Dynamic Focusing of Large Arrays for Wireless Power Transfer and Beyond

We present architectures, circuits, and algorithms for dynamic 3-D lensing and focusing of electromagnetic power in radiative near- and far-field regions by arrays that can be arbitrary and nonuniform. They can benefit applications such as wireless power transfer at a distance (WPT-AD), volumetric sensing and imaging, high-throughput communications, and optical phased arrays. Theoretical limits on system performance are calculated. An adaptive algorithm focuses the power at the receiver(s) without prior knowledge of its location(s). It uses orthogonal bases to change the phases of multiple elements simultaneously to enhance the dynamic range. One class of such 2-D orthogonal and pseudo-orthogonal masks is constructed using the Hadamard and pseudo-Hadamard matrices. Generation and recovery units (GU and RU) work collaboratively to focus energy quickly and reliably with no need for factory calibration. Orthogonality enables batch processing in high-latency and low-rate communication settings. Secondary vector-based calculations allow instantaneous refocusing at different locations using element-wise calculations. An emulator enables further evaluation of the system. We demonstrate modular WPT-AD GUs of up to 400 elements utilizing arrays of 65-nm CMOS ICs to focus power on RUs that convert the RF power to dc. Each RFIC synthesizes 16 independently phase-controlled RF outputs around 10 GHz from a common single low-frequency reference. Detailed measurements demonstrate the feasibility and effectiveness of RF lensing techniques presented in this article. More than 2 W of dc power can be recovered through a wireless transfer at distances greater than 1 m. The system can dynamically project power at various angles and at distances greater than 10 m. These developments are another step toward unified wireless power, sensing, and communication solutions in the future

Brain-Computer Interface Controlled Functional Electrical Stimulation System for Ankle Movement

Abstract Background Many neurological conditions, such as stroke, spinal cord injury, and traumatic brain injury, can cause chronic gait function impairment due to foot-drop. Current physiotherapy techniques provide only a limited degree of motor function recovery in these individuals, and therefore novel therapies are needed. Brain-computer interface (BCI) is a relatively novel technology with a potential to restore, substitute, or augment lost motor behaviors in patients with neurological injuries. Here, we describe the first successful integration of a noninvasive electroencephalogram (EEG)-based BCI with a noninvasive functional electrical stimulation (FES) system that enables the direct brain control of foot dorsiflexion in able-bodied individuals. Methods A noninvasive EEG-based BCI system was integrated with a noninvasive FES system for foot dorsiflexion. Subjects underwent computer-cued epochs of repetitive foot dorsiflexion and idling while their EEG signals were recorded and stored for offline analysis. The analysis generated a prediction model that allowed EEG data to be analyzed and classified in real time during online BCI operation. The real-time online performance of the integrated BCI-FES system was tested in a group of five able-bodied subjects who used repetitive foot dorsiflexion to elicit BCI-FES mediated dorsiflexion of the contralateral foot. Results Five able-bodied subjects performed 10 alternations of idling and repetitive foot dorsifiexion to trigger BCI-FES mediated dorsifiexion of the contralateral foot. The epochs of BCI-FES mediated foot dorsifiexion were highly correlated with the epochs of voluntary foot dorsifiexion (correlation coefficient ranged between 0.59 and 0.77) with latencies ranging from 1.4 sec to 3.1 sec. In addition, all subjects achieved a 100% BCI-FES response (no omissions), and one subject had a single false alarm. Conclusions This study suggests that the integration of a noninvasive BCI with a lower-extremity FES system is feasible. With additional modifications, the proposed BCI-FES system may offer a novel and effective therapy in the neuro-rehabilitation of individuals with lower extremity paralysis due to neurological injuries

Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b)

Background: Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) and glucose-6-phosphate transporter (SLC37A4), respectively. The high rates of consanguineous marriages in Iran provide a desirable context to facilitate finding the homozygous pathogenic mutations. This study designates to evaluate the clinical and genetic characteristics of patients with GSD1b to assess the possible genotype-phenotype correlation. Results: Autozygosity mapping was performed on nineteen GSD suspected families to suggest the causative loci. The mapping was done using two panels of short tandem repeat (STR) markers linked to the corresponding genes. The patients with autozygous haplotype block for the markers flanking the genes were selected for direct sequencing. Six patients showed autozygosity in the candidate markers for SLC37A4. Three causative variants were detected. The recurrent mutation of c.10421043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G > A (p.G122E) in the homozygous state were identified in the SLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. A novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Severe and moderate neutropenia was observed in patients with frameshift and missense variants, respectively. The sibling with the whole gene deletion has shown both severe neutropenia and leukopenia. Conclusions: The results showed that the hematological findings may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed. © 2020 The Author(s)

Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7) diagnosed genetically. © 2018 John Wiley & Sons Ltd

Changes in Bone Turnover, Inflammatory, Oxidative Stress, and Metabolic Markers in Women Consuming Iron plus Vitamin D Supplements: a Randomized Clinical Trial

We aimed to investigate whether combination of vitamin D and iron supplementation, comparing vitamin D alone, could modify bone turnover, inflammatory, oxidative stress, and metabolic markers. Eighty-seven women with hemoglobin (Hb) � 12.7 g/dL and 25OHD � 29 ng/mL vitamin D deficiency/insufficiency aged 18�45 years were randomly assigned into two groups: (1) receiving either 1000 IU/day vitamin D3 plus 27 mg/day iron (D-Fe); (2) vitamin D3 plus placebo supplements (D-P), for 12 weeks. In D-Fe group, significant decrease in red blood cells (RBC) (P = 0.001) and hematocrit (Hct) (P = 0.004) and increases in mean corpuscular hemoglobin concentration (MCHC) (P = 0.001), 25OHD (P < 0.001), osteocalcin (P < 0.001), high-density cholesterol (HDL) (P = 0.041), and fasting blood sugar (FBS) (P < 0.001) were observed. D-P group showed significant decrease in RBC (P < 0.001), Hb (P < 0.001), Hct (P < 0.001), mean corpuscular volume (MCV) (P = 0.004), mean corpuscular hemoglobin (MCH) (P < 0.001), MCHC (P = 0.005), serum ferritin (P < 0.001), and low-density cholesterol (LDL) (P = 0.016) and increases of 25OHD (P < 0.001), osteocalcin (P < 0.001), C-terminal telopeptide (CTX) (P = 0.025), triglyceride (TG) (P = 0.004), FBS (P < 0.001), and interleukin-6 (IL-6) (P = 0.001) at week 12. After the intervention, the D-P group had between-group increases in mean change in the osteocalcin (P = 0.007) and IL-6 (P = 0.033), and decreases in the RBC (P < 0.001), Hb (P < 0.001), Hct (P < 0.001), and MCV (P = 0.001), compared with the D-Fe group. There were significant between-group changes in MCH (P < 0.001), MCHC (P < 0.001), ferritin (P < 0.001), and serum iron (P = 0.018). Iron�vitamin D co-supplementation does not yield added benefits for improvement of bone turnover, inflammatory, oxidative stress, and metabolic markers, whereas, vitamin D alone may have some detrimental effects on inflammatory and metabolic markers. IRCT registration number: IRCT201409082365N9 © 2020, Springer Science+Business Media, LLC, part of Springer Nature

Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi�Bickel Syndrome

Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG�s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG�s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. © Copyright © 2021 Eghbali, Fatemi, Salehpour, Abiri, Saei, Talebi, Olyaei, Yassaee and Modarressi

Molecular genetic diagnosis of Glanzmann syndrome in Iranian population; Reporting novel and recurrent mutations

Background: Glanzmann thrombasthenia (GT) is a rare autosomal recessive abnormality of platelet aggregation with quantitative and/or qualitative abnormality of αIIbβ3 integrin. The αIIbβ3 is a platelet fibrinogen receptor, which is required for platelet aggregation, firm adhesion, and also spreading. The disease is more prevalent in the populations with a higher rate of consanguineous marriages as in some Middle Eastern populations including Iraq, Jordan, and Iran. Different types of mutations in ITGA2B and ITGB3 genes have been previously reported to cause the disease. Result: In this study, 16 patients with the clinical diagnosis of GT were studied. Direct sequencing of the exons and exon-intron boundaries of the above genes revealed mutations in 14 patients (detection rate: 87.5). Briefly, out of fifteen types of identified mutations, 14 were novel. Seven mutations in the ITGB3 gene included 4 missense c.2T > C, c.155 G > T, c. 538 G > A, c.1990 G > T, one nonsense mutation c.1303 G > T, a small deletion c.1656-1658delCTC and a deletion of one nucleotide c.401delA. Mutations in the ITGA2B were 8 different mutations consisting 2 missense c.286 T > A, c.842 C > T, 2 deletions c.1899 del T, c.189-319-236del, an insertion c.1071-1072insG and one splice site mutations c.409-3 C > G, one synonymous mutation that might alter the normal splicing process c.1392 A > G and a nonsense mutation c.1555 C > T. The causative mutation in 2 patients remained unknown. Using long-range PCR and sequencing, we found a rather large deletion. The break point of this deletion covers 319 nt from the last part of the first intron and 48 nt from the beginning of the second exon of ITGA2B gene. The deletion was also detected in two unrelated patients with the same ethnicity. In addition, in silico analyses of novel mutations were performed. Conclusion: There was no recurrent mutation in the studied population. This may be due to either small sample size or the heterogeneity of the studied population. © 2019 The Author(s)

Development and validation of a novel panel of 16 STR markers for simultaneous diagnosis of β-thalassemia, aneuploidy screening, maternal cell contamination detection and fetal sample authenticity in PND and PGD/PGS cases

Prenatal diagnosis (PND) may be complicated with sample mix-up; maternal cell contamination, non-paternity and allele drop out at different stages of diagnosis. Aneuploidy screening if combined with PND for a given single gene disorder, can help to detect any common aneuploidy as well as aiding sample authenticity and other probable complications which may arise during such procedures. This study was carried out to evaluate the effectiveness of a novel panel of STR markers combined as a multiplex PCR kit (HapScreen� kit) for the detection of β-thalassemia, aneuploidy screening, ruling in/out maternal cell contamination (MCC), and sample authenticity. The kit uses 7 STR markers linked to β-globin gene (HBB) as well as using 9 markers for quantitative analysis of chromosomes 21, 18, 13, X and Y. Selection of the markers was to do linkage analysis with β-globin gene, segregation analysis and to perform a preliminary aneuploidy screening of fetal samples respectively. These markers (linked to the β-globin gene) were tested on more than 2185 samples and showed high heterozygosity values (68.4�91.4). From 2185 fetal cases we found 3 cases of non-paternity, 5 cases of MCC, one case of sample mix-up and one case of trisomy 21 which otherwise may have end up to misdiagnosis. This kit was also successfully used on 231 blastomeres for 29 cases of pre-implantation genetic diagnosis (PGD) and screening (PGS). The markers used for simultaneous analysis of haplotype segregation and aneuploidy screening proved to be very valuable to confirm results obtained from direct mutation detection methods (i.e. ARMS, MLPA and sequencing) and aneuploidy screening. © 2019, The Author(s)

Replication of TCF7L2 rs7903146 association with type 2 diabetes in an Iranian population

The transcription factor 7-like 2 gene (TCF7L2) rs7903146 T allele is constantly associated with Type 2 diabetes in various populations and ethnic groups. Nevertheless, this has not been observed in two studies involving Arab populations. The aim of the present study was to investigate the association between TCF7L2 rs7903146 in an Iranian population. Type 2 diabetes patients (N = 258) and normal healthy control subjects (N = 168) from the same area, were examined. The ARMS- PCR (Amplification Refractory Mutation System) technique, subsequently validated by direct sequencing, was used for genotyping. Allele and genotype frequencies were significantly different between patients and controls TT vs. CT + CC [p 0.0081 OR 3.4 95%CI (1.27-11.9)] and T vs. C allele [p 0.02 OR 1.4 95%CI (1.03-1.9)]. Our data thus confirm the association between the rs7903146 T allele and T2D in an Iranian population, contrary to previous reports in Arab populations. This can possibly be attributed to differences in ethnic background or the effects of environmental factors

Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements. Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI 25 kg/m²). Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome