Robustness of Physics-Informed Neural Networks to Noise in Sensor Data

Physics-Informed Neural Networks (PINNs) have been shown to be an effective way of incorporating physics-based domain knowledge into neural network models for many important real-world systems. They have been particularly effective as a means of inferring system information based on data, even in cases where data is scarce. Most of the current work however assumes the availability of high-quality data. In this work, we further conduct a preliminary investigation of the robustness of physics-informed neural networks to the magnitude of noise in the data. Interestingly, our experiments reveal that the inclusion of physics in the neural network is sufficient to negate the impact of noise in data originating from hypothetical low quality sensors with high signal-to-noise ratios of up to 1. The resultant predictions for this test case are seen to still match the predictive value obtained for equivalent data obtained from high-quality sensors with potentially 10x less noise. This further implies the utility of physics-informed neural network modeling for making sense of data from sensor networks in the future, especially with the advent of Industry 4.0 and the increasing trend towards ubiquitous deployment of low-cost sensors which are typically noisier

Design of Turing Systems with Physics-Informed Neural Networks

Reaction-diffusion (Turing) systems are fundamental to the formation of spatial patterns in nature and engineering. These systems are governed by a set of non-linear partial differential equations containing parameters that determine the rate of constituent diffusion and reaction. Critically, these parameters, such as diffusion coefficient, heavily influence the mode and type of the final pattern, and quantitative characterization and knowledge of these parameters can aid in bio-mimetic design or understanding of real-world systems. However, the use of numerical methods to infer these parameters can be difficult and computationally expensive. Typically, adjoint solvers may be used, but they are frequently unstable for very non-linear systems. Alternatively, massive amounts of iterative forward simulations are used to find the best match, but this is extremely effortful. Recently, physics-informed neural networks have been proposed as a means for data-driven discovery of partial differential equations, and have seen success in various applications. Thus, we investigate the use of physics-informed neural networks as a tool to infer key parameters in reaction-diffusion systems in the steady-state for scientific discovery or design. Our proof-of-concept results show that the method is able to infer parameters for different pattern modes and types with errors of less than 10\%. In addition, the stochastic nature of this method can be exploited to provide multiple parameter alternatives to the desired pattern, highlighting the versatility of this method for bio-mimetic design. This work thus demonstrates the utility of physics-informed neural networks for inverse parameter inference of reaction-diffusion systems to enhance scientific discovery and design

A novel deep intronic variant strongly associates with Alkaptonuria.

Alkaptonuria is a rare autosomal recessive inherited disorder of tyrosine metabolism, which causes ochronosis, arthropathy, cardiac valvular calcification, and urolithiasis. The epidemiology of alkaptonuria in East Asia is not clear. In this study, patients diagnosed with alkaptonuria from January 2010 to June 2020 were reviewed. Their clinical and molecular features were further compared with those of patients from other countries. Three patients were found to have alkaptonuria. Mutation analyses of the homogentisate 1,2-dioxygenase gene (HGD) showed four novel variants c.16-2063 A > C, p.(Thr196Ile), p.(Gly344AspfsTer25), and p.(Gly362Arg) in six mutated alleles (83.3%). RNA sequencing revealed that c.16-2063 A > C activates a cryptic exon, causing protein truncation p.(Tyr5_Ile6insValTer17). A literature search identified another 6 patients with alkaptonuria in East Asia; including our cases, 13 of the 18 mutated alleles have not been reported elsewhere in the world. Alkaptonuria is rare in Taiwan and East Asia, with HGD variants being mostly novel and private

Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism

ObjectiveCongenital hyperinsulinism (CHI) is a group of clinically and genetically heterogeneous disorders characterized by dysregulated insulin secretion. The aim of the study was to elucidate genetic etiologies of Taiwanese children with the most severe diazoxide-unresponsive CHI and analyze their genotype-phenotype correlations.MethodsWe combined Sanger with whole exome sequencing (WES) to analyze CHI-related genes. The allele frequency of the most common variant was estimated by single-nucleotide polymorphism haplotype analysis. The functional effects of the ATP-sensitive potassium (KATP) channel variants were assessed using patch clamp recording and Western blot.ResultsNine of 13 (69%) patients with ten different pathogenic variants (7 in ABCC8, 2 in KCNJ11 and 1 in GCK) were identified by the combined sequencing. The variant ABCC8 p.T1042QfsX75 identified in three probands was located in a specific haplotype. Functional study revealed the human SUR1 (hSUR1)-L366F KATP channels failed to respond to intracellular MgADP and diazoxide while hSUR1-R797Q and hSUR1-R1393C KATP channels were defective in trafficking. One patient had a de novo dominant mutation in the GCK gene (p.I211F), and WES revealed mosaicism of this variant from another patient.ConclusionPathogenic variants in KATP channels are the most common underlying cause of diazoxide-unresponsive CHI in the Taiwanese cohort. The p.T1042QfsX75 variant in the ABCC8 gene is highly suggestive of a founder effect. The I211F mutation in the GCK gene and three rare SUR1 variants associated with defective gating (p.L366F) or traffic (p.R797Q and p.R1393C) KATP channels are also associated with the diazoxide-unresponsive phenotype

Multiple Clinical Manifestations and Diagnostic Challenges of Incontinentia Pigmenti—12 Years' Experience in 1 Medical Center

Incontinentia pigmenti (IP) is a rare X-linked dominant disorder that involves ectodermal tissues of multiple systems. Previous reports are few in Taiwan. To contribute toward better understanding of IP, we describe and discuss the clinical features of cases that were diagnosed in a medical center during the past 12 years. Methods: The medical records of all patients with IP between July 1995 and June 2007 were reviewed retrospectively. The demographics, physical findings, pathology reports, molecular study reports, eosinophil counts and outcome were recorded. Results: A total of 4 patients, 3 female and 1 male neonate, who met the criteria for the diagnosis of IP were enrolled. Among these cases, 3 were not diagnosed with IP at initial presentation but were regarded to have infectious diseases. A definite family history of 3 consecutive generations was proved not only by clinical manifestations but also by molecular study in 1 patient. The patient also had retinal and vitreous body hemorrhage, which rapidly progressed to retinal detachment of the right eye in 2 months. Another patient presenting with stage III hyperpigmentation at birth had an extremely rare finding of left foot deformity. The male patient had unilateral and localized vesicular lesions over his left thigh. Conclusion: Diagnosis of IP is difficult in the neonatal period. Referral to experienced specialists is necessary. Multiple clinical characteristics of IP and rapid progression of ophthalmologic manifestations can be demonstrated through our study. Furthermore, 3 of the 4 cases in our study are the very first reports in Taiwan

Combined Methylmalonic Aciduria and Homocystinuria cblC Type of a Taiwanese Infant With c.609G>A and c.567dupT Mutations in the MMACHC Gene

Combined methylmalonic aciduria and homocystinuria, cobalamin (cbl)C type (cblC disease), the most common inborn error of vitamin B12, is a rare disorder of intracellular cbl metabolism because of mutations in the MMACHC gene located in chromosome region 1p34.1. It has become possible to establish phenotype–genotype correlations and to observe ethnicity-related trends. This article provides detailed clinical manifestations and outcomes of a Taiwanese infant boy with early-onset cblC disease, heterozygous for c.609G>A and c.567dupT mutations, although there is limited information about cases with c.609G>A or c.567dupT mutation in the literature. He had no significant clinical abnormality during his neonatal period, whereas elevated C3 level was noted at newborn screening. He presented later with life-threatening manifestations and failure to thrive, which resolved through our treatment, although delayed development was still noted at 6 months of age. To date, all reported cblC patients with the c.609G>A mutation have been East Asians. Therefore, we suggest that c.609G>A should be included in the initial mutation screening tests for a cblC patient in East Asian populations

