Initial experience with the Oncotype DX assay in decision-making for adjuvant therapy of early oestrogen receptor-positive breast cancer in Hong Kong

published_or_final_versio

A novel long non-coding natural antisense RNA is a negative regulator of Nos1 gene expression

Long non-coding natural antisense transcripts (NATs) are widespread in eukaryotic species. Although recent studies indicate that long NATs are engaged in the regulation of gene expression, the precise functional roles of the vast majority of them are unknown. Here we report that a long NAT (Mm-antiNos1 RNA) complementary to mRNA encoding the neuronal isoform of nitric oxide synthase (Nos1) is expressed in the mouse brain and is transcribed from the non-template strand of the Nos1 locus. Nos1 produces nitric oxide (NO), a major signaling molecule in the CNS implicated in many important functions including neuronal differentiation and memory formation. We show that the newly discovered NAT negatively regulates Nos1 gene expression. Moreover, our quantitative studies of the temporal expression profiles of Mm-antiNos1 RNA in the mouse brain during embryonic development and postnatal life indicate that it may be involved in the regulation of NO-dependent neurogenesis

Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo

Whether neurons can restore their original connectivity patterns during circuit repair is unclear. Taking advantage of the regenerative capacity of zebrafish retina, we show here the remarkable specificity by which surviving neurons reassemble their connectivity upon regeneration of their major input. H3 horizontal cells (HCs) normally avoid red and green cones, and prefer ultraviolet over blue cones. Upon ablation of the major (ultraviolet) input, H3 HCs do not immediately increase connectivity with other cone types. Instead, H3 dendrites retract and re-extend to contact new ultraviolet cones. But, if regeneration is delayed or absent, blue-cone synaptogenesis increases and ectopic synapses are made with red and green cones. Thus, cues directing synapse specificity can be maintained following input loss, but only within a limited time period. Further, we postulate that signals from the major input that shape the H3 HC's wiring pattern during development persist to restrict miswiring after damage

Functional Organization of Locomotor Interneurons in the Ventral Lumbar Spinal Cord of the Newborn Rat

Although the mammalian locomotor CPG has been localized to the lumbar spinal cord, the functional-anatomical organization of flexor and extensor interneurons has not been characterized. Here, we tested the hypothesis that flexor and extensor interneuronal networks for walking are physically segregated in the lumbar spinal cord. For this purpose, we performed optical recordings and lesion experiments from a horizontally sectioned lumbar spinal cord isolated from neonate rats. This ventral hemi spinal cord preparation produces well-organized fictive locomotion when superfused with 5-HT/NMDA. The dorsal surface of the preparation was visualized using the Ca2+ indicator fluo-4 AM, while simultaneously monitoring motor output at ventral roots L2 and L5. Using calcium imaging, we provided a general mapping view of the interneurons that maintained a stable phase relationship with motor output. We showed that the dorsal surface of L1 segment contains a higher density of locomotor rhythmic cells than the other segments. Moreover, L1 segment lesioning induced the most important changes in the locomotor activity in comparison with lesions at the T13 or L2 segments. However, no lesions led to selective disruption of either flexor or extensor output. In addition, this study found no evidence of functional parcellation of locomotor interneurons into flexor and extensor pools at the dorsal-ventral midline of the lumbar spinal cord of the rat

Saliva Viral Load Better Correlates with Clinical and Immunological Profiles in Children with Coronavirus Disease 2019

BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 2020. NPS and saliva viral loads were correlated (r=0.315, p=0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r=-0.532, p<0.001) and saliva (r=-0.417, p<0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p<0.05), and were inversely correlated with total lymphocyte (r=-0.43), CD3 (r=-0.55), CD4 (r=-0.60), CD8 (r=-0.41), B (r=-0.482), and NK (r=-0.416) lymphocyte counts (all p<0.05). Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS

Artificial intelligence and visual analytics in geographical space and cyberspace: Research opportunities and challenges

In recent decades, we have witnessed great advances on the Internet of Things, mobile devices, sensor-based systems, and resulting big data infrastructures, which have gradually, yet fundamentally influenced the way people interact with and in the digital and physical world. Many human activities now not only operate in geographical (physical) space but also in cyberspace. Such changes have triggered a paradigm shift in geographic information science (GIScience), as cyberspace brings new perspectives for the roles played by spatial and temporal dimensions, e.g., the dilemma of placelessness and possible timelessness. As a discipline at the brink of even bigger changes made possible by machine learning and artificial intelligence, this paper highlights the challenges and opportunities associated with geographical space in relation to cyberspace, with a particular focus on data analytics and visualization, including extended AI capabilities and virtual reality representations. Consequently, we encourage the creation of synergies between the processing and analysis of geographical and cyber data to improve sustainability and solve complex problems with geospatial applications and other digital advancements in urban and environmental sciences

Spirituality and end-of-life care in disadvantaged men dying of prostate cancer

Despite the positive influence of spiritual coping on the acceptance of a cancer diagnosis, higher spirituality is associated with receipt of more high intensity care at the end of life. The purpose of our study was to assess the association between spirituality and type of end-of-life care received by disadvantaged men with prostate cancer. We studied low-income, uninsured men in IMPACT, a state-funded public assistance program, who had died since its inception in 2001. Of the 60 men who died, we included the 35 who completed a spirituality questionnaire at program enrollment. We abstracted sociodemographic and clinical information as well as treatment within IMPACT, including zolendroic acid, chemotherapy, hospice use, and palliative radiation therapy. We measured spirituality with the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being questionnaire (FACIT-Sp) and compared end-of-life care received between subjects with low and high FACIT-Sp scores using chi-squared analyses. A higher proportion of men with high (33%) versus low (13%) spirituality scores enrolled in hospice, although our analysis was not adequately powered to demonstrate statistical significance. Likewise, we saw a trend toward increased receipt of palliative radiation among those with higher spirituality (37% vs. 25%, P = 0.69). The differences in end-of-life care received among those with low and high spirituality varied little by the FACIT-Sp peace and faith subscales. End-of-life care was similar between men with lower and higher spirituality. Men with higher spirituality trended toward greater hospice use, suggesting that they redirected the focus of their care from curative to palliative goals

Feasibility investigation of direct laser cutting process of metal foam with high pore density

To avoid damage to the pore structure of metal foam, a laser cutting process for efficiently and directly cutting metal foam into regular shapes is proposed. After analyzing the proposed laser cutting process, its effects when applied to three different types of metal material (copper, ferroalloy, and nickel) and two levels of pore density, namely 90 and 110 pores per inch (PPI), were investigated. The results show that metal foam with a good surface quality can be obtained without damaging the pore structure by using the proposed laser cutting process. Of the three metal types considered, the highest material removal rate (MRR) and material oxidation rate (MOR) were observed for ferroalloy foam. Of the two pore densities, metal foam of 90 PPI showed a larger material removal rate than metal foam of 110 PPI. The MRR and MOR increased with an increase in the laser output power and decrease in the scanning speed. Using a central composite experimental design method, optimized processing parameters of 26 W laser output power and 475 mm/s scanning speed were adopted to cut the metal foam with a high pore density