Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer.

BACKGROUND: This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks+ Escherichia coli (pks+E.coli+), pks+E.coli- (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum). METHODS: We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR. RESULTS: Pks+E.coli+ was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks+E.coli+ and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks+E.coli- (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01). CONCLUSION: Intratumoral pks+E.coli+ but not pks+E.coli- are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause.

Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: experiences from a nationwide newborn screening programme.

BACKGROUND: Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres. METHODS: In this long-term follow-up study, we analysed the outcomes of very early ERT with premedication hydrocortisone in patients with IOPD. Out of 1 228 539 infants screened between 1 January 2010 and 28 February 2021, 33 newborns had confirmed IOPD in Taipei Veterans General Hospital. Twenty-six were regularly treated and monitored at Taipei Veterans General Hospital. Echocardiographic parameters, biomarkers, IgG antibodies against alglucosidase alpha, pulmonary function variables and developmental status were all assessed regularly over an average follow-up duration of 6.18±3.14 years. We compared the long-term treatment outcomes of our patients with those of other research groups. RESULTS: The average age at ERT initiation was 9.75±3.17 days for patients with classic IOPD. The average of the latest antialglucosidase alpha IgG titre was 669.23±1159.23. All enrolled patients had normal heart sizes, motor milestones, cognitive function and pulmonary function that were near-normal to normal. Compared with patients in other studies, our patients had better outcomes in all aspects. CONCLUSION: Very early ERT using our rapid diagnostic and treatment strategy enabled our patients with IOPD to have better outcomes than patients in other medical centres.

Early Surgery for Infective Endocarditis Complicated With Neurologic Injury.

OBJECTIVES: To estimate the association between early surgery and the risk of mortality in patients with left-sided infective endocarditis in the context of stroke. DESIGN: Retrospective cohort study. SETTING: This study was a multiinstitution study based on the Chang Gung Research Database, which contains electronic medical records from 7 hospitals in northern and southern Taiwan; these include 2 medical centers, 2 regional hospitals, and 3 district hospitals. PARTICIPANTS: Patients with active left-sided infective endocarditis who underwent valve surgery between September 2002 and December 2018. INTERVENTIONS: The authors divided patients into 2 groups, with versus without preoperative neurologic complications, had undergone early (within 7 d) or later surgery, and with brain ischemia or hemorrhage. MEASUREMENTS AND MAIN RESULTS: Three hundred ninety-two patients with a median time from diagnosis to surgery of 6 days were included. No significant differences in postoperative stroke, in-hospital mortality, or follow-up outcomes were observed between the patients with and without neurologic complications. Among the patients with preoperative neurologic complications, patients who underwent early surgery had a lower 30-day postoperative mortality rate (13.1% v 25.8%; hazard ratio, 0.21; 95% CI 0.07-0.67). In the subgroup analysis of the comparison between brain ischemia and hemorrhage groups, there was no significant between-group difference in the in-hospital outcomes or outcomes after discharge. CONCLUSIONS: Early cardiac surgery may be associated with more favorable clinical outcomes in patients with preoperative neurologic complications. Thus, preoperative neurologic complications should not delay surgical interventions.

High incidence of cerebrovascular lesions on magnetic resonance imaging in pediatric COVID-19 during omicron outbreak - A retrospective case series.

BACKGROUND: The incidence of pediatric hospitalizations has significantly increased since the spread of the omicron variant of COVID-19. Changes of characteristics in respiratory and neurological symptoms have been reported. We performed a retrospective, cross-sectional study to characterize the MRI change in children with an emphasis on the change of cerebral vasculatures. METHODS: We retrospectively collected clinical and MRI data of 31 pediatric patients with neurological symptoms during the acute infection and abnormalities on MRI during the outbreak of omicron variant from April 2022 to June 2022 in Taiwan. The clinical manifestations and MRI abnormalities were collected and proportion of patients with vascular abnormalities was calculated. RESULTS: Among 31 pediatric patients with post-COVID-19 neurological symptoms, MRI abnormalities were observed in 15 (48.4%), predominantly encephalitis/encephalopathy (73.3%). Notable MRI findings included focal diffusion-weighted imaging (DWI) hyperintensity in cerebral cortex and thalamus, diffuse cortical T2/DWI hyperintensity, and lesions in the medulla, pons, cerebellum, and splenium of corpus callosum. Vascular abnormalities were seen in 12 (80%) patients with MRI abnormalities, mainly affecting the middle cerebral arteries. The spectrum of neurological manifestations ranged from seizures to Alice in Wonderland syndrome, underscoring the diverse impact of COVID-19 on pediatric patients. CONCLUSION: A high proportion of vascular abnormalities was observed in pediatric patients with neurological involvements, suggesting that vascular involvement is an important mechanism of neurological manifestations in omicron variant infection.

