bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of disease-specific biomarkers for the early detection of bronchopulmonary dysplasia
Authors: Kindt Alida S. D. , Förster Kai M. , Cochius-den Otter Suzan C. M. , Flemmer Andreas W. , Hauck Stefanie M. , Flatley Andrew , Kamphuis Juliette , Karrasch Stefan , Behr Jürgen , Franz Axel , Härtel Christoph , Krumsiek Jan , Tibboel Dick , Hilgendorff Anne 
Published: May 2022

Abstract
Objective
To demonstrate and validate the improvement of current risk stratification for bronchopulmonary dysplasia (BPD) early after birth by plasma protein markers (sialic acid-binding Ig-like lectin 14 (SIGLEC-14), basal cell adhesion molecule (BCAM), angiopoietin-like 3 protein (ANGPTL-3)) in extremely premature infants.

Methods and results
Proteome screening in first-week-of-life plasma samples of n = 52 preterm infants <32 weeks gestational age (GA) on two proteomic platforms (SomaLogic®, Olink-Proteomics®) confirmed three biomarkers with significant predictive power: BCAM, SIGLEC-14, and ANGPTL-3. We demonstrate high sensitivity (0.92) and specificity (0.86) under consideration of GA, show the proteins’ critical contribution to the predictive power of known clinical risk factors, e.g., birth weight and GA, and predicted the duration of mechanical ventilation, oxygen supplementation, as well as neonatal intensive care stay. We confirmed significant predictive power for BPD cases when switching to a clinically applicable method (enzyme-linked immunosorbent assay) in an independent sample set (n = 25, p < 0.001) and demonstrated disease specificity in different cohorts of neonatal and adult lung disease.

Conclusion
While successfully addressing typical challenges of clinical biomarker studies, we demonstrated the potential of BCAM, SIGLEC-14, and ANGPTL-3 to inform future clinical decision making in the preterm infant at risk for BPD.

Trial registration
Deutsches Register Klinische Studien (DRKS) No. 00004600; https://www.drks.de.

Impact

The urgent need for biomarkers that enable early decision making and personalized monitoring strategies in preterm infants with BPD is challenged by targeted marker analyses, cohort size, and disease heterogeneity.

We demonstrate the potential of the plasma proteins BCAM, SIGLEC-14, and ANGPTL-3 to identify infants with BPD early after birth while improving the predictive power of clinical variables, confirming the robustness toward proteome assays and proving disease specificity.

Our comprehensive analysis enables a phase-III clinical trial that allows full implementation of the biomarkers into clinical routine to enable early risk stratification in preterms with BPD.
Altered hippocampus and amygdala subregion connectome hierarchy in major depressive disorder
Authors: Jacob Yael , Morris Laurel S. , Verma Gaurav , Rutter Sarah B. , Balchandani Priti , Murrough James W. 
Published: May 2022

AbstractThe hippocampus and amygdala limbic structures are critical to the etiology of major depressive disorder (MDD). However, there are no high-resolution characterizations of the role of their subregions in the whole brain network (connectome). Connectomic examination of these subregions can uncover disorder-related patterns that are otherwise missed when treated as single structures. 38 MDD patients and 40 healthy controls (HC) underwent anatomical and diffusion imaging using 7-Tesla MRI. Whole-brain segmentation was performed along with hippocampus and amygdala subregion segmentation, each representing a node in the connectome. Graph theory analysis was applied to examine the importance of the limbic subregions within the brain network using centrality features measured bynode strength(sum of weights of the node’s connections),Betweenness(number of shortest paths that traverse the node), andclustering coefficient(how connected the node’s neighbors are to one another and forming a cluster). Compared to HC, MDD patients showed decreased node strength of the right hippocampus cornu ammonis (CA) 3/4, indicating decreased connectivity to the rest of the brain, and decreased clustering coefficient of the right dentate gyrus, implying it is less embedded in a cluster. Additionally, within the MDD group, the greater the embedding of the right amygdala central nucleus (CeA) in a cluster, the greater the severity of depressive symptoms. The altered role of these limbic subregions in the whole-brain connectome is related to diagnosis and depression severity, contributing to our understanding of the limbic system involvement in MDD and may elucidate the underlying mechanisms of depression.
Pirtobrutinib inhibits wild-type and mutant Bruton’s tyrosine kinase-mediated signaling in chronic lymphocytic leukemia
Authors: Aslan Burcu , Kismali Gorkem , Iles Lakesla R. , Manyam Ganiraju C. , Ayres Mary L. , Chen Lisa S. , Gagea Mihai , Bertilaccio Maria Teresa Sabrina , Wierda William G. , Gandhi Varsha 
Published: May 2022

