedforward neural network (FNN) used these spectral data to predict the sugar content of the Syzygium samarangense and obtained the lowest mean absolute error (MAE) of 0.400° Brix and 0.408° Brix, respectively. Secondly, the absolute mean of the integrated gradient method was used to extract multiple signature bands from the CNN and FNN models for sugariness prediction. A total of thirty sets of six signature bands were selected from the CNN and FNN models, which were trained by using the spectral data with five bandwidths in the visible (VIS), visible to near-infrared (VISNIR), and visible to short-waved infrared (VISWIR) wavelengths ranging from 400 to 700 nm, 400 to 1000 nm, and 400 to 1700 nm. Lastly, these signature-band data were used to train the CNN and FNN models for sugar content prediction. The FNN model using VISWIR signature bands with a bandwidth of ± 12.5 nm had a minimum MAE of 0.390°Brix compared to the others. The CNN model using VISWIR signature bands with a bandwidth of ± 10 nm had the lowest MAE of 0.549° Brix compared to the other CNN models. The MAEs of the models with only six spectral bands were even better than those with tens or hundreds of spectral bands. These results reveal that six signature bands have the potential to be used in a small and compact multispectral device to predict the sugar content of the Syzygium samarangense.

Background/Purpose: Precise detection of respiratory pathogens by molecular method potentially may shorten the time to diagnose and reduce unnecessary antibiotic use. Methods: Medical records of hospitalized children from January 2020 to June 2021 with acute respiratory illness who received a FilmArray RP for respiratory pathogens were reviewed and compared with data from diagnosis-matched patients without receiving the test. Results: In total, 283 patients and 150 diagnosis-matched controls were included. Single pathogen was detected in 84.3% (193/229) of the patients. The most common pathogen was human rhinovirus/enterovirus (31.6%, 84/266), followed by respiratory syncytial virus (18.8%, 50/266) and adenovirus (15%, 40/266). Although antimicrobial days of therapy (DOT) was significantly longer in FilmArray group than the control [7.1 ± 4.9 days vs 5.7 ± 2.7 days, P = 0.002], the former showed a higher intensive care unit (ICU) admission rate (3.9% vs 0%; P = 0.010). All ICU admissions were in FilmArray RP-positive group. There was no difference in antimicrobial DOT between FilmArray RP-positive and the negative groups, in all admissions, even after excluding ICU admissions. Antimicrobial DOT was shorter in the positive than negative group in patients with lower respiratory tract infections without admission to ICU [median (IQR): 6 (4–9) days vs 9 (4–12) days, P = 0.047]. Conclusions: Shorter antimicrobial DOTs were identified in children with lower respiratory tract infection admitted to general pediatric ward and with an identifiable respiratory pathogen, indicating a role of the multiplex PCR in reducing antimicrobial use for children with respiratory tract infection.

Background: Secondary vaccine failure was the principal mechanic of measles reemergence in countries with high measles vaccine coverage. The information on neutralizing antibody (nAb) prevalence, epidemiological factors of waned immunity and immune response after reimmunization was essential to measles control but largely lacking in Taiwan. Methods: The nAb and factors of wanned immunity to measles were evaluated in a cohort of 333 subjects aged 11–30 years in 2010. The longitudinal immune response to reimmunization (n = 30) and potential virus exposure (n = 24) were assessed in young healthcare workers (HCWs) during a hospital outbreak. The nAb titer was used to define susceptibility to measles disease (

Invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) diseases caused by clonal complex 398 MRSA without animal contact have become a new emerging threat. We report a case of bacteremic mediastinitis caused by a Panton-Valentine leukocidin-positive community-associated sequence type 1232 MRSA in a Taiwanese baby aged 4 months without animal contact.

Abstract Background The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer adopts new criteria for tumor size, and for determining pTis, pT1a(mi), and pT1a. The latter is based on the size of stromal invasion. It is quite challenging for lung pathologists. Methods All patients who had undergone surgical resection for pulmonary adenocarcinoma (ADC) at Chung Shan Medical University Hospital between January 2014 and April 2018 were reviewed, and restaged according to the eighth AJCC staging system. The clinical characteristics and survival of patients with tumor stage 0 (pTis), I or II were analyzed. Results In total, 376 patients were analyzed. None of the pTis, pT1a(mi), or pT1a tumors recurred during the follow‐up period up to 5 years, but pT1b, pT1c, pT2a, and pT2b tumors all had a few tumor recurrences (p

Background: We conducted a longitudinal survey for methicillin-resistant Staphylococcus aureus (MRSA) carriage in nursing homes and long-term care facilities (LTCFs) in northern Taiwan. Methods: From July 2016 to February 2017, healthcare workers and residents in four institutions were enrolled. One swab sample from nares and another swab sample from umbilicus were obtained from each participant for detection of MRSA at enrolment and then follow-up samples were collected every two months for additional three times if feasible. Results: We enrolled a total of 194 participants, including 127 residents and 67 healthcare workers. MRSA colonization rates were 23.2%, 22.8%, 20.7% and 18.6% at enrolment, the 2-, 4-, and 6-month follow-up survey, respectively, and the cumulative colonization rate was 40.2%. The MRSA detection rate was significantly higher at Institution 2 (70.7%) than that at other three institutions (25.7% ∼ 35%) (p

