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A biocompatible Lossen rearrangement in Escherichia coli
Get PDFNature has evolved an exquisite yet limited set of chemical reactions that underpin the function of all living organisms. By contrast, the field of synthetic organic chemistry can access reactivity not observed in nature, and integration of these abiotic reactions within living systems offers an elegant solution to the sustainable synthesis of many industrial chemicals from renewable feedstocks. Here we report a biocompatible Lossen rearrangement that is catalysed by phosphate in the bacterium Escherichia coli for the transformation of activated acyl hydroxamates to primary amine-containing metabolites in living cells. Through auxotroph rescue, we demonstrate how this new-to-nature reaction can be used to control microbial growth and chemistry by generating the essential metabolite para-aminobenzoic acid. The Lossen rearrangement substrate can also be synthesized from polyethylene terephthalate and applied to whole-cell biocatalytic reactions and fermentations generating industrial small molecules (including the drug paracetamol), paving the way for a general strategy to bioremediate and upcycle plastic waste in native and engineered biological systems
Validation of nutritional screening tools in patients undergoing cancer surgery in low- and middle-income countries
Get PDFApproximately one-third of patients are severely malnourished prior to surgery in low- and middle-income countries (LMICs). Identifying the most appropriate tool for detecting malnutrition is a critical first step toward enabling effective treatment interventions. Therefore, this study aimed to assess the validity and reliability of nutritional screening tools in patients with cancer scheduled for surgery in LMICs. Participants included adults undergoing either curative elective or palliative surgeries in Ghana, India, and the Philippines. Nutritional status was assessed using anthropometric measurements, the Malnutrition Universal Screening Tool (MUST), and the Patient-Generated Subjective Global Assessment (PG-SGA). Data were analysed using Bland-Altman plots with confidence intervals (CIs) and intra-class correlation coefficients (ICCs) to assess inter-rater reliability. Sensitivity and specificity tests were conducted using the Area Under the Receiver Operating Characteristics Curve (AUROC). A total of 167 participants were recruited, with a mean age of 53.3 years (SD 14.7) and a mean body mass index (BMI) of 23.0 kg/m2 (SD 4.9). The proportion of participants identified as at risk of malnutrition was 53.3% using MUST, 47.3% using PG-SGA SF, and 66% using the full PG-SGA. When compared to the PG-SGA, MUST and PG-SGA SF had AUROCs of 0.78 (95% CI: 0.73-0.87) and 0.76 (95% CI: 0.68-0.83), respectively. MUST demonstrated a sensitivity of 85% and a specificity of 25%, while PG-SGA SF showed a sensitivity of 93% and a specificity of 42%. Excellent inter-rater agreement was observed for anthropometric measurements, with ICC values >0.9 across all assessments. Both MUST and PG-SGA SF demonstrated good sensitivity when compared to PG-SGA. However, PG-SGA SF demonstrated slightly greater specificity than MUST. Based on these findings, PG-SGA SF is recommended for preoperative nutritional screening in LMICs.</p
Long-term spatial patterns in COVID-19 booster vaccine uptake
Get PDFBACKGROUND: Vaccination is a critical tool for controlling infectious diseases, with its use to protect against COVID-19 being a prime example. Where a disease is highly transmissible, even a small proportion of unprotected individuals can have substantial implications for disease burden and control. As factors such as deprivation and ethnicity have been shown to influence uptake rates, identifying how uptake varies with socio-demographic indicators is critical for reducing hesitancy and issues of access and identifying plausible future uptake patterns.METHODS: We analyse COVID-19 booster vaccinations in Scotland, subdivided by age, sex, dose and location. Linking to public demographic data, we use Random Forests to fit patterns in first booster uptake, with systematic variation restricted to ~ 1km in urban areas. We introduce a method to predict future distributions using our first booster model, assuming existing trends over deprivation will persist. This provides a quantitative estimate of the impact of changing motivations and efforts to increase uptake.RESULTS: While age and sex have the greatest impact on the model fit, there is a substantial influence of community deprivation and the proportion of residents belonging to a black or minority ethnicity. Differences between first and second boosters suggest in the longer-term that the impact of deprivation is likely to increase.CONCLUSIONS: This would further the disproportionate impact of COVID-19 on deprived communities. Our methods are based solely on public demographic data and routinely recorded vaccination data, and would be easily adaptable to other countries and vaccination campaigns where data recording is similar.</p
Computed tomographic and clinical findings in domestic rabbits (Oryctolagus cuniculus domesticus) with pulmonary emphysema
Get PDFPulmonary emphysema (PE) is a poorly understood condition in rabbits. This retrospective case-control study investigated the CT and clinical findings of rabbits with PE. Institutional archive review identified 724 thoracic CT studies of 529 rabbits, including 76 PE-positive studies of 59/529 rabbits. Twenty-five PE-negative cases were selected randomly as a control group. The mean age of affected rabbits was 9 years (range 5-13 years). Cranial lung lobes were more commonly affected (p < .01). The X-ray attenuation in Hounsfield units (HU) of the emphysematous lung areas (median -905 HU) was significantly lower than in nonemphysematous lung lobes of the case (median -667 HU) and control group (median -652 HU). There was significantly lower X-ray attenuation in peripheral and bullous emphysema than in diffuse emphysema. There was no statistical correlation between clinical lower respiratory signs and PE presence. However, the small portion (n = 6, 10.2%) of affected rabbits with severe respiratory signs, such as open-mouth breathing and cyanotic mucous membranes, all had advanced PE and poor outcome. Secondary changes attributable to PE included pathologic rib fractures in 3 (5.1%) and bulla rupture leading to pneumothorax in 2 (3.4%) rabbits. Of the 15 rabbits with repeat examinations, PE was progressive in 12 (80%) and static in 3 (20%). PE is a common condition in rabbits that is readily detectable with CT. The progressive nature of PE should be considered when detected in asymptomatic rabbits. In rabbits with severe lower respiratory signs, PE should be considered as a potential cause.</p
Bayesian model selection for analyzing predictor-dependent directional data
Get PDFThe need for models for directional data is increasing, driven primarily by the necessity of analyzing peak hours in 24-hour services. Motivated by the need to analyze demand data for a 24-hour bike rental service in Seoul and the factors influencing demand fluctuations across distinct hours, we develop a Bayesian nonparametric density regression modeling framework for the case of a circular response and linear covariates, allowing model selection. Our proposal is based on a linear dependent Dirichlet process mixture of projected normal distributions, accommodating asymmetrical and multimodal shapes, in conjunction with discrete spike-and-slab priors, to enable model selection. A further advantage of our approach is that it enables model averaging, thereby properly accounting for model uncertainty. The simulation study shows that, across various scenarios, our model (i) successfully recovers the true functional form of the conditional density and (ii) selects the correct model, with accuracy improving as the sample size increases. The application of our method suggests that weather conditions significantly impact bike demand. The approach also allows us to predict peak rental times, revealing that, for instance, on a typical summer day, bike demand decreases between 8 am and 4 pm, while in winter, it drops during the early morning
RNA-binding proteins DND1 and NANOS3 cooperatively suppress the entry of germ cell lineage
Get PDFSpecification of primordial germ cells (PGCs) establishes germline development during early embryogenesis, yet the underlying mechanisms in humans remain largely unknown. Here, we reveal the functional roles of germline-specific RNA-binding protein (RBP) DND1 in human PGC (hPGC) specification. We discovered that DND1 forms a complex with another RBP, NANOS3, to restrict hPGC specification. Furthermore, by analyzing the mRNAs bound by DND1 and NANOS3, we found that DND1 facilitates the binding of NANOS3 to hPGC-like cells-related mRNAs. We identified SOX4 mRNAs as the key downstream factor for the DND1 and NANOS3 complex. Mechanistically, DND1 and NANOS3 function in processing bodies (P-bodies) to repress the translation of SOX4 mRNAs, with NANOS3 mediating the interaction between DND1 and the translational repressor 4E-T. Altogether, these findings identify the RBP complex formed by DND1 and NANOS3 functioning as a “braking system” to restrict the entry of germ cell fate in humans.</p
User engagement in a digital health intervention designed for young people who have experienced technology-assisted sexual abuse (i-Minds trial)
Get PDFBackgroundTechnology-assisted sexual abuse (TASA) mostly involves the production and non-consensual sharing of sexual images; however, evidence-based support for young people (YP) who have experienced TASA is scant. Digital Health Interventions (DHIs) have the potential to increase access to support and provide timely therapeutic input in a familiar format to YP. However, studies describing engagement with DHIs is nascent. Our objective is to describe engagement patterns for YP people who used the i-Minds app.MethodsThe i-Minds app is a co-designed mentalisation-based DHI for YP who have experienced TASA. Usage data was collected during the 6-week intervention window using Matomo analytics software and analysed according to the AMUsED framework.ResultsForty-one participants were onboarded to the app. Of these, 95 % completed the introductory mandatory module, and nearly half completed the remaining three modules. Median duration of app engagement was 33 days. Most participants used the app on weekdays in the afternoon. Demographic variables, namely gender not matching with sex assigned at birth/prefer not to disclose and higher baseline clinical severity were associated with higher app engagement.ConclusionsParticipants showed high module completeness and engagement duration, suggesting the potential for real-world use. Potential participant-level predictors of engagement, such as gender identity and severity of TASA related traumatic stress and emotional distress, were identified. Achieving satisfactory engagement in DHIs is challenging yet necessary for delivering effective interventions. Future studies should explore participant-level predictors of engagement to inform real-world use of DHIs with a diverse sample