Neurological manifestations of SARS-CoV-2 infection in children in Taiwan: A cross-section, multicenter study.

BACKGROUND: The SARS-CoV-2 virus has been a global public health threat since December 2019. This study aims to investigate the neurological characteristics and risk factors of coronavirus disease 2019 (COVID-19) in Taiwanese children, using data from a collaborative registry. METHODS: A retrospective, cross-sectional, multi-center study was done using an online network of pediatric neurological COVID-19 cohort collaborative registry. RESULTS: A total of 11160 COVID-19-associated emergency department (ED) visits and 1079 hospitalizations were analyzed. Seizures were the most common specific neurological symptom, while encephalitis and acute disseminated encephalomyelitis (ADEM) was the most prevalent severe involvement. In ED patients with neurological manifestations, severe neurological diagnosis was associated with visual hallucination, seizure with/without fever, behavior change, decreased GCS, myoclonic jerk, decreased activity/fatigue, and lethargy. In hospitalized patients with neurological manifestations, severe neurological diagnosis was associated with behavior change, visual hallucination, decreased GCS, seizure with/without fever, myoclonic jerk, fatigue, and hypoglycemia at admission. Encephalitis/ADEM was the only risk factor for poor neurological outcomes at discharge in hospitalized patients. CONCLUSION: Neurological complications are common in pediatric COVID-19. Visual hallucination, seizure, behavior change, myoclonic jerk, decreased GCS, and hypoglycemia at admission are the most important warning signs of severe neurological involvement such as encephalitis/ADEM.

Ocular circulation change in optic disc melanocytoma - a case report and a review of the literature.

BACKGROUND: Ocular circulation in optic disc melanocytoma (ODM) has not yet been well evaluated. We quantitatively evaluated longitudinal changes in the morphology and circulation hemodynamics of the disc and macula using optical coherence tomography angiography (OCTA) and laser speckle flowgraphy (LSFG) in a patient with optic disc melanocytoma. CASE PRESENTATION: A 50-year-old woman was referred to our hospital due to a dark pigmented tumor over the superior optic disc area of the left eye noted on physical examination. At the first visit, the patient's best-corrected visual acuity (BCVA) was 20/20 in both eyes, and the intraocular pressure (IOP) was 17 and 18 mmHg in the left and right eyes, respectively. Fluorescein angiography (FA) showed blockage of fluorescence in the topography of the lesion, and indocyanine green angiography (ICGA) showed hypofluorescence at all times. On LSFG, a low mean blur rate (MBR) was noted in the optic disc all area (MBRa) and tissue (MBRt) compared to the contralateral eye at the first visit and at the 3-month follow-up. A relatively low MBR was also detected in the macular area of the affected eye and the tumor itself. OCTA detected blood vessel networks in the deep retinal layer of the tumor. The visual field showed no specific defects. During follow-up, there was no tumor enlargement or vision decrease. CONCLUSIONS: We found that a lower MBR of the disc and macula area was noted on LSFG in this patient with optic disc melanocytoma, and it was continually observed at the 3-month follow-up. Although blood vessel networks in the deep retinal layer of the tumor were detected by OCTA, vascular compromise in the surrounding disc area and macula was found. Therefore, these results further increase our knowledge about the role that circulation impairment plays in the pathogenesis of the disease while vision is unaffected.

Cytomegalovirus Glycoprotein B Genotype in Patients with Anterior Segment Infection.

