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With the advent of rapid automated in silico identification of biosynthetic gene clusters (BGCs), genomics presents vast opportunities to accelerate natural product (NP) discovery. However, prolific NP producers, Streptomyces, are exceptionally GC-rich (>80%) and highly repetitive within BGCs. These pose challenges in sequencing and high-quality genome assembly which are currently circumvented via intensive sequencing. Here, we outline a more cost-effective workflow using multiplex Illumina and Oxford Nanopore sequencing with hybrid long-short read assembly algorithms to generate high quality genomes. Our protocol involves subjecting long read-derived assemblies to up to 4 rounds of polishing with short reads to yield accurate BGC predictions. We successfully sequenced and assembled 8 GC-rich Streptomyces genomes whose lengths range from 7.1 to 12.1 Mb with a median N50 of 8.2 Mb. Taxonomic analysis revealed previous misrepresentation among these strains and allowed us to propose a potentially new species, Streptomyces sydneybrenneri. Further comprehensive characterization of their biosynthetic, pan-genomic and antibiotic resistance features especially for molecules derived from type I polyketide synthase (PKS) BGCs reflected their potential as alternative NP hosts. Thus, the genome assemblies and insights presented here are envisioned to serve as gateway for the scientific community to expand their avenues in NP discovery.

Aim: We describe a cohort of five patients with limb-girdle muscular dystrophy (LGMD) 2G/LGMD-R7 in a South-east Asian cohort. Background: LGMD2G/LGMD-R7-telethonin-related is caused by mutations in the TCAP gene that encodes for telethonin. Methods: We identified consecutive patients with LGMD2G/LGMD-R7-telethonin-related, diagnosed at the National Neuroscience Institute (NNI) and National University Hospital (NUH) between January 2000 and June 2021. Results: At onset, three patients presented with proximal lower limb weakness, one patient presented with Achilles tendon contractures, and one patient presented with delayed gross motor milestones. At last follow up, three patients had a limb girdle pattern of muscle weakness and two had a facioscapular humeral pattern of weakness. Whole body muscle MRI performed for one patient with a facioscapular-humeral pattern of weakness showed a pattern of muscle atrophy similar to facioscapular-humeral dystrophy. One patient had histological features consistent with myofibrillar myopathy; electron microscopy confirmed the disruption of myofibrillar architecture. One patients also had reduced staining to telethonin antibody on immunohistochemistry. Conclusion: We report the unique clinical and histological features of a Southeast Asian cohort of five patients with LGMD2G/LGMD-R7-telethonin-related muscular dystrophy and further expand its clinical and histopathological spectrum.

ObjectiveIn an earlier study, several tested International Pharmaceutical Federation (FIP) pictograms did not achieve validity among older adults in Singapore. In this study, for 27 unvalidated FIP pictograms, we (1) developed variants of each pictogram, (2) elicited the most-preferred variant, and (3) assessed the validity of the most-preferred variant among older Singaporeans.MethodsIn phase 1, up to three variants of the 27 pictograms were developed, based on older adults' feedback from a previous study. In phase 2, the most-preferred variant of 26 pictograms, which had two or three variants, was selected by 100 older participants. In phase 3, the 27 most-preferred variants (including the pictogram with only one variant) were assessed for validity - transparency and translucency - among 278 older participants (10 pictograms per participant). To evaluate transparency, participants were first asked: "If you see this picture on a medicine label, what do you think it means?" for each assigned pictogram. If they responded, they were asked, "How do you know?", and if not, they were told, "Tell me everything you see in this picture". Then, participants were shown their assigned pictograms again, one by one, and the pictogram's intended meaning was revealed to evaluate translucency. Pictograms were classified as valid (≥66% participants interpreted its intended meaning correctly [transparency criterion] and ≥85% participants rated its representativeness as ≥ 5 [translucency criterion]), partially valid (only transparency criterion fulfilled) or not valid.ResultsIn phase 1, 77 variants of the 27 pictograms were developed. In phase 2, a majority of the most-preferred variants were selected by >50% participants. In phase 3, 10 (37.0%) of the 27 pictograms tested were considered valid, and five (18.5%) were partially valid. A higher proportion of pictograms portraying dose and route of administration and precautions were valid or partially valid, versus those depicting indications or side effects.ConclusionContextual redesigning and selection of pharmaceutical pictograms, which initially failed to achieve validity in a population, contributed to their validation.InnovationThe redesigned validated pictograms from this study can be incorporated into relevant patient information materials in clinical practice.