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has been an important nosocomial pathogen in our neonatal units since 1990s. To understand the longitudinal changing molecular epidemiology of these MRSA isolates, we conducted this study. Materials: From 2003 to 2018, we collected clinical MRSA isolates from 536 infants hospitalized at neonatal units of a medical center in northern Taiwan. First isolate from each infant was characterized. Results: The case/isolate number ranged from 7 cases/isolates (the lowest) in 2010 to 71 cases/isolates (the highest) in 2004. Of the 536 isolates, a total of 15 pulsotypes were identified. Three major clones were identified and characterized as sequence type (ST) 239/pulsotype A/staphylococcal chromosomal cassette (SCC) mec III/Panton-Valentine leukocidin (PVL)-negative, accounting for 22.2% of the isolates, ST59/pulsotype C/SCCmec IV/PVL-negative, accounting for 34.3% and ST59/pulsotype D/SCCmec VT/PVL-positive, accounting for 30.0%. The first clone (hospital strains) dominated in the first two years, and became weakened from 2005 through 2016. Clonal complex (CC) 59 (combined the second and third clones) dominated (>50% of the isolates) from 2005 through 2018. One community clone (ST573) demonstrated a marked increase since 2007 and vanished abruptly since 2010. Several minor MRSA clones emerged after 2010. Conclusion: The molecular epidemiology of MRSA isolates in our neonatal units from 2003 to 2018 revealed that an epidemic as well as endemic hospital clone of ST239 dominated before 2005 and was replaced by the local community clone of CC59 thereafter.

Public safety concern of the ChAdOx1 vaccine has led to an alternative immunisation strategy against SARS-CoV-2, with this heterologous schedule widely adopted and officially recommended in many countries. Here, the authors report the immunogenicity and safety outcomes of heterologous prime-boost immunisation with ChAdOx1 and a spike-2P subunit vaccine in a single-blinded, randomised trial.

Abstract Background Targeting the HGF/MET signaling pathway has been a viable therapeutic strategy for various cancer types due to hyperactivation of HGF/MET axis occurs frequently that leads to detrimental cancer progression and recurrence. Deciphering novel molecule mechanisms underlying complex HGF/MET signaling network is therefore critical to development of effective therapeutics for treating MET-dependent malignancies. Results Using isobaric mass tag-based quantitative proteomics approach, we identified IFITM3, an interferon-induced transmembrane protein that was highly expressed in micro-dissected gastric cancer (GC) tumor regions relative to adjacent non-tumor epithelia. Analyses of GC clinical specimens revealed that expression IFITM3 was closely correlated to advanced pathological stages. IFITM3 has been reported as a PIP3 scaffold protein that promotes PI3K signaling. In present study, we unprecedentedly unraveled that IFITM3 associated with MET and AKT to facilitate HGF/MET mediated AKT signaling crosstalk in suppressing FOXO3, consequently leading to c-MYC mediated GC progression. In addition, gene ontology analyses of the clinical GC cohort revealed significant correlation between IFITM3-associated genes and targets of c-MYC, which is a crucial downstream effector of HGF/MET pathway in cancer progression. Moreover, we demonstrated ectopic expression of IFITM3 suppressed FOXO3 expression, consequently led to c-MYC induction to promote tumor growth, cell metastasis, cancer stemness as well as chemoresistance. Conversely, depletion of IFITM3 resulted in suppression of HGF triggered cellular growth and migration via inhibition of AKT/c-MYC signaling in GC. Conclusions In summary, our present study unveiled a novel regulatory mechanism for c-MYC-driven oncogenesis underlined by IFITM3-mediated signaling crosstalk between MET associated AKT signaling cascade.

With an aging population and the numerous health impacts associated with old age, the identification of anti-aging drugs has become an important new research direction. Although mitochondria have been recognized to affect aging, anti-aging drugs specifically targeting the mitochondria are less well characterized. In this study, diphenyleneiodonium (DPI) was identified as a potential senomorphic drug that functions by promoting mitochondrial fission. DPI significantly reduced the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and increased the number of proliferating Ki-67 positive cells in BrdU or irradiation stress-induced senescent NIH3T3 cells or IMR90 cells and mouse embryonic fibroblasts (MEFs) replicative senescent cells. Cell cycle arrest genes and senescence-associated secretory phenotype (SASP) factors were downregulated with DPI treatment. In addition, the oxygen consumption rate (OCR) of mitochondrial respiration showed that DPI significantly reduced senescence-associated hyper OCR. Mechanistically, DPI promoted mitochondrial fission by enhancing AMPK/MFF phosphorylation and DRP1 mitochondrial translocation. Inhibition of DRP1 by Mdivi-1 abolished DPI-induced mitochondrial fission and the anti-senescence phenotype. Importantly, Eighty-eight-week-old mice treated with DPI had significantly reduced numbers of SA-β-gal positive cells and reduced expression of cell cycle arrest genes and SASP factors in their livers and kidneys. Pathological and functional assays showed DPI treatment not only reduced liver fibrosis and immune cell infiltration but also improved aged-related physical impairments in aged mice. Taken together, our study identified a potential anti-aging compound that exerts its effects through modulation of mitochondrial morphology.

Abstract 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.

Background/purpose: Superspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE. Methods: We performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied. Results: Patient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (Rt) was 0.9 (8/9). Conclusion: The host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (Rt, pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.

Background: Bacillus cereus is a well-known pathogen for self-limited foodborne illness, and rarely an opportunistic pathogen associated with invasive infections among immunocompromised patients. Nosocomial outbreaks have been rarely reported. Methods: Between August and November 2019, four preterm neonates in neonatal care units of a medical center developed late-onset B. cereus bacteremia. An investigation was carried out. Forty-eight environmental specimens were obtained from these neonatal units, skin surface and environmental objects of Patient 4 for the detection of this organism 19 days after the onset of illness of Patient 4. B. cereus isolates from Patient 4, five unrelated patients and environmental objects if identified were further characterized by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results: All four infants survived after vancomycin-containing treatment. Patient 4 developed diffuse cerebritis, brain abscess with severe neurologic sequelae. Of the 48 environmental samplings, 26 specimens showed positive for B. cereus, with one major clone (sequence type 365) accounting for 73%. The isolate from Patient 4 (ST427) was identical to one isolate collected from environmental objects in the same unit. After extensive cleaning of the environment and re-institution of the sterilization procedure of hospital linens, which was ceased since two months before the outbreak, no more cases was identified in these units for at least one year. Conclusions: We documented a cluster of B. cereus bacteremia involving four preterm infants, which might be associated with cessation of the procedure for linen sterilization and was successfully controlled by re-institution of this procedure.

Background: Mycoplasma pneumoniae is a major pathogen for community-acquired pneumonia and frequently causes outbreaks in children. M. pneumoniae-specific antibody response is detected upon acute infection and the serology is widely used in the clinical setting. Nevertheless, the cellular basis for antigen-specific antibody response to acute M. pneumoniae infection is largely undetermined in children. Methods: Hospitalized children with community-acquired pneumonia were enrolled and the infection with M. pneumoniae was confirmed with positive PCR result and negative findings for other pathogens. The M. pneumoniae P1-specific antibody-secreting B cell (ASC) response was examined with the ex vivo enzyme-linked immunosorbent spot assay and the relationships between the ASC frequency and serological level and clinical parameters within M. pneumoniae patients were studied. Results: A robust M. pneumoniae P1-specific ASC response was detected in the peripheral blood among M. pneumoniae-positive patients. By contrast, no M. pneumoniae-specific ASCs were detected among M. pneumoniae-negative patients. The IgM-secreting B cells are the predominant class and account for over 60% of total circulating M. pneumoniae-specific ASCs in the acute phase of illness. The M. pneumoniae P1-specific ASC frequency significantly correlated with the fever duration, and the IgG ASC frequency significantly correlated with serological titer among patients. Conclusion: A rapid and potent elicitation of peripheral M. pneumoniae-specific ASC response to acute infection provides the cellular basis of antigen-specific humoral response and indicates the potential of cell-based diagnostic tool for acute M. pneumoniae infection. Our findings warrant further investigations into functional and molecular aspects of antibody immunity to M. pneumoniae.

Objectives This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC).Design This observational time–motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses.Setting Outpatient and inpatient administration units of a single medical centre in Taiwan.Participants The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses.Result Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak.Conclusion Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic.

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.

Abstract Sugariness is one of the most important indicators to measure the quality of Syzygium samarangense, which is also known as the wax apple. In general, farmers used to measure sugariness by testing the extracted juice of the wax apple products. Such a destructive way to measure sugariness is not only labor-consuming but also wasting products. Therefore, non-destructive and quick techniques for measuring sugariness would be significant for wax apple supply chains. Traditionally, the non-destructive method to predict the sugariness or the other indicators of the fruits was based on the reflectance spectra or Hyperspectral Images (HSIs) using linear regression such as Multi-Linear Regression (MLR), Principal Component Regression (PCR), and Partial Least Square Regression (PLSR), etc. However, these regression methods are usually too simple to precisely estimate the complicated mapping between the reflectance spectra or HSIs and the sugariness. This study presents the deep learning methods for sugariness prediction using the reflectance spectra or HSIs from the bottom of the wax apple. A non-destructive imaging system fabricated with two spectrum sensors and light sources is implemented to acquire the visible and infrared lights with a range of wavelengths. In particular, a specialized Convolutional Neural Network (CNN) with hyperspectral imaging is proposed by investigating the effect of different wavelength bands for sugariness prediction. Rather than extracting spatial features, the proposed CNN model was designed to extract spectral features of HSIs. In the experiments, the ground-truth value of sugariness is obtained from a commercial refractometer. The experimental results show that using the whole band range between 400 and 1700 nm achieves the best performance in terms of °Brix error. CNN models attain the °Brix error of ± 0.552, smaller than ± 0.597 using Feedforward Neural Network (FNN). Significantly, the CNN’s test results show that the minor error in the interval 0 to 10°Brix and 10 to 11°Brix are ± 0.551 and ± 0.408, these results indicate that the model would have the capability to predict if sugariness is below 10°Brix or not, which would be similar to the human tongue. These results are much better than ± 1.441 and ± 1.379 by using PCR and PLSR, respectively. Moreover, this study provides the test error in each °Brix interval within one Brix, and the results show that the test error is varied considerably within different °Brix intervals, especially on PCR and PLSR. On the other hand, FNN and CNN obtain robust results in terms of test error.

