bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of MITS counseling and informed consent processes in Pakistan, India, Bangladesh, Kenya, and Ethiopia
Authors: Feroz Anam Shahil , Paganelli Christina , Bunei Milka , Eshetu Beza , Parveen Shahana , Reza Sayyeda , Sanji Chaitali , Tikmani Shiyam Sunder , Goudar Shivaprasad S. , Goudar Guruprasad , Saleem Sarah , McClure Elizabeth M. , Goldenberg Robert L.
Published: August 2020

Globally, more than 5 million stillbirths and neonatal deaths occur annually. For many, the cause of death (CoD) is unknown. Minimally invasive tissue sampling (MITS) has been increasingly used in postmortem examinations for ascertaining the CoD in stillbirths and neonates. Our study compared the counseling and consent methods used in MITS projects in five countries in Africa and south Asia. Key informant interviews were conducted with researchers to describe the characteristics and backgrounds of counselors, the environment and timing of consent and perceived facilitators and barriers encountered during the consent process. Counselors at all sites had backgrounds in social science, psychology and counseling or clinical expertise in obstetrics/gynecology or pediatrics. All counsellors received training about techniques for building rapport and offering emotional support to families; training duration and methods differed across sites. Counselling environments varied significantly; some sites allocated a separate room, others counselled families at the bedside or nursing stations. All counsellors had a central role in explaining the MITS procedure to families in their local languages. Most sites did not use visual aids during the process, relying solely on verbal descriptions. In most sites, parents were approached within one hour of death. The time needed for decision making by families varied from a few minutes to 24 h. In most sites, extended family took part in the decision making. Because many parents wanted burial as soon as possible, counsellors ensured that MITS would be conducted promptly after receiving consent. Barriers to consent included decreased comprehension of information due to the emotional and psychological impact of grief. Moreover, having more family members engaged in decision-making increased the complexity of counselling and achieving consensus to consent for the procedure. While each site adapted their approach to fit the context, consistencies and similarities across sites were observed.
Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia–reperfusion arrhythmias
Authors: Tang Jian , Gao Hong , Liu Yanqiu , Song Jing , Feng Yurong , Wang Guilong , He Youqin
Published: August 2020

Background

Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored.

Methods

Sprague-Dawley (SD) rats were randomly divided into two groups (n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA–mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR).

Results

Eight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA–mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17.

Conclusions

Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia–RA.
Correction to: Very long chain fatty acids are an important marker of nutritional status in patients with anorexia nervosa: a case control study
Authors: Shimizu Miki , Kawai Keisuke , Yamashita Makoto , Shoji Masayasu , Takakura Shu , Hata Tomokazu , Nakashima Megumi , Tatsushima Keita , Tanaka Kazunari , Sudo Nobuyuki
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: LncRNA AK023391 promotes tumorigenesis and invasion of gastric cancer through activation of the PI3K/Akt signaling pathway
Authors: Huang Yanxia , Zhang Jing , Hou Lidan , Wang Ge , Liu Hui , Zhang Rui , Chen Xiaoyu , Zhu Jinshui
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Cancer-associated adipocytes: emerging supporters in breast cancer
Authors: Zhao Chongru , Wu Min , Zeng Ning , Xiong Mingchen , Hu Weijie , Lv Wenchang , Yi Yi , Zhang Qi , Wu Yiping
Published: August 2020

Breast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC.
Transcriptomics of cumulus cells – a window into oocyte maturation in humans
Authors: Wyse Brandon A. , Fuchs Weizman Noga , Kadish Seth , Balakier Hanna , Sangaralingam Mugundhine , Librach Clifford L.
Published: August 2020

Background

Cumulus cells (CC) encapsulate growing oocytes and support their growth and development. Transcriptomic signatures of CC have the potential to serve as valuable non-invasive biomarkers for oocyte competency and potential. The present sibling cumulus-oocyte-complex (COC) cohort study aimed at defining functional variations between oocytes of different maturity exposed to the same stimulation conditions, by assessing the transcriptomic signatures of their corresponding CC. CC were collected from 18 patients with both germinal vesicle and metaphase II oocytes from the same cycle to keep the biological variability between samples to a minimum. RNA sequencing, differential expression, pathway analysis, and leading-edge were performed to highlight functional differences between CC encapsulating oocytes of different maturity.

Results

Transcriptomic signatures representing CC encapsulating oocytes of different maturity clustered separately on principal component analysis with 1818 genes differentially expressed. CCs encapsulating mature oocytes were more transcriptionally synchronized when compared with CCs encapsulating immature oocytes. Moreover, the transcriptional activity was lower, albeit not absent, in CC encapsulating mature oocytes, with 2407 fewer transcripts detected than in CC encapsulating immature (germinal vesicle - GV) oocytes. Hallmark pathways and ovarian processes that were affected by oocyte maturity included cell cycle regulation, steroid metabolism, apoptosis, extracellular matrix remodeling, and inflammation.

Conclusions

Herein we review our findings and discuss how they align with previous literature addressing transcriptomic signatures of oocyte maturation. Our findings support the available literature and enhance it with several genes and pathways, which have not been previously implicated in promoting human oocyte maturation. This study lays the ground for future functional studies that can enhance our understanding of human oocyte maturation.
HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer
Authors: Nanou Afroditi , Zeune Leonie Laura , Bidard Francois-Clement , Pierga Jean-Yves , Terstappen Leonardus Wendelinus Mathias Marie
Published: August 2020

Background

Tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) in the blood of metastatic cancer patients associate with poor outcomes. In this study, we explored the human epidermal growth factor receptor 2 (HER2) expression on CTCs and tdEVs of metastatic breast cancer patients.

Methods

Blood samples from 98 patients (CLCC-IC-2006-04 study) were originally processed with the CellSearch® system using the CTC kit and anti-HER2 as an additional marker in the staining cocktail. CTCs and tdEVs were automatically enumerated from the generated CellSearch images using the open-source ACCEPT software.

Results

CTCs and tdEVs were subdivided based on their cytokeratin (CK) and HER2 phenotype into CK+HER2−, CK−HER2+, and CK+HER2+. The inclusion of anti-HER2 increased the percentage of informative samples with ≥ 1 detectable CTC from 89 to 95%. CK− CTCs and tdEVs correlated equally well with the clinical outcome as CK+ CTCs and tdEVs. Inter- and intra-patient heterogeneity was found for the CTC/tdEV phenotypes, and the presence of 2 or 3 classes of CTCs/tdEVs was associated with worse prognosis compared to a uniform CTC/tdEV phenotype present (1 class). The use of ≥ 7% HER2+CK+ tdEVs can predict HER2 expression of the tissue with 74% sensitivity and specificity using the HER2 amplification status of the primary tumor as a classification variable.

Conclusions

HER2 can be detected on CTCs and tdEVs not expressing CK, and these CK− CTCs/tdEVs have similar clinical relevance to CTCs and tdEVs expressing CK. tdEVs perform better than CTCs in predicting the HER2 status of the primary tissue. CTC and tdEV heterogeneity in the blood of patients is inversely associated with overall survival.
Induction of long-lived potential aestivation states in laboratory An. gambiae mosquitoes
Authors: Krajacich Benjamin J. , Sullivan Margery , Faiman Roy , Veru Laura , Graber Leland , Lehmann Tovi
Published: August 2020

Background

How anopheline mosquitoes persist through the long dry season in Africa remains a gap in our understanding of these malaria vectors. To span this period in locations such as the Sahelian zone of Mali, mosquitoes must either migrate to areas of permanent water, recolonize areas as they again become favorable, or survive in harsh conditions including high temperatures, low humidity, and an absence of surface water (required for breeding). Adult mosquitoes surviving through this season must dramatically extend their typical lifespan (averaging 2–3 weeks) to 7 months. Previous work has found evidence that the malaria mosquitoAn. coluzzii, survives over 200 days in the wild between rainy seasons in a presumed state of aestivation (hibernation), but this state has so far not been replicated in laboratory conditions. The inability to recapitulate aestivation in the lab hinders addressing key questions such as how this state is induced, how it affects malaria vector competence, and its impact on disease transmission.

Methods

In effort to induce aestivation, we held laboratory mosquitoes in climate-controlled incubators with a range of conditions that adjusted humidity (40–85% RH), temperature (18–27 °C), and light conditions (8–12 h of light) and evaluated their survivorship. These conditions were chosen to mimic the late rainy and dry seasons as well as relevant extremes these mosquitoes may experience during aestivation.

Results

We found that by priming mosquitoes in conditions simulating the late wet season in Mali, and maintaining mosquitoes in reduced light/temperature, mean mosquito survival increased from 18.34 ± 0.65 to 48.02 ± 2.87 days, median survival increased from 19 (95% CI 17–21) to 50 days (95% CI 40–58), and the maximum longevity increased from 38 to 109 days (P-adj < 0.001). While this increase falls short of the 200 + day survival seen in field mosquitoes, this extension is substantially higher than previously found through environmental or dietary modulation and is hard to reconcile with states other than aestivation. This finding will provide a platform for future characterization of this state, and allow for comparison to field collected samples.
Evaluation of a new live recombinant vaccine against cutaneous leishmaniasis in BALB/c mice
Authors: Salari Samira , Sharifi Iraj , Keyhani Ali Reza , Ghasemi Nejad Almani Pooya
Published: August 2020

Background

Leishmaniasis is a serious health problem in some parts of the world. In spite of the many known leishmaniasis control measures, the disease has continued to increase in endemic areas, and no effective vaccine has been discovered.

Methods

In this study,Leishmania tarentulaewas used as a living factory for the production of two LACK and KMP11 immunogenic antigens in the mice body, and safety profiles were investigated. The sequences of the KMP11 and LACKL. majorantigens were synthesized in the pLEXSY-neo 2.1 plasmid and cloned intoE. colistrain Top10, and after being linearized with theSwaIenzyme, they were transfected into the genome ofL. tarentolae. TheL. tarentolae-LACK/KMP11/EGFPin the stationary phase with CpG ODN as an adjuvant was used for vaccination in BALB/c mice. Vaccination was performed into the left footpad. Three weeks later, the booster was injected in the same manner. To examine the effectiveness of the injected vaccine, pathogenicL. major(MRHO/IR/75/ER) was injected into the right footpad of all mice three weeks following the booster vaccination. In order to assess humoral immunity, the levels of IgG1, and IgG2a antibodies before and 6 weeks after the challenge were studied in the groups. In addition, in order to investigate cellular immunity in the groups, the study measured IFN-γ, IL-5, TNF-α, IL-6 and IL-17 cytokines before, 3 weeks and 8 weeks after the challenge, and also the parasite load in the lymph node with real-time PCR.

Results

The lowest level of the parasitic load was observed in the G1 group (mice vaccinated withL. tarentolae-LACK/KMP11/EGFPwith CpG) in comparison with other groups (L. tarentolae-LACK/KMP11/EGFP +non-CpG (G2);L. tarentolae-EGFP + CpG (G3, control);L. tarentolae-EGFP + non-CpG (G4, control); and mice injected with PBS (G5, control). Moreover, the evaluation of immune response showed a delayed-type hypersensitivity towards Th1.

Conclusions

According to the results of this study, the live recombinant vaccine ofL. tarentolae-LACK/KMP11/EGFPwith the CpG adjuvant reduced the parasitic load and footpad induration in infected mice. The long-term effects of this vaccine can be evaluated in volunteers as a clinical trial in future planning.
Modeling and analysis of Hi-C data by HiSIF identifies characteristic promoter-distal loops
Authors: Zhou Yufan , Cheng Xiaolong , Yang Yini , Li Tian , Li Jingwei , Huang Tim H.-M. , Wang Junbai , Lin Shili , Jin Victor X.
Published: August 2020

Current computational methods on Hi-C analysis focused on identifying Mb-size domains often failed to unveil the underlying functional and mechanistic relationship of chromatin structure and gene regulation. We developed a novel computational method HiSIF to identify genome-wide interacting loci. We illustrated HiSIF outperformed other tools for identifying chromatin loops. We applied it to Hi-C data in breast cancer cells and identified 21 genes with gained loops showing worse relapse-free survival in endocrine-treated patients, suggesting the genes with enhanced loops can be used for prognostic signatures for measuring the outcome of the endocrine treatment. HiSIF is available at https://github.com/yufanzhouonline/HiSIF.
Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment—a distinct inflammatory pattern for oligoarticular juvenile arthritis
Authors: Schmidt Tobias , Berthold Elisabet , Arve-Butler Sabine , Gullstrand Birgitta , Mossberg Anki , Kahn Fredrik , Bengtsson Anders A. , Månsson Bengt , Kahn Robin
Published: August 2020

Background

Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes’ and macrophages’ effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA).

Methods

Paired synovial fluid, blood samples (n = 13), and synovial biopsies (n = 3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro. Monocyte/macrophage distribution, polarization, and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence, and in situ hybridization.

Results

Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNγ)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p < 0.001), CD86 (p < 0.001), and CD206 (p < 0.001), but not CD163, as compared to paired circulating monocytes. Additionally, polarization was extensively explored at the mRNA level and synovial fluid monocytes differentially expressed classical markers of M1(IFNγ)/M2(IL-4) polarization compared to circulating monocytes. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p < 0.01). Synovial fluid induced M2 markers (CD16 and CD206), but not M1 (CD40) or CD86 in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies.

Conclusion

Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.
The “pandemic” increase in lung ultrasound use in response to Covid-19: can we complement computed tomography findings? A narrative review
Authors: Vetrugno Luigi , Baciarello Marco , Bignami Elena , Bonetti Andrea , Saturno Francesco , Orso Daniele , Girometti Rossano , Cereser Lorenzo , Bove Tiziana
Published: August 2020

Coronavirus disease of 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has rapidly spread to a global pandemic in March 2020. This emergency condition has been putting a severe strain on healthcare systems worldwide, and a prompt, dynamic response is instrumental in its management. While a definite diagnosis is based on microbiological evidence, the relationship between lung ultrasound (LU) and high-resolution computed tomography (HRCT) in the diagnosis and management of COVID-19 is less clear. Lung ultrasound is a point-of-care imaging tool that proved to be useful in the identification and severity assessment of different pulmonary conditions, particularly in the setting of emergency and critical care patients in intensive care units; HRCT of the thorax is regarded as the mainstay of imaging evaluation of lung disorders, enabling characterization and quantification of pulmonary involvement. Aims of this review are to describe LU and chest HRCT main imaging features of COVID-19 pneumonia, and to provide state-of-the-art insights regarding the integrated role of these techniques in the clinical decision-making process of patients affected by this infectious disease.
Genome-wide profiling of DNA methylation and gene expression identifies candidate genes for human diabetic neuropathy
Authors: Guo Kai , Eid Stephanie A. , Elzinga Sarah E. , Pacut Crystal , Feldman Eva L. , Hur Junguk
Published: August 2020

Background

Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes (T2D). Although the cellular and molecular mechanisms of DPN are poorly understood, we and others have shown that altered gene expression and DNA methylation are implicated in disease pathogenesis. However, how DNA methylation might functionally impact gene expression and contribute to nerve damage remains unclear. Here, we analyzed genome-wide transcriptomic and methylomic profiles of sural nerves from T2D patients with DPN.

Results

Unbiased clustering of transcriptomics data separated samples into groups, which correlated with HbA1c levels. Accordingly, we found 998 differentially expressed genes (DEGs) and 929 differentially methylated genes (DMGs) between the groups with the highest and lowest HbA1c levels. Functional enrichment analysis revealed that DEGs and DMGs were enriched for pathways known to play a role in DPN, including those related to the immune system, extracellular matrix (ECM), and axon guidance. To understand the interaction between the transcriptome and methylome in DPN, we performed an integrated analysis of the overlapping genes between DEGs and DMGs. Integrated functional and network analysis identified genes and pathways modulating functions such as immune response, ECM regulation, and PI3K-Akt signaling.

Conclusion

These results suggest for the first time that DNA methylation is a mechanism regulating gene expression in DPN. Overall, DPN patients with high HbA1c have distinct alterations in sural nerve DNA methylome and transcriptome, suggesting that optimal glycemic control in DPN patients is an important factor in maintaining epigenetic homeostasis and nerve function.
Radiomics in medical imaging—“how-to” guide and critical reflection
Authors: van Timmeren Janita E. , Cester Davide , Tanadini-Lang Stephanie , Alkadhi Hatem , Baessler Bettina
Published: August 2020

Radiomics is a quantitative approach to medical imaging, which aims at enhancing the existing data available to clinicians by means of advanced mathematical analysis. Through mathematical extraction of the spatial distribution of signal intensities and pixel interrelationships, radiomics quantifies textural information by using analysis methods from the field of artificial intelligence. Various studies from different fields in imaging have been published so far, highlighting the potential of radiomics to enhance clinical decision-making. However, the field faces several important challenges, which are mainly caused by the various technical factors influencing the extracted radiomic features.

The aim of the present review is twofold: first, we present the typical workflow of a radiomics analysis and deliver a practical “how-to” guide for a typical radiomics analysis. Second, we discuss the current limitations of radiomics, suggest potential improvements, and summarize relevant literature on the subject.
Structured reporting of chest CT in COVID-19 pneumonia: a consensus proposal
Authors: Neri E. , Coppola F. , Larici A. R. , Sverzellati N. , Mazzei M. A. , Sacco P. , Dalpiaz G. , Feragalli B. , Miele V. , Grassi R.
Published: August 2020

Objectives

The need of a standardized reporting scheme and language, in imaging of COVID-19 pneumonia, has been welcomed by major scientific societies. The aim of the study was to build the reporting scheme of chest CT in COVID-19 pneumonia.

Methods

A team of experts, of the Italian Society of Medical and Interventional Radiology (SIRM), has been recruited to compose a consensus panel. They used a modified Delphi process to build a reporting scheme and expressed a level of agreement for each section of the report. To measure the internal consistency of the panelist ratings for each section of the report, a quality analysis based on the average inter-item correlation was performed with Cronbach’s alpha (Cα) correlation coefficient.

Results

The overall mean score of the experts and the sum of score were 3.1 (std.dev. ± 0.11) and 122 in the second round, and improved to 3.75 (std.dev. ± 0.40) and 154 in the third round. The Cronbach’s alpha (Cα) correlation coefficient was 0.741 (acceptable) in the second round and improved to 0.789 in the third round. The final report was built in the management of radiology report template (MRRT) and includesn= 4 items in the procedure information,n= 5 items in the clinical information,n= 16 in the findings, andn= 3 in the impression, with overall 28 items.

Conclusions

The proposed structured report could be of help both for expert radiologists and for the less experienced who are faced with the management of these patients. The structured report is conceived as a guideline, to recommend the key items/findings of chest CT in COVID-19 pneumonia.
Involvement of miRNA203 in the proliferation of epidermal stem cells during the process of DM chronic wound healing through Wnt signal pathways
Authors: Liu Jian , Shu Bin , Zhou Ziheng , Xu Yingbin , Liu Yiling , Wang Peng , Xiong Kun , Xie Julin
Published: August 2020

Background

The biological role of miR-203 and the underlying mechanisms on the proliferation of epidermal stem cells (ESCs) have not yet been reported during the progression of chronic wound healing in diabetes mellitus. Our previous studies have observed that the expression of miR-203 showed a marked upregulation and ESC proliferation capacity was impaired in diabetes mellitus skin wounds in rats.

Methods

Wound models were established in normal rats and rats with type 2 diabetes. Expression level of miR-203 and the alteration of ESCs’ number and function were detected. ESCs were isolated from the back skin of fetal rats to assess the effects of glucose in vitro. An antagomir to miR-203 was used to assess its effect on ESCs. Using microarray analysis, we further identified potential target genes and signaling pathways of miR-203.

Results

We found that high glucose significantly upregulated the expression of miR-203 and subsequently reduced the number of ESCs and impaired their proliferation capacity. Meanwhile, over-expression of miR-203 reduced the ESCs’ numbers and impaired the proliferation capacity via downregulation of the Notch and Wnt signaling pathways. Conversely, inhibition of miR-203 enhanced the proliferation capacity. Additionally, silencing miR-203 in skin of rats with type 2 diabetes accelerated wound healing and improved healing quality via the upregulation of the Notch and Wnt signaling pathways. Finally, over-expression of miR-203 downregulated genes ROCK2, MAPK8, MAPK9, and PRKCA.

Conclusion

Our findings demonstrated that induced expression of miR-203 by high glucose in type 2 diabetic rats decreased the number of ESCs and impaired ESC proliferation capacity via downregulating genes related to Notch and Wnt signaling pathways, resulting in a delayed wound healing.
Plasticity of Paneth cells and their ability to regulate intestinal stem cells
Authors: Mei Xianglin , Gu Ming , Li Meiying
Published: August 2020

Paneth cells (PCs) are located at the bottom of small intestinal crypts and play an important role in maintaining the stability of the intestinal tract. Previous studies reported on how PCs shape the intestinal microbiota or the response to the immune system. Recent studies have determined that PCs play an important role in the regulation of the homeostasis of intestinal epithelial cells. PCs can regulate the function and homeostasis of intestinal stem cells through several mechanisms. On the one hand, under pathological conditions, PCs can be dedifferentiated into stem cells to promote the repair of intestinal tissues. On the other hand, PCs can regulate stem cell proliferation by secreting a variety of hormones (such as wnt3a) or metabolic intermediates. In addition, we summarise key signalling pathways that affect PC differentiation and mutual effect with intestinal stem cells. In this review, we introduce the diverse functions of PCs in the intestine.
Reparative effect of mesenchymal stromal cells on endothelial cells after hypoxic and inflammatory injury
Authors: Sierra-Parraga Jesus M. , Merino Ana , Eijken Marco , Leuvenink Henri , Ploeg Rutger , Møller Bjarne K. , Jespersen Bente , Baan Carla C. , Hoogduijn Martin J.
Published: August 2020

Background

The renal endothelium is a prime target for ischemia-reperfusion injury (IRI) during donation and transplantation procedures. Mesenchymal stromal cells (MSC) have been shown to ameliorate kidney function after IRI. However, whether this involves repair of the endothelium is not clear. Therefore, our objective is to study potential regenerative effects of MSC on injured endothelial cells and to identify the molecular mechanisms involved.

Methods

Human umbilical vein endothelial cells (HUVEC) were submitted to hypoxia and reoxygenation and TNF-α treatment. To determine whether physical interaction or soluble factors released by MSC were responsible for the potential regenerative effects of MSC on endothelial cells, dose-response experiments were performed in co-culture and transwell conditions and with secretome-deficient MSC.

Results

MSC showed increased migration and adhesion to injured HUVEC, mediated by CD29 and CD44 on the MSC membrane. MSC decreased membrane injury marker expression, oxidative stress levels, and monolayer permeability of injured HUVEC, which was observed only when allowing both physical and paracrine interaction between MSC and HUVEC. Furthermore, viable MSC in direct contact with injured HUVEC improved wound healing capacity by 45% and completely restored their angiogenic capacity. In addition, MSC exhibited an increased ability to migrate through an injured HUVEC monolayer compared to non-injured HUVEC in vitro.

Conclusions

These results show that MSC have regenerative effects on injured HUVEC via a mechanism which requires both physical and paracrine interaction. The identification of specific effector molecules involved in MSC-HUVEC interaction will allow targeted modification of MSC to apply and enhance the therapeutic effects of MSC in IRI.
Management of retinitis pigmentosa by Wharton’s jelly-derived mesenchymal stem cells: prospective analysis of 1-year results
Authors: Özmert Emin , Arslan Umut
Published: August 2020

Purpose

The aim of the study was to investigate annual structural and functional results, and their correlation with inheritance pattern of retinitis pigmentosa (RP) patients who were treated with Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs).

Material and methods

This prospective, sequential, open-label phase-3 clinical study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology, between April 2019 and May 2020. The study included 34 eyes from 32 retinitis pigmentosa patients of various genotypes who were enrolled in the stem cells clinical trial. The patients were followed for 12 months after the WJ-MSCs transplantation into subtenon space and evaluated with consecutive examinations. Genetic mutations were investigated using a retinitis pigmentosa panel sequencing method consisting of 90 genes. All patients underwent a complete routine ophthalmic examination with best corrected visual acuity, optical coherence tomography angiography, visual field, and full-field electroretinography. Quantitative data obtained from baseline (T0), 6th month (T1), and 12th month (T2) examinations were compared.

Results

According to timepoints at T0, T1, and T2: The mean outer retinal thickness was 100.3 μm, 119.1 μm, and 118.0 μm, respectively (p = 0.01; T0 < T1, T2). The mean horizontal ellipsoid zone width were 2.65 mm, 2.70 mm, and 2.69 mm respectively (p = 0.01; T0 < T1, T2). The mean best corrected visual acuity (BCVA) were 70.5 letters, 80.6 letters, and 79.9 letters, respectively (p = 0.01; T0 < T1, T2). The mean fundus perimetry deviation index (FPDI) was 8.0%, 11.4%, and 11.6%, respectively (p = 0.01; T0 < T1, T2). The mean full-field flicker ERG parameters at T0, T1, and T2: amplitudes were 2.4 mV, 5.0 mV, and 4.6 mV, respectively (p = 0.01; T0 < T1, T2). Implicit time were 43.3 ms, 37.9 ms, and 38.6 ms, respectively (p = 0.01; T0 > T1, T2). According to inheritance pattern, BCVA, FPDI, ERG amplitude, and implicit time data improved significantly in autosomal dominant (AD) and in autosomal recessive (AR) RP at 1 year follow-up (pAD = 0.01, pAR = 0.01; pAD = pAR > pX-linked). No ocular or systemic adverse events related to the surgical methods and/or WJ-MSCs were observed during the 1 year follow-up period.

Conclusion

Subtenon transplantation of WJ-MSCs was found to be effective and safe in the treatment of RP during the first year, similar to the sixth month’s results. In autosomal dominant and autosomal recessive inheritance of RP, regardless of the genetic mutations, subtenon administration of WJ-MSCs can be considered an effective and safe option without any adverse effect for slowing or stopping the disease progression.

Trial registration

ClinicalTrials.gov,NCT04224207. Registered 8 January 2020
Derivation of dynamical integral inequalities based on two-dimensional time scales theory
Authors: Khan Zareen A. , Jarad Fahd , Khan Aziz , Khan Hasib
Published: August 2020

The main goal of this paper is to set up some new estimates of a specific class of dynamic integral inequalities (DII) which are partially linear on a time scale$\mathbb{T}$Twith two independent variables. These, from the one hand, sum up and, on the other hand, offer a helpful method for both the qualitative and quantitative study of dynamic equations on time scales. Some applications are taken into consideration to show the validity of the fundamental results.
Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, prevents the development of cyclosporine A nephrotoxicity in a rat model
Authors: Morita Shinya , Shinoda Kazunobu , Yoshida Tadashi , Shimoda Masayuki , Kanno Yoshihiko , Mizuno Ryuichi , Kono Hidaka , Asanuma Hiroshi , Nakagawa Ken , Umezawa Kazuo , Oya Mototsugu
Published: August 2020

Background

Cyclosporine A (CsA) is an essential immunosuppressant in organ transplantation. However, its chronic nephrotoxicity is an obstacle to long allograft survival that has not been overcome. Nuclear factor-κB (NF-κB) is activated in the renal tissue in CsA nephropathy. In this study, we aimed to investigate the effect of the specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in a rat model of CsA nephrotoxicity.

Methods

We administered CsA (15 mg/kg) daily for 28 days to Sprague-Dawley rats that underwent 5/6 nephrectomy under a low-salt diet. We administered DHMEQ (8 mg/kg) simultaneously with CsA to the treatment group, daily for 28 days and evaluated its effect on CsA nephrotoxicity.

Results

DHMEQ significantly inhibited NF-κB activation and nuclear translocation due to CsA treatment. Elevated serum urea nitrogen and creatinine levels due to repeated CsA administration were significantly decreased by DHMEQ treatment (serum urea nitrogen in CsA + DHMEQ vs CsA vs control, 69 ± 6.4 vs 113.5 ± 8.8 vs 43.1 ± 1.1 mg/dL, respectively,p < 0.0001; serum creatinine in CsA + DHMEQ vs CsA vs control, 0.75 ± 0.02 vs 0.91 ± 0.02 vs 0.49 ± 0.02 mg/dL, respectively, p < 0.0001), and creatinine clearance was restored in the treatment group (CsA + DHMEQ vs CsA vs control, 2.57 ± 0.09 vs 1.94 ± 0.12 vs 4.61 ± 0.18 ml/min/kg, respectively, p < 0.0001). However, DHMEQ treatment did not alter the inhibitory effect of CsA on urinary protein secretion. The development of renal fibrosis due to chronic CsA nephrotoxicity was significantly inhibited by DHMEQ treatment (CsA + DHMEQ vs CsA vs control, 13.4 ± 7.1 vs 35.6 ± 18.4 vs 9.4 ± 5.4%, respectively, p < 0.0001), and these results reflected the results of renal functional assessment. DHMEQ treatment also had an inhibitory effect on the increased expression of chemokines, monocyte chemoattractant protein-1, and chemokine (c-c motif) ligand 5 due to repeated CsA administration, which inhibited the infiltration of macrophages and neutrophils into the renal tissue.

Conclusions

These findings suggest that DHMEQ treatment in combination therapy with CsA-based immunosuppression is beneficial to prevent the development of CsA-induced nephrotoxicity.
Method development for acetyl octapeptide-3 analysis by liquid chromatography-tandem mass spectrometry
Authors: Ji Moongi , Lee Hyeon-Seong , Kim Youngbae , Seo Chan , Choi Subin , Oh Songjin , Min Jeuk , Park Hyung-Jin , Kim Jung Dong , Jeong Do Hyeon , Paik Man-Jeong
Published: August 2020

Background

Acetyl octapeptide-3 (SNAP-8) is an antiaging peptide that is more effective than acetyl hexapeptide-3, which is more stable than botulinum toxin and effectively relieves facial wrinkles. Products containing SNAP-8 such as patch are producing, but analytical method has not been reported to determination of SNAP-8.

Method

Mobile phase, collision energy, and desolvation line temperature were optimized, and mass spectral data set for SNAP-8 was newly constructed by liquid chromatography-triple quadrupole mass spectrometer in multiple reaction monitoring mode.

Results

The developed method showed good linearity (r ≥ 0.9971) with limit of quantification of 0.0125 ng/mL, repeatability (% relative standard deviation = 0.02 to 0.12) and accuracy (% relative error = − 1.68 to 1.44) under optimal conditions. This method was successfully applied to a biodegradable microneedle patch loaded with SNAP-8.

Conclusion

The present method for the quantification of SNAP-8 may be useful for quality control in the cosmetic fields.
BLAST-QC: automated analysis of BLAST results
Authors: Torkian Behzad , Hann Spencer , Preisner Eva , Norman R. Sean
Published: August 2020

Background

The Basic Local Alignment Search Tool (BLAST) from NCBI is the preferred utility for sequence alignment and identification for bioinformatics and genomics research. Among researchers using NCBI’s BLAST software, it is well known that analyzing the results of a large BLAST search can be tedious and time-consuming. Furthermore, with the recent discussions over the effects of parameters such as ‘-max_target_seqs’ on the BLAST heuristic search process, the use of these search options are questionable. This leaves using a stand-alone parser as one of the only options of condensing these large datasets, and with few available for download online, the task is left to the researcher to create a specialized piece of software anytime they need to analyze BLAST results. The need for a streamlined and fast script that solves these issues and can be easily implemented into a variety of bioinformatics and genomics workflows was the initial motivation for developing this software.

Results

In this study, we demonstrate the effectiveness of BLAST-QC for analysis of BLAST results and its desirability over the other available options. Applying genetic sequence data from our bioinformatic workflows, we establish BLAST_QC’s superior runtime when compared to existing parsers developed with commonly used BioPerl and BioPython modules, as well as C and Java implementations of the BLAST_QC program. We discuss the ‘max_target_seqs’ parameter, the usage of and controversy around the use of the parameter, and offer a solution by demonstrating the ability of our software to provide the functionality this parameter was assumed to produce, as well as a variety of other parsing options. Executions of the script on example datasets are given, demonstrating the implemented functionality and providing test-cases of the program. BLAST-QC is designed to be integrated into existing software, and we establish its effectiveness as a module of workflows or other processes.

Conclusions

BLAST-QC provides the community with a simple, lightweight and portable Python script that allows for easy quality control of BLAST results while avoiding the drawbacks of other options. This includes the uncertain results of applying the -max_target_seqs parameter or relying on the cumbersome dependencies of other options like BioPerl, Java, etc. which add complexity and run time when running large data sets of sequences. BLAST-QC is ideal for use in high-throughput workflows and pipelines common in bioinformatic and genomic research, and the script has been designed for portability and easy integration into whatever type of processes the user may be running.
Comparative evaluation of Salicornia bigelovii oil planted under different treatments
Authors: El-Araby R. , Rezk A. I. , El-Enin S. A. Abo , Nofal O. A. , El-Nasharty A. B.
Published: August 2020

Background

Assessment of the oil % in a representative sample ofSalicorniabigeloviiseeds with different extraction methods using some of the organic solvents to reach the best economic one and determination of the effect ofS.bigeloviicultivation under different conditions of irrigation and fertilization on the percentage, composition, and nutrition value of oil were done. From the International Training Centre-Mariut, Alexandria, we obtained representative samples ofSalicornia bigeloviiseeds which are collected from the sea coast and 17 samples ofS.bigeloviiseeds which are subjected to different treatments of irrigation and fertilization. The oil % in a blank sample (B) was determined using different solvents (hexane, hexane-isopropanol, and ethanol) with variant methods (shaker, conventional, and ultrasonic). Oil % in 17 samples was evaluated by the ultrasonic probe technique using ethanol. The oil composition was determined in all samples by GC analysis. The phenolic and flavonoid contents in the residue were determined with the Folin-Ciocalteu reagent and colorimetric method, respectively.

Results

The ethanol has higher extraction efficiency and the ultrasonic probe recovered higher oil % in the blank sample. Seventeen samples ofS.bigeloviicultivated under different combined treatments of fertilization and irrigation recorded oil % less than the blank sample. The fatty acids profile cleared that the oil of cultivated samples (17 samples) had power for biodiesel production with high ignition properties and good stability due to the high cetane number and a high percentage of palmitic acid. The nutrition value of the blank sample is higher than that of the other 17 samples. The polyunsaturated fatty acids in the blank sample represent > 63% of the total fatty acids.

Conclusion

The different combined treatments of fertilization and irrigation ofS.bigeloviichanged the fatty acid profiles of all samples, palmitic, stearic, oleic, and linoleic acids were recognized as the most abundant saturated fatty acids. The total phenolic and flavonoid contents differed in the sample to another one but less than their contents in the blank sample.
Alternative uses for tannery wastes: a review of environmental, sustainability, and science
Authors: Rigueto Cesar Vinicius Toniciolli , Rosseto Marieli , Krein Daniela Dal Castel , Ostwald Bruna Elisangela Pessini , Massuda Lillian Avila , Zanella Bárbara Belém , Dettmer Aline
Published: August 2020

The manufacture of leather covers a wide productive chain and beyond contributes to the economic flow. The various stages of leather processing result in high volumes of solid waste. In Brazil, a daily generation of 375 tons of solid waste is estimated, and landfills are still the most used route to its destination. In this review, emphasis will be given to researches that have sought alternatives for the use of solid waste from the tannery industry. Among the main applications of solid tannery wastes, the following stand out production of adsorbent materials, biodiesel, biogas, biopolymers, applications in agriculture and other applications involving extraction/recovery of compounds of industrial/commercial interest, isolation of microorganisms and production of enzymes and applications in the animal diet. In each alternative of waste application, the technologies used, the opportunities, and the challenges faced are mentioned. We hope that this review can provide valuable information to promote the broad understanding of the possibilities that tannery solid wastes has for the development of biodegradable and agricultural products, wastewater treatment, extraction of compounds of industrial and commercial interest, among others.

Graphical abstract
Tolerance analysis of non-depolarizing double-pass polarimetry
Authors: Yu Yimin , Baba-Ali Nabila , Gallatin Gregg M.
Published: August 2020

Double-pass polarimetry measures the polarization properties of a sample over a range of polar angles and all azimuths. Here, we present a tolerance analysis of all the optical elements in both the calibration and measurement procedures to predict the sensitivities of the double-pass polarimeter. The calibration procedure is described by a Mueller matrix based on the eigenvalue calibration method (ECM) [1]. Our numerical results from the calibration and measurement in the Mueller matrix description with tolerances limited by systematic and stochastic noise from specifications of commercially available hardware components are in good agreement with previous experimental observations. Furthermore, by using the orientation Zernike polynomials (OZP) which are an extension of the Jones matrix formalism, similar to the Zernike polynomials wavefront expansion, the pupil distribution of the polarization properties of non-depolarizing samples under test are expanded. Using polar angles ranging up to 25∘, we predict a sensitivity of 0.5% for diattenuation and 0.3∘for retardance using the root mean square (RMS) of the corresponding OZP coefficients as a measure of the error. This numerical tool provides an approach for further improving the sensitivities of polarimeters via error budgeting and replacing sensitive components with those having better precision.