bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the regulation mechanism of grapevine microRNA172 family members during flower development
Authors: Sun Xin , Wang Mengqi , Leng Xiangpeng , Zhang Kekun , Liu Gengsen , Fang Jinggui 
Published: September 2020

Abstract
Background
Grapevine (Vitis vinifera L.), which has important nutritional values and health benefits, is one of the most economically important fruit crops cultivated worldwide. Several studies showed a large number of microRNAs (VvmiRNAs) involved in the modulation of grape growth and development, and many VvmiRNA families have multiple members. However, the way by which various members from the same miRNA family work is unclear, particularly in grapes.

Results
In this study, an important conserved VvmiR172 family (VvmiR172s) and their targets were set as a good example for elucidating the interaction degree, mechanism, and spatio-temporal traits of diverse members from the same miRNA family. miR-RACE and Stem-loop RT-PCR were used to identify the spatio-temporal expressions of various members of VvmiR172s; together with RLM-RACE, PPM-RACE, Western blot, transgenic technologies, their interaction degree, and regulation mechanism were further validated. The expression of VvmiR172c was significantly higher than that of VvmiR172a, b, and d and showed a positive correlation with the abundance of VvAP2 cleavage products. These findings indicated that VvmiR172c might be one of the main action factors of the VvmiR172 family in flower development. The ability of VvmiR172c to cleave target genes differed due to divergence in complementary degree with VvAP2 and expression levels of various members. In VvmiR172 transgenic lines, we observed that 35S::VvmiR172c resulted in the earliest and abundant flowering, indicating the strong function of VvmiR172c. In contrast, the non-significant phenotypic changes were detected in the VvAP2 transgenic lines. The qRT-PCR and Western bolt results demonstrated that VvmiR172c plays a major role in targeting VvAP2.

Conclusions
VvmiR172 up-regulated the expression of NtFT and decreased the expression of NtFLC. The up/down regulation of VvmiR172c was the most pronounced. The functions of four VvmiR172 members in grape differed, and miR172c had the strongest regulation on AP2.
Increased creatine demand during pregnancy in Arginine: Glycine Amidino-Transferase deficiency: a case report
Authors: Alessandrì Maria Grazia , Strigini Francesca , Cioni Giovanni , Battini Roberta 
Published: September 2020

Abstract
Background
Creatine (Cr), an amino acid derivative, is one of the most important sources of energy acting as both a spatial and temporal energy buffer through its phosphorylated analogue phosphocreatine (PCr) and creatine kinase (CK). Maternal Cr biosynthesis and metabolism seem to play an important role in pregnancy, as shown in preclinical and in healthy human pregnancy studies. Patients with Arginine:Glycine Amidino-Transferase deficiency (AGAT-d), due to the deficit of the first enzyme involved in Cr synthesis, are at a disadvantage due to their failure to synthesize Cr and their dependence on external intake, in contrast to normal subjects, where changes in Cr biosynthesis supply their needs.
We report the outcomes of a pregnancy in an AGAT-d woman, and the challenge we faced in managing her treatment with oral Cr to ensure optimal conditions for her fetus.

Case presentation
A 22-year-old AGAT-d woman referred to our Institute for the management of her first conception at 11 weeks of fetal gestational age. Sonographic monitoring at 20 w GA indicated a reduction of fetal growth, in particular of the head circumference that was below the 3rd centile. Biochemical monitoring of Cr in biological fluids of the mother revealed a decline of the Cr concentrations, in particular in the urine sample, requiring prompt correction of the Cr dose. At 35 weeks of gestation the patient delivered a male infant, heterozygous for GATM mutation, with normal brain Cr levels; at one year the baby achieved typical developmental milestones.

Conclusions
This rare pregnancy demonstrates that Cr levels in the blood and urine of the mother with AGAT-d decreased since the first months of gestation. The increase of the Cr daily dose administered to the mother seems to have produced beneficial effects also on the fetus.
Machine-learning strategies for testing patterns of morphological variation in small samples: sexual dimorphism in gray wolf (Canis lupus) crania
Authors: MacLeod Norman , Kolska Horwitz Liora 
Published: September 2020

AbstractBackgroundStudies of mammalian sexual dimorphism have traditionally involved the measurement of selected dimensions of particular skeletal elements and use of single data-analysis procedures. Consequently, such studies have been limited by a variety of both practical and conceptual constraints. To compare and contrast what might be gained from a more exploratory, multifactorial approach to the quantitative assessment of form-variation, images of a small sample of modern Israeli gray wolf (Canis lupus) crania were analyzed via elliptical Fourier analysis of cranial outlines, a Naïve Bayes machine-learning approach to the analysis of these same outline data, and a deep-learning analysis of whole images in which all aspects of these cranial morphologies were represented. The statistical significance and stability of each discriminant result were tested using bootstrap and jackknife procedures.ResultsOur results reveal no evidence for statistically significant sexual size dimorphism, but significant sex-mediated shape dimorphism. These are consistent with the findings of prior wolf sexual dimorphism studies and extend these studies by identifying new aspects of dimorphic variation. Additionally, our results suggest that shape-based sexual dimorphism in theC. lupuscranial complex may be more widespread morphologically than had been appreciated by previous researchers.ConclusionOur results suggest that size and shape dimorphism can be detected in small samples and may be dissociated in mammalian morphologies. This result is particularly noteworthy in that it implies there may be a need to refine allometric hypothesis tests that seek to account for phenotypic sexual dimorphism. The methods we employed in this investigation are fully generalizable and can be applied to a wide range of biological materials and could facilitate the rapid evaluation of a diverse array of morphological/phenomic hypotheses.
COVID-19 length of hospital stay: a systematic review and data synthesis
Authors: Rees Eleanor M. , Nightingale Emily S. , Jafari Yalda , Waterlow Naomi R. , Clifford Samuel , B. Pearson Carl A. , Group CMMID Working , Jombart Thibaut , Procter Simon R. , Knight Gwenan M. 
Published: September 2020

AbstractBackgroundThe COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.MethodsWe performed a systematic review of early evidence on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach, we provide distributions for total hospital and ICU LoS from studies in China and elsewhere, for use by the community.ResultsWe identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies—four each within and outside China—with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR 10–19) days for China, compared with 5 (IQR 3–9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5–13) days for China and 7 (4–11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.ConclusionPatients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.
Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model
Authors: Zeng Huihui , Li Tiao , He Xue , Cai Shan , Luo Hong , Chen Ping , Chen Yan 
Published: September 2020

Abstract
Background
Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are triggered has never been conducted.

Method
The total reactive oxygen species (ROS) level, pulmonary apoptosis and B-cell lymphoma/leukemia-2 (Bcl-2) expression, an apoptosis regulator, were detected in samples from COPD patients. Bisulfite sequencing PCR (BSP) was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), a vital DNA methyltransferase enzyme, in the lungs of patients was confirmed through western blotting. To find out interactions between oxidative stress and DNA methylation in emphysema, mouse models were built with antioxidant treatment and DNMT1 silencing, and were examined with the pulmonary apoptosis, Bcl-2 and DNMT1 levels, and epigenetic alterations of Bcl-2.

Results
Higher ROS levels and pulmonary apoptosis were observed in COPD patients than in healthy controls. Downregulated Bcl-2 expression with increased promoter methylation and DNMT1 protein expression was found in COPD patients. Antioxidant treatment reduced the level of ROS, DNMT1 protein and emphysematous progression in the smoking models. Following DNMT1 blockade, smoking models showed improved lung function, pulmonary apoptosis, emphysematous progression, and increased Bcl-2 protein level with less promoter methylation than emphysema mice.

Conclusion
Cigarette-induced oxidative stress mediates pulmonary apoptosis and hypermethylation of the Bcl-2 promoter in emphysema models through DNMT1.
Application of different types of CRISPR/Cas-based systems in bacteria
Authors: Liu Zhenquan , Dong Huina , Cui Yali , Cong Lina , Zhang Dawei 
Published: September 2020

AbstractAs important genome editing tools, CRISPR/Cas systems, especially those based on type II Cas9 and type V Cas12a, are widely used in genetic and metabolic engineering of bacteria. However, the intrinsic toxicity of Cas9 and Cas12a-mediated CRISPR/Cas tools can lead to cell death in some strains, which led to the development of endogenous type I and III CRISPR/Cas systems. However, these systems are hindered by complicated development and limited applications. Thus, further development and optimization of CRISPR/Cas systems is needed. Here, we briefly summarize the mechanisms of different types of CRISPR/Cas systems as genetic manipulation tools and compare their features to provide a reference for selecting different CRISPR/Cas tools. Then, we show the use of CRISPR/Cas technology for bacterial strain evolution and metabolic engineering, including genome editing, gene expression regulation and the base editor tool. Finally, we offer a view of future directions for bacterial CRISPR/Cas technology.
Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities
Authors: Gruenberg Maria , Moniz Clara Antunes , Hofmann Natalie E. , Koepfli Cristian , Robinson Leanne J. , Nate Elma , Monteiro Wuelton Marcelo , de Melo Gisely Cardoso , Kuehn Andrea , Siqueira Andre M. , Nguitragool Wang , Bassat Quique , Lacerda Marcus , Sattabongkot Jetsumon , Mueller Ivo , Felger Ingrid 
Published: September 2020

Abstract
Background
The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome.

Methods
Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities.

Results
In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Brazil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG.

Conclusion
The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diagnostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement. Improving sensitivity in P. vivax surveillance by us-qPCR is of particular benefit, because the additionally detected P. vivax infections signal the potential presence of hypnozoites and subsequent risk of relapse and further transmission.
Ultra-sensitive RDT performance and antigen dynamics in a high-transmission Plasmodium falciparum setting in Mali
Authors: Reichert Emily N. , Hume Jen C. C. , Sagara Issaka , Healy Sara A. , Assadou Mahamadoun H. , Guindo Merepen A. , Barney Rebecca , Rashid Andy , Yang Ihn Kyung , Golden Allison , Domingo Gonzalo J. , Duffy Patrick E. , Slater Hannah C. 
Published: September 2020

Abstract
Background
The recent expansion of tools designed to accurately quantify malaria parasite-produced antigens has enabled us to evaluate the performance of rapid diagnostic tests (RDTs) as a function of the antigens they detect—typically histidine rich protein 2 (HRP2) or lactate dehydrogenase (LDH).

Methods
For this analysis, whole blood specimens from a longitudinal study in Bancoumana, Mali were used to evaluate the performance of the ultra-sensitive HRP2-based Alere™ Malaria Ag P.f RDT (uRDT). The samples were collected as part of a transmission-blocking vaccine trial in a high transmission region for Plasmodium falciparum malaria. Furthermore, antigen dynamics after successful anti-malarial drug treatment were evaluated in these samples using the Q-Plex Human Malaria Array (4-Plex) to quantify antigen concentrations.

Results
The uRDT had a 50% probability of a positive result at 207 pg/mL HRP2 [95% credible interval (CrI) 160–268]. Individuals with symptomatic infection remained positive by uRDT for a median of 33 days [95% confidence interval (CI) 28–47] post anti-malarial drug treatment. Biphasic exponential decay models accurately captured the population level post-treatment dynamics of both HRP2 and Plasmodium LDH (pLDH), with the latter decaying more rapidly. Motivated by these differences in rates of decay, a novel algorithm that used HRP2:pLDH ratios to predict if an individual had active versus recently cleared P. falciparum infection was developed. The algorithm had 77.5% accuracy in correctly classifying antigen-positive individuals as those with and without active infection.

Conclusions
These results characterize the performance of the ultra-sensitive RDT and demonstrate the potential for emerging antigen-quantifying technologies in the field of malaria diagnostics to be helpful tools in distinguishing between active versus recently cleared malaria infections.
Multifunctional nanobubbles carrying indocyanine green and paclitaxel for molecular imaging and the treatment of prostate cancer
Authors: Lan Minmin , Zhu Lianhua , Wang Yixuan , Shen Daijia , Fang Kejing , Liu Yu , Peng Yanli , Qiao Bin , Guo Yanli 
Published: September 2020

Abstract

Background
Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to deliver drugs, effectively increasing the content of the drug in the tumour area and reducing potential side effects, thereby successfully contributing to the treatment of tumours.

Results
In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs) and studied their applications in ultrasound imaging of prostate cancer as well as their therapeutic effects on prostate cancer when combined with UTND. ICG-PTX NBs were prepared by the mechanical oscillation method. The particle size and zeta potential of the ICG-PTX NBs were 469.5 ± 32.87 nm and − 21.70 ± 1.22 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 2.52%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging, including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect was positively correlated with their concentration. The imaging effects of tumour xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumour xenografts in vivo, the ICG-PTX NBs + US group showed more significant inhibition of cell proliferation and the promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs and the ICG-PTX NBs + US groups were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organs showed no obvious abnormalities in the ICG-PTX NBs and the ICG-PTX NBs + US groups.

Conclusions
ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent that can achieve multimodal imaging, including ultrasound, fluorescence and photoacoustic imaging, and can succeed in the local treatment of prostate cancer providing a potential novel method for integrated research on prostate cancer diagnosis and treatment.
Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme
Authors: Choi Jinyeong , Kim Gaeun , Cho Su Bin , Im Hyung-Jun 
Published: September 2020

AbstractRadiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date.
Construction of prognostic predictor by comprehensive analyzing alternative splicing events for colon adenocarcinoma
Authors: Qu Yaqi , Chen Yujia , Zhang Le , Tian Lifei 
Published: September 2020

Abstract
Background
Colon adenocarcinoma (COAD) is one of the most common malignant tumors, with high incidence and mortality rates worldwide. Reliable prognostic biomarkers are needed to guide clinical practice.

Methods
Comprehensive gene expression with alternative splicing (AS) profiles for each patient was downloaded using the SpliceSeq database from The Cancer Genome Atlas. Cox regression analysis was conducted to screen for prognostic AS events. The R package limma was used to screen differentially expressed genes (DEGs) between normal and tumor samples in the COAD cohort. A Venn plot analysis was performed between DEGs and prognostic AS events, and the DEGs that co-occurred with prognostic AS events (DEGAS) were identified. The top 30 most-connected DEGAS in protein–protein interaction analysis were identified through Cox proportional hazards regression to establish prognostic models.

Results
In total, 350 patients were included in the study. A total of 22,451 AS events were detected, of which 2004 from 1439 genes were significantly associated with survival time. By overlapping these 1439 genes with 6455 DEGs, 211 DEGs with AS events were identified. After the construction of the protein–protein interaction network, the top 30 hub genes were included in a multivariate analysis. Finally, a risk score based on 12 genes associated with overall survival was established (P < 0.05). The area under the curve was 0.782. The risk score was an independent predictor (P < 0.001).

Conclusions
By exploring survival-associated AS events, a powerful prognostic predictor consisting of 12 DEGAS was built. This study aims to propose a novel method to provide treatment targets for COAD and guide clinical practice in the future.