bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundHow 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.MethodsIn 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.ResultsWe 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

AbstractBackgroundLeishmaniasis 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.MethodsIn 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.ResultsThe 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.ConclusionsAccording 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

AbstractCurrent 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

Abstract
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

AbstractCoronavirus 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

Abstract
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

AbstractRadiomics 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

AbstractObjectivesThe 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.MethodsA 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.ResultsThe 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.ConclusionsThe 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

Abstract
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

AbstractPaneth 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

Abstract
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

AbstractPurposeThe 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 methodsThis 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.ResultsAccording 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.ConclusionSubtenon 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 registrationClinicalTrials.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

AbstractThe 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.