BackgroundTreatment responsiveness to corticosteroids is excellent for cryptogenic organizing pneumonia (COP) and sarcoidosis, but suboptimal for idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). We hypothesise that the differential expression of IL-17 contributes to variable corticosteroid sensitivity in different interstitial lung diseases.ObjectiveTo determine the associations among expression of IL-17, glucocorticoid receptor-β and responsiveness to corticosteroid treatment in interstitial lung diseases.MethodsImmunohistochemical (IHC) staining was performed on formalin-fixed paraffin-embedded (FFPE) lung tissues obtained by bronchoscopic, CT-guided or surgical biopsies, and quantified by both cell counting (% positive cells) by individuals and by software IHC Profiler plugin of ImageJ (opacity density score). We studied the effect of IL-17 on corticosteroid sensitivity in human fibroblast MRC5 cell line.ResultsCompared with specimens from patients with COP (n =13) and sarcoidosis (n =13), those from IPF patients (n = 21) had greater GR-β and IL-17 expression and neutrophil infiltration. Radiographic progression after oral corticosteroid treatment was positively correlated with the expression in IL-17 and GR-β/GR-α ratio in all patients (COP, sarcoidosis and IPF) and also within the IPF subgroup only. IL-17 expression level was positively associated with GR-β and GR-β/GR-α ratio. In MRC5 cells, exogenous IL-17 increased the production of collagen I and up-regulated GR-β expression and dexamethasone’s suppressive effect on collagen I production was impaired by IL-17, and silencing IL-17 receptor A gene attenuated the effect of IL-17.ConclusionUp-regulation of GR-β/GR-α ratio by IL-17 could be associated with the relative corticosteroid-insensitivity of IPF.

Fibrocytes are bloodborne mesenchymal progenitors which accumulate and differentiate at the disease site. We investigated whether hypoxemia activates fibrocytes, accelerating airflow limitation and exercise intolerance in chronic obstructive pulmonary disease (COPD) patients. Flow cytometry was used to determine collagen I+/CD45+ fibrocytes and α-smooth muscle actin+ differentiating fibrocytes within peripheral blood and cultured cells, as well as the expression of CXC chemokine receptor 4 (CXCR4), epidermal growth factor receptor (EGFR), connective tissue growth factor (CTGF) and hypoxia-inducible factor (HIF)-1α. Fibrocytes in lung specimens were identified by confocal microscopy. Compared to non-desaturators, COPD desaturators (peripheral blood oxygen saturation ≤88% during exercise) had greater number of fibrocytes in peripheral blood and lung specimens, paralleled with faster yearly lung function decline and a 6-minute walk distance. Fibrocytes from desaturators expressed more EGFR, CXCR4, CTGF, and HIF-1α, with a higher capacity of proliferation and myofibroblastic differentiation. Hypoxia (5% oxygen) increased the expression of EGFR, CXCR4, CTGF, and HIF-1α, the number and differentiation in fibrocytes. These effects were attenuated by EGFR inhibitor gefitinib, HIF-1α gene silencing, and anti-CTGF antibody. These data elucidate that hypoxemia triggers fibrocyte activation through the EGFR/HIF-1α axis, aggravating airflow obstruction in COPD.

Background: Cervical lymphadenopathy is among the cardinal manifestations of Kikuchi disease (KD). The incidences and locations of extra-cervical lymph nodes (LNs) involvement in KD have not been comprehensively reported. Methods: From 2003 to 2016, 60 patients with pathologically confirmed KD and with computed tomography and/or whole-body inflammation scans at diagnosis were retrospectively identified. The locations, sizes and characteristics of all affected LNs were analyzed by extensive review of the image studies. The clinical and laboratory parameters were abstracted from medical records and the associations with extra-cervical LNs involvement were identified. Results: Female accounted for 35 (58.3%) patients and the median age of all patients was 21.3 years (ranges, 3–64 years). Of 59 patients with evaluable neck images, 42 (71.2%) and 16 (27.1%) patients presented with unilateral and bilateral nodal involvement, respectively, with the most common locations at level II, III and IV by Som's classification. The largest LNs appeared most commonly in level II. The incidences of extra-cervical lymphadenopathy in abdomen, pelvis, inguina, axilla and mediastinum with available images were respectively 52.9% (9/17), 47.1% (8/17), 41.2% (7/17), 30.6% (11/36) and 14.3% (8/56). When compared to cases with solitary cervical lymphadenopathy, the cases with extra-cervical lymphadenopathy had significantly greater incidences of bilateral cervical lymphadenopathy (P = .0379) and leukopenia (P = .0173). Conclusion: Unilateral cervical lymphadenopathy was the most frequent form of LNs involvement of KD. Extra-cervical lymphadenopathy was not uncommon and was associated with the appearance of bilateral distribution of cervical LNs and leukopenia.

Abstract 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.

