3D facial landmarks are known to be diagnostically relevant biometrics for many genetic syndromes. The objective of this study was to extend a state-of-the-art image-based 2D facial landmarking ...algorithm for the challenging task of 3D landmark identification on subjects with genetic syndromes, who often have moderate to severe facial dysmorphia. The automatic 3D facial landmarking algorithm presented here uses 2D image-based facial detection and landmarking models to identify 12 landmarks on 3D facial surface scans. The landmarking algorithm was evaluated using a test set of 444 facial scans with ground truth landmarks identified by two different human observers. Three hundred and sixty nine of the subjects in the test set had a genetic syndrome that is associated with facial dysmorphology. For comparison purposes, the manual landmarks were also used to initialize a non-linear surface-based registration of a non-syndromic atlas to each subject scan. Compared to the average intra- and inter-observer landmark distances of 1.1 mm and 1.5 mm respectively, the average distance between the manual landmark positions and those produced by the automatic image-based landmarking algorithm was 2.5 mm. The average error of the registration-based approach was 3.1 mm. Comparing the distributions of Procrustes distances from the mean for each landmarking approach showed that the surface registration algorithm produces a systemic bias towards the atlas shape. In summary, the image-based automatic landmarking approach performed well on this challenging test set, outperforming a semi-automatic surface registration approach, and producing landmark errors that are comparable to state-of-the-art 3D geometry-based facial landmarking algorithms evaluated on non-syndromic subjects.
Off-grid connected objects are widely used for environmental monitoring applications such as air and water quality, soil salinity, weather forecasting and more. In recent studies, mechanical energy ...harvesting using triboelectric nanogenerators (TENGs) have gained in efficiency, even though the design of these TENGs was kept simple. In this context, the durability of the mechanical contact between triboelectric materials is challenged. This is why, free-standing balls have been proposed to reduce the friction in TENGs instead of foils, which are commonly used. Thus, a non-contact gravitational TENG at state-of-the-art performances is proposed in this work. This two-stage design is based on free-standing balls in a rotor and a contactless capacitive coupler. The power generation has been investigated for these two stages according to analytical models. A new methodology to extract the Norton model parameters from a moving TENG is suggested. Through an optimized interdigitated design of the capacitive coupler, a 27-fold increase of the primary stage power is demonstrated and a state-of-the-art peak output power density of 24.45 W m−2 is reached. This study is a leading-edge example of how TENGs could be adopted to power small remote apparatus, in addition of battery.
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•A state-of-the-art output power density of 24.45 W m−2 is generated by a two-stage non-contact gravitational TENG.•Comprehensive analytical models are established and a new methodology for extracting Norton model parameters is proposed.•Design of an interdigitated capacitive coupler to boost output current, resulting in high power generation at low speed.
The past decade has witnessed a rapid evolution in rare disease (RD) research, fueled by the availability of genome-wide (exome and genome) sequencing. In 2011, as this transformative technology was ...introduced to the research community, the Care4Rare Canada Consortium was launched: initially as FORGE, followed by Care4Rare, and Care4Rare SOLVE. Over what amounted to three eras of diagnosis and discovery, the Care4Rare Consortium used exome sequencing and, more recently, genome and other 'omic technologies to identify the molecular cause of unsolved RDs. We achieved a diagnostic yield of 34% (623/1,806 of participating families), including the discovery of deleterious variants in 121 genes not previously associated with disease, and we continue to study candidate variants in novel genes for 145 families. The Consortium has made significant contributions to RD research, including development of platforms for data collection and sharing and instigating a Canadian network to catalyze functional characterization research of novel genes. The Consortium was instrumental to implementing genome-wide sequencing as a publicly funded test for RD diagnosis in Canada. Despite the successes of the past decade, the challenge of solving all RDs remains enormous, and the work is far from over. We must leverage clinical and 'omic data for secondary use, develop tools and policies to support safe data sharing, continue to explore the utility of new and emerging technologies, and optimize research protocols to delineate complex disease mechanisms. Successful approaches in each of these realms is required to offer diagnostic clarity to all families with RDs.
