Search

We systematically analyze audio key finding to determine factors important to system design, and the selection and evaluation of solutions. First, we present a basic system, fuzzy analysis spiral array center of effect generator algorithm, with three key determination policies: nearest-neighbor (NN), relative distance (RD), and average distance (AD). AD achieved a 79% accuracy rate in an evaluation on 410 classical pieces, more than 8% higher RD and NN. We show why audio key finding sometimes outperforms symbolic key finding. We next propose three extensions to the basic key finding system—the modified spiral array (mSA), fundamental frequency identification (F0), and post-weight balancing (PWB)—to improve performance, with evaluations using Chopin's Preludes (Romantic repertoire was the most challenging). F0 provided the greatest improvement in the first 8 seconds, while mSA gave the best performance after 8 seconds. Case studies examine when all systems were correct, or all incorrect.

Background: Differences in disease behaviour and genotypes are described in Asian and Western interstitial lung disease (ILD) cohorts. Short leukocyte telomere length (LTL) correlates with poor outcomes in Western ILD cohorts but its significance in Asian populations is unknown. We aim to characterise the burden and clinical implications of short LTL in Singaporean ILD patients., Methods: Patients diagnosed with ILD at Singapore General Hospital were prospectively recruited and compared against 36 healthy controls. The primary outcome was transplant-free survival. Genomic DNA from peripheral blood was extracted and LTL measured using quantitative polymerase chain reaction assay (qPCR)., Results: Amongst 165 patients, 37% had short LTL. There was a higher proportion of combined pulmonary fibrosis and emphysema (CPFE) patients with short LTL (n = 21, 34.4% vs n = 16, 15.4%; p < 0.001). Short LTL patients had reduced survival at 12-, 24- and 36-months and median survival of 24 months (p < 0.001) which remained significant following adjustment for smoking, GAP Stage and radiological UIP pattern (Hazard Ratio (HR), 2.74; 95%CI:1.46, 5.11; p = 0.002). They had increased respiratory-related mortality and acute exacerbation incidences. Despite similar baseline lung function, short LTL patients had a faster decline in absolute forced vital capacity (FVC) of -105.3 (95% CI: 151.4, -59.1) mL/year compared to -58.2 (95% CI: 82.9, -33.6) mL/year (p < 0.001) in normal LTL patients., Conclusion: Short LTL correlated with increased mortality and faster lung function decline in our Singaporean ILD cohort with a magnitude similar to that in Western ILD cohorts. Further research is needed to integrate LTL assessment into clinical practice., Competing Interests: Declaration of competing interest MLW Kam reports having received research funding from Singapore General Hospital, Singapore and Singapore Health Services (Singhealth), Singapore and having received speaker honorarium from Boehringer Ingelheim, Singapore. YH Tan reports having received speaker honorarium from Boehringer Ingelheim, Singapore. SY Low reports having received research funding, consulting fees, speaker honorarium and support for meetings and travel from Boehringer Ingelheim, Singapore and speaker honorarium from Astra Zeneca, Singapore. JYY Ngeow reports having received research funding from Astra Zeneca, Singapore and the National Medical Research Council Clinician Scientist Award, Singapore. The other authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Monoallelic or biallelic RAD51C germline mutations results in chromosome instability disorders such as Fanconi anemia and cancers. The bona fide function of RAD51C is to assist RAD51 nucleoprotein filament onto single-strand DNA to complete homologous recombination (HR) repair. In addition to HR repair, the role of RAD51C in DNA replication is emerging when replication forks are transiently or irreversibly stalled. We identified novel RAD51C variants of uncertain significance (VUS) from breast, ovarian, pancreatic and gastric cancer patients and functionally characterized the effect of these variants in replication fork protection and double-strand breaks (DSB's) repair. In RAD51C-deficient Chinese hamster CL-V4B cells, expression of RAD51C F164S, A87E, L134S and E49K variants heightened sensitivity to mitomycin C (MMC), etoposide and PARP inhibition. Differently, expression of subset of RAD51C variants R24L, R24W and R212H displayed mild sensitivity to MMC, etoposide and PARP inhibition. Further functional characterization of a subset of variants revealed that Rad51C F164S, A87E, L134S and E49K variants displayed reduced RAD51 foci formation and increased overall nuclear single strand DNA levels in the presence of replication stress. Additionally, DNA fiber assay revealed that RAD51C F164S, A87E, L134S and E49K variants displayed defective replication fork protection upon prolonged fork stalling. Investigations using patient-derived lymphoblastoid cell line carrying heterozygous RAD51C L134S variant showed an impairment in RAD51 chromatin association and replication fork protection, suggestive of deleteriousness of this VUS variant. Overall, our findings provide more insights into molecular roles of RAD51C in replication fork integrity maintenance and in DSB repair., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Motivation: DNA fibre assay has a potential application in genomic medicine, cancer and stem cell research at the single-molecule level. A major challenge for the clinical and research implementation of DNA fibre assays is the slow speed in which manual analysis takes place as it limits the clinical actionability. While automatic detection of DNA fibres speeds up this process considerably, current publicly available software have limited features in terms of their user interface for manual correction of results, which in turn limit their accuracy and ability to account for atypical structures that may be important in diagnosis or investigative studies. We recognize that core improvements can be made to the GUI to allow for direct interaction with automatic results to preserve accuracy as well as enhance the versatility of automatic DNA fibre detection for use in variety of situations., Results: To address the unmet needs of diverse DNA fibre analysis investigations, we propose DNA Stranding, an open-source software that is able to perform accurate fibre length quantification (13.22% mean relative error) and fibre pattern recognition (R > 0.93) with up to six fibre patterns supported. With the graphical interface, we developed, user can conduct semi-automatic analyses which benefits from the advantages of both automatic and manual processes to improve workflow efficiency without compromising accuracy., Availability and Implementation: The software package is available at https://github.com/lgole/DNAStranding., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)

