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Introduction: Central venous catheter (CVC) placement is commonly performed in children. We aim to develop simple formulas to predict CVC intravascular length to minimise radiation exposure associated with the procedure. Methods: 124 paediatric patients who received tunnelled neck CVCs and subsequent CT thorax at Hong Kong Children's Hospital from January 2020 to July 2022 were reviewed retrospectively. Formula development cohorts were subdivided by insertion sites—9 right external jugular vein (REJV), 41 right internal jugular vein (RIJV), 14 left external jugular vein (LEJV), 10 left internal jugular vein (LIJV). Using measurements from CT by two radiologists, formulas predicting the CVC intravascular length based on height and insertion sites were developed using a linear regression model. These formulas were tested with validation cohorts (10 randomly selected cases in REJV and RIJV groups respectively). Validation cohorts were not available for LEJV and LIJV groups due to small sample sizes. Result: The goodness-of-fit (R^2) of all formulas are above 0.8. In the validation cohorts, the REJV formula was predictive of intravascular CVC length within 1 cm in 70% of CVC with mean absolute difference of 0.63 cm (SD 0.48 cm), and the RIJV formula was predictive of intravascular CVC length within 1 cm in 80% of CVC with mean absolute difference of 0.67 cm (SD 0.53 cm). Conclusion: Intravascular CVC length can be estimated using simple formulas based on height and insertion sites. Further prospective validation of the LEJV and LIJV formulas is needed. [ABSTRACT FROM AUTHOR]

Quantum error correction is essential for realizing the full potential of large-scale quantum information processing devices1,2. Fundamental to its experimental realization is the repetitive detection of errors via projective measurements of quantum correlations among qubits, as well as corrections using conditional feedback3. Repetitive application of such tasks requires that they neither induce unwanted crosstalk nor impede further control operations, which is challenging owing to the need to dissipatively couple qubits to the classical world for detection and reinitialization. For trapped ions, state readout involves scattering large numbers of resonant photons, which increases the probability of stray light causing errors on nearby qubits and leads to undesirable recoil heating of the ion motion. Here we demonstrate up to 50 sequential measurements of correlations between two beryllium ion microwave qubits using an ancillary optical qubit in a calcium ion, and implement feedback that allows us to stabilize two-qubit subspaces as well as Bell states, a class of maximally entangled states. Multi-qubit mixed-species gates are used to transfer information within the register from the qubit to the ancilla, enabling readout with negligible crosstalk to the data qubits. Heating of the ion motion during detection is mitigated by recooling all three ions using light that interacts with only the calcium ion, known as sympathetic cooling. A key element of our experimental setup is a powerful classical control system that features flexible in-sequence processing for feedback control. The methods employed here provide essential tools for scaling trapped-ion quantum computing, quantum-state control and entanglement-enhanced quantum metrology4. [ABSTRACT FROM AUTHOR]

This paper presents a study of the waves generated by a solid block landslide moving along a horizontal boundary. The landslide was controlled using a mechanical system in a series of physical experiments, and laser-induced fluorescence measurements resolved both spatial and temporal variations in the free surface elevation. During its constant-velocity motion, the landslide transferred energy into 'trapped' offshore-propagating waves within a narrow frequency band. The wave trapping is demonstrated by investigating the wave dispersion characteristics using a two-dimensional Fourier Transform. The first of the trailing waves broke at Froude numbers greater than or equal to 0.625. The parametric dependence of the largest-amplitude waves and the potential energy within the wave field are discussed. The experimental results were compared to the predictions of an incompressible Navier-Stokes solver with and without turbulence models. The numerical model under-predicted the measured wave amplitudes, although it accurately predicted the measured wave phasing. The turbulent model more accurately predicted the shapes of the trailing waves. Both experimental and numerical results confirmed that investigations into wave generation by submerged objects moving at constant velocity should also consider the initial acceleration of the object, as this affects the overall evolution of the wave field. The applicability of the horizontal-boundary results to more realistic field scenarios is discussed. [ABSTRACT FROM AUTHOR]

The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective owing to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling analysis. Our results revealed that the miR-509 is highly expressed in the primary tumors, whereas the expression of this microRNA is significantly decreased in the brain metastatic lesions. MicroRNA target prediction and the analysis of cytokine array for the cells ectopically expressed with miR-509 demonstrated that this microRNA was capable of modulating the two genes essential for brain invasion, RhoC and TNF-α that affect the invasion of cancer cells and permeability of BBB, respectively. Importantly, high levels of TNF-α and RhoC-induced MMP9 were significantly correlated with brain metastasis-free survival of breast cancer patients. Furthermore, the results of our in vivo experiments indicate that miR-509 significantly suppressed the ability of cancer cells to metastasize to the brain. These findings suggest that miR-509 has a critical role in brain metastasis of breast cancer by modulating the RhoC-TNF-α network and that this miR-509 axis may represent a potential therapeutic target or serve as a prognostic tool for brain metastasis. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is an essential step for tumor progression, although the mechanisms driving EMT are still not fully understood. In an effort to investigate these mechanisms, we observed that heregulin (HRG)-mediated activation of HER2, or HER2 overexpression, resulted in EMT, which is accompanied with increased expression of a known EMT regulator Slug, but not TWIST or Snail. We then investigated how HER2 induced Slug expression and found, for the first time, that there are four consensus HSF sequence-binding elements (HSEs), the binding sites for heat shock factor-1 (HSF-1), located in the Slug promoter. HSF-1 bound to and transactivated the Slug promoter independent of heat shock, leading to Slug expression in breast cancer cells. Mutation of the putative HSEs ablated Slug transcriptional activation induced by HRG or HSF-1 overexpression. Knockdown of HSF-1 expression by siRNA reduced Slug expression and HRG-induced EMT. The positive association between HSF-1 and Slug was confirmed by immunohistochemical staining of a cohort of 100 invasive breast carcinoma specimens. While investigating how HER2 activated HSF-1 independent of heat shock, we observed that HER2 activation resulted in concurrent phosphorylation of Akt and HSF-1. We then observed, also for the first time, that Akt directly interacted with HSF-1 and phosphorylated HSF-1 at S326. Inhibition of Akt using siRNA, dominant-negative Akt mutant, or small molecule inhibitors prevented HRG-induced HSF-1 activation and Slug expression. Conversely, constitutively active Akt induced HSF-1 phosphorylation and Slug expression. HSF-1 knockdown reduced the ability of Akt to induce Slug expression, indicating an essential role that HSF-1 plays in Akt-induced Slug upregulation. Altogether, our study uncovered the existence of a novel Akt-HSF-1 signaling axis that leads to Slug upregulation and EMT, and potentially contributes to progression of HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

The Hedgehog signaling pathway is one of the most dysregulated pathways in human cancers. The glioma-associated oncogene homolog 1 (GLI1) transcription factor is the terminal effector of the Hedgehog pathway, frequently activated in human breast cancer and an emerging target of breast cancer therapy. While somatic mutations in the human GLI1 gene have never been reported in any cell or tumor type, we recently uncovered the existence of a novel alternatively spliced, truncated GLI1 (tGLI1) that has an in-frame deletion of 41 codons spanning the entire exon 3 and part of exon 4 of the GLI1 gene. Using glioblastoma models, we showed that tGLI1 has gained the ability to promote glioblastoma migration and invasion via its gain-of-function transcriptional activity. However, the pathological impact of tGLI1 on breast cancer remains undefined. Here, we report that tGLI1 is frequently expressed in human breast cancer cell lines and primary specimens we have examined to date, but is undetectable in normal breast tissues. We found for the first time that tGLI1, but not GLI1, binds to and enhances the human vascular endothelial growth factor-A (VEGF-A) gene promoter, leading to its upregulation. Consequently, tGLI1-expressing MDA-MB-231 breast cancer cells secret higher levels of VEGF-A and contain a higher propensity, than the isogenic cells with control vector and GLI1, to stimulate in vitro angiogenesis of human vascular endothelial cells. We further showed that tGLI1 has gained the ability to enhance the motility and invasiveness of breast cancer cells in a proliferation-independent manner and that this functional gain is associated with increased expression of migration/invasion-associated genes, CD24, MMP-2 and MMP-9. tGLI1 has also acquired the property to facilitate anchorage-independent growth of breast cancer cells. Collectively, our results define tGLI1 as a gain-of-function GLI1 transcription factor and a novel mediator of the behavior of clinically more aggressive breast cancer. [ABSTRACT FROM AUTHOR]

