Diagnosing Sarcopenia with AI-Aided Ultrasound (DINOSAUR)—A Pilot Study

Background: Sarcopenia has been recognized as a determining factor in surgical outcomes and is associated with an increased risk of postoperative complications and readmission. Diagnosis is currently based on clinical guidelines, which includes assessment of skeletal muscle mass but not quality. Ultrasound has been proposed as a useful point-of-care diagnostic tool to assess muscle quality, but no validated cut-offs for sarcopenia have been reported. Using novel automated artificial intelligence (AI) software to interpret ultrasound images may assist in mitigating the operator-dependent nature of the modality. Our study aims to evaluate the fidelity of AI-aided ultrasound as a reliable and reproducible modality to assess muscle quality and diagnose sarcopenia in surgical patients. Methods: Thirty-six adult participants from an outpatient clinic were recruited for this prospective cohort study. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 guidelines. Ultrasonography of the rectus femoris muscle was performed, and images were analyzed by an AI software (MuscleSound® (Version 5.69.0)) to derive muscle parameters including intramuscular adipose tissue (IMAT) as a proxy of muscle quality. A receiver operative characteristic (ROC) curve was used to assess the predictive capability of IMAT and its derivatives, with area under the curve (AUC) as a measure of overall diagnostic accuracy. To evaluate consistency between ultrasound users of different experience, intra- and inter-rater reliability of muscle ultrasound parameters was analyzed in a separate cohort using intraclass correlation coefficients (ICC) and Bland–Altman plots. Results:The median age was 69.5 years (range: 26–87), and the prevalence of sarcopenia in the cohort was 30.6%. The ROC curve plotted with IMAT index (IMAT% divided by muscle area) yielded an AUC of 0.727 (95% CI: 0.551–0.904). An optimal cut-off point of 4.827%/cm2 for IMAT index was determined with a Youden’s Index of 0.498. We also demonstrated that IMAT index has excellent intra-rater reliability (ICC = 0.938, CI: 0.905–0.961) and good inter-rater reliability (ICC = 0.776, CI: 0.627–0.866). In Bland–Altman plots, the limits of agreement were from −1.489 to 1.566 and −2.107 to 4.562, respectively. Discussion: IMAT index obtained via ultrasound has the potential to act as a point-of-care evaluation for sarcopenia screening and diagnosis, with good intra- and inter-rater reliability. The proposed IMAT index cut-off maximizes sensitivity for case finding, supporting its use as an easily implementable point-of-care test in the community for sarcopenia screening. Further research incorporating other ultrasound parameters of muscle quality may provide the basis for a more robust diagnostic tool to help predict surgical risk and outcomes.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Backbone boogie : dance the osteoporosis away!

This paper presents Backbone Boogie: Dance the Osteoporosis Away!, a health communications campaign seeking to promote the early prevention of osteoporosis through dance, initiated by three final-year students from Wee Kim Wee School of Communication and Information, Nanyang Technological University, Singapore. The campaign focuses on raising awareness of this health issue and encouraging the adoption of dance as a regular form of exercise among working women in Singapore aged 30 to 50. Based on the formative research gathered, reducing susceptibility to osteoporosis was found to be largely dependent on early prevention through a combination of calcium, vitamin D and regular weight-bearing exercise. Exercise was the least known aspect of osteoporosis prevention by the target audience and about 50% did not regularly exercise at all. Dance was also found to be the osteogenic exercise they were most keen to take up. Hence, campaign activities were to focus on increasing awareness of osteoporosis, the importance of exercise in osteoporosis prevention, and to introduce dance as an easy way to start exercising regularly. Offline outreach was unfortunately disrupted by the outbreak of COVID-19, necessitating a switch to a fully digital campaign. Combined with several other factors, the campaign unfortunately was not successful in meeting its objectives. An evaluation of the campaign’s effectiveness showed an increase in knowledge of osteoporosis and the need for early prevention. While post-campaign survey analysis found that more women exposed to the campaign have started dancing to prevent osteoporosis, awareness regarding the importance of dance in osteoporosis prevention was not proportionately increased.Bachelor of Communication Studie

Can a healthy climate make us happier?: a study on climate change and other effects affecting happiness

Combating climate change is a shared responsibility. It affects the livelihood of all living species on Earth through the access to resources and the physical environment, which impacts our health, happiness, and economic activities. For this reason, we expect individuals to have a preference for certain types of climate. Using data obtained from the World Values Survey, this paper estimates the impact of climate change on self-reported happiness and how this relationship varies across space and time. In this paper, maximum temperature (tmx) is selected as the climate change variable. Our estimates suggest that the self-reported levels of happiness fall as the severity of climate change increases. We have also determined that countries in different regions of the world report varying levels of happiness given their geographical climate. Colder countries record increased happiness as they move closer to the ideal temperature range while warmer countries are reporting higher levels of unhappiness with a marginal increase in tmx. To gain further insights on the relationship between happiness and tmx, this paper extends into studying further effects of this relationship by including interaction terms - “tmx x male”, “tmx x employed” and “tmx x education” and quadratic terms.Bachelor of Social Sciences in Economic

Hope of India : an evaluation of information communication technologies in rural Indian healthcare.

