Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127 594 people from 20 countries (PURE): a prospective cohort study.

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.

Integrating health, nutrition, and environmental impacts of foods: a life cycle impact assessment and modelling analysis of foods in Canada.

BACKGROUND: Given the urgency of transitioning towards sustainable nutrition, dietary shifts that provide co-benefits to human health and the environment are imperative. There is currently no database of the environmental impacts of foods that reflects Canada's unique geographical and agri-climatic context and regional inputs and emissions. To determine sustainable diets, harmonising nutritional considerations with environmental impacts is also essential for an equitable comparison of foods. We aimed to develop a Canadian Food Life Cycle Inventory database and a multidimensional index to enable a joint assessment of the health and environmental impacts of foods in Canada. METHODS: The Canadian Food Life Cycle Inventory database uses life cycle assessment methodology to evaluate environmental impacts. The datasets mirror Canada's food consumption patterns, averaging the spectrum of agricultural practices weighted by domestic production and import shares. The database is structured according to the nomenclature and categorisation of the Canadian Nutrient File. Environmental sustainability is assessed using a cradle-to-grave approach, including indicators such as greenhouse gas emissions, eutrophication, particulate matter, freshwater usage, land use, non-renewable energy consumption, and food loss and waste. Environmental impacts are quantified through an environmental impact score (EIS) assigned to each impact category for a given food. The EIS-nutrition (EIS-N) integrates the evaluation of nutritional quality with environmental impacts using Nutri-Score, a validated food nutrient-profiling tool. The EIS-N is modelled as a ratio of the EIS to the Nutri-Score values. FINDINGS: Preliminary results show the greatest environmental impacts for animal-based foods, particularly beef, in agreement with current literature. Foods with greater nutritional quality also generally show greater environmental sustainability, with some exceptions for particular impact categories. INTERPRETATION: The database and index have potential to serve as powerful tools to support researchers, policy makers, and consumers, harnessing big data to drive efficient food and climate solutions for systems transformation. FUNDING: Province of Ontario and University of Toronto, CIHR SMART Healthy Cities Training Platform, and University of Toronto's Temerty Faculty of Medicine.

Prehospital identification of intracerebral haemorrhage: a scoping review of early clinical features and portable devices.

INTRODUCTION: Prehospital identification of intracerebral haemorrhage (ICH) in suspected stroke cases may enable the initiation of appropriate treatments and facilitate better-informed transport decisions. This scoping review aims to examine the literature to identify early clinical features and portable devices for the detection of ICH in the prehospital setting. METHODS: Three databases were searched via Ovid (MEDLINE, EMBASE and CENTRAL) from inception to August 2022 using prespecified search strategies. One reviewer screened all titles, abstracts and full-text articles for eligibility, while a second reviewer independently screened 20% of the literature during each screening stage. Data extracted were tabulated to summarise the key findings. RESULTS: A total of 6803 articles were screened for eligibility, of which 22 studies were included for analysis. Among them, 15 studies reported on early clinical features, while 7 considered portable devices. Associations between age, sex and comorbidities with the presence of ICH varied across studies. However, most studies reported that patients with ICH exhibited more severe neurological deficits (n=6) and higher blood pressure levels (n=11) at onset compared with other stroke and non-stroke diagnoses. Four technologies were identified for ICH detection: microwave imaging technology, volumetric impedance phase shift spectroscopy, transcranial ultrasound and electroencephalography. Microwave and ultrasound imaging techniques showed promise in distinguishing ICH from other diagnoses. CONCLUSION: This scoping review has identified potential clinical features for the identification of ICH in suspected stroke patients. However, the considerable heterogeneity among the included studies precludes meta-analysis of available data. Moreover, we have explored portable devices to enhance ICH identification. While these devices have shown promise in detecting ICH, further technological development is required to distinguish between stroke subtypes (ICH vs ischaemic stroke) and non-stroke diagnoses.

Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations.

Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes. We present data for 109 anticancer drug combinations from AstraZeneca's oncology small molecule portfolio screened in 755 pan-cancer cell lines. Combinations were screened in a 7 × 7 concentration matrix, with more than 4 million measurements of sensitivity, producing an exceptionally data-rich resource. We implement a new approach using combination Emax (viability effect) and highest single agent (HSA) to assess combination benefit. We designed a clinical translatability workflow to identify combinations with clearly defined patient populations, rationale for tolerability based on tumor type and combination-specific "emergent" biomarkers, and exposures relevant to clinical doses. We describe three actionable combinations in defined cancer types, confirmed in vitro and in vivo, with a focus on hematologic cancers and apoptotic targets. SIGNIFICANCE: We present the largest cancer drug combination screen published to date with 7 × 7 concentration response matrices for 109 combinations in more than 750 cell lines, complemented by multi-omics predictors of response and identification of "emergent" combination biomarkers. We prioritize hits to optimize clinical translatability, and experimentally validate novel combination hypotheses.

Fish diversity of Colombian Andes-Amazon streams at the end of conflict is a reference for conservation before increased land use.

Reference conditions are difficult to find in the Anthropocene but essential for effective biodiversity conservation. Aquatic ecosystems in the Andes-Amazon transition zone of Colombia are now at high risk due to expanded human activities after peace agreements in 2016 ended armed conflict because lands formerly controlled by FARC and other armed groups are now prone to agricultural and urban expansion. Particularly, expanding human land use may reduce fish diversity across the altitudinal gradient, especially in the premontane streams (i.e., <500 m a.s.l.) because lands are more amenable to human use than at greater altitudes. We evaluated fish α-diversity (measured as species richness, total abundance, and effective species number) and ß-diversity (spatial and temporal) in 12 sites over 8 years bracketing the end of armed conflict. All α-diversity and ß-diversity analyses were evaluated relative to categorical altitude (< or >500 m) and continuous altitude. Strong differences in fish community structure among sites occurred as a function of altitude. Fish communities exhibit altitudinal biodiversity gradients that are consistent in space and time, and that need to be accounted for conservation and management considerations. Our results provide a reference to identify short- and long-term changes due to impending human land use at a critical moment for the conservation of tropical fish diversity. Similar studies in other areas of the upper Amazon Basin are needed to evaluate effects of subsequent human activities on diversity patterns and our study area to compare to reference conditions reported here.

The effect of cystic echinococcosis (hydatid disease) on carcase weight in cattle in eastern Australia.

Cystic echinococcosis is caused by the zoonotic tapeworm Echinococcus granulosus. There has been ongoing controversy over whether it causes weight loss in cattle. Recently implemented recording of comorbidities at processors has provided opportunity to investigate this effect. Using prevalence-based observational data from 1,648,049 adult cattle processed in seven states and territories in Australia (2019-2022), we explored associations between carcase weight, hydatid cysts, comorbidities, sex, age, and region. Linear mixed-effect regression models estimated the effect of cystic echinococcosis on carcase weight, guided by directed acyclic graphs to reduce bias. The highest, previously unreported, prevalence was in the southeast Queensland region. The estimated effect of cystic echinococcosis cysts on carcase weight ranged from a gain of 0.32 kg/carcase (standard error [se] 0.58 kg; two-tooth 2022) to a loss of -5.45 kg/carcase (se 0.63 kg; six-tooth 2019) with most point estimates (11/16) between 0 and -2.5 kg across all cattle grouped by year and dentition. This effect size would be practically undetectable in live cattle which is an important finding; cattle producers are unlikely to observe increased productivity through weight gain from cystic echinococcosis prevention in cattle, and awareness to strengthen prevention in domestic dogs around cattle properties to reduce human risk remains a public health focus.

Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.

BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. FINDINGS: Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 71·5% of baseline in the macitentan group and to 87·6% in the placebo group (geometric means ratio 0·81, 95% CI 0·70-0·95, p=0·0098). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). INTERPRETATION: In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. FUNDING: Actelion Pharmaceuticals Ltd.

Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism.

RATIONALE: Chronic Thromboembolic Pulmonary Hypertension involves formation and non-resolution of thrombus, dysregulated inflammation, angiogenesis and the development of a small vessel vasculopathy. OBJECTIVES: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors. METHODS: We conducted a genome-wide association study on 1907 European cases and 10363 European controls. We co-analysed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism and idiopathic pulmonary arterial hypertension. MEASUREMENTS AND MAIN RESULTS: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our co-analysis we demonstrate further associations with chronic thromboembolic pulmonary hypertension at the F2, TSPAN15, SLC44A2 and F5 loci but find no statistically significant associations shared with idiopathic pulmonary arterial hypertension. CONCLUSIONS: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations to pulmonary embolism and to deep vein thrombosis.

