bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pancancer overexpressed NFYC Antisense 1 controls cell cycle mitotic progression through in cis and in trans modes of action
Authors: Pandini Cecilia , Pagani Giulia , Tassinari Martina , Vitale Emanuele , Bezzecchi Eugenia , Saadeldin Mona Kamal , Doldi Valentina , Giannuzzi Giuliana , Mantovani Roberto , Chiara Matteo , Ciarrocchi Alessia , Gandellini Paolo 
Published: March 2024

AbstractAntisense RNAs (asRNAs) represent an underappreciated yet crucial layer of gene expression regulation. Generally thought to modulate their sense genes in cis through sequence complementarity or their act of transcription, asRNAs can also regulate different molecular targets in trans, in the nucleus or in the cytoplasm. Here, we performed an in-depth molecular characterization of NFYCAntisense1 (NFYC-AS1), the asRNA transcribed head-to-head to NFYC subunit of the proliferation-associated NF-Y transcription factor. Our results show that NFYC-AS1 is a prevalently nuclear asRNA peaking early in the cell cycle. Comparative genomics suggests a narrow phylogenetic distribution, with a probable origin in the common ancestor of mammalian lineages. NFYC-AS1 is overexpressed pancancer, preferentially in association with RB1 mutations. Knockdown of NFYC-AS1 by antisense oligonucleotides impairs cell growth in lung squamous cell carcinoma and small cell lung cancer cells, a phenotype recapitulated by CRISPR/Cas9-deletion of its transcription start site. Surprisingly, expression of the sense gene is affected only when endogenous transcription of NFYC-AS1 is manipulated. This suggests that regulation of cell proliferation is at least in part independent of the in cis transcription-mediated effect on NFYC and is possibly exerted by RNA-dependent in trans effects converging on the regulation of G2/M cell cycle phase genes. Accordingly, NFYC-AS1-depleted cells are stuck in mitosis, indicating defects in mitotic progression. Overall, NFYC-AS1 emerged as a cell cycle-regulating asRNA with dual action, holding therapeutic potential in different cancer types, including the very aggressive RB1-mutated tumors.
The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial
Authors: Hsiehchen David , Beg Muhammad S. , Kainthla Radhika , Lohrey Jay , Kazmi Syed M. , Khosama Leticia , Maxwell Mary Claire , Kline Heather , Katz Courtney , Hassan Asim , Kubota Naoto , Siglinsky Ellen , Pillai Anil K. , Youssoufian Hagop , Mockbee Colleen , Culm Kerry , Uhlik Mark , Benjamin Laura , Brekken Rolf A. , Ahn Chul , Singal Amit G. , Zhu Hao , Hoshida Yujin , Yopp Adam C. 
Published: March 2024

AbstractImmune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3–11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.
Energy system for evaluation of modification methods on energy transfer efficiency and optimization of membranes
Authors: Li Tian , Zhou Hong , Ding Wei , Wang Jinjun , Zhang Tiancheng 
Published: March 2024

AbstractSaving energy is crucial for utilizing membrane technology, but there is no energy parameter for understanding the relationships among membrane performance and energy. Here, φ is defined as the energy transfer efficiency of the membrane, and its numerical expression of membrane performance is poor (e.g., in the range of 10−23). The method of modifying membranes is a crucial determinant for developing membrane science, but researchers using current parameters to evaluate modification methods might lead to erroneous conclusions. Hence, the newly established system θ is used to analyze the influence of different modification methods on energy consumption, which not only establish the relationship between different modification methods but also provide the research routes for future optimization methods. The main conclusions are as follows: (1) The current modification methods influence on the energy transfer efficiency of the pristine membrane by about 0.4902–3.278 × 104 times; (2) Using scientific data certifies that the modified support layer of the membranes is a more effective method for reducing the energy consumption than the modified activity layer of the membranes; (3) The establishment of this system provides data support for analyzing the advantages and disadvantages of modification methods, and provides guidance for how to optimize the modification methods of membranes. Therefore, this study not only fills key knowledge gaps in membrane science, but also provides theoretical support for how to optimize membrane modification methods.
Bone scan findings of Paget’s disease of bone in patients with VCP Multisystem Proteinopathy 1
Authors: Columbres Rod Carlo Agram , Din Sarosh , Gibbs Liliane , Kimonis Virginia 
Published: March 2024