(1) The glycoprotein B (gB) on the viral envelope, encoded by the most widely characterised polymorphic gene, gpUL55, is responsible for cytomegalovirus (CMV) entry into the host and could serve as a potential marker of pathogenicity. The aim of the present study is to investigate the distribution of the CMV gB genotype in anterior segment infection in Taiwan and its correlation with clinical manifestations and outcomes. (2) Fifty-seven patients with CMV anterior segment infection were identified according to clinical features and positivity for CMV DNA in aqueous humour samples. CMV gB genotyping was performed through polymerase chain reaction assays. Patients' medical records were retrospectively reviewed. (3) Among the 57 aqueous humour samples tested for gB, 40 (70.28%) had multiple gB genotypes, and only 17 (29.82%) had a single gB genotype. Compared with single-genotype infection, multiple-genotype infection was correlated with higher CMV loads (p < 0.001) but not correlated with outcome. A higher proportion of patients with the gB3 genotype had received filtering surgery before antiviral treatment than those without the gB3 genotype (p = 0.046). (4) Multiple-genotype infection was highly prevalent in CMV anterior segment infection in Taiwan, and gB1 and gB3 were predominant. Multiple-genotype infection was correlated with higher CMV loads but not with specific clinical manifestations or prognostic outcomes. The gB3 genotype may be correlated with poor intraocular pressure control.

Expeditious Discovery of Small-Molecule Thermoresponsive Ionic Liquid Materials: A Review.

Ionic liquids (ILs) are a class of low-melting molten salts (<100 °C) constituted entirely of ions, and their research has gained tremendous attention in line with their remarkably growing applications (>124,000 publications dated 30 August 2023 from the Web of ScienceTM). In this review, we first briefly discussed the recent developments and unique characteristics of ILs and zwitterionic liquids (ZILs). Compared to molecular solvents and other conventional organic compounds, (zwitter) ionic liquids carry negligible volatility and are potentially recyclable and reusable. For structures, both ILs and ZILs can be systematically tailor-designed and engineered and are synthetically fine-tunable. As such, ionic liquids, including chiral, supported, task-specific ILs, have been widely used as powerful ionic solvents as well as valuable additives and catalysts for many chemical reactions. Moreover, ILs have demonstrated their value for use as polymerase chain reaction (PCR) enhancers for DNA amplification, chemoselective artificial olfaction for targeted VOC analysis, and recognition-based affinity extraction. As the major focus of this review, we extensively discussed that small-molecule thermoresponsive ILs (TILs) and ZILs (zwitterionic TILs) are new types of smart materials and can be expeditiously discovered through the structure and phase separation (SPS) relationship study by the combinatorial approach. Using this SPS platform developed in our laboratory, we first depicted the rapid discovery of N,N-dialkylcycloammonium and 1,3,4-trialkyl-1,2,3-triazolium TILs that concomitantly exhibited LCST (lower critical solution temperature) phase transition in water and displayed biochemically attractive Tc values. Both smart IL materials were suited for applications to proteins and other biomolecules. Zwitterionic TILs are ZILs whose cations and anions are tethered together covalently and are thermoresponsive to temperature changes. These zwitterionic TIL materials can serve as excellent extraction solvents, through temperature change, for biomolecules such as proteins since they differ from the common TIL problems often associated with unwanted ion exchanges during extractions. These unique structural characteristics of zwitterionic TIL materials greatly reduce and may avoid the denaturation of proteins under physiological conditions. Lastly, we argued that both rational structural design and combinatorial library synthesis of small-molecule TIL materials should take into consideration the important issues of their cytotoxicity and biosafety to the ecosystem, potentially causing harm to the environment and directly endangering human health. Finally, we would concur that before precise prediction and quantitative simulation of TIL structures can be realized, combinatorial chemistry may be the most convenient and effective technology platform to discover TIL expeditiously. Through our rational TIL design and combinatorial library synthesis and screening, we have demonstrated its power to discover novel chemical structures of both TILs and zwitterionic TILs. Undoubtedly, we will continue developing new small-molecule TIL structures and studying their applications related to other thermoresponsive materials.

Effects of parents' voice on reducing heel puncture pain in high-risk newborns: A randomized controlled trial.

