bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of continuous versus intermittent infusion cyclosporine and impact on transplant related outcomes in allogeneic transplant recipients
Authors: Engle Jeff A , Wasko Justin A , Rogosheske John , Defor Todd E , Rashidi Armin 
Published: November 2020

Introduction Continuous infusion (CIVI) cyclosporine (CsA) is an alternative for allograft recipients intolerant of twice daily infusions (TDI). The importance of achieving therapeutic levels of CsA early after allogeneic HCT has been demonstrated in previous studies. Our study evaluated the incidence of acute graft versus host disease (GVHD) and survival among patients receiving CIVI vs. TDI CsA during their first allogeneic HCT. Methods A retrospective study of adult patients undergoing first allogeneic HCT at the University of Minnesota Medical Center between 2011 and 2017. Patients were grouped according to the administration method. The primary outcome was the occurrence of acute grade II-IV GVHD by day +180. Secondary outcomes included the 1-year incidence of chronic GVHD, relapse, and overall survival. Results 42 patients intolerant of TDI CsA received CsA via CIVI for >48 hours for a median of 9 days (range, 3–32 days). CsA concentrations were similar between groups. We found no difference between the rates of grade II–IV acute (45% vs 53%, p = 0.59) or chronic (17% vs 30%, p = 0.20) GVHD or overall survival (57% vs 67%, p = 0.10). Subgroup analysis of patients that received myeloablative conditioning or umbilical cord blood did not reveal significant differences in GVHD or overall survival. Cumulative incidence of relapse was higher among the continuous infusion group (39% vs. 23%, p < 0.01). Conclusion Due to the finding of increased risk of relapse, cyclosporine should be administered as traditional twice daily infusion unless necessary. A prospective clinical trial is needed to confirm these results.
MiR-9-5p Inhibits the Proliferation, Migration and Invasion of Choroidal Melanoma by Targeting BRAF
Authors: Ying Manman , Feng Hao , Zhang Xiaonan , Liu Ran , Ning Hong 
Published: November 2020

Objective: According to different reports, miR-9-5p either facilitates or suppresses the occurrence of tumors. BRAF is a serine/threonine kinase involved in the MAPK pathway and is a proto-oncogene promoting the progression of many tumors, especially melanoma. The present study aimed to reveal the mechanism of action of miR-9-5p and BRAF in choroidal melanoma (CM). Methods: RT-qPCR was used to detect the expression of miR-9-5p in CM cells after transfection with miR-9-5p mimics and inhibitor. EdU assay and Transwell assay, respectively, showed the proliferation, migration and invasion of CM cells after transfection with miR-9-5p mimics and inhibitor. A bioinformatics website was used for target prediction and the dual luciferase reporter assay was used to verify the interaction between miR-9-5p and BRAF. RT-qPCR and Western blot were performed to examine the expression of BRAF mRNA and protein, respectively. The BRAF protein was knocked down by siRNAs and then examined by Western blot. The effects of BRAF in CM cells were investigated by EdU assay and Transwell assay. Overexpressing BRAF and transfecting miR-9-5p mimics into choroidal melanoma cells confirmed the interaction between miR-9-5p and BRAF. Results: miR-9-5p could bind to the BRAF mRNA 3’UTR and inhibit the transcription and translation of BRAF, thereby suppressing the proliferation, migration and invasion of CM cell lines. Moreover, silencing BRAF inhibited the progression of CM cells. Conclusions: In conclusion, this study is the first to investigate the association among BRAF, miR-9-5p and the progression of CM cells. In addition, the interaction between BRAF and miR-9-5p was explored for the first time in CM. Thus, our study suggests that miR-9-5p, BRAF and their interaction may act as potential therapeutic targets for CM.
Retinal Manifestations of Incontinentia Pigmenti: A Case Series of 14 Patients Highlighting the Importance of Intravenous Fluorescein Angiography and the Benefits of Early Laser Photocoagulation
Authors: Bryan Jaimie , Issa Reda , Bakall Benjamin , Welch Matthew , Bryan J. Shepard 
Published: November 2020

