bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated complete human skin architecture restoration after wounding by nanogenerator-driven electrostimulation
Authors: Liu Aiping , Long Yin , Li Jun , Gu Long , Karim Aos , Wang Xudong , Gibson Angela L. F. 
Published: September 2021

Abstract
Background
Electrostimulation (ES) therapy for wound healing is limited in clinical use due to barriers such as cumbersome equipment and intermittent delivery of therapy.

Methods
We adapted a human skin xenograft model that can be used to directly examine the nanogenerator-driven ES (NG-ES) effects on human skin in vivo—an essential translational step toward clinical application of the NG-ES technique for wound healing.

Results
We show that NG-ES leads to rapid wound closure with complete restoration of normal skin architecture within 7 days compared to more than 30 days in the literature. NG-ES accelerates the inflammatory phase of wound healing with more rapid resolution of neutrophils and macrophages and enhances wound bed perfusion with more robust neovascularization.

Conclusion
Our results support the translational evaluation and optimization of the NG-ES technology to deliver convenient, efficient wound healing therapy for use in human wounds.

Graphic abstract
CYT387, a potent IKBKE inhibitor, suppresses human glioblastoma progression by activating the Hippo pathway
Authors: Wang Xin , Lu Jie , Li Jing , Liu Yang , Guo Gaochao , Huang Qiang 
Published: September 2021

AbstractRecent studies have showed that IKBKE is overexpressed in several kinds of cancers and that IKBKE-knockdown inhibits tumor progression. In this article, we first verified that two glioblastoma cell lines, U87-MG and LN-229, were sensitive to CYT387 by measuring the half maximal inhibitory concentration (IC50) with a CCK-8 assay and then demonstrated that CYT387, as a potent IKBKE inhibitor, suppressed glioblastoma cell proliferation, migration and invasion. Additionally, CYT387 induced cell apoptosis and arrested the cell cycle at the G2/M checkpoint in vitro. Furthermore, we showed that CYT387 did not simply inhibit IKBKE activity but also decreased IKBKE expression at the protein level rather than at the mRNA level. We discovered that CYT387 restrained malignant tumor progression by activating the Hippo pathway in vitro. By coimmunoprecipitation (co-IP), we showed that IKBKE interacted with TEAD2 and YAP1, thus accelerating TEAD2 and YAP1 transport into the nucleus. In subsequent in vivo experiments, we found that CYT387 inhibited subcutaneous nude mouse tumor growth but had little impact on intracranial orthotopic xenografts, probably due to a limited ability to penetrate the blood–brain barrier (BBB). These results suggest that CYT387 has potential as a new antiglioblastoma drug, but an approach to allow passage through the blood–brain barrier (BBB) is needed.
Detection of chikungunya virus in the Southern region, Saudi Arabia
Authors: Hakami Abdulrahim R. , Alshamrani Abdullah A. , Alqahtani Mohamad , Alraey Yasser , Alhefzi Razan A. , Alasmari Sultan , Makkawi Mohamed , Dobie Gasim , Mir Mushtaq , Alshahrani Mohamed , Dera Ayed , Alfaifi Mohammed , Al Shahrani Mesfer , Matari Ahmad , Asiry Ali Essa 
Published: September 2021

AbstractBackground and aimDespite the fact that the chikungunya viral infection is a neglected disease, complications such as hemorrhagic fever, arthritis, and lymphopenia remain a health concern. The aim of this study was to determine the prevalence of the chikungunya virus in the Southern Region, Saudi Arabia. Enzyme immunoassay and polymerase chain reaction have been compared between samples.Materials and methodsForty samples from two southern hospitals in Saudi Arabia were collected between December 2019 and February 2020 and screened for chikungunya virus IgG antibodies and for viral RNA. Selection criteria were based on hematological parameters and rheumatological profiles such as rheumatoid factor, c-reactive protein, anti-nuclear antibody, and anti-cyclic citrullinated peptide (anti-CCP) of out-patients.ResultsOne confirmed case of chikungunya virus was detected using the ELISA test. However, no viral RNA was detected in any of the samples. This suggests that the virus is cleared rapidly in patients.ConclusionChikungunya is a neglected viral disease in Saudi Arabia. Future work should focus on detailed investigation of this viral infection and its vectors.
Effectiveness of a smartphone-based educational intervention to improve breastfeeding
Authors: Seyyedi Navisa , Rahmatnezhad Leili , Mesgarzadeh Maryam , Khalkhali Hamidreza , Seyyedi Negisa , Rahimi Bahlol 
Published: September 2021

Abstract
Background
Exclusive breastfeeding (EBF) is essential during the first six months of life and confers countless benefits to mothers and infants. This study aimed to assess the effectiveness of a smartphone-based educational intervention to improve new mothers’ breastfeeding for infants younger than six months of age in Urmia, Iran.

