Fractional averaging theory for discrete fractional-order system with impulses.

In this paper, we improve the averaging theory on both finite and infinite time intervals for discrete fractional-order systems with impulses. By employing new techniques, generalized impulsive discrete fractional-order Gronwall inequality is introduced. In addition, the closeness of solutions for the discrete fractional-order systems with impulses and the averaged discrete fractional-order systems with impulses is derived. Finally, three examples are provided to illustrate the efficiency of our main results.

An intronic splice-site variant in MBTPS2 underlies ichthyosis follicularis with atrichia and photophobia syndrome.

Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome is a rare genodermatosis characterized by a classic triad of follicular ichthyosis, alopecia, and photophobia. We report a Chinese patient displaying features of IFAP triad along with painful palmoplantar keratoderma, recurrent infections, periorificial keratotic plaques, nail dystrophy, and pachyonychia. Whole-exome sequencing revealed an intronic variant (NM_015884.3: exon7:c.970+5G>A) in the gene MBTPS2. Sanger sequencing confirmed that the variant segerated with phenotype in the family. Sequencing of cDNAs derived from the patient indicated the variant introduced a new splice donor site, leading to partial skipping of exon 7 (r.951_970del). An in vitro mini-gene assay also revealed abnormal splicing of exon 7. This study presents a case complicated with X-linked IFAP syndrome and Olmsted syndrome, and highlights the significance of using validation assays to identify the pathogenicity of intronic variants in MBTPS2.

Corrigendum: Case report: Challenges in the diagnosis of a case of Mal de Meleda and a therapeutic attempt of ixekizumab and Adalimumab.

[This corrects the article DOI: 10.3389/fmed.2022.821301.].

A novel mutation in SPINK5 gene underlies a case of atypical Netherton syndrome.

Netherton syndrome (NS, OMIM #256500) is a rare autosomal recessive disease characterized by a triad of congenital ichthyosiform erythroderma (CIE) or ichthyosis linearis circumflexa (ILC), trichorrhexis invaginata (TI), and atopic predisposition. The disease is caused by a mutation in the SPINK5 gene (serine protease inhibitor of Kazal type 5) encoding LEKTI (lymphoepithelial Kazal type-related inhibitor). We performed whole-exome sequencing on one Chinese NS family and made genotype-phenotype correlation analysis on the patients clinically diagnosed with NS or congenital ichthyosis erythroderma. We identified a novel frameshift mutation c.2474_2475del (p.Glu825Glyfs*2) in the SPINK5 gene. The N-terminal mutations of LEKTI cause a severer phenotype, while the C-terminal mutations of LEKT1 are related to a milder phenotype. Our findings suggest that Netherton syndrome may be underestimated clinically, and our findings further expand the reservoir of SPINK5 mutations in Netherton syndrome.

Case Report: Challenges in the Diagnosis of a Case of Mal de Meleda and a Therapeutic Attempt of Ixekizumab and Adalimumab.

Background: Mal de Meleda (MDM, OMIM 248300) is an autosomal recessive disease characterized by symmetrical and progressive palmoplantar hyperkeratosis soon after birth. Mutations in SLURP1 gene could lead to MDM. Clinically, MDM is easily misdiagnosed as other types of keratoderma due to phenotypic variation and overlap. Objective and Methods: A patient with suspected MDM was confirmed by the combination of next-generation sequencing and Exomiser, and the patient was attempted with the treatment of Ixekizumab and Adalimumab. Results: A homozygous mutation c.256G>A (p.Gly86Arg) in the SLURP1 gene was identified in the patient. The inflammatory erythemas on his hands, feet and buttocks were mildly relieved after the treatment of high dose of Ixekizumab. Conclusions: Our findings helps to enhance the understanding of MDM. Ixekizumab may be a potential strategy to treat MDM.

Case Report: Chanarin-Dorfman Syndrome: A Novel Homozygous Mutation in ABHD5 Gene in a Chinese Case and Genotype-Phenotype Correlation Analysis.

The Chanarin-Dorfman syndrome (CDS) is a rare, autosomal recessively inherited genetic disease, whch is associated with a decrease in the lipolysis activity in multiple tissue cells. The clinical phenotype involves multiple organs and systems, including liver, eyes, ears, skeletal muscle and central nervous system. Mutations in ABHD5/CGI58 gene have been confirmed to be associated with CDS. We performed whole exome sequencing on a Chinese CDS patient with skin ichthyosis features mimicking lamellar ichthyosis, ectropion, sensorineural hearing loss, and lipid storage in peripheral blood neutrophils. A novel homozygous missense mutation (p.L154R) in ABHD5 gene was detected in this patient. Genotype-phenotype analysis in reported CDS patients revealed no particular correlation. Our findings further enrich the reservoir of ABHD5 mutations in CDS.

Case Report: A Case of Hailey-Hailey Disease Mimicking Condyloma Acuminatum and a Novel Splice-Site Mutation of ATP2C1 Gene.

Hailey-Hailey disease (HHD) is a rare autosomal-dominant blistering disorder characterized by recurrent vesicular and erosive lesions at intertriginous sites. We described a 24-year-old male who presented with multiple bright red verrucous papules in his mons pubis, bilateral groins, scrotum, perineum, and crissum, clinically resembling condyloma acuminatum. The histopathology showed extensive acantholysis with the characteristic appearance of a dilapidated brick-wall. The mutation analysis revealed a novel splice-site mutation in the ATP2C1 gene. The patient was definitely diagnosed with HHD. The antibacterial treatments resulted in a dramatic improvement. Our findings help to broaden the understanding of clinical manifestations of HHD and improve the clinical diagnosis and treatment of this disease.

Food and feed trade has greatly impacted global land and nitrogen use efficiencies over 1961-2017.

International trade of agricultural products has complicated and far-reaching impacts on land and nitrogen use efficiencies. We analysed the productivity of cropland and livestock and associated use of feed and fertilizer efficiency for over 240 countries, and estimated these countries' cumulative contributions to imports and exports of 190 agricultural products for the period 1961-2017. Crop trade has increased global land and partial fertilizer nitrogen productivities in terms of protein production, which equalled savings of 2,270 Mha cropland and 480 Tg synthetic fertilizer nitrogen over the analysed period. However, crop trade decreased global cropland productivity when productivity is expressed on an energy (per calorie) basis. Agricultural trade has generally moved towards optimality, that is, has increased global land and nitrogen use efficiencies during 1961-2017, but remains at a relatively low level. Overall, mixed impacts of trade on resource use indicate the need to rethink trade patterns and improve their optimality.

Identification of a Novel Mutation in SASH1 Gene in a Chinese Family With Dyschromatosis Universalis Hereditaria and Genotype-Phenotype Correlation Analysis.

Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by mottled hyperpigmented and hypopigmented macules. SASH1 and ABCB6 have been identified as the causative genes for this disorder. We performed whole exome sequencing on a Chinese family with DUH and genotype-phenotype correlation analysis in DUH and lentiginous phenotype patients. A novel heterozygous missense mutation p.Q518P in SASH1 gene was detected in this family. A majority of patients with SASH1 mutations presented as a distinct clinical phenotype clearly different from that in patients with ABCB6 mutations. Our findings further enrich the reservoir of SASH1 mutations in DUH. The clinical phenotypic difference between SASH1 and ABCB6 variants is suggestive of a close phenotype-genotype link in DUH.

Detection of functional networks within white matter using independent component analysis.

Spontaneous fluctuations in MRI signals from gray matter (GM) in the brain are interpreted as originating from variations in neural activity, and their inter-regional correlations may be analyzed to reveal functional connectivity. However, most studies of intrinsic neuronal activity have ignored the spontaneous fluctuations that also arise in white matter (WM). In this work, we explore spontaneous fluctuations in resting state MRI signals in WM based on spatial independent component analyses (ICA), a data-driven approach that separates signals into independent sources without making specific modeling assumptions. ICA has become widely accepted as a valuable approach for identifying functional connectivity within cortex but has been rarely applied to derive equivalent structures within WM. Here, BOLD signal changes in WM of a group of subjects performing motor tasks were first detected using ICA, and a spatial component whose time course was consistent with the task was found, demonstrating the analysis is sensitive to evoked BOLD signals in WM. Secondly, multiple spatial components were derived by applying ICA to identify those voxels in WM whose MRI signals showed similar temporal behaviors in a resting state. These functionally-related structures are grossly symmetric and coincide with corresponding tracts identified from diffusion MRI. Finally, functional connectivity was quantified by calculating correlations between pairs of structures to explore the synchronicity of resting state BOLD signals across WM regions, and the experimental results revealed that there exist two distinct groupings of functional correlations in WM tracts at rest. Our study provides further insights into the nature of activation patterns, functional responses and connectivity in WM, and support previous suggestions that BOLD signals in WM show similarities with cortical activations and are characterized by distinct underlying structures in tasks and at rest.