After a decade of collaborative network science in Canada and three eras of RD gene discovery, the Care4Rare Canada Consortium recognized it was time to reflect on the lessons learned from our successes to best meet the challenges of RD diagnosis and discovery in the decade to come.
We performed unbiased analysis of steroid-related compounds to identify novel Alzheimer's disease (AD) plasma biomarkers using liquid chromatography-atmospheric pressure chemical ionization-mass ...spectroscopy. The analysis revealed that desmosterol was found to be decreased in AD plasma versus controls. To precisely quantify variations in desmosterol, we established an analytical method to measure desmosterol and cholesterol. Using this LC-based method, we discovered that desmosterol and the desmosterol/cholesterol ratio are significantly decreased in AD. Finally, the validation of this assay using 109 clinical samples confirmed the decrease of desmosterol in AD as well as a change in the desmosterol/cholesterol ratio in AD. Interestingly, we could also observe a difference between mild cognitive impairment and control. In addition, the decrease of desmosterol was somewhat more significant in females. Receiver operating characteristic (ROC) analysis between controls and AD, using plasma desmosterol shows a score of 0.80, indicating a good discrimination power for this marker in the two reference populations and confirms the potential usefulness of measuring plasma desmosterol levels for diagnosing AD. Further analysis showed a significant correlation of plasma desmosterol with Mini-Mental State Examination scores. Although larger sample populations will be needed to confirm this diagnostic marker sensitivity, our studies demonstrate a sensitive and accurate method of detecting plasma desmosterol concentration and suggest that plasma desmosterol could become a powerful new specific biomarker for early and easy AD diagnosis.
DING proteins, named after their conserved N-terminus, form an overlooked protein family whose members were generally discovered through serendipity. It is characterized by an unusually high sequence ...conservation, even between distantly related species, and by an outstanding diversity of activities and ligands. They all share a demonstrated capacity to bind phosphate with high affinity or at least a predicted phosphate-binding site. However, DING protein genes are conspicuously absent from databases. The many novel family members identified in recent years have confirmed that DING proteins are ubiquitous not only in animals and plants but probably also in prokaryotes. At the functional level, there is increasing evidence that they participate in many health-related processes such as cancers as well as bacterial (Pseudomonas) and viral (HIV) infections, by mechanisms that are now beginning to be understood. They thus represent potent targets for the development of novel therapeutic approaches, especially against HIV. The few genomic sequences that are now available are starting to give some clues on why DING protein genes and mRNAs are well conserved and difficult to clone. This could open a new era of research, of both fundamental and applied importance.
One of the primary difficulties in treating patients with genetic syndromes is diagnosing their condition. Many syndromes are associated with characteristic facial features that can be imaged and ...utilized by computer-assisted diagnosis systems. In this work, we develop a novel 3D facial surface modeling approach with the objective of maximizing diagnostic model interpretability within a flexible deep learning framework. Therefore, an invertible normalizing flow architecture is introduced to enable both inferential and generative tasks in a unified and efficient manner. The proposed model can be used (1) to infer syndrome diagnosis and other demographic variables given a 3D facial surface scan and (2) to explain model inferences to non-technical users via multiple interpretability mechanisms. The model was trained and evaluated on more than 4700 facial surface scans from subjects with 47 different syndromes. For the challenging task of predicting syndrome diagnosis given a new 3D facial surface scan, age, and sex of a subject, the model achieves a competitive overall top-1 accuracy of 71%, and a mean sensitivity of 43% across all syndrome classes. We believe that invertible models such as the one presented in this work can achieve competitive inferential performance while greatly increasing model interpretability in the domain of medical diagnosis.