AbstractPirtobrutinib (LOXO-305), a reversible inhibitor of Bruton’s tyrosine kinase (BTK), was designed as an alternative strategy to treat ibrutinib-resistant disease that develops due to C481 kinase domain mutations. The clinical activity of pirtobrutinib has been demonstrated in CLL, but the mechanism of action has not been investigated. We evaluated pirtobrutinib in 4 model systems: first, MEC-1, a CLL cell line overexpressing BTKWT, BTKC481S, or BTKC481R; second, murine models driven by MEC-1 overexpressing BTKWT or BTKC481S; third, in vitro incubations of primary CLL cells; and finally, CLL patients during pirtobrutinib therapy (NCT03740529, ClinicalTrials.gov). Pirtobrutinib inhibited BTK activation as well as downstream signaling in MEC-1 isogenic cells overexpressing BTKWT, BTKC481S, or BTKC481R. In mice, overall survival was short due to aggressive disease. Pirtobrutinib treatment for 2 weeks led to reduction of spleen and liver weight in BTKWT and BTKC481S cells, respectively. In vitro incubations of CLL cells harboring wild-type or mutant BTK had inhibition of the BCR pathway with either ibrutinib or pirtobrutinib treatment. Pirtobrutinib therapy resulted in inhibition of BTK phosphorylation and downstream signaling initially in all cases irrespective of their BTK profile, but these effects started to revert in cases with other BCR pathway mutations such as PLCG2 or PLEKHG5. Levels of CCL3 and CCL4 in plasma were marginally higher in patients with mutated BTK; however, there was a bimodal distribution. Both chemokines were decreased at early time points and mimicked BCR pathway protein changes. Collectively, these results demonstrate that pirtobrutinib is an effective BTK inhibitor for CLL harboring wild-type or mutant BTK as observed by changes in CCL3 and CCL4 biomarkers and suggest that alterations in BCR pathway signaling are the mechanism for its clinical effects. Long-term evaluation is needed for BTK gatekeeper residue variation along with pathologic kinase substitution or mutations in other proteins in the BCR pathway.
Ixovex-1, a novel oncolytic E1B-mutated adenovirus
Authors: Anwar Mohiemen , Arendt Maja-Louise , Ramachandran Mohanraj , Carlsson Anette , Essand Magnus , Akusjärvi Göran , Alusi Ghasan , Öberg Daniel 
Published: May 2022

AbstractThere is a great demand for improved oncolytic viruses that selectively replicate within cancer cells while sparing normal cells. Here, we describe a novel oncolytic adenovirus, Ixovex-1, that obtains a cancer-selective replication phenotype by modulating the level of expression of the different, alternatively spliced E1B mRNA isoforms. Ixovex-1 is a recombinant adenovirus that carries a single point mutation in the E1B-93R 3’ splice acceptor site that results in overexpression of the E1B-156R splice isoform. In this paper, we studied the characteristics of this novel oncolytic adenovirus by validating its in vitro behaviour in a panel of normal cells and cancer cells. We additionally studied its anti-tumour efficacy in vivo. Ixovex-1 significantly inhibited tumour growth and prolonged survival of mice in an immune-deficient lung carcinoma tumour implantation model. In complementation experiments, overexpression of E1B-156R was shown to increase the oncolytic index of both Ad5wt and ONYX-015. In contrast to prior viruses of similar type, Ixovex-1 includes a functional E3B region for better in vivo efficacy. Throughout this study, the Ixovex-1 virus has been proven to be superior in competency compared to a virus with multiple deletions.
Emerging functions of circular RNA in the regulation of adipocyte metabolism and obesity
Authors: Zhang Yuanyuan , Tian Zhichen , Ye Haibo , Sun Xiaomei , Zhang Huiming , Sun Yujia , Mao Yongjiang , Yang Zhangping , Li Mingxun 
Published: May 2022

