Computational methods reveal novel functionalities of PIWI-interacting RNAs in human papillomavirus-induced head and neck squamous cell carcinoma.

Human papillomavirus (HPV) infection is the fastest growing cause of head and neck squamous cell carcinoma (HNSCC) today, but its role in malignant transformation remains unclear. This study aimed to conduct a comprehensive investigation of PIWI-interacting RNA (piRNA) alterations and functionalities in HPV-induced HNSCC. Using 77 RNA-sequencing datasets from TCGA, we examined differential expression of piRNAs between HPV16(+) HNSCC and HPV(-) Normal samples, identifying a panel of 30 HPV-dysregulated piRNAs. We then computationally investigated the potential mechanistic significances of these transcripts in HPV-induced HNSCC, identifying our panel of piRNAs to associate with the protein PIWIL4 as well as the RTL family of retrotransposon-like genes, possibly through direct binding interactions. We also recognized several HPV-dysregulated transcripts for their correlations with well-documented mutations and copy number variations in HNSCC as well as HNSCC clinical variables, demonstrating the potential ability of our piRNAs to play important roles in large-scale modulation of HNSCC in addition to their direct, smaller-scale interactions in this malignancy. The differential expression of key piRNAs, including NONHSAT077364, NONHSAT102574, and NONHSAT128479, was verified in vitro by evaluating endogenous expression in HPV(+) cancer vs. HPV(-) normal cell lines. Overall, our novel study provides a rigorous investigation of piRNA dysregulation in HPV-related HNSCC, and lends critical insight into the idea that these small regulatory transcripts may play crucial and previously unidentified roles in tumor pathogenesis and progression

Variation of high mannose chains of Tamm-Horsfall glycoprotein confers differential binding to type 1-fimbriated Escherichia coli.

Tamm-Horsfall glycoprotein (THP), the most abundant protein in mammalian urine, has been implicated in defending the urinary tract against infections by type 1-fimbriated Escherichia coli. Recent experimental evidence indicates that the defensive capability of THP relies on its single high mannose chain, which binds to E. coli FimH lectin and competes with mannosylated uroplakin receptors on the bladder surface. Here we describe several major differences, on both structural and functional levels, between human THP (hTHP) and pig THP (pTHP). pTHP contains a much higher proportion (47%) of Man5GlcNAc2 than does hTHP (8%). FimH-expressing E. coli adhere to monomeric pTHP at an approximately 3-fold higher level than to monomeric hTHP. This suggests that the shorter high mannose chain (Man5GlcNAc2) is a much better binder for FimH than the longer chains (Man6-7GlcNAc2) and that pTHP is a more potent urinary defense factor than hTHP. In addition, unlike hTHP whose polyantennary glycans are exclusively capped by sialic acid and sulfate groups, those of pTHP are also terminated by Galalpha1,3Gal epitope. This is consistent with the fact that the outer medulla of pig kidney expresses the alpha1,3-galactosyltransferase, which is completely absent in human kidney. Finally, pTHP is more resistant to leukocyte elastase hydrolysis than hTHP, thus explaining why pTHP is much less prone to urinary degradation than hTHP. These results demonstrate for the first time that the species variations of the glycomoiety of THP can lead to the differential binding of THP to type 1-fimbriated E. coli and that the differences in high mannose processing may reflect species-specific adaptation of urinary defenses against E. coli infections

Approaches to the Security Analysis of Power Systems: Defence Strategies Against Malicious Threats

This report is intended to provide a conceptual framework for assessing the security risk to power systems assets and operations related to malicious attacks. The problem is analysed with reference to all the actors involved and the possible targets. The specific nature of the malicious attacks is discussed and representations in terms of strategic interaction are proposed. Models based on Game Theory and Multi Agent Systems techniques specifically developed for the representation of malicious attacks against power systems are presented and illustrated with reference to applications to small-scale test systems.JRC.G.6-Sensors, radar technologies and cybersecurit

Recent developments of acupuncture in Australia and the way forward

Almost one in ten Australians has received acupuncture treatment by acupuncturists and/or medical doctors in private clinics. The majority of Australian health insurance funds offer rebates for acupuncture. Statutory regulations for acupuncture have been implemented in the State of Victoria, Australia. Six acupuncture degree courses have been approved by the Chinese Medicine Registration Board of Victoria and/or accredited by the Australian Acupuncture and Chinese Medicine Association. Furthermore, a number of clinical trials of acupuncture on allergic rhinitis, pain and women's health were carried out in Australia. Recent developments of acupuncture in Australia indicate that through adequate and appropriate evaluation, acupuncture begins to integrate into mainstream health care in Australia

Commuter Count: Inferring Travel Patterns from Location Data

In this Working Paper we analyse computational strategies for using aggregated spatio-temporal population data acquired from telecommunications networks to infer travel and movement patterns between geographical regions. Specifically, we focus on hour-by-hour cellphone counts for the SA-2 geographical regions covering the whole of New Zealand. This Working Paper describes the implementation of the inference algorithms, their ability to produce models of travel patterns during the day, and lays out opportunities for future development.Comment: Submitted to Covid-19 Modelling Aotearo

Comparing the Outcomes of Face-to-Face and Synchronous Online Research Mentor Training Using Propensity Score Matching