Background: Norovirus (NoV) and rotavirus (RV) are among the most common causes of acute gastroenteritis (AGE) of all ages worldwide. There have been scanty reports of the epidemiology data of NoV AGE from clinical virologic laboratory. Methods: All stool specimens sent to the virologic laboratory in a medical center in Taiwan for detection of both NoV (by reverse transcription-polymerase chain reaction) and RV (by enzyme immunoassay) from 2013 to 2018 were included for analysis. Results: A total of 15,991 specimens, annually ranging from 2430 in 2017–2915 in 2013, were included. 48.0% and 73.1% of the specimens were obtained from children aged

Background: Echovirus 11 emerged as a predominant enterovirus strain and was associated with neonatal mortalities in Taiwan in 2018. We investigated an echovirus 11 outbreak in the neonatal intensive care units (NICUs) in a tertiary hospital in northern Taiwan and analyzed infection control efforts. Methods: Between May and June 2018, an outbreak of 10 infants with echovirus 11 infections occurred in the NICUs. Comprehensive surveillance, including virus isolation, real-time reverse transcription-polymerase chain reaction (RT-PCR), and consequential degenerate hybrid oligonucleotide primer (CODEHOP) methods, were arranged for specimens (rectal or throat swabs), which were obtained from all contacts, newly admitted cases, and suspected cases during the outbreak since June 2. Results: Ten cases were identified with echovirus 11 infection in this outbreak. Eight of these 10 confirmed cases were identified by viral isolation, and the remaining two cases were identified by RT-PCR surveillance. In addition to confirmed cases, the surveillance of 19 contacts, 47 newly admitted cases, and nine suspected cases showed negative results. All confirmed cases eventually recovered. Conclusion: RT-PCR and CODEHOP methods significantly shorten the time of laboratory diagnosis of enterovirus infection compared with conventional methods. The outbreak of echovirus 11 in the NICUs was caused by three imported cases and was successfully controlled by the implementation of isolation, rapid surveillance, reinforced disinfection, and infection control measures. Key Words: echovirus 11, outbreak, neonatal intensive care unit

Background: The vancomycin trough level (VTL) is the most widely used pharmacokinetic parameter for monitoring its clinical efficacy. Whether the VTL is affected in patients receiving different vancomycin products has not previously been determined. Methods: From 2005 to 2015, five vancomycin products, including the innovator (designated as VAN-Lilly) and four generic versions (designated as VAN-A, VAN-B, VAN-C and VAN-D), were sequentially used in a teaching hospital. The initial VTLs were compared between patients who received different vancomycin products after propensity score (PS) weighting and matching for clinical covariates. Results: Among 8735 patients with initial VTL levels available for analysis, a significant association was identified between the VTL and different vancomycin products in children aged 1 month to 12 years (P

Japanese encephalitis (JE) is a mosquito-borne viral infection which is prevalent in Taiwan. The virus circulates in an enzootic cycle in pigs which serve as amplifying hosts. Outbreaks typically occur during summer. A universal vaccination program using 4-shot mouse brain-derived inactivated vaccine has successfully controlled JE epidemics in Taiwan since 1968. More than 90% of JE cases in recent years were older than 20 years in Taiwan. Because of several drawbacks, mouse brain-derived vaccine has been replaced by newer generation JE vaccines, including inactivated Vero cell-derived vaccine and live chimeric vaccine. The present article describes the recommendations in Taiwan for the use of new JE vaccines and the schedules for shifting between different JE vaccines. Key Words: epidemiology, immunization schedule, Japanese encephalitis, vaccination

Abstract 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.

Global methicillin-resistant Staphylococcus aureus (MRSA) strains were dominated by few genetic lineages, suggesting their inherent advantage of competitive fitness. The information of genome evolution and population structures of prevalent MRSA strains can help gain a better understanding of the success of the pandemic clones. Whole-genome sequencing was performed in 340 MRSA isolates belonging to three prevalent lineages, including ST59 (129 isolates), ST239/241 (140 isolates), and ST5 (71 isolates), collected from 1996 to 2016 in Taiwan. The time-scaled phylogeny and evolutionary pathways were estimated by Bayesian analysis using Markov chain Monte Carlo. The toxome, resistome, and plasmids were characterized by screening the raw reads with a public database. ST59, ST239/241, and ST5 MRSA were estimated to emerge in 1974, 1979, and 1995, respectively, in Taiwan. ST59 evolved through two major pathways, generating two subclones in 1980 and 1984. Both ST59 subclones remained prevalent in the healthcare and community environments in late 2010s. ST239/241 diverged into three subclones, respectively, in 1989, 1993, and 1995. The 1995-emerging ST239 subclone predominated after 2000 by replacing two previous early subclones. ST5 could be subdivided into two clades within 3 years of introduction, but no substantial difference of genomic profiles was identified in the strains of distinct clades. Each of the three pandemic MRSA lineages harbored its own specific toxome, resistome, and plasmids. The frequently identified genetic diversities between the subclones of the same lineage were genes mediating immune evasion, leukocidins, enterotoxins, and resistance to aminoglycosides. In conclusion, MRSA ST59 and ST239/241 emerged in the 1970s and evolved drastically during 1980 and 1995, resulting in three successful subclones prevailing in Taiwan. ST5 was introduced late in 1995 without a significant genetic drift during 20 years of evolution.