Methods
A randomized controlled trial study was conducted from January to December 2019 with 40 new mothers and their first child aged < 3 months, assigned to the intervention (mobile app education + routine care) and control groups (routine care). The mean age of infants was 1.25 and 0.98 months for each group consequently. The designed app content categorized according to seven sections (the importance of breastfeeding, behavioral methods, complementary feeding and EBF, pumping and manual expression, managing common breast-related and breastfeeding problems, breastfeeding tips in special situations, and common queries) for educating the required knowledge to nursing mothers.

Results
Forty mothers were assessed for primary outcomes in each group. At three months, the mothers’ knowledge, attitude, and practice (KAP) had meaningful differences in the intervention group compared to the control group. In the intervention group, the degree of changes in knowledge and attitude were 5.67 ± 0.94 and 8.75 ± 1.37 respectively more than the control group (p < 0.001, p < 0.001). However, this amount for the practice score was 0.8 ± 0.49 which is considered to be marginally significant (p = 0.063). During the study, the mothers’ breastfeeding self-efficacy showed significant progress in favor of the intervention group. The score enhancement was 26.85 ± 7.13 for the intervention group and only 0.40 ± 5.17 for the control group that was confirmed to be significant (p < 0.001).

Conclusion
The smartphone-based app for educating new mothers on breastfeeding had a significantly positive effect on breastfeeding self-efficacy and maternal KAP. In future studies, the intervention can be tested in both prenatal and postpartum periods.
Phenotype, genotype and long-term prognosis of 40 Chinese patients with isobutyryl-CoA dehydrogenase deficiency and a review of variant spectra in ACAD8
Authors: Feng Junqi , Yang Chenxi , Zhu Ling , Zhang Yuchen , Zhao Xiaoxu , Chen Chi , Chen Qi-xing , Shu Qiang , Jiang Pingping , Tong Fan 
Published: September 2021

Abstract
Background
Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive metabolic disorder resulting from variants in ACAD8, and is poorly understood, as only dozens of cases have been reported previously. Based on a newborn screening program, we evaluated the incidence, phenotype and genotype of IBDD as well as the prognosis. Moreover, we reviewed the variant spectrum in ACAD8 associated with IBDD.

Methods
Forty unrelated patients with IBDD were retrospectively screened for newborns between Jan 2012 and Dec 2020. Tandem mass spectrometry (MS/MS) was used to determine the concentrations of C4-acylcarnitine, C4/C2 (acetylcarnitine), and C4/C3 (propionylcarnitine). All suspected cases were genetically tested by metabolic genes panel.

Results
The incidence of IBDD here was 1: 62,599. All patients presented continuously elevated C4-acylcarnitine levels with higher ratios of C4/C2 and C4/C3. Isobutyrylglycine occurred in only 8 patients. During follow-up, four patients had a transient motor delay, and two patients had growth delay. Notably, one case harbored both ACAD8 compound heterozygous variants and a KMT2A de novo variant (c.2739del, p.E914Rfs*35), with IBDD and Wiedemann–Steiner syndrome together, had exact severe global developmental delay. All patients were regularly monitored once they were diagnosed, and each patient gradually had a normal diet after 6 months of age. After 3–108 months of follow-up, most individuals were healthy except the case harboring the KMT2A variant. A total of 16 novel variants in ACAD8, c.4_5delCT, c.109C > T, c.110–2A > T, c.236G > A, c.259G > A, c.381–14G > A, c.413delA, c.473A > G, c.500delG, c.758 T > G, c.842–1G > A, c.911A > T, c.989G > A, c.1150G > C, c.1157A > G and c.1165C > T, were identified. Along with a literature review on 51 ACAD8 variants in 81 IBDD patients, we found that the most common variant was c.286G > A (27.2%), which has been observed solely in the Chinese population to date, followed by c.1000C > T (8.6%), c.1176G > T (3.7%) and c.455 T > C (3.1%).

