bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining ultrafiltration and diffusive gradients in thin films techniques for speciation/fractionation of Cu and Zn in cytosol of liver of Nile tilapia (Oreochromis niloticus)
Authors: Gemeiner Hendryk , Menegário Amauri Antonio , Eismann Carlos Eduardo , Elias Lucas Pellegrini , Pedrobom Jorge Henrique , Dourado Thiago de Araujo , Chang Hung Kiang , da Conceição Fabiano Tomazini , Moruzzi Rodrigo Braga 
Published: March 2023

Abstract
This work aims to evaluate the size and lability of Cu and Zn bound to proteins in the cytosol of fish liver of Oreochromis niloticus by employing solid-phase extraction (SPE), diffusive gradients in thin films (DGT), and ultrafiltration (UF). SPE was carried out using Chelex-100. DGT containing Chelex-100 as binding agent was employed. Analyte concentrations were determined by ICP-MS. Total Cu and Zn concentrations in cytosol (1 g of fish liver in 5 ml of Tris–HCl) ranged from 39.6 to 44.3 ng ml−1 and 1498 to 2106 ng ml−1, respectively. Data from UF (10–30 kDa) suggested that Cu and Zn in cytosol were associated with ∼70% and 95%, respectively, with high-molecular-weight proteins. Cu-metallothionein was not selectively detected (although 28% of Cu was associated with low-molecular-weight proteins). However, information about the specific proteins in the cytosol will require coupling UF with organic mass spectrometry. Data from SPE showed the presence of labile Cu species of ∼17%, while the fraction of labile Zn species was &gt;55%. However, data from DGT suggested a fraction of labile Cu species only of 7% and a labile Zn fraction of 5%. This data, as compared with previous data from literature, suggests that the DGT technique gave a more plausible estimation of the labile pool of Zn and Cu in cytosol. The combination of results from UF and DGT is capable of contributing to the knowledge about the labile and low-molecular pool of Cu and Zn.
The hereditary N363K POLE exonuclease mutant extends PPAP tumor spectrum to glioblastomas by causing DNA damage and aneuploidy in addition to increased mismatch mutagenicity
Authors: Labrousse Guillaume , Vande Perre Pierre , Parra Genis , Jaffrelot Marion , Leroy Laura , Chibon Frederic , Escudie Frederic , Selves Janick , Hoffmann Jean-Sebastien , Guimbaud Rosine , Lutzmann Malik 
Published: March 2023

Abstract
The exonuclease domain of DNA polymerases epsilon's catalytic subunit (POLE) removes misincorporated nucleotides, called proofreading. POLE-exonuclease mutations cause colorectal- and endometrial cancers with an extreme burden of single nucleotide substitutions. We recently reported that particularly the hereditary POLE exonuclease mutation N363K predisposes in addition to aggressive giant cell glioblastomas. We knocked-in this mutation homozygously into human cell lines and compared its properties to knock-ins of the likewise hereditary POLE L424V mutation and to a complete proofreading-inactivating mutation (exo-null). We found that N363K cells have higher mutation rates as both L424V- or exo-null mutant cells. In contrast to L424V cells, N363K cells expose a growth defect, replication stress and DNA damage. In non-transformed cells, these burdens lead to aneuploidy but macroscopically normal nuclei. In contrast, transformed N363K cells phenocopy the enlarged and disorganized nuclei of giant cell glioblastomas. Taken together, our data characterize a POLE exonuclease domain mutant that not only causes single nucleotide hypermutation, but in addition DNA damage and chromosome instability, leading to an extended tumor spectrum. Our results expand the understanding of the polymerase exonuclease domain and suggest that an assessment of both the mutational potential and the genetic instability might refine classification and treatment of POLE-mutated tumors.
Meta-Analysis of 49 Roche Oncology Trials Comparing Blinded Independent Central Review (BICR) and Local Evaluation to Assess the Value of BICR
Authors: Lian Qinshu , Fredrickson Jill , Boudier Kamila , Rothkegel Christiane , Hilton Magalie , Hillebrecht Alexander , McDonald Andrew , Xu Na 
Published: March 2023

Abstract

Background
Blinded independent central review (BICR) of radiographic images is frequently conducted in oncology trials to address the potential bias of local evaluation (LE) of endpoints such as progression-free survival (PFS) and objective response rate (ORR). Given that BICR is a complex and costly process, we evaluated the agreement between LE- and BICR-based treatment effect results and the impact of BICR on regulatory decision-making.

