bluuebunny/crossref_metadata_2025 huggingface dataset:
Propionic acid disrupts endocytosis, cell cycle, and cellular respiration in yeast
Authors: Micalizzi Emma W. , Golshani Ashkan , Smith Myron L.
Published: August 2021

Objective

We previously identified propionic acid as a microbially-produced volatile organic compound with fungicidal activity against several pathogenic fungi. The purpose of this work is to better understand how propionic acid affects fungi by examining some of the effects of this compound on the yeast cell.

Results

We show that propionic acid causes a dramatic increase in the uptake of lucifer yellow in yeast cells, which is consistent with enhanced endocytosis. Additionally, using a propidium iodide assay, we show that propionic acid treatment causes a significant increase in the proportion of yeast cells in G1 and a significant decrease in the proportion of cells in G2, suggesting that propionic acid causes a cell cycle arrest in yeast. Finally, we show that the reduction of MTT is attenuated in yeast cells treated with propionic acid, indicating that propionic acid disrupts cellular respiration. Understanding the effects of propionic acid on the yeast cell may aid in assessing the broader utility of this compound.
Application of bacteriophage as food preservative to control enteropathogenic Escherichia coli (EPEC)
Authors: Waturangi Diana Elizabeth , Kasriady Cecillia Pingkan , Guntama Geofany , Sahulata Amelinda Minerva , Lestari Diana , Magdalena Stella
Published: August 2021

Objectives

This study was conducted to characterize lytic bacteriophages infecting enteropathogenic Escherichia coli (EPEC) on several types of food and analyze their ability as phage biocontrol to be used as a food preservative. Characterization was done for bacteriophage morphology and stability, along with the determination of minimum multiplicity of infection (miMOI), and application of bacteriophage in the food matrix.

Results

Out of the five samples, BL EPEC bacteriophage exhibited the highest titer of 2.05  ×  109 PFU/mL, with a wide range of pH tolerance, and high thermal tolerance. BL EPEC also showed the least reduction after 168 h of incubation, with a rate of 0.90  ×  10–3 log10 per hour. Bacteriophages from BL EPEC and CS EPEC showed an ideal value of miMOI of 0.01. As a food preservative, BL EPEC bacteriophage was able to reduce bacteria in food samples with a reduction above 0.24 log10 in lettuce and approximately 1.84 log10 in milk. From this study we found that BL EPEC bacteriophage showed the greatest potential to be used as phage biocontrol to improve food safety
Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer
Authors: Soto Javier Andrés , Rodríguez-Antolín Carlos , Vera Olga , Pernía Olga , Esteban-Rodríguez Isabel , Dolores Diestro Maria , Benitez Javier , Sánchez-Cabo Fátima , Alvarez Rafael , De Castro Javier , Ibanez de Cáceres Inmaculada
Published: August 2021

Background

In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies.

Methods

We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls.

Results

We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines.

Conclusions

Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient’s progression and therapeutic response.
Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer
Authors: Silva Romina , Moran Bruce , Baird Anne-Marie , O’Rourke Colm J. , Finn Stephen P. , McDermott Ray , Watson William , Gallagher William M. , Brennan Donal J. , Perry Antoinette S.
Published: August 2021

Background

Disease progression and therapeutic resistance are hallmarks of advanced stage prostate cancer (PCa), which remains a major cause of cancer-related mortality around the world. Longitudinal studies, coupled with the use of liquid biopsies, offer a potentially new and minimally invasive platform to study the dynamics of tumour progression. Our aim was to investigate the dynamics of personal DNA methylomic profiles of metastatic PCa (mPCa) patients, during disease progression and therapy administration.

Results

Forty-eight plasma samples from 9 mPCa patients were collected, longitudinally, over 13–21 months. After circulating cell-free DNA (cfDNA) isolation, DNA methylation was profiled using the Infinium MethylationEPIC BeadChip. The top 5% most variable probes across time, within each individual, were utilised to study dynamic methylation patterns during disease progression and therapeutic response. Statistical testing was carried out to identify differentially methylated genes (DMGs) in cfDNA, which were subsequently validated in two independent mPCa (cfDNA and FFPE tissue) cohorts. Individual cfDNA global methylation patterns were temporally stable throughout the disease course. However, a proportion of CpG sites presented a dynamic temporal pattern that was consistent with clinical events, including different therapies, and were prominently associated with genes linked to immune response pathways. Additionally, study of the tumour fraction of cfDNA identified > 2000 DMGs with dynamic methylation patterns.

Conclusions

Longitudinal assessment of cfDNA methylation in mPCa patients unveiled dynamic patterns associated with disease progression and therapy administration, thus highlighting the potential of using liquid biopsies to study PCa evolution at a methylomic level.
HDAC6 inactivates Runx2 promoter to block osteogenesis of bone marrow stromal cells in age-related bone loss of mice
Authors: Ma Chao , Gao Juan , Liang Jun , Dai Weixiang , Wang Zhenfei , Xia Mengjiao , Chen Tao , Huang Sen , Na Jian , Xu Long , Feng Shiming , Dai Kerong , Liu Guangwang
Published: August 2021

Background

Senile osteoporosis can cause bone fragility and increased risk for fractures and has been one of the most prevalent and severe diseases affecting the elderly population worldwidely. The underlying mechanisms are currently intensive areas of investigation. In age-related bone loss, decreased bone formation overweighs increased bone resorption. The molecular mechanisms underlying defective bone formation in age-related bone loss are not completely understood. In particular, the specific role of histone acetylation in age-related bone loss has not been examined thoroughly.

