Fine-mode aerosol optical depth (fAOD) is a vital proxy for the concentration of anthropogenic aerosols in the atmosphere. Currently, the limited data length and high uncertainty of the satellite-based data diminish the applicability of fAOD for climate research. Here, we propose a novel pretrained deep learning framework that can extract information underlying each satellite pixel and use it to create new latent features that can be employed for improving retrieval accuracy in regions without in situ data. With the proposed model, we developed a new global fAOD (at 0.5 μm) data from 2001 to 2020, resulting in a 10% improvement in the overall correlation coefficient (R) during site-based independent validation and a 15% enhancement in non-AERONET site areas validation. Over the past two decades, there has been a noticeable downward trend in global fAOD (-1.39 × 10-3/year). Compared to the general deep-learning model, our method reduces the global trend\'s previously overestimated magnitude by 7% per year. China has experienced the most significant decline (-5.07 × 10-3/year), which is 3 times greater than the global trend. Conversely, India has shown a significant increase (7.86 × 10-4/year). This study bridges the gap between sparse in situ observations and abundant satellite measurements, thereby improving predictive models for global patterns of fAOD and other climate factors.

Aerosol Optical Depth (AOD) data derived from satellites is crucial for estimating spatially-resolved PM concentrations, but existing AOD data over land remain affected by several limitations (e.g., data gaps, coarser resolution, higher uncertainty or lack of size fraction data), which weakens the AOD-PM relationship. We developed a 0.1° resolution daily AOD data set over Europe over the period 2003-2020, based on two-stage Quantile Machine Learning (QML) frameworks. Our approach first fills gaps in satellite AOD data and then constructs three components\' models to obtain reliable full-coverage AOD along with Fine-mode AOD (fAOD) and Coarse-mode AOD (cAOD). These models are based on AERONET (AErosol RObotic NETwork) observations, Gap-filled satellite AOD, climate and atmospheric composition reanalyses. Our QML AOD products exhibit better quality with an out-of-sample R2 equal to 0.68 for AOD, 0.66 for fAOD and 0.65 for cAOD, which is 23-92 %, 11-13 % and 115-132 % higher than the corresponding satellite or reanalysis products, respectively. Over 91.6 %, 81.6 %, and 88.9 % of QML AOD, fAOD and cAOD predictions fall within ±20 % Expected Error (EE) envelopes, respectively. Previous studies reported that a weak satellite AOD-PM correlation across Europe (Pearson correlation coefficient (PCC) around 0.1). Our QML products exhibit higher correlations with ground-level PMs, particularly when broadly matched by size: AOD with PM10, fAOD with PM2.5, cAOD with PM coarse (R = 0.41, 0.45 and 0.26, respectively). Different AOD fractions more effectively distinct PM size fractions, than total AOD. Our QML aerosol dataset and models pioneer full-coverage, daily high-resolution monitoring of fine-mode and coarse-mode aerosols, effectively addressing existing AOD challenges for further PMs exposures\' estimations. This dataset opens avenues for more in-depth exploration of the impacts of aerosols on human health, climate, visibility, and biogeochemical processes, offering valuable insights for air quality management and environmental health risk assessment.

This study compared the anthropometric parameters of patients with fatty acid oxidation disorders (FAOD) and healthy controls, showing an increased prevalence of abnormal body weight (overweight and obesity) in the FAOD group. First, differences in BMI, BMI percentiles and z-scores, and weight and weight percentiles were compared in a cohort of 39 patients with FAOD and 156 healthy controls, as well as between patients born before and after the introduction of a populational newborn screening programme (NBS) in 2014 in Poland. We also performed a systematic literature review yielding 12 studies mentioning anthropometric parameters in 80 FAOD patients and 121 control subjects, followed by a meta-analysis of data from 8 studies and our cohort. There were significant differences in body weight percentiles (p = 0.001), BMI (p = 0.022), BMI percentiles (p = 0.003) and BMI z-scores (p = 0.001) between FAOD patients and controls in our cohort but not between pre- and post-newborn-screening patients. The meta-analysis did not show any differences in weight and BMI in all tested subgroups, i.e., all FAOD patients vs. controls, medium-chain acyl-CoA dehydrogenase (MCADD) patients vs. controls and patients with FAOD types other than MCAD vs. controls. These results, however, should be interpreted with caution due to the overall low quality of evidence as assessed by GRADE, the small sample sizes and the significant heterogeneity of the included data.

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.

Despite their extremely small size, fine-mode aerosols have significant impacts on the environment, climate, and human health. However, current understandings of global changes in fine-mode aerosols are limited. In this study, we employed newly developed satellite retrieval data and an attentive interpretable deep learning model to explore the status, changes, and association factors of the global fine-mode aerosol optical depth (fAOD) and aerosol fine-mode fraction (FMF) from 2008 to 2017. At the global scale, the results show a significant increasing trend in land FMF (2.34 × 10-3/year); however, the FMF over the ocean and the fAOD over land and ocean did not reveal significant trends. Between 2008 and 2017, high levels of both fAOD (>0.30) and FMF (>0.75) were identified over China, southeastern Asia, India, and Africa. Seasonally, global land FMF showed high values in summer (>0.70) and low values in spring (<0.65), while land fAOD was high in summer (>0.15) but low in winter (<0.13). Importantly, Australia and Mexico experienced significant increasing trends in FMF during all four seasons. At the regional scale, a significant decline in fAOD was identified in China, which indicates that government emission controls and reductions have been effective in recent decades. The deep learning model was used to interpret the result and showed that O3 was significantly associated with changes in both the FMF and fAOD. This finding suggests the importance of synergizing the regulations for both O3 and fine particles. Our work comprehensively examined global spatial and seasonal fAOD and FMF changes and provides a holistic understanding of global anthropogenic impacts.