AbstractAs noncoding RNAs, circular RNAs (circRNAs) are covalently enclosed endogenous biomolecules in eukaryotes that have tissue specificity and cell specificity. circRNAs were once considered a rare splicing byproduct. With the development of high-throughput sequencing, it has been confirmed that they are expressed in thousands of mammalian genes. To date, only a few circRNA functions and regulatory mechanisms have been verified. Adipose is the main tissue for body energy storage and energy supply. Adipocyte metabolism is a physiological process involving a series of genes and affects biological activities in the body, such as energy metabolism, immunity, and signal transmission. When adipocyte formation is dysregulated, it will cause a series of diseases, such as atherosclerosis, obesity, fatty liver, and diabetes. In recent years, many noncoding RNAs involved in adipocyte metabolism have been revealed. This review provides a comprehensive overview of the basic structure and biosynthetic mechanism of circRNAs, and further discusses the circRNAs related to adipocyte formation in adipose tissue and liver. Our review will provide a reference for further elucidating the genetic regulation mechanism of circRNAs involved in adipocyte metabolism.
Calibration after bootstrap for accurate uncertainty quantification in regression models
Authors: Palmer Glenn , Du Siqi , Politowicz Alexander , Emory Joshua Paul , Yang Xiyu , Gautam Anupraas , Gupta Grishma , Li Zhelong , Jacobs Ryan , Morgan Dane 
Published: May 2022

AbstractObtaining accurate estimates of machine learning model uncertainties on newly predicted data is essential for understanding the accuracy of the model and whether its predictions can be trusted. A common approach to such uncertainty quantification is to estimate the variance from an ensemble of models, which are often generated by the generally applicable bootstrap method. In this work, we demonstrate that the direct bootstrap ensemble standard deviation is not an accurate estimate of uncertainty but that it can be simply calibrated to dramatically improve its accuracy. We demonstrate the effectiveness of this calibration method for both synthetic data and numerous physical datasets from the field of Materials Science and Engineering. The approach is motivated by applications in physical and biological science but is quite general and should be applicable for uncertainty quantification in a wide range of machine learning regression models.
Influence of diet on acute endocannabinoidome mediator levels post exercise in active women, a crossover randomized study
Authors: Forteza Fabiola , Bourdeau-Julien Isabelle , Nguyen Guillaume Q. , Guevara Agudelo Fredy Alexander , Rochefort Gabrielle , Parent Lydiane , Rakotoarivelo Volatiana , Feutry Perrine , Martin Cyril , Perron Julie , Lamarche Benoît , Flamand Nicolas , Veilleux Alain , Billaut François , Di Marzo Vincenzo , Raymond Frédéric 
Published: May 2022

