bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isotope ratio-based quantification of carbon assimilation highlights the role of plastidial isoprenoid precursor availability in photosynthesis
Authors: Bergman Matthew E. , González-Cabanelas Diego , Wright Louwrance P. , Walker Berkley J. , Phillips Michael A. 
Published: March 2021

Abstract
Background
We report a method to estimate carbon assimilation based on isotope ratio-mass spectrometry (IRMS) of 13CO2 labeled plant tissue. Photosynthetic carbon assimilation is the principal experimental observable which integrates important aspects of primary plant metabolism. It is traditionally measured through gas exchange. Despite its centrality in plant research, gas exchange performs poorly with rosette growth habits typical of Arabidopsis thaliana, mutant lines with limited biomass, and accounts poorly for leaf shading.

Results
IRMS-based carbon assimilation values from plants labeled at different light intensities were compared to those obtained by gas exchange, and the two methods yielded similar values. Using this method, we observed a strong correlation between 13C content and labeling time (R2 = 0.999) for 158 wild-type plants labeled for 6 to 42 min. Plants cultivated under different light regimes showed a linear response with respect to carbon assimilation, varying from 7.38 nmol 13C mg−1 leaf tissue min−1 at 80 PAR to 19.27 nmol 13C mg−1 leaf tissue min−1 at 500 PAR. We applied this method to examine the link between inhibition of the 2C-methyl-d-erythritol-4-phosphate (MEP) pathway and suppression of photosynthesis. A significant decrease in carbon assimilation was observed when metabolic activity in the MEP pathway was compromised by mutation or herbicides targeting the MEP pathway. Mutants affected in MEP pathway genes 1-DEOXY-d-XYLULOSE 5-PHOSPHATE SYNTHASE (DXS) or 1-HYDROXY-2-METHYL-2-(E)-BUTENYL 4-DIPHOSPHATE SYNTHASE (HDS) showed assimilation rates 36% and 61% lower than wild type. Similarly, wild type plants treated with the MEP pathway inhibitors clomazone or fosmidomycin showed reductions of 52% and 43%, respectively, while inhibition of the analogous mevalonic acid pathway, which supplies the same isoprenoid intermediates in the cytosol, did not, suggesting inhibition of photosynthesis was specific to disruption of the MEP pathway.

Conclusions
This method provides an alternative to gas exchange that offers several advantages: resilience to differences in leaf overlap, measurements based on tissue mass rather than leaf surface area, and compatibility with mutant Arabidopsis lines which are not amenable to gas exchange measurements due to low biomass and limited leaf surface area. It is suitable for screening large numbers of replicates simultaneously as well as post-hoc analysis of previously labeled plant tissue and is complementary to downstream detection of isotopic label in targeted metabolite pools.
Combination of dirty mass volume and APACHE II score predicts mortality in patients with colorectal perforation
Authors: Ishikawa Daichi , Takehara Yukako , Takata Atsushi , Takamura Kazuhito , Sato Hirohiko 
Published: March 2021

Abstract
Background
“Dirty mass” is a specific computed tomography (CT) finding that is seen frequently in colorectal perforation. The prognostic significance of this finding for mortality is unclear.

Methods
Fifty-eight consecutive patients with colorectal perforation who underwent emergency surgery were retrospectively reviewed in the study. Dirty mass identified on multi-detector row CT (MDCT) was 3D-reconstructed and its volume was calculated using Ziostation software. Dirty mass volume and other clinical characteristics were compared between survivor (n = 45) and mortality groups (n = 13) to identify predictive factors for mortality. Mann–Whitney U test and Χ2 test were used in univariate analysis and logistic regression analysis was used in multivariate analysis.

Results
Dirty mass was identified in 36/58 patients (62.1%) and located next to perforated colorectum in all cases. Receiver-operating characteristic (ROC) curve analysis identified the highest peak at 96.3 cm3, with sensitivity of 0.643 and specificity of 0.864. Univariate analysis revealed dirty mass volume, acute disseminated intravascular coagulation (DIC) score, acute physiology and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score as prognostic markers for mortality (p<0.01). Multivariate analysis revealed dirty mass volume and APACHE II score as independent prognostic indicators for mortality. Mortality was stratified by dividing patients into four groups according to dirty mass volume and APACHE II score.