Consumption of
MCC1274 has been shown to improve memory and prevent brain atrophy in populations with mild cognitive impairment (MCI). Preclinical in vivo studies using Alzheimer's disease (AD) ...models indicate that this probiotic protects against brain inflammation. There is growing evidence that lipid droplets are associated with brain inflammation, and lipid-associated proteins called perilipins could play an important role in neurodegenerative diseases such as dementia. In this study, we found that
MCC1274 cell extracts significantly decreased the expression of perilipin 4 (
), which encodes a lipid droplet docking protein whose expression is known to be increased during inflammation in SH-SY5Y cells. Niacin, an MCC1274 cell extract component, increased
expression by itself. Moreover, MCC1274 cell extracts and niacin blocked the PLIN4 induction caused by oxidative stress in SH-SY5Y cells, reduced lipid droplet formation, and prevented IL-6 cytokine production. These results offer a possible explanation for the effect of this strain on brain inflammation.
Artisanal and small-scale gold mining (ASGM) in Tanzania results in occupational exposures and environmental contamination to toxic chemical elements such as arsenic and mercury. Populations living ...in such areas may be exposed by various routes, and prenatal exposure to arsenic and mercury has been associated with adverse birth outcomes and developmental delays. The aim of this study was to determine if levels of arsenic and mercury differed among pregnant women living in areas with and without ASGM activities in Northern Tanzania. This cross-sectional study is part of the ongoing Mining and Health prospective longitudinal study. Spot urine samples and dried blood spots were collected at the antenatal health clinics from pregnant women (n = 1056) at 16–27 weeks gestation. Urine samples were analyzed for total arsenic (T-As) and dried blood spots were analyzed for total mercury (T-Hg). Women in the ASGM cohort had median T-As levels (9.4 μg/L; IQR: 4.9-15.1) and T-Hg levels (1.2 μg/L; IQR: 0.8-1.86) that were significantly higher than the median T-As levels (6.28 μg/L; IQR: 3.7-14.1) and T-Hg levels (0.66 μg/L; IQR: 0.3-1.2) of women in the non-ASGM cohort (Mann-Whitney U test, T-As: z = −9.881, p = 0.0005; T-Hg: z = −3.502, p < 0.0001). Among pregnant women from ASGM areas, 25% had urinary T-As and 75% had blood T-Hg above the established human biomonitoring reference values of 15 and 0.80 μg/L. In the ASGM cohort, lower maternal education and low socioeconomic status increased the odds of higher T-As levels by 20% (p < 0.05) and 10% (p < 0.05), respectively. Women involved in mining activities and those of low socioeconomic status had increased odds of higher T-Hg by 70% (p < 0.001) and 10% (p < 0.05), respectively. Arsenic and mercury concentrations among women in non-ASGM areas suggest exposure sources beyond ASGM activities that need to be identified. Arsenic and mercury levels in women in Tanzania are of public health concern and their association with adverse birth and child developmental outcomes will be examined in future studies on this cohort.
•Women from ASGM areas had higher levels of arsenic and mercury than non-ASGM women.•75.5% of pregnant women in gold mining areas had mercury blood levels >0.80 μg/L.•In non-ASGM areas, pregnant women had relatively high levels of arsenic and mercury.•Sociodemographic and socioeconomic factors were associated with arsenic and mercury.
In 2002/2003, the National Epidemiologic Database for the Study of Autism in Canada started capturing information on children diagnosed with autism in different regions of the country. Based on data ...collected through 2008 in Newfoundland and Labrador and 2010 in Prince Edward Island and Southeastern Ontario, the estimated average annual percent increases in prevalence among children 2–14 years of age ranged from 9.7 % (95 % CI 7.8–11.6) to 14.6 % (95 % CI 11.3–18.0). Differential in-migration and identification of previously undetected cases may have contributed in part to the increases observed, but we cannot rule out the possibility of a true increase in incidence, particularly given the lack of a leveling-off of prevalence among the 6- to 9-year olds.
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