In this study, propensity score matching (PSM) was conducted to examine differences in the effectiveness of research mentor training (RMT) implemented using two modes-face-to-face or synchronous online training. This study investigated each training mode and assessed participants\u27 perceived gains in mentoring skills, ability to meet mentees\u27 expectations, and overall quality of mentoring, as well as intention to make changes to their mentoring practices. Additional factors that may contribute to participant outcomes were also examined. In total, 152 mentors trained using a synchronous online platform and 655 mentors trained in in-person workshops were analyzed using the PSM method. Mentors were matched based on similar characteristics, including mentee\u27s career stage, mentor\u27s title, mentor\u27s prior mentoring experience, mentor\u27s race/ethnicity and sex, and mentor\u27s years of experience; results show that both face-to-face and synchronous online modes of RMT are effective. Findings indicated that the training mode did not significantly impact the mentors\u27 perceived training outcomes. Factors associated with the reported training outcomes included dosage (hours of training), facilitator effectiveness, race/ethnicity, and previous mentoring experience. The results of this study demonstrate that mentors\u27 perceived training outcomes are comparable regardless of the training modality used-online versus face-to-face

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Effective Application of Knowledge Management in Evidence-based Chinese Medicine: A Case Study

Chinese medicine (CM) practice, as a knowledge-based industry, has not embraced knowledge management (KM) techniques widely. However, KM may facilitate the adaptation and promotion of evidence-based CM. A KM framework was introduced to its activities in evidence-based CM through the development of a CM portal. A codification strategy was used to codify and store knowledge systematically in a database. Several approaches were developed and implemented to address specific needs for CM such as centralizing the information, encouraging collective efforts, promoting integration of explicit and tacit knowledge, and developing a flexible technology and support system. Following the established KM framework, the RMIT Chinese Medicine Portal (www.chinese-medicine.com.au) was built up with four major components: organizational knowledge, knowledge workers, KM processes and information technology. Knowledge on Chinese herbs was classified into core, advanced and innovative categories, which involved the development of the monograph template. A working group was organized including CM, pharmacology and information technology professionals to implement this proposal with following sequential development stages: knowledge creation/acquisition, storage/organization, distribution and application. User interface and web language were also defined and accomplished. This case study demonstrates the applicability of KM in evidence-based CM through a multidisciplinary collaboration, such as, an effective collaboration between CM and information technology. The study also shows the potential of KM application in other disciplines of complementary and alternative medicine

A Metabolic Activation Mechanism of 7H-Dibenzo[c,g]carbazole via O-Quinone. Part 2: Covalent Adducts of 7H-Dibenzo[c,g]carbazole-3,4-dione with Nucleic Acid Bases and Nucleosides

7H-Dibenzo[c,g]carbazole (DBC) is a potent multispecies, multisite carcinogen present in the environment. The metabolic activation pathways of DBC are not completely known. It is hypothesized that DBC may be metabolically activated by oxidation to the reactive Michael acceptor o-quinones, which can form stable and depurinating DNA adducts. The synthesis of DBC-3,4-dione has been previously reported by this research group. In the present article, we describe the synthesis and chemical structural elucidation of nine DBC-nucleic acid adducts produced from reactions of DBC-3,4-dione with Ade, Cyt, 2′-deoxyguanosine (dGuo), 2′- deoxycytidine (dCyd), and Guo. Adducts were isolated from reaction mixtures by HPLC and analyzed using MS including elemental compositions and collision-activated dissociation (CAD), 1H NMR, and two-dimensional chemical shift correlation spectroscopy (COSY) NMR. The adducts, 7-[3,4-dione-DBC-1-yl]-Ade, N4-[3,4-dione-DBC-1-yl]-Cyt, 5-[3,4-dione-DBC-1-yl]-Cyt, two conformational isomers of N2-[3,4-dihydroxy-DBC-1-yl]-dGuo, and two conformational isomers of N2-[3,4-dihydroxy-DBC-1-yl]-Guo, were characterized. Two adducts from reactions of DBC-3,4-dione with dCyd were identified by MS but not fully characterized by NMR due to instability of the adducts. Under similar conditions, the reactions of DBC-3,4-dione with Gua and 2′-deoxyadenosine (dAdo) did not result in an identifiable adduct. Liver DNA adducts from mice treated topically with DBC-3,4-dione (100 µg) in dimethyl sulfoxide/acetone (15/85, 100 µL) were identified with 32P-postlabeling. The major adduct chromatographically matched one of the adducts formed from livers of DBC-treated mouse (adduct 3) using identical conditions

Efficacy and Safety of a Chinese Herbal Medicine Formula (RCM-104) in the Management of Simple Obesity: A Randomized, Placebo-Controlled Clinical Trial

Objective. This study was to evaluate the efficacy and safety of a Chinese herbal medicine formula (RCM-104) for the management of simple obesity. Method. Obese subjects aged between 18 and 60 years were selected for 12-week, double-blind, randomized, placebo-controlled trial. Subjects were randomly assigned to take 4 capsules of either the RCM-104 formula (n = 59) or placebo (n = 58), 3 times daily for 12 weeks. Measures of BW, BMI and WC, HC, WHR and BF composition were assessed at baseline and once every four weeks during the 12 week treatment period. Results. Of the 117 subjects randomised, 92 were included in the ITT analysis. The weight, BMI and BF in RCM-104 group were reduced by 1.5 kg, 0.6 kg/m2 and 0.9% and those in the placebo group were increased by 0.5 kg, 0.2 kg/m2 and 0.1% respectively. There were significant differences in BW and BMI (P < 0.05) between the two groups. Eleven items of the WLQOQ were significantly improved in the RCM-104 group while only 2 items were significantly improved in the placebo group. Adverse events were minor in both groups. Conclusion. RCM-104 treatment appears to be well tolerated and beneficial in reducing BW and BMI in obese subjects