Conclusion
The concentration of C4-acylcarnitine in NBS plus subsequent genetic testing is necessary for IBDD diagnosis. Both the genotypes and ACAD8 variants in IBDD are highly heterogeneous, and no significant correlations between genotype and phenotype are present here in patients with IBDD. Our IBDD cohort with detaied clinical characteristics, genotypes and long-term prognosis will be helpful for the diagnosis and management of patients with IBDD in the future.
Outcomes of pregnancies with trisomy 16 mosaicism detected by NIPT: a series of case reports
Authors: Peng Haishan , Yang Jiexia , Wang Dongmei , Guo Fangfang , Hou Yaping , Yin Aihua 
Published: September 2021

Abstract
Background
Trisomy 16 (T16) is thought to be the most frequent chromosome abnormality at conception, which is often associated with a high risk of abnormal outcomes.

Methods
A retrospective analysis of 14 cases with high risk of T16 by noninvasive prenatal testing (NIPT) was conducted. All cases in the analysis involved prenatal diagnosis, karyotyping and chromosomal microarray analysis.

Case reports
NIPT detected 12 cases of T16 and 2 cases of T16 mosaicism. Prenatal diagnosis confirmed 5 true positive cases and 9 false positive cases. Among the 5 true positive cases, 3 cases had ultrasound abnormalities. All of the 9 false positive cases continued their pregnancies. The newborns who were from these 9 false positive cases except 1 case (case 7) had low birth weights (< 2.5 kg) and there were also 2 premature deliveries.

Conclusion
NIPT serves as a fast and early prenatal screening method, giving clues to chromosome abnormalities and providing guidance for managing pregnancy. Confined placental mosaicism in 16 pregnancies may be at higher risk for preterm delivery.
Side-by-side comparison of the effects of Gq- and Gi-DREADD-mediated astrocyte modulation on intracellular calcium dynamics and synaptic plasticity in the hippocampal CA1
Authors: Van Den Herrewegen Yana , Sanderson Thomas M. , Sahu Surajit , De Bundel Dimitri , Bortolotto Zuner A. , Smolders Ilse 
Published: September 2021

AbstractAstrocytes express a plethora of G protein-coupled receptors (GPCRs) that are crucial for shaping synaptic activity. Upon GPCR activation, astrocytes can respond with transient variations in intracellular Ca2+. In addition, Ca2+-dependent and/or Ca2+-independent release of gliotransmitters can occur, allowing them to engage in bidirectional neuron-astrocyte communication. The development of designer receptors exclusively activated by designer drugs (DREADDs) has facilitated many new discoveries on the roles of astrocytes in both physiological and pathological conditions. They are an excellent tool, as they can target endogenous GPCR-mediated intracellular signal transduction pathways specifically in astrocytes. With increasing interest and accumulating research on this topic, several discrepancies on astrocytic Ca2+ signalling and astrocyte-mediated effects on synaptic plasticity have emerged, preventing a clear-cut consensus about the downstream effects of DREADDs in astrocytes. In the present study, we performed a side-by-side evaluation of the effects of bath application of the DREADD agonist, clozapine-N-oxide (10 µM), on Gq- and Gi-DREADD activation in mouse CA1 hippocampal astrocytes. In doing so, we aimed to avoid confounding factors, such as differences in experimental procedures, and to directly compare the actions of both DREADDs on astrocytic intracellular Ca2+ dynamics and synaptic plasticity in acute hippocampal slices. We used an adeno-associated viral vector approach to transduce dorsal hippocampi of male, 8-week-old C57BL6/J mice, to drive expression of either the Gq-DREADD or Gi-DREADD in CA1 astrocytes. A viral vector lacking the DREADD construct was used to generate controls. Here, we show that agonism of Gq-DREADDs, but not Gi-DREADDs, induced consistent increases in spontaneous astrocytic Ca2+ events. Moreover, we demonstrate that both Gq-DREADD as well as Gi-DREADD-mediated activation of CA1 astrocytes induces long-lasting synaptic potentiation in the hippocampal CA1 Schaffer collateral pathway in the absence of a high frequency stimulus. Moreover, we report for the first time that astrocytic Gi-DREADD activation is sufficient to elicit de novo potentiation. Our data demonstrate that activation of either Gq or Gi pathways drives synaptic potentiation through Ca2+-dependent and Ca2+-independent mechanisms, respectively.
Acceptability and feasibility of strategies to promote healthy dietary choices in UK secondary school canteens: a qualitative study
Authors: Murphy Marie , Mensah Daniel , Mylona Elena , Oyebode Oyinlola 
Published: September 2021

Abstract
Objective
To explore the acceptability and feasibility of choice architecture strategies for dietary change in UK secondary school canteens from the perspectives of pupils, school staff and catering providers through qualitative focus groups and interviews.

Results
Three focus groups with adolescents (n = 15; mean age 13.7 years; standard deviation 1.9) and eight interviews with school staff and caterers recruited from one school and catering provider in Coventry UK were undertaken. The most acceptable choice architecture strategies for intervening to drive healthy dietary choices are those that make use of proximity and positioning, on the basis that convenience was one of the main drivers for food/drink selections. Acknowledging adolescents’ desire for autonomy and for food to be familiar and predictable was considered important in enhancing acceptability. Challenges to the feasibility of nudge strategies included concerns about behavioural issues, increased food waste, and a decline in uptake of canteen purchases. The design of food choice architecture interventions for secondary school settings should consider the specific characteristics of this age group and setting to ensure successful implementation.
Analysis of the regional difference in the number of multi-drug prescriptions and its predictors in Japan, 2015–2018
Authors: Okui Tasuku , Park Jinsang 
Published: September 2021

Abstract
Objective
Polypharmacy and multi-drug prescription are major public health problems in Japan, but only a few studies have investigated the regional differences. By revealing regional differences in the multi-drug prescriptions, we can infer regions with high rates of multimorbidity or inappropriate prescribing. This study revealed regional differences in multi-drug prescriptions (the number of simultaneous prescriptions of seven or more internal medicines) and investigated the factors affecting the difference using the National Database of Health Insurance Claims and Specific Health Checkups of Japan data.

Results
The standardized claim ratio (SCR) of the number of multi-drug prescriptions, which corrected the difference in sex and age distribution of prefectures, varied depending on prefectures. A panel data analysis investigating the association between the SCR and explanatory variables (Medical institutions, socioeconomic factors, and physical characteristics of people in prefectures) revealed that the number of public assistance recipients per 1,000 persons was positively and significantly associated with the SCR (Standardized partial regression coefficient = 0.244, p-value = 0.038). In conclusion, regional differences in the number of the multi-drug prescriptions were revealed in Japan, suggesting that public assistance recipients tend to experience multi-drug prescriptions.
Phylogenetically diverse bacteria isolated from tattoo inks, an azo dye-rich environment, decolorize a wide range of azo dyes
Authors: Nho Seong Won , Cui Xuewen , Kweon Ohgew , Jin Jinshan , Chen Huizhong , Moon Mi Sun , Kim Seong-Jae , Cerniglia Carl E. 
Published: September 2021

Abstract
Purpose
There has been an interest in the microbial azo dye degradation as an optional method for the treatment of azo dye-containing wastes. Tattoo ink is an extremely unique azo dye-rich environment, which have never been explored in terms of microorganisms capable of degrading azo dyes. Previously, we isolated 81 phylogenetically diverse bacteria, belonging to 18 genera and 52 species, contaminated in tattoo inks. In this study, we investigated if these bacteria, which can survive in the azo dye-rich environment, have an ability to degrade azo dyes.

Methods
We conducted a two-step azo dye degradation (or decolorization) assay. In step 1, a high-throughput degradability assay was done for 79 bacterial isolates using Methyl Red and Orange II. In step 2, a further degradation assay was done for 10 selected bacteria with a representative of 11 azo dyes, including 3 commercial tattoo ink azo dyes. Degradation of azo dyes were calculated from measuring optical absorbance of soluble dyes at specific wavelengths.

Results
The initial high-throughput azo dye assay (step 1) showed that 79 isolates had a complete or partial degradation of azo dyes; > 90% of Methyl Red and Orange II were degraded within 24 h, by 74 and 20 isolates, respectively. A further evaluation of azo dye degradability for 10 selected isolates in step 2 showed that the isolates, belonging to Bacillus, Brevibacillus, Paenibacillus, and Pseudomonas, exhibited an excellent decolorization ability for a wide range of azo dyes.

Conclusions
This study showed that phylogenetically diverse bacteria, isolated from azo dye-rich tattoo inks, is able to degrade a diverse range of azo dyes, including 3 azo dyes used in commercial tattoo inks. Some of the strains would be good candidates for future studies to provide a systematic understanding of azo dye degradation mechanisms.
Study on the diversity of epiphytic bacteria on corn and alfalfa using Illumina MiSeq/NovaSeq high-throughput sequencing system
Authors: Wu Meixiao , Wang Yuehua , Wang Yijing , Wang Xuefei , Yu Ming , Liu Guixia , Tang Hui 
Published: September 2021

Abstract
Purpose
To investigate the diversity of the epiphytic bacteria on corn (Zea mays) and alfalfa (Medicago sativa) collected in Hengshui City and Xingtai City, Hebei Province, China, and explore crops suitable for natural silage.