A Plant-Based Cholesterol-Lowering Diet Score Correlates with Serum LDL-Cholesterol Levels.

BACKGROUND: A cholesterol-lowering diet score was previously developed for epidemiological studies; its association with serum lipid profile was not confirmed yet. METHODS: The score was developed as an adaptation of the dietary portfolio for cholesterol reduction, assigning one point for adherence to seven dietary indicators and ranging from 0 (null adherence) to 7 (highest adherence). The score was calculated for breast cancer patients enrolled in the DEDiCa study using a 7-day food record; serum lipid profile, including total and low-density lipoprotein cholesterol (LDL-C), was evaluated in serum at baseline. RESULTS: Patients with the highest adherence to the cholesterol-lowering diet (i.e., score ≥ 4) reported lower LDL-C level than women with score 0-1 (median: 107 mg/dL and 122 mg/dL, respectively; p < 0.01). The proportion of women with LDL-C above the recommended limit of 116 mg/dL was 60.0% with score 0-1 and 42.6% with score ≥4. Although the score directly correlates with consumption of foods from vegetal sources, it was mildly associated with the healthful plant-based diet index (r-Spearman = 0.51) and the Mediterranean Diet Adherence Screener (r-Spearman = 0.30) Conclusions: These results provide experimental evidence that the cholesterol-lowering diet score is capable of detecting a specific plant-based dietary pattern that affects circulating cholesterol levels.

Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2.

BACKGROUND: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. OBJECTIVE: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. STUDY DESIGN: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. RESULTS: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups. CONCLUSION: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

Accreditation of antimicrobial stewardship programmes: addressing a global need to tackle antimicrobial resistance.

Accreditation of healthcare services provides quality assurance of hospital practice to support safe and effective care for patients. Accreditation programmes focused on antimicrobial stewardship (AMS) have been developed in high-income countries (HIC) and recently the WHO has developed a toolkit to support AMS practice in low and middle-income (LMIC) countries. BSAC has developed their Global Antimicrobial Stewardship Accreditation Scheme (GAMSAS) for hospitals based on globally applicable standards. GAMSAS aims to support healthcare organizations to build measurable AMS programmes and to support spread of best practice. GAMSAS involves a desktop assessment by BSAC experts followed by a hospital visit to gather further insight into how a hospital's AMS programme operates. A final report of compliance with the GAMSAS standards and a recommendation about accreditation at one of three levels is formally approved at a GAMSAS panel meeting involving well-established global experts in AMS. The BSAC GAMSAS team reflect on progress during the first year and ambitions for future spread.

The effects of inulin-type fructans on cardiovascular disease risk factors: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Inulin-type fructans (ITF) are the leading prebiotics in the market. Available evidence provides conflicting results regarding the beneficial effects of ITF on cardiovascular disease risk factors. OBJECTIVES: This study aimed to evaluate the effects of ITF supplementation on cardiovascular disease risk factors in adults. METHODS: We searched MEDLINE, EMBASE, Emcare, AMED, CINAHL, and the Cochrane Library databases from inception through May 15, 2022. Eligible randomized controlled trials (RCTs) administered ITF or placebo (for example, control, foods, diets) to adults for ≥2 weeks and reported one or more of the following: low, very-low, or high-density lipoprotein cholesterol (LDL-C, VLDL-C, HDL-C); total cholesterol; apolipoprotein A1 or B; triglycerides; fasting blood glucose; body mass index; body weight; waist circumference; waist-to-hip ratio; systolic or diastolic blood pressure; or hemoglobin A1c. Two reviewers independently and in duplicate screened studies, extracted data, and assessed risk of bias. We pooled data using random-effects model, and assessed the certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We identified 1767 studies and included 55 RCTs with 2518 participants in meta-analyses. The pooled estimate showed that ITF supplementation reduced LDL-C [mean difference (MD) -0.14 mmol/L, 95% confidence interval (95% CI: -0.24, -0.05), 38 RCTs, 1879 participants, very low CoE], triglycerides (MD -0.06 mmol/L, 95% CI: -0.12, -0.01, 40 RCTs, 1732 participants, low CoE), and body weight (MD -0.97 kg, 95% CI: -1.28, -0.66, 36 RCTs, 1672 participants, low CoE) but little to no significant effect on other cardiovascular disease risk factors. The effects were larger when study duration was ≥6 weeks and in pre-obese and obese participants. CONCLUSION: ITF may reduce low-density lipoprotein, triglycerides, and body weight. However, due to low to very low CoE, further well-designed and executed trials are needed to confirm these effects. PROSPERO REGISTRATION NUMBER: CRD42019136745.

Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants.

BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.

Electrical tuning of quantum light emitters in hBN for free space and telecom optical bands.

Quantum light emitters (also known as single photon emitters) are known to be the heart of quantum information technologies. Irrespective of possessing ideal single photon emitter properties, quantum emitters in 2-D hBN defect structures, exhibit constrained quantum light emission within the 300-700 nm range. However, this emission range cannot fully satisfy the needs of an efficient quantum communication applications such as quantum key distribution (QKD), which demands the quantum light emission in fiber optic telecom wavelength bands (from 1260 to 1625 nm) and the free space optical (FSO) (UV-C-solar blind band-100 to 280 nm) wavelength ranges. Hence, there is a necessity to tune the quantum light emission into these two bands. However, the most promising technique to tune the quantum light emitters in hBN here, is still a matter of debate and till date there is no experimental and theoretical assurances. Hence, this work will focus on one of the most promising simple techniques known as Stark electrical tuning of the quantum light emission of hBN defect structures (NBVN, VB, CB, CBVN, CBCN, CBCNCBCN complex, and VBO2). These hBN defects are designed and sandwiched as metal/graphene/hBN defect structure/graphene/metal heterostructure and electrically tuned towards FSO and fiber optic bands (tuning range from UV-C to O-band IR region) region, using constrained DFT computations. The external electric field predicted to yield an atomic bond angle tilt associated with this point defect structure creates out-of-plane dipole moments, enabling the tuning of quantum emission. This electrical tuning technique leads to a simple passive photonic component which enables easier compatibility with quantum circuits and it is found to be one of the perfect alternative solutions, which does not require much external hardware setup to implement as compared to earlier published strain induced tuning experiments.

Comparing Predictive Performance of Time Invariant and Time Variant Clinical Prediction Models in Cardiac Surgery.

Clinical prediction models are increasingly used across healthcare to support clinical decision making. Existing methods and models are time-invariant and thus ignore the changes in populations and healthcare practice that occur over time. We aimed to compare the performance of time-invariant with time-variant models in UK National Adult Cardiac Surgery Audit data from Manchester University NHS Foundation Trust between 2009 and 2019. Data from 2009-2011 were used for initial model fitting, and data from 2012-2019 for validation and updating. We fitted four models to the data: a time-invariant logistic regression model (not updated), a logistic model which was updated every year and validated it in each subsequent year, a logistic regression model where the intercept is a function of calendar time (not updated), and a continually updating Bayesian logistic model which was updated with each new observation and continuously validated. We report predictive performance over the complete validation cohort and for each year in the validation data. Over the complete validation data, the Bayesian model had the best predictive performance.

Compatibility in Missing Data Handling Across the Prediction Model Pipeline: A Simulation Study.

Careful handling of missing data is crucial to ensure that clinical prediction models are developed, validated, and implemented in a robust manner. We determined the bias in estimating predictive performance of different combinations of approaches for handling missing data across validation and implementation. We found four strategies that are compatible across the model pipeline and have provided recommendations for handling missing data between model validation and implementation under different missingness mechanisms.

Plant-Based Milk Consumption and Growth in Children 1-10 Years of Age.