Purpose: Genetic testing has clinical utility in the management of patients with hereditary cancer syndromes. However, the increased likelihood of encountering a variant of uncertain significance in individuals of non-European descent such as Asians may be challenging to both clinicians and patients. This study aims to evaluate the impact of variant reclassification in an Asian country with variants of uncertain significance reported in cancer predisposition genes., Methods: A retrospective analysis of patients seen at the Cancer Genetics Service at the National Cancer Centre Singapore between February 2014 and March 2020 was conducted. The frequency, direction, and time to variant reclassification were evaluated by comparing the reclassified report against the original report., Results: A total of 1,412 variants of uncertain significance were reported in 49.9% (845 of 1,695) of patients. Over 6 years, 6.7% (94 of 1,412) of variants were reclassified. Most variants of uncertain significance (94.1%, 80 of 85) were downgraded to benign or likely benign variant, with a smaller proportion of variants of uncertain significance (5.9%, 5 of 85) upgraded to pathogenic or likely pathogenic variant. Actionable variants of uncertain significance upgrades and pathogenic or likely pathogenic variant downgrades, which resulted in management changes, happened in 31.0% (39 of 126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s), respectively., Conclusion: We propose a clinical guideline to standardize management of patients reported to have variants of uncertain significance. Management should be based on the patient's personal history, family history, and variant interpretation. For clinically relevant or suspicious variants of uncertain significance, follow-up is recommended every 2 years, as actionable reclassifications may happen during this period.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact, and Singapore has seen 33,000 confirmed cases. Patients with cancer, their caregivers, and health care workers (HCWs) need to balance the challenges associated with COVID-19 while ensuring that cancer care is not compromised. This study aimed to evaluate the psychological effect of COVID-19 on these groups and the prevalence of burnout among HCWs., Methods: A cross-sectional survey of patients, caregivers, and HCWs at the National Cancer Centre Singapore was performed over 17 days during the lockdown. The Generalized Anxiety Disorder-7 and Maslach Burnout Inventory were used to assess for anxiety and burnout, respectively. Self-reported fears related to COVID-19 were collected., Results: A total of 624 patients, 408 caregivers, and 421 HCWs participated in the study, with a response rate of 84%, 88%, and 92% respectively. Sixty-six percent of patients, 72.8% of caregivers, and 41.6% of HCWs reported a high level of fear from COVID-19. The top concern of patients was the wide community spread of COVID-19. Caregivers were primarily worried about patients dying alone. HCWs were most worried about the relatively mild symptoms of COVID-19. The prevalence of anxiety was 19.1%, 22.5%, and 14.0% for patients, caregivers, and HCWs, respectively. Patients who were nongraduates and married, and caregivers who were married were more anxious. The prevalence of burnout in HCWs was 43.5%, with more anxious and fearful HCWs reporting higher burnout rates., Conclusion: Fears and anxiety related to COVID-19 are high. Burnout among HCWs is similar to rates reported prepandemic. An individualized approach to target the specific fears of each group will be crucial to maintain the well-being of these vulnerable groups and prevent burnout of HCWs.