Geographic and gender-specific disparity can be observed in nasopharyngeal carcinoma (NPC). While screening and more effective therapies, such as induction chemotherapy, could improve survival rates, they are costly. This study aims to explore the correlation between healthcare expenditure and the mortality-to-incidence ratio (MIR) in NPC. Data were obtained from the World Health Organization and the Global Cancer Observatory. The correlation was evaluated by Spearman’s rank correlation coefficient. Most new cases and deaths occur in Asia, and more males are affected than females. Our study shows that countries with higher MIRs have lower levels of health expenditure regardless of the NPC’s gender-specific incidence. Correspondingly, MIRs are all significantly negatively associated with current health expenditure (CHE) per capita and CHE as a percentage of gross domestic product (CHE/GDP) in both genders. CHE per capita and CHE/GDP have a significant impact on NPC outcomes. Moreover, economic status is a potential major factor in MIR differences between countries.

Abstract Background Indigenous typhoid fever was continuing to be identified in Taiwan which has not been endemic for the enteric fever for more than 20 years. The source and transmission by which the local patients acquired typhoid and the population structure of the indigenous typhoid strains remain not well characterized. Methods During 2001 and 2014, non-duplicated clinical Salmonella enterica serovar Typhi isolates in a hospital were analyzed by whole-genome sequencing (WGS) and determined for pulsotypes. Maximum likelihood phylogeny was constructed by nucleotide alterations in core genomes and compared to the framework of global typhoid strains. Potential source and transmission were traced by correlating the phylogeny and the temporal relationship between isolates. Results A total of 43 S. Typhi isolates from indigenous cases were analyzed and a majority (39, 90.7%) of them were belonged to six WGS-defined genotypes prevailing mainly in Southeast Asia. Genotype 3.4.0 and a multidrug-resistant type 4.3.1 (also known as pandemic H58 haplotype) were associated respectively with two solitary small-scale outbreaks, implying a transmission mode of importation followed by outbreak. Twelve isolates with nearly identical core genomes were belonged to genotype 3.2.1 but were categorized into three different pulsotypes. The 3.2.1 isolates were identified across 13 years and involved in three clusters and a sporadic case, indicating sustained local transmission of the same strain. The remaining indigenous isolates belonging to three genotypes (2.1, 3.1.2, and 3.0.0) were of substantial genetic diversity and isolated at different time points, indicating independent event of each case. Conclusions Indigenous typhoid in Taiwan occurred mainly with the forms of small-scale outbreaks or sporadic events likely by contracting imported strains which prevailed in Southeast Asia. Sustained local transmission of certain strain was also evident by WGS analysis, but not by conventional pulsotyping, highlighting the importance of continuing molecular surveillance of typhoid fever with adequate tools in the non-endemic region.

Abstract Background Current advancements in neoadjuvant therapy and total mesorectal excision have engendered increased local control. However, the survival benefit of preoperative radiotherapy (RT; 5 × 5 Gy) in rectal cancer patients remains inadequate, primarily because of systemic recurrence. In this retrospective single-center study, the effects of monthly tegafur–uracil maintenance (≥6 cycles) after 12 fluorouracil-based adjuvant chemotherapy cycles on 3-year relapse-free survival (RFS) was estimated in ypStage III rectal cancer patients. Methods Of ypStage III rectal cancer patients who received preoperative RT (5 × 5 Gy) in January 2006–December 2015, those who had ypStage III cancer after preoperative radiation, radical resection, and postoperative chemotherapy were enrolled; excluded patients had ypStage I and II rectal cancer, had double cancer, had synchronous distant metastasis, had local excision, received preoperative chemoradiation, and were lost to follow-up within 1 year after cancer treatment. Included patients received either maintenance therapy or observation after postoperative chemotherapy. The primary endpoint was the effect of maintenance therapy on 3-year RFS. We set the median follow-up duration to be 69.7 (range, 15.4–148.3) months. Results Of 259 ypStage III rectal cancer patients, 102 (59 men and 43 women) were enrolled based on the inclusion criteria. The maintenance and observation groups comprised 55 and 57 patients, respectively (mean age = 62.2 and 65.7 years, respectively; p = 0.185). The 3-year RFS observed in the maintenance group (85.1%) was longer than that observed in the observation group (67.5%; p = 0.039). Multivariate analysis proved the following to be independent prognostic factors for RFS: higher metastatic lymph node ratio (LNR ≥0.3), tegafur–uracil maintenance (≥6 cycles), and lower rectal cancer (

Background: A resurgence of mumps was noted recently and outbreaks were increasingly reported in populations with high vaccine coverage. We aimed to evaluate the seroprevalence to mumps in Taiwan, where a two-dose childhood mumps-containing vaccine program, with a high coverage rate, had been implemented for >20 years. Methods: The anti-mumps IgG was determined in 3552 participants of all ages in Taiwan. The age-specific seropositivity rates were calculated and the sociodemographic variables associated with the seronegative sera were analyzed with a logistic regression method. Results: The overall seroprevalence to mumps was 71%, with a higher rate in adults ≥19 years old than in the pediatric population

Abstract Background There have been no reports regarding clinical features and molecular characteristics of childhood methicillin-susceptible Staphylococcus aureus (MSSA) infections in Taiwan. Methods We prospectively collected clinical S. aureus isolates from patients aged