Fatty acid oxidation disorders (FAOD) are a group of rare, autosomal recessive, metabolic disorders caused by variants of the genes for the enzymes and proteins involved in the transport and metabolism of fatty acids in the mitochondria. Those affected by FAOD are unable to convert fatty acids into tricarboxylic acid cycle intermediates such as acetyl-coenzyme A, resulting in decreased adenosine triphosphate and glucose for use as energy in a variety of high-energy-requiring organ systems. Signs and symptoms may manifest in infants but often also appear in adolescents or adults during times of increased metabolic demand, such as fasting, physiologic stress, and prolonged exercise. Patients with FAOD present with a highly heterogeneous clinical spectrum. The most common clinical presentations include hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, rhabdomyolysis, and skeletal myopathy, as well as peripheral neuropathy and retinopathy in some subtypes. Despite efforts to detect FAOD through newborn screening and manage patients early, symptom onset can be sudden and serious, even resulting in death. Therefore, it is critical to identify quickly and accurately the key signs and symptoms of patients with FAOD to manage metabolic decompensations and prevent serious comorbidities.

Long-chain fatty acid oxidation disorders (LC-FAOD) lead to accumulation of high concentrations of potentially toxic fatty acid intermediates. Newborn screening and early intervention have reduced mortality, but most patients continue to experience frequent hospitalizations and significant morbidity despite treatment. The deficient energy state can cause serious liver, muscle, and heart disease, and may be associated with an increased risk of sudden death. Triheptanoin is a medium odd-chain fatty acid. Anaplerotic metabolites of triheptanoin have the potential to replace deficient tricarboxylic acid (TCA) cycle intermediates, resulting in net glucose production as a novel energy source for the treatment of LC-FAOD.
A single-arm, open-label, multicenter Phase 2 safety and efficacy study evaluated patients with severe LC-FAOD evidenced by ongoing related musculoskeletal, cardiac, and/or hepatic events despite treatment. After a four-week run-in on current regimen, investigational triheptanoin (UX007) was titrated to a target dose of 25-35% of total daily caloric intake. Patients were evaluated on several age/condition-eligible endpoints, including submaximal exercise tests to assess muscle function/endurance (12-minute walk test; 12MWT) and exercise tolerance (cycle ergometry), and health related quality of life (HR-QoL). Results through 24weeks of treatment are presented; total study duration is 78weeks.
Twenty-nine patients (0.8 to 58years) were enrolled; most qualified based on severe musculoskeletal disease. Twenty-five patients (86%) completed the 24-week treatment period. At Week 18, eligible patients (n=8) demonstrated a 28% increase (LS mean=+181.9 meters; p=0.087) from baseline (673.4meters) in 12MWT distance. At Week 24, eligible patients (n=7) showed a 60% increase in watts generated (LS mean=+409.3W; p=0.149) over baseline (744.6W) for the exercise tolerance test. Improvements in exercise tests were supported by significant improvements from baseline in the adult (n=5) self-reported SF-12v2 physical component summary score (LS mean=+8.9; p<0.001). No difference from baseline was seen in pediatric parent-reported (n=5) scores (SF-10) at Week 24. Eighteen patients (62%) had treatment-related adverse events, predominantly gastrointestinal (55%), mild-to-moderate in severity, similar to that seen with prior treatment with medium chain triglyceride (MCT) oil. One patient experienced a treatment-related serious adverse event of gastroenteritis. One patient discontinued from study due to diarrhea of moderate severity; the majority of patients (25/29; 86%) elected to continue treatment in the extension period.
In patients with severe LC-FAOD, UX007 interim study results demonstrated improved exercise endurance and tolerance, and were associated with positive changes in self-reported HR-QoL.

IEM screening by ESI/MS/MS was introduced in Singapore in 2006. There were two phases; a pilot study followed by implementation of the current program. The pilot study was over a 4 year period. During the pilot study, a total of 61,313 newborns were screened, and 20 cases of IEM were diagnosed (detection rate of 1:3065; positive predictive value (PPV) of 11%). Regular self-review, participation in external quality assessment and the Region 4 Genetic collaborative programs (http://www.region4genetics.org/) had led to the robust development of our current NBS MS/MS program. Overall, from July 2006 to April 2014, we screened a total of 177,267 newborns. The mean age at the time of sampling was 47.9h. Transportation of samples to the testing laboratory averaged 0.92 day. Upon receipt of sample, the NBS result was available within 1.64 days and within 3.8 days if a second tier test was required. Using absolute cut-off values in place of the initial 99th percentile reference range for the analyte markers and the introduction of two 2nd tier tests (MMA and Succinylacetone) had significantly reduced the high recall rate from an initial 1.5% during the period 2006-07 to 0.12% in 2013. The NBS MS/MS program was supported by a centralized confirmatory/diagnostic testing laboratory and a rapid response team of metabolic specialists. The detection rate was 1: 3165 (1:2727 if maternal conditions were also included). There were 23 newborns affected with organic acidemias (incidence: 1:6565), 23 with fatty acid oxidation disorders (incidence: 1:6565), and 10 with amino acidopathies (incidence 1:17,726). The performance metrics for the screening test were acceptable (sensitivity: 95.59%, specificity: 99.85%, PPV: 20%, FPR: 0.15). Participation in the NBS MS/MS program by hospitals was voluntary, and in 2013, the uptake rate was 71% of the annual births. We hope that newborn screening by MS/MS will become a standard of care for all babies in Singapore.