Objective: This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease., Cases: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy., Discussion: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To compare accelerated corneal crosslinking (CXL) alone, CXL with simultaneous intrastromal corneal ring segments (CXL-ICRS), and CXL with simultaneous topography-guided photorefractive keratectomy (CXL-TG-PRK) in progressive keratoconus, pellucid marginal degeneration (PMD), or laser in situ keratomileusis (LASIK)-induced ectasia., Setting: The Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada., Design: Prospective nonrandomized interventional study., Methods: Visual and topographical outcomes using a comparative analysis adjusting for preoperative maximum keratometry (Kmax) were evaluated 1 year postoperatively., Results: Four hundred fifty-two eyes from 375 patients with progressive keratoconus, PMD, or LASIK-induced ectasia that underwent accelerated (9 mW/cm, 10 minutes) CXL alone (n = 204), CXL-ICRS (n = 126), or CXL-TG-PRK (n = 122) were included. Change in logarithm of the minimum angle of resolution uncorrected distance visual acuity was significant with CXL-ICRS (-0.31; 95% CI, -0.38 to -0.24) and CXL-TG-PRK (-0.16; 95% CI, -0.24 to -0.09), but not with CXL alone. No significant differences in change were found between the 3 groups. Change in corrected distance visual acuity (CDVA) was significant in all 3 groups: -0.12 (95% CI, -0.15 to -0.10) with CXL alone, -0.23 (95% CI, -0.27 to -0.20) with CXL-ICRS, and -0.17 (95% CI, -0.21 to -0.13) with CXL-TG-PRK. Improvement in CDVA was greater with CXL-ICRS than with CXL alone (-0.08 ± 0.02; P < .0001) and CXL-TG-PRK (-0.05 ± 0.02; P = .005). Change in Kmax was significant with CXL-ICRS [-3.21 diopters (D); 95% CI, -3.98 to -2.45] and CXL-TG-PRK (-3.69 D; 95% CI, -4.49 to -2.90), but not with CXL alone (-0.05 D; 95% CI, -0.66 to 0.55)., Conclusions: CXL alone might be best for keratoconic patients who meet the inclusion criteria. CXL-ICRS might be more effective for eyes with more irregular astigmatism and worse CDVA and CXL-TG-PRK for eyes requiring improvements in irregular astigmatism but still have good CDVA.

Introduction: This study aimed to compare the core, abdominal wall, and plantar temperatures of well jaundiced term infants undergoing phototherapy with or without clingfilm covering the lower two-thirds of the upper end of their bassinets., Methods: This was a randomised controlled trial carried out in a tertiary university hospital on normal healthy term infants undergoing phototherapy. 106 eligible infants were randomised to receive phototherapy with (n=52) or without (n=54) the use of clingfilm during a two-hour period. Subsequently, after nappy change and feeding, they were crossed over to receive phototherapy without or with the clingfilm in place, respectively. Their body temperatures were measured at zero and two hours after phototherapy., Results: There was no significant difference in their core, abdominal wall and plantar temperatures at baseline and after two hours of phototherapy (p-value is greater than 0.05) between infants with and without the use of clingfilm. Irrespective of the use of clingfilm, there was significant (p-value is less than 0.001) increase in core body temperatures after two hours of continuous phototherapy, with resultant hyperthermia (greater than 37.5 degree Celsius) in 42 percent of infants when under clingfilm and 35.8 percent when without clingfilm. A few (2.8 percent) infants, though statistically not significant, became mildly hypothermic after two hours of phototherapy when clingfilm was not used (p-value is greater than 0.05)., Conclusion: Hyperthermia was common during phototherapy, irrespective of the use of clingfilm. Hypothermia was rare and the preventive role of clingfilm is not certain.

Neuroleptic malignant syndrome is an uncommon condition characterised by hyperthermia, rigidity, altered mentation and autonomic instability. Recognition of this condition is essential because its complications are potentially lethal, leading to death in 20% of patients. Not all cases of this syndrome are associated with the use of neuroleptics and there is an increasing number of reports of this condition occurring after withdrawal of therapy with dopaminergic drugs, typically in patients with Parkinsonism. In this setting, there is tremendous potential for misdiagnosis and delay in institution of treatment because of the traditional and common association of the syndrome with the use of neuroleptics only. We report a case of neuroleptic malignant syndrome in a patient with Parkinsonism subsequent to the withdrawal of levodopa and bromocriptine.