Expanding the clinical and genetic landscape of (developmental) epileptic encephalopathy with spike-and-wave activation in sleep: results from studies of a Turkish cohort.

The terms developmental epileptic encephalopathy with spike-and-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) designate a spectrum of conditions that are typified by different combinations of motor, cognitive, language, and behavioral regression linked to robust spike-and-wave activity during sleep. In this study, we aimed at describing the clinical and molecular findings in "(developmental) epileptic encephalopathy with spike-and-wave activation in sleep" (D)EE-SWAS) patients as well as at contributing to the genetic etiologic spectrum of (D)EE-SWAS. Single nucleotide polymorphism (SNP) array and whole-exome sequencing (WES) techniques were used to determine the underlying genetic etiologies. Of the 24 patients included in the study, 8 (33%) were female and 16 (67%) were male. The median age at onset of the first seizure was 4 years and the median age at diagnosis of (D)EE-SWAS was 5 years. Of the 24 cases included in the study, 13 were compatible with the clinical diagnosis of DEE-SWAS and 11 were compatible with the clinical diagnosis of EE-SWAS. Abnormal perinatal history was present in four cases (17%), and two cases (8%) had a family history of epilepsy. Approximately two-thirds (63%) of all patients had abnormalities detected on brain computerized tomography/magnetic resonance (CT/MR) imaging. After SNP array and WES analysis, the genetic etiology was revealed in 7 out of 24 (29%) cases. Three of the variants detected were novel (SLC12A5, DLG4, SLC9A6). This study revealed for the first time that Smith-Magenis syndrome, SCN8A-related DEE type 13 and SLC12A5 gene variation are involved in the genetic etiology of (D)EE-SWAS. (D)EE-SWAS is a genetically diverse disorder with underlying copy number variations and single-gene abnormalities. In the current investigation, rare novel variations in genes known to be related to (D)EE-SWAS and not previously reported genes to be related to (D)EE-SWAS were discovered, adding to the molecular genetic spectrum. Molecular etiology enables the patient and family to receive thorough and accurate genetic counseling as well as a personalized medicine approach.

Natural history of ENPP1 deficiency: Nationwide Turkish Cohort Study of autosomal-recessive hypophosphataemic rickets type 2.

OBJECTIVE: Autosomal-recessive hypophosphataemic rickets type 2 (ARHR2) is a rare disease that is reported in survivors of generalized arterial calcification of infancy (GACI). DESIGN, PATIENTS AND MEASUREMENT: The objective of this study was to characterize a multicenter paediatric cohort with ARHR2 due to ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) deficiency and with a diagnosis of GACI or GACI-related findings. The clinical, biochemical and genetic characteristics of the patients were retrospectively retrieved. RESULTS: We identified 18 patients from 13 families diagnosed with ARHR2. Fifteen of the patients had an ENPP1 variation confirmed with genetic analyses, and three were siblings of one of these patients, who had clinically diagnosed hypophosphataemic rickets (HRs) with the same presentation. From nine centres, 18 patients, of whom 12 (66.7%) were females, were included in the study. The mean age at diagnosis was 4.2 ± 2.2 (1.6-9) years. The most frequently reported clinical findings on admission were limb deformities (66.6%) and short stature (44.4%). At diagnosis, the mean height SD was -2.2 ± 1.3. Five of the patients were diagnosed with GACI in the neonatal period and treated with bisphosphonates. Other patients were initially diagnosed with ARHR2, but after the detection of a biallelic variant in the ENPP1 gene, it was understood that they previously had clinical findings associated with GACI. Three patients had hearing loss, and two had cervical fusion. After the treatment of HRs, one patient developed calcification, and one developed intimal proliferation. CONCLUSION: ARHR2 represents one manifestation of ENPP1 deficiency that usually manifests later in life than GACI. The history of calcifications or comorbidities that might be associated with GACI will facilitate the diagnosis in patients with ARHR2, and patients receiving calcitriol and phosphate medication should be carefully monitored for signs of calcification or intimal proliferation.

Cu-In Dual Sites with Sulfur Defects Toward Superior Ethanol Electrosynthesis from CO2 Electrolysis.

The electrosynthesis of multi-carbon chemicals from excess CO2 is an area of great interest for research and commercial applications. However, improving both the yield of CO2 -to-ethanol conversion and the stability of the catalyst at the same time is proving to be a challenging issue. Here we propose to stabilize active Cu(I) and In dual sites with sulfur defects through an electro-driven intercalation strategy, which leads to the delocalization of electron density that enhances orbital hybridizations between the Cu-C and In-H bonds. Hence, the energy barrier for the rate-limiting *CHO formation step is reduced toward the key *OCHCHO* formation during ethanol production, which is also facilitated by the combined Cu site enabling C-C coupling and In site with a higher oxygen affinity based on both thermodynamic and kinetic calculations. Accordingly, such dual-site catalyst achieves a high partial current density toward ethanol of 409 ± 15 mA/cm2 for over 120 hours. Furthermore, a scaled-up flow cell is assembled with an industrial-relevant current of 5.7 A for over 36 hours, in which the carbon loss is less than 2.5% and single-pass carbon efficiency is around 19%. This article is protected by copyright. All rights reserved.

Highly Flexible and Acid-Alkali Resistant TiN Nanomesh Transparent Electrodes for Next-Generation Optoelectronic Devices.

Transparent electrodes are vital for optoelectronic devices, but their development has been constrained by the limitations of existing materials such as indium tin oxide (ITO) and newer alternatives. All face issues of robustness, flexibility, conductivity, and stability in harsh environments. Addressing this challenge, we developed a flexible, low-cost titanium nitride (TiN) nanomesh transparent electrode showcasing exceptional acid-alkali resistance. The TiN nanomesh electrode, created by depositing a TiN coating on a naturally cracked gel film substrate via a sputtering method, maintains a stable electrical performance through thousands of bending cycles. It exhibits outstanding chemical stability, resisting strong acid and alkali corrosion, which is a key hurdle for current electrodes when in contact with acidic/alkaline materials and solvents during device fabrication. This, coupled with superior light transmission and conductivity (88% at 550 nm with a sheet resistance of ∼200 Ω/sq), challenges the reliance on conventional materials. Our TiN nanomesh electrode, successfully applied in electric heaters and electrically controlled thermochromic devices, offers broad potential beyond harsh environment applications. It enables alternative possibilities for the design and fabrication of future optoelectronics for advancements in this pivotal field.

Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients.

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.

Spreading Solution Additives Governs the Quality of Polystyrene Particle-Based Two-Dimensional Opals.

Two-dimensional polystyrene sphere opals are important materials for nanotechnology applications and fundamental nanoscience research. They are a facile and inexpensive nanofabrication tool, but the quality factor of these opals has drastic differences between reports. Additives like ethanol, ions, and organic molecules in the aqueous particle spreading solution are known to affect the quality factor and growth efficiency of the produced opals. However, a systematic study on the effect and optimization of some of the most effective additives has not been reported until now. Here, we investigate the influence of additives on the growth efficiency and quality factor of such monolayers formed at the air-water interface without the use of a Langmuir-Blodgett trough. The additives induced large variations in the monolayer quality factor and growth efficiency, and we found that the ideal additive content of the spreading agents is 30 wt % < cethanol < 70 wt %, 0 < cH2SO4 < 30.5 mM, and 0 < csty < 255.0 mM. This study provides a guideline for the rational composition and additive content of the spreading solution to obtain high-quality two-dimensional opals for further applications in nanofabrication and photonics and will enable researchers and application engineers to produce standardized nanofabrication materials.

Origin of the spectral red-shift and polarization patterns of self-assembled InGaN nanostructures on GaN nanowires.

The luminescence of InxGa1-xN nanowires (NWs) is frequently reported with large red-shifts as compared to the theoretical value expected from the average In content. Both compositional fluctuations and radial built-in fields were considered accountable for this effect, depending on the size, structure, composition, and surrounding medium of the NWs. In the present work, the emission properties of InGaN/GaN NWs grown by plasma-assisted molecular beam epitaxy are investigated in a comprehensive study combining ultraviolet-Raman and photoluminescence spectroscopy (PL) on vertical arrays, polarization-dependent PL on bundles of a few NWs, scanning transmission electron microscopy, energy-dispersive X-ray spectroscopy, and calculations of the band profiles. The roles of inhomogeneous In distribution and radial fields in the context of optical emission properties are addressed. The radial built-in fields are found to be modest, with a maximum surface band bending below 350 meV. On the other hand, variations in the local In content have been observed that give rise to potential fluctuations whose impact on the emission properties is shown to prevail over band-bending effects. Two luminescence bands with large positive and moderate negative polarization ratios of ≈+80% and ≤-60%, respectively, were observed. The red-shift in the luminescence is associated with In-rich inclusions in the NWs due to thermodynamic decomposition during growth. The negative polarization anisotropy is suggested to result from spontaneously formed superlattices in the In-rich regions of the NWs. The NWs show a preferred orthogonal absorption due to the dielectric boundary conditions and highlight the extreme sensitivity of these structures towards light polarization.

Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome.

OBJECTIVE: Joubert syndrome is a neurodevelopmental disorder with a distinctive hindbrain malformation called molar tooth sign, causing motor and cognitive impairments. More than 40 genes have been associated with Joubert syndrome. We aim to describe a group of Joubert syndrome patients clinically and genetically emphasizing organ involvement. METHODS: We retrospectively collected clinical information and molecular diagnosis data of 22 patients with Joubert syndrome from multiple facilities. Clinical exome or whole-exome sequencing were performed to identify causal variations in genes. RESULTS: The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber's congenital amaurosis, ptosis, and optic nerve coloboma. Portal hypertension and esophageal varices as liver and polycystic kidney disease and nephronophthisis as kidney involvement was encountered in our patients. The HYLS1 gene, which commonly causes hydrolethalus syndrome 1, was also associated with Joubert syndrome in one of our patients. A mild phenotype with hypophyseal hormone deficiencies without the classical molar tooth sign was observed with compound heterozygous and likely pathogenic variants not reported before in the KATNIP gene. CONCLUSION: Some rare variants that display prominent genetic heterogeneity with variable severity are first reported in our patients. In our study of 22 Joubert syndrome patients, CPLANE1 is the most affected gene, and Joubert syndrome as a ciliopathy is possible without a classical molar tooth sign, like in the KATNIP gene-affected patients.

Oxidation States Regulation of Cobalt Active Sites through Crystal Surface Engineering for Enhanced Polysulfide Conversion in Lithium-Sulfur Batteries.

In this work, unique Co3 O4 /N-doped reduced graphene oxide (Co3 O4 /N-rGO) composites as favorable sulfur immobilizers and promoters for lithium-sulfur (Li-S) batteries are developed. The prepared Co3 O4  nanopolyhedrons (Co3 O4 -NP) and Co3 O4  nanocubes mainly expose (112) and (001) surfaces, respectively, with different atomic configurations of Co2+ /Co3+ sites. Experiments and theoretical calculations confirm that the octahedral coordination Co3+ (Co3+ Oh ) sites with different oxidation states from tetrahedral coordination Co2+ sites optimize the adsorption and catalytic conversion of lithium polysulfides. Specially, the Co3 O4 -NP crystals loaded on N-rGO expose (112) planes with ample Co3+ Oh active sites, exhibiting stronger adsorbability and superior catalytic activity for polysulfides, thus inhibiting the shuttle effect. Therefore, the S@Co3 O4 -NP/N-rGO cathodes deliver excellent electrochemical properties, for example, stable cyclability at 1 C with a low capacity decay rate of 0.058% over 500 cycles, superb rate capability up to 3 C, and high areal capacity of 4.1 mAh cm-2 . This catalyst's design incorporating crystal surface engineering and oxidation state regulation strategies also provides new approaches for addressing the complicated issues of Li-S batteries.

Electro-Microfluidic Assembly Platform for Manipulating Colloidal Structures inside Water-in-Oil Emulsion Droplets.

Colloidal assembly is a key strategy in nature and artificial device. Hereby, an electromicrofluidic assembly platform (eMAP) is proposed and validated to achieve 3D colloidal assembly and manipulation within water droplets. The water-in-oil emulsion droplets autoposition in the eMAP driven by dielectrophoresis, where the (di)electrowetting effect induces droplet deformation, facilitating quadratic growth of the electric field in water droplet to achieve "far-field" dielectrophoretic colloidal assembly. Reconfigurable 3D colloidal configurations are observed and dynamically programmed via applied electric fields, colloidal properties, and droplet size. Binary and ternary colloidal assemblies in one droplet allow designable chemical and physical anisotropies for functional materials and devices. Integration of eMAP in high throughput enables mass production of functional microcapsules, and programmable optoelectronic units for display devices. This eMAP is a valuable reference for expanding fundamental and practical exploration of colloidal systems.

Primary adrenal insufficiency in a patient with biallelic QRSL1 mutations.

Background: Biallelic QRSL1 mutations cause mitochondrial 'combined oxidative phosphorylation deficiency-40' (COXPD40). COXPD40 has been reported to be invariably lethal in infancy. Adrenal insufficiency was weakly reported and investigated among seven previously reported patients with COXPD40. Objective: We report the clinical, biochemical, molecular, and functional characteristics of a patient with adrenal insufficiency due to COXPD40. Methods: The medical history and adrenal function tests were examined. Genetic analysis was performed using whole-exome sequencing. Mitochondrial function was tested using mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) enzyme assays. Results: An 8-year-old boy was investigated for adrenal insufficiency. He also had mild developmental delay, sensorineural hearing loss, hypertrophic cardiomyopathy, nephrocalcinosis, elevated parathyroid hormone and creatine kinase, and lactic acidosis. Biallelic novel QRSL1 variants (c.300T>A;Y100* and c.610G>A;G204R) were identified. Oxidative damage in mitochondria was shown by reduced MMP and SOD assays in the patient compared to controls (P < 0.0001). Adrenal function tests revealed a 'primary adrenal insufficiency other than congenital adrenal hyperplasia' (non-CAH PAI) with an isolated glucocorticoid deficiency. In the 8-year follow-up, having the longest survival of reported COXPD40 patients, he had preserved mineralocorticoid functions and gonadal steroidogenesis. Conclusion: Biallelic QRSL1 mutations can cause non-CAH PAI. Adrenal functions should be monitored in mitochondrial disorders to improve clinical outcomes.

Nanosphere Lithography: A Versatile Approach to Develop Transparent Conductive Films for Optoelectronic Applications.

Transparent conductive films (TCFs) are irreplaceable components in most optoelectronic applications such as solar cells, organic light-emitting diodes, sensors, smart windows, and bioelectronics. The shortcomings of existing traditional transparent conductors demand the development of new material systems that are both transparent and electrically conductive, with variable functionality to meet the requirements of new generation optoelectronic devices. In this respect, TCFs with periodic or irregular nanomesh structures have recently emerged as promising candidates, which possess superior mechanical properties in comparison with conventional metal oxide TCFs. Among the methods for nanomesh TCFs fabrication, nanosphere lithography (NSL) has proven to be a versatile platform, with which a wide range of morphologically distinct nanomesh TCFs have been demonstrated. These materials are not only functionally diverse, but also have advantages in terms of device compatibility. This review provides a comprehensive description of the NSL process and its most relevant derivatives to fabricate nanomesh TCFs. The structure-property relationships of these materials are elaborated and an overview of their application in different technologies across disciplines related to optoelectronics is given. It is concluded with a perspective on current shortcomings and future directions to further advance the field.

One-Pot Synthesis of One-Dimensional Multijunction Semiconductor Nanochains from Cu1.94S, CdS, and ZnS for Photocatalytic Hydrogen Generation.

Chains of alternating semiconductor nanocrystals are complex nanostructures that can offer control over photogenerated charge carriers dynamics and quantized electronic states. We develop a simple one-pot colloidal synthesis of complex Cu1.94S-CdS and Cu1.94S-ZnS nanochains exploiting an equilibrium driving ion exchange mechanism. The chain length of the heterostructures can be tuned using a concentration dependent cation exchange mechanism controlled by the precursor concentrations, which enables the synthesis of monodisperse and uniform Cu1.94S-CdS-Cu1.94S nanochains featuring three epitaxial junctions. These seamless junctions enable efficient separation of photogenerated charge carriers, which can be harvested for photocatalytic applications. We demonstrate the superior photocatalytic activity of these noble metal free materials through solar hydrogen generation at a hydrogen evolution rate of 22.01 mmol g-1 h-1, which is 1.5-fold that of Pt/CdS heterostructure photocatalyst particles.

Lithography-free synthesis of periodic, vertically-aligned, multi-walled carbon nanotube arrays.

Until now, the growth of periodic vertically aligned multi-walled carbon nanotube (VA-MWCNT) arrays was dependent on at least one lithography step during fabrication. Here, we demonstrate a lithography-free fabrication method to grow hexagonal arrays of self-standing VA-MWCNTs with tunable pitch and MWCNT size. The MWCNTs are synthesized by plasma enhanced chemical vapor deposition (PECVD) from Ni catalyst particles. Template guided dewetting of a thin Ni film on a hexagonally close-packed silica particle monolayer provides periodically distributed Ni catalyst particles as seeds for the growth of the periodic MWCNT arrays. The diameter of the silica particles directly controls the pitch of the periodic VA-MWCNT arrays from 600 nm to as small as 160 nm. The diameter and length of the individual MWCNTs can also be readily adjusted and are a function of the Ni particle size and PECVD time. This unique method of lithography-free growth of periodic VA-MWCNT arrays can be utilized for the fabrication of large-scale biomimetic materials.

Epilepsy in patients with familial hemiplegic migraine.

OBJECTIVE: The coexistence of epilepsy in familial hemiplegic migraine (FHM) has not been reviewed systematically. We investigated the associations of epilepsy in patients with FHM with CACNA1A, ATP1A2, SCN1A or PRRT2 mutations along with clinical and genetic data. MATERIALS AND METHODS: We performed a search in the PubMed bibliographic database and the Cochrane Library was screened for eligible studies, from April 1997 to December 2020. Additionally, Online Mendelian Inheritance in Man (OMIM) was searched for mutations in the CACNA1A, ATP1A2, SCN1A and PRRT2 genes. Brief reports, letters, and original articles about FHM and epilepsy were included in the review if their mutations and clinical course of diseases were identified. RESULTS: Of the included patients with FHM whose information could be accessed, there were 28 families and 195 individuals, 78 of whom had epilepsy; 30 patients had focal epilepsy and 30 patients had generalized epilepsy. All mutations except ATP1A2, which could not be evaluated due to insufficient data, revealed first epilepsy then HM. In 60 patients for whom the epilepsy prognosis was evaluated, only 3.5% of patients were drug-resistant, and the remainder had a self-limited course or responded to anti-epileptic drug treatment. CONCLUSION: Mutations in all three and possibly four FHM genes can cause epilepsy. Contrary to our expectations, the well-known epilepsy gene SCN1A mutations are not the leading cause; the highest number of cases associated with epilepsy belongs to the ATP1A2 mutation. Drug-resistant forms of epilepsy are rare in all FHM mutations, and this information is important for counseling patients.

Bimetallic Hollow Tubular NiCoOx as a Bifunctional Electrocatalyst for Enhanced Oxygen Reduction and Evolution Reaction.

The development of high-efficiency oxygen electrocatalysts with earth-abundant transition metals rather than scarce noble metals has aroused growing interests due to their potential for energy storage and conversion applications. Herein, we developed a facile strategy to synthesize hollow tubular bimetallic Ni-Co oxide rooted with dense nanosheets for enhanced bifunctionality and facilitated redox reaction kinetics. Owing to the rational design of morphology and well-dispersed Ni and Co ions, the bimetallic samples exhibit admirable bifunctional electrocatalytic activities. This bimetallic Ni-Co oxide shows superior oxygen electrocatalytic performance in comparison with the monometallic Ni and Co oxides, according to the electrocatalytic synergistic effect from the bimetallic system. The optimized sample with the specific mass ratio of Ni and Co displays the oxygen reduction reaction (ORR) property comparable to commercial Pt/C and oxygen evolution reaction (OER) performance superior to commercial RuO2. The electrochemical tests and structural characterizations offer in-depth dissection on the electrocatalytic behaviors, especially the superb stability in both ORR and OER tests, as well as the outstanding resistance to methanol poisoning, representing a promising candidate in the renewable energy field.

Materials design of vertically coupled plasmonic arrays.

Plasmonic metasurfaces have important applications in life science, optics, and catalysis. However, their industrial usage is limited by the challenges of high throughput nanofabrication. A promising solution is the transfer of a pattern into a substrate using block copolymers, nanostructured stamps or molds to create binary, three dimensional templates, which can then be decorated with plasmonically active metals. Here, we report on the optical properties of quasi-Babinet complementary arrays in the non-retarded regime investigated by finite-difference time-domain simulations. The structures consist of a nanopillar support, which is covered with metal disks on top of the pillars and a quasi-Babinet complementary hole array film at the base of the pillars. Strong vertical plasmonic coupling occurs for small separation distances of the plasmonic slabs. We present a comprehensive study of the near and far-field properties of such vertically coupled plasmonic arrays varying their critical geometric dimension and the employed metals with their intrinsic plasmonic material properties. In particular, we consider gold, silver, copper, aluminum, nickel, and palladium. Furthermore, the effect of the refractive index n of the nanopillar support between the range of n = 1.4 to n = 3.4 is investigated. The plasmonic slabs show tunable extraordinary transmission and large electric near-field enhancements, which are strongly dependent on the employed material and geometry. Further, we show that the templates are suitable for plasmonic heterostructures commonly used in plasmon-enhanced photocatalysis.

Constructing Co3S4 Nanosheets Coating N-Doped Carbon Nanofibers as Freestanding Sulfur Host for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) have shown great potential as a rival for next generation batteries, for its relatively high theoretical capacity and eco-friendly properties. Nevertheless, blocked by the shuttle effect of lithium polysulfides (LPSs, Li2S4-Li2S8) and insulation of sulfur, LSBs show rapid capacity loss and cannot achieve the practical application. Herein, a composite of carbon nanofibers coated by Co3S4 nanosheets (denoted as CNF@Co3S4) is successfully synthesized as freestanding sulfur host to optimize the interaction with sulfur species. The combination of the two materials can lead extraordinary cycling and rate performance by alleviating the shuttle of LPSs effectively. N-doped carbon nanofibers serve as long-range conductive networks and Co3S4 nanosheets can accelerate the conversion of LPSs through its electrocatalytic and chemical adsorption ability. Benefiting from the unique structure, the transporting rate of Li+ can be enhanced. Distribution of Li+ is uniform for enough exposed negative active sites. As a result, the cell with CNF@Co3S4 as sulfur host is able to stabilize at 710 mA h g-1 at 1 C after 200 cycles with average coulombic efficiency of 97.8% in a sulfur loading of 1.7 mg cm-2 and deliver 4.1 mA h cm-2 at 0.1 C even in 6.8 mg cm-2 for 100 cycles.