The obesity epidemic is a global health concern with Asian countries facing one of the most rapid rises in obesity rates. However, given the underwhelming long-term efficacy of weight loss strategies, especially in Asia, this review aims to explore barriers and facilitators to weight management of patients with overweight and obesity in Asia.Medline, CINAHL, PsycINFO and Web of Science were searched for articles discussing barriers and facilitators of treatment to obesity from both healthcare professionals (HCPs) and patients. Qualitative and mixed method studies from Asia were included. Key quotes were extracted, coded, and thematically analysed with reference to Thomas and Harden's methodology.A total of 26 articles were included in this review. From the patients' perspective, three main themes were identified, factors influencing poor eating behaviour, inhibiting lifestyle modifications, and facilitating lifestyle modifications. Patients highlighted several barriers including the lack of social support, physiological limitations to exercise and low health literacy. Rigid sociocultural norms and lack of accessible healthcare services, exercise facilities and healthy food exacerbated the barriers. Facilitators to lifestyle modifications consisted of strong support systems and high health literacy. HCPs agreed that low health literacy, lack of social support and patient motivation impeded patients' weight loss attempts but were unaware of the other barriers they faced.There are discrepancies between ideas of barriers and facilitators of HCPs and patients. A mixture of population-level, primary care, and personal interventions are required to address this disparity and enhanced health literacy would improve weight loss outcomes.

Objectives: Various techniques for dorsal hand vein (DHV) pattern extraction have been introduced using small datasets with poor and inconsistent segmentation. This work compared manual segmentation with our proposed hybrid automatic segmentation method (HHM) for this classification problem.Methods: Manual segmentation involved selecting a region-of-interest (ROI) in images from the Bosphorus dataset to generate ground truth data. The HHM combined histogram equalization and morphological and thresholding-based algorithms to localize veins from hand images. The data were divided into training, validation, and testing sets with an 8:1:1 ratio before training AlexNet. We considered three image augmentation strategies to enlarge our training sets. The best training hyperparameters were found using the manually segmented dataset.Results: We obtained a good test accuracy (91.5%) using the model trained with manually segmented images. The HHM method showed slightly inferior performance (76.5%). Considerable improvement was observed in the test accuracy of the model trained with the inclusion of automatically segmented and augmented images (84%), with low false acceptance and false rejection rates (0.00035% and 0.095%, respectively). A comparison with past studies further demonstrated the competitiveness of our technique.Conclusions: Our technique can be feasible for extracting the ROI in DHV images. This strategy provides higher consistency and greater efficiency than the manual approach.

This study aims to analyze and compare the strategies, methods and tools used by various institutions in the world and different countries in detecting fraud. Currently, Fraud has become a common thing in the world of economics and business. As one of the preventive measures, robust detection is required. Methods and ways of detecting fraud are constantly changing and improving. Where every country certainly has a strategy in dealing with fraud cases to protect the country's economy. Without an appropriate strategy, it will facilitate further crime. This research will also explain fraud detection methods that have been applied by various institutions. The data before and after the Covid period did not show a very significant difference, so it can be concluded that whether external influences from outside the company did not significantly influence the occurrence of fraud in the company. Therefore, if we do not aware about the strategies, methods, and tools for detecting cases of fraud in companies, we will never know whether the company is in good condition or not.