BACKGROUND: High-risk newborns, such as premature or severely ill infants, often experience painful treatments and separation from their parents. While previous studies have focused on the positive impacts of a mother's voice on newborns' physiology and pain response, research on the father's voice and vocal acoustics in high-risk newborns is limited. AIM: To examine whether parents' voices reduce heel puncture pain in high-risk newborns and the relationship between parents' vocal acoustics, physiological parameters and pain response. STUDY DESIGN: A randomized controlled clinical trial was conducted with 105 high-risk newborn-parent dyads. Participants were randomly assigned to three groups: recorded mother's voice, recorded father's voice or control group without any recorded voice. Outcome measures included heart rate, respiratory rate, oxygen saturation and pain response assessed using the Neonatal Infant Pain Scale. Data analysis utilized generalized estimation equations, and parents' vocal acoustics were analysed using Praat voice credit software. RESULTS: The mother's voice group exhibited significantly lower heart rates at 1, 5 and 10 min after the procedure, along with lower respiratory rates and pain levels at 5 and 10 min after the procedure compared with the control group. Similarly, the father's voice group demonstrated significantly lower heart rates at 1 and 5 min after the procedure, decreased respiratory rates at 5 and 10 min after the procedure and reduced pain levels at 1 and 5 to 10 min after the procedure compared with the control group. Higher minimum and mean pitches in parents' voices correlated with slower heart rates, while slower parental speech was associated with reduced newborn pain. CONCLUSION: Both maternal and paternal vocal interventions alleviated pain during heel puncture procedures among high-risk newborns. RELEVANCE TO CLINICAL PRACTICE: The noninvasive intervention serves as a reference for parental participation in care. Nurses can help parents to intervene with the acoustic characteristics that alleviate pain among high-risk newborns.

Personal and household PM2.5 and black carbon exposure measures and respiratory symptoms in 8 low- and middle-income countries.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements. OBJECTIVE: To examine associations between household and personal fine particulate matter (PM2.5) and black carbon (BC) measures and respiratory symptoms. METHODS: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates. RESULTS: The median (interquartile range) of household and personal PM2.5 was 73.5 (119.1) and 65.3 (91.5) µg/m3, and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10-5 m-1, respectively. We observed associations between household PM2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision. CONCLUSIONS: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms.

Abusive head trauma: current practice of investigation and management in Taiwan.

INTRODUCTION: Abusive head trauma (AHT) is a worldwide leading cause of fatal head injuries in children under 2 years. This study aims to present the development of child protection medical service in Taiwan in the past decade. MATERIALS AND METHODS: This study reviews the evolution of the pediatric protection network and the cross-system professional training in Taiwan from 2013 to 2022. The recommendations of Taiwan Pediatric Association on the prevention and management of AHT and the Medical Professionals Manual of Child Abuse and Neglect proposed by the Ministry of Health and Welfare were reviewed. RESULTS: Considering the impact of the high incidence of severe sequelae and the mortality caused by of AHT, 10 regional centers for child protection medical service were founded in Taiwan to identify, recognize, and properly manage cases of AHT, which is easily overlooked by the healthcare providers. The child protection network across the healthcare, social welfare administration, and judicial systems facilitate the early detection, management, and proper disposition of the children with AHT. CONCLUSION: An increasing of the incidence of AHT is expected after the setting up of the child protection network and the continuing cross-system professional trainings. There is more consensus of the diagnosis and management of AHT than before in Taiwan. However, there is no end to protecting children from AHT.

Eye motor manifestations in children with neurometabolic disorders.

Neurometabolic diseases are complex group of rare neurogenetic disorders, which are difficult to diagnose. Patients may have toxic metabolite accumulation, inadequate energy supply, or neurotransmitter deficiency, resulting in a variety of clinical manifestations and severity with enzyme activity or transporter function defects. Multiple organ involvement is frequently seen, among which neurological symptoms and signs are one of the most encountered problems. Ocular motor problems deserve special attention for it occurs in some inborn error of metabolism. Furthermore, some are early signs or characteristic findings of certain diseases, such as the gaze palsy in Niemann-Pick disease type C and Gaucher disease or oculogyric crisis in neurotransmitter diseases. Early recognition and intervention are important for better prognosis in treatable neurometabolic disorders. In addition, ways to evaluate and describe eye movement problems also help to demonstrate the severity or clinical progression for those diagnosed with certain neurometabolic diseases. However, the complexity of eye movement and ocular motor control renders our clinical observation, recording and even anatomic localization of abnormal eye movements. Clinicians are more likely to detect early signs and unravel problems by gaining awareness of abnormal eye movement. This study amied to approach neurometabolic diseases in children via eye motor manifestations.

Emerging impacts of ionic liquids on eco-environmental safety and human health.

