bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program
Authors: Granai Massimo , Mundo Lucia , Akarca Ayse U. , Siciliano Maria Chiara , Rizvi Hasan , Mancini Virginia , Onyango Noel , Nyagol Joshua , Abinya Nicholas Othieno , Maha Ibrahim , Margielewska Sandra , Wei Wenbin , Bibas Michele , Piccaluga Pier Paolo , Quintanilla-Martinez Leticia , Fend Falko , Lazzi Stefano , Leoncini Lorenzo , Marafioti Teresa 
Published: May 2020

Abstract
Background
The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood.

Methods
In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis.

Results
Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway.

Conclusion
In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.
Novel therapeutic strategies targeting telomere maintenance mechanisms in high-risk neuroblastoma
Authors: George S. L. , Parmar V. , Lorenzi F. , Marshall L. V. , Jamin Y. , Poon E. , Angelini P. , Chesler L. 
Published: May 2020

AbstractThe majority of high-risk neuroblastomas can be divided into three distinct molecular subgroups defined by the presence of MYCN amplification, upstream TERT rearrangements or alternative lengthening of telomeres (ALT). The common defining feature of all three subgroups is altered telomere maintenance; MYCN amplification and upstream TERT rearrangements drive high levels of telomerase expression whereas ALT is a telomerase independent telomere maintenance mechanism. As all three telomere maintenance mechanisms are independently associated with poor outcomes, the development of strategies to selectively target either telomerase expressing or ALT cells holds great promise as a therapeutic approach that is applicable to the majority of children with aggressive disease.Here we summarise the biology of telomere maintenance and the molecular drivers of aggressive neuroblastoma before describing the most promising therapeutic strategies to target both telomerase expressing and ALT cancers. For telomerase-expressing neuroblastoma the most promising targeted agent to date is 6-thio-2′-deoxyguanosine, however clinical development of this agent is required. In osteosarcoma cell lines with ALT, selective sensitivity to ATR inhibition has been reported. However, we present data showing that in fact ALT neuroblastoma cells are more resistant to the clinical ATR inhibitor AZD6738 compared to other neuroblastoma subtypes. More recently a number of additional candidate compounds have been shown to show selectivity for ALT cancers, such as Tetra-Pt (bpy), a compound targeting the telomeric G-quadruplex and pifithrin-α, a putative p53 inhibitor. Further pre-clinical evaluation of these compounds in neuroblastoma models is warranted.In summary, telomere maintenance targeting strategies offer a significant opportunity to develop effective new therapies, applicable to a large proportion of children with high-risk neuroblastoma. In parallel to clinical development, more pre-clinical research specifically for neuroblastoma is urgently needed, if we are to improve survival for this common poor outcome tumour of childhood.
Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets
Authors: Marquina-Sanchez Brenda , Fortelny Nikolaus , Farlik Matthias , Vieira Andhira , Collombat Patrick , Bock Christoph , Kubicek Stefan 
Published: May 2020

Abstract
Background
Single-cell RNA-seq (scRNA-seq) is emerging as a powerful tool to dissect cell-specific effects of drug treatment in complex tissues. This application requires high levels of precision, robustness, and quantitative accuracy—beyond those achievable with existing methods for mainly qualitative single-cell analysis. Here, we establish the use of standardized reference cells as spike-in controls for accurate and robust dissection of single-cell drug responses.

Results
We find that contamination by cell-free RNA can constitute up to 20% of reads in human primary tissue samples, and we show that the ensuing biases can be removed effectively using a novel bioinformatics algorithm. Applying our method to both human and mouse pancreatic islets treated ex vivo, we obtain an accurate and quantitative assessment of cell-specific drug effects on the transcriptome. We observe that FOXO inhibition induces dedifferentiation of both alpha and beta cells, while artemether treatment upregulates insulin and other beta cell marker genes in a subset of alpha cells. In beta cells, dedifferentiation and insulin repression upon artemether treatment occurs predominantly in mouse but not in human samples.

Conclusions
This new method for quantitative, error-correcting, scRNA-seq data normalization using spike-in reference cells helps clarify complex cell-specific effects of pharmacological perturbations with single-cell resolution and high quantitative accuracy.
Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures
Authors: Begik Oguzhan , Lucas Morghan C. , Liu Huanle , Ramirez Jose Miguel , Mattick John S. , Novoa Eva Maria 
Published: May 2020

Abstract
Background
RNA modifications play central roles in cellular fate and differentiation. However, the machinery responsible for placing, removing, and recognizing more than 170 RNA modifications remains largely uncharacterized and poorly annotated, and we currently lack integrative studies that identify which RNA modification-related proteins (RMPs) may be dysregulated in each cancer type.

Results
Here, we perform a comprehensive annotation and evolutionary analysis of human RMPs, as well as an integrative analysis of their expression patterns across 32 tissues, 10 species, and 13,358 paired tumor-normal human samples. Our analysis reveals an unanticipated heterogeneity of RMP expression patterns across mammalian tissues, with a vast proportion of duplicated enzymes displaying testis-specific expression, suggesting a key role for RNA modifications in sperm formation and possibly intergenerational inheritance. We uncover many RMPs that are dysregulated in various types of cancer, and whose expression levels are predictive of cancer progression. Surprisingly, we find that several commonly studied RNA modification enzymes such as METTL3 or FTO are not significantly upregulated in most cancer types, whereas several less-characterized RMPs, such as LAGE3 and HENMT1, are dysregulated in many cancers.

Conclusions
Our analyses reveal an unanticipated heterogeneity in the expression patterns of RMPs across mammalian tissues and uncover a large proportion of dysregulated RMPs in multiple cancer types. We provide novel targets for future cancer research studies targeting the human epitranscriptome, as well as foundations to understand cell type-specific behaviors that are orchestrated by RNA modifications.
Construction and analysis of an artificial consortium based on the fast-growing cyanobacterium Synechococcus elongatus UTEX 2973 to produce the platform chemical 3-hydroxypropionic acid from CO2
Authors: Zhang Li , Chen Lei , Diao Jinjin , Song Xinyu , Shi Mengliang , Zhang Weiwen 
Published: May 2020

AbstractBackgroundCyanobacterial carbohydrates, such as sucrose, have been considered as potential renewable feedstock to support the production of fuels and chemicals. However, the separation and purification processes of these carbohydrates will increase the production cost of chemicals. Co-culture fermentation has been proposed as an efficient and economical way to utilize these cyanobacterial carbohydrates. However, studies on the application of co-culture systems to achieve green biosynthesis of platform chemicals are still rare.ResultsIn this study, we successfully achieved one-step conversion of sucrose derived from cyanobacteria to fine chemicals by constructing a microbial consortium consisting of the fast-growing cyanobacteriumSynechococcus elongatusUTEX 2973 andEscherichia colito sequentially produce sucrose and then the platform chemical 3-hydroxypropionic acid (3-HP) from CO2under photoautotrophic growth conditions. First, efforts were made to overexpress the sucrose permease-coding genecscBunder the strong promoterPcpc560inS. elongatusUTEX 2973 for efficient sucrose secretion. Second, the sucrose catabolic pathway and malonyl-CoA-dependent 3-HP biosynthetic pathway were introduced intoE. coliBL21 (DE3) for heterologous biosynthesis of 3-HP from sucrose. By optimizing the cultivation temperature from 37 to 30 °C, a stable artificial consortium system was constructed with the capability of producing 3-HP at up to 68.29 mg/L directly from CO2. In addition, cell growth ofS. elongatusUTEX 2973 in the consortium was enhanced, probably due to the quick quenching of reactive oxygen species (ROS) in the system byE. coli, which in turn improved the photosynthesis of cyanobacteria.ConclusionThe study demonstrated the feasibility of the one-step conversion of sucrose to fine chemicals using an artificial consortium system. The study also confirmed that heterotrophic bacteria could promote the cell growth of cyanobacteria by relieving oxidative stress in this microbial consortium, which further suggests the potential value of this system for future industrial applications.
Cattle gastrointestinal nematode egg-spiked faecal samples: high recovery rates using the Mini-FLOTAC technique
Authors: Amadesi Alessandra , Bosco Antonio , Rinaldi Laura , Cringoli Giuseppe , Claerebout Edwin , Maurelli Maria Paola 
Published: May 2020

Abstract
Background
Faecal egg count (FEC) techniques are commonly used to detect gastrointestinal nematodes (GINs) in cattle and to determine anthelmintic efficacy/resistance through the faecal egg count reduction test (FECRT). Mini-FLOTAC is one of the techniques recommended for a standardised FEC/FECRT of helminth eggs in cattle. However, only one paper evaluated the recovery rate of GIN eggs by Mini-FLOTAC (compared to McMaster and modified-Wisconsin method) in cattle, using only a level of contamination of 200 eggs per gram (EPG) of faeces and using GIN eggs collected from goat faeces to spike faecal samples from cattle. To further study the recovery rate of GIN eggs from cattle faeces, this study was conducted in two laboratories, one in Belgium and one in Italy to evaluate the sensitivity, accuracy, precision and reproducibility of the Mini-FLOTAC and McMaster techniques (at two reading levels: grids and chambers) for the detection of GIN eggs in spiked bovine faecal samples.

Methods
In both countries, spiked cattle faecal samples with five different levels of egg contamination (10, 50, 100, 200 and 500 EPG) of GINs were used. The study was performed in both laboratories by the same expert operator and using the same standard operating procedures (SOPs) for the Mini-FLOTAC and McMaster techniques. Sensitivity, accuracy and precision were calculated for each technique and for each level of contamination. Statistical analyses were performed to evaluate differences in performance between the two techniques.

Results
Mini-FLOTAC had a higher sensitivity (100% at all EPG levels for Mini-FLOTAC vs 0–66.6% for McMaster chambers and grids at levels< 100 EPG), a higher accuracy (98.1% mean value for Mini-FLOTAC vs 83.2% for McMaster grids and 63.8% for McMaster chambers) and a lower coefficient of variation (10.0% for Mini-FLOTAC vs 47.5% for McMaster grids and 69.4% for McMaster chambers) than McMaster. There was no significant difference in the recovery of GIN eggs between the two studies performed in Belgium and in Italy.

Conclusions
The high GIN egg recovery rate detected by Mini-FLOTAC and the similar results obtained in Belgium and in Italy indicated that the diagnostic performance of a FEC technique was not dependent on the laboratory environment.
MiR-153 reduces stem cell-like phenotype and tumor growth of lung adenocarcinoma by targeting Jagged1
Authors: Zhao Guoli , Zhang Yueying , Zhao Zhonghua , Cai Haibo , Zhao Xiaogang , Yang Tong , Chen Weijun , Yao Chengfang , Wang Zhaopeng , Wang Zhaoxia , Han Chen , Wang Hengxiao 
Published: May 2020

Abstract
Background
Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemo-resistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC.

Methods
The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis.

Results
MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis.

Conclusion
MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.
Investigation of memory-enhancing botanical mixture and their isolated compounds for inhibition of amyloid-β and tau aggregation
Authors: Baek Seungyeop , Park Sohui , Shin Jisu , Lee Jun-Seok , Kim Hye Yun , Han Gyoonhee , Kim YoungSoo 
Published: May 2020

AbstractAlzheimer’s disease (AD) is a neurodegenerative disease characterized by the abnormal assembly of amyloid-β (Aβ) and tau aggregates in the brain. When Aβ and tau proteins misfold, progressive brain cell death, synaptic loss, atrophy, and cognitive decline are observed. Here, we report that the memory-enhancing botanical natural product mixture, HX106N, efficiently inhibits formation of Aβ oligomers and fibrils and aggregation of tau. HX106N is a botanical mixture extract ofDimocarpus longan,Liriope platyphylla,Salvia miltiorrhizaandGastrodia elata. In previous clinical studies, HX106N showed increased working memory performances of individuals of subjective memory complaints. However, the drug mechanism and responsible ingredients of HX106N has been unclear yet. In this study, we expanded the investigation of the drug mode of action to the single chemical level by identifying four active components of HX106N, among 14 isolated molecules, with significant inhibitory function against Aβ aggregation. We found that salvianolic acids A, B, E and rosmarinic acid, isolated from the botanical mixture, have potency to inhibit the protein misfolding.
RNA modifications in brain tumorigenesis
Authors: Huang Albert Z. , Delaidelli Alberto , Sorensen Poul H. 
Published: May 2020

AbstractRNA modifications are emerging as critical regulators in cancer biology, thanks to their ability to influence gene expression and the predominant protein isoforms expressed during cell proliferation, migration, and other pro-oncogenic properties. The reversibility and dynamic nature of post-transcriptional RNA modifications allow cells to quickly adapt to microenvironmental changes. Recent literature has revealed that the deregulation of RNA modifications can promote a plethora of developmental diseases, including tumorigenesis. In this review, we will focus on four key post-transcriptional RNA modifications which have been identified as contributors to the pathogenesis of brain tumors: m6A, alternative polyadenylation, alternative splicing and adenosine to inosine modifications. In addition to the role of RNA modifications in brain tumor progression, we will also discuss potential opportunities to target these processes to improve the dismal prognosis for brain tumors.
Observations of equatorial plasma bubbles using a low-cost 630.0-nm all-sky imager in Ishigaki Island, Japan
Authors: Hosokawa Keisuke , Takami Kohei , Saito Susumu , Ogawa Yasunobu , Otsuka Yuichi , Shiokawa Kazuo , Chen Chia-Hung , Lin Chien-Hung 
Published: May 2020

AbstractHere, we introduce a low-cost airglow imaging system developed for observing plasma bubble signatures in 630.0-nm airglow emission from the F region of the ionosphere. The system is composed of a small camera, optical filter, and fish-eye lens, and is operated using free software that automatically records video from the camera. A pilot system was deployed in Ishigaki Island in the southern part of Japan (Lat 24.4, Lon 124.4, Mlat 19.6) and was operated for ~ 1.5 years from 2014 to 2016 corresponding to the recent solar maximum period. The pilot observations demonstrated that it was difficult to identify the plasma bubble signature in the raw image captured every 4 s. However, the quality of the image could be improved by reducing the random noise of instrumental origin through an integration of 30 consecutive raw images obtained in 2 min and further by subtracting the 1-h averaged background image. We compared the deviation images to those from a co-existing airglow imager of OMTIs, which is equipped with a back-illuminated cooled CCD camera with a high quantum efficiency of ~ 90%. It was confirmed that the low-cost airglow imager is capable of imaging the spatial structure of plasma bubbles, including their bifurcating traces. The results of these pilot observations in Ishigaki Island will allow us to distribute the low-cost imager in a wide area and construct a network for monitoring plasma bubbles and their space weather impacts on satellite navigation systems.
Ultrathin Descemet stripping automated endothelial keratoplasty versus Descemet membrane endothelial keratoplasty: a fellow-eye comparison
Authors: Mencucci Rita , Favuzza Eleonora , Marziali Elisa , Cennamo Michela , Mazzotta Cosimo , Lucenteforte Ersilia , Virgili Gianni , Rizzo Stanislao 
Published: May 2020

Abstract
Background
To compare the visual outcome and patients’ satisfaction after ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) performed on fellow eyes of the same patients.

Methods
In this retrospective study, the records of 18 pseudophakic patients affected by Fuchs endothelial dystrophy who underwent DMEK in one eye and UT-DSAEK in the fellow eye were reviewed. Best corrected visual acuity (BCVA), corneal pachymetry, keratometry, corneal aberrations, photopic and mesopic contrast sensitivity, and endothelial cell counts measured 12 months after surgery in either eye were analyzed and compared. The results of a satisfaction questionnaire were also reviewed.

Results
Twelve months after surgery, BCVA was not significantly different in UT-DSAEK and DMEK eyes (0.10 ± 0.04 and 0.07 ± 0.07 logMAR, respectively); at both 4- and 6 mm optical zones total and posterior corneal higher order aberrations (HOAs), posterior astigmatism and total coma were significantly lower after DMEK; BCVA in both groups was significantly correlated mainly with anterior corneal aberrations; contrast sensitivity was higher after DMEK especially in mesopic conditions and at medium spatial frequencies; the endothelial cell density was similar, although slightly higher in the UT-DSAEK group (p = 0.10). The satisfaction questionnaire showed that although patients were highly satisfied from both procedures, more than half of them preferred DMEK and reported a more comfortable and quicker postoperative recovery.

Conclusions
DMEK and UT-DSAEK showed no evidence of difference in terms of postoperative BCVA, although DMEK had a better performance in terms of contrast sensitivity, posterior corneal aberrations and overall patient satisfaction.
Percutaneous transluminal angioplasty with carbon dioxide for peripheral arterial disease after kidney transplantation: a case report with literature review
Authors: Banshodani Masataka , Marubayashi Seiji , Shintaku Sadanori , Sato Tomoyasu , Moriishi Misaki , Tsuchiya Shinichiro , Ohdan Hideki , Kawanishi Hideki 
Published: May 2020

Abstract
Background
Arteriosclerosis may progress and lead to peripheral arterial disease (PAD) during the waiting period until kidney transplantation in end-stage kidney disease (ESKD) patients. Additionally, contrast-induced nephropathy (CIN) of a kidney allograft after the examination and treatment for PAD is problematic. Here, we report the case of a kidney transplant recipient with PAD in the lower extremities who underwent percutaneous transluminal angioplasty (PTA) with carbon dioxide to prevent CIN incidence.

Case presentation
A 57-year-old woman underwent a cadaveric kidney transplant when she was 49 years old. Immunosuppression was maintained with tacrolimus, methylprednisolone, and mycophenolate mofetil. Her post-transplant course was uneventful, and serum creatinine level was maintained at 1.1–1.3 mg/dL. Intermittent claudication of the lower legs began 3 years after transplantation. Under saline intravenous rehydration, computed tomographic angiographies were performed, and the patient was diagnosed with PAD in the bilateral lower extremities. Total PTA was performed thrice for PAD in the lower extremities via a combination of carbon dioxide and iodinated contrast medium to prevent CIN incidence at 3, 4, and 7 years after kidney transplantation. The patient’s recoveries were uneventful. One year later, the serum creatinine level was maintained at 0.9–1.1 mg/dL, and since then, the patient has shown no evidence of recurrence.

Conclusions
In a kidney transplant recipient with PAD, PTA with carbon dioxide was effective to minimize the volumes of iodinated contrast medium and prevent CIN incidence.
Current efforts and challenges facing responses to 2019-nCoV in Africa
Authors: Lucero-Prisno Don Eliseo , Adebisi Yusuff Adebayo , Lin Xu 
Published: May 2020

AbstractThe novel coronavirus is a pandemic that has started to creep into Africa thus making the virus a truly global, health security threat. The number of new 2019-nCoV cases has been rising in Africa, though currently lower than the cases reported outside the region. African countries have activated their Emergency Operations Centres to coordinate responses and preparedness activities to the pandemic. A series of measures such as restricting travel, case detection and contact tracing, mandatory quarantine, guidance and information to the public among other efforts are being implemented across Africa. However, the presence of porous borders, the double burden of communicable and non-communicable diseases, poverty, poor health literacy, infodemic and family clustering, and most of all, weak health systems, may make containment challenging. It is important for African countries to continue to intensify efforts and address the challenges to effectively respond to the uncertainty the pandemic poses.