In this study, Grey model (GM) and artificial neural network (ANN) were employed to predict suspended solids (SSeff) and chemical oxygen demand (CODeff) in the effluent from a wastewater treatment plant in industrial park of Taiwan. When constructing model or predicting, the influent quality or online monitoring parameters were adopted as the input variables. ANN was also adopted for comparison. The results indicated that the minimum MAPEs of 16.13 and 9.85% for SSeff and CODeff could be achieved using GMs when online monitoring parameters were taken as the input variables. Although a good fitness could be achieved using ANN, they required a large quantity of data. Contrarily, GM only required a small amount of data (at least four data) and the prediction results were even better than those of ANN. Therefore, GM could be applied successfully in predicting effluent when the information was not sufficient. The results also indicated that these simple online monitoring parameters could be applied on prediction of effluent quality well. [ABSTRACT FROM AUTHOR]

Small interfering RNA (siRNA) mediates sequence-specific RNA cleavage and represents a potential approach to treat the infection of human immunodeficiency virus (HIV). Expression of a single siRNA species frequently led to the emergence of HIV escape variants. Thus, multiple siRNAs targeted to different regions in the HIV-1 genome may be required. However, overexpression of different anti-HIV siRNA genes from multiple pol III promoters can induce cell toxicity, thus may not be a viable option in the setting of human gene therapy trials. In the current study, we evaluated the strategy of using pol II promoters to drive the expression of siRNAs against HIV-1. We replaced the stem sequence in the stem-loop structure of the well-characterized miR-30a with siRNA sequences and showed that designed microRNA (miRNA) could be expressed from pol II promoters. We demonstrated efficient inhibition of HIV-1 replication with such designed miRNA, but the efficacy was directly correlated with the expression level. Both the vector copy number and the promoter strength directly affected the ability of the siRNA to inhibit HIV-1 replication. We also showed that a combination of pol II and pol III promoters to express two different siRNAs increased the efficacy against HIV-1 replication without comprising cell viability.Gene Therapy (2007) 14, 1503–1512; doi:10.1038/sj.gt.3303011; published online 6 September 2007 [ABSTRACT FROM AUTHOR]

The association between hypogonadism, quality of life (QoL), and erectile dysfunction (ED) among the middle-aged and aged male in Taiwan is evaluated. A total of 680 study subjects aged 40 years old were recruited from Northern (n=276), Middle (n=238), and Southern (n=202) Taiwan, respectively. ED was diagnosed by score of International Index of Erectile Function (IIEF-5). Taiwan version questionnaire for QoL includes domain 1 (physical domain), domain 2 (psychological domain), domain 3 (social relationship domain), and domain 4 (environmental domain) was used to measure QoL. Blood hormones, including FSH, LH, Prolactin, SHBG, total testosterone (TT), calculated free testosterone (cFT), and bioavailable testosterone (Bio-T), were determined. Logistic regression analysis was used to estimate crude and multivariate-adjusted odds ratio of risk factors and its 95% confidence interval. A significantly inverse association between concentration of serum cFT and Bio-T, and severity of ED was observed. Scores of QoL of Domain 1–4 were significantly decreased with the increament of severity of ED. Significant correlations were found between IIEF scores and four domains of QoL, respectively. After adjustment for age, cFT and Bio-T, study subjects with ED (IIEF21) would have significantly high risk of low level of QoL in four domains. In conclusion, a significant association between low levels of serum calculated cFT, Bio-T, and severity of ED was found. In addition, abnormal erectile function significantly associated with low level of QoL in four domains.International Journal of Impotence Research (2007) 19, 69–75. doi:10.1038/sj.ijir.3901480; published online 11 May 2006 [ABSTRACT FROM AUTHOR]

