Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy.

Ionizable lipids are a key component of lipid nanoparticles, the leading nonviral messenger RNA delivery technology. Here, to advance the identification of ionizable lipids beyond current methods, which rely on experimental screening and/or rational design, we introduce lipid optimization using neural networks, a deep-learning strategy for ionizable lipid design. We created a dataset of >9,000 lipid nanoparticle activity measurements and used it to train a directed message-passing neural network for prediction of nucleic acid delivery with diverse lipid structures.

Over-reliance on land for carbon dioxide removal in net-zero climate pledges.

Achieving net-zero climate targets requires some level of carbon dioxide removal. Current assessments focus on tonnes of CO removed, without specifying what form these removals will take. Here, we show that countries' climate pledges require approximately 1 (0.

Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.

Objective: Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.

External validation of models to estimate gestational age in the second and third trimester using ultrasound: A prospective multicentre observational study.

Objectives: Accurate assessment of gestational age (GA) is important at both individual and population levels. The most accurate way to estimate GA in women who book late in pregnancy is unknown. The aim of this study was to externally validate the accuracy of equations for GA estimation in late pregnancy and to identify the best equation for estimating GA in women who do not receive an ultrasound scan until the second or third trimester.

Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy.

Introduction: Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD.

Statistical Characterisation of Fetal Anatomy in Simple Obstetric Ultrasound Video Sweeps.

Objective: We present a statistical characterisation of fetal anatomies in obstetric ultrasound video sweeps where the transducer follows a fixed trajectory on the maternal abdomen.

Methods: Large-scale, frame-level manual annotations of fetal anatomies (head, spine, abdomen, pelvis, femur) were used to compute common frame-level anatomy detection patterns expected for breech, cephalic, and transverse fetal presentations, with respect to video sweep paths. The patterns, termed statistical heatmaps, quantify the expected anatomies seen in a simple obstetric ultrasound video sweep protocol.

Intermittent Versus Sustained Hypoxemia from Sleep-disordered Breathing: Outcomes in Patients with Chronic Lung Disease and High Altitude.

In a variety of physiologic and pathologic states, people may experience both chronic sustained hypoxemia and intermittent hypoxemia ("combined" or "overlap" hypoxemia). In general, hypoxemia in such instances predicts a variety of maladaptive outcomes, including excess cardiovascular disease or mortality. However, hypoxemia may be one of the myriad phenotypic effects in such states, making it difficult to ascertain whether adverse outcomes are primarily driven by hypoxemia, and if so, whether these effects are due to intermittent versus sustained hypoxemia.

Respiratory syncytial virus disease morbidity in Australian infants aged 0 to 6 months: a systematic review with narrative synthesis.

Background: A significant proportion of the global respiratory syncytial virus (RSV) associated morbidity is accounted for by infants aged 0 to 6 months, who are particularly vulnerable to severe disease. In 2015, 44% of global hospitalisations in infants in this age group were secondary to RSV. The objective of this systematic review is to appraise and synthesise the local evidence of RSV infection morbidity among Australian infants aged 0 to 6 months and to assess the implications for future immunisation strategies.

Engineering a dual vaccine against COVID-19 and tuberculosis.

The COVID-19 pandemic, caused by SARS-CoV-2 virus, has been one of the top public health threats across the world over the past three years. BCG is currently the only licensed vaccine for tuberculosis, one of the deadliest infectious diseases in the world, that is caused by . In the past decades, recombinant BCG has been studied as a novel vaccine vector for other infectious diseases in humans besides tuberculosis, such as viral infections.

An Unexpected Cause of Lung Disease Identified After Lung Transplantation.

A 54-year-old woman with systemic lupus erythematosus with associated interstitial lung disease (ILD) presented to the lung transplant clinic for assessment of candidacy for transplantation. She was initially diagnosed with ILD based on clinical and radiographic features (never underwent lung biopsy). In addition, she had associated mixed group I/III pulmonary arterial hypertension.

Does simulation training result in improved on-call outcomes among newly appointed radiology registrars?

Aim: To quantify the impact of a marked increase in radiology trainee numbers and the compensatory introduction of formal simulation on-call training by investigating the discrepancy rates among on-call radiologists in training before and after the introduction of structured simulation training.