Materials and Methods
Meta-analyses were performed using hazard ratios (HRs) for PFS and odds ratios (ORs) for ORR from all randomized Roche-supported oncology clinical trials during 2006-2020 that had both LE and BICR results (49 studies with a total of over 32 000 patients).

Results
Overall, the evaluation bias of LE overestimating the treatment effect compared with BICR based on PFS was numerically small and not clinically meaningful, especially for double-blind studies (HR ratio between BICR and LE: 1.044). A larger bias is more likely to occur in studies with open-label design, smaller sample sizes, or an unequal randomization ratio. The majority (87%) of the PFS comparisons led to the same statistical inference by BICR and LE. For ORR, a high degree of agreement between BICR and LE results was also observed (OR ratio of 1.065), although the agreement was slightly lower than for PFS.

Conclusion
BICR did not notably impact the study interpretation nor drive the sponsor’s regulatory submission decisions. Hence, if bias can be diminished by appropriate means, LE is deemed as reliable as BICR for certain study settings.
Emerging Trends in Immunotherapy for Adult Sarcomas
Authors: Husain Marium , Chen Luxi , Liebner David , Beane Joal , Rubinstein Mark , Pollock Raphael , Verschraegen Claire , Tinoco Gabriel 
Published: March 2023

Abstract
Soft-tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that arise from the oncogenic transformation of mesenchymal tissue. There are over 100 distinct STS histological and molecular subtypes with unique clinical, therapeutic, and prognostic features with variable responses to therapy regimens. Given the quality-of-life concerns and limited efficacy with current regimens, including cytotoxic chemotherapy, there is a need for novel therapies and regimens to treat advanced STS. Although immune checkpoint inhibitors have demonstrated significant improvements in survival outcomes in other cancer types, there remains ambiguous data on the impact of immunotherapy in sarcoma. Biomarkers like PD-1/PD-L1 are not always predictive of outcomes. Therefore, researching emerging novel therapies, such as CAR-T and adoptive cell therapies, is critical to understanding STS biology, STS tumor immune microenvironment immunomodulatory strategies that improve immune response, and survival outcomes. We discuss the underlying biology of the STS tumor immune microenvironment, immunomodulatory strategies that augment pre-existing immune responses, and novel approaches to develop sarcoma-specific antigen-based therapies.
The translational landscape of bread wheat during grain development
Authors: Guo Yiwen , Chen Yongming , Wang Yongfa , Wu Xiaojia , Zhang Xiaoyu , Mao Weiwei , Yu Hongjian , Guo Kai , Xu Jin , Ma Liang , Guo Weilong , Hu Zhaorong , Xin Mingming , Yao Yingyin , Ni Zhongfu , Sun Qixin , Peng Huiru 
Published: March 2023

