bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Iris-Claw Phakic Lens Implant versus Corneal Laser Techniques in High Myopia: A Five-Year Follow-Up Study
Authors: Castro-Luna Gracia , Sánchez-Liñán Noelia , Alaskar Hazem , Pérez-Rueda Antonio , Nievas-Soriano Bruno José
Published: September 2022

Background. This study aimed to compare the efficacy and safety of Femto-LASIK, PRK, and Artiflex/Artisan phakic lens implantation in the surgical correction of myopia at different moments of postoperative follow-up; to propose a linear predictive model of visual acuity without correction at five years of refractive procedures; and to evaluate its validity. Methods. A retrospective observational analysis was performed. Patients were clinically reviewed after three months, one year, two years, and five years. Univariate and bivariate analyses and a multivariate linear regression model were performed. Results. Six hundred seventy-nine eyes were analyzed: 18.9% Artiflex, 2.8% Artisan, 42.3% Femto-LASIK, and 36.1% PRK. There were significant differences in effectiveness and safety after five years when comparing Artiflex/Artisan versus PRK and Femto-LASIK (p < 0.01). The linear regression model explained 30.32% of the patients’ visual acuity variability after five years. Conclusions. PRK surgery, Femto-Lasik, and Artiflex/Artisan type phakic lens implantation are effective, safe, and predictable techniques with stable refractive results. Phakic lenses magnify myopic patients who improve their UCVA and BCVA. Concerning phakic lens implantation, corneal endothelial cells remain stable. The predictive model calculated that surgery with a phakic lens increased the UCVA result at five years, and surgery with PRK slightly decreased the long-term results.
Effective Electro-Activation Process of Hydrogen Peroxide/Peroxydisulfate Induced by Atomic Hydrogen for Rapid Oxidation of Norfloxacin over the Carbon-Based Pd Nanocatalyst
Authors: Yang Ling , Cui Mengmeng , Cheng Shiyu , Zhang Shaoqi , Li Ying , Luo Te , Zheng Tianyu , Li Hua
Published: September 2022

Peroxydisulfate (PDS) can be activated by electrochemistry, for which using atom H* as an activator is feasibly favorable in theoretical and experimental applications. Studies have shown that atomic H* can cleave the peroxide bond as a single-electron reducing agent in Na2S2O8 to generate SO4•−, thus achieving the degradation of pollutants. Herein, Pd nanoparticles synthesized by in an in situ solution were dispersed in carbon black and then loaded on carbon felt, called Pd/C@CF, as the cathode for peroxydisulfate activation. This showed an ideal degradation effect on a small electrode (10 mm × 10 mm). Cyclic voltammetry (CV) and linear sweep voltammetry (LSV) tests were taken to verify the significant increase in the yield of the reduction of Na2S2O8 by H*. The degradation experiments and free-radical scavenging experiment confirmed that the atomic H* was the dominant component triggering the activation of PDS to generate SO4•−. A Pd/C@CF composite electrodes have low pH dependence, high stability and recyclability, etc., which has many potential practical applications in wastewater treatment. In addition, H* can also reduce H2O2 to •OH by breaking the peroxide bond, so the removal of pollutants by the same amount of H2O2 and Na2S2O8 under the same conditions is compared, and their application prospects are analyzed and compared.
HiPDERL: An Improved Implementation of the PDERL Viewshed Algorithm and Accuracy Analysis
Authors: Cheng Haozhe , Dou Wanfeng
Published: September 2022

Terrain viewshed analysis based on the digital elevation model (DEM) is of significant application value. A lot of viewshed analysis algorithms have been proposed, including R3 as the accurate one and others as efficient ones. The R3 algorithm is accurate because of its comprehensive but time-consuming computation, while the others are efficient due to proper approximation. However, no algorithm is capable of taking advantage of both until one algorithm is proposed, which is based on a ‘proximity-direction-elevation’ (PDE) coordinate system and named the PDE spatial reference line (PDERL) algorithm. The original research proves the PDERL algorithm is perfectly accurate by theory and experimental results, in comparison with R3 as standard, and even more efficient than R3. However, the original research does not mention the cases where the observer is placed on grid points, and the original implementation does not produce very accurate results in practice. It is important to find out and correct the errors. In this paper, a checking algorithm for PDERL is proposed to allow further investigation of errors. With the fundamental ideas of PDERL unchallenged, an improved implementation of the PDERL algorithm is proposed, named HiPDERL. By experimental results, this paper proves HiPDERL utilizes the potential of PDERL on accuracy at the cost of a little efficiency when the observer is placed on grid points.
A Novel Beta-Glucosidase Gene for Plant Type Was Identified by Genome-Wide Association Study and Gene Co-Expression Analysis in Widespread Bermudagrass
Authors: Gan Lu , Chen Minghui , Zhang Jingxue , Fan Jibiao , Yan Xuebing
Published: September 2022

Bermudagrass (Cynodon spp.) is one of the most widely distributed warm-season grasses globally. The growth habits and plant type of bermudagrass are strongly associated with the applied purpose of the landscape, livestock, and eco-remediation. Therefore, persistent efforts are made to investigate the genetic basis of plant type and growth habits of bermudagrass. Here, we dissect the genetic diversity of 91 wild bermudagrass resources by genome-wide association studies (GWAS) combined with weighted gene co-expression analysis (WGCNA). This work is based on the RNA-seq data and the genome of African bermudagrass (Cynodon transvaalensis Burtt Davy). Sixteen reliable single-nucleotide polymorphisms (SNPs) in transcribed regions were identified to be associated with the plant height and IAA content in diverse bermudagrass by GWAS. The integration of the results from WGCNA indicates that beta-glucosidase 31 (CdBGLU31) is a candidate gene underlying a G/A SNP signal. Furthermore, both qRT-PCR and correlation coefficient analyses indicate that CdBGLU31 might play a comprehensive role in plant height and IAA biosynthesis and signal. In addition, we observe lower plant height in Arabidopsis bglu11 mutants (homologs of CdBGLU31). It uncovers the breeding selection history of different plant types from diverse bermudagrass and provides new insights into the molecular function of CdBGLU31 both in plant types and in IAA biosynthetic pathways.
Lead Disrupts Mitochondrial Morphology and Function through Induction of ER Stress in Model of Neurotoxicity
Authors: Zhang Jianbin , Su Peng , Xue Chong , Wang Diya , Zhao Fang , Shen Xuefeng , Luo Wenjing
Published: September 2022

Lead exposure may weaken the ability of learning and memory in the nervous system through mitochondrial paramorphia and dysfunction. However, the underlying mechanism has not been fully elucidated. In our works, with SD rats, primary culture of hippocampal neuron and PC12 cell line model were built up and behavioral tests were performed to determine the learning and memory insults; Western blot, immunological staining, and electron microscope were then conducted to determine endoplasmic reticulum stress and mitochondrial paramorphia and dysfunction. Co-immunoprecipitation were performed to investigate potential protein–protein interaction. The results show that lead exposure may cripple rats’ learning and memory capability by inducing endoplasmic reticulum stress and mitochondrial paramorphia and dysfunction. Furthermore, we clarify that enhanced MFN2 ubiquitination degradation mediated by PINK1 may account for mitochondrial paramorphia and endoplasmic reticulum stress. Our work may provide important clues for research on the mechanism of how Pb exposure leads to nervous system damage.
Pancreatic Cancer Cells Induce MicroRNA Deregulation in Platelets
Authors: Díaz-Blancas Jorge Yassen , Dominguez-Rosado Ismael , Chan-Nuñez Carlos , Melendez-Zajgla Jorge , Maldonado Vilma
Published: September 2022

Pancreatic cancer is a pathology with a high mortality rate since it is detected at advanced stages, so the search for early-stage diagnostic biomarkers is essential. Liquid biopsies are currently being explored for this purpose and educated platelets are a good candidate, since they are known to present a bidirectional interaction with tumor cells. In this work, we analyzed the effects of platelets on cancer cells’ viability, as determined by MTT, migration using transwell assays, clonogenicity in soft agar and stemness by dilution assays and stem markers’ expression. We found that the co-culture of platelets and pancreatic cancer cells increased the proliferation and migration capacity of BXCP3 cells, augmented clonogenicity and induced higher levels of Nanog, Sox2 and Oct4 expression. As platelets can provide horizontal transfer of microRNAs, we also determined the differential expression of miRNAs in platelets obtained from a small cohort of pancreatic cancer patients and healthy subjects. We found clear differences in the expression of several miRNAs between platelets of patients with cancer healthy subjects. Moreover, when we analyzed microRNAs from the platelets of the pancreatic juice and blood derived from each of the cancer patients, interestingly we find differences between the blood- and pancreatic juice-derived platelets suggesting the presence of different subpopulations of platelets in cancer patients, which warrant further analysis.
NGF-Induced Upregulation of CGRP in Orofacial Pain Induced by Tooth Movement Is Dependent on Atp6v0a1 and Vesicle Release
Authors: Tao Tianjin , Liu Yi , Zhang Jingqi , Lai Wenli , Long Hu
Published: September 2022

The nerve growth factor (NGF) and calcitonin gene-related peptide (CGRP) play a crucial role in the regulation of orofacial pain. It has been demonstrated that CGRP increases orofacial pain induced by NGF. V-type proton ATPase subunit an isoform 1 (Atp6v0a1) is involved in the exocytosis pathway, especially in vesicular transport in neurons. The objective was to examine the role of Atp6v0a1 in NGF-induced upregulation of CGRP in orofacial pain induced by experimental tooth movement. Orofacial pain was elicited by ligating closed-coil springs between incisors and molars in Sprague–Dawley rats. Gene and protein expression levels were determined through real-time polymerase chain reaction, immunostaining, and fluorescence in situ hybridization. Lentivirus vectors carrying Atp6v0a1 shRNA were used to knockdown the expression of Atp6v0a1 in TG and SH-SY5Y neurons. The release of vesicles in SH-SY5Y neurons was observed by using fluorescence dye FM1-43, and the release of CGRP was detected by Enzyme-Linked Immunosorbent Assy. Orofacial pain was evaluated through the rat grimace scale. Our results revealed that intraganglionic administration of NGF and Atp6v0a1 shRNA upregulated and downregulated CGRP in trigeminal ganglia (TG) and trigeminal subnucleus caudalis (Vc), respectively, and the orofacial pain was also exacerbated and alleviated, respectively, following administration of NGF and Atp6v0a1 shRNA. Besides, intraganglionic administration of NGF simultaneously caused the downregulation of Atp6v0a1 in TG. Moreover, the release of vesicles and CGRP in SH-SY5Y neurons was interfered by NGF and Atp6v0a1 shRNA. In conclusion, in the orofacial pain induced by experimental tooth movement, NGF induced the upregulation of CGRP in TG and Vc, and this process is dependent on Atp6v0a1 and vesicle release, suggesting that they are involved in the transmission of nociceptive information in orofacial pain.
Decreased Expression of the Slc31a1 Gene and Cytoplasmic Relocalization of Membrane CTR1 Protein in Renal Epithelial Cells: A Potent Protective Mechanism against Copper Nephrotoxicity in a Mouse Model of Menkes Disease
Authors: Haberkiewicz Olga , Lipiński Paweł , Starzyński Rafał R. , Jończy Aneta , Kurowska Patrycja , Ogórek Mateusz , Bednarz Aleksandra , Herman Sylwia , Hatala Dawid , Grzmil Paweł , Rajfur Zenon , Baster Zbigniew , Lenartowicz Małgorzata
Published: September 2022

Kidneys play an especial role in copper redistribution in the organism. The epithelial cells of proximal tubules perform the functions of both copper uptake from the primary urine and release to the blood. These cells are equipped on their apical and basal membrane with copper transporters CTR1 and ATP7A. Mosaic mutant mice displaying a functional dysfunction of ATP7A are an established model of Menkes disease. These mice exhibit systemic copper deficiency despite renal copper overload, enhanced by copper therapy, which is indispensable for their life span extension. The aim of this study was to analyze the expression of Slc31a1 and Slc31a2 genes (encoding CTR1/CTR2 proteins) and the cellular localization of the CTR1 protein in suckling, young and adult mosaic mutants. Our results indicate that in the kidney of both intact and copper-injected 14-day-old mutants showing high renal copper content, CTR1 mRNA level is not up-regulated compared to wild-type mice given a copper injection. The expression of the Slc31a1 gene in 45-day-old mice is even reduced compared with intact wild-type animals. In suckling and young copper-injected mutants, the CTR1 protein is relocalized from the apical membrane to the cytoplasm of epithelial cells of proximal tubules, the process which prevents copper transport from the primary urine and, thus, protects cells against copper toxicity.
Plasticity towards Rigidity: A Macrophage Conundrum in Pulmonary Fibrosis
Authors: Sari Ezgi , He Chao , Margaroli Camilla
Published: September 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic, and ultimately fatal diffuse parenchymal lung disease. The molecular mechanisms of fibrosis in IPF patients are not fully understood and there is a lack of effective treatments. For decades, different types of drugs such as immunosuppressants and antioxidants have been tested, usually with unsuccessful results. Although two antifibrotic drugs (Nintedanib and Pirfenidone) are approved and used for the treatment of IPF, side effects are common, and they only slow down disease progression without improving patients’ survival. Macrophages are central to lung homeostasis, wound healing, and injury. Depending on the stimulus in the microenvironment, macrophages may contribute to fibrosis, but also, they may play a role in the amelioration of fibrosis. In this review, we explore the role of macrophages in IPF in relation to the fibrotic processes, epithelial–mesenchymal transition (EMT), and their crosstalk with resident and recruited cells and we emphasized the importance of macrophages in finding new treatments.
Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing
Authors: Czamara Darina , Cruceanu Cristiana , Lahti-Pulkkinen Marius , Dieckmann Linda , Ködel Maik , Sauer Susann , Rex-Haffner Monika , Sammallahti Sara , Kajantie Eero , Laivuori Hannele , Lahti Jari , Räikkönen Katri , Binder Elisabeth B.
Published: September 2022

Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22–13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth.
Exploring Amodiaquine’s Repurposing Potential in Breast Cancer Treatment—Assessment of In-Vitro Efficacy & Mechanism of Action
Authors: Parvathaneni Vineela , Chilamakuri Rameswari , Kulkarni Nishant S. , Baig Nabeela F. , Agarwal Saurabh , Gupta Vivek
Published: September 2022