HyGenar:An LLM-driven hybrid genetic algorithm for few-shot grammar generation
Get PDFGrammar plays a critical role in natural language processing and text/code generation by enabling the definition of syntax, the creation of parsers, and guiding structured outputs. Although large language models (LLMs) demonstrate impressive capabilities across domains, their ability to infer and generate grammars has not yet been thoroughly explored. In this paper, we aim to study and improve the ability of LLMs for few-shot grammar generation, where grammars are inferred from sets of a small number of positive and negative examples and generated in Backus-Naur Form. To explore this, we introduced a novel dataset comprising 540 structured grammar generation challenges, devised 6 metrics, and evaluated 8 various LLMs against it. Our findings reveal that existing LLMs perform sub-optimally in grammar generation. To address this, we propose an LLM-driven hybrid genetic algorithm, namely HyGenar, to optimize grammar generation. HyGenar achieves substantial improvements in both the syntactic and semantic correctness of generated grammars across LLMs. The code is open-source and available at https://github.com/RutaTang/HyGenar
Associations between the use of fitness and diet tracking technology and disordered eating behaviour:A systematic review
Get PDFBACKGROUND: The fitness and wellbeing technology industry is growing rapidly. Concerns are emerging regarding whether these may increase disordered eating behaviours. This review is the first to systematically examine the relationship between fitness and diet tracker use and disordered eating in general and clinical populations.METHODS: The following databases were searched: EMBASE, Medline/PubMed, PsychInfo, CINAHL Plus, ERIC, SportDiscus, ASSIA, Social Science Premium, Sociological Abstracts, Sports Medicine and Educational Health, SCOPUS, Cochrane Library, and ProQuest Dissertation and Theses Global. Studies were selected using predetermined inclusion and exclusion criteria. A narrative synthesis was used, and results were reported by disordered eating outcome.RESULTS: Twenty-seven studies were included in the final review. Cross-sectional studies revealed reasonably consistent evidence of an association between disordered eating and fitness and diet tracker use, specifically regarding global disordered eating, dietary restraint, excessive exercise, and disordered muscle-orientated behaviour. However, this association was not replicated in experimental research.CONCLUSION: While fitness and diet tracker use is a correlate of disordered eating, it is currently not possible to conclude if they increase disordered eating, or the direction of this relationship. Future research should determine the nature of this relationship and possible mechanisms to ensure their safe use in vulnerable populations.</p
Economical epidemiology, pathological populations, and the long history of the demographic and health survey
Get PDFThis article examines the history of population health surveillance in modern Africa, considering the Demographic and Health Survey (DHS) programme as a bridge between twentieth and twenty-first century epidemiology. Tracing this tradition of surveillance from pre-war Britain, through its extension into the British Empire, and its subsequent employment in post-colonial demography, this article makes two related arguments. The first, that surveys like the DHS complement and encourage economic logics in medicine. Focussing initially on questions of human capital, cross-sectional surveys have tended to promote and promise efficiency in terms of medical research and interventions, thereby reducing the need for extensive and expensive infrastructure. In Africa, this utility has meant that cross-sectional surveillance gained particular traction in the context of colonisation and again following the widespread implementation of Structural Adjustment Programmes from the early 1980s. The second argument takes that the collection of demographic and social data means that these surveys represent a unique form of surveillance medicine, one which encourages associations between illness, family, and society at large. Epidemiology drawn from these data promotes this pathologisation of population, binding the epistemology of contemporary Global Health to old ideas, and siting subaltern families and communities as a prime locus of disease
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