This research paper evaluates issues faced by rural community healthcare workers under India's National Rural Health Mission scheme, in particular Accredited Social Health Activists (ASHAs), primarily women whose main role is to aid pregnant women in childbirth. In November-December 2008, we conducted a series of in-depth interviews with ASHAs (13), other rural healthcare workers (14), patients (10) and doctors (18). Their usage of information and communication technologies (ICTs) within the healthcare system was investigated. The Value of ICTs model (Chib, Lwin, Santoso, Hsu & Ang, 2008) and Technology-Community-Management Vulnerabilities model (Chib & Komathi, in press) covered the four main benefits of using ICTs in healthcare: opportunity production, capabilities enhancement, social enabling and knowledge generator, as well as obstacles to the usage of ICTs that include economic, technological, socio-cultural and infrastructural barriers. Findings showed that the models were applicable in the Indian rural healthcare situation. The dominant form of ICT used was mobile phones, which allowed ASHAs to reach their fellow colleagues and doctors easily. During emergencies, they were able to call the ambulance service, which greatly increased their work efficiency and service quality. Organizational barriers turned out to be significant issues. These include the low ASHA job satisfaction, inadequate job training, and systemic inaccessibility, particularly to Public Health Centers (PHCs) in areas with difficult access. Recommendations are provided on improving the current healthcare situation via ICTs to bridge the gap between rural healthcare workers and higher authorities, and to improve the welfare of healthcare workers through better job training and stable benefits. ASHAs can play a significant role in the health of rural communities, particularly in providing maternal and infant healthcare, through programmatic measures administered in collaboration with the health authorities.Bachelor of Communication Studie

Site-selective Chlorination of Pyrrolic Heterocycles by Flavin Dependent Enzyme PrnC

Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. Whilst there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation has been lacking. Here we describe the first in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modelling and site mutagenesis studies identified three key residues in the catalytic pocket. Moderate resolution map using single-particle cryogenic electron microscopy (CryoEM) reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and was applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide, Fludioxonil

Therapeutic modulation of the bile acid pool by Cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice

Bile acids (BAs) are surfactant molecules that regulate the intestinal absorption of lipids. Thus, the modulation of BAs represents a potential therapy for nonalcoholic fatty liver disease (NAFLD), which is characterized by hepatic accumulation of fat and is a major cause of liver disease worldwide. Cyp8b1 is a critical modulator of the hydrophobicity index of the BA pool. As a therapeutic proof of concept, we aimed to determine the impact of Cyp8b1 inhibition in vivo on BA pool composition and as protection against NAFLD. Inhibition of Cyp8b1 expression in mice led to a remodeling of the BA pool, which altered its signaling properties and decreased intestinal fat absorption. In a model of cholesterol-induced NAFLD, Cyp8b1 knockdown significantly decreased steatosis and hepatic lipid content, which has been associated with an increase in fecal lipid and BA excretion. Moreover, inhibition of Cyp8b1 not only decreased hepatic lipid accumulation, but also resulted in the clearance of previously accumulated hepatic cholesterol, which led to a regression in hepatic steatosis. Taken together, our data demonstrate that Cyp8b1 inhibition is a viable therapeutic target of crucial interest for metabolic diseases, such as NAFLD.-Chevre, R., Trigueros-Motos, L., Castaño, D., Chua, T., Corlianò, M., Patankar, J. V., Sng, L., Sim, L., Juin, T. L., Carissimo, G., Ng, L. F. P., Yi, C. N. J., Eliathamby, C. C., Groen, A. K., Hayden, M. R., Singaraja, R. R. Therapeutic modulation of the bile acid pool by Cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mic

PARP4 interacts with hnRNPM to regulate splicing during lung cancer progression

Abstract Background The identification of cancer driver genes from sequencing data has been crucial in deepening our understanding of tumor biology and expanding targeted therapy options. However, apart from the most commonly altered genes, the mechanisms underlying the contribution of other mutations to cancer acquisition remain understudied. Leveraging on our whole-exome sequencing of the largest Asian lung adenocarcinoma (LUAD) cohort (n = 302), we now functionally assess the mechanistic role of a novel driver, PARP4. Methods In vitro and in vivo tumorigenicity assays were used to study the functional effects of PARP4 loss and mutation in multiple lung cancer cell lines. Interactomics analysis by quantitative mass spectrometry was conducted to identify PARP4’s interaction partners. Transcriptomic data from cell lines and patient tumors were used to investigate splicing alterations. Results PARP4 depletion or mutation (I1039T) promotes the tumorigenicity of KRAS- or EGFR-driven lung cancer cells. Disruption of the vault complex, with which PARP4 is commonly associated, did not alter tumorigenicity, indicating that PARP4’s tumor suppressive activity is mediated independently. The splicing regulator hnRNPM is a potentially novel PARP4 interaction partner, the loss of which likewise promotes tumor formation. hnRNPM loss results in splicing perturbations, with a propensity for dysregulated intronic splicing that was similarly observed in PARP4 knockdown cells and in LUAD cohort patients with PARP4 copy number loss. Conclusions PARP4 is a novel modulator of lung adenocarcinoma, where its tumor suppressive activity is mediated not through the vault complex—unlike conventionally thought, but in association with its novel interaction partner hnRNPM, thus suggesting a role for splicing dysregulation in LUAD tumorigenesis

Domain-specific p53 mutants activate EGFR by distinct mechanisms exposing tissue-independent therapeutic vulnerabilities

Here the authors identify distinct mechanisms by which domain-specific p53 mutations activate cancer cell growth via the epidermal growth factor receptor (EGFR). These mechanisms affect sensitivity to EGFR inhibitors, opening avenues for targeted therapy

Genomic landscape of lung adenocarcinoma in East Asians

Lung cancer is the world's leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts. Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs