bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis
Authors: Sun Qingsong , Luo Man , Gao Zhiwei , Han Xiang , Wu Weiqin , Zhao Hongmei
Published: July 2021

Background

Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI.

Methods

We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI.

Result

TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis.

Conclusion

OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.
RETRACTED ARTICLE: LncRNA PCGEM1 induces proliferation and migration in non-small cell lung cancer cells through modulating the miR-590-3p/SOX11 axis
Authors: Wen Huanshun , Feng Hongxiang , Ma Qianli , Liang Chaoyang
Published: July 2021

Background

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers. As reported, long non-coding RNAs (lncRNAs) induce various biological behaviors in cancers. LncRNA PCGEM1 prostate-specific transcript (PCGEM1) is reported to exert carcinogenic effect on certain cancers. Our research aimed to explore the role of PCGEM1 in NSCLC.

Methods

We enrolled forty NSCLC patients to explore PCGEM1 expression in clinical NSCLC tissues. Colony formation assay, CCK-8, Transwell assay were conducted to reveal cell proliferation, viability, migration and invasion. Luciferase reporter assay, RNA pull down, and RIP assay were performed to investigate the downstream axis of PCGEM1.

Results

PCGEM1 was significantly upregulated in NSCLC cells and tissues. Subsequently, in vitro loss-of-function experiments illustrated the carcinogenic role of PCGEM1 in NSCLC through promoting viability, proliferation, migration, and invasion. MiR-590-3p was confirmed to be a downstream gene of PCGEM1. Furthermore, SRY-box transcription factor 11 (SOX11) was verified to be a target of miR-590-3p. Additionally, rescue experiments indicated that miR-590-3p inhibitor or pcDNA3.1/SOX11 rescued the impacts of downregulated PCGEM1 on NSCLC cell proliferation, viability, migration and invasion.

Conclusions

LncRNA PCGEM1 aggravated proliferative and migrative abilities in NSCLC via the miR-590-3p/SOX11 axis.
Comparative study of renal drainage with different ureteral stents subject to extrinsic ureteral obstruction using an in vitro ureter-stent model
Authors: Shilo Yaniv , Modai Jonathan , Leibovici Dan , Dror Ishai , Berkowitz Brian
Published: July 2021

Background

To compare the efficacy of different ureteral stents subject to extrinsic ureteral obstruction (EUO), in a controlled in vitro stented ureter experiment.

Methods

We employ an in vitro ureter-stent experimental set-up, with latex tubing simulating flexible ureters attached to vessels simulating renal units and bladders. The flow behavior of five ureteral stents—polymeric 8F, tandem 6F, tandem 7F, endopyelotomy and metal—was tested under a ureteral deformation configuration of 40°, with 2000 g external force over a 3.5 cm length of the ureter. A constant fluid flow was applied through the ureter-stent configurations, and pressure fluctuations in the renal unit were monitored. We considered a renal unit pressure of 10 cmH2O or flow discontinuation in the bladder as stent failure. Urine containing debris was mimicked by use of a colloidal solution.

Results

Of all assessed ureteral stents, under EUO conditions, only the single 8F stents remained patent throughout the length of the experiment. All other stents—tandem 6F and 7F, single 7F, metal and endopyelotomy—displayed limitations.

Conclusions

Tandem and metal stents show no superiority over large luminal polymeric stents for EUO treatment in this in vitro model. Larger luminal stents offer excellent resistance to external pressure and allow adequate colloidal flow. The need for frequent exchange and bladder irritation should also be considered in the choice of stent configuration for treatment of kidney drainage under EUO.
Salivary metabolites associated with a 5-year tooth loss identified in a population-based setting
Authors: Andörfer Leonie , Holtfreter Birte , Weiss Stefan , Matthes Rutger , Pitchika Vinay , Schmidt Carsten Oliver , Samietz Stefanie , Kastenmüller Gabi , Nauck Matthias , Völker Uwe , Völzke Henry , Csonka Laszlo N. , Suhre Karsten , Pietzner Maik , Kocher Thomas
Published: July 2021

Background

Periodontitis is among the most common chronic diseases worldwide, and it is one of the main reasons for tooth loss. Comprehensive profiling of the metabolite content of the saliva can enable the identification of novel pathways associated with periodontitis and highlight non-invasive markers to facilitate time and cost-effective screening efforts for the presence of periodontitis and the prediction of tooth loss.

Methods

We first investigated cross-sectional associations of 13 oral health variables with saliva levels of 562 metabolites, measured by untargeted mass spectrometry among a sub-sample (n = 938) of the Study of Health in Pomerania (SHIP-2) using linear regression models adjusting for common confounders. We took forward any candidate metabolite associated with at least two oral variables, to test for an association with a 5-year tooth loss over and above baseline oral health status using negative binomial regression models.

Results

We identified 84 saliva metabolites that were associated with at least one oral variable cross-sectionally, for a subset of which we observed robust replication in an independent study. Out of 34 metabolites associated with more than two oral variables, baseline saliva levels of nine metabolites were positively associated with a 5-year tooth loss. Across all analyses, the metabolites 2-pyrrolidineacetic acid and butyrylputrescine were the most consistent candidate metabolites, likely reflecting oral dysbiosis. Other candidate metabolites likely reflected tissue destruction and cell proliferation.

Conclusions

Untargeted metabolic profiling of saliva replicated metabolic signatures of periodontal status and revealed novel metabolites associated with periodontitis and future tooth loss.
Expression of antibody fragments in Saccharomyces cerevisiae strains evolved for enhanced protein secretion
Authors: Wang Yanyan , Li Xiaowei , Chen Xin , Nielsen Jens , Petranovic Dina , Siewers Verena
Published: July 2021

Monoclonal antibodies, antibody fragments and fusion proteins derived thereof have revolutionized the practice of medicine. Major challenges faced by the biopharmaceutical industry are however high production costs, long processing times and low productivities associated with their production in mammalian cell lines. The yeastSaccharomyces cerevisiae, a well-characterized eukaryotic cell factory possessing the capacity of post­translational modifications, has been industrially exploited as a secretion host for production of a range of products, including pharmaceuticals. However, due to the incompatible surface glycosylation, few antibody molecules have been functionally expressed inS. cerevisiae. Here, three non-glycosylated antibody fragments from human and the Camelidae family were chosen for expression in aS. cerevisiaestrain (HA) previously evolved for high α-amylase secretion. These included the Fab fragment Ranibizumab (Ran), the scFv peptide Pexelizumab (Pex), and a nanobody consisting of a single V-type domain (Nan). Both secretion and biological activities of the antibody fragments were confirmed. In addition, the secretion level of each protein was compared in the wild type (LA) and two evolved strains (HA and MA) with different secretory capacities. We found that the secretion of Ran and Nan was positively correlated with the strains’ secretory capacity, while Pex was most efficiently secreted in the parental strain. To investigate the mechanisms for different secretion abilities in these selected yeast strains for the different antibody fragments, RNA-seq analysis was performed. The results showed that several bioprocesses were significantly enriched for differentially expressed genes when comparing the enriched terms between HA.Nan vs. LA.Nan and HA.Pex vs. LA.Pex, including amino acid metabolism, protein synthesis, cell cycle and others, which indicates that there are unique physiological needs for each antibody fragment secretion.
JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4
Authors: Jing Chao , Liu Dandan , Lai Qingchuan , Li Linqi , Zhou Mengqian , Ye Beibei , Wu Yue , Li Hong , Yue Kai , Wu Yansheng , Duan Yuansheng , Wang Xudong
Published: July 2021

Background

Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC.

Methods

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC.

Results

The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC.

Conclusions

These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.
MALBoost: a web-based application for gene regulatory network analysis in Plasmodium falciparum
Authors: van Wyk Roelof , van Biljon Riëtte , Birkholtz Lyn-Marie
Published: July 2021

Background

Gene Regulatory Networks (GRN) produce powerful insights into transcriptional regulation in cells. The power of GRNs has been underutilized in malaria research. The Arboreto library was incorporated into a user-friendly web-based application for malaria researchers (http://malboost.bi.up.ac.za). This application will assist researchers with gaining an in depth understanding of transcriptomic datasets.

Methods

The web application for MALBoost was built in Python-Flask with Redis and Celery workers for queue submission handling, which execute the Arboreto suite algorithms. A submission of 5–50 regulators and total expression set of 5200 genes is permitted. The program runs in a point-and-click web user interface built using Bootstrap4 templates. Post-analysis submission, users are redirected to a status page with run time estimates and ultimately a download button upon completion. Result updates or failure updates will be emailed to the users.

Results

A web-based application with an easy-to-use interface is presented with a use case validation of AP2-G and AP2-I. The validation set incorporates cross-referencing with ChIP-seq and transcriptome datasets. For AP2-G, 5 ChIP-seq targets were significantly enriched with seven more targets presenting with strong evidence of validated targets.

Conclusion

The MALBoost application provides the first tool for easy interfacing and efficiently allows gene regulatory network construction for Plasmodium. Additionally, access is provided to a pre-compiled network for use as reference framework. Validation for sexually committed ring-stage parasite targets of AP2-G, suggests the algorithm was effective in resolving “traditionally” low-level signatures even in bulk RNA datasets.
Presentation of a participatory approach to develop preventive measures to reduce COVID-19 transmission in child care
Authors: Diebig Mathias , Gritzka Susan , Dragano Nico , Angerer Peter
Published: July 2021

Background

It can be suspected that work in child care facilities is associated with an elevated exposure risk towards SARS-CoV-2 infections. It is still unclear under which conditions employees in those facilities can safely pursue their work. Preventive workplace-related measures to reduce transmission dynamics in this work environment need to be developed. These measures need to build on a solid scientific foundation and be ready for practical use at the same time. Therefore, the aim of the study is to present a participatory approach to identify, minimize, and eliminate workplace-specific COVID-19 transmission within child care. The approach presented combines quantitative as well as qualitative elements and includes a screening of critical workplace conditions and the development of preventive measures to foster a safe workplace design.

Methods

First, 428 employees of different child care facilities in a large German city reported their subjective risk of infection, fear of infection, and support received by the employer. Second, the participants commented in detail about high risk conditions during work. Third, employees provided suggestions for preventive measures. We conducted a qualitative analysis of free text answers to evaluate which aspects are perceived as critical from an employee perspective.

Results

Participants provided valuable and practicable ideas on how to design and improve preventive measures to reduce COVID-19 transmission in child care dealing with structural conditions, the interaction with the parents, the implementation of preventive measures and recommendations for policy makers.

Conclusions

These new insights help to organize pandemic risk management in order to align theoretical based measures with the practical realization. We encourage researchers to adapt the approach presented to other work areas in order to foster participation of employees in work design to reduce COVID-19 transmission.
A study on the association between accessory maxillary ostium and maxillary sinus mucosal thickening using cone beam computed tomography
Authors: Shetty Shishir , Al Bayatti Saad Wahby , Al-Rawi Natheer Hashim , Samsudin Rani , Marei Hesham , Shetty Raghavendra , Abdelmagyd Hossam Abdelatty , Reddy Sesha
Published: July 2021

Background

Accessory maxillary ostium (AMO) has a major role to play in the aetiology of maxillary sinusitis. Mucosal thickening is one of the key radiographic features of chronic maxillary sinusitis. The aim of this study was to identify the location of the AMOs and investigate the association between Mucosal Thickening [MT] and AMO using Cone Beam Computed Tomography [CBCT].

Methods

CBCT scans of 400 maxillary sinuses from the records of 200 patients who seeked various dental treatments at the Thumbay Dental Hospital, Gulf Medical University, Ajman, United Arab Emirates were evaluated. The incidence, anatomical position and maximal length of accessory maxillary ostia (AMO) in the maxillary antrum were reviewed using CBCT by two examiners. The association between MTs and AMOs were also analysed.

Results

Among the 200 CBCT scans, 131 belonged to male patients and 69 scans belonged to female subjects within the age group of 18–65 years (mean age 41.32 years). AMOs were found in 142 maxillary antra (35.5 %). The inter-observer reliability for using CBCT to detect AMO was (k = 0.83). There was no significant difference in the frequency of AMOs when the age (P = 0.19) and gender (P = 0.54) distribution were considered. Sinuses with AMOs, showed significantly greater frequency of MTs (p = 0.001). AMOs with maximal length of less than 1mm were most commonly observed (51.40 %). AMOs with larger greater maximal length were associated with higher degrees of MT. The location of the AMOs, were not affected by the degree of MT.

Conclusions

The study demonstrates a clear association between degree of MT and occurrence of AMO in the maxillary sinus. However, the location of the AMO is independent of the degree of the MT. There is a greater probability of finding an AMO in the maxillary sinus if the MT in the sinus is more than 3 mm.
A new quantitative evaluation system for distal radioulnar joint instability using a three-dimensional electromagnetic sensor
Authors: Mukohara Shintaro , Mifune Yutaka , Inui Atsuyuki , Nishimoto Hanako , Kurosawa Takashi , Yamaura Kohei , Yoshikawa Tomoya , Shinohara Issei , Hoshino Yuichi , Nagamune Kouki , Kuroda Ryosuke
Published: July 2021

Background

The accurate assessment of distal radioulnar joint (DRUJ) instability is still challenging as there is no established objective evaluation method. This study aimed to develop a noninvasive measurement method using a three-dimensional electromagnetic sensor system (EMS) to quantitatively assess and characterize the normal DRUJ movement in healthy volunteers.

Methods

The DRUJ movement was mimicked using both a block model and saw bone. Movement of the models was measured by EMS, and the accuracy and reproducibility of the measurements were assessed. In vivo measurement was performed in a sitting position with the elbow flexed and the forearm pronated. One sensor each was attached to the distal radial shaft and the ulnar head. The examiners fixed the distal radius and the carpal bones, moved the ulnar head from the dorsal to the volar side and measured the dorsovolar translation. The volar translation was measured by EMS and ultrasonography, and the correlation coefficient was calculated. The dorsovolar translation was evaluated in 14 healthy volunteers (7 men and 7 women) by three hand surgeons. The intraclass and inter-rater correlation coefficients (ICCs), the differences between the dominant and non-dominant sides and between men and women were assessed.

Results

The accuracy and reproducibility assessment results of the EMS showed high accuracy and reproducibility. In the comparison between EMS and ultrasonography, the correlation coefficient was 0.920 (p= 0.16 × 10-3). The ICC (1,5) for the intra-rater reliability was 0.856, and the ICC (2,5) for inter-rater reliability was 0.868. The mean ulnar head translation and difference between dominant and non-dominant sides were 6.00 ± 1.16 mm (mean ± SD) and − 0.12 ± 0.40 mm, respectively. There were no significant differences between any of the parameters.

Conclusions

A new measurement method using EMS could evaluate DRUJ movement with high accuracy, reproducibility, and intra- and inter-rater reliability. In healthy volunteers, the dorsovolar ulnar head translation was 6.00 mm. The difference between the dominant and non-dominant sides was < 1.0 mm with no significant difference. EMS provided an objective, non-invasive, real-time assessment of dynamic changes in the DRUJ. These findings could be useful in the treatment of patients with DRUJ instability.
Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly
Authors: Karcher Nicolai , Nigro Eleonora , Punčochář Michal , Blanco-Míguez Aitor , Ciciani Matteo , Manghi Paolo , Zolfo Moreno , Cumbo Fabio , Manara Serena , Golzato Davide , Cereseto Anna , Arumugam Manimozhiyan , Bui Thi Phuong Nam , Tytgat Hanne L. P. , Valles-Colomer Mireia , de Vos Willem M. , Segata Nicola
Published: July 2021

Background

Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored.

Results

We present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila, the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila, that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon.

Conclusions

We uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.
DeepProg: an ensemble of deep-learning and machine-learning models for prognosis prediction using multi-omics data
Authors: Poirion Olivier B. , Jing Zheng , Chaudhary Kumardeep , Huang Sijia , Garmire Lana X.
Published: July 2021

Multi-omics data are good resources for prognosis and survival prediction; however, these are difficult to integrate computationally. We introduce DeepProg, a novel ensemble framework of deep-learning and machine-learning approaches that robustly predicts patient survival subtypes using multi-omics data. It identifies two optimal survival subtypes in most cancers and yields significantly better risk-stratification than other multi-omics integration methods. DeepProg is highly predictive, exemplified by two liver cancer (C-index 0.73–0.80) and five breast cancer datasets (C-index 0.68–0.73). Pan-cancer analysis associates common genomic signatures in poor survival subtypes with extracellular matrix modeling, immune deregulation, and mitosis processes. DeepProg is freely available at https://github.com/lanagarmire/DeepProg
Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma
Authors: Meiller Clément , Montagne François , Hirsch Theo Z. , Caruso Stefano , de Wolf Julien , Bayard Quentin , Assié Jean-Baptiste , Meunier Léa , Blum Yuna , Quetel Lisa , Gibault Laure , Pintilie Ecaterina , Badoual Cécile , Humez Sarah , Galateau-Sallé Françoise , Copin Marie-Christine , Letouzé Eric , Scherpereel Arnaud , Zucman-Rossi Jessica , Le Pimpec-Barthes Françoise , Jaurand Marie-Claude , Jean Didier
Published: July 2021

Background

Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples.

Methods

Intra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic, or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed.

Results

Sequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed the contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment, were observed and led to a switch from a hot to a cold immune profile in three patients.

Conclusions

This comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic, and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support the need for multi-sampling for the implementation of molecular-based precision medicine.
Imaging of gallbladder metastasis
Authors: Cocco Giulio , Delli Pizzi Andrea , Basilico Raffaella , Fabiani Stefano , Taraschi Alessio Lino , Pascucci Luca , Boccatonda Andrea , Catalano Orlando , Schiavone Cosima
Published: July 2021

Gallbladder metastasis (GM) is a rare condition, often with a late diagnosis or detected upon autopsy. There is no extensive literature on the imaging diagnosis of GM. Here we present a comprehensive review of the literature with the aim of helping to interpret the clinical findings and imaging features of such patients. Few studies on GM are reported in literature. GM by melanoma accounts for about 55.6% of cases. The remaining cases origin from breast cancer (13.6%), hepatocellular carcinoma (13.6%), renal cell carcinoma (6.8%), lung cancer (4.5%), lymphoma (3.5%) and gastric cancer (2.4%). The most common clinical presentation of GM is abdominal pain from cholecystitis due to obstruction of the cystic duct. The main ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) findings that clinicians and radiologists should consider in their everyday medical activity were discussed. The diagnosis of GM was often achieved through a combination of more than one imaging modality. In more than 90% of cases, the diagnosis of GM is often late and combined with other organs involvement in the terminal stage of the malignancy. The knowledge of the clinical features and different imaging techniques through careful evaluation of the gallbladder can help to achieve early diagnosis and avoid misdiagnosis or false negative results.
Synthetic data for annotation and extraction of family history information from clinical text
Authors: Brekke Pål H. , Rama Taraka , Pilán Ildikó , Nytrø Øystein , Øvrelid Lilja
Published: July 2021

Background

The limited availability of clinical texts for Natural Language Processing purposes is hindering the progress of the field. This article investigates the use of synthetic data for the annotation and automated extraction of family history information from Norwegian clinical text. We make use of incrementally developed synthetic clinical text describing patients’ family history relating to cases of cardiac disease and present a general methodology which integrates the synthetically produced clinical statements and annotation guideline development. The resulting synthetic corpus contains 477 sentences and 6030 tokens. In this work we experimentally assess the validity and applicability of the annotated synthetic corpus using machine learning techniques and furthermore evaluate the system trained on synthetic text on a corpus of real clinical text, consisting of de-identified records for patients with genetic heart disease.

Results

For entity recognition, an SVM trained on synthetic data had class weighted precision, recall and F1-scores of 0.83, 0.81 and 0.82, respectively. For relation extraction precision, recall and F1-scores were 0.74, 0.75 and 0.74.

Conclusions

A system for extraction of family history information developed on synthetic data generalizes well to real, clinical notes with a small loss of accuracy. The methodology outlined in this paper may be useful in other situations where limited availability of clinical text hinders NLP tasks. Both the annotation guidelines and the annotated synthetic corpus are made freely available and as such constitutes the first publicly available resource of Norwegian clinical text.
Acceleration of performance recovery and competitiveness through non-banking financing in SMEs based on green economy: impact of Covid-19 pandemic
Authors: Sriyono  , Biduri Sarwendah , Proyogi Bayu
Published: July 2021

Many previous studies have examined the effects of Covid-19 on small-medium enterprises but never discussed how to accelerate small-medium enterprise performance. This study aims to accelerate the recovery of small-medium enterprise performance affected by Covid-19. This research type is interpretive qualitative, data validity test using credibility and transferability test, data analysis technique using research data reduction, presenting data, and drawing conclusions. The conclusions obtained in this study are financing coming from non-banks when the Covid-19 pandemic conditions are very beneficial for small-medium enterprises, and small-medium enterprises are still able to compete globally.
In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria
Authors: Askari Parvin , Namaei Mohammad Hasan , Ghazvini Kiarash , Hosseini Mehran
Published: July 2021

Background

Melittin is one of the most studied antimicrobial peptides, and severalin vitroexperiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap betweenin vitroandin vivostudies.

Methods

In the first step,in vitrotoxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR)Acinetobacter baumannii, methicillin-resistantStaphylococcus aureus(MRSA), and KPC-producingKlebsiella pneumonia(KPC-KP) pathogens were tested using bothin vitroandin vivomethods.

Results

Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50value of 4.98 mg/kg in BALB/c mice.In vitroantimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads.

Conclusions

These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.
Loading and release of cancer chemotherapy drugs utilizing simultaneous temperature and pH-responsive nanohybrid
Authors: Dahri Mohammad , Akbarialiabad Hossein , Jahromi Ahmad Miri , Maleki Reza
Published: July 2021

Background

Recently, the development of nanocarriers and the improvement of their biochemical properties have became of great importance. Single-walled carbon nanotubes (SWCNT) have many applications in drug delivery systems (DDS) as a common carbon-based structure. In the current work, the penetration, co-loading, and co-release of Doxorubicin (DOX) and Paclitaxel (PAX), as two cancer chemotherapy agents, were investigated using a novel modified copolymer with functionalized SWCNT.

Results

This study proposes a dual-responsive smart carrier that is sensitive to pH and temperature. The carrier consists of functionalized SWNT and Dimethyl acrylamide-trimethyl chitosan (DMAA-TMC) grafting on SWCNT. This suggested carrier was investigated by utilizing molecular simulations. Interaction energies between DOX, PAX, and carrier as well as the affinity of drugs to the nanocarrier were studied. The energy analysis of drug release and adsorption presented that DOX and PAX delivery using this carrier is selective and sensitive at healthy and cancerous conditions. The attraction of DMAA-TMC, as a biodegradable and biocompatible copolymer, with SWCNT showed that degradation mechanism in acidic environment deformed the copolymer. This leads to a smart release mechanism in an acidic cancerous tissue. Additionally, it improves hydrophilicity, optimum nano-particle size, and cell cytotoxicity concerns.

Conclusions

The simulation results manifested a significant contribution of DMAA-TMC in the adsorption and release of cancer chemotherapy drugs in normal and neoplastic tissues. The interaction of copolymer also improves the biocompatibility and biodegradability of the SWCNT. Smart drug delivery carrier can be a valuable nanohybrid for loading, transporting, and releasing of cancer chemotherapy drugs.

Graphical abstract
Short antimicrobial peptidomimetic SAMP-5 effective against multidrug-resistant gram-negative bacteria
Authors: Kim Eun Young , Han So Hee , Kim Jong Min , Kim Seon-Myung , Shin Song Yub
Published: July 2021

SAMP-5 is a short histidine-derived antimicrobial peptidomimetic with pendant dialkylated tail. In this study, we evaluated the potential of SAMP-5 as an antimicrobial agent to combat multidrug-resistant gram-negative bacteria. SAMP-5 showed potent antimicrobial activity (minimum inhibitory concentration 16-64 μg/ml) comparable to melittin against multidrug-resistant Escherichia coli (MDREC) and multidrug-resistant (MDRPA). SAMP-5 displayed no cytotoxicity against three mammalian cells such as mouse macrophage RAW264.7, mouse embryonic fibroblast NIH-3T3, and human bone marrow SH-SY5Y cells at the concentration of 128 μg/ml. SAMP-5 showed resistance to proteolytic degradation with pepsin, trypsin, α-chymotrypsin, and proteinase K. Importantly, unlike ciprofloxacin, no antibiotic resistance against SAMP-5 arose for Pseudomonas aeruginosa during 7 days of serial passage at 0.5 × MIC. Moreover, SAMP-5 showed synergy or additive effects against MDRPA and MDREC, when it combined with chloramphenicol, ciprofloxacin, and oxacillin. Collectively, our results suggested that SAMP-5 is a promising alternative and adjuvant to treat infections caused by multidrug-resistant gram-negative bacteria.
Permeable characteristics of surface film deposited on LiMn2O4 positive electrode revealed by redox-active indicator
Authors: Kim Hyun-seung , Yang Jin Hyuk , Han Ji Woo , Thao Le Thi , Ryu Ji Heon , Oh Seung M. , Kim Ki Jae
Published: July 2021

Herein, the ferrocene redox indicator-based surface film characteristics of spinel lithium manganese oxide (LMO) were evaluated. The pre-cycling of spinel LMO generated a film on the LMO surface. The surface film deposited on LMO surface suppresses further electrolyte decomposition, while the penetration of approximately 0.7 nm-sized redox indicator is not prevented. The facile self-discharge of LMO and regeneration current from the ferrocenium molecule was observed from the redox indicator in a specifically designed four-electrode cell. From this electrochemical behavior, a small-sized HF molecule attack on the LMO surface through a carbonate-based electrolyte-derived film is defined; hence, the prevention of small-sized molecules into the deposited surface film is crucial for the enhancement of LiMn2O4-based lithium-ion batteries.
Pathogenesis and management of gastrointestinal inflammation and fibrosis: from inflammatory bowel diseases to endoscopic surgery
Authors: Iwata Kentaro , Mikami Yohei , Kato Motohiko , Yahagi Naohisa , Kanai Takanori
Published: July 2021

Gastrointestinal fibrosis is a state of accumulated biological entropy caused by a dysregulated tissue repair response. Acute or chronic inflammation in the gastrointestinal tract, including inflammatory bowel disease, particularly Crohn’s disease, induces fibrosis and strictures, which often require surgical or endoscopic intervention. Recent technical advances in endoscopic surgical techniques raise the possibility of gastrointestinal stricture after an extended resection. Compared to recent progress in controlling inflammation, our understanding of the pathogenesis of gastrointestinal fibrosis is limited, which requires the development of prevention and treatment strategies. Here, we focus on gastrointestinal fibrosis in Crohn’s disease and post-endoscopic submucosal dissection (ESD) stricture, and we review the relevant literature.
The need for adaptable global guidance in health systems strengthening for musculoskeletal health: a qualitative study of international key informants
Authors: Briggs Andrew M. , Jordan Joanne E. , Kopansky-Giles Deborah , Sharma Saurab , March Lyn , Schneider Carmen Huckel , Mishrra Swatee , Young James J. , Slater Helen
Published: July 2021

Background

Musculoskeletal (MSK) conditions, MSK pain and MSK injury/trauma are the largest contributors to the global burden of disability, yet global guidance to arrest the rising disability burden is lacking. We aimed to explore contemporary context, challenges and opportunities at a global level and relevant to health systems strengthening for MSK health, as identified by international key informants (KIs) to inform a global MSK health strategic response.

Methods

An in-depth qualitative study was undertaken with international KIs, purposively sampled across high-income and low and middle-income countries (LMICs). KIs identified as representatives of peak global and international organisations (clinical/professional, advocacy, national government and the World Health Organization), thought leaders, and people with lived experience in advocacy roles. Verbatim transcripts of individual semi-structured interviews were analysed inductively using a grounded theory method. Data were organised into categories describing 1) contemporary context; 2) goals; 3) guiding principles; 4) accelerators for action; and 5) strategic priority areas (pillars), to build a data-driven logic model. Here, we report on categories 1–4 of the logic model.

Results

Thirty-one KIs from 20 countries (40% LMICs) affiliated with 25 organisations participated. Six themes described contemporary context (category 1): 1) MSK health is afforded relatively lower priority status compared with other health conditions and is poorly legitimised; 2) improving MSK health is more than just healthcare; 3) global guidance for country-level system strengthening is needed; 4) impact of COVID-19 on MSK health; 5) multiple inequities associated with MSK health; and 6) complexity in health service delivery for MSK health. Five guiding principles (category 3) focussed on adaptability; inclusiveness through co-design; prevention and reducing disability; a lifecourse approach; and equity and value-based care. Goals (category 2) and seven accelerators for action (category 4) were also derived.

Conclusion

KIs strongly supported the creation of an adaptable global strategy to catalyse and steward country-level health systems strengthening responses for MSK health. The data-driven logic model provides a blueprint for global agencies and countries to initiate appropriate whole-of-health system reforms to improve population-level prevention and management of MSK health. Contextual considerations about MSK health and accelerators for action should be considered in reform activities.
Hypothermic treatment reduces matrix metalloproteinase-9 expression and damage in the liver following asphyxial cardiac arrest in rats
Authors: Kim Donghwi , Kim Bora , Sim Hyejin , Lee Tae-Kyeong , Tae Hyun-Jin , Lee Jae-Chul , Park Joon Ha , Cho Jun Hwi , Won Moo-Ho , Park Yoonsoo , Ahn Ji Hyeon
Published: July 2021

Background

Hypothermic treatment is known to protect organs against cardiac arrest (CA) and improves survival rate. However, few studies have evaluated the effects of hypothermia on CA-induced liver damages. This study was designed to analyzed the possible protective effects of hypothermia on the liver after asphyxial CA (ACA). Rats were randomly subjected to 5 min of ACA followed by return of spontaneous circulation (ROSC). Body temperature was controlled at 37 ± 0.5 °C (normothermia group) or 33 ± 0.5 °C (hypothermia group) for 4 h after ROSC. Liver tissues were extracted and examined at 6 h, 12 h, 1 day, and 2 days after ROSC.

Results

The expression of infiltrated neutrophil marker CD11b and matrix metallopeptidase-9 (MMP9) was investigated via immunohistochemistry. Morphological damage was assessed via hematoxylin and eosin (H & E) staining. Hypothermic treatment improved the survival rate at 6 h, 12 h, 1 day, and 2 days after ACA. Based on immunohistochemical analysis, the expression of CD11b and MMP9 was significantly increased from 6 h after ACA in the normothermia group. However, the expressions of CD11b and MMP9 was significantly decreased in the hypothermia group compared with that of the normothermia group. In addition, in the results of H & E, sinusoidal dilatation and vacuolization were apparent after ACA; however, these ACA-induced structural changes were reduced by the 4 h-long hypothermia.

Conclusions

In conclusion, hypothermic treatment for 4 h inhibited the increases in CD11b and MMP9 expression and reduced the morphological damages in the liver following ACA in rats. This study suggests that hypothermic treatment after ACA reduces liver damages by regulating the expression of CD11b and MMP9.
How does manufacturing output affect export behaviors in emerging market economies? Evidence from a dynamic panel ARDL for ten biggest emerging market economies
Authors: Sankaran Arumugam , Krishna Arjun , Vadivel Arjunan
Published: July 2021

Realizing the export-led economic growth potential, the study aims to check the dynamic influence of manufacturing output premised on learning effects model on the export behavior of emerging market economies. Among the mean group and pooled mean group models in the umbrella method of autoregressive-distributed lag econometric technique, the latter one was chosen as it has added advantages. Also, it is supported by the Hausman test. The findings articulate that manufacturing value-added is an important ingredient, which influences the export testifying the existence of dynamic learning effects in export growth. A dynamic model of acquiring sophistication among exporters pinpoints the learning effects technique of exports. The export competitiveness is actualized through a dynamic learning process. The policy suggestion in this regard is to pace up mechanization of the economies, foster measures to reduce supply rigidities and labor market inflexibilities, and assist small and medium-scale enterprises and other types of firms in finding fresh avenues of long-term investment from foreign and advocating domestic supplies.
Associations Between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus
Authors: Wu Chi-Shin , Hsu Le-Yin , Pan Yi-Jiun , Wang Shi-Heng
Published: July 2021

Context

Comorbid depression in patients with diabetes deteriorates the prognosis. Antidepressants might attenuate the adverse effects of depression; however, they are associated with cardiometabolic adverse effects.

Objective

This study aimed to explore the association between antidepressant treatment and advanced diabetic complications and mortality among patients with depression and diabetes mellitus.

Methods

We conducted a nationwide retrospective cohort study of 36 276 patients with depression and newly treated diabetes mellitus using Taiwan’s universal health insurance database. Antidepressant treatment patterns within a 6-month window were classified into none, poor, partial, and regular use, and we accounted for time-dependent variables in the Cox proportional hazards regression analysis with adjustment for time-dependent comorbidity and concomitant use of medications. Different classes of antidepressants were compared. Macro- and microvascular complications, as well as all-cause mortality, were the main outcomes. Benzodiazepines were chosen as negative control exposure.

Results

Compared with poor use of antidepressants, regular use was associated with a 0.92-fold decreased risk of macrovascular complications and a 0.86-fold decreased risk of all-cause mortality but not associated with microvascular complications. Regular use of selective serotonin reuptake inhibitors was associated with a 0.83- and 0.75-fold decreased risk of macrovascular complications and all-cause mortality, respectively. Regular use of tricyclic or tetracyclic antidepressants was associated with a 0.78-fold decreased risk of all-cause mortality. Regular use of benzodiazepine showed no association with diabetic outcomes.

Conclusion

Regular antidepressant use was associated with lower risk of advanced diabetic complications compared with poor adherence. Clinicians should emphasize antidepressant treatment adherence among patients with depression and diabetes mellitus.