Clinical characteristics and long-term outcome of Taiwanese children with congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a rare condition causing severe hypoglycemia in neonates and infants due to dysregulation of insulin secretion. This study aimed to review 20 years' experience in the management of Taiwanese children with CHI. Methods: Between 1990 and 2010, children diagnosed with CHI and followed up at the Pediatric Endocrine Clinic of the National Taiwan University Hospital were enrolled. Their medical records were thoroughly reviewed. Results: In total, 13 patients (8 boys and 5 girls) were enrolled, including six patients with onset of hypoglycemia within 1 month of age and seven patients at 4.0 ± 2.1 months of age. The birth weight standard deviation scores of these two age groups were 4.6 ± 1.8 and 1.4 ± 1.3 standard deviation score, respectively (p < 0.01). Initial intravenous glucose infusion at rates of 22.9 ± 5.3 mg/kg/min and 13.4 ± 5.6 mg/kg/min, respectively, were mandatory to maintain euglycemia in these two groups (p < 0.05). All received pancreatectomy after failure of initial medical treatment. Twelve patients were followed up for a period of 2.5–19.8 years. Eight of them remained euglycemic without any medication and three patients developed diabetes mellitus. Seven of the nine patients who underwent intelligence evaluation had normal mental outcomes. Mental retardation of two patients was too severe to be evaluated. All four patients with mental retardation had a delay in the maintenance of euglycemia, and three of them also had seizure disorder. Conclusion: The age at onset of hypoglycemia reflects the severity of CHI. Early diagnosis and appropriate treatment are important for favorable mental outcomes

Supraclavicular versus Infraclavicular Subclavian Vein Catheterization in Infants

Central venous catheterization is an important procedure for infant patients for a number of different purposes, including nutritional support, surgical operation, hemodynamic monitoring, and multiple lines for critical care medications. Subclavian vein catheterization (SVC) is one of the central vein catheterization techniques. SVC can be performed from 4 different locations: right supraclavicular (RSC), left supraclavicular (LSC), right infraclavicular (RIC), and left infraclavicular (LIC). The purpose of this study was to evaluate the relative effectiveness and complication risks of these 4 SVC locations in infants. Methods: In our pediatric intensive care unit, which is part of a tertiary medical center, a well-trained fellow doctor performed the following catheterizations: 21 RSC, 24 LSC, 24 RIC, and 22 LIC, for a total of 91 SVC operations in infants. The patients were placed in the Trendelenburg position. The site of puncture was decided by the operator. Statistical significance was analyzed according to Fisher's exact test and 2-sample t test. Results: The overall success rate was 90.1% (82 out of 91 operations). No statistically significant differences were noted among these 4 groups, either in the success or complication rate. There were 6 cases of arterial puncture (5 supraclavicular and 1 infraclavicular, p = 0.09), 2 cases of pneumothorax (1 RSC and 1 RIC), and 2 cases of malpositioned catheter (1 RSC and 1 RIC). There was no mortality. Conclusion: In our study, we found that there was no statistically significant difference among the 4 SVC locations in effectiveness of operation or in risk of complication. There was a tendency to damage the subclavian arteries through the supraclavicular route

Twelve-year review of galactosemia newborn screening in Taiwan: Evolving methods and insights

Background: Galactosemia was introduced into Taiwan's routine newborn screening (NBS) program in 1985. This study presents a 12-year experience, emphasizing disease diagnosis and screening performance. Method: NBS for galactosemia utilized dried blood spot samples taken 48–72 h post-delivery, with total galactose (TGal) level as the primary marker. Newborns with critical TGal levels were referred immediately, while those with borderline TGal underwent a recall test. GALT activity measurement was applied simultaneously as the second-tier marker. Further confirmatory tests, such as whole exome sequencing (WES), were conducted upon referral. Results: From January 1st, 2011, to December 31st, 2022, 51 cases were identified from 817,906 newborns. Of these, nine individuals had persistently elevated TGal. Diagnoses included one case of GALT deficiency, one of GALM deficiency, and seven of GALE deficiencies. Notably, the classic galactosemia patient (GALT deficiency) presented with extreme high TGal and was referred to the hospital for diet management immediately. All affected patients were instructed to adopt a galactose-restricted diet. By the median age of 2.5 years, all exhibited normal development and liver function. Conclusion: The incidence of classical galactosemia and its variants is extremely low in Taiwan. Incorporating WES into NBS has improved our ability to detect various galactosemia forms, enriching our understanding of the genetic underpinnings. While these newly discovered forms often present with milder initial elevations in TGal, specific biochemical investigations and regular monitoring are essential to understanding the long-term implications and outcomes