bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aldosterone synthase (CYP11B2) deficiency among Palestinian infants: Three novel variants and genetic heterogeneity
Authors: Faingelernt Yaniv , Hershkovitz Eli , Abu‐Libdeh Bassam , Abedrabbo Amal , Abu‐Rmaileh Amro Sara , Zarivach Raz , Zangen David , Lavi Eran , Haim Alon , Parvari Ruti , Abu‐Libdeh Abdulsalam 
Published: January 2021

AbstractAldosterone synthase deficiency (ASD) is a rare potentially life‐threatening genetic disorder that usually presents during infancy due to pathogenic variants in the CYP11B2 gene. Knowledge about CYP11B2 variants in the Arab population is scarce. Here, we present and analyze five Palestinian patients and their different novel pathogenic variants. Data on clinical presentation, electrolytes, plasma renin activity, and steroid hormone levels of five patients diagnosed with ASD were summarized. Sequencing of the CYP11B2 gene exons was followed by evolutionary conservation analysis and structural modeling of the variants. All patients were from highly consanguineous Palestinian families. The patients presented at 1–4 months of age with recurrent vomiting, poor weight gain, hyponatremia, hyperkalemia, and low aldosterone levels. Genetic analysis of the CYP11B2 gene revealed three homozygous pathogenic variants: p.Ser344Profs*9, p.G452W in two patients from an extended family, and p.Q338stop. A previously described pathogenic variant was found in one patient: p.G288S. We described four different CYP11B2 gene pathogenic variants in a relatively small population. Our findings may contribute to the future early diagnosis and therapy for patients with ASD among Arab patients who present with failure to thrive and compatible electrolyte disturbances.
Human disease genes website series: An international, open and dynamic library for up‐to‐date clinical information
Authors: Dingemans Alexander J. M. , Stremmelaar Diante E. , Vissers Lisenka E. L. M. , Jansen Sandra , Nabais Sá Maria J. , van Remortele Angela , Jonis Noraly , Truijen Kim , van de Ven Sam , Ewals Jeroen , Verbruggen Michel , Koolen David A. , Brunner Han G. , Eichler Evan E. , Gecz Jozef , de Vries Bert B. A. 
Published: January 2021

AbstractSince the introduction of next‐generation sequencing, an increasing number of disorders have been discovered to have genetic etiology. To address diverse clinical questions and coordinate research activities that arise with the identification of these rare disorders, we developed the Human Disease Genes website series (HDG website series): an international digital library that records detailed information on the clinical phenotype of novel genetic variants in the human genome (https://humandiseasegenes.info/). Each gene website is moderated by a dedicated team of clinicians and researchers, focused on specific genes, and provides up‐to‐date—including unpublished—clinical information. The HDG website series is expanding rapidly with 424 genes currently adopted by 325 moderators from across the globe. On average, a gene website has detailed phenotypic information of 14.4 patients. There are multiple examples of added value, one being the ARID1B gene website, which was recently utilized in research to collect clinical information of 81 new patients. Additionally, several gene websites have more data available than currently published in the literature. In conclusion, the HDG website series provides an easily accessible, open and up‐to‐date clinical data resource for patients with pathogenic variants of individual genes. This is a valuable resource not only for clinicians dealing with rare genetic disorders such as developmental delay and autism, but other professionals working in diagnostics and basic research. Since the HDG website series is a dynamic platform, its data also include the phenotype of yet unpublished patients curated by professionals providing higher quality clinical detail to improve management of these rare disorders.
Evidence that FGFRL1 contributes to congenital diaphragmatic hernia development in humans
Authors: Gofin Yoel , Mackay Laura Palmer , Machol Keren , Keswani Sundeep , Potocki Lorraine , Di Gregorio Eleonora , Naretto Valeria Giorgia , Brusco Alfredo , Hernandez‐Garcia Andres , Scott Daryl A. 
Published: January 2021