Emerging evidences suggest the existence of a new mode of epidermal growth factor receptor (EGFR) signalling pathway in which activated EGFR undergoes nuclear translocalization and subsequently regulates gene expression and potentially mediates other cellular processes. This signalling route is distinct from the better-characterized, traditional EGFR pathway that involves transduction of mitogenic signals through activation of multiple signalling cascades. Transcriptional activity of nuclear EGFR appears to depend on its C-terminal transactivation domain and its physical and functional interaction with other transcription factors that contain DNA-binding activity. Likely via its ability to upregulate gene expression, nuclear EGFR pathway is associated with major characteristics of more aggressive tumours: increased proliferative potential, nitric oxide synthesis, and accelerated G1/S cell cycle progression. A role of nuclear EGFR in prognostic prediction is further suggested in patients with breast carcinomas and oropharyngeal squamous cell carcinomas. It is noted that significant advances were made towards the knowledge of the nuclear EGFR pathway; however, many aspects of this new pathway remain unresolved and will be discussed in this review. As a number of other receptor tyrosine kinases (RTKs) and cytokine receptors also undergo similar nuclear translocalization, a better understanding of the physiological and malignant nature of the nuclear EGFR pathway will likely shed light into the biology of cancer with nuclear RTKs. [ABSTRACT FROM AUTHOR]

BACKGROUND: The increased health risks associated with obesity have been found to occur in Asians at lower body mass indices (BMIs). To determine the optimal cut-off values for overweight or obesity in Taiwan, we examined the relationships between four anthropometric indices and cardiovascular risk factors. METHODS: The data were collected from four health-screening centers from 1998 to 2000 in Taiwan. Included were 55 563 subjects (26 359 men and 29 204 women, mean age = 37.3 ± 10.9 and 37.0± 11.1 y, respectively). None had known major systemic diseases or were taking medication. Individual body weight, height, waist circumference (WC), and a series of tests related to cardiovascular risk (blood pressure, fasting plasma glucose, triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol) were assessed and their relationships were examined. Receiver operating characteristic (ROC) analysis was used to find out the optimal cut-off values of various anthropometric indices to predict hypertension, diabetes mellitus and dyslipidemia. RESULTS: Of the four anthropometric indices we studied, waist-to-height ratio (WHtR) in women was found to have the largest areas under the ROC curve (women=0.755, 95% Cl 0.748-0.763) relative to at least one risk factor (ie hypertension or diabetes or dyslipidemia). The optimal cut-off values for overweight or obesity from our study in men and women showed that BMIs of 23.6 and 22.1 kg/m², WCs of 80.5 and 71.5 cm, waist-to-hip ratios (WHpR) of 0.85 and 0.76, and WHtR of 0.48 and 0.45, respectively, may be more appropriate in Taiwan. CONCLUSIONS: WHtR may be a better indicator for screening overweight- or obesity-related CVD risk factors than the other three indexes (BMI, WC and WHpR) in Taiwan. Our study also supported the hypothesis that the cut-off values using BMI and WC to define obesity should be much lower in Taiwan than in Western countries. [ABSTRACT FROM AUTHOR]

Examines the relationships between four anthropometric measurements and cardiovascular risk factors in Taiwan. Collection of data from four nationwide health screen centers in Taiwan from 1998 to 1999; Measurement of individual body weight, height, waist circumference, and cardiovascular risk factors.

The J chain is a component of polymeric immunoglobulin (Ig) molecules and may play an important role in their polymerization and the transport of polymeric Ig across epithelial cells. In this study, the primary structure of the chicken J chain was determined by sequencing cDNA clones. The cDNA had an open reading frame of 476 nucleotides encoding a putative protein of 158 amino acid residues including the signal sequence. The 3′ untranslated region consisted of 1216 nucleotides and a poly(A) tail. The deduced amino acid sequence of the chicken J chain had a high degree of homology to that of human, cow, rabbit, mouse, frog, and earthworm, with eight conserved Cys residues identical to the mammalian J chains. Northern blot hybridization performed with total RNA from various chicken tissues revealed high levels of J-chain mRNA expression in spleen, intestine, Harderian gland, and bursa of Fabricius, and low levels in the thymus. The J chain was expressed in the bursa as early as day 15 of embryogenesis. These data indicated that the chicken J-chain gene displays a high degree of homology with that of other species, and is expressed at an early stage of development of the chicken immune system. [ABSTRACT FROM AUTHOR]

Spindle cell carcinoma is a rare tumor commonly occurring in the upper aerodigestive tract. We report a 62-year-old male with spindle cell sarcomatous change located at the hepatic hilum, resulting in obstructive jaundice. The patient died after an extended resective operation. The rare disease and its histogenesis is discussed. [ABSTRACT FROM AUTHOR]

Conversion of osmified tracheal cartilage constituents into an array of laminar interference gratings has been attained by three tandem reactions. Oxidation of semithin, LR white-embedded cartilage sections by acetic anhydride in dimethyl sulfoxide is the first step in the conversion process. Subsequent addition reactions of oxidized cartilage pyranoses and furanoses with thiocarbohydrazide constitutes the second step. Reduction of silver proteinate by thiocarbohydrazones and the concomitant coating of cartilage constituents with silver gratings completes the conversion of cartilage sections into a system of layered interference filters. In transmitted light, all components of converted cartilage display vivid structural colors, which allow detailed microscopic analysis of structurally colored cellular and extracellular cartilage constituents. [ABSTRACT FROM AUTHOR]

Proteins in lysosomal membranes, lysosomes and within the transtubular network are readily accessible for electron microscopic analysis by a new three-step method. Oxidative deamination of tissue-bound amino acids by ninhydrin in a queous dimethyl sulfoxide and the concomitant formation of corresponding carbonyl groups comprise the first step. The addition reaction of thiocarbohydrazide to tissue-bound carbonyl groups comprises the second step, while the reduction of silver proteinate by tissue-bound thiocarbohydrazones is the final step of this sequential method. Glutaraldehyde-fixed and osmified ultrathin sections of rat liver embedded in LR White were oxidatively deaminated for 24 h by 1% w/v ninhydrin in aqueous 75% v/v dimethyl sulfoxide (DMSO). They were then incubated for 40 min in aqueous 1% w/v thiocarbohydrazide (TCH) and stained for 30 min at 50° C with silver proteinate (SP). The ninhydrin-dimethyl sulfoxide-thiocarbohydrazidesilver proteinate (N-DMSO-TCH-SP) reaction proved to be chemically specific and highly selective for ultrastructural resolution of the internal structure of lysosomes and their protein components. We conclude that the N-DMSO-TCH-SP reaction is the method of choice for cytochemical elucidation of the protein ultrastructure of lysosomes and their enzymatic aggregates. [ABSTRACT FROM AUTHOR]

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Interbreeding between domesticated and wild animals occurs in several species. This gene flow has long been anticipated to induce genetic changes in life-history traits of wild populations, thereby influencing population dynamics and viability. Here, we show that individuals with high levels of introgression (domesticated ancestry) have altered age and size at maturation in 62 wild Atlantic salmon Salmo salar populations, including seven ancestral populations to breeding lines of the domesticated salmon. This study documents widespread changes to life-history traits in wild animal populations following gene flow from selectively bred, domesticated conspecifics. The continued high abundance of escaped, domesticated Atlantic salmon thus threatens wild Atlantic salmon populations by inducing genetic changes in fitness-related traits. Our results represent key evidence and a timely warning concerning the potential ecological impacts of the globally increasing use of domesticated animals.