Conclusions
The combination of dirty mass volume and APACHE II score could stratify the postoperative mortality risk in patients with colorectal perforation. According to the risk stratification, surgeons might be able to decide the surgical procedures and intensity of postoperative management.
Construction and validation of nomogram to predict distant metastasis in osteosarcoma: a retrospective study
Authors: Lu Shouliang , Wang Yanhua , Liu Guangfei , Wang Lu , Wu Pengfei , Li Yong , Cheng Cai 
Published: March 2021

Abstract
Background
Osteosarcoma is most common malignant bone tumors. OS patients with metastasis have a poor prognosis. There are few tools to assess metastasis; we want to establish a nomogram to evaluate metastasis of osteosarcoma.

Methods
Data from the Surveillance, Epidemiology, and End Results (SEER) database of patients with osteosarcoma were retrieved for retrospective analysis. We identify risk factors through univariate logistic regression and multivariate logistic regression analysis. Based on the results of multivariate analysis, we established a nomogram to predict metastasis of patients with osteosarcoma and used the concordance index (C-index) and calibration curves to test models.

Results
One thousand fifteen cases were obtained from the SEER database. In the univariate and multivariate logistic regression analysis, age, primary site, grade, T stage, and surgery are risk factors. The nomogram for metastasis was constructed based on these factors. The C-index of the training and validation cohort was 0.754 and 0.716. This means that the nomogram predictions of patients with metastasis are correct, and the calibration plots also show the good prediction performance of the nomogram.

Conclusion
We successfully develop the nomogram which can reliably predict metastasis in different patients with osteosarcoma and it only required basic information of patients. The nomogram that we developed can help clinicians better predict the metastasis with OS and determine postoperative treatment strategies.
Angioplasty for the treatment of left brachiocephalic vein aneurysm: a case report
Authors: Gui Long , Xu Hongbo , Ning Chengdong , Huang Niuliu , Pan Yu 
Published: March 2021

Abstract
Background
Brachiocephalic vein aneurysm is a rare vascular malformation, which is often reported in case reports. At present it has attracted much attention due to the serious complications, such as vein aneurysm rupture, pulmonary embolism, venous thrombosis, etc. We report a case of left brachiocephalic vein aneurysm with compression symptoms.

Case presentation
a 52-year-old male who was admitted to our hospital with irritating cough for more than 1 month. Chest contrast-enhanced CT showed a localized expansion of 5.2 cm in diameter of the left brachiocephalic vein in the anterior mediastinum. The patient received venous angioplasty with brachiocephalic vein aneurysm resection, and the postoperative recovery was well.

Conclusion
Surgical operation is an effecive treatment method for brachiocephalic vein aneurysm, but it is still necessary to choose the appropriate way according to the type, size, location, lesion scope and complications of the vein aneurysm.
Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study
Authors: Zito Marino Federica , Sabetta Rosalaura , Pagliuca Francesca , Brunelli Matteo , Aquino Gabriella , Perdonà Sisto , Botti Gerardo , Facchini Gaetano , Fiorentino Francesco , Di Lauro Giovanni , De Sio Marco , De Vita Ferdinando , Toni Giorgio , Borges Dos Reis Rodolfo , Neder Luciano , Franco Renato 
Published: March 2021

Abstract
Background
The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30–50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue.

Methods
We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC.

Results
The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 − 15 %- versus 6 out of 60 − 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 − 10 %- versus 4 out of 60 − 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity.

