bluuebunny/crossref_metadata_2025 huggingface dataset:
White matter hyperintensities: a marker for apathy in Parkinson’s disease without dementia?
Authors: Zhang Yu , Zhang Guo yong , Zhang Zi en , He An qi , Gan Jing , Liu Zhenguo
Published: August 2020

Objective

The objective of this study was to assess the relationship between white matter hyperintensities (WMH) and the occurrence and progression of apathy in Parkinson’s disease (PD).

Methods

We recruited patients with PD who underwent baseline evaluation, which included apathy assessment and magnetic resonance imaging (MRI) head scans. After 2.5 years of follow‐up, we re‐evaluated patient apathy symptoms. The severity and location of WMH were assessed with fluid‐attenuated inversion recovery (FLAIR) sequences using the Fazekas visual rating scale. Logistic regression and linear regression analyses of baseline WMH characteristics were conducted to explore the potential association between apathy and WMH.

Results

A total of 141 PD patients were recruited. The apathy group had a higher proportion of male patients, advanced disease, and depression, which was coupled with a lower quality of life. Morever, higher WMH severity was significantly associated with apathy. Logistic regression analyses demonstrated that WMH severity was a risk factor for apathy. In addition, linear regression analysis also suggests that apathy severity is positively correlated with baseline WMH Fazekas scales (ϐ = 0.959, P < 0.001). Baseline WMH severity was also a risk factor for apathy progression.

Interpretation

WMH is associated with apathy and could be a promising marker to predict apathy progression in PD.
Sequential Electrodeposition of Bifunctional Catalytically Active Structures in MoO3/Ni–NiO Composite Electrocatalysts for Selective Hydrogen and Oxygen Evolution
Authors: Li Xiaopeng , Wang Yang , Wang Jiajun , Da Yumin , Zhang Jinfeng , Li Lanlan , Zhong Cheng , Deng Yida , Han Xiaopeng , Hu Wenbin
Published: August 2020

Exploring earth‐abundant and highly efficient electrocatalysts is critical for further development of water electrolyzer systems. Integrating bifunctional catalytically active sites into one multi‐component might greatly improve the overall water‐splitting performance. In this work, amorphous NiO nanosheets coupled with ultrafine Ni and MoO3 nanoparticles (MoO3/Ni–NiO), which contains two heterostructures (i.e., Ni–NiO and MoO3–NiO), is fabricated via a novel sequential electrodeposition strategy. The as‐synthesized MoO3/Ni–NiO composite exhibits superior electrocatalytic properties, affording low overpotentials of 62 mV at 10 mA cm−2 and 347 mV at 100 mA cm−2 for catalyzing the hydrogen and the oxygen evolution reaction (HER/OER), respectively. Moreover, the MoO3/Ni–NiO hybrid enables the overall alkaline water‐splitting at a low cell voltage of 1.55 V to achieve 10 mA cm−2 with outstanding catalytic durability, significantly outperforming the noble‐metal catalysts and many materials previously reported. Experimental and theoretical investigations collectively demonstrate the generated Ni–NiO and MoO3–NiO heterostructures significantly reduce the energetic barrier and act as catalytically active centers for selective HER and OER, synergistically accelerating the overall water‐splitting process. This work helps to fundamentally understand the heterostructure‐dependent mechanism, providing guidance for the rational design and oriented construction of hybrid nanomaterials for diverse catalytic processes.
Formation Mechanism and Size Prediction Models for Double Emulsion CO2 Solvents
Authors: Kim Seonggon , Xu Ronghuan , Lim Hwan Suk , Kang Yong Tae
Published: August 2020

Double‐layered emulsion is a structure that has one more layer over the droplet, which is developed to protect the core material and is applicable to various fields such as food, cosmetic and CO2 capture. However, the mechanism of double emulsion formation is not well established. In this study, the manufacturing process of hybrid double layered emulsion CO2 solvents is analyzed to clarify the mechanism of droplet formation and to control encapsulation of chemical absorbent. The droplet formation models are developed by considering dimensionless numbers, which can predict the size of inner and middle droplets of the double emulsion structure. The droplet formation models are verified experimentally. The number of encapsulated solvents can be precisely controlled according to optimum frequencies at which the inner and middle droplets are effectively formed. In particular, the middle phase, which is the ultraviolet curable material, protects inner cores and the thickness of middle phase (shell thickness) can be predicted. Optimum ratio of middle droplet diameter to inner droplet diameter is in the range of 0.7–0.93. The optimal conditions of droplet formation are proposed by the developed models, and it can be extended to other microfluidic devices.
Dual‐Targeting Photosensitizer‐Peptide Amphiphile Conjugate for Enzyme‐Triggered Drug Delivery and Synergistic Chemo‐Photodynamic Tumor Therapy
Authors: Cheng Yin‐Jia , Qin Si‐Yong , Liu Wen‐Long , Ma Yi‐Han , Chen Xiao‐Sui , Zhang Ai‐Qing , Zhang Xian‐Zheng
Published: August 2020

Chemo‐photodynamic therapy is an attractive strategy in tumor treatment. However, the combination of chemotherapeutic drug and photosensitizer in nanocarriers always elevates the risk of composition uncertainty. Here, a dual‐targeting photosensitizer‐peptide amphiphile conjugate (PpIX‐GGGK(TPP)GG‐GFLG‐R7‐RGD or pPAC) is designed to encapsulate doxorubicin (DOX) for enhanced chemo‐photodynamic tumor therapy. The amphiphilic nature of pPAC leads to the formation of core‐shell structured nanomicelles in aqueous media, where DOX is loaded in the inner core. The DOX@pPAC nanomicelle displays efficient tumor cellular uptake via integrin receptor‐mediated endocytosis using RGD peptide. After successful cell internalization with the aid of R8 peptide, DOX@pPAC exhibits rapid release of DOX and protoporphyrin IX‐peptide conjugate (PpIX‐peptide) due to the Cathepsin B‐triggered hydrolysis of GFLG linker. Simultaneously, triphenylphosphonium TPP cation will accumulate photosensitizer PpIX in subcellular mitochondria, followed by in situ generation of phototoxic reactive oxygen species (ROS) under light irradiation. In vitro investigations demonstrate that the synergistic chemotherapy and photodynamic therapy (PDT) of fabricated nanomicelles can significantly maximize the therapeutic effect against tumor cells with the minimal off‐target cytotoxicity. This work may provide an all‐in‐one nanosystem toward enhanced chemo‐photodynamic tumor therapy.
All‐Solution‐Processed Ultrahigh Broadband and Wide‐Angle Perfect Absorber Based on Mxene–Gold Nanoparticles
Authors: Ali Wajid , Mideksa Megersa F. , Hou Ke , Li Hongdong , Wang Xiaoli , Tang Zhiyong
Published: August 2020

Broadband perfect absorbers are of great importance for various applications such as stealth technologies, thermal photovoltaic cells, optical communication, photodetection, and photovoltaic devices. However, they are often made by lithographic techniques with high cost and complexity, which hinders their practical applications. The design of broadband and ultrahigh absorber at low cost and ease in fabrication is still a big challenge in the field of optics. Here, an all‐solution‐processed plasmonic perfect absorber is proposed and demonstrated by incorporating Mxene Ti3C2Tx (Tx = F, O or OH) and gold nanoparticles (NPs) in metal–insulator–metal configuration. The absorption of the designed plasmonic absorber can reach up to 99% with polarization‐ and angle‐independence in a broad range of wavelengths from ultraviolet to near‐infrared region. This ultrahigh and broadband absorbance is attributed to the synergy of plasmon resonance, magnetic resonance, and cavity effect between gold NPs layer and Mxene film, which is further corroborated by simulations of the finite element method for both random and patterned orientation of the gold nanoparticles. The excellent optical property together with the easy fabrication method paves the way for preparing photon‐absorbing nanostructures in photocatalysis and solar photovoltaics.
Multiresolution Imaging Using Bioluminescence Resonance Energy Transfer Identifies Distinct Biodistribution Profiles of Extracellular Vesicles and Exomeres with Redirected Tropism
Authors: Wu Anthony Yan‐Tang , Sung Yun‐Chieh , Chen Yen‐Ju , Chou Steven Ting‐Yu , Guo Vanessa , Chien Jasper Che‐Yung , Ko John Jun‐Sheng , Yang Alan Ling , Huang Hsi‐Chien , Chuang Ju‐Chen , Wu Syuan , Ho Meng‐Ru , Ericsson Maria , Lin Wan‐Wan , Cheung Chantal Hoi Yin , Juan Hsueh‐Fen , Ueda Koji , Chen Yunching , Lai Charles Pin‐Kuang
Published: August 2020

Extracellular particles (EPs) including extracellular vesicles (EVs) and exomeres play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamics in vivo have remained largely unresolved in detail due to the lack of a suitable method. Therefore, a bioluminescence resonance energy transfer (BRET)‐based reporter, PalmGRET, is created to enable pan‐EP labeling ranging from exomeres (<50 nm) to small (<200 nm) and medium and large (>200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking, and quantification of the EPs from whole animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET, and fluorescence. Using PalmGRET, it is shown that EPs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. It is further demonstrated that gene knockdown of lung‐tropic membrane proteins, solute carrier organic anion transporter family member 2A1, alanine aminopeptidase/Cd13, and chloride intracellular channel 1 decreases HCC‐EP distribution to the lungs and yields distinct biodistribution profiles. It is anticipated that EP‐specific imaging, quantitative assays, and detailed in vivo characterization are a starting point for more accurate and comprehensive in vivo models of EP biology and therapeutic design.
Graphene–Polyurethane Coatings for Deformable Conductors and Electromagnetic Interference Shielding
Authors: Cataldi Pietro , Papageorgiou Dimitrios G. , Pinter Gergo , Kretinin Andrey V. , Sampson William W. , Young Robert J. , Bissett Mark , Kinloch Ian A.
Published: August 2020

Electrically conductive, polymeric materials that maintain their conductivity even when under significant mechanical deformation are needed for actuator electrodes, conformable electromagnetic shielding, stretchable tactile sensors, and flexible energy storage. The challenge for these materials is that the percolated, electrically conductive networks tend to separate even at low strains, leading to significant piezoresistance. Herein, deformable conductors are fabricated by spray‐coating a nitrile substrate with a graphene–elastomer solution. The electrical resistance of the coatings shows a decrease after thousands of bending cycles and a slight increase after repeated folding‐unfolding events. The deformable conductors double their electrical resistance at 12% strain and are washable without changing their electrical properties. The conductivity–strain behavior is modeled by considering the nanofiller separation upon deformation. To boost the conductivity at higher strains, the production process is adapted by stretching the nitrile substrate before spraying, after which it is released. This adaption meant that the electrical resistance doubles at 25% strain. The electrical resistance is found sufficiently low to give a 1.9 dB µm−1 shielding in the 8–12 GHz electromagnetic band. The physical and electrical properties, including the electro magnetic screening, of the flexible conductors, are found to deteriorate upon cycling but can be recovered through reheating the coating.
Biochar affects growth and shoot nitrogen in four crops for two soils
Authors: Olszyk David , Shiroyama Tamotsu , Novak Jeffrey , Cantrell Keri , Sigua Gilbert , Watts Donald , Johnson Mark G.
Published: August 2020

To address the need for information on biochar effects on crop growth and nitrogen (N), a greenhouse study was conducted with carrot, lettuce, soybean, and sweet corn using sandy loam (Coxville series) and loamy sand (Norfolk series) soils and a variety of biochars. Biochar was produced from pine chips (PC), poultry litter (PL), swine solids (SS), switchgrass (SG), and two blends of PC plus PL (50/50% [55] and 80/20% [82], wt/wt), with each feedstock pyrolyzed at 350, 500, or 700 ˚C. The results confirmed that biochar can increase crop growth; however, the responses varied with crop, soil, and feedstock and to a lesser extent with pyrolysis temperature. In general, lettuce had large increases in shoot and root dry weights vs. no‐biochar controls with many biochars, primarily the SS and 55 blend and to a lesser extent with 82 followed by PL, and then PC and SG, especially when grown in the Coxville soil. Biochar had more limited effects on carrot, sweet corn, and soybean weights. Some biochars decreased crop growth (e.g., PL at 700 ˚C) for soybean shoot and pod dry weights with the Norfolk soil. Shoot N concentrations decreased with SS, 55, and 82 for carrot, lettuce, and sweet corn with the Norfolk soil but tended to increase for soybean. Shoot N uptake increased or decreased depending on biochar feedstock and temperature, crop, and soil. These results confirm that biochar can increase crop growth and affect shoot N, which is essential for crop growth.
Carinata growth, yield, and chemical composition responses to nitrogen fertilizer management
Authors: Seepaul Ramdeo , Mulvaney Michael J. , Small Ian M. , George Sheeja , Wright David L.
Published: August 2020

Production of carinata (Brassica carinata A. Braun) as a winter crop in the Southeast United States presents a unique opportunity for growers to produce significant amounts of biofuel feedstock to meet domestic energy needs. Field experiments were conducted to quantify the effects of N application rates (0, 45, 90, and 135 kg N ha−1) and split management (single, two‐way split, or three‐way split of 90 kg N ha−1 applied at planting, bolting, and flowering) on carinata growth, yield, and chemical composition. In Study 1, plant height, mainstem node numbers, primary and secondary branches, pod length, pods numbers, and seeds per pod increased quadratically with N application rate. Averaged over the 5 yr, seed yield response to N application rate was quadratic and ranged from 1,245 kg ha−1 with 0 kg N ha−1 to 2,444 kg ha−1 with 117 kg N ha−1. The economic optimum nitrogen rate (EONR) occurred at 103 kg N ha–1, which produced 2,427 kg seed ha−1 representing a US$386 ha−1 profit margin. Except for protein, N application rate did not have an effect on glucosinolates and fatty acid composition. In Study 2, a split application of N had variable effects on carinata growth; however, seed yield did not vary with split management or timing of N averaging 3,905 kg ha−1. Split management and N source did not have an effect on seed chemical composition. These results suggest that carinata grown at the EONR of 103 kg N ha−1 can maximize seed and oil production in the Southeast.
Ridge‐furrow and film‐mulching sowing practices enhance enzyme activity and alter fungi communities
Authors: Huang Chunguo , Yang Wenping , Chen Yinglong , Han Xiaoli , Khan Shahbaz , Gao Zhiqiang , Yang Zhenping
Published: August 2020

The activities of soil resident enzymes and fungal communities are critical for soil health and ecosystem functionality. However, their dynamics in response to variations in sowing techniques are poorly understood. This study aimed to investigate the effects of wide‐ridge and narrow‐furrow (WR&NF), film‐mulching ridge (FMR), and conventional drilling (CD) practices on the activities of soil‐residing enzymes and fungal communities in a dryland wheat field on the Loess Plateau. Photometrically, unbuffered, and colorimetric methods were employed to determine the activities of alkaline phosphatases, urease, and sucrase enzymes, respectively. Soil fungal diversity and community composition was measured via the Illumina Miseq 2500 sequencing method. The results revealed that WR&NF and FMR practices significantly enhanced the soil activities of alkaline phosphatases, urease, and sucrase, while improving soil fungal communities including Chytridiomycota phylum and Phoma (Ascomycota), Olpidium (Chytridiomycota), and Trichosporon (Basidiomycota) genera. Both the enzymatic activities and fungal community compositions of the soils under study varied from rhizosphere to non‐rhizosphere, as well as at different soil depths. Remarkably, several soil fungal genera, including Cystofilobasidium (Basidiomycota), Triparticalcar (Chytridiomycota), and Guehomyces (Basidiomycota) were more abundant in the subsoil than topsoil. In general, we observed that ridge‐furrow and film‐mulching practices enhanced the enzyme activities and improved fungal communities of soils. Therefore, the wide‐ridge and narrow‐furrow sowing technique is recommended as an environmentally compatible practice to benefit the arid wheat (Triticum aestivum L.) fields of the Loess Plateau.
Rotational Pattern Recognition by Spiking Correlated Neural Network Based on Dual‐Gated MoS2 Neuristor
Authors: Bao Lin , Wang Zongwei , Yu Zhizhen , Ling Yaotian , Cai Yimao , Huang Ru
Published: August 2020

Beyond the great success in machine learning (ML), the engineering community has been actively exploring neuromorphic computing systems based on spiking neural networks (SNNs). In the preliminary SNN, the neuronal information is simply encoded by the firing rate, which limits the volume of information in a certain spike pattern. Studies of the biological nervous system have discovered neuronal cooperativity, where flow of neural information is collaboratively encoded and carried by the spatiotemporal stamp and the correlated neuronal activity. In this study, by encoding the control pattern on the dual gates, a MoS2‐based neuristor is exploited to program spatiotemporal information and neuronal correlations via the device's internal dynamics as well as the network topology, and a spiking correlated neural network (SCNN) is demonstrated. This correlated neural network not only succeeds in identifying the patterns with translational and rotational symmetry but also correctly reveals the rotated angles. Compared with conventional SNNs, the dimension of information flow in SCNNs can be greatly enlarged by taking advantage of the synergy between the rate coding and the neuronal correlations. This proof‐of‐concept work provides the potential to achieve high‐volume information processing with the simplified circuitry of neuromorphic computing systems.
Distributed Situational Awareness in Robot Swarms
Authors: Jones Simon , Milner Emma , Sooriyabandara Mahesh , Hauert Sabine
Published: August 2020

Many‐robot systems are becoming a reality for large companies that can invest in bespoke solutions. These systems often require carefully engineered infrastructure and a central planner to coordinate the robots. Outside these controlled environments, robots typically generate a shared situational awareness of the world and state of their task. This requires sophisticated mapping, perception, and control, with changes to the environment or tasks causing challenges to robot deployment. The assumption that centralized situational awareness is needed to deal with real‐world complexity may be holding back the field from deploying many‐robot systems. Yet potential applications are wide‐ranging, including environmental monitoring, construction, agriculture, and logistics. Mainstream adoption requires usability out‐of‐the‐box, in unstructured environments, at a reasonable cost. Distributed situational awareness is proposed as a method to design many‐robot systems differently. Distributed situational awareness allows swarms of low‐cost robots to rapidly and accurately capture the state of an environment and act accordingly, with no central data storage, modeling, or control. Its distributed nature enhances resilience and redundancy while reducing reliance on infrastructure and central planners. Deploying distributed situational awareness however requires new tools to design hardware and algorithms, demonstrate that it works and is safe, and is intuitive for users of the swarm.
In‐Memory Binary Vector–Matrix Multiplication Based on Complementary Resistive Switches
Authors: Ziegler Tobias , Waser Rainer , Wouters Dirk J. , Menzel Stephan
Published: August 2020

This work studies a computation in‐memory concept for binary multiply‐accumulate operations based on complementary resistive switches (CRS). By exploiting the in‐memory boolean exclusive OR (XOR) operation of single CRS devices, the Hamming Distance (HD) can be calculated if the center electrodes of multiple CRS cells are connected. This HD is linearly encoded in the voltage drop of the common electrode, and from it the result of a binary multiply‐accumulate operation can be calculated. A small‐scale demonstration is experimentally realized and the feasibility of the in‐memory computation concept is confirmed. A simulation study identifies the low resistance state (LRS) variability as the main reason for the variations in the output voltage. The application as a potential hardware accelerator for the inference step of binary neural networks is investigated. Therefore, a 1‐layer fully connected neural network is trained on a binarized version of the MNIST data set and the inference step of the test data set is simulated. The concept achieves a prediction accuracy of approximately 86%.
Adolescent growth and BMI and their associations with early childhood growth in an urban South African cohort
Authors: Nyati Lukhanyo H. , Pettifor John M. , Ong Ken K. , Norris Shane A.
Published: August 2020

Objectives

The timing and magnitude of adolescent growth may be influenced by ethnicity and early life factors. We aimed to (a) characterize ethnic differences in the magnitude, timing, and intensity of adolescent growth in height, weight, and BMI; (b) assess the effect of early childhood growth on adolescent growth in black children.

Methods

Data were from the Birth to Twenty Plus cohort (Bt20+) in Johannesburg, South Africa (n = 3273). Height, weight, and BMI were modeled with ethnic comparisons using the SuperImposition by Translation and Rotation for 2089 participants who had data from 7 to 23 years. Relative weight gain and relative linear growth between 0 and 24 months and 24 and 60 months were generated. Multiple regression analyses were used to assess associations between childhood and adolescent growth.

Results

White children were 5 cm (SE: 0.7) taller than black children through adolescence. Black boys had a later timing of adolescent height (0.65 years ±0.12) than white boys, which in black girls was 0.24 years (0.11) earlier than in white girls. Black girls had faster BMI velocity than white girls. Among black children, birth weight and both relative weight gain 0 to 24 and relative linear growth between 3 and 24 months and 24 and 60 months were positively associated with the magnitude of adolescent growth and negatively associated with timing.

Conclusion

Sex dimorphism in ethnic differences in timing of adolescent height growth may reflect some yet unexplained drivers for rapid weight gain and obesity in black females but not black males. Rapid weight gain in early life may contribute to faster adiposity accrual in adolescence.
A novel homozygous variant in REN in a family presenting with classic features of disorders involving the renin–angiotensin pathway, without renal tubular dysgenesis
Authors: Dilliott Allison A. , Wang Jian , Brown Emma , Singh Gagandeep , Shkrum Michael J. , Clin Madeleine , Rupar Charles Anthony , Hegele Robert A. , Siu Victoria Mok
Published: August 2020

Autosomal recessively inherited pathogenic variants in genes associated with the renin–angiotensin–aldosterone system (RAAS) result in early onset oligohydramnios and clinical features of the Potter sequence, typically in association with proximal renal tubules dysgenesis. We describe two siblings and a first cousin who had severe oligohydramnios in the second trimester, and presented at birth with loose skin, wide fontanelles and sutures, and pulmonary insufficiency. Two had refractory hypotension during their brief lives and one received palliative care after birth. All were found to have a homozygous nonsense variant, REN: c.891delG; p.Tyr287*, on exome sequencing. Autopsy limited to the genitourinary system in two of the children revealed normal renal tubular histology in both. Immunoblotting confirmed diminished expression of renin within cultured skin fibroblasts. To our knowledge, this is the first identification of an association between biallelic variants in REN and oligohydramnios in the absence of renal tubular dysgenesis. Due to its role in the RAAS, it has previously been proposed that the decreased expression of REN results in hypotension, ischemia, and decreased urine production. We suggest sequencing of genes in the RAAS, including REN, should be considered in cases of severe early onset oligohydramnios, even when renal morphology and histology are normal.
The latest FADS: Functional analysis of GLDN patient variants and classification of GLDN‐associated AMC as a type of viable fetal akinesia deformation sequence
Authors: Mis Emily K. , Al‐Ali Samir , Ji Weizhen , Spencer‐Manzon Michele , Konstantino Monica , Khokha Mustafa K. , Jeffries Lauren , Lakhani Saquib A.
Published: August 2020

Recessive variants in the GLDN gene, which encodes the gliomedin protein and is involved in nervous system development, have recently been associated with Arthrogryposis Multiplex Congenita (AMC), a heterogenous condition characterized by congenital contractures of more than one joint. Two cohorts of patients with GLDN‐associated AMC have previously been described, evolving the understanding of the condition from lethal to survivable with the provision of significant neonatal support. Here, we describe one additional patient currently living with the syndrome, having one novel variant, p.Leu365Phe, for which we provide functional data supporting its pathogenicity. We additionally provide experimental data for four other previously reported variants lacking functional evidence, including p.Arg393Lys, the second variant present in our patient. We discuss unique and defining clinical features, adding calcium‐related findings which appear to be recurrent in the GLDN cohort. Finally, we compare all previously reported patients and draw new conclusions about scope of illness, with emphasis on the finding of pulmonary hypoplasia, suggesting that AMC secondary to GLDN variants may be best fitted under the umbrella of fetal akinesia deformation sequence (FADS).
Birth prevalence of achondroplasia: A systematic literature review and meta‐analysis
Authors: Foreman Pamela K. , van Kessel Femke , van Hoorn Rosa , van den Bosch Judith , Shediac Renée , Landis Sarah
Published: August 2020

Achondroplasia is a genetic disorder that results in disproportionate short stature. The true prevalence of achondroplasia is unknown as estimates vary widely. This systematic literature review and meta‐analysis was conducted to better estimate worldwide achondroplasia birth prevalence. PubMed, Embase, Scielo, and Google Scholar were searched, complemented by manual searching, for peer‐reviewed articles published between 1950 and 2019. Eligible articles were identified by two independent researchers using predefined selection criteria. Birth prevalence estimates were extracted for analysis, and the quality of evidence was assessed. A meta‐analysis using a quality effects approach based on the inverse variance fixed effect model was conducted. The search identified 955 unique articles, of which 52 were eligible and included. Based on the meta‐analysis, the worldwide birth prevalence of achondroplasia was estimated to be 4.6 per 100,000. Substantial regional variation was observed with a considerably higher birth prevalence reported in North Africa and the Middle East compared to other regions, particularly Europe and the Americas. Higher birth prevalence was also reported in specialized care settings. Significant heterogeneity (HigginsI2of 84.3) was present and some indication of publication bias was detected, based on visual asymmetry of the Doi plot with a Furuya‐Kanamori index of 2.73. Analysis of pooled data from the current literature yields a worldwide achondroplasia birth prevalence of approximately 4.6 per 100,000, with considerable regional variation. Careful interpretation of these findings is advised as included studies are of broadly varying methodological quality.
Congenital ichthyosis in Prader–Willi syndrome associated with maternal chromosome 15 uniparental disomy: Case report and review of autosomal recessive conditions unmasked by UPD
Authors: Muthusamy Karthik , Macke Erica L. , Klee Eric W. , Tebben Peter J. , Hand Jennifer L. , Hasadsri Linda , Marcou Cherisse A. , Schimmenti Lisa A.
Published: August 2020

Prader–Willi syndrome (PWS) is a prototypic genetic condition related to imprinting. Causative mechanisms include paternal 15q11‐q13 deletion, maternal chromosome 15 uniparental disomy (UPD15), Prader–Willi Syndrome/Angelman Syndrome (PWS/AS) critical region imprinting defects, and complex chromosomal rearrangements. Maternal UPD15‐related PWS poses risks of concomitant autosomal recessive (AR) disorders when the mother carries a pathogenic variant in one of the genes on chromosome 15 associated with autosomal recessive inherited disease. Co‐occurrence of autosomal recessive conditions in the setting of UPD leads to increased complexity of the clinical phenotype, and may delay the diagnosis of PWS. We report a patient with PWS and associated congenital ichthyosis due to maternal UPD15, and a homozygous novel pathogenic variant in ceramide synthase 3 (CERS3). We also review the literature of associated disorders reported in the setting of maternal UPD15‐related PWS and provide a summary of the previously described CERS3 variants. This represents the second case of autosomal recessive congenital ichthyosis (ARCI) in the setting of PWS and UPD15. There needs to be a high index of suspicion of this genetic mechanism when there is unexpected phenotype or evolution of the clinical course in a patient with PWS.
Update of the genotype and phenotype ofKMT2DandKDM6Aby genetic screening of 100 patients with clinically suspected Kabuki syndrome
Authors: Murakami Hiroaki , Tsurusaki Yoshinori , Enomoto Keisuke , Kuroda Yukiko , Yokoi Takayuki , Furuya Noritaka , Yoshihashi Hiroshi , Minatogawa Mari , Abe‐Hatano Chihiro , Ohashi Ikuko , Nishimura Naoto , Kumaki Tatsuro , Enomoto Yumi , Naruto Takuya , Iwasaki Fuminori , Harada Noriaki , Ishikawa Aki , Kawame Hiroshi , Sameshima Kiyoko , Yamaguchi Yu , Kobayashi Masahisa , Tominaga Makiko , Ishikiriyama Satoshi , Tanaka Toshiaki , Suzumura Hiroshi , Ninomiya Shinsuke , Kondo Akane , Kaname Tadashi , Kosaki Kenjiro , Masuno Mitsuo , Kuroki Yoshikazu , Kurosawa Kenji
Published: August 2020

Kabuki syndrome is characterized by a variable degree of intellectual disability, characteristic facial features, and complications in various organs. Many variants have been identified in two causative genes, that is, lysine methyltransferase 2D (KMT2D) and lysine demethylase 6A (KDM6A). In this study, we present the results of genetic screening of 100 patients with a suspected diagnosis of Kabuki syndrome in our center from July 2010 to June 2018. We identified 76 variants (43 novel) inKMT2Dand 4 variants (3 novel) inKDM6Aas pathogenic or likely pathogenic. Rare variants included a deep splicing variant (c.14000‐8C>G) confirmed by RNA sequencing and an 18% mosaicism level for aKMT2Dmutation. We also characterized a case with a blended phenotype consisting of Kabuki syndrome, osteogenesis imperfecta, and 16p13.11 microdeletion. We summarized the clinical phenotypes of 44 patients including a patient who developed cervical cancer of unknown origin at 16 years of age. This study presents important details of patients with Kabuki syndrome including rare clinical cases and expands our genetic understanding of this syndrome, which will help clinicians and researchers better manage and understand patients with Kabuki syndrome they may encounter.
Pre‐ and postnatal findings in a patient with a recombinant chromosome rec(8)(qter→q21.11::p23.3→qter) due to a paternal pericentric inversion inv(8)(p23.3q21.11) and review of the literature
Authors: Habhab Wisam , Mau‐Holzmann Ulrike , Singer Sylke , Rieß Angelika , Kagan Karl‐Oliver , Gerbig Ines , Schäferhoff Karin , Dufke Andreas , Kehrer Martin
Published: August 2020

Recombinant chromosome 8 (Rec8) syndrome (San Luis Valley [SLV] syndrome; OMIM #179613) is a rare chromosome disorder associated with intellectual disability, congenital heart defects, variable skeletal and urogenital anomalies, and dysmorphic features. It is characterized by a partial terminal deletion of 8p and a partial terminal duplication of 8q, which is usually due to meiotic recombination of a pericentric inversion of chromosome 8 of a healthy carrier parent. There are only few reports of cases with breakpoints defined at the molecular level by molecular karyotyping. We report on a case of Rec8 syndrome with previously unreported breakpoints in a male fetus with intrauterine growth restriction, hypogenesis of the corpus callosum, bilateral cleft lip/palate, and congenital heart defect. Cytogenetic analysis revealed a recombinant chromosome 8 [46,XY,rec(8)(qter→q21.11::p23.3→qter)] secondary to a paternal pericentric inversion [46,XY,inv(8)(p23.3q21.11)]. Molecular karyotyping correspondingly showed a terminal copy number loss of 1.4 Mb (arr[hg19] 8p23.3(158048_1514749)×1) and a terminal copy number gain of chromosome band 8q21.11q24.3 of 69.8 Mb (arr[hg19] 8q21.11q24.3(76477367_146295771)×3). To our knowledge, this is the fourth reported case diagnosed prenatally. We describe the postnatal clinical course of the male newborn. Furthermore, we review and compare the phenotypic features and breakpoints of 74 reported Rec8/SLV cases.
Tuberous sclerosis complex (TSC), lymphangioleiomyomatosis, and COVID‐19: The experience of a TSC clinic in Italy
Authors: Peron Angela , La Briola Francesca , Bruschi Fabio , Terraneo Silvia , Vannicola Chiara , Previtali Roberto , Perazzoli Sabrina , Morenghi Emanuela , Bulfamante Gaetano , Vignoli Aglaia , Canevini Maria Paola
Published: August 2020

Individuals with comorbidities are at higher risk of coronavirus disease 2019 (COVID‐19) and worse outcome, but little information has been available about patients with genetic diseases and COVID‐19. This study aims at evaluating the presence and outcome of COVID‐19 in a cohort of Italian patients with tuberous sclerosis complex (TSC) and/or lymphangioleiomyomatosis (LAM), and at reviewing the possible effects of mTOR inhibitors on SARS‐CoV‐2 infection. We included 102 unselected individuals with a diagnosis of TSC and/or LAM assessed between January 1, 2020 and April 24, 2020 (29% children, 71% adults). Twenty‐six patients were on mTOR inhibitors. Demographic data, TSC manifestations, presence, and outcomes in individuals with confirmed or suspected SARS‐CoV‐2 infection were evaluated. Health status and outcomes of all patients on mTOR inhibitors were assessed. One patient with severe TSC had polymerase chain reaction (PCR)‐confirmed SARS‐CoV‐2 infection, was admitted to ICU, and died. Nine additional patients either met the definition of suspect case or presented with at least two of the most common symptoms of SARS‐CoV‐2 infection. All recovered fully. None of the patients treated with mTOR inhibitors for their underlying comorbidities was diagnosed with COVID‐19, and those who showed suspicious respiratory symptoms recovered fully. This cohort study provides preliminary information on COVID‐19 in people with TSC in Italy and suggests feasibility to systematically evaluate the role of mTOR inhibitors in SARS‐CoV‐2 infection.
Spondyloepiphyseal dysplasia type Stanescu: Expanding the clinical and molecular spectrum of a very rare type II collagenopathy
Authors: Travessa André M. , Díaz‐González Francisca , Mirco Teresa , Oliveira‐Ramos Filipa , Parrón‐Pajares Manuel , Heath Karen E. , Sousa Ana Berta
Published: August 2020

Spondyloepiphyseal dysplasia type Stanescu (SED‐S) is a very rare type II collagenopathy. We describe an 8‐year‐old boy who presented with short trunk, C2‐C3 vertebral fusion, hand, foot, leg and thigh pain, stiffness and limited joint mobility, and waddling gait. Radiographs showed platyspondyly with anterior wedging and endplate irregularities, broad femoral necks, and large epiphyses and epiphyseal equivalents. Differential diagnosis included progressive pseudorheumatoid dysplasia and SED‐S. A skeletal dysplasia custom‐designed NGS panel was performed and the heterozygous pathogenic variant c.620G>A; p.(Gly207Glu) in COL2A1 was detected, establishing the diagnosis of SED‐S. Vertebral fusions, observed in our patient, have not been previously described in this dysplasia. This variant has not been previously associated with SED‐S, but was reported in two other families with spondyloepiphyseal dysplasia. Thus, this case expands the clinical and mutational spectrum of SED‐S and demonstrates that SED‐S significantly overlaps with other skeletal dysplasias.
Indigenous women's experiences of domestic and family violence, help‐seeking and recovery in regional Queensland
Authors: Meyer Silke , Stambe Rose‐Marie
Published: August 2020

Indigenous women are disproportionately affected by the prevalence and severity of domestic and family violence (DFV) perpetrated by men against women in Australia. The impact of their experiences is further exacerbated by the level of social and cultural marginalisation affecting Indigenous communities, families and individuals along with regional, rural or remote living. The pervasive, ongoing impact of colonisation, dispossession and transgenerational trauma continues to shape the experiences of Indigenous women and their communities, including their help‐seeking decisions and opportunities, and their level of trust in and access to adequate and culturally sensitive support services. In this paper, we explore the experiences of Indigenous women affected by DFV in two regional Australian settings through face‐to‐face interviews with women (n = 13) and community stakeholders (n = 18). The findings of this study highlight the complex role of social and cultural marginalisation, spiritual (dis)connectedness and role of family as both a stressor and a protective factor. Implications for policy and practice are discussed.
Zoom, Zooming, Zoomed into the Future! Moving to Optimist from Skeptic on Online Mediation
Authors: Creo Robert A.
Published: August 2020

Last month, I was asked to present a continuing legal education program to between 60 and 100 government attorneys working for the Commonwealth of Pennsylvania who were active as mediators and mediation participants.
Precision prevention of Alzheimer's and other dementias: Anticipating future needs in the control of risk factors and implementation of disease‐modifying therapies
Authors: Frisoni Giovanni B. , Molinuevo José Luis , Altomare Daniele , Carrera Emmanuel , Barkhof Frederik , Berkhof Johannes , Delrieu Julien , Dubois Bruno , Kivipelto Miia , Nordberg Agneta , Schott Jonathan M. , van der Flier Wiesje M. , Vellas Bruno , Jessen Frank , Scheltens Philip , Ritchie Craig
Published: August 2020

Empirical evidence suggests that a fair proportion of dementia cases are preventable, that some preventive actions can be taken immediately, and others may soon be implemented. Primary prevention may target cognitively normal persons with modifiable risk factors through lifestyle and multiple domain interventions (including general cardiovascular health). While the effect on individuals may be modest, it might have a large societal impact by decreasing overall dementia incidence by up to 35%. Secondary prevention will target cognitively normal persons at high risk of dementia due to Alzheimer's disease pathology with future anti‐amyloid, anti‐tau, or other drugs. This approach is likely to have major benefits to both individuals and society. Memory clinics will need structural and functional changes to adapt to novel technologies and increased patients’ demands, and brand‐new services may need to be developed with specific skills on risk profiling, risk communication, and personalized risk reduction plans.
Redox Dyshomeostasis Strategy for Hypoxic Tumor Therapy Based on DNAzyme‐Loaded Electrophilic ZIFs
Authors: Li Yanli , Zhao Peiran , Gong Teng , Wang Han , Jiang Xingwu , Cheng Hui , Liu Yanyan , Wu Yelin , Bu Wenbo
Published: August 2020

Redox homeostasis is one of the main reasons for reactive oxygen species (ROS) tolerance in hypoxic tumors, limiting ROS‐mediated tumor therapy. Proposed herein is a redox dyshomeostasis (RDH) strategy based on a nanoplatform, FeCysPW@ZIF‐82@CAT Dz, to disrupt redox homeostasis, and its application to improve ROS‐mediated hypoxic tumor therapy. Once endocytosed by tumor cells, the catalase DNAzyme (CAT Dz) loaded zeolitic imidazole framework‐82 (ZIF‐82@CAT Dz) shell can be degraded into Zn2+as cofactors for CAT Dz mediated CAT silencing and electrophilic ligands for glutathione (GSH) depletion under hypoxia, both of which lead to intracellular RDH and H2O2accumulation. These “disordered” cells show reduced resistance to ROS and are effectively killed by ferrous cysteine‐phosphotungstate (FeCysPW) induced chemodynamic therapy (CDT). In vitro and in vivo data demonstrate that the pH/hypoxia/H2O2triple stimuli responsive nanocomposite can efficiently kill hypoxic tumors. Overall, the RDH strategy provides a new way of thinking about ROS‐mediated treatment of hypoxic tumors.
Enzymatic Building‐Block Synthesis for Solid‐Phase Automated Glycan Assembly
Authors: Marchesi Andrea , Parmeggiani Fabio , Louçano João , Mattey Ashley P. , Huang Kun , Gupta Tanistha , Salwiczek Mario , Flitsch Sabine L.
Published: August 2020

Automated chemical oligosaccharide synthesis is an attractive concept that has been successfully applied to a large number of target structures, but requires excess quantities of suitably protected and activated building blocks. Herein we demonstrate the use of biocatalysis to supply such reagents for automated synthesis. By using the promiscuous NmLgtB‐B β1‐4 galactosyltransferase from Neisseria meningitidis we demonstrate fast and robust access to the LacNAc motif, common to many cell‐surface glycans, starting from either lactose or sucrose as glycosyl donors. The enzymatic product was shown to be successfully incorporated as a complete unit into a tetrasaccharide target by automated assembly.
Multivalent‐Interaction‐Driven Assembly of Discrete, Flexible, and Asymmetric Supramolecular Protein Nano‐Prisms
Authors: Han Suyeong , Kim Yu‐na , Jo Gyunghee , Kim Young Eun , Kim Ho Min , Choi Jeong‐Mo , Jung Yongwon
Published: August 2020

Current approaches to design monodisperse protein assemblies require rigid, tight, and symmetric interactions between oligomeric protein units. Herein, we introduce a new multivalent‐interaction‐driven assembly strategy that allows flexible, spaced, and asymmetric assembly between protein oligomers. We discovered that two polygonal protein oligomers (ranging from triangle to hexagon) dominantly form a discrete and stable two‐layered protein prism nanostructure via multivalent interactions between fused binding pairs. We demonstrated that protein nano‐prisms with long flexible peptide linkers (over 80 amino acids) between protein oligomer layers could be discretely formed. Oligomers with different structures could also be monodispersely assembled into two‐layered but asymmetric protein nano‐prisms. Furthermore, producing higher‐order architectures with multiple oligomer layers, for example, 3‐layered nano‐prisms or nanotubes, was also feasible.
Reversible Soft Mechanochemical Control of Biaryl Conformations through Crosslinking in a 3D Macromolecular Network
Authors: Kelber Julien B. , Bensalah‐Ledoux Amina , Zahouani Sarah , Baguenard Bruno , Schaaf Pierre , Chaumont Alain , Guy Stephan , Jierry Loïc
Published: August 2020

Tuning the dihedral angle (DA) of axially chiral compounds can impact biological activity, catalyst efficiency, molecular motor performance, or chiroptical properties. Herein, we report gradual, controlled, and reversible changes in molecular conformation of a covalently linked binaphthyl moiety within a 3D polymeric network by application of a macroscopic stretching force. We managed direct observation of DA changes by measuring the circular dichroism signal of an optically pure BINOL‐crosslinked elastomer network. Stretching the elastomer resulted in a widening of the DA between naphthyl rings when the BINOL was doubly grafted to the elastomer network; no effect was observed when a single naphthyl ring of the BINOL was grafted to the elastomer network. We have determined that ca. 170 % extension of the elastomers led to the transfer of a mechanical force to the BINOL moiety of 2.5 kcal mol−1 Å−1 (ca. 175 pN) in magnitude and results in the opening of the DA of BINOL up to 130°.
Cucurbituril‐Based Biomacromolecular Assemblies
Authors: Liu Yao‐Hua , Zhang Ying‐Ming , Yu Hua‐Jiang , Liu Yu
Published: August 2020

The construction of controlled biomacromolecular assemblies has become a thriving area of supramolecular chemistry. In this context, cucurbiturils (CBs), a class of macrocyclic receptors having robust skeletons, hydrophobic cavities, and carbonyl‐laced portals, have been drawn into the limelight because of their advantageous molecular recognition characteristics with a variety of biomacromolecules, including peptides, nucleic acids, and proteins. In this minireview, we focus on the impressive advances in CB‐based biomacromolecular assemblies, such as in biosensors and assays, the regulation of biochemical reactions, and the treatment of serious diseases. CB‐promoted subcellular bioimaging has also been demonstrated in different organelles. The case studies presented herein demonstrate the numerous applications, from fundamental research to translational applications, of diverse CB‐based supra/biomacromolecular architectures.
Compaction of RNA Duplexes in the Cell**
Authors: Collauto Alberto , von Bülow Sören , Gophane Dnyaneshwar B. , Saha Subham , Stelzl Lukas S. , Hummer Gerhard , Sigurdsson Snorri T. , Prisner Thomas F.
Published: August 2020

The structure and flexibility of RNA depends sensitively on the microenvironment. Using pulsed electron‐electron double‐resonance (PELDOR)/double electron‐electron resonance (DEER) spectroscopy combined with advanced labeling techniques, we show that the structure of double‐stranded RNA (dsRNA) changes upon internalization into Xenopus lævis oocytes. Compared to dilute solution, the dsRNA A‐helix is more compact in cells. We recapitulate this compaction in a densely crowded protein solution. Atomic‐resolution molecular dynamics simulations of dsRNA semi‐quantitatively capture the compaction, and identify non‐specific electrostatic interactions between proteins and dsRNA as a possible driver of this effect.