Materials And Methods: The first 100 cases reported by a cohort of Specialty Trainee Year 2 doctors (ST2), having commenced on-call reporting, were analysed. This included registrars working in two major tertiary centres.

Inpatient Transition From Intravenous to Inhaled Treprostinil in a Pediatric Patient.

We report a case of a 7-year old male with idiopathic pulmonary arterial hypertension, successfully transitioned from an intravenous infusion to inhaled treprostinil during inpatient admission, after his intentional removal of multiple central venous catheters. He had no clinical, echocardiographic, or serum biomarker evidence of loss of control of pulmonary arterial hypertension during the 4-day transition. The patient was discharged home without complications, and 3 weeks after discharge the patient's pulmonary hypertension remained well controlled per clinical and echocardiographic evidence, including a significantly improved 6-minute walk distance test.

Automatic Image Guidance for Assessment of Placenta Location in Ultrasound Video Sweeps.

Ultrasound-based assistive tools are aimed at reducing the high skill needed to interpret a scan by providing automatic image guidance. This may encourage uptake of ultrasound (US) clinical assessments in rural settings in low- and middle-income countries (LMICs), where well-trained sonographers can be scarce. This paper describes a new method that automatically generates an assistive video overlay to provide image guidance to a user to assess placenta location.

Developing Clinical Artificial Intelligence for Obstetric Ultrasound to Improve Access in Underserved Regions: Protocol for a Computer-Assisted Low-Cost Point-of-Care UltraSound (CALOPUS) Study.

Background: The World Health Organization recommends a package of pregnancy care that includes obstetric ultrasound scans. There are significant barriers to universal access to antenatal ultrasound, particularly because of the cost and need for maintenance of ultrasound equipment and a lack of trained personnel. As low-cost, handheld ultrasound devices have become widely available, the current roadblock is the global shortage of health care providers trained in obstetric scanning.

Separation sign: novel ultrasound sign for ruling out diagnosis of placenta accreta spectrum.

Objective: To assess the performance of the 'separation sign' as a predictor of normal placental separation in a large cohort of women at risk for placenta accreta spectrum (PAS) and in a high-risk subgroup with placenta previa or anterior low-lying placenta and at least one previous Cesarean delivery.

Methods: This was a prospective study of women at risk for PAS referred to a specialist clinic at between 22 and 38 weeks' gestation. All women underwent ultrasound assessment for the presence of the separation sign, which detects the difference in elasticity between the myometrium and the placenta, characterized by different rates of rebound after an ultrasound probe is used to apply pressure over the uteroplacental interface.

Second and third trimester estimation of gestational age using ultrasound or maternal symphysis-fundal height measurements: A systematic review.

Many vulnerable women seek antenatal care late in pregnancy. How should gestational age be determined? We examine all available studies estimating GA >20 weeks. Ultrasound is much better than fundal height, and using cerebellar measurement appears to be the most accurate.

Ultrasound Diagnosis of the Small and Large Fetus.

Antenatal imaging is crucial in the management of high-risk pregnancies. Accurate dating relies on acquisition of reliable and reproducible ultrasound images and measurements. Quality image acquisition is necessary for assessing fetal growth and performing Doppler measurements to help diagnose pregnancy complications, stratify risk, and guide management.

Quantification of intra-articular fibrosis in patients with stiff knee arthroplasties using metal-reduction MRI.

Aims: Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties.

Characterization and Comparison of Primary Care Appointment Utilization Patterns Among Military Health System Beneficiaries.

Introduction: The role of primary care in the United States is vitally important to improving health outcomes, minimizing waste, and controlling cost. The Military Health System is tasked with both caring for its beneficiaries and ensuring the medical readiness of active duty service members, who often have needs unique to those in the civilian population. Balancing the number of individuals assigned to a primary care clinician with the clinician's capacity to meet their medical needs and anticipated appointment demand is a fundamental cornerstone of effective primary care clinic management in any setting.

Publisher Correction: A global database of Holocene paleotemperature records.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Alcohol-related emergency department visits, hospitalizations, and co-occurring injuries, active component, U.S. Armed Forces, 2009-2018.

The military has a high prevalence of alcohol misuse, which can lead to injuries and negative health outcomes. This report characterizes the rate of alcohol- related emergency department and inpatient encounters in the military and the percentage of encounters with co-occurring injury. Between January 2009 and December 2018, there were 75.