Conclusions
Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %.
Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.
Projection-dependent heterogeneity of cerebellar granule cell calcium responses
Authors: Rhee Jun Kyu , Park Heeyoun , Kim Taegon , Yamamoto Yukio , Tanaka-Yamamoto Keiko 
Published: March 2021

AbstractCerebellar granule cells (GCs) relay mossy fiber (MF) inputs to Purkinje cell dendrites via their axons, the parallel fibers (PFs), which are individually located at a given sublayer of the molecular layer (ML). Although a certain degree of heterogeneity among GCs has been recently reported, variability of GC responses to MF inputs has never been associated with their most notable structural variability, location of their projecting PFs in the ML. Here, we utilize an adeno-associated virus (AAV)-mediated labeling technique that enables us to categorize GCs according to the location of their PFs, and compare the Ca2+ responses to MF stimulations between three groups of GCs, consisting of either GCs having PFs at the deep (D-GCs), middle (M-GCs), or superficial (S-GCs) sublayer. Our structural analysis revealed that there was no correlation between position of GC soma in the GC layer and location of its PF in the ML, confirming that our AAV-mediated labeling was important to test the projection-dependent variability of the Ca2+ responses in GCs. We then found that the Ca2+ responses of D-GCs differed from those of M-GCs. Pharmacological experiments implied that the different Ca2+ responses were mainly attributable to varied distributions of GABAA receptors (GABAARs) at the synaptic and extrasynaptic regions of GC dendrites. In addition to GABAAR distributions, amounts of extrasynaptic NMDA receptors appear to be also varied, because Ca2+ responses were different between D-GCs and M-GCs when glutamate spillover was enhanced. Whereas the Ca2+ responses of S-GCs were mostly equivalent to those of D-GCs and M-GCs, the blockade of GABA uptake resulted in larger Ca2+ responses in S-GCs compared with D-GCs and M-GCs, implying existence of mechanisms leading to more excitability in S-GCs with increased GABA release. Thus, this study reveals MF stimulation-mediated non-uniform Ca2+ responses in the cerebellar GCs associated with the location of their PFs in the ML, and raises a possibility that combination of inherent functional variability of GCs and their specific axonal projection contributes to the information processing through the GCs.
Impaired pattern separation in Tg2576 mice is associated with hyperexcitable dentate gyrus caused by Kv4.1 downregulation
Authors: Kim Kyung-Ran , Kim Yoonsub , Jeong Hyeon-Ju , Kang Jong-Sun , Lee Sang Hun , Kim Yujin , Lee Suk-Ho , Ho Won-Kyung 
Published: March 2021

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that causes memory loss. Most AD researches have focused on neurodegeneration mechanisms. Considering that neurodegenerative changes are not reversible, understanding early functional changes before neurodegeneration is critical to develop new strategies for early detection and treatment of AD. We found that Tg2576 mice exhibited impaired pattern separation at the early preclinical stage. Based on previous studies suggesting a critical role of dentate gyrus (DG) in pattern separation, we investigated functional changes in DG of Tg2576 mice. We found that granule cells in DG (DG-GCs) in Tg2576 mice showed increased action potential firing in response to long depolarizations and reduced 4-AP sensitive K+-currents compared to DG-GCs in wild-type (WT) mice. Among Kv4 family channels, Kv4.1 mRNA expression in DG was significantly lower in Tg2576 mice. We confirmed that Kv4.1 protein expression was reduced in Tg2576, and this reduction was restored by antioxidant treatment. Hyperexcitable DG and impaired pattern separation in Tg2576 mice were also recovered by antioxidant treatment. These results highlight the hyperexcitability of DG-GCs as a pathophysiologic mechanism underlying early cognitive deficits in AD and Kv4.1 as a new target for AD pathogenesis in relation to increased oxidative stress.
MTSplice predicts effects of genetic variants on tissue-specific splicing
Authors: Cheng Jun , Çelik Muhammed Hasan , Kundaje Anshul , Gagneur Julien 
Published: March 2021