Due to the heterogeneity of breast cancer, current available treatment options are moderately effective at best. Hence, it is highly recommended to comprehend different subtypes, understand pathogenic mechanisms involved, and develop treatment modalities. The repurposing of an old FDA approved anti-malarial drug, amodiaquine (AQ) presents an outstanding opportunity to explore its efficacy in treating majority of breast cancer subtypes. Cytotoxicity, scratch assay, vasculogenic mimicry study, and clonogenic assay were employed to determine AQ’s ability to inhibit cell viability, cell migration, vascular formation, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of AQ in MCF-7 and MDAMB-231 cell lines. Apoptosis assays, cell cycle analysis, RT-qPCR assays, and Western blot studies were performed to determine AQ’s ability to induce apoptosis, cell cycle changes, gene expression changes, and induction of autophagy marker proteins. The results from in-vitro studies confirmed the potential of AQ as an anti-cancer drug. In different breast cancer cell lines tested, AQ significantly induces cytotoxicity, inhibit colony formation, inhibit cell migration, reduces 3D spheroid volume, induces apoptosis, blocks cell cycle progression, inhibit expression of cancer related genes, and induces LC3BII protein to inhibit autophagy. Our results demonstrate that amodiaquine is a promising drug to repurpose for breast cancer treatment, which needs numerous efforts from further studies.
Macropore Regulation of Hydroxyapatite Osteoinduction via Microfluidic Pathway
Authors: Shi Feng , Fang Xin , Zhou Teng , Huang Xu , Duan Ke , Wang Jianxin , Qu Shuxin , Zhi Wei , Weng Jie
Published: September 2022

Macroporous characteristics have been shown to play a key role in the osteoinductivity of hydroxyapatite ceramics, but the physics underlying the new bone formation and distribution in such scaffolds still remain elusive. The work here has emphasized the osteoinductive capacity of porous hydroxyapatite scaffolds containing different macroporous sizes (200–400 μm, 1200–1500 μm) and geometries (star shape, spherical shape). The assumption is that both the size and shape of a macropore structure may affect the microfluidic pathways in the scaffolds, which results in the different bone formations and distribution. Herein, a mathematical model and an animal experiment were proposed to support this hypothesis. The results showed that the porous scaffolds with the spherical macropores and large pore sizes (1200–1500 μm) had higher new bone production and more uniform new bone distribution than others. A finite element analysis suggested that the macropore shape affected the distribution of the medium–high velocity flow field, while the macropore size effected microfluid speed and the value of the shear stress in the scaffolds. Additionally, the result of scaffolds implanted into the dorsal muscle having a higher new bone mass than the abdominal cavity suggested that the mechanical load of the host tissue could play a key role in the microfluidic pathway mechanism. All these findings suggested that the osteoinduction of these scaffolds depends on both the microfluid velocity and shear stress generated by the macropore size and shape. This study, therefore, provides new insights into the inherent osteoinductive mechanisms of bioceramics, and may offer clues toward a rational design of bioceramic scaffolds with improved osteoinductivity.
Eco-Friendly Solution Based on Rosmarinus officinalis Hydro-Alcoholic Extract to Prevent Biodeterioration of Cultural Heritage Objects and Buildings
Authors: Corbu Viorica Maria , Gheorghe-Barbu Irina , Marinas Ioana Cristina , Avramescu Sorin Marius , Pecete Ionut , Geanǎ Elisabeta Irina , Chifiriuc Mariana Carmen
Published: September 2022

Biodeterioration of cultural heritage is caused by different organisms capable of inducing complex alteration processes. The present study aimed to evaluate the efficiency of Rosmarinus officinalis hydro-alcoholic extract to inhibit the growth of deteriogenic microbial strains. For this, the physico-chemical characterization of the vegetal extract by UHPLC–MS/MS, its antimicrobial and antibiofilm activity on a representative number of biodeteriogenic microbial strains, as well as the antioxidant activity determined by DPPH, CUPRAC, FRAP, TEAC methods, were performed. The extract had a total phenol content of 15.62 ± 0.97 mg GAE/mL of which approximately 8.53% were flavonoids. The polyphenolic profile included carnosic acid, carnosol, rosmarinic acid and hesperidin as major components. The extract exhibited good and wide spectrum antimicrobial activity, with low MIC (minimal inhibitory concentration) values against fungal strains such as Aspergillus clavatus (MIC = 1.2 mg/mL) and bacterial strains such as Arthrobacter globiformis (MIC = 0.78 mg/mL) or Bacillus cereus (MIC = 1.56 mg/mL). The rosemary extract inhibited the adherence capacity to the inert substrate of Penicillium chrysogenum strains isolated from wooden objects or textiles and B. thuringiensis strains. A potential mechanism of R. officinalis antimicrobial activity could be represented by the release of nitric oxide (NO), a universal signalling molecule for stress management. Moreover, the treatment of microbial cultures with subinhibitory concentrations has modulated the production of microbial enzymes and organic acids involved in biodeterioration, with the effect depending on the studied microbial strain, isolation source and the tested soluble factor. This paper reports for the first time the potential of R. officinalis hydro-alcoholic extract for the development of eco-friendly solutions dedicated to the conservation/safeguarding of tangible cultural heritage.
Cellular and Molecular Biological Alterations after Photon, Proton, and Carbon Ions Irradiation in Human Chondrosarcoma Cells Linked with High-Quality Physics Data
Authors: Lohberger Birgit , Barna Sandra , Glänzer Dietmar , Eck Nicole , Kerschbaum-Gruber Sylvia , Stasny Katharina , Leithner Andreas , Georg Dietmar
Published: September 2022

Chondrosarcomas are particularly difficult to treat due to their resistance to chemotherapy and radiotherapy. However, particle therapy can enhance local control and patient survival rates. To improve our understanding of the basic cellular radiation response, as a function of dose and linear energy transfer (LET), we developed a novel water phantom-based setup for cell culture experiments and characterized it dosimetrically. In a direct comparison, human chondrosarcoma cell lines were analyzed with regard to their viability, cell proliferation, cell cycle, and DNA repair behavior after irradiation with X-ray, proton, and carbon ions. Our results clearly showed that cell viability and proliferation were inhibited according to the increasing ionization density, i.e., LET, of the irradiation modes. Furthermore, a prominent G2/M arrest was shown. Gene expression profiling proved the upregulation of the senescence genes CDKN1A (p21), CDKN2A (p16NK4a), BMI1, and FOXO4 after particle irradiation. Both proton or C-ion irradiation caused a positive regulation of the repair genes ATM, NBN, ATXR, and XPC, and a highly significant increase in XRCC1/2/3, ERCC1, XPC, and PCNA expression, with C-ions appearing to activate DNA repair mechanisms more effectively. The link between the physical data and the cellular responses is an important contribution to the improvement of the treatment system.
Hepatic Sam68 Regulates Systemic Glucose Homeostasis and Insulin Sensitivity
Authors: Qiao Aijun , Ma Wenxia , Jiang Ying , Han Chaoshan , Yan Baolong , Zhou Junlan , Qin Gangjian
Published: September 2022

Hepatic glucose production (HGP) is an important component of glucose homeostasis, and deregulated HGP, particularly through gluconeogenesis, contributes to hyperglycemia and pathology of type-2 diabetes (T2D). It has been shown that the gluconeogenic gene expression is governed primarily by the transcription factor cAMP-response element (CRE)-binding protein (CREB) and its coactivator, CREB-regulated transcriptional coactivator 2 (CRTC2). Recently, we have discovered that Sam68, an adaptor protein and Src kinase substrate, potently promotes hepatic gluconeogenesis by promoting CRTC2 stability; however, the detailed mechanisms remain unclear. Here we show that in response to glucagon, Sam68 increases CREB/CRTC2 transactivity by interacting with CRTC2 in the CREB/CRTC2 complex and occupying the CRE motif of promoters, leading to gluconeogenic gene expression and glucose production. In hepatocytes, glucagon promotes Sam68 nuclear import, whereas insulin elicits its nuclear export. Furthermore, ablation of Sam68 in hepatocytes protects mice from high-fat diet (HFD)-induced hyperglycemia and significantly increased hepatic and peripheral insulin sensitivities. Thus, hepatic Sam68 potentiates CREB/CRTC2-mediated glucose production, contributes to the pathogenesis of insulin resistance, and may serve as a therapeutic target for T2D.
Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer
Authors: Razali Nurul Nadirah , Raja Ali Raja Affendi , Muhammad Nawawi Khairul Najmi , Yahaya Azyani , Mokhtar Norfilza M.
Published: September 2022

Chronic relapsing inflammatory bowel disease is strongly linked to an increased risk of colitis-associated cancer (CAC). One of the well-known inflammatory carcinogenesis pathways, phosphatidylinositol 3-kinase (PI3K), was identified to be a crucial mechanism in long-standing ulcerative colitis (UC). The goal of this study was to identify somatic variants in the cytokine-induced PI3K-related genes in UC, colorectal cancer (CRC) and CAC. Thirty biopsies (n = 8 long-standing UC, n = 11 CRC, n = 8 paired normal colorectal mucosa and n = 3 CAC) were subjected to targeted sequencing on 13 PI3K-related genes using Illumina sequencing and the SureSelectXT Target Enrichment System. The Genome Analysis Toolkit was used to analyze variants, while ANNOVAR was employed to detect annotations. There were 5116 intronic, 355 exonic, 172 untranslated region (UTR) and 59 noncoding intronic variations detected across all samples. Apart from a very small number of frameshifts, the distribution of missense and synonymous variants was almost equal. We discovered changed levels of IL23R, IL12Rß1, IL12Rß2, TYK2, JAK2 and OSMR in more than 50% of the samples. The IL23R variant in the UTR region, rs10889677, was identified to be a possible variant that might potentially connect CAC with UC and CRC. Additional secondary structure prediction using RNAfold revealed that mutant structures were more unstable than wildtype structures. Further functional research on the potential variants is, therefore, highly recommended since it may provide insight on the relationship between inflammation and cancer risk in the cytokine-induced PI3K pathway.
Apoptotic Body-Rich Media from Tenocytes Enhance Proliferation and Migration of Tenocytes and Bone Marrow Stromal Cells
Authors: Dong Chenhui , Gingery Anne , Amadio Peter C. , An Kai-Nan , Moran Steven L. , Zhao Chunfeng
Published: September 2022

The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed.
Early Detection of Cervical Cancer by Fluorescence Lifetime Imaging Microscopy Combined with Unsupervised Machine Learning
Authors: Ji Mingmei , Zhong Jiahui , Xue Runzhe , Su Wenhua , Kong Yawei , Fei Yiyan , Ma Jiong , Wang Yulan , Mi Lan
Published: September 2022

Cervical cancer has high morbidity and mortality rates, affecting hundreds of thousands of women worldwide and requiring more accurate screening for early intervention and follow-up treatment. Cytology is the current dominant clinical screening approach, and though it has been used for decades, it has unsatisfactory sensitivity and specificity. In this work, fluorescence lifetime imaging microscopy (FLIM) was used for the imaging of exfoliated cervical cells in which an endogenous coenzyme involved in metabolism, namely, reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H], was detected to evaluate the metabolic status of cells. FLIM images from 71 participants were analyzed by the unsupervised machine learning method to build a prediction model for cervical cancer risk. The FLIM method combined with unsupervised machine learning (FLIM-ML) had a sensitivity and specificity of 90.9% and 100%, respectively, significantly higher than those of the cytology approach. One cancer recurrence case was predicted as high-risk several months earlier using this method as compared to using current clinical methods, implying that FLIM-ML may be very helpful for follow-up cancer care. This study illustrates the clinical applicability of FLIM-ML as a detection method for cervical cancer screening and a convenient tool for follow-up cancer care.
COVID-19 Vaccine Acceptance during Pregnancy and Influencing Factors in South Korea
Authors: Yoon Heesu , Choi Bo Yun , Seong Won Joon , Cho Geum Joon , Na Sunghun , Jung Young Mi , Jo Ji Hye , Ko Hyun Sun , Park Joong Shin
Published: September 2022

Pregnant women were excluded from vaccination against Coronavirus 2019 (COVID-19) until September 2021 in South Korea. Although vaccination for pregnant women started in October 2021, vaccine acceptance in pregnant women is yet unknown. This cross-sectional study aimed to investigate COVID-19 vaccine acceptance during pregnancy and influencing factors. An anonymous survey was distributed in obstetrics departments to all pregnant or postpartum women, during the prenatal or postpartum visit. The proportion of self-reported COVID-19 vaccination during pregnancy among 436 women was 26.6%. Pregnancy-related independent factors influencing maternal COVID-19 vaccination were “received vaccine information about from obstetrics and gynecology (OBGYN) doctors” (OR 3.41, 95% CI 2.05–5.65), “cohabitant COVID-19 vaccination” (OR 2.43, 95% CI 1.06–5.59), and “second trimester” (OR 7.35, 95% CI 1.54–35.15). In women who did not want to get vaccinated, the most common reason for COVID-19 vaccination hesitancy was concern that COVID-19 vaccine might affect the fetus (91.7%, 243/266), followed by distrust in COVID-19 vaccine effectiveness (42.6%, 113/266). This study showed that providing information about maternal COVID-19 vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Providing updated evidence of COVID-19 vaccine efficacy and safety in pregnant women may be also helpful for increasing vaccine acceptance.
The Role of Drones in Out-of-Hospital Cardiac Arrest: A Scoping Review
Authors: Lim Joseph Chun Liang , Loh Nicole , Lam Hsin Hui , Lee Jin Wee , Liu Nan , Yeo Jun Wei , Ho Andrew Fu Wah
Published: September 2022

Drones may be able to deliver automated external defibrillators (AEDs) directly to bystanders of out-of-hospital cardiac arrest (OHCA) events, improving survival outcomes by facilitating early defibrillation. We aimed to provide an overview of the available literature on the role and impact of drones in AED delivery in OHCA. We conducted this scoping review using the PRISMA-ScR and Arksey and O’Malley framework, and systematically searched five bibliographical databases (Medline, EMBASE, Cochrane CENTRAL, PsychInfo and Scopus) from inception until 28 February 2022. After excluding duplicate articles, title/abstract screening followed by full text review was conducted by three independent authors. Data from the included articles were abstracted and analysed, with a focus on potential time savings of drone networks in delivering AEDs in OHCA, and factors that influence its implementation. Out of the 26 included studies, 23 conducted simulations or physical trials to optimise drone network configuration and evaluate time savings from drone delivery of AEDs, compared to the current emergency medical services (EMS), along with 1 prospective trial conducted in Sweden and 2 qualitative studies. Improvements in response times varied across the studies, with greater time savings in rural areas. However, emergency call to AED attachment time was not reduced in the sole prospective study and a South Korean study that accounted for weather and topography. With growing interest in drones and their potential use in AED delivery spurring new research in the field, our included studies demonstrate the potential advantages of unmanned aerial vehicle (UAV) network implementation in controlled environments to deliver AEDs faster than current EMS. However, for these time savings to translate to reduced times to defibrillation and improvement in OHCA outcomes, careful evaluation and addressing of real-world delays, challenges, and barriers to drone use in AED delivery is required.
Left Main Coronary Artery Disease—Current Management and Future Perspectives
Authors: Dąbrowski Emil Julian , Kożuch Marcin , Dobrzycki Sławomir
Published: September 2022

Due to its anatomical features, patients with an obstruction of the left main coronary artery (LMCA) have an increased risk of death. For years, coronary artery bypass grafting (CABG) has been considered as a gold standard for revascularization. However, notable advancements in the field of percutaneous coronary intervention (PCI) led to its acknowledgement as an important treatment alternative, especially in patients with low and intermediate anatomical complexity. Although recent years brought several random clinical trials that investigated the safety and efficacy of the percutaneous approach in LMCA, there are still uncertainties regarding optimal revascularization strategies. In this paper, we provide a comprehensive review of state-of-the-art diagnostic and treatment methods of LMCA disease, focusing on percutaneous methods.
Efficacy of Classic Ear Molding for Neonatal Ear Deformity: Case Series and Literature Review
Authors: Kim Jeonghoon , Jo Taehee , Choi Jaehoon , Kim Junhyung , Jeong Woonhyeok
Published: September 2022

Background: We analyzed an original case series of the classic ear-molding method and evaluated the efficacy and complication rate of the method compared to commercial ear-molding products by meta-analysis to draw conclusions on the efficacy of the classic method. Methods: From January 2019 to March 2022, we selected patients who underwent classic ear molding for newborn ear deformities at our institution and reviewed the patient age, treatment time, efficiency and complications. Additionally, the PubMed, EMBASE, and Scopus databases were searched, and meta-analysis (following the PRISMA guidelines) was performed. Results: In the case study, the success rate (excellent and good outcomes) of the classic ear-molding method was 92.6%. The mean age at application and mean duration of application were 5.81 ± 6.09 days and 32.13 ± 7.90 days, respectively. In the systematic review, the classic method group showed a statistically smaller success rate (proportion of 0.79) and statistically smaller complication rate (proportion of 0.05) than the commercial product group (proportion of 0.83). Conclusions: Compared with commercial products, classic ear molding has remarkable and comparable therapeutic effects on neonatal auricular deformities. Additionally, the classic ear-molding method is more suitable for infants with auricular deformities from socioeconomically vulnerable areas. Thus, the classic ear-molding method could be a better option for congenital ear anomalies than commercial ear-molding products.
Effects of Reminiscence Therapy on Cognition, Depression and Quality of Life in Elderly People with Alzheimer’s Disease: A Systematic Review of Randomized Controlled Trials
Authors: Cammisuli Davide Maria , Cipriani Gabriele , Giusti Emanuele Maria , Castelnuovo Gianluca
Published: September 2022

Background: Patients with Alzheimer’s disease (AD) present with cognitive function deterioration, neuropsychiatric symptoms (NPS)—especially depression—and low quality of life (QoL). Management of AD remains difficult, especially in the elderly. Reminiscence therapy (RT) is a well-known cognitive rehabilitation intervention that can be adopted in nursing and residential care homes to restore autobiographical memory, ameliorate NPS, and improve the QoL of people with dementia. However, the evidence-based efficacy of RT for elderly patients with AD remains to be determined. Methods: Here, we synthesized findings of randomized controlled trials (RCTs) exploring the effects of RT on cognition, depression, and QoL in elderly people with AD, according to the most recent PRISMA statement. We searched for RCTs in PubMed, Web of Science, and Cochrane Central Register of Controlled Trials, and in trial registries (i.e., clinicaltrials.gov and International Clinical Trials Registry Platform of the World Health Organization). Two review authors extracted data of interest, with cognition, depression, and QoL measures as outcomes. Results: A total of five articles were included in the final analysis. Findings globally showed that RT, both administered in individual or group sessions at least once a week for 30–35 min over a period of 12 weeks, is effective in supporting global cognition, ameliorating depression, and improving specific aspects of the QoL in elderly people with AD. Conclusions: RT has the potential to be a routine non-pharmacological therapy for elderly people with AD, thanks to its wider effects on the individual in terms of cognitive vitality and emotional status promotion, with positive implications for patient’s daily life. Despite such evidences, caution should be used in findings’ generalizability in relation to the paucity of existing RCTs with long-term follow-up.
Prevention of Surgery-Induced Dry Eye by Diquafosol Eyedrops after Femtosecond Laser-Assisted Cataract Surgery
Authors: Yamazaki Kenichiro , Yoneyama Junko , Kimoto Ryuta , Shibata Yuko , Mimura Tatsuya
Published: September 2022

Purpose: To analyze the protective effects of diquafosol eyedrops on the ocular surface following femtosecond laser-assisted cataract surgery (FLACS). Design: A prospective, randomized contralateral study. Methods: Bilateral FLACS with a trifocal IOL (PanOptix) implantation was performed in 40 eyes in 20 patients (10 males, 10 females, average age 68.8 ± 6.3 years old). Patients received 3% diquafosol eyedrops six times daily in one randomly chosen eye (diquafosol group), and physiological saline six times a day in the other eye (control group). Other medication included 1.5% levofloxacin, 0.1% dexamethasone and 0.1% diclofenac three times daily in both eyes. The pre and post-operative tear break-up time (BUT), superficial punctate keratopathy (SPK) scores and visual function were compared between both eyes, and all patients answered the dry-eye-related quality of life score (DEQS) questionnaire. Results: The BUT between groups was similar pre-operatively and on the first day post-op; however, the BUT was statistically longer in the diquafosol group compared to saline at 1 week (5.5/3.7 s) and 2 weeks (4.8/3.0 s) (p < 0.05). There was no difference in the SPK score, best corrected distance visual acuity, tear meniscus height, contrast sensitivity, DEQS and Schirmer test at all time points. Spherical aberration was statistically lower in the diquafosol group at 1 week. The protective effects of diquafosol on the BUT was more pronounced in patients with a pre-operative BUT of less than 5 s compared with those with a BUT longer than 6 s. Conclusions: Diquafosol eyedrops prevented the shortening of the BUT following FLACS, even in patients with short pre-operative BUT values.
Influence of Stratification and Bottom Boundary Layer on the Classical Ekman Model
Authors: Santander-Rodríguez Viviana , Díez-Minguito Manuel , Espinoza-Andaluz Mayken
Published: September 2022

A depth understanding of the different processes of water movements produced by the wind surface stress yields a better description and improvement of the marine food chain and ecosystem. The classical Ekman model proposes a hypothetical ocean, excluding the influence of continents and the Coriolis force. It also assumes infinite depth and a constant vertical eddy viscosity. The current study aims to understand how the vertical velocity profile is affected by the variation of the eddy viscosity coefficient (kz) and the consideration of a finite depth. The study uses an ideal analytical model with the Ekman classical model as a starting point. It has been demonstrated that, for a very stratified profile, when the depth is not considered infinity, the Ekman transport tends to a direction smaller than 80°. It differs from the classical Ekman model, which proposes an approximated angle equal to 90°. Considering the modified model, it was also found that the surface current deviation is smaller than 40°, which differs from the 45° proposed by the classical model. In addition, it was determined that for ocean depths smaller than 180 m, the maximum velocity does not occur at the water surface, as in the classical model, but at deeper levels.
Efficacy of Plant-Derived Fungicides at Inhibiting Batrachochytrium salamandrivorans Growth
Authors: Tompros Adrianna , Wilber Mark Q. , Fenton Andy , Carter Edward Davis , Gray Matthew J.
Published: September 2022

The emerging fungal amphibian pathogen, Batrachochytrium salamandrivorans (Bsal), is currently spreading across Europe and given its estimated invasion potential, has the capacity to decimate salamander populations worldwide. Fungicides are a promising in situ management strategy for Bsal due to their ability to treat the environment and infected individuals. However, antifungal drugs or pesticides could adversely affect the environment and non-target hosts, thus identifying safe, effective candidate fungicides for in situ treatment is needed. Here, we estimated the inhibitory fungicidal efficacy of five plant-derived fungicides (thymol, curcumin, allicin, 6-gingerol, and Pond Pimafix®) and one chemical fungicide (Virkon® Aquatic) against Bsal zoospores in vitro. We used a broth microdilution method in 48-well plates to test the efficacy of six concentrations per fungicide on Bsal zoospore viability. Following plate incubation, we performed cell viability assays and agar plate growth trials to estimate the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each fungicide. All six fungicides exhibited inhibitory and fungicidal effects against Bsal growth, with estimated MIC concentrations ranging from 60 to 0.156 μg/mL for the different compounds. Allicin showed the greatest efficacy (i.e., lowest MIC and MFC) against Bsal zoospores followed by curcumin, Pond Pimafix®, thymol, 6-gingerol, and Virkon® Aquatic, respectively. Our results provide evidence that plant-derived fungicides are effective at inhibiting and killing Bsal zoospores in vitro and may be useful for in situ treatment. Additional studies are needed to estimate the efficacy of these fungicides at inactivating Bsal in the environment and treating Bsal-infected amphibians.
A First Draft of the Core Fungal Microbiome of Schedonorus arundinaceus with and without Its Fungal Mutualist Epichloë coenophiala
Authors: Dale Jenna C. M. , Newman Jonathan A.
Published: September 2022

Tall fescue (Schedonorus arundinaceus) is a cool-season grass which is commonly infected with the fungal endophyte Epichloë coenophiala. Although the relationship between tall fescue and E. coenophiala is well-studied, less is known about its broader fungal communities. We used next-generation sequencing of the ITS2 region to describe the complete foliar fungal microbiomes in a set of field-grown tall fescue plants over two years, and whether these fungal communities were affected by the presence of Epichloë. We used the Georgia 5 cultivar of tall fescue, grown in the field for six years prior to sampling. Plants were either uninfected with E. coenophiala, or they were infected with one of two E. coenophiala strains: The common toxic strain or the AR542 strain (sold commerically as MaxQ). We observed 3487 amplicon sequence variants (ASVs) across all plants and identified 43 ASVs which may make up a potential core microbiome. Fungal communities did not differ strongly between Epichloë treatments, but did show a great deal of variation between the two years. Plant fitness also changed over time but was not influenced by E. coenophiala infection.