AbstractMultisystem Proteinopathy 1 (MSP1) disease is a rare genetic disorder caused by mutations in the Valosin-Containing Protein (VCP) gene with clinical features of inclusion body myopathy (IBM), frontotemporal dementia (FTD), and Paget’s disease of bone (PDB). We performed bone scan imaging in twelve patients (6 females, 6 males) with confirmed VCP gene mutation six (50%) of which has myopathy alone, four (33%) with both PDB and myopathy, and two (15%) were presymptomatic carriers. We aim to characterize the PDB in diagnosed individuals, and potentially identify PDB in the myopathy and presymptomatic groups. Interestingly, two patients with previously undiagnosed PDB had positive diagnostic findings on the bone scan and subsequent radiograph imaging. Among the individuals with PDB, increased radiotracer uptake of the affected bones were of typical distribution as seen in conventional PDB and those reported in other MSP1 cohorts which are the thoracic spine and ribs (75%), pelvis (75%), shoulder (75%) and calvarium (15%). Overall, we show that technetium-99m bone scans done at regular intervals are a sensitive screening tool in patients with MSP1 associated VCP variants at risk for PDB. However, diagnostic confirmation should be coupled with clinical history, biochemical analysis, and skeletal radiographs to facilitate early treatment and prevention complications, acknowledging its limited specificity.
Pulmonary vascular reactivity in growth restricted fetuses using computational modelling and machine learning analysis of fetal Doppler waveforms
Authors: Vellvé Kilian , Garcia-Canadilla Patricia , Nogueira Mariana , Youssef Lina , Arranz Angela , Nakaki Ayako , Boada David , Blanco Isabel , Faner Rosa , Figueras Francesc , Agustí Àlvar , Gratacós Eduard , Crovetto Francesca , Bijnens Bart , Crispi Fàtima 
Published: March 2024

AbstractThe aim of this study was to investigate the pulmonary vasculature in baseline conditions and after maternal hyperoxygenation in growth restricted fetuses (FGR). A prospective cohort study of singleton pregnancies including 97 FGR and 111 normally grown fetuses was carried out. Ultrasound Doppler of the pulmonary vessels was obtained at 24–37 weeks of gestation and data were acquired before and after oxygen administration. After, Machine Learning (ML) and a computational model were used on the Doppler waveforms to classify individuals and estimate pulmonary vascular resistance (PVR). Our results showed lower mean velocity time integral (VTI) in the main pulmonary and intrapulmonary arteries in baseline conditions in FGR individuals. Delta changes of the main pulmonary artery VTI and intrapulmonary artery pulsatility index before and after hyperoxygenation were significantly greater in FGR when compared with controls. Also, ML identified two clusters: A (including 66% controls and 34% FGR) with similar Doppler traces over time and B (including 33% controls and 67% FGR) with changes after hyperoxygenation. The computational model estimated the ratio of PVR before and after maternal hyperoxygenation which was closer to 1 in cluster A (cluster A 0.98 ± 0.33 vs cluster B 0.78 ± 0.28, p = 0.0156). Doppler ultrasound allows the detection of significant changes in pulmonary vasculature in most FGR at baseline, and distinct responses to hyperoxygenation. Future studies are warranted to assess its potential applicability in the clinical management of FGR.
A comparative study of 11 non-linear regression models highlighting autoencoder, DBN, and SVR, enhanced by SHAP importance analysis in soybean branching prediction
Authors: Zhou Wei , Yan Zhengxiao , Zhang Liting 
Published: March 2024

AbstractTo explore a robust tool for advancing digital breeding practices through an artificial intelligence-driven phenotype prediction expert system, we undertook a thorough analysis of 11 non-linear regression models. Our investigation specifically emphasized the significance of Support Vector Regression (SVR) and SHapley Additive exPlanations (SHAP) in predicting soybean branching. By using branching data (phenotype) of 1918 soybean accessions and 42 k SNP (Single Nucleotide Polymorphism) polymorphic data (genotype), this study systematically compared 11 non-linear regression AI models, including four deep learning models (DBN (deep belief network) regression, ANN (artificial neural network) regression, Autoencoders regression, and MLP (multilayer perceptron) regression) and seven machine learning models (e.g., SVR (support vector regression), XGBoost (eXtreme Gradient Boosting) regression, Random Forest regression, LightGBM regression, GPs (Gaussian processes) regression, Decision Tree regression, and Polynomial regression). After being evaluated by four valuation metrics: R2 (R-squared), MAE (Mean Absolute Error), MSE (Mean Squared Error), and MAPE (Mean Absolute Percentage Error), it was found that the SVR, Polynomial Regression, DBN, and Autoencoder outperformed other models and could obtain a better prediction accuracy when they were used for phenotype prediction. In the assessment of deep learning approaches, we exemplified the SVR model, conducting analyses on feature importance and gene ontology (GO) enrichment to provide comprehensive support. After comprehensively comparing four feature importance algorithms, no notable distinction was observed in the feature importance ranking scores across the four algorithms, namely Variable Ranking, Permutation, SHAP, and Correlation Matrix, but the SHAP value could provide rich information on genes with negative contributions, and SHAP importance was chosen for feature selection. The results of this study offer valuable insights into AI-mediated plant breeding, addressing challenges faced by traditional breeding programs. The method developed has broad applicability in phenotype prediction, minor QTL (quantitative trait loci) mining, and plant smart-breeding systems, contributing significantly to the advancement of AI-based breeding practices and transitioning from experience-based to data-based breeding.
Palaeoproteomic investigation of an ancient human skeleton with abnormal deposition of dental calculus
Authors: Uchida-Fukuhara Yoko , Shimamura Shigeru , Sawafuji Rikai , Nishiuchi Takumi , Yoneda Minoru , Ishida Hajime , Matsumura Hirofumi , Tsutaya Takumi 
Published: March 2024

AbstractDetailed investigation of extremely severe pathological conditions in ancient human skeletons is important as it could shed light on the breadth of potential interactions between humans and disease etiologies in the past. Here, we applied palaeoproteomics to investigate an ancient human skeletal individual with severe oral pathology, focusing our research on bacterial pathogenic factors and host defense response. This female skeleton, from the Okhotsk period (i.e., fifth to thirteenth century) of Northern Japan, poses relevant amounts of abnormal dental calculus deposition and exhibits oral dysfunction due to severe periodontal disease. A shotgun mass-spectrometry analysis identified 81 human proteins and 15 bacterial proteins from the calculus of the subject. We identified two pathogenic or bioinvasive proteins originating from two of the three “red complex” bacteria, the core species associated with severe periodontal disease in modern humans, as well as two additional bioinvasive proteins of periodontal-associated bacteria. Moreover, we discovered defense response system-associated human proteins, although their proportion was mostly similar to those reported in ancient and modern human individuals with lower calculus deposition. These results suggest that the bacterial etiology was similar and the host defense response was not necessarily more intense in ancient individuals with significant amounts of abnormal dental calculus deposition.
Evidence for disrupted copper availability in human spinal cord supports CuII(atsm) as a treatment option for sporadic cases of ALS
Authors: Hilton James B. W. , Kysenius Kai , Liddell Jeffrey R. , Mercer Stephen W. , Paul Bence , Beckman Joseph S. , McLean Catriona A. , White Anthony R. , Donnelly Paul S. , Bush Ashley I. , Hare Dominic J. , Roberts Blaine R. , Crouch Peter J. 
Published: March 2024

AbstractThe copper compound CuII(atsm) has progressed to phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). CuII(atsm) is neuroprotective in mutant SOD1 mouse models of ALS where its activity is ascribed in part to improving availability of essential copper. However, SOD1 mutations cause only ~ 2% of ALS cases and therapeutic relevance of copper availability in sporadic ALS is unresolved. Herein we assessed spinal cord tissue from human cases of sporadic ALS for copper-related changes. We found that when compared to control cases the natural distribution of spinal cord copper was disrupted in sporadic ALS. A standout feature was decreased copper levels in the ventral grey matter, the primary anatomical site of neuronal loss in ALS. Altered expression of genes involved in copper handling indicated disrupted copper availability, and this was evident in decreased copper-dependent ferroxidase activity despite increased abundance of the ferroxidases ceruloplasmin and hephaestin. Mice expressing mutant SOD1 recapitulate salient features of ALS and the unsatiated requirement for copper in these mice is a biochemical target for CuII(atsm). Our results from human spinal cord indicate a therapeutic mechanism of action for CuII(atsm) involving copper availability may also be pertinent to sporadic cases of ALS.
Antagonistic properties against Fusarium sporotrichioides and glycosylation of HT-2 and T-2 toxins by selected Trichoderma strains
Authors: Modrzewska Marta , Popowski Dominik , Błaszczyk Lidia , Stępień Łukasz , Urbaniak Monika , Bryła Marcin , Cramer Benedikt , Humpf Hans-Ulrich , Twarużek Magdalena 
Published: March 2024

AbstractThe present study assessed the ability of Trichoderma to combat F. sporotrichioides, focusing on their antagonistic properties. Tests showed that Trichoderma effectively inhibited F. sporotrichioides mycelial growth, particularly with T. atroviride strains. In co-cultures on rice grains, Trichoderma almost completely reduced the biosynthesis of T-2 and HT-2 toxins by Fusarium. T-2 toxin-α-glucoside (T-2-3α-G), HT-2 toxin-α-glucoside (HT-2-3α-G), and HT-2 toxin-β-glucoside (HT-2-3β-G) were observed in the common culture medium, while these substances were not present in the control medium. The study also revealed unique metabolites and varying metabolomic profiles in joint cultures of Trichoderma and Fusarium, suggesting complex interactions. This research offers insights into the processes of biocontrol by Trichoderma, highlighting its potential as a sustainable solution for managing cereal plant pathogens and ensuring food safety.
Automatically listing senior members of departments as co-authors is highly prevalent in health sciences: meta-analysis of survey research
Authors: Meursinge Reynders Reint A. , Cavagnetto Davide , ter Riet Gerben , Di Girolamo Nicola , Malički Mario 
Published: March 2024

AbstractA systematic review with meta-analysis was conducted to assess the prevalence of automatically listing (a) senior member(s) of a department as co-author(s) on all submitted articles in health sciences and the prevalence of degrees of support on a 5-point justification scale. Survey research was searched in PubMed, Lens.org, and Dimensions.ai. until January 5 2023. We assessed the methodological quality of studies and conducted quantitative syntheses. We identified 15 eligible surveys, that provided 67 results, all of which were rated as having low quality. A pooled estimate of 20% [95% CI 16–25] (10 surveys, 3619 respondents) of researchers in various health sciences reported that a senior member of their department was automatically listed as an author on all submitted articles. Furthermore, 28% [95% CI 22–34] of researchers (10 surveys, 2180 respondents) felt that this practice was ‘never’, 24% [95% CI 22–27] ‘rarely’, 25% [95% CI 23–28] ‘sometimes’, 13% [95% CI 9–17] ‘most of the time’, and 8% [95% CI 6–9] ‘always justified’. The practice of automatically assigning senior members of departments as co-authors on all submitted manuscripts may be common in the health sciences; with those admitting to this practice finding it unjustified in most cases.Registration of the protocol The protocol was registered in Open Science Framework. Link: https://osf.io/4eywp/.
Novel theory and potential applications of central diastolic pressure decay time constant
Authors: Bikia Vasiliki , Segers Patrick , Rovas Georgios , Anagnostopoulos Sokratis , Stergiopulos Nikolaos 
Published: March 2024

AbstractCentral aortic diastolic pressure decay time constant ($${\uptau }$$
τ
) is according to the two-element Windkessel model equal to the product of total peripheral resistance ($$R$$
R
) times total arterial compliance ($$C$$
C
). As such, it is related to arterial stiffness, which has considerable pathophysiological relevance in the assessment of vascular health. This study aimed to investigate the relationship of the constant $${\uptau }$$
τ
with the product $$T\frac{MBP}{{cPP}}$$

T

MBP

cPP

, given by heart period ($$T$$
T
) times the ratio of mean blood pressure (MBP) to central pulse pressure ($$cPP$$

cPP

). The relationship was derived by performing linear fitting on an in silico population of n1 = 3818 virtual subjects, and was subsequently evaluated on in vivo data (n2 = 2263) from the large Asklepios study. The resulted expression was found to be $${\uptau } = k^{\prime}T\frac{MBP}{{cPP}},$$

τ
=

k
′

T

MBP

cPP

,

with $$k^{\prime} = 0.7$$

k
′

=
0.7

(R2 = 0.9). The evaluation of the equation on the in vivo human data reported high agreement between the estimated and reference $${\uptau }$$
τ
values, with a correlation coefficient equal to 0.94 and a normalized RMSE equal to 5.5%. Moreover, the analysis provided evidence that the coefficient $$k^{\prime}$$

k
′

is age- and gender-independent. The proposed formula provides novel theoretical insights in the relationship between $${\uptau }$$
τ
and central blood pressure features. In addition, it may allow for the evaluation of $${\uptau }$$
τ
without the need for acquiring the entire central blood pressure wave, especially when an approximation of the $$cPP$$

cPP

is feasible. This study adds to the current literature by contributing to the accessibility of an additional biomarker, such as the central diastolic pressure decay time constant, for the improved assessment of vascular ageing.
CTX-M-127 with I176F mutations found in bacteria isolates from Bangladeshi circulating banknotes
Authors: Ali Md. Zannat , Srinivasan Sankaranarayanan , Akter Selina 
Published: March 2024

AbstractExtended-spectrum beta-lactamase (ESBL)-producing organisms are widely recognized as clinically relevant causes of difficult-to-treat infections. CTX-M has formed a rapidly growing family distributed worldwide among a wide range of clinical bacteria, particularly members of Enterobacteriaceae. Circulating banknotes, exchanged daily among people, pose a potential vehicle for transmitting multidrug resistance. We screened for ESBL-carrying bacteria in the present study and reported CTX-M mutations in Bangladesh's banknotes. We sequenced the genes and performed homology modeling using the Swiss model with CTX-M-15 (4HBT) as a template. Then, we performed molecular docking of mecillinam with the template and the generated model using Autodock 4.2 (Release 4.2.6). After docking, we visually inspected the complexes built using Autodock tools for polar contacts and pi-pi interactions in PyMOL 2.5.4. Our partially sequenced blaCTX-M was related to blaCTX-M-10 and blaCTX-M-15. We observed multiple single-nucleotide substitution mutations, i.e., G613T (silent mutation), A626T (I176F), and A503G (N135D). Homology modeling showed high similarity when the model was superimposed over the template. The orientation of Asn (135) in the template and Asp (135) in the model does not show a significant difference. Likewise, Ile (176) in the template and Phe (176) in the model offer the same orientation. Our generated model could bind to Lys237, Ser240, and Asp135 residues with the lowest binding energy on docking. Our predicted binding of the mecillinam to the mutated D-135 residue in the model indicates contributions and supports previous reports proposing CTX-M-15 to CTX-M-127 mutational conversion on the mecillinum resistance phenotype.