AbstractThe dynamics of gene expression in crop grains has typically been investigated at the transcriptional level. However, this approach neglects translational regulation, a widespread mechanism that rapidly modulates gene expression to increase the plasticity of organisms. Here, we performed ribosome profiling and polysome profiling to obtain a comprehensive translatome data set of developing bread wheat (Triticum aestivum) grains. We further investigated the genome-wide translational dynamics during grain development, revealing that the translation of many functional genes is modulated in a stage-specific manner. The unbalanced translation between subgenomes is pervasive, which increases the expression flexibility of allohexaploid wheat. In addition, we uncovered widespread previously unannotated translation events, including upstream open reading frames (uORFs), downstream open reading frames (dORFs), and open reading frames (ORFs) in long noncoding RNAs, and characterized the temporal expression dynamics of small ORFs. We demonstrated that uORFs act as cis-regulatory elements that can repress or even enhance the translation of mRNAs. Gene translation may be combinatorially modulated by uORFs, dORFs, and microRNAs. In summary, our study presents a translatomic resource that provides a comprehensive and detailed overview of the translational regulation in developing bread wheat grains. This resource will facilitate future crop improvements for optimal yield and quality.
The transcribed centromeric geneOsMRPL15is essential for pollen development in rice
Authors: Xie En , Chen Jiawei , Wang Bingxin , Shen Yi , Tang Ding , Du Guijie , Li Yafei , Cheng Zhukuan 
Published: March 2023

AbstractCentromeres consist of highly repetitive sequences that are challenging to map, clone, and sequence. Active genes exist in centromeric regions, but their biological functions are difficult to explore owing to extreme suppression of recombination in these regions. In this study, we used the CRISPR/Cas9 system to knock out the transcribed gene Mitochondrial Ribosomal Protein L15 (OsMRPL15), located in the centromeric region of rice (Oryza sativa) chromosome 8, resulting in gametophyte sterility. Osmrpl15 pollen was completely sterile, with abnormalities appearing at the tricellular stage including the absence of starch granules and disrupted mitochondrial structure. Loss of OsMRPL15 caused abnormal accumulation of mitoribosomal proteins and large subunit rRNA in pollen mitochondria. Moreover, the biosynthesis of several proteins in mitochondria was defective, and expression of mitochondrial genes was upregulated at the mRNA level. Osmrpl15 pollen contained smaller amounts of intermediates related to starch metabolism than wild-type pollen, while biosynthesis of several amino acids was upregulated, possibly to compensate for defective mitochondrial protein biosynthesis and initiate consumption of carbohydrates necessary for starch biosynthesis. These results provide further insight into how defects in mitoribosome development cause gametophyte male sterility.
CRISPR-assisted transcription activation by phase-separation proteins
Authors: Liu Jiaqi , Chen Yuxi , Nong Baoting , Luo Xiao , Cui Kaixin , Li Zhan , Zhang Pengfei , Tan Wenqiong , Yang Yue , Ma Wenbin , Liang Puping , Songyang Zhou 
Published: March 2023

Abstract
The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
A Tale of Two Cities: Mainland Chinese Buyers in the Hong Kong Housing Market
Authors: Fan Yi , Hu Maggie Rong , Wan Wayne Xinwei , Wang Zhenping 
Published: March 2023

Abstract
This article examines the impact of mainland Chinese buyers in the Hong Kong housing market, using complete transaction records between 2001 and 2017. We find that mainland buyers pay an average price premium of 1.4% compared with locals. The premiums are estimated to be 3.5% for large-sized luxury units and 1.6% for homes in central locations. The mechanisms that underlie the price premiums include a hedging effect, residential sorting, and information barriers, of which the hedging motive has the strongest impact. Mainland buyers’ price premiums rise significantly when the Chinese currency depreciates or China Economic Policy Uncertainty increases. Our study sheds light on the impact and mechanism of the ““China shock” on the global housing markets.
Verification of the sampling procedure for radioactivity analysis of waste and industrial material
Authors: Rajačić Milica M , Todorović Dragana J , Andrić Velibor Đ , Nikolić Jelena K , Janković Marija M , Pantelić Gordana K , Vukanac Ivana S 
Published: March 2023

Abstract
In accordance with ISO/IEC 17025:2017, the testing laboratory needs to verify its ability to properly perform methods. For radiological testing, the sampling does not affect the results directly, but it has to ensure that sample adequately represents the tested material. To verify the procedure, a sampling of red mud and bauxite ore was conducted. All samples were measured in identical geometry by HPGe spectrometer. The counting rates per unit mass in the recorded spectra were compared. For each measurement series, the mean and standard deviations of respected peaks were calculated, as well as average and standard deviation of all series. The obtained results of each individual series were considered satisfactory, i.e. sampling procedure ensures the representativeness of the bulk material, if it is within ± two standard deviations of the average of the mean values.
Development of phantom for current modulation quality assurance test on computed tomography
Authors: de Camargo Gustavo E , Carneiro Glaube N , Real Jessica V , Doro Renato B , Malthez Anna L M C 
Published: March 2023

Abstract
Automatic tube current modulation (ATCM) in computed tomography (CT) is a powerful tool for reducing the dose delivery to the patient during the scan. A phantom is used to perform the ATCM quality control (QC) test, assessing how the CT system adapts the tube current as a function of object size. Considering quality assurance recommendations (Brazilian and international), we developed a dedicated phantom for the ATCM test. The phantom was built-in high-density polyethylene in a cylindric shape with three different sizes. To verify the applicability of this phantom, we tested it in two different CT scanners (Toshiba and Philips). The results demonstrated concordance between a discrete change in phantom size, and the corresponding change in the tube current, indicating that the CT system could adapt current when a discrete attenuation shift occurred. The developed phantom might be used in ATCM QC tests.
The first record of fossilized soft parts in ossified tendons and implications for the understanding of tendon mineralization
Authors: Surmik Dawid , Słowiak-Morkovina Justyna , Szczygielski Tomasz , Wojtyniak Marcin , Środek Dorota , Dulski Mateusz , Balin Katarzyna , Krzykawski Tomasz , Pawlicki Roman 
Published: March 2023

AbstractPreservation of soft parts (collagen fibres, blood vessels and cells) in extinct vertebrates is rare and usually limited to fossilized bone and cartilage. Well-preserved coarse collagenous fibre bundles embedded in a mineralized matrix of tendons, as well as numerous hollow, tubular structures consistent morphologically with fibril bundles, blood vessels and associated cells, were identified in ossified tendons of Late Cretaceous ornithischians from North America and Central East Asia. Detailed, high-accuracy imaging, along with spectroscopic characterization of those fibrous structures and comparison with ossified tendons of modern-day turkeys, support the proposition that physiologically driven tendon ossification is common for avians and non-avian dinosaurs. The examined soft parts were preserved through the pathway of iron-induced crosslinking and alumino-silification, documenting a variety of pathways for the preservation of soft parts, depending on the burial environment. For the first time, the structure of dinosaur fossilized tendons is analysed in detail, revealing shared histogenetic principles with modern birds and the nature of preservation.
Use of prehospital reverse shock index times Glasgow Coma Scale to identify children who require the most immediate trauma care
Authors: Reppucci Marina L. , Cooper Emily , Nolan Margo M. , Lyttle Bailey D. , Gallagher Lauren T. , Jujare Swati , Stevens Jenny , Moulton Steven L. , Bensard Denis D. , Acker Shannon N. 
Published: March 2023

BACKGROUND
Appropriate prehospital trauma triage ensures transport of children to facilities that provide specialized trauma care. There are currently no objective and generalizable scoring tool for emergency medical services to facilitate such decisions. An abnormal reverse shock index times Glasgow Coma Scale (rSIG), which is calculated using readily available parameters, has been shown to be associated with severely injured children. This study sought to determine if rSIG could be used in the prehospital setting to identify injured children who require the highest levels of care.

METHODS
Patients (1–18 years old) transferred from the scene to a level 1 pediatric trauma center from 2010 to 2020 with complete prehospital and emergency department vital signs, and Glasgow Coma Scale (GCS) scores were included. Reverse shock index times GCS was calculated as previously described ((systolic blood pressure/heart rate) × GCS), and the following cutoffs were used: ≤13.1, ≤16.5, and ≤20.1 for 1- to 6-, 7- to 12-, and 13- to 18-year-old patients, respectively. Trauma activation level and clinical outcomes upon arrival to the pediatric trauma center were collected.