Introduction: Obesity is thought to be a negative predictor of sexual function, but the relationship between body mass index (BMI) and sexual function has been inconsistent. Other factors such as body image and self-esteem may mediate this relationship. This study examined the association of BMI, body image and self-esteem with sexual function in young women. Method: A total of 514 sexually active women aged 21 to 35 years completed an anonymised online questionnaire that used 3 scales to assess body image, self-esteem and female sexual function: Body Image States Scale (BISS), Rosenberg Self-Esteem Scale (RSES) and Female Sexual Function Index (FSFI). Higher scores for BISS, RSES and FSFI indicate more positive body image, higher self-esteem and better sexual function, respectively. Spearman correlation assessed the association among BMI, BISS and RSES scores, and with FSFI scores. Linear and multivariable logistic regression identified risk factors associated with sexual dysfunction (FSFI

Polystyrene waste pollutes the environment and poses a significant health risk to humans, animals, and marine ecology. This study aims to evaluate the effectiveness of degradation on expanded (EPS) and extruded (XPS) polystyrene with different diets using superworms (Zophobas atratus larvae) obtained in Malaysia. The growth and development of the larvae after consumption of EPS and XPS and the gut microbial community changes in response to high polystyrene consumption diets were also identified. The oatmeal, wheat bran, and cornmeal were used as supplement diets and showed significantly enhanced EPS and XPS consumption and degradation compared to sole diet treatment. Gel permeation chromatography was carried out using egested frass of Z. atratus larvae to characterize depolymerization of EPS and XPS, indicating a significant reduction in the average molecular weight and average molecular weight. The highest reduction occurred in the presence of oatmeal. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy analyses indicated functional group changes and chemical modification occurred with depolymerization and partial oxidation of EPS and XPS. The larvae length increased, while the number of instars and duration of larvae became shorter with the addition of supplement diets. Oatmeal is predominantly effective among other supplements in assisting Z. atratus larvae with EPS and XPS degradation. The results of this study support the ubiquity of polystyrene biodegradation in Z. atratus and the next-generation sequencing studies. Kluyvera sp., Klebsiella sp., and Enterobacter sp. were found to be strongly associated with degrading EPS and XPS polystyrene with oatmeal as a supplemental diet.

This study examines the connection between ability, motivation, opportunity-enhancing HRM practices and corporate environmental citizenship. Organisational learning capability is also introduced as a moderator between the connections of AMO-enhancing HRM practices and corporate environmental citizenship. Systematic sampling technique was utilized to determine the study sample with a total response of 150. The study found that ability and opportunity-enhancing HRM practices are related to corporate environmental citizenship except for motivation-enhancing HRM practices. Similarly, organisational learning capability has no moderating effect on such relationships. In addition to that, this study has provided a comprehensive understanding of corporate environmental citizenship in the construction industry in Malaysia. This substantially adds a new dimension to the literature.

A slow-release fertilizer is important to improve soil conditions and enhances food security through continuous plant supply. With urea as a nitrogen source, kaolin as a carrier, acrylic acid as a reaction monomer, potassium persulfate as an initiator, N, N '- methylene bisacrylamide as a crosslinking agent, under the action of cyclohexane and sorbitan monostearate, kaolin based slow-release fertilizer was synthesized by reverse suspension method for the first time. The optimum conditions for the synthesized polymer were 0.6 g kaolin, 2 g urea and 80 ℃ temperature. The maximum water absorption capacity of the slow-release fertilizer was as high as 219.75 g/g. The water retention performance lasted for at least 10 days, and the slow-release property lasted for at least 28 days. The release of nitrogen content was slow and stable. The FTIR analysis indicated that the cross-linking occurred between kaolin, urea, and resin meanwhile, the SEM analysis supported that the product had a special network structure with a rough and porous surface. TGA analysis confirmed the stability of the kaolin-based slow-release fertilizer. The findings fully validated that the synthesis method of slow-release fertilizer was feasible and has the potential to be a popular commercialized product be popularized in areas lacking water or fertilizer.

New tetracycline derivatives exhibit broad-spectrum antimicrobial activities. This study aimed to assess the in vitro activity of eravacycline against common Enterobacterales.Clinical Enterobacterales isolates were collected between 2017 and 2021. The minimum inhibitory concentration (MIC) was determined using a broth microdilution test.We identified Klebsiella pneumoniae (n = 300), Escherichia coli (n = 300), Klebsiella oxytoca (n = 100), Enterobacter cloacae complex (n = 100), Citrobacter freundii (n = 100), and Proteus mirabilis (n = 100). All P. mirabilis strains were resistant to eravacycline. Excluding P. mirabilis, the susceptibility rates to eravacycline, omadacycline, and tigecycline were 75.2%, 66.9%, and 73%, respectively. The MICThis study provides the MIC and susceptibility rate of eravacycline for common Enterobacterales. Eravacycline could be a therapeutic choice for cefotaxime non-susceptible or meropenem non-susceptible Enterobacterales, especially K. oxytoca, C. freundii, and E. coli.

Alternative polyadenylation (APA) enables a gene to generate multiple transcripts with different 3′ ends, which is dynamic across different cell types or conditions. Many computational methods have been developed to characterize sample-specific APA using the corresponding RNA-seq data, but suffered from high error rate on both polyadenylation site (PAS) identification and quantification of PAS usage (PAU), and bias toward 3′ untranslated regions. Here we developed a tool for APA identification and quantification (APAIQ) from RNA-seq data, which can accurately identify PAS and quantify PAU in a transcriptome-wide manner. Using 3′ end-seq data as the benchmark, we showed that APAIQ outperforms current methods on PAS identification and PAU quantification, including DaPars2, Aptardi, mountainClimber, SANPolyA, and QAPA. Finally, applying APAIQ on 421 RNA-seq samples from liver cancer patients, we identified >540 tumor-associated APA events and experimentally validated two intronic polyadenylation candidates, demonstrating its capacity to unveil cancer-related APA with a large-scale RNA-seq data set.

International audience; This letter presents a new type of E-band vertically aligned carbon nanotubes (VACNTs)-based air-filled waveguide (AFWG). This original concept is based on the use of bundle of VACNTs as equivalent WG’s metallic lateral walls. The WG is designed by applying a full-wave three dimensions electromagnetic software and an equivalent VACNTs bulk model. Then, the WG is fabricated using a CMOS compatible CNTs transfer process and a dedicated assembly process. For the first time, the concept of the CNTs-based AFWG is validated by measurements, and an experimental attenuation constant is estimated at 0.5 dB/mm between 81 and 86 GHz.

Introduction: There has been a rapid evolution in the treatment strategies for metastatic castration-resistant prostate cancer (mCRPC) following the identification of targetable mutations, making genetic testing essential for patient selection. Although several international guidelines recommend genetic testing for patients with mCRPC, there is a lack of locally endorsed clinical practice guidelines in Singapore. Method: A multidisciplinary specialist panel with representation from medical and radiation oncology, urology, pathology, interventional radiology, and medical genetics discussed the challenges associated with patient selection, genetic counselling and sample processing in mCRPC. Results: A clinical model for incorporating genetic testing into routine clinical practice in Singapore was formulated. Tumour testing with an assay that is able to detect both somatic and germline mutations should be utilised. The panel also recommended the “mainstreaming” approach for genetic counselling in which pre-test counselling is conducted by the managing clinician and post-test discussion with a genetic counsellor, to alleviate the bottlenecks at genetic counselling stage in Singapore. The need for training of clinicians to provide pre-test genetic counselling and educating the laboratory personnel for appropriate sample processing that facilitates downstream genetic testing was recognised. Molecular tumour boards and multidisciplinary discussions are recommended to guide therapeutic decisions in mCRPC. The panel also highlighted the issue of reimbursement for genetic testing to reduce patient-borne costs and increase the reach of genetic testing among this patient population. Conclusion: This article aims to provide strategic and implementable recommendations to overcome the challenges in genetic testing for patients with mCRPC in Singapore. Keywords: Clinical model, genetic counselling, genetic testing, homologous recombination repair genes, metastatic castration-resistant prostate cancer

Background: Circular frames for ankle fusion are reserved for complex clinical scenarios. The literature is heterogenous and conflicting. We aim to present the indications and outcomes of this procedure. Methods: A retrospective cohort study based on a prospective database of frame surgeries performed in a tertiary institution. Inclusion criteria were patients undergoing complex ankle fusion with circular frames between 2005 and 2020, with a minimum 12-month follow-up. Data were collected on patient demographics, surgical indications, comorbidities, surgical procedures, external fixator time (EFT), length of stay (LOS), radiologic and clinical outcomes, and adverse events. Factors influencing radiologic and clinical outcomes were analyzed. Results: 47 patients were included, with a median follow-up of 30 months (interquartile range [IQR] 20-40). The median age at time of surgery was 63.5 years (IQR 58-71). Patients had a median of 2 previous surgeries (IQR 1-3). The median LOS was 8.5 days, and median EFT was 237 days (IQR 166-280). Simultaneous limb lengthening (median 3.3 cm, IQR 1.9-3.5) was performed in 11 patients, increasing the EFT by a mean of 4 months. Primary and final union rates were 91.5% and 95.7%, respectively. At last follow-up, ASAMI bone scores were excellent or good in 87.2%. ASAMI functional scores were good in 79.1%. Patient satisfaction was 83.7%. In addition, 97.7% of patients experienced adverse events, most commonly pin-site related, with major complications in 30.2% and reoperations in 60.5%. There were 3 amputations. Adverse events were associated with increased age, poor soft tissue condition, severe deformities, subtalar fusions, peripheral neuropathy, peripheral vascular disease, and prolonged EFT. Conclusion: Complex ankle fusion using circular frames can achieve good outcomes, however time in frame may be prolonged with a high rate of adverse events. Identified risk factors for poorer outcomes should be considered in patient counselling and prognostication. Level of Evidence: Level III, prognostic.

Sex-driven immune differences can affect tumor progression and the landscape of the tumor microenvironment. Deeper understanding of these differences in males and females can inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing and protein analyses uncovered a subpopulation of myeloid cells in pancreatic lesions associated with an immune-excluded tumor phenotype and effector T-cell exhaustion exclusively in females. This myeloid subpopulation was positively correlated with poor survival and genetic signatures of M2-like macrophages and T-cell exhaustion in females. The G-protein coupled receptor formyl peptide receptor 2 (FPR2) mediated these immunosuppressive effects. In vitro, treatment of myeloid cells with a specific FPR2 antagonist prevented exhaustion and enhanced cytotoxicity of effector cells. Proteomic analysis revealed high expression of immunosuppressive secretory proteins PGE2 and galectin-9, enriched integrin pathway, and reduced proinflammatory signals like TNFα and IFNγ in female M2-like macrophages upon FPR2 agonist treatment. In addition, myeloid cells treated with FPR2 agonists induced TIM3 and PD-1 expression only in female T cells. Treatment with anti-TIM3 antibodies reversed T-cell exhaustion and stimulated their ability to infiltrate and kill pancreatic spheroids. In vivo, progression of syngeneic pancreatic tumors was significantly suppressed in FPR2 knockout (KO) female mice compared with wild-type (WT) female mice and to WT and FPR2 KO male mice. In female mice, inoculation of tumors with FPR2 KO macrophages significantly reduced tumor growth compared with WT macrophages. Overall, this study identified an immunosuppressive function of FPR2 in females, highlighting a potential sex-specific precision immunotherapy strategy. Significance: FPR2 is a sex-dependent mediator of macrophage function in pancreatic cancer and can be targeted to reprogram macrophages and stimulate antitumor immunity in females.

Purpose The post-pandemic recognises changes are required; universities need to rethink their e-servicescapes strategies by offering different approaches to enhance students’ learning. This study aims to draw on learning self-efficacy trajectories and propose a conceptual model for exploring the predictive validity of satisfaction. In addition, it explores the mediating role of e-servicescapes and the moderating relationship effect of mature and younger students. Design/methodology/approach Learning self-efficacies is incorporated into the design of the model in an attempt to understand student cognition. The influences of e-servicescape on adopting online preferences and satisfaction are also examined. The model was empirically validated by surveying 266 respondents. Structural equation modelling and multi-group analysis were used to analyse the data. Findings The results of this study show learning self-efficacies has no significant influence on satisfaction. Yet, they showed a significant influence on e-servicescapes. E-servicescapes positively influenced satisfaction and preference for adopting online learning. E-servicescapes also had a mediating effect between self-efficacy to complete a course and satisfaction, as well as self-efficacy to interact with instructors and satisfaction. It had a negative suppressed effect on social interaction. Originality/value The research makes the following contributions. Firstly, the conceptualised model identifies an association between learning self-efficacies and e-servicescapes, suggesting universities as service providers can maximise the value offerings of their customer assets. Secondly, e-servicescapes demonstrate a full mediating effect between self-efficacies and satisfaction, indicating that if universities are to compete successfully in dynamic markets, they should co-create value in their e-servicescapes domain to increase satisfaction. Thirdly, the study recognises the need for a hybrid system of both face-to-face and online delivery because the multi-group analysis shows mature age preference for online learning is required to make this transformation successful.

Purpose The purpose of this study is to describe and assess the impact of multi-domain biopsychosocial (BPS) recovery on outcomes following lumbar spine fusion. We hypothesized that discrete patterns of BPS recovery (e.g., clusters) would be identified, and then associated with postoperative outcomes and preoperative patient data. Methods Patient-reported outcomes for pain, disability, depression, anxiety, fatigue, and social roles were collected at multiple timepoints for patients undergoing lumbar fusion between baseline and one year. Multivariable latent class mixed models assessed composite recovery as a function of (1) pain, (2) pain and disability, and (3) pain, disability, and additional BPS factors. Patients were assigned to clusters based on their composite recovery trajectories over time. Results Using all BPS outcomes from 510 patients undergoing lumbar fusion, three multi-domain postoperative recovery clusters were identified: Gradual BPS Responders (11%), Rapid BPS Responders (36%), and Rebound Responders (53%). Modeling recovery from pain alone or pain and disability alone failed to generate meaningful or distinct recovery clusters. BPS recovery clusters were associated with number of levels fused and preoperative opioid use. Postoperative opioid use (p p Conclusion This study describes distinct clusters of recovery following lumbar spine fusion derived from multiple BPS factors, which are related to patient-specific preoperative factors and postoperative outcomes. Understanding postoperative recovery trajectories across multiple health domains will advance our understanding of how BPS factors interact with surgical outcomes and could inform personalized care plans.

Learning and teaching is no longer the exclusive domain of teaching academics and is increasingly reliant on third-space professionals, in particular learning designers. The sharing of the design of the learning and teaching space is underlined by the increasing collaboration between teaching academics and learning designers. This qualitative study explores how these two key stakeholders understand learning technology, which is critical to shaping the teaching and learning process in contemporary higher education. Foucauldian discourse and power were employed as the theoretical lens to analyse semi-structured interviews with 12 teaching academics and 5 learning designers at a large Australian university. Although learning designers and teaching academics share a mutual interest in improving the learning and teaching process, the findings also revealed five discourses where practice was contested: centralisation, surveillance, institutional homogenisation, responsibility, and efficiency. This article calls for a new focus on the collaborative aspect of the learning design and teaching process that is constantly (re)negotiated between these two main stakeholders. Implications for practice or policy: Teaching academics and learning designers should develop practices that recognise the collaborative nature of learning technology in higher education. Universities should develop practices and policies that reduce tensions within the five identified discourses of learning technology to ensure a more collaborative teaching academic-learning designer relationship.