Background: Human rhinovirus (HRV) can cause severe illnesses in hospitalized patients. However, there are no studies regarding the prevalence of HRV infection, particularly the recently identified HRV-C, in hospitalized patients reported from Taiwan. Methods: Respiratory specimens collected from 487 hospitalized patients in designated wards between 2013 and 2014 in a medical center in northern Taiwan were retrospectively detected for HRV. Positive specimens were further determined for genotyping. Medical charts of the HRV-positive patients were reviewed retrospectively. Results: Totally, 76 patients (15.6%) were HRV positive, of which 60 were pediatric patients. HRV-A was identified in 41 (54%) patients, HRV-B in 6 patients (7.9%) and HRV-C in 29 patients (38%). A total of 47 different genotypes were identified. HRV infections were predominant during fall and winter seasons. 21.1% were affected by HRV alone and 78.9% were found to be co-infected with other microorganisms. The detection rate of HRV in children (18.6%) was significantly higher than in adults (9.6%). Compared with pediatric patients, adult patients were significantly associated with underlying disease, Pneumocystis jirovesii pneumonia co-infection, a diagnosis of pneumonia, fatal outcome, hospital acquisition of HRV, antibiotics administration and requiring intensive care, while pediatric patients were significantly associated with viral co-infection. Conclusions: HRV was a common cause of respiratory tract infection in Taiwan, particularly in pediatric patients. Eighty percent of HRV-infected inpatients had other microorganisms co-infection. Adult patients were more likely to be associated with a severe respiratory disease entity. Keywords: Rhinovirus, Respiratory tract infection, Hospitalized patients, Taiwan

Background/purpose: Staphylococcus aureus (S. aureus) causes diseases ranging from mild skin infections to invasive diseases. Carriage of S. aureus, including methicillin-resistant S. aureus (MRSA), is a significant risk factor for subsequent staphylococcal infection. Several studies discussed MRSA colonization in Taiwan, but mostly in northern Taiwan. This is the first study that estimates the prevalence of MRSA nasal colonization in healthy children and identifies the potential risk factors in central Taiwan. Methods: A total of 3144 healthy children aged 2–60 months who visited Taichung Veterans General Hospital (TCVGH) were screened for nasal S. aureus carriage from July 2005 to December 2010. Questionnaires included demographic information and potential risk factors for carriage of S. aureus were completed by parents/guardians. Results: Prevalence of MSSA and MRSA were 12.09% and 5.25%, respectively. The youngest group aged 2–6 months had the highest S. aureus carriage rate, and the carriage rate revealed a peak in summer. The nasal colonization of Streptococcus pneumoniae (S. pneumoniae) was a protective factor against S. aureus colonization. 85% of the MRSA colonizing isolates belonged to clonal complex 59/staphylococcal cassette chromosome type IV or VT, the local community clone in Taiwan. Conclusion: An increasing trend of MRSA nasal carriage rate in Taiwan had been brought forward, however, it was not observed in central Taiwan during the period of 2005–2010. We found a summer peak on both MRSA and MSSA carriages. Keywords: Central Taiwan, Children, Methicillin-resistant Staphylococcus aureus colonization

Background: Robotic nipple-sparing mastectomy (R-NSM), which uses the da Vinci surgical platform (Intuitive Surgical, Sunnyvale, CA, USA), could perform NSM and immediate breast reconstruction through small and inconspicuous extramammary axillary incision. Its application in the management of early breast cancer or risk-reducing mastectomy had been reported in some series and a growing number of R-NSM were performed worldwide. The authors would like to present a single-center experience of R-NSM as well as review of the current literature.Materials and Methods: The medical records of patients who underwent R-NSM for breast cancer during the period from March 2017 to July 2018 were retrieved from a prospectively collected database. A review of case series of R-NSM in the current literature were also performed through the PubMed database to determine the effectiveness and oncologic safety of R-NSM.Results: A total of 37 breast cancer patients who received 46 R-NSM procedures were included in the study. Thirty-nine cases (84.8%) were performed for therapeutic purpose. No R-NSM procedure was converted to conventional or endoscopic mastectomy. One (2.6%, 1/39) R-NSM procedure was found to have positive margin involvement. The rate of total nipple-areolar complex (NAC) necrosis was 0%, and no implant loss or local recurrence was observed during a mean follow-up of 10.9 ± 8.2 months. In the joint collective analysis and review of the current literature, a total of 138 R-NSM procedures were available for analysis, and 59 of them were for therapeutic indications. The overall conversion rate was 2.2% (3/138), total NAC necrosis rate was 0%, implant loss rate was 0.8% (1/128), and margin involved rate was 1.7% (1/59). No local recurrence case was reported.Conclusion: From our preliminary experience and review of the current literature, R-NSM is a feasible and safe alternative for NSM in the management of breast cancer. The long-term oncological outcomes, however, will only be determined with longer follow-up.

Background and Objectives: PNU-74654, a Wnt/β-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.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been increasingly reported worldwide and are associated with nasal colonization. In Taiwan, available data disclosed a similar trend. We conducted a study for the updated childhood nasal MRSA carriage. Methods: From July 2005 to December 2010, children aged between 2 months and 5 years who presented for a well-child health care visit to a medical center or from kindergarten/daycare center were invited and a nasal swab specimen was obtained for the detection of MRSA. All MRSA isolates were characterized. Results: A total of 3226 children were included and the rate of nasal MRSA carriage was 10.2%. Children aged 2–6 months and >3 years were significantly associated with MRSA carriage, while pneumococcus colonization (p = 0.033) and breastfeeding (p = 0.025) were negatively associated with MRSA carriage. Of the 330 MRSA isolates, a total of 13 pulsotypes with two major patterns (type C, 47.0% and D, 29%) were identified. Most MRSA isolates belonged to two major clones, characterized as sequence type 59 (ST59)/pulsotype C/staphylococcal cassette chromosome (SCCmec) IV/Panton-Valentine leukocidin (PVL)-negative (45.8%) and ST59/pulsotype D/SCCmec VT/PVL-positive (22.7%). Two new clones as ST 508/SCCmec IV (9.7%) and ST573/SCCmec IV (7.3%) emerged and increased markedly since 2007. Conclusion: Between 2005 and 2010, 10.2% of healthy children in northern Taiwan carried MRSA in anterior nares, with the highest carriage rate for infants aged 2–6 months. Two emerging clones, ST 508 and ST 573, were identified and the clinical significance needs further surveillance. Keywords: Methicillin-resistant Staphylococcus aureus, Community-associated, Sequence type 59, Taiwan, Children, Colonization

An effective antiseptic agent is an essential component of a central venous catheter (CVC) care bundle, to protect against catheter-related bloodstream infections (CRBSIs). We conducted a trial to compare the incidences of CRBSI and the growth of insertion site flora in patients with CVC using 2% chlorhexidine gluconate–alcohol (CHG) or 10% povidone-iodine–alcohol (PVI) in the CVC care bundle. Patients who were admitted to two medical intensive care units (ICUs) and had CVC placement for >48 h were enrolled. Using a two-way crossover design with two six-month interventions, the ICUs were assigned to use either CHG or PVI in their care bundles. A total of 446 catheters in 390 subjects were enrolled in the study. The detection rate of flora was greater in the PVI group on both day 7 (26.6% versus 6.3%, p < 0.001) and day 14 (43.2% versus 15.8%, p < 0.001). The incidence rate of CRBSI was higher in the PVI group compared to the CHG group (2.15 vs. 0 events per 1000-catheter-days, p = 0.001), although the significance was lost in the multivariate analysis. In conclusion, 2% CHG was superior to 10% PVI in the CVC care bundle in terms of the inhibition of skin flora growth at CVC insertion sites and was potentially associated with lower incidence rates of CRBSI.

The genomic evolution in vivo in persistent infection was critical information for understanding how methicillin-resistant Staphylococcus aureus (MRSA) was adapted to host environments with high antibiotic selective pressure. Thirty-two successive MRSA blood isolates with incremental non-susceptibility to vancomycin (VISA), daptomycin (DRSA), and/or linezolid (LRSA) were isolated from a patient failing multiple courses of antimicrobial therapy during 1,356 days of bacteremia. Whole genome sequencing (WGS) for all consecutive isolates were conducted to characterize the evolutionary pathways, resistance-associated mutations and their temporal relationship with antimicrobial treatment. The WGS-based phylogeny categorized the isogenic strains into three major clades, I (22 isolates), II (7 isolates), and III (3 isolates), respectively, harboring a median (range) of 7 (1–30), 62 (53–65), and 118 (100–130) non-synonymous mutations when compared to the very first isolate. Clade I strains were further grouped into early and late subclades, which, respectively, shared the most recent common ancestor with Clade III strains at day 393.7 and Clade II strain at day 662.5. Clade I and Clade III strains were characterized, respectively, with high rates of VISA (9/22, 40.9%) and VISA-and-DRSA phenotype (2/3, 66.7%). Linezolid-resistance including VISA-DRSA-and-LRSA phenotype was exclusively identified in Clade II strains after eight courses of linezolid treatment. The LRSA displayed a small colony variant phenotype and were associated with G2576T mutations in domain V region of 23S rRNA. Substantial loss of mobile elements or alleles mediating resistance or virulence were identified during the evolution of multi-resistance. However, the gene loss might not be correlated to the development of VISA, DRSA, or LRSA phenotype. In conclusion, MRSA in persistent bacteremia was adapted to harsh host environment through multiple pathways involving both resistance-associated mutations and extensive gene loss.

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-β-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.

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.

Enhancements in the diagnostic capabilities using host biomarkers are currently much needed where sensitivity and specificity issues plague the diagnosis of Hand, Foot and Mouth Disease (HFMD) in pediatrics clinical samples. We investigated miRNome profiles of HFMD saliva samples against healthy children and developed miRNA-based diagnosis models. Our 6-miRNA scoring model predicted HFMD with an overall accuracy of 85.11% in the training set and 92.86% in the blinded test set of Singapore cohort. Blinded evaluation of the model in Taiwan HFMD cases resulted in 77.08% accuracy with the 6-miRNA model and 68.75% with the 4-miRNA model. The strongest predictor of HFMD in all of the panels, hsa-miR-221 was found to be consistently and significantly downregulated in all of our HFMD cohorts. This is the first study to prove that HFMD infection could be diagnosed by circulating miRNAs in patient's saliva. Moreover, this study also serves as a stepping stone towards the future development of other infectious disease diagnosis workflows using novel biomarkers. Keywords: miRNA, Biomarker, Saliva, HFMD, Machine learning