AbstractThe extended endocannabinoid system, also termed endocannabinoidome, participates in multiple metabolic functions in health and disease. Physical activity can both have an acute and chronic impact on endocannabinoid mediators, as does diet. In this crossover randomized controlled study, we investigated the influence of diet on the peripheral response to acute maximal aerobic exercise in a sample of active adult women (n = 7) with no underlying metabolic conditions. We compared the impact of 7-day standardized Mediterranean diet (MedDiet) and control diet inspired by Canadian macronutrient intake (CanDiet) on endocannabinoidome and short-chain fatty acid metabolites post maximal aerobic exercise. Overall, plasmatic endocannabinoids, their congeners and some polyunsaturated fatty acids increased significantly post maximal aerobic exercise upon cessation of exercise and recovered their initial values within 1 h after exercise. Most N-acylethanolamines and polyunsaturated fatty acids increased directly after exercise when the participants had consumed the MedDiet, but not when they had consumed the CanDiet. This impact was different for monoacylglycerol endocannabinoid congeners, which in most cases reacted similarly to acute exercise while on the MedDiet or the CanDiet. Fecal microbiota was only minimally affected by the diet in this cohort. This study demonstrates that endocannabinoidome mediators respond to acute maximal aerobic exercise in a way that is dependent on the diet consumed in the week prior to exercise.
Gaseous NO2 induces various envelope alterations in Pseudomonas fluorescens MFAF76a
Authors: Chautrand Thibault , Depayras Ségolène , Souak Djouhar , Kondakova Tatiana , Barreau Magalie , Kentache Takfarinas , Hardouin Julie , Tahrioui Ali , Thoumire Olivier , Konto-Ghiorghi Yoan , Barbey Corinne , Ladam Guy , Chevalier Sylvie , Heipieper Hermann J. , Orange Nicole , Duclairoir-Poc Cécile 
Published: May 2022

AbstractAnthropogenic atmospheric pollution and immune response regularly expose bacteria to toxic nitrogen oxides such as NO•and NO2. These reactive molecules can damage a wide variety of biomolecules such as DNA, proteins and lipids. Several components of the bacterial envelope are susceptible to be damaged by reactive nitrogen species. Furthermore, the hydrophobic core of the membranes favors the reactivity of nitrogen oxides with other molecules, making membranes an important factor in the chemistry of nitrosative stress. Since bacteria are often exposed to endogenous or exogenous nitrogen oxides, they have acquired protection mechanisms against the deleterious effects of these molecules. By exposing bacteria to gaseous NO2, this work aims to analyze the physiological effects of NO2on the cell envelope of the airborne bacteriumPseudomonas fluorescensMFAF76a and its potential adaptive responses. Electron microscopy showed that exposure to NO2leads to morphological alterations of the cell envelope. Furthermore, the proteomic profiling data revealed that these cell envelope alterations might be partly explained by modifications of the synthesis pathways of multiple cell envelope components, such as peptidoglycan, lipid A, and phospholipids. Together these results provide important insights into the potential adaptive responses to NO2exposure inP. fluorescensMFAF76a needing further investigations.
Density-functional-theory simulations of the water and ice adhesion on silicene quantum dots
Authors: Duan Tianpei , Wu Wei , Choy Kwang-Leong 
Published: May 2022

AbstractThe absorption of water and ice on silicon is important to understand for many applications and safety concerns for electronic devices as most of them are fabricated using silicon. Meanwhile, recently silicene nanostructures have attracted much attention due to their potential applications in electronic devices such as gas or humidity sensors. However, for the moment, the theoretical study of the interaction between water molecules and silicene nanostructures is still rare although there is already theoretical work on the effect of water molecules on the silicene periodic structure. The specific conditions such as the finite size effect, the edge saturation of the silicene nanostructure, and the distance between the water/ice and the silicene at the initial onset of the contact have not been carefully considered before. Here we have modelled the absorption of a water molecule and a square ice on the silicene nanodot by using hybrid-exchange density-functional theory, complemented by the Van der Waals forces correction. Three different sizes of silicene nanodots have been chosen for simulations, namely $$3\times 3$$

3
×
3

, $$4\times 4$$

4
×
4

, and $$5\times 5$$

5
×
5

, with and without the hydrogen saturation on the edge. Our calculations suggest that the silicene nanodots chosen here are both hydrophilic and ice-philic. The water molecule and the square ice have tilted angles towards the silicene nanodot plane at ~ 70º and ~ 45º, respectively, which could be owing to the zig–zag structure on silicene. The absorption energies are size dependent for unsaturated silicene nanodots, whereas almost size independent for the hydrogen saturated cases. Our work on the single water molecule absorption energy on silicene nanodots is qualitatively in agreement with the previous theoretical and experimental work. However, the ice structure on silicene is yet to be validated by the relevant experiments. Our calculation results not only further complement the current paucity of water-to-silicene-nanostructure contact mechanisms, but also lead to the first study of square-ice contact mechanisms for silicene. Our findings presented here could be useful for the future design of semiconducting devices based on silicene nanostructures, especially in the humid and low-temperature environments.
Metabolome dynamics during wheat domestication
Authors: Ben-Abu Yuval , Itsko Mark 
Published: May 2022

AbstractOne of the most important crops worldwide is wheat. Wheat domestication took place about 10,000 years ago. Not only that its wild progenitors have been discovered and phenotypically characterized, but their genomes were also sequenced and compared to modern wheat. While comparative genomics is essential to track genes that contribute to improvement in crop yield, comparative analyses of functional biological end-products, such as metabolites, are still lacking. With the advent of rigorous mass-spectrometry technologies, it is now possible to address that problem on a big-data scale. In attempt to reveal classes of metabolites, which are associated with wheat domestication, we analyzed the metabolomes of wheat kernel samples from various wheat lines. These wheat lines represented subspecies of tetraploid wheat along primary and secondary domestications, including wild emmer, domesticated emmer, landraces durum, and modern durum. We detected that the groups of plant metabolites such as plant-defense metabolites, antioxidants and plant hormones underwent significant changes during wheat domestication. Our data suggest that these metabolites may have contributed to the improvement in the agricultural fitness of wheat. Closer evaluation of specific metabolic pathways may result in the future in genetically-engineered high-yield crops.
6-Bromo-2-naphthol from Silene armeria extract sensitizes Acinetobacter baumannii strains to polymyxin
Authors: Kang Mingyeong , Kim Wonjae , Lee Jaebok , Jung Hye Su , Jeon Che Ok , Park Woojun 
Published: May 2022

AbstractThe overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which are resistant to various antibiotics. Combination therapies using natural compounds with antibiotics have been found to have synergistic effects against several pathogens. Synergistic natural compounds can potentiate the effects of polymyxins for the treatment of Acinetobacter baumannii infection. Out of 120 types of plant extracts, only Silene armeria extract (SAE) showed a synergistic effect with polymyxin B (PMB) in our fractional inhibitory concentration and time-kill analyses. The survival rate of G. mellonella infected with A. baumannii ATCC 17978 increased following the synergistic treatment. Interestingly, the addition of osmolytes, such as trehalose, canceled the synergistic effect of SAE with PMB; however, the underlying mechanism remains unclear. Quadrupole time-of-flight liquid chromatography-mass spectrometry revealed 6-bromo-2-naphthol (6B2N) to be a major active compound that exhibited synergistic effects with PMB. Pretreatment with 6B2N made A. baumannii cells more susceptible to PMB exposure in a time- and concentration-dependent manner, indicating that 6B2N exhibits consequential synergistic action with PMB. Moreover, the exposure of 6B2N-treated cells to PMB led to higher membrane leakage and permeability. The present findings provide a promising approach for utilizing plant extracts as adjuvants to reduce the toxicity of PMB in A. baumannii infection.
Machine learning-assisted lens-loaded cavity response optimization for improved direction-of-arrival estimation
Authors: Abbasi Muhammad Ali Babar , Akinsolu Mobayode O. , Liu Bo , Yurduseven Okan , Fusco Vincent F. , Imran Muhammad Ali 
Published: May 2022

AbstractThis paper presents a millimeter-wave direction of arrival estimation (DoA) technique powered by dynamic aperture optimization. The frequency-diverse medium in this work is a lens-loaded oversized mmWave cavity that hosts quasi-random wave-chaotic radiation modes. The presence of the lens is shown to confine the radiation within the field of view and improve the gain of each radiation mode; hence, enhancing the accuracy of the DoA estimation. It is also shown