Methods
The Illumina MiSeq/NovaSeq high-throughput sequencing system was used to conduct paired-end sequencing of the community DNA fragments from the surface of corn and alfalfa collected in Hengshui and Xingtai. QIIME2 and R software were used to sort and calculate the number of sequences and taxonomic units for each sample. Thereafter, the alpha and beta diversity indices at of species level were calculated, and the abundance and distribution of taxa were analyzed and compared between samples.

Result
At phylum level, the dominant groups were Proteobacteria (70%), Firmicutes (13%), Actinobacteria (9%), and Bacteroidetes (7%). Meanwhile, the dominant genera were Pseudomonas (8%), Acinetobacter (4%), Chryseobacterium (3%), and Hymenobacter (1%). Enterobacteriaceae (24%) were the most predominant bacteria in both the corn and alfalfa samples. Alpha diversity analysis and beta diversity indices revealed that the diversity of epiphytic microbial communities was significantly affected by plant species but not by region. The diversity and richness of the epiphytic bacterial community of alfalfa were significantly higher than those of corn.

Conclusion
This study contributes to the expanding knowledge on the diversity of epiphytic bacteria in corn and alfalfa silage and provides a basis for the selection of raw materials.
Sorafenib-related generalized eruptive keratoacanthomas (Grzybowski syndrome): a case report
Authors: Abbas M. Nazim , Tan Wei Son , Kichenadasse Ganessan 
Published: September 2021

Abstract
Background
Sorafenib is an oral multikinase inhibitor that targets Raf serine/threonine receptor tyrosine kinases and inhibits tumor cell growth and angiogenesis. Cutaneous toxicities of sorafenib are common, including cutaneous eruptions (such as truncal erythema and seborrheic-dermatitis-like changes) and hand–foot syndrome. Keratoacanthomas and squamous cell carcinomas have been reported previously; however, we report a case of multiple eruptive keratoacanthomas in the form of Grzybowski syndrome after initiation of sorafenib.

Case presentation
We report a 63-year-old Caucasian male who developed multiple cutaneous eruptive keratoacanthomas after starting sorafenib 400 mg twice daily. He had a known history of hepatitis-C-related cirrhosis and hepatocellular carcinoma, and previously had actinic keratosis and skin squamous cell carcinoma excision. Approximately two and a half months after starting sorafenib, the patient initially developed two lesions, one on each forearm, and after excision, these lesions demonstrated histological features of squamous cell carcinoma. One month later, the patient presented with approximately 48 new skin lesions of varying size on the back, bilateral upper limbs, and face requiring excisional biopsy of a large number of these lesions. Histopathology showed eruptive invasive keratoacanthomas (Grzybowski syndrome). Sorafenib was temporarily stopped and subsequently restarted at a lower dose. Acitretin 25 mg daily was commenced after few weeks, and no further keratoacanthomas developed during his treatment.

Conclusions
We report a unique case of sorafenib-associated Grzybowski syndrome. Temporary interruption and dose reduction of sorafenib and use of acitretin appeared to prevent further development of keratoacanthomas.
Investigation of pharmacological mechanism of natural product using pathway fingerprints similarity based on “drug-target-pathway” heterogenous network
Authors: Guo Feifei , Jiang Chunhong , Xi Yujie , Wang Dan , Zhang Yi , Xie Ning , Guan Yi , Zhang Fangbo , Yang Hongjun 
Published: September 2021

AbstractNatural products from traditional medicine inherit bioactivity from their source herbs. However, the pharmacological mechanism of natural products is often unclear and studied insufficiently. Pathway fingerprint similarity based on “drug-target-pathway” heterogeneous network provides new insight into Mechanism of Action (MoA) for natural products compared with reference drugs, which are selected approved drugs with similar bioactivity. Natural products with similar pathway fingerprints may have similar MoA to approved drugs. In our study, XYPI, an andrographolide derivative, had similar anti-inflammatory activity to Glucocorticoids (GCs) and non-steroidal anti-inflammatory drugs (NSAIDs), and GCs and NSAIDs have completely different MoA. Based on similarity evaluation, XYPI has similar pathway fingerprints as NSAIDs, but has similar target profile with GCs. The expression pattern of genes in LPS-activated macrophages after XYPI treatment is similar to that after NSAID but not GC treatment, and this experimental result is consistent with the computational prediction based on pathway fingerprints. These results imply that the pathway fingerprints of drugs have potential for drug similarity evaluation. This study used XYPI as an example to propose a new approach for investigating the pharmacological mechanism of natural products using pathway fingerprint similarity based on a “drug-target-pathway” heterogeneous network.