AbstractWe develop the free and open-source model Multi-tissue Splicing (MTSplice) to predict the effects of genetic variants on splicing of cassette exons in 56 human tissues. MTSplice combines MMSplice, which models constitutive regulatory sequences, with a new neural network that models tissue-specific regulatory sequences. MTSplice outperforms MMSplice on predicting tissue-specific variations associated with genetic variants in most tissues of the GTEx dataset, with largest improvements on brain tissues. Furthermore, MTSplice predicts that autism-associated de novo mutations are enriched for variants affecting splicing specifically in the brain. We foresee that MTSplice will aid interpreting variants associated with tissue-specific disorders.
Homopolish: a method for the removal of systematic errors in nanopore sequencing by homologous polishing
Authors: Huang Yao-Ting , Liu Po-Yu , Shih Pei-Wen 
Published: March 2021

AbstractNanopore sequencing has been widely used for the reconstruction of microbial genomes. Owing to higher error rates, errors on the genome are corrected via neural networks trained by Nanopore reads. However, the systematic errors usually remain uncorrected. This paper designs a model that is trained by homologous sequences for the correction of Nanopore systematic errors. The developed program, Homopolish, outperforms Medaka and HELEN in bacteria, viruses, fungi, and metagenomic datasets. When combined with Medaka/HELEN, the genome quality can exceed Q50 on R9.4 flow cells. We show that Nanopore-only sequencing can produce high-quality microbial genomes sufficient for downstream analysis.
Assessment of remifentanil for rapid sequence induction and intubation in patients at risk of pulmonary aspiration of gastric contents compared to rapid-onset paralytic agents: study protocol for a non-inferiority simple blind randomized controlled trial (the REMICRUSH study)
Authors: Grillot Nicolas , Garot Matthias , Lasocki Sigismond , Huet Olivier , Bouzat Pierre , Le Moal Charlène , Oudot Mathieu , Chatel-Josse Nolwenn , El Amine Younes , Danguy des Déserts Marc , Bruneau Nathalie , Cinotti Raphael , David Jean-Stéphane , Langeron Olivier , Minville Vincent , Tching-Sin Martine , Faurel-Paul Elodie , Lerebourg Céline , Flattres-Duchaussoy Delphine , Jobert Alexandra , Asehnoune Karim , Feuillet Fanny , Roquilly Antoine 
Published: March 2021

Abstract
Background
Rapid-onset paralytic agents are recommended to achieve muscle relaxation and facilitate tracheal intubation during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents. However, opioids are frequently used in this setting. The study’s objective is to demonstrate the non-inferiority of remifentanil compared to rapid-onset paralytic agents, in association with an hypnotic drug, for tracheal intubation in patients undergoing procedure under general anesthesia and at risk of pulmonary aspiration of gastric contents.

Methods
The REMICRUSH (Remifentanil for Rapid Sequence Induction of Anaesthesia) study is a multicenter, single-blinded, non-inferiority randomized controlled trial comparing remifentanil (3 to 4 μg/kg) with rapid-onset paralytic agents (succinylcholine or rocuronium 1 mg/kg) for rapid sequence induction in 1150 adult surgical patients requiring tracheal intubation during general anesthesia. Enrolment started in October 2019 in 15 French anesthesia units. The expected date of the final follow-up is October 2021. The primary outcome is the proportion of successful tracheal intubation without major complications. A non-inferiority margin of 7% was chosen. Analyses of the intent-to-treat and per-protocol populations are planned.

Discussion
The REMICRUSH trial protocol has been approved by the ethics committee of The Comité de Protection des Personnes Sud-Ouest et Outre-Mer II and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The REMICRUSH trial is the first randomized controlled trial powered to investigate whether remifentanil with hypnotics is non-inferior to rapid-onset paralytic agents with hypnotic in rapid sequence induction of anesthesia for full stomach patients considering successful tracheal intubation without major complication.

Trial registration
ClinicalTrials.gov NCT03960801. Registered on May 23, 2019.
Clinical study on the effect of multifocal contact lenses on myopia progression in myopia school children
Authors: Hieda Osamu , Nakamura Yo , Hiraoka Takahiro , Kojima Miho , Oshika Tetsuro , Sotozono Chie 
Published: March 2021

Abstract
Background
The efficacy of peripheral low add multifocal soft contact lenses (SCLs) for suppressing the progression of myopia is controversial. The aim of the on-going present clinical study is to investigate whether or not multifocal SCLs with + 0.50 diopters (D) addition suppress the progression of myopia in myopic elementary school children.

Design
Prospective randomized controlled trial.

Subjects and methods
The study plans to include a total of 100 myopic school children. Target subjects are primary school male and female students with mild to moderate myopia. Children who have eye-related diseases other than myopia are excluded from the study, because they may affect the evaluation of the outcome. Subjects will be randomly assigned to wear daily disposable multifocal contact lenses with + 0.50D addition or daily disposable SCLs. Subjects will wear contact lenses on both eyes and will be observed for 2 years under a double-masked examination. Primary outcome is a change in the axial length over the 2-year period.

Objectives
The purpose of this study is to identify whether or not multifocal SCLs with + 0.5D addition suppress the progression of myopia in myopic elementary school children as compared with standard SCLs.

Trial registration
1. UMIN (University Hospital Medical Information Network) UMIN000027940. Registered on July 21, 2017
2. JRCT (Japan Registry of Clinical Trials) jRCTs052180172. Registered on March 26, 2019
Promising proteins detected by Western blot from Echinococcus granulosus protoscoleces for predicting early post-surgical outcomes in CE-affected Tunisian children
Authors: Salah Eya Ben , Barrera Coralie , Mosbahi Sana , Gottstein Bruno , Siles-Lucas Mar , Belhassen Samia , Nouri Abdellatif , BABBA Hamouda , Millon Laurence , Sakly Wahiba 
Published: March 2021

AbstractBackgroundCystic echinococcosis (CE) affects predominantly young patients in highly endemic areas. Improved serological methods are needed for the follow-up of CE cases, especially given the high rates of post-surgical relapse that require detection as soon as possible.MethodsWe designed a study to investigate the value of antigenic proteins extracted fromEchinococcus granulosus(E. granulosus) protoscoleces, and of recombinant B2t and 2B2t proteins, for assessing the efficacy of surgical treatment carried out on CE-affected children. This study was performed on 278 plasma samples collected from 59 Tunisian children surgically treated for CE and monitored for 3 years post-surgery. The patients were classified according to post-surgical outcomes into a “non-relapsed” (NRCE) and a “relapsed” (RCE) group. We performed in-house ELISAs to measure anti-B2t and anti-2B2t IgG and immunoblotting for the detection of IgG against SDS-PAGE-resolvedE. granulosusprotoscoleces-specific antigens. The Wilcoxon test was applied to assess anti-B2t and anti-2B2t IgG levels. We applied the Cochran Q test to compare the distribution of immunoblotting antigenic bands between 1-month and 1-year post-surgery.ResultsThe probability of being “relapse-free” when a decrease in antibody titers occurred between 1 month and 1 year post-surgery was 81% and 75%, respectively, for anti-B2t and anti-2B2t IgG. We identified five protoscolex protein bands of 20, 26/27, 30, 40 and 46 kDa as highly immunoreactive by immunoblot for both RCE and NRCE patients at 1 month post-surgery, and significantly lower immunoreactivity after 1 year (p < 10–4) for NRCE compared to RCE patients. The proteins at 26/27 and 40 kDa displayed the best performance in predicting the outcome, with an 84% probability of being relapse-free when the reactivity against the 40 kDa antigen, the doublet at 26/27 kDa, or both was absent or disappeared between 1 month and 1 year post-surgery, and a 93% probability of being relapsed when both bands remained reactive or increased in intensity between the two time points.ConclusionsThe B2t protein could be useful for the prediction of CE early post-surgical outcomes. The proteins ofE. granulosusprotoscoleces, especially the doublet P26/27 and P40, could be promising predictive biomarkers for the post-surgical follow-up of CE cases as well.Graphical Abstract