Owing to their unique physicochemical properties, ionic liquids (ILs) have been rapidly applied in diverse areas, such as organic synthesis, electrochemistry, analytical chemistry, functional materials, pharmaceutics, and biomedicine. The increase in the production and application of ILs has resulted in their release into aquatic and terrestrial environments. Because of their low vapor pressure, ILs cause very little pollution in the atmosphere compared to organic solvents. However, ILs are highly persistent in aquatic and terrestrial environments due to their stability, and therefore, potentially threaten the safety of eco-environments and human health. Specifically, the environmental translocation and retention of ILs, or their accumulation in organisms, are all related to their physiochemical properties, such as hydrophobicity. Based on results of ecotoxicity, cytotoxicity, and toxicity in mammalian models, the mechanisms involved in IL-induced toxicity include damage of cell membranes and induction of oxidative stress. Recently, artificial intelligence and machine learning techniques have been used in mining and modeling toxicity data to make meaningful predictions. Major future challenges are also discussed. This review will accelerate our understanding of the safety issues of ILs and serve as a guideline for the design of the next generation of ILs.

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.

BACKGROUND: Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. METHODS: The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. RESULTS: Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. CONCLUSIONS: These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

Predicting visual acuity in Bietti crystalline dystrophy: evaluation of image parameters.

BACKGROUND: To analyze multiple imaging modalities in patients with Bietti crystalline dystrophy (BCD) and to investigate which factors from these modalities are associated with best corrected visual acuity (BCVA). METHODS: In this retrospective study, 40 eyes from 22 patients with BCD were included and were separated into group 1 (BCVA ≤20/200) and group 2 (BCVA > 20/200). Data including BCVA and characteristic findings from near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF), and spectral domain-optic coherence tomography (SD-OCT) were analyzed and compared. The outcome measures of multimodal imaging were evaluated for correlation with BCVA. RESULTS: NIR is a good diagnostic tool for detecting either crystalline or sclerotic vessels in BCD. Patients in group 1 tended to have a thinner choroid (P = 0.047) with ellipsoid zone (EZ) disruption (P = 0.011). Calculation of the area under the curve indicated that EZ disruption detected on SD-OCT could be a good predictor of legal blindness in BCD. CONCLUSION: For the diagnosis of BCD, NIR could be a good diagnostic tool. Of the studied imaging modalities, we found that EZ disruption at the fovea were strongly associated with legal blindness, which could be easily assessed by SD-OCT.

Conjunctival melanoma: A 20-year survey in a comprehensive medical center.

BACKGROUND: To better understand population-specific tumor characteristics and behavior of conjunctival melanoma in Asian. METHODS: A retrospective cohort enrolled patients with primary conjunctival melanoma treated and followed up at Chang Gung Memorial Hospital (CGMH) in Taiwan between 1995 and 2015. Basic characteristics such as age, gender, tumor size, cell type, location, and TNM stage were recorded. Prognostic parameters included disease free interval, local recurrence, distant metastasis, and survival were analyzed. RESULTS: There were 20 patients enrolled in the study hospital between 1995 and 2015. All were histological proved by pathologists. Their mean age at diagnosis was 57.8 ± 15.9 years. The mean follow-up time was 68.7 ± 55.8 months. Mean tumor thickness was 6.5 ± 5.9 mm. Six patients developed local recurrence. Twelve patients had distant metastasis. Ten patients died from conjunctival melanoma. The 10 patients had greater mean tumor thickness (8.4 ± 7.5 mm) and shorter mean survival time (40.2 ± 24.1 months). Tumor thickness was found as a prognostic factor for survival time (HR = 1.15, P = 0.01). Age, gender, T stage, and tumor location were not significantly associated with survival. CONCLUSION: Different tumor characteristics were found in this cohort. Higher metastasis and mortality rate could suggest a more aggressive disease pattern. Tumor thickness was indicated as a prognostic factor for survival time and was greater in size in cases with distant metastasis. Early and more invasive intervention with closely follow-up may be indicated in these cases.

DMAS Beamforming with Complementary Subset Transmit for Ultrasound Coherence-Based Power Doppler Detection in Multi-Angle Plane-Wave Imaging.