BACKGROUND: The effects of plant-based milk consumption on the growth of children are unclear. OBJECTIVES: We aimed to evaluate the relationship between plant-based milk consumption and BMI in childhood. Secondary objectives were to examine the association with height and whether these relationships are mediated by dairy milk intake and modified by age or the type of plant-based milk consumed. METHODS: A prospective cohort study was conducted in healthy children aged 1-10 y through the TARGet Kids! primary care research network in Toronto, Canada. Linear mixed-effect modeling and logistic generalized estimating equations were used to evaluate the association between plant-based milk consumption (number of 250 mL cups/d) and BMI. A mediation analysis was conducted to examine whether dairy milk intake mediated these relationships. Effect modification by age and type of plant-based milk was explored. RESULTS: Among 7195 children (mean age: 3.1 y; 52.3% male), higher plant-based milk consumption was associated with lower BMI (P = 0.0002) and height (P = 0.005). No association was found with BMI categories. Lower dairy milk intake partially mediated these relationships. A child aged 5 y who consumed 3 cups of plant-based milk compared with 3 cups of dairy milk had a lower weight of 0.5 kg and lower height of 0.8 cm. Associations did not change over time and were similar for children who consumed soy milk compared with other plant-based milks. CONCLUSIONS: Plant-based milk consumption was associated with lower BMI and height, but both were within the normal range on average. Future longitudinal studies are needed to determine whether these associations persist over time.

Perioperative extracorporeal membrane oxygenation support for pulmonary endarterectomy: A 17-year experience from the UK national cohort.

BACKGROUND: Pulmonary endarterectomy (PEA) is the guideline-recommended treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, some patients develop severe cardiopulmonary compromise before surgery, intraoperatively, or early postoperatively. This may result from advanced CTEPH, reperfusion pulmonary edema, massive endobronchial bleeding, or right ventricular (RV) failure secondary to residual pulmonary hypertension. Conventional cardiorespiratory support is ineffective when these complications are severe. Since 2005, we used extracorporeal membrane oxygenation (ECMO) as a rescue therapy for this group. We review our experience with ECMO support in these patients. METHODS: This study was a retrospective analysis of patients who received perioperative ECMO for PEA from a single national center from August 2005 to July 2022. Data were prospectively collected. RESULTS: One hundred and ten patients (4.7%) had extreme cardiorespiratory compromise requiring perioperative ECMO. Nine were established on ECMO before PEA. Of those who received ECMO postoperatively, 39 were for refractory reperfusion lung injury, 20 for RV failure, 31 for endobronchial bleeding, and the remaining 11 were for "other" reasons, such as cardiopulmonary resuscitation following late tamponade and aspiration pneumonitis. Sixty-two (56.4%) were successfully weaned from ECMO. Fifty-seven patients left the hospital alive, giving a salvage rate of 51.8%. Distal disease (Jamieson Type III) and significant residual pulmonary hypertension were also predictors of mortality on ECMO support. Overall, 5- and 10-year survival in patients who were discharged alive following ECMO support was 73.9% (SE: 6.1%) and 58.2% (SE: 9.5%), respectively. CONCLUSIONS: Perioperative ECMO support has an appropriate role as rescue therapy for this group. Over 50% survived to hospital discharge. These patients had satisfactory longer-term survival.

A comparative study of protein structure prediction tools for challenging targets: Snake venom toxins.

Protein structure determination is a critical aspect of biological research, enabling us to understand protein function and potential applications. Recent advances in deep learning and artificial intelligence have led to the development of several protein structure prediction tools, such as AlphaFold2 and ColabFold. However, their performance has primarily been evaluated on well-characterised proteins and their ability to predict sturtctures of proteins lacking experimental structures, such as many snake venom toxins, has been less scrutinised. In this study, we evaluated three modelling tools on their prediction of over 1000 snake venom toxin structures for which no experimental structures exist. Our findings show that AlphaFold2 (AF2) performed the best across all assessed parameters. We also observed that ColabFold (CF) only scored slightly worse than AF2, while being computationally less intensive. All tools struggled with regions of intrinsic disorder, such as loops and propeptide regions, and performed well in predicting the structure of functional domains. Overall, our study highlights the importance of exercising caution when working with proteins with no experimental structures available, particularly those that are large and contain flexible regions. Nonetheless, leveraging computational structure prediction tools can provide valuable insights into the modelling of protein interactions with different targets and reveal potential binding sites, active sites, and conformational changes, as well as into the design of potential molecular binders for reagent, diagnostic, or therapeutic purposes.