AbstractFibroblast growth factor receptor‐like 1 (FGFRL1) encodes a transmembrane protein that is related to fibroblast growth factor receptors but lacks an intercellular tyrosine kinase domain. in vitro studies suggest that FGFRL1 inhibits cell proliferation and promotes cell differentiation and cell adhesion. Mice that lack FGFRL1 die shortly after birth from respiratory distress and have abnormally thin diaphragms whose muscular hypoplasia allows the liver to protrude into the thoracic cavity. Haploinsufficiency of FGFRL1 has been hypothesized to contribute to the development of congenital diaphragmatic hernia (CDH) associated with Wolf‐Hirschhorn syndrome. However, data from both humans and mice suggest that disruption of one copy of FGFRL1 alone is insufficient to cause diaphragm defects. Here we report a female fetus with CDH whose 4p16.3 deletion allows us to refine the Wolf‐Hirschhorn syndrome CDH critical region to an approximately 1.9 Mb region that contains FGFRL1. We also report a male infant with isolated left‐sided diaphragm agenesis who carried compound heterozygous missense variants in FGFRL1. These cases provide additional evidence that deleterious FGFRL1 variants may contribute to the development of CDH in humans.
Interfamilial clinical variability in four Polish families with cranioectodermal dysplasia and identical compound heterozygous variants in WDR35
Authors: Walczak‐Sztulpa Joanna , Wawrocka Anna , Stańczyk Małgorzata , Pesz Karolina , Dudarewicz Lech , Chrul Sławomir , Bukowska‐Olech Ewelina , Wieczorek‐Cichecka Nina , Arts Heleen H. , Oud Machteld M. , Śmigiel Robert , Grenda Ryszard , Obersztyn Ewa , Chrzanowska Krystyna H. , Latos‐Bieleńska Anna 
Published: January 2021

AbstractCranioectodermal dysplasia (CED) is a rare autosomal recessive disorder primarily characterized by craniofacial, skeletal, and ectodermal abnormalities. CED is a chondrodysplasia, which is part of a spectrum of clinically and genetically heterogeneous diseases that result from disruptions in cilia. Pathogenic variants in genes encoding components of the ciliary transport machinery are known to cause CED. Intra‐ and interfamilial clinical variability has been reported in a few CED studies and the findings of this study align with these observations. Here, we report on five CED patients from four Polish families with identical compound heterozygous variants [c.1922T>G p.(Leu641Ter) and c.2522A>T; p.(Asp841Val)] in WDR35. The frequent occurrence of both identified changes in Polish CED families suggests that these variants may be founder mutations. Clinical evaluation of the CED patients revealed interfamilial clinical variability among the patients. This includes differences in skeletal and ectodermal features as well as variability in development, progression, and severity of renal and liver insufficiency. This is the first report showing significant interfamilial clinical variability in a series of CED patients from unrelated families with identical compound heterozygous variants in WDR35. Our findings strongly indicate that other genetic and non‐genetic factors may modulate the progression and expression of the patients' phenotypes.
AIFM1‐associated X‐linked spondylometaphyseal dysplasia with cerebral hypomyelination
Authors: Edgerley Katharine , Barnicoat Angela , Offiah Amaka C. , Calder Alistair D. , Mankad Kshitij , Thomas Nicholas Simon , Bunyan David J. , Williams Maggie , Buxton Chris , Majumdar Arniban , Vijayakumar Kayal , Hilliard Tom , Turner James , Burren Christine P. , Monsell Fergal , Smithson Sarah F. 
Published: January 2021

AbstractSpondylometaphyseal dysplasia with cerebral hypomyelination (SMD‐H) is a very rare but distinctive phenotype, unusually combining spondylometaphyseal dysplasia with hypomyelinating leukodystrophy. Recently, SMD‐H has been associated with variants confined to a specific intra‐genic locus involving Exon 7, suggesting that AIFM1 plays an important role in bone development and metabolism as well as cerebral myelination. Here we describe two further affected boys, one with a novel intronic variant associated with skipping of Exon 7 of AIFM1 and the other a synonymous variant within Exon 7 of AIFM1. We describe their clinical course and radiological and genetic findings, providing further insight into the natural history of this condition.
First reported adult patient with retinal dystrophy and leukodystrophy caused by a novel ACBD5 variant: A case report and review of literature
Authors: Bartlett Michelle , Nasiri Nima , Pressman Rena , Bademci Guney , Forghani Irman 
Published: January 2021

AbstractPeroxisomes play an essential role in lipid metabolism via interaction with other intracellular organelles. The information about the role of the Acyl‐CoA‐binding domain containing‐protein 5 (ACBD5) in these interactions in human cells is emerging. Moreover, a few patients with retinal dystrophy and leukodystrophy caused by pathogenic variants in ACBD5 have been recently introduced. Here, we present a 36‐year‐old female with retinal dystrophy, leukodystrophy, and psychomotor regression due to a novel homozygous variant in ACBD5. Our study adds to the growing knowledge of this peroxisomal disorder by providing phenotypic details of the first adult patient.
Hyperinsulinism in an individual with an EP300 variant of Rubinstein‐Taybi syndrome
Authors: Wild K. Taylor , Nomakuchi Tomoki T. , Sheppard Sarah E. , Leavens Karla F. , De León Diva D. , Zackai Elaine H. 
Published: January 2021

AbstractRubinstein‐Taybi syndrome (RSTS) is an autosomal dominant genetic syndrome characterized by distinct facial features, broad thumbs, growth restriction, microcephaly, intellectual disability, and developmental delay. Pathogenic variants in both CREBBP and EP300 have been associated with RSTS. Here we present a case of a female with hyperinsulinism and features consistent with RSTS, found to have a pathogenic variant in EP300. While there have been a few rare case reports of hyperinsulinism in RSTS, we suggest that hyperinsulinism might be a more prominent feature in EP300 variant RSTS than previously recognized.
Antibacterial activity and mechanism of piperazine polymer
Authors: Zhang Maolan , Wang Yuanliang , Zeng Guoming , Yang Shuang , Liao Xiaoling , Sun Da 
Published: January 2021

AbstractPiperazine polymers poly(ethylenediaminetetraacetic dianhydride‐co‐piperazine) (PE) and MGF‐Ct24E‐modified poly(ethylenediaminetetraacetic dianhydride‐co‐piperazine) (PEM) showed good antibacterial activity. Considering their different applications, the effects of time, pH, and inoculation concentration of these antibacterials against Escherichia coli (E. coli) in unique environments were evaluated in this study. The results indicated that the MIC and MBC values of the polymers increased after the introduction of MGF‐Ct24E into PE, but the two types of polymers still exhibited good antibacterial activity in a short time period under acidic conditions. In addition, we investigated the effect of the piperazine polymers on bacterial cell structure. It was clear that PE and PEM could destroy the bacterial cell wall, cell membrane and DNA, and their specific mechanism may be different. For PE, its carboxyl group could react with peptidoglycans on the E.coli cell wall to form holes on the bacterial surface, allowing PE to penetrate into the bacterial cell to damage DNA. For PEM, the alkaline MGF‐Ct24E could adsorb E.coli and make it shrink, meanwhile, the PE component created small holes on the bacterial walls and membranes, and inserted into the bacteria to result in bactericidal effect. These findings reveal the potential usefulness of PE and PEM in biomedical applications.
Improvement of water resistance of wheat flour‐based adhesives by thermal–chemical treatment and chemical crosslinking
Authors: Bai Yumei , Zhao Fan , Shen Jun , Zhang Yuehong 
Published: January 2021

AbstractA water‐resistant adhesive for plywood panels for engineered wood floors was developed using thermal–chemically treated wheat flour (WF), polyvinyl alcohol (PVA), and polymeric diphenylmethane diisocyanate (p‐MDI) as the cross‐linker. The thermal–chemical treatment was performed at 100°C in the presence of sulfuric acid or sodium dodecyl sulfate (SDS). Fourier transform infrared spectroscopy, X‐ray diffraction spectroscopy, and scanning electron microscopy were used to investigate the chemical structure, crystalline degree, and morphology change, respectively, of the thermal–chemically treated WF. The boiling water‐insoluble content and acetaldehyde values of the thermal–chemically treated WF were also evaluated and compared with those of the controls—native WF and thermally treated WF alone. The bond property evaluation showed that the water resistance of the thermal‐SDS‐treated WF (T‐SDS‐WF)‐based adhesive was significantly improved, which is mainly attributed to the formation of a three‐dimensional crosslinking network resulting from self‐crosslinking of the wheat protein, the Maillard reaction between the wheat starch and wheat protein, and the increased crosslinking between T‐SDS‐WF and p‐MDI. Overall, the developed WF‐based adhesive is a promising bio‐based candidate in the production of plywood for engineered wood floors.
Fabrication of poly(PEGMA) surface with controllable thickness gradient and its mediation on the gradient adhesion of cells
Authors: Tu Chenxi , Zhou Tong , Deng Liwen , Gao Changyou 
Published: January 2021

AbstractThe gradient surface shows enormous potential in the development of tissue engineering, biosensor, microfluidic control, and particle sorting. In this work, a poly(polyethyleneglycol methacrylate) (poly(PEGMA)) gradient surface was prepared through surface‐initiated activators regenerated by electron transfer atom transfer radical polymerization (SI‐AGRET ATRP). The effect of various parameters on the thickness growth of poly(PEGMA) film were analyzed, among which the excessive reducing agent was utmost important. The reducing agents supported the regeneration of CuI and eliminated the disturbance of air, maintaining the "living polymerization" of poly(PEGMA) up to 73.1 nm under tested conditions. The physicochemical properties of the fabricated surfaces were characterized by ellipsometry, X‐ray photoelectron spectroscopy, water contact angle. The thickness slope of gradient poly(PEGMA) was controllable in a nanoscale range. The gradient surface was further grafted with CRGD (Cys‐Arg‐Gly‐Asp) peptides onto the poly(PEGMA‐co‐[glycidyl methacrylate]) blocks via the ring‐opening reaction between epoxy and amino groups, which showed a gradient change in water contact angle and adhesion of endothelial cells.
High water‐absorbent and fast‐expanding PMMA bone cement with double‐bridged structure
Authors: Chen Lei , Tang Yufei , Zhao Kang , Liu Jiaxin , Jiang Xiashu , Sun Yani , Zhao Yan , Tan Quanchang , Yang Zhao , Wu Zixiang 
Published: January 2021

AbstractThe volume shrinkage of polymethyl methacrylate (PMMA) bone cement has been solved by the expandable additives. However, the water absorption and swelling capacity of composite were not maximized as the rapid solidification of the cement and the poor connectivity of the additives in the matrix. In this study, the double‐bridged structure was constructed in PMMA‐based bone cement. Poly(methyl methacrylate‐acrylic acid)‐graphene oxide [P(MMA‐AA)‐GO] was synthesized by the dispersion polymerization, graphene oxide (GO) with sheet layer formed a bridging effect between the poly(methyl methacrylate‐acrylic acid) [P(MMA‐AA)], accelerating water absorption; hydroxyethyl methacrylate in the liquid formed capillary networks, which bridged all the expansion units, increasing the pathways of water transfer in the matrix. The double‐bridged structure in the composite synergistically accelerated water absorption and swelling, causing complete water absorption and swelling performance before solidification, with maximum water absorption and swelling ratios of 125.2 ± 3.2% and 115.2 ± 4.7%, respectively. Surprisingly, the compressive strength of the composite had also been improved, and the maximum value was 78.3 ± 3.2 MPa, which satisfied the minimum compressive strength of acrylic implants in ISO 5833‐2002 and ASTM F451‐2016. This biomaterial exhibited a promising application prospect as its excellent expansion capacity and mechanical properties.
Evaluation of mechanical properties and hydrophobicity of room‐temperature, moisture‐curable polysilazane coatings
Authors: Zhan Ying , Grottenmüller Ralf , Li Wei , Javaid Farhan , Riedel Ralf 
Published: January 2021

AbstractPolysilazane coatings have a broad need in real‐life applications, which require low processing or working temperature. In this work, five commercially available polysilazanes have been spin‐coated on polycarbonate substrates and cured in ambient environment and temperature to obtain transparent, crack‐free, and dense films. The degree of crosslinking is found to have a significant impact on the hardness and Young's modulus of the polysilazane films but has a minor influence on the film thickness and hydrophobicity. Among all five polysilazane coatings, the inorganic perhydropolysilazane‐based coating exhibits the largest hardness (2.05 ± 0.01 GPa) and Young's modulus (10.76 ± 0.03 GPa) after 7 days of curing, while the polyorganosilazane‐derived films exhibit higher hydrophobicity. The molecular structure of polysilazanes plays a key role in mechanical properties and hydrophobicity of the associated films, as well as the adhesion of coatings to substrates, providing an intuitive and reliable way for selecting a suitable polysilazane coating material for a specific application.
Upregulation of TRPM8 can promote the colon cancer liver metastasis through mediating Akt/GSK‐3 signal pathway
Authors: Liu Jia‐Jun , Li Long‐Zhu , Xu Peng 
Published: January 2021

AbstractThis study aims to clarify the function of transient receptor potential melastatin 8 (TRPM8) in colon cancer liver metastasis. First, TRPM8 expression was determined by Western blotting in colon cancer patients with/without liver metastasis. Second, colon cancer cells were grouped into Mock, siCON, and siTRPM8 groups. Then, a series of in vitro experiments were conducted. Last, CT26 cells were used to construct colon cancer liver metastasis models on mice in vivo, followed by comparison of liver metastasis and determination of AKT/glycogen synthase kinase‐3β (GSK‐3β) pathway. Consequently, TRPM8 was upregulated in both colon cancer patients with/without liver metastasis, especially in those with metastasis. Compared with Mock and siCON groups, cells in siTRPM8 group demonstrated significant decreases in clone numbers, cell invasion, and migration; and obvious downregulations of p‐AKT/AKT, p‐GSK3β/GSK3β, Snail, and Vimentin, with an upregulation of E‐cadherin. For in vivo experiments, a sharp decrease was observed in metastatic liver of mice in siTRPM8 group, with significant downregulations of p‐AKT/AKT, p‐GSK3β/GSK3β, Snail, and Vimentin and an upregulation of E‐cadherin, as compared with Mock and siCON groups. Thus, TRPM8 was upregulated in colon cancer patients with liver metastasis, and silencing TRPM8 may suppress the progression and epithelial–mesenchymal transition of colon cancer cells to block its liver metastasis possibly by inhibiting AKT/GSK‐3β pathway.
RETRACTED: Downregulation of SDCBP inhibits cell proliferation and induces apoptosis by regulating PI3K/AKT/mTOR pathway in gastric carcinoma
Authors: Qian Bo , Yao Zhiheng , Yang Yang , Li Na , Wang Qiao 
Published: January 2021

AbstractSyndecan‐binding protein (SDCBP) has been reported to critically process a core role in tumorigenesis. This study was conducted to characterize a novel regulatory network of SDCBP in gastric carcinoma (GC) cells. Our findings indicated that overexpression of SDCBP promoted the proliferation of GC cell and increased proliferating cell nuclear antigen (PCNA) expression. Moreover, the overexpression of SDCBP suppressed the apoptosis of GC cell along with a decrease of Bax/Bcl‐2 ratio and induction of PI3K/AKT/mTOR activation. However, knockdown of SDCBP exhibited opposed effects on GC cells. Furthermore, silencing SDCBP significantly inhibited GC cell viability and PCNA expression accompanied with the upregulated cell apoptosis and Bax/Bcl‐2 ratio, which was regulated by PI3K/AKT/mTOR signaling pathway. And it was further determined that PI3K inhibitor LY294002, AKT inhibitor Torin1, and mTOR inhibitor MK‐2206 suppressed the apoptosis. In conclusion, SDCBP promotes the growth ability of GC by inducing the PCNA expression and inhibiting GC cell apoptosis via inactivation of the PI3K/AKT/mTOR pathway.
Proteomic analysis of human follicular fluid from polycystic ovary syndrome patients
Authors: Sim Young‐Jin , Ryu A‐Reum , Lee Mi‐Young 
Published: January 2021

AbstractComparative proteomic profiling of human follicular fluid (HFF) from polycystic ovary syndrome (PCOS) and non‐PCOS patients who displayed low levels of fertility was carried out via two‐dimensional gel electrophoresis (2‐DE) combined with mass spectrometry. HFF, an important reproductive fluid, was used for the proteomic analysis of PCOS patients to determine the effect of PCOS on folliculogenesis. HFF was obtained from 10 women (average age, 35 years) undergoing in vitro fertilization at two hospitals. The proteins of HFF were separated using 2‐DE analysis and validated by Western blot assay. Approximately 250 protein spots were separated on the 2‐DE gel. Among them, the expression levels of seven proteins were found to change at least 1.5‐fold in the PCOS patient group. Three protein spots, albumin, uncharacterized protein 1, and uncharacterized protein 2, were downregulated in PCOS patients. However, four protein spots, gelsolin, vitamin D binding protein, serum albumin, and complement factor B, were upregulated in PCOS patient group. These proteins may serve as a panel of potential pathological biomarkers during fertilization and oocyte development.
Comparative study of rapid ATP bioluminescence assay and conventional plate count method for development of rapid disinfecting activity test
Authors: Ishimaru Masako , Noda Hideyuki , Matsumoto Erino , Koshi Hiroyuki , Otake Hideyuki 
Published: January 2021

AbstractAntimicrobial activity is tested when developing disinfectants, pharmaceutical products, cosmetics, and many other consumer products. However, the plate count method, the conventional way to count the number of microorganisms, needs several days of culture. Consequently, a means of rapid microbial detection is strongly desired to replace this method. We have already developed a rapid and sensitive microbial adenosine triphosphate (ATP) detection system utilizing ATP bioluminescence, which can quantify microbial ATP within 1 h. To apply this technique to antibacterial activity tests, the ATP method should be proved equal or superior to the conventional method. In this study, we conducted disinfectant activity tests comparing the ATP method and the plate count method, using polyhexamethylene biguanide (PHMB) in different concentrations (0–10 ppm) as a model disinfectant against Staphylococcus aureus and Aspergillus brasiliensis. We found that the log reduction of intracellular ATP had a positive correlation with the log reduction of the plate count. Moreover, the ATP method was able to distinguish different conditions of injured microbial cells that were observed using scanning electron microscopy, whereas colony counting detects only culturable cells. The ATP method is thus a rapid and useful alternative to the conventional method in the field of antimicrobial activity testing.