RESULTS
There were 247 patients included in the analysis; 66.0% (163) had an abnormal prehospital rSIG. Patients with an abnormal rSIG had a higher rate of highest-level trauma activation compared with those with a normal rSIG (38.7% vs. 20.2%, p = 0.013). Patients with an abnormal prehospital rSIG also had higher rates of intubation (28.8% vs. 9.52%, p < 0.001), intracranial pressure monitor (9.20 vs. 1.19%, p = 0.032), need for blood (19.6% vs. 8.33%, p = 0.034), laparotomy (7.98% vs. 1.19%, p = 0.039), and intensive care unit admission (54.6% vs. 40.5%, p = 0.049).

CONCLUSION
Reverse shock index times GCS may assist emergency medical service providers in early identification and triage of severely injured children. An abnormal rSIG in the emergency department is associated with higher rates of intubation, need for blood transfusion, intracranial pressure monitoring, laparotomy, and intensive care unit admission. Use of this metric may help to speed the identification, care, and treatment of any injured child.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Uncovering the link between gut microbiome, highly processed food consumption and diet quality through bioinformatics methods
Authors: Molina Víctor Manuel López , Lacruz-Pleguezuelos Blanca , Carrillo de Santa Pau Enrique , Marcos-Zambrano Laura Judith 
Published: March 2023

AbstractThe consumption of highly processed foods, along with other dietary and lifestyle poor habits, has an impact on health by increasing the risk of several non-communicable pathologies, such as diabetes. Gut microbiome composition, in specific, can be modulated by nutrients, deriving in different metabolic outcomes that have an influence on this high disease susceptibility and making it a possible therapeutic target for these comorbidities. In this work, gut microbiome of 60 and 46 individuals from 2 different studies focused, among other aspects, on diet-microbiome interactions, was characterised. By means of differential abundance analyses and supervised machine learning techniques based on random forest, gradient boosting and support vector machines, a set of microbial genera that could be potential biomarkers for the differentiation of individuals with poorer dietary patterns was discovered, after comparing coincidences in these taxa among classifiers and testing them for significant differences. Among these,Dialister,PhoceaandPseudoflavonifractorwere suggested to have a role in the way highly processed foods affect health negatively, along withPrevotellaceae NK3B31 groupand an undetermined genus fromMuribaculaceaein the opposite sense. Furthermore, all the identified genera in this study had already been linked to type 2 diabetes, among whichBacteroidesandPseudoflavonifractorproved to be differentially abundant in groups of individuals with different levels of biomarkers for this disease. Nevertheless, further research via longitudinal studies and experimental validation of these genera should be carried out to confirm the association of these taxa with diet and diabetes.
Along-Tract Statistical Mapping of Microstructural Abnormalities in Bipolar Disorder: A Pilot Study
Authors: Nabulsi Leila , Chandio Bramsh Q. , Dhinagar Nikhil , Laltoo Emily , McPhilemy Genevieve , Martyn Fiona M. , Hallahan Brian , McDonald Colm , Thompson Paul M. , Cannon Dara M. 
Published: March 2023

AbstractInvestigating brain circuitry involved in bipolar disorder (BD) is key to discovering brain biomarkers for genetic and interventional studies of the disorder. Even so, prior research has not provided a fine-scale spatial mapping of brain microstructural differences in BD. In this pilot diffusion MRI dataset, we used BUndle ANalytics (BUAN), a recently developed analytic approach for tractography, to extract, map, and visualize the profile of microstructural abnormalities on a 3D model of fiber tracts in people with BD (N=38) and healthy controls (N=49), and investigate along-tract white matter (WM) microstructural differences between these groups. Using the BUAN pipeline, BD was associated with lower mean Fractional Anisotropy (FA) in fronto-limbic and interhemispheric pathways and higher mean FA in posterior bundles relative to controls. BUAN combines tractography and anatomical information to capture distinct along-tract effects on WM microstructure that may aid in classifying diseases based on anatomical differences.