Methods

We employed 6- and 18-month-old mice to investigate the mechanisms of defective bone formation in age-related bone loss. Bone marrow stromal cells (BMSCs) were induced to undergo in vitro osteogenic differentiation. Chromatin immunoprecipitation (ChIP) was used to investigate the binding of histone deacetylases (HDACs) on Runx2 promoter in BMSCs. Luciferase reporter and transient transfection assay were employed to study Runx2 gene expression modulation by HDAC and androgen receptor (AR). siRNA and HDAC6 inhibitor, Tubastatin A, were used to inhibit HDAC6 in vitro. And systemic administration of Tubastatin A was used to block HDAC6 in vivo.

Results

Age-related trabecular bone loss was observed in 18-month-old mice compared with 6-month-old mice. In vitro osteogenic differentiation potential of BMSCs from 18-month-old mice was weaker than 6-month-old mice, in which there was Runx2 expression inactivation in BMSCs of 18-month-old mice compared with 6-month-old mice, which was attributable to HDAC6-mediated histone hypoacetylation in Runx2 promoter. There was competitive binding of HDAC6 and AR on Runx2 promoter to modulate Runx2 expression in BMSCs. More importantly, through siRNA- or specific inhibitor-mediated HDAC6 inhibition, we could activate Runx2 expression, rescue in vitro osteogenesis potential of BMSCs, and alleviate in vivo age-related bone loss of mice.

Conclusion

HDAC6 accumulation and histone hypoacetylation on Runx2 promoter contributed to the attenuation of in vitro osteogenic differentiation potential of BMSCs from aged mice. Through HDAC6 inhibition, we could activate Runx2 expression and osteogenic differentiation potential of BMSCs from aged mice and alleviate the age-related bone loss of aged mice. Our study will benefit not only for understanding the age-related bone loss, but also for finding new therapies to treat senile osteoporosis.
Pimecrolimus interferes the therapeutic efficacy of human mesenchymal stem cells in atopic dermatitis by regulating NFAT-COX2 signaling
Authors: Shin Nari , Jung Namhee , Lee Seung-Eun , Kong Dasom , Kim Nam Gyo , Kook Myung Geun , Park Hwanhee , Choi Soon Won , Lee Seunghee , Kang Kyung-Sun
Published: August 2021

Background

Human mesenchymal stem cells (hMSCs) therapy has recently been considered a promising treatment for atopic dermatitis (AD) due to their immunomodulation and tissue regeneration ability. In our previous studies, we demonstrated that hMSCs alleviate allergic inflammation in murine AD model by inhibiting the activation of mast cells and B cells. Also our phase I/IIa clinical trial showed clinical efficacy and safety of hMSCs in moderate-to-severe adult AD patients. However, hMSCs therapy against atopic dermatitis have had poor results in clinical field. Therefore, we investigated the reason behind this result. We hypothesized that drug–cell interaction could interfere with the therapeutic efficacy of stem cells, and investigated whether coadministration with pimecrolimus, one of the topical calcineurin inhibitors, could influence the therapeutic potential of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) in AD.

Methods

hUCB-MSCs were subcutaneously injected to AD-induced mice with or without pimecrolimus topical application. To examine whether pimecrolimus influenced the immunomodulatory activity of hUCB-MSCs, hUCB-MSCs were treated with pimecrolimus.

Results

Pimecrolimus disturbed the therapeutic effect of hUCB-MSCs when they were co-administered in murine AD model. Moreover, the inhibitory functions of hUCB-MSCs against type 2 helper T (Th2) cell differentiation and mast cell activation were also deteriorated by pimecrolimus treatment. Interestingly, we found that pimecrolimus decreased the production of PGE2, one of the most critical immunomodulatory factors in hUCB-MSCs. And we demonstrated that pimecrolimus downregulated COX2-PGE2axis by inhibiting nuclear translocation of NFAT3.

Conclusions

Coadministration of pimecrolimus with hMSCs could interfere with the therapeutic efficacy of hMSCs in atopic dermatitis, and this is the first study that figured out the interaction of hMSCs with other drugs in cell therapy of atopic dermatitis. Therefore, this study might give rise to improvement of the clinical application of hMSCs therapy and facilitate the widespread application of hMSCs in clinical field.
A novel conjunctive microenvironment derived from human subcutaneous adipose tissue contributes to physiology of its superficial layer
Authors: Baptista Leandra Santos , Côrtes Isis , Montenegro Bianca , Claudio-da-Silva Cesar , Bouschbacher Marielle , Jobeili Lara , Auxenfans Celine , Sigaudo-Roussel Dominique
Published: August 2021

Background

In human subcutaneous adipose tissue, the superficial fascia distinguishes superficial and deep microenvironments showing extensions called retinacula cutis. The superficial subcutaneous adipose tissue has been described as hyperplastic and the deep subcutaneous adipose tissue as inflammatory. However, few studies have described stromal-vascular fraction (SVF) content and adipose-derived stromal/stem cells (ASCs) behavior derived from superficial and deep subcutaneous adipose tissue. In this study, we analyzed a third conjunctive microenvironment: the retinacula cutis superficialis derived from superficial subcutaneous adipose tissue.

Methods

The samples of abdominal human subcutaneous adipose tissue were obtained during plastic aesthetic surgery in France (Declaration DC-2008-162) and Brazil (Protocol 145/09).

Results

The SVF content was characterized in situ by immunofluorescence and ex vivo by flow cytometry revealing a high content of pre-adipocytes rather in superficial subcutaneous adipose tissue microenvironment. Adipogenic assays revealed higher percentage of lipid accumulation area in ASCs from superficial subcutaneous adipose tissue compared with retinacula cutis superficialis (p < 0.0001) and deep subcutaneous adipose tissue (p < 0.0001). The high adipogenic potential of superficial subcutaneous adipose tissue was corroborated by an up-regulation of adipocyte fatty acid-binding protein (FABP4) compared with retinacula cutis superficialis (p < 0.0001) and deep subcutaneous adipose tissue (p < 0.0001) and of C/EBPα (CCAAT/enhancer-binding protein alpha) compared with retinacula cutis superficialis (p < 0.0001) and deep subcutaneous adipose tissue (p < 0.0001) microenvironments. Curiously, ASCs from retinacula cutis superficialis showed a higher level of adiponectin receptor gene compared with superficial subcutaneous adipose tissue (p = 0.0409), widely known as an anti-inflammatory hormone. Non-induced ASCs from retinacula cutis superficialis showed higher secretion of human vascular endothelial growth factor (VEGF), compared with superficial (p = 0.0485) and deep (p = 0.0112) subcutaneous adipose tissue and with adipogenic-induced ASCs from superficial (p = 0.0175) and deep (p = 0.0328) subcutaneous adipose tissue. Furthermore, ASCs from retinacula cutis superficialis showed higher secretion of Chemokine (C–C motif) ligand 5 (CCL5) compared with non-induced (p = 0.0029) and induced (p = 0.0089) superficial subcutaneous adipose tissue.

Conclusions

This study highlights the contribution to ASCs from retinacula cutis superficialis in their angiogenic property previously described for the whole superficial subcutaneous adipose tissue besides supporting its adipogenic potential for superficial subcutaneous adipose tissue.
Targeted gene correction and functional recovery in achondroplasia patient-derived iPSCs
Authors: Zou Huan , Guan Mingfeng , Li Yundong , Luo Fang , Wang Wenyuan , Qin Yiren
Published: August 2021

Background

Achondroplasia (ACH) is the most common genetic form of dwarfism and belongs to dominant monogenic disorder caused by a gain-of-function point mutation in the transmembrane region of FGFR3. There are no effective treatments for ACH. Stem cells and gene-editing technology provide us with effective methods and ideas for ACH research and treatment.

Methods

We generated non-integrated iPSCs from an ACH girl’s skin and an ACH boy’s urine by Sendai virus. The mutation of ACH iPSCs was precisely corrected by CRISPR-Cas9.

Results

Chondrogenic differentiation ability of ACH iPSCs was confined compared with that of healthy iPSCs. Chondrogenic differentiation ability of corrected ACH iPSCs could be restored. These corrected iPSCs displayed pluripotency, maintained normal karyotype, and demonstrated none of off-target indels.

Conclusions

This study may provide an important theoretical and experimental basis for the ACH research and treatment.
Bioreactance reliably detects preload responsiveness by the end-expiratory occlusion test when averaging and refresh times are shortened
Authors: Gavelli Francesco , Beurton Alexandra , Teboul Jean-Louis , De Vita Nello , Azzolina Danila , Shi Rui , Pavot Arthur , Monnet Xavier
Published: August 2021

Background

The end-expiratory occlusion (EEXPO) test detects preload responsiveness, but it is 15 s long and induces small changes in cardiac index (CI). It is doubtful whether the Starling bioreactance device, which averages CI over 24 s and refreshes the displayed value every 4 s (Starling-24.4), can detect the EEXPO-induced changes in CI (ΔCI). Our primary goal was to test whether this Starling device version detects preload responsiveness through EEXPO. We also tested whether shortening the averaging and refresh times to 8 s and one second, respectively, (Starling-8.1) improves the accuracy of the device in detecting preload responsiveness using EEXPO.

Methods

In 42 mechanically ventilated patients, during a 15-s EEXPO, we measured ∆CI through calibrated pulse contour analysis (CIpulse, PiCCO2 device) and using the Starling device. For the latter, we considered both CIStarling-24.4 from the commercial version and CIStarling-8.1 derived from the raw data. For relative ∆CIStarling-24.4 and ∆CIStarling-8.1 during EEXPO, we calculated the area under the receiver operating characteristic curve (AUROC) to detect preload responsiveness, defined as an increase in CIpulse ≥ 10% during passive leg raising (PLR). For both methods, the correlation coefficient vs. ∆CIpulse was calculated.

Results

Twenty-six patients were preload responders and sixteen non preload-responders. The AUROC for ∆CIStarling-24.4 was significantly lower compared to ∆CIStarling-8.1 (0.680 ± 0.086 vs. 0.899 ± 0.049, respectively; p = 0.027). A significant correlation was observed between ∆CIStarling-8.1 and ∆CIpulse (r = 0.42; p = 0.009), but not between ∆CIStarling-24.4 and ∆CIpulse. During PLR, both ∆CIStarling-24.4 and ∆CIStarling-8.1 reliably detected preload responsiveness.

Conclusions

Shortening the averaging and refresh times of the bioreactance signal to 8 s and one second, respectively, increases the reliability of the Starling device in detection of EEXPO-induced ∆CI.

Trial registration: No. IDRCB:2018-A02825-50. Registered 13 December 2018.
Continuous energy consumption measure approach using a DMA double-buffering technique
Authors: Vaquerizo-Hdez Daniel , Muñoz Pablo , Barrero David F. , R-Moreno Maria D.
Published: August 2021

Measuring the consumption of electronic devices is a difficult and sensitive task. Data acquisition (DAQ) systems are often used to determine such consumption. In theory, measuring energy consumption is straight forward, just by acquiring current and voltage signals we can determine the consumption. However, a number of issues arise when a fine analysis is required. The main problem is that sampling frequencies have to be high enough to detect variations in the assessed signals over time. In that regard, some popular DAQ systems are based on RISC ARM processors for microcontrollers combined with analog-to-digital converters to meet high-frequency acquisition requirements. The efficient use of direct memory access (DMA) modules combined with pipelined processing in a microcontroller allows to improve the sample rate overcoming the processing time and the internal communication protocol limitations. This paper presents a novel approach for high-frequency energy measurement composed of a DMA rate improvement (data acquisition logic), a data processing logic and a low-cost hardware. The contribution of the paper is the combination of a double-buffered signal acquisition mechanism and an algorithm that computes the device’s energy consumption using parallel data processing. The combination of these elements enables a high-frequency (continuous) energy consumption measurement of an electronic device, improving the accuracy and reducing the cost of existing systems. We have validated our approach by measuring the energy consumed by elemental circuits and wireless sensors networks (WSNs) motes. The results indicate that the energy measurement error is less than 5% and that the proposed method is suitable to measure WSN motes even during sleep cycles, enabling a better characterization of their consumption profile.
Patient-reported outcome measures in pediatric palliative care—a protocol for a scoping review
Authors: Holmen Heidi , Winger Anette , Steindal Simen A. , Castor Charlotte , Kvarme Lisbeth Gravdal , Riiser Kirsti , Mariussen Kari L. , Lee Anja
Published: August 2021

Background

In pediatric palliative care (PPC), there is a need to involve the child’s voice in situations regarding their symptoms and care needs. Patient-reported outcome measures (PROMs) can be tools to systematically gather data reported from the child or a proxy if the child is not capable to self-report in order to provide the services they need. There has been a rapid development in PROM research the last decade, and there is a need for an overview of current knowledge and experiences in the field. Thus, we aim to explore and summarize what is known from the published research about PROMs in PPC.

Methods

We propose a scoping review following the framework by Arksey and O’Malley and the PRISMA Extension for Scoping Reviews checklist. A systematic search will be performed in the following databases: Medical Literature Analysis and Retrieval System Online (Medline), Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), American Psychological Association (APA) PsycInfo, Health and Psychosocial Instruments (HaPI), and Allied and Complementary Medicine Database (AMED). The search will be followed by snowballing to identify key papers and significant researchers for additional citations. Covidence will facilitate the independent review of eligible citations, and data will be extracted and presented descriptively, and thematically analyzed using NVivo.

Discussion

The scoping review suggested in this protocol will identify PROMs which have been proposed in PPC and clarify the experiences with their use. The findings of this review will be relevant for researchers and healthcare personnel caring for children and adolescents in PPC. In addition, by highlighting knowledge gaps about the use of PROMs in PPC, this review will point out future needs within this field of research, which is crucial for improving quality of care in PPC.

Systematic review registration

https://osf.io/yfch2/.
Security-Aware computation offloading for Mobile edge computing-Enabled smart city
Authors: Peng Kai , Liu Peichen , Tao Peng , Huang Qingjia
Published: August 2021

Smart city has obtained increasing attention from both academic and industry which has the potential to improve human living standards. A smart city consists of a great number of smart devices which are generating large amounts of data and emerging applications all the time. However, the computing capacity of smart devices are limited. Fortunately, the emergence of MEC can solve the above problem. However, the resources of edge servers in MEC are limited and the capabilities of edge servers are heterogeneous. It is important to improve the average resource utilization of all edge servers and keep load balancing of edge server cluster simultaneously. On the other hand, quite a few numbers of applications are delay-sensitive, it is necessary to ensure the security of these applications. In this paper, we consider joint optimization of mobile device and edge server in MEC-enabled smart city, improving the overall performance of the system. Technically, a new multi-objective computation offloading method is implemented to reduce time consumption, energy consumption, and keep load balancing of edge servers, as well as increase average resource utilization of edge servers while meeting the deadline constraint of delay-sensitive applications. Sufficient experiments have been conducted to prove the effectiveness and superiority of our proposed method in different scenarios.
Assessing parents’ awareness about children’s “first thousand days of life”: a descriptive and analytical study
Authors: Bagheri Fatemeh , Nakhaee Nouzar , Jahani Yones , Khajouei Reza
Published: August 2021

Background

Many adulthood illnesses are rooted in childhood, especially in the “first thousand days of life”. Despite parents’ role in children’s development, no study has examined parental awareness concerning this period. This study aimed to examine the awareness of parents concerning the “first thousand days of life” and the relationship between parents’ demographics and their awareness.

Methods

This study was conducted on 135 parents in Kerman, Iran, using a valid and reliable questionnaire developed by researchers based on the opinion of experts and relevant references. The relationship between participants’ demographics and their awareness was examined by multiple regression. The relationship between homogeneity of couples’ education degree and awareness was analyzed using ANOVA. Chi-square was used to examine the relationship between information sources and parents’ familiarity and to compare parents’ preferred sources.

Results

The average parental awareness was 41.96 ± 11.90. Eighty-three percent of the parents have not heard about the “first thousand days of life”. The source of information for 57% of the parents was friends and relatives (p < 0.0001). Overall, 87% of the parents desired to know about this period, and 47% liked using mobile applications for information (p < 0.0001).

Conclusions

Parents’ awareness about the “first thousand days of life” is lower than the average. Since the source of information concerning this period for most parents is friends and relatives and most parents are very interested in obtaining information, it is recommended that policy-makers use the capacity of other sources to increase parents’ awareness. Given the greater tendency of parents to obtain information through mobile applications, we suggest investing more in this source.
Technologies for recovery and reuse of plant nutrients from human excreta and domestic wastewater: a protocol for a systematic map and living evidence platform
Authors: Macura Biljana , Thomas James , Metson Geneviève S. , McConville Jennifer R. , Johannesdottir Solveig L. , Seddon Dan , Harder Robin
Published: August 2021

Background

Research and development on the recovery and reuse of nutrients found in human excreta and domestic wastewater has intensified over the past years, continuously producing new knowledge and technologies. However, research impact and knowledge transfer are limited. In particular, uptake and upscaling of new and innovative solutions in practice remain a key challenge. Achieving a more circular use of nutrients thus goes beyond technological innovation and will benefit from a synthesis of existing research being readily available to various stakeholders in the field. The aim of the systematic map and online evidence platform described in this protocol is threefold. First, to collate and summarise scientific research on technologies that facilitate the recovery and reuse of plant nutrients and organic matter found in human excreta and domestic and municipal wastewater. Second, to present this evidence in a way that can be easily navigated by stakeholders. Third, to report on new relevant research evidence to stakeholders as it becomes available.

Methods

Firstly, we will produce a baseline systematic map, which will consist of an extension of two previous related syntheses. In a next stage, with help of machine learning and other automation technologies, the baseline systematic map will be transformed into ‘living mode’ that allows for a continually updated evidence platform. The baseline systematic map searches will be performed in 4 bibliographic sources and Google Scholar. All searches will be performed in English. Coding and meta-data extraction will include bibliographic information, locations as well as the recovery and reuse pathways. The living mode will mostly rely on automation technologies in EPPI-Reviewer and the Microsoft Academic database. The new records will be automatically identified and ranked in terms of eligibility. Records above a certain ‘cut-off’ threshold will be manually screened for eligibility. The threshold will be devised based on the empirically informed machine learning model. The evidence from the baseline systematic map and living mode will be embedded in an online evidence platform that in an interactive manner allows stakeholders to visualise and explore the systematic map findings, including knowledge gaps and clusters.
The curative effect analysis of peripherally inserted central venous catheter catheterization for tumor patients under the guidance of new medical guide wire
Authors: Xiao Weizhu
Published: August 2021

Objective

To report a method of PICC catheterization with the aid of a new medical guide wire, and to discuss the curative effect.

Methods

Five hundred and thirteen patients who visited our hospital from January 2013 to December 2019 for PICC catheterization were selected as study subjects. Random number method was used to group patients. General information was recorded for both groups. Patients in the observation group received catheterization with the aid of a new medical guide wire. The control group received catheterization via conventional guide wire. The success rate of the first catheterization, the success rate of the catheterization, the timing of the catheterization, the complications and the position of the catheter end were compared between the two groups.

Results

There was no significant difference in general information between the two groups. After analyzing the puncture situation of the two groups, it was found that the average catheterization time of the observation group was shorter than that of the control group, and the difference was statistically significant. Patients in the observation group had higher success rate of one-time catheterization and catheterization success rate, and the difference was statistically significant. The incidences of occult thrombosis, phlebitis and catheter blockage in the observation group were lower than those in the control group, and the difference was statistically significant. The incidence of dominant thrombosis and bleeding at puncture point in the observation group was also lower than that in the control group, but the difference was not statistically significant.

Conclusion

The new type of medical guide wire component is effective for PICC catheterization and worthy of further promotion.
Association of rs9939609-FTO with metabolic syndrome components among women from Mayan communities of Chiapas, Mexico
Authors: Ortega Pilar E. Núñez , Meneses María E. , Delgado-Enciso Iván , Irecta-Nájera César Antonio , Castro-Quezada Itandehui , Solís-Hernández Roberto , Flores-Guillén Elena , García-Miranda Rosario , Valladares-Salgado Adán , Locia-Morales Daniel , Ochoa-Díaz-López Héctor
Published: August 2021

Background

Metabolic syndrome (MetS) is a complex cluster of risk factors, considered as a polygenic and multifactorial entity. The objective of this study was to determine the association of rs9939609-FTO polymorphism and MetS components in adult women of Mayan communities of Chiapas.

Methods

In a cross-sectional study, sociodemographic, anthropometric, clinical, and biochemical data were obtained from 291 adult women from three regions of Chiapas, Mexico. The prevalence of MetS and the allele and genotype frequencies of the rs9939609-FTO were estimated. Multivariate logistic regression models were used to assess the association of the single nucleotide polymorphism (SNP) with each of the MetS components.

Results

The MetS prevalence was 60%. We found a statistically significant association between rs9939609-FTO and hyperglycemia in the dominant model (OR 2.6; 95% CI 1.3–5.3; p = 0.007).

Conclusions

Women from Mayan communities of Chiapas presented a high prevalence of MetS and a relevant association of the FTO variant with hyperglycemia. This is the first study carried out in these Mayan indigenous communities from Chiapas.
The influence of changing reward of electronic consumer goods on burglary and theft offences in Western market-based countries in the years prior to and during the crime drop
Authors: Quinn Liam , Clare Joseph
Published: August 2021

It is widely recognised that burglary and theft offence trends have broadly moved in parallel in ‘Western’ market-based countries since the 1950s. Most researchers have focussed on the trend from the early 1990s onwards, when burglary and theft offence rates plummeted. One major proposed explanation for this trend, relates to improved security. This paper draws on the longitudinal variations in reward of electronic consumer goods to propose a complementary account. This argument is supported by criminological theory, empirical evidence, and historical trends of specific property crime offences. The paper concludes by explaining that reward and security operate in partnership to influence the opportunity for crime, which provides an optimal account for burglary and theft offence trends over the last 40 years.
Longitudinal study on the effects of growth-promoting and therapeutic antibiotics on the dynamics of chicken cloacal and litter microbiomes and resistomes
Authors: Gupta Chhedi Lal , Blum Shlomo E. , Kattusamy Karuppasamy , Daniel Tali , Druyan Shelly , Shapira Roni , Krifucks Oleg , Zhu Yong-Guan , Zhou Xin-Yuan , Su Jian-Qiang , Cytryn Eddie
Published: August 2021

Background

Therapeutic and growth-promoting antibiotics are frequently used in broiler production. Indirect evidence indicates that these practices are linked to the proliferation of antimicrobial resistance (AMR), the spread of antibiotic-resistant bacteria from food animals to humans, and the environment, but there is a lack of comprehensive experimental data supporting this. We investigated the effects of growth promotor (bacitracin) and therapeutic (enrofloxacin) antibiotic administration on AMR in broilers for the duration of a production cycle, using a holistic approach that integrated both culture-dependent and culture-independent methods. We specifically focused on pathogen-harboring families (Enterobacteriaceae,Enterococcaceae, andStaphylococcaceae).

Results

Antibiotic-resistant bacteria and antibiotic resistance genes were ubiquitous in chicken cloaca and litter regardless of antibiotic administration. Environment (cloaca vs. litter) and growth stage were the primary drivers of variation in the microbiomes and resistomes, with increased bacterial diversity and a general decrease in abundance of the pathogen-harboring families with age. Bacitracin-fed groups had higher levels of bacitracin resistance genes and of vancomycin-resistantEnterococcaceae(totalEnterococcaceaecounts were not higher). Although metagenomic analyses classified 28–76% of theEnterococcaceaeas the commensal human pathogensE. faecalisandE. faecium, culture-based analysis suggested that approximately 98% of the vancomycin-resistantEnterococcaceaewere avian and not human-associated, suggesting differences in the taxonomic profiles of the resistant and non-resistant strains. Enrofloxacin treatments had varying effects, but generally facilitated increased relative abundance of multidrug-resistantEnterobacteriaceaestrains, which were primarilyE. coli. Metagenomic approaches revealed a diverse array ofStaphylococcusspp., but the opportunistic pathogenS. aureusand methicillin resistance genes were not detected in culture-based or metagenomic analyses.Camphylobacteriaceaewere significantly more abundant in the cloacal samples, especially in enrofloxacin-treated chickens, where a metagenome-assembledC. jejunigenome harboring fluoroquinolone and β-lactam resistance genes was identified.

Conclusions

Within a “farm-to-fork, one health” perspective, considering the evidence that bacitracin and enrofloxacin used in poultry production can select for resistance, we recommend their use be regulated. Furthermore, we suggest routine surveillance of ESBLE. coli, vancomycin-resistantE. faecalisandE. faecium, and fluoroquinolone-resistantC. jejunistrains considering their pathogenic nature and capacity to disseminate AMR to the environment.
Evaluation of low-pass genome sequencing in polygenic risk score calculation for Parkinson’s disease
Authors: Kim Sungjae , Shin Jong-Yeon , Kwon Nak-Jung , Kim Chang-Uk , Kim Changhoon , Lee Chong Sik , Seo Jeong-Sun
Published: August 2021

Background

Low-pass sequencing (LPS) has been extensively investigated for applicability to various genetic studies due to its advantages over genotype array data including cost-effectiveness. Predicting the risk of complex diseases such as Parkinson’s disease (PD) using polygenic risk score (PRS) based on the genetic variations has shown decent prediction accuracy. Although ultra-LPS has been shown to be effective in PRS calculation, array data has been favored to the majority of PRS analysis, especially for PD.

Results

Using eight high-coverage WGS, we assessed imputation approaches for downsampled LPS data ranging from 0.5 × to 7.0 × . We demonstrated that uncertain genotype calls of LPS diminished imputation accuracy, and an imputation approach using genotype likelihoods was plausible for LPS. Additionally, comparing imputation accuracies between LPS and simulated array illustrated that LPS had higher accuracies particularly at rare frequencies. To evaluate ultra-low coverage data in PRS calculation for PD, we prepared low-coverage WGS and genotype array of 87 PD cases and 101 controls. Genotype imputation of array and downsampled LPS were conducted using a population-specific reference panel, and we calculated risk scores based on the PD-associated SNPs from an East Asian meta-GWAS. The PRS models discriminated cases and controls as previously reported when both LPS and genotype array were used. Also strong correlations in PRS models for PD between LPS and genotype array were discovered.

Conclusions

Overall, this study highlights the potentials of LPS under 1.0 × followed by genotype imputation in PRS calculation and suggests LPS as attractive alternatives to genotype array in the area of precision medicine for PD.
Deubiquitinases in hematological malignancies
Authors: Lei Hu , Wang Jiaqi , Hu Jiacheng , Zhu Qian , Wu Yingli
Published: August 2021

Deubiquitinases (DUBs) are enzymes that control the stability, interactions or localization of most cellular proteins by removing their ubiquitin modification. In recent years, some DUBs, such as USP7, USP9X and USP10, have been identified as promising therapeutic targets in hematological malignancies. Importantly, some potent inhibitors targeting the oncogenic DUBs have been developed, showing promising inhibitory efficacy in preclinical models, and some have even undergone clinical trials. Different DUBs perform distinct function in diverse hematological malignancies, such as oncogenic, tumor suppressor or context-dependent effects. Therefore, exploring the biological roles of DUBs and their downstream effectors will provide new insights and therapeutic targets for the occurrence and development of hematological malignancies. We summarize the DUBs involved in different categories of hematological malignancies including leukemia, multiple myeloma and lymphoma. We also present the recent development of DUB inhibitors and their applications in hematological malignancies. Together, we demonstrate DUBs as potential therapeutic drug targets in hematological malignancies.
Disease-, region- and cell type specific diversity of α-synuclein carboxy terminal truncations in synucleinopathies
Authors: Hass Ethan W. , Sorrentino Zachary A. , Xia Yuxing , Lloyd Grace M. , Trojanowski John Q. , Prokop Stefan , Giasson Benoit I.
Published: August 2021

Synucleinopathies, including Parkinson’s disease (PD), Lewy body dementia (LBD), Alzheimer’s disease with amygdala restricted Lewy bodies (AD/ALB), and multiple system atrophy (MSA) comprise a spectrum of neurodegenerative disorders characterized by the presence of distinct pathological α-synuclein (αSyn) inclusions. Experimental and pathological studies support the notion that αSyn aggregates contribute to cellular demise and dysfunction with disease progression associated with a prion-like spread of αSyn aggregates via conformational templating. The initiating event(s) and factors that contribute to diverse forms of synucleinopathies remain poorly understood. A major post-translational modification of αSyn associated with pathological inclusions is a diverse array of specific truncations within the carboxy terminal region. While these modifications have been shown experimentally to induce and promote αSyn aggregation, little is known about their disease-, region- and cell type specific distribution. To this end, we generated a series of monoclonal antibodies specific to neo-epitopes in αSyn truncated after residues 103, 115, 119, 122, 125, and 129. Immunocytochemical investigations using these new tools revealed striking differences in the αSyn truncation pattern between different synucleinopathies, brain regions and specific cellular populations. In LBD, neuronal inclusions in the substantia nigra and amygdala were positive for αSyn cleaved after residues 103, 119, 122, and 125, but not 115. In contrast, in the same patients' brain αSyn cleaved at residue 115, as well as 103, 119 and 122 were abundant in the dorsal motor nucleus of the vagus. In patients with AD/ALB, these modifications were only weakly or not detected in amygdala αSyn inclusions. αSyn truncated at residues 103, 115, 119, and 125 was readily present in MSA glial cytoplasmic inclusions, but 122 cleaved αSyn was only weakly or not present. Conversely, MSA neuronal pathology in the pontine nuclei was strongly reactive to the αSyn x-122 neo-epitope but did not display any reactivity for αSyn 103 cleavage. These studies demonstrate significant disease-, region- and cell type specific differences in carboxy terminal αSyn processing associated with pathological inclusions that likely contributes to their distinct strain-like prion properties and promotes the diversity displayed in the degrees of these insidious diseases.
Lithosphere–asthenosphere boundary beneath the Sea of Japan from transdimensional inversion of S-receiver functions
Authors: Akuhara Takeshi , Nakahigashi Kazuo , Shinohara Masanao , Yamada Tomoaki , Shiobara Hajime , Yamashita Yusuke , Mochizuki Kimihiro , Uehira Kenji
Published: August 2021

The evolution history of the Sea of Japan back-arc basin remains under debate, involving the opening of sub-basins such as the Japan and Yamato Basins. Detailed knowledge of the lithospheric structure will provide the key to understanding tectonic history. This study identifies the lithosphere–asthenosphere boundary (LAB) beneath the Sea of Japan back-arc basin using S-receiver functions (S-RFs). The study area, including the Japan and Yamato Basins, has been instrumented with broadband ocean-bottom seismometers (OBSs). S-RFs from these OBSs show negative Sp phases preceding the direct S arrivals, suggesting the LAB. The S-RFs also show abnormally reduced amplitudes. For further qualitative interpretation of these findings, we conduct transdimensional Bayesian inversion for S-wave velocity models. This less-subjective Bayesian approach clarifies that the low-velocity seafloor sediments and damped deconvolution contribute to the amplitude reduction, illuminating the necessity of such considerations for similar receiver function works. Inverted velocity structures show a sharp velocity decrease at the mantle depths, which we consider the LAB. The obtained LAB depths vary among sites: ~ 45 km beneath the Japan and Yamato Basins and ~ 70 km beneath the Yamato Rise, a bathymetric high between the two basins. The thick lithosphere beneath the Yamato Rise most likely reflects its continental origin. However, the thickness is still thin compared to that of eastern Asia, suggesting lithosphere extension by rifting. Notably, the Japan and Yamato Basins show a comparable lithospheric thickness, although the crustal thickness beneath the Yamato Basin is known to be anomalously thick. This consistency in the lithospheric thickness implies that both basins undergo similar back-arc opening processes.
Three-dimensional inversion of audio-magnetotelluric data acquired from the crater area of Mt. Tokachidake, Japan
Authors: Tanaka Ryo , Yamaya Yusuke , Tamura Makoto , Hashimoto Takeshi , Okazaki Noritoshi , Takahashi Ryo , Mogi Toru
Published: August 2021

Subvolcanic hydrothermal systems can lead to hydrothermal eruptions as well as unrest phenomena without an eruptive event. Historical eruptions and recent unrest events, including ground inflation, demagnetization, and a gradual decrease in the plume height, at Mt. Tokachidake, central Hokkaido, Japan, are related to such a subvolcanic hydrothermal system. This study investigates the three-dimensional (3-D) resistivity structure of Mt. Tokachidake to image its subvolcanic hydrothermal system. A 3-D inversion of the magnetotelluric data, acquired at 22 sites around the crater area, was performed while accounting for the topography. Our resistivity model was characterized by a high-resistivity layer at a shallow depth (50–100 m) and two conductors near the active crater and dormant crater. The high-resistivity layer was interpreted to be composed of dense lava, which acts as a caprock surrounding the conductor. The high conductivity beneath the active crater can be explained by the presence of hydrothermal fluid in fractured or leached zones within the low-permeability lava layer, as the sources of ground inflation and demagnetization were identified within the conductive zone immediately beneath the resistive layer. The resistivity structure was used to estimate the volume of hydrothermal fluid within the pore space. The minimum volume of hydrothermal fluid beneath the active crater that can explain the resistivity structure was estimated to be 3 × 106 m3. This estimate is comparable to the water volume that was associated with the long runout and highly fluidized lahar in 1926. The resistivity structure and volume of hydrothermal fluid presented in this study can be used as a reference for further numerical simulations, which aim to reveal the mechanisms of recent unrest events and assess the risk of hazards, such as lahar.