Conventional ultrasonic coherent plane-wave (PW) compounding corresponds to Delay-and-Sum (DAS) beamforming of low-resolution images from distinct PW transmit angles. Nonetheless, the trade-off between the level of clutter artifacts and the number of PW transmit angle may compromise the image quality in ultrafast acquisition. Delay-Multiply-and-Sum (DMAS) beamforming in the dimension of PW transmit angle is capable of suppressing clutter interference and is readily compatible with the conventional method. In DMAS, a tunable p value is used to modulate the signal coherence estimated from the low-resolution images to produce the final high-resolution output and does not require huge memory allocation to record all the received channel data in multi-angle PW imaging. In this study, DMAS beamforming is used to construct a novel coherence-based power Doppler detection together with the complementary subset transmit (CST) technique to further reduce the noise level. For p = 2.0 as an example, simulation results indicate that the DMAS beamforming alone can improve the Doppler SNR by 8.2 dB compared to DAS counterpart. Another 6-dB increase in Doppler SNR can be further obtained when the CST technique is combined with DMAS beamforming with sufficient ensemble averaging. The CST technique can also be performed with DAS beamforming, though the improvement in Doppler SNR and CNR is relatively minor. Experimental results also agree with the simulations. Nonetheless, since the DMAS beamforming involves multiplicative operation, clutter filtering in the ensemble direction has to be performed on the low-resolution images before DMAS to remove the stationary tissue without coupling from the flow signal.

Structural Engineering and Optimization of Zwitterionic Salts for Expeditious Discovery of Thermoresponsive Materials.

This work reported the discovery of N-triflimide (NTf)-based zwitter-ionic liquids (ZILs) that exhibit UCST-type phase transitions in water, and their further structural optimization in fine-tuning polarity to ultimately afford newfangled thermosensitive materials carrying attractive and biocompatible Tc values that clearly demonstrated the true value of the tunability of ZIL structure. This research established that with non-aromatic, acyclic ZILs as small-molecule thermoresponsive materials, their mixing and de-mixing with water triggered by temperatures are entirely reversible.

[2,2](5,8)Picenophanedienes: Syntheses, Structural Analyses, Molecular Dynamics, and Reversible Intramolecular Structure Conversion.

This study presents an important and efficient synthetic approach to 5,8-dibromo-2,11-di-tert-butylpicene (3), with multigram scale, which was then converted to a new series of picenophanes (6-10). The tub-shaped [2,2](5,8)picenophanediene 8 with two cis-ethylene linkers was explored using X-ray crystallography. The tub-to-tub inversion proceed through the successive bending of the linkers and the barrier for isopropyl-substituted derivative 10 was experimentally estimated to be 18.7 kcal/mol. Picenophanes with a large π-system and semi-rigid structure exhibited anomalous photophysical properties. The ethano-bridged picenophane shows the weak exciton delocalization while the cis-ethylene-bridged picenophane exhibits dual emission rendered by the weakly delocalized exciton and excimer. With the aid of the ultrafast time-resolved emission spectroscopy, the mechanism of the excimer formation is resolved, showing a unique behavior of two-state reversible reaction with fast structural deformation whose lifetime is around 20 ps at 298 K. This work demonstrates that the slight difference in the bridge of tub-shaped picenophanes renders distinct photophysical behavior, revealing the potential of harnessing inter-moiety reaction in the picenophane systems.

Sacubitril/Valsartan Therapy Ameliorates Ventricular Tachyarrhythmia Inducibility in a Rabbit Myocardial Infarction Model.

BACKGROUND: Coronary artery disease is the most common cause of heart failure (HF) in developed countries. The aim of this study was to elucidate the mechanisms of reduction of arrhythmias after sacubitril/valsartan (LCZ696) therapy in a myocardial infarction (MI)-HF rabbit model. METHODS AND RESULTS: Chronic MI in rabbits with HF were divided into 3 groups: placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4 weeks of therapy, an electrophysiologic study and a dual voltage-calcium optical mapping study were performed. The LCZ696 group had significantly better left ventricular ejection fraction and lower ventricular tachyarrhythmia inducibility than the valsartan and placebo groups. The most common ventricular tachyarrhythmia pattern was 1 or 2 ectopic beats originating from the peri-infarct areas, followed by re-entrant beats surrounding phase singularity points. Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action-potential duration, shorter intracellular calcium tau constant, faster conduction velocity, and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression. CONCLUSIONS: In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated postinfarct heart function impairment and electrophysiologic remodeling and altered CaMKII-p expression, leading to reduced ventricular tachyarrhythmia inducibility.