Purpose: This case series describes the nature and frequency of retinal manifestations in patients with incontinentia pigmenti (IP). Methods: This is a retrospective single-center case series of all known patients with IP who presented to Associated Retina Consultants (Phoenix, AZ) between May 2016 and April 2019. Twenty-eight eyes of 14 patients with a dermatologic diagnosis of IP were included (n = 28). Most patients underwent examination under anesthesia with fundus photographs and intravenous fluorescein angiography (IVFA). Results: Of the 28 eyes, 8 (28.6%) had abnormal retinal findings on fundus examination. Of the 26 eyes that had IVFA, 10 (38.5%) had abnormal findings: Seven eyes (26.9%) had peripheral ischemia, 2 (7.7%) had previous peripheral laser scarring, and 2 (7.7%) had active peripheral neovascularization. Three eyes with normal examination results were found to have mild ischemia by IVFA. Patients with ischemia confirmed by IVFA were treated with laser photocoagulation. During follow-up, 4 previously treated eyes received additional laser photocoagulation. No patients showed vision loss, vitreous hemorrhage, retinal detachment, or adverse effects of treatment. No patients required vitreoretinal surgery. Conclusions: IP is a potentially blinding disease. Our case series demonstrates the efficacy of early treatment and the importance of ancillary testing with IVFA and fundus photography.
Active Akt signaling triggers CLL toward Richter transformation via overactivation of Notch1
Authors: Kohlhaas Vivien , Blakemore Stuart James , Al-Maarri Mona , Nickel Nadine , Pal Martin , Roth Andreas , Hövelmeyer Nadine , Schäfer Stephan C. , Knittel Gero , Lohneis Philipp , Nikolic Milos , Wiederstein Janica L. , Franitza Marek , Georgomonolis Theodoros , Reinart Nina , Herling Marco , Herling Carmen , Hartmann Elena M. , Rosenwald Andreas , Klapper Wolfram , Büttner Reinhard , Moia Riccardo , Rossi Davide , Boldorini Renzo , Gaidano Gianluca , Frenzel Lukas P. , Reinhardt Hans Christian , Brüning Jens C. , Hallek Michael , Krüger Marcus , Peifer Martin , Pallasch Christian P. , Wunderlich F. Thomas 
Published: November 2020

Abstract
Richter’s transformation (RT) is an aggressive lymphoma that occurs upon progression from chronic lymphocytic leukemia (CLL). Transformation has been associated with genetic aberrations in the CLL phase involving TP53, CDKN2A, MYC, and NOTCH1; however, a significant proportion of RT cases lack CLL phase–associated events. Here, we report that high levels of AKT phosphorylation occur both in high-risk CLL patients harboring TP53 and NOTCH1 mutations as well as in patients with RT. Genetic overactivation of Akt in the murine Eµ-TCL1 CLL mouse model resulted in CLL transformation to RT with significantly reduced survival and an aggressive lymphoma phenotype. In the absence of recurrent mutations, we identified a profile of genomic aberrations intermediate between CLL and diffuse large B-cell lymphoma. Multiomics assessment by phosphoproteomic/proteomic and single-cell transcriptomic profiles of this Akt-induced murine RT revealed an S100 protein-defined subcluster of highly aggressive lymphoma cells that developed from CLL cells, through activation of Notch via Notch ligand expressed by T cells. Constitutively active Notch1 similarly induced RT of murine CLL. We identify Akt activation as an initiator of CLL transformation toward aggressive lymphoma by inducing Notch signaling between RT cells and microenvironmental T cells.
Container-aided integrative QTL and RNA-seq analysis of Collaborative Cross mice supports distinct sex-oriented molecular modes of response in obesity
Authors: Binenbaum Ilona , Atamni Hanifa Abu-Toamih , Fotakis Georgios , Kontogianni Georgia , Koutsandreas Theodoros , Pilalis Eleftherios , Mott Richard , Himmelbauer Heinz , Iraqi Fuad A. , Chatziioannou Aristotelis A. 
Published: November 2020

AbstractBackgroundThe Collaborative Cross (CC) mouse population is a valuable resource to study the genetic basis of complex traits, such as obesity. Although the development of obesity is influenced by environmental factors, underlying genetic mechanisms play a crucial role in the response to these factors. The interplay between the genetic background and the gene expression pattern can provide further insight into this response, but we lack robust and easily reproducible workflows to integrate genomic and transcriptomic information in the CC mouse population.ResultsWe established an automated and reproducible integrative workflow to analyse complex traits in the CC mouse genetic reference panel at the genomic and transcriptomic levels. We implemented the analytical workflow to assess the underlying genetic mechanisms of host susceptibility to diet induced obesity and integrated these results with diet induced changes in the hepatic gene expression of susceptible and resistant mice. Hepatic gene expression differs significantly between obese and non-obese mice, with a significant sex effect, where male and female mice exhibit different responses and coping mechanisms.ConclusionIntegration of the data showed that different genes but similar pathways are involved in the genetic susceptibility and disturbed in diet induced obesity. Genetic mechanisms underlying susceptibility to high-fat diet induced obesity are different in female and male mice. The clear distinction we observed in the systemic response to the high-fat diet challenge and to obesity between male and female mice points to the need for further research into distinct sex-related mechanisms in metabolic disease.
High-throughput sequencing analysis of the rhizosphere arbuscular mycorrhizal fungi (AMF) community composition associated with Ferula sinkiangensis
Authors: Luo Yunfeng , Wang Zhongke , He Yaling , Li Guifang , Lv Xinhua , Zhuang Li 
Published: November 2020

Abstract

Background
Ferula sinkiangensis is an increasingly endangered medicinal plant. Arbuscular mycorrhiza fungi (AMF) are symbiotic microorganisms that live in the soil wherein they enhance nutrient uptake, stress resistance, and pathogen defense in host plants. While such AMF have the potential to contribute to the cultivation of Ferula sinkiangensis, the composition of AMF communities associated with Ferula sinkiangensis and the relationship between these fungi and other pertinent abiotic factors still remains to be clarified.

Results
Herein, we collected rhizosphere and surrounding soil samples at a range of depths (0–20, 20–40, and 40–60 cm) and a range of slope positions (bottom, middle, top). These samples were then subjected to analyses of soil physicochemical properties and high-throughput sequencing (Illumina MiSeq). We determined that Glomus and Diversispora species were highly enriched in all samples. We further found that AMF diversity and richness varied significantly as a function of slope position, with this variation primarily being tied to differences in relative Glomus and Diversispora abundance. In contrast, no significant relationship was observed between soil depth and overall AMF composition, although some AMF species were found to be sensitive to soil depth. Many factors significantly affected AMF community composition, including organic matter content, total nitrogen, total potassium, ammonium nitrogen, nitrate nitrogen, available potassium, total dissolvable salt levels, pH, soil water content, and slope position. We further determined that Shannon diversity index values in these communities were positively correlated with total phosphorus, nitrate-nitrogen levels, and pH values (P < 0.05), whereas total phosphorus, total dissolvable salt levels, and pH were positively correlated with Chao1 values (P < 0.05).

Conclusion
In summary, our data revealed that Glomus and Diversispora are key AMF genera found within Ferula sinkiangensis rhizosphere soil. These fungi are closely associated with specific environmental and soil physicochemical properties, and these soil sample properties also differed significantly as a function of slope position (P < 0.05). Together, our results provide new insights regarding the relationship between AMF species and Ferula sinkiangensis, offering a theoretical basis for further studies of their development.
Tissue-specific expression analysis of Na+ and Cl− transporter genes associated with salt removal ability in rice leaf sheath
Authors: Neang Sarin , Goto Itsuki , Skoulding Nicola Stephanie , Cartagena Joyce A. , Kano-Nakata Mana , Yamauchi Akira , Mitsuya Shiro 
Published: November 2020

Abstract

Background
A significant mechanism of salt-tolerance in rice is the ability to remove Na+ and Cl− in the leaf sheath, which limits the entry of these toxic ions into the leaf blade. The leaf sheath removes Na+ mainly in the basal parts, and Cl− mainly in the apical parts. These ions are unloaded from the xylem vessels in the peripheral part and sequestered into the fundamental parenchyma cells at the central part of the leaf sheath.

Results
This study aimed to identify associated Na+ and Cl− transporter genes with this salt removal ability in the leaf sheath of rice variety FL 478. From 21 known candidate Na+ and Cl− transporter rice genes, we determined the salt responsiveness of the expression of these genes in the basal and apical parts, where Na+ or Cl− ions were highly accumulated under salinity. We also compared the expression levels of these transporter genes between the peripheral and central parts of leaf sheaths. The expression of 8 Na+ transporter genes and 3 Cl− transporter genes was up-regulated in the basal and apical parts of leaf sheaths under salinity. Within these genes, OsHKT1;5 and OsSLAH1 were expressed highly in the peripheral part, indicating the involvement of these genes in Na+ and Cl− unloading from xylem vessels. OsNHX2, OsNHX3, OsNPF2.4 were expressed highly in the central part, which suggests that these genes may function in sequestration of Na+ and Cl− in fundamental parenchyma cells in the central part of leaf sheaths under salinity. Furthermore, high expression levels of 4 candidate genes under salinity were associated with the genotypic variation of salt removal ability in the leaf sheath.

Conclusions
These results indicate that the salt removal ability in rice leaf sheath may be regulated by expressing various Na+ or Cl− transporter genes tissue-specifically in peripheral and central parts. Moreover, some genes were identified as candidates whose expression levels were associated with the genotypic variation of salt removal ability in the leaf sheath. These findings will enhance the understanding of the molecular mechanism of salt removal ability in rice leaf sheath, which is useful for breeding salt-tolerant rice varieties.
The molecular basis for allelic differences suggests Restorer-of-fertility 1 is a complex locus in sugar beet (Beta vulgaris L.)
Authors: Arakawa Takumi , Matsunaga Muneyuki , Matsui Katsunori , Itoh Kanna , Kuroda Yosuke , Matsuhira Hiroaki , Kitazaki Kazuyoshi , Kubo Tomohiko 
Published: November 2020

AbstractBackgroundCytoplasmic male sterility (CMS) is a widely used trait for hybrid seed production in many crops. Sugar beet CMS is associated with a unique mitochondrial protein named preSATP6 that forms a 250-kDa complex.Restorer-of-fertility 1(Rf1) is a nuclear gene that suppresses CMS and is, hence, one of the targets of sugar beet breeding.Rf1has dominant, semi-dominant and recessive alleles, suggesting that it may be a multi-allelic locus; however, the molecular basis for differences in genetic action is obscure. Molecular cloning ofRf1revealed a gene (orf20) whose protein products produced in transgenics can bind with preSATP6 to generate a novel 200-kDa complex. The complex is also detected in fertility-restored anthers concomitant with a decrease in the amount of the 250-kDa complex. Molecular diversity of theRf1locus involves organizational diversity of a gene cluster composed oforf20-like genes (RF-Oma1s). We examined the possibility that members of the clusteredRF-Oma1in this locus could be associated with fertility restoration.ResultsSix yet uncharacterizedRF-Oma1s from dominant and recessive alleles were examined to determine whether they could generate the 200-kDa complex. Analyses of transgenic calli revealed that threeRF-Oma1s from a dominant allele could generate the 200-kDa complex, suggesting that clusteredRF-Oma1s in the dominant allele can participate in fertility restoration. None of the three copies from two recessive alleles was 200-kDa generative. The absence of this ability was confirmed by analyzing mitochondrial complexes in anthers of plants having these recessive alleles. Together with our previous data, we designed a set of PCR primers specific to the 200-kDa generativeRF-Oma1s. The amount of mRNA measured by this primer set inversely correlated with the amount of the 250-kDa complex in anthers and positively correlated with the strength of theRf1alleles.ConclusionsFertility restoration by sugar beetRf1can involve multipleRF-Oma1s clustered in the locus, implying that stacking 200-kDa generative copies in the locus strengthens the efficacy, whereas the absence of 200-kDa generative copies in the locus makes the allele recessive irrespective of the copy number. We propose that sugar beetRf1is a complex locus.
Midterm postoperative prognosis of patients with severe left heart valvular disease combined with moderate or severe pulmonary hypertension treated with treprostinil
Authors: Xu Ning , Huang Shu-Ting , Sun Kai-Peng , Wang Zeng-Chun , Cao Hua , Chen Qiang 
Published: November 2020

Abstract

Background
To investigate the midterm postoperative prognosis of patients with severe left heart valvular disease combined with moderate or severe pulmonary hypertension (PAH) using subcutaneous injection of treprostinil.

Methods
A retrospective study was conducted on 61 patients with severe left heart valvular disease combined with moderate or severe PAH who had undergone mechanical mitral and/or aortic valve replacement from April 2018 to October 2018. The patients were divided into the treprostinil group and the conventional treatment group according to whether they received treprostinil. The patients were assessed by SwanGanz catheterization, echocardiography, the 6-min walk test (6-MWT), the Borg dyspnoea score and the SF-36 questionnaire.

Results
Compared with the preoperative data, the mPAP measured by SwanGanz catheterization, the results of the 6-MWT and the Borg score were significantly improved in both groups during the 1 year follow-up (P < 0.05). Regarding the comparison between the groups, the results in group T were significantly better than those in group C, including the results of the 6-MWT and the general health, vitality and mental health of SF-36 during the 1 year follow-up (P < 0.05).

Conclusions
Continuous subcutaneous infusion of treprostinil was not capable of decreasing pulmonary pressures in patients with severe left heart valvular disease combined with moderate or severe PAH during 1 year follow-up, although which some of our data suggest that might improve the symptoms and quality of life of these patients.
An implementation science approach for developing and implementing a dietitian-led model of care for gestational diabetes: a pre-post study
Authors: MELONCELLI Nina , BARNETT Adrian , de JERSEY Susan 
Published: November 2020

Abstract

Background
There is strong evidence that women with gestational diabetes mellitus (GDM) who receive a minimum of three appointments with a dietitian may require medication less often. The aim of this study was to evaluate the impact of a dietitian-led model of care on clinical outcomes and to understand the utility of the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework as a prospective tool for implementation.

Methods
This was a pre-post intervention study measuring outcomes before-and-after changing a gestational diabetes (GDM) model of care and included women with GDM managed at a large, regional hospital in Queensland, Australia. The i-PARIHS framework was used to develop, implement and evaluate a dietitian-led model of care which increased dietetic input for women with GDM to a minimum of one initial education and two review appointments. The outcomes were adherence to the schedule of appointments, clinician perspective of the implementation process, pharmacotherapy use, gestational age at commencement of pharmacotherapy and birth weight. Pre- and post- comparisons of outcomes were made using t-tests and chi-squared tests.

Results
Adherence to the dietetic schedule of appointments was significantly increased from 29 to 82% (p < 0.001) but pharmacotherapy use also increased by 10% (p = 0.10). There were significantly more women in the post-intervention group who were diagnosed with GDM prior to 24 weeks gestation, a strong independent predictor of pharmacotherapy use. Infant birthweight remained unchanged. The i-PARIHS framework was used as a diagnostic tool and checklist in the model of care development phase; a facilitation tool during the implementation phase; and during the evaluation phase was used as a reflection tool to identify how the i-PARIHS constructs and their interactions that may have impacted on clinical outcomes.

Conclusions
The i-PARIHS framework was found to be useful in the development, implementation and evaluation of a dietitian-led model of care which saw almost 90% of women with GDM meet the minimum schedule of dietetic appointments.
Risk factors for neonatal bronchopulmonary dysplasia in extremely preterm premature rupture of membranes: a retrospective study
Authors: Nakamura Eishin , Matsunaga Shigetaka , Ono Yoshihisa , Takai Yasushi , Seki Hiroyuki 
Published: November 2020

Abstract

Background
Determination of the optimal timing for termination of pregnancy in cases of preterm premature rupture of membranes (pPROM) during the extremely preterm period is still difficult. Bronchopulmonary dysplasia (BPD) is a major disease widely taken into account when determining the prognosis of respiratory disorders in a neonate. Many aspects of this disease remain unclear. With the aim of further improving the prognosis of neonates born to mothers with pPROM, this study examined cases who were diagnosed with pPROM before 28 weeks of gestation. The study analysed risk factors for neonatal BPD.

Methods
This study included 73 subjects with singleton pregnancy, diagnosed with pPROM during the gestational period from 22 weeks and 0 days to 27 weeks and 6 days. The following factors were retrospectively examined: the gestational week at which pPROM was diagnosed, the gestational week at which delivery occurred, the period for which the volume of amniotic fluid was maintained, and neonatal BPD as a complication. Receiver operating characteristic (ROC) curve analyses were conducted to analyse the relationship of the onset of BPD with the duration of oligohydramnios and the gestational weeks of delivery.

Results
The mean gestational week at which a diagnosis of amniorrhexis was made was 24.5 ± 1.9 weeks (mean ± SD), and that at which delivery occurred was 27.0 ± 3.0 weeks. Fifty-seven cases (78.1%) were diagnosed with oligohydramnios, the mean duration of which was 17.4 ± 20.5 days. The mean birth weight of neonates was 1000 ± 455 g, of which 49 (67.1%) were diagnosed with BPD following birth. No neonates died in this study. The ROC curve indicated that the cut-off values for the duration of oligohydramnios and gestational age at delivery were 4 days and 24.1 weeks, respectively. Multivariate analysis indicated that the duration of oligohydramnios for more than 4 days before delivery and preterm delivery at less than 24.1 weeks were risk factors for the onset of BPD.

Conclusions
Our findings suggest that duration of oligohydramnios for more than 4 days before delivery and preterm delivery less than 24.1 weeks are risk factors for BPD in cases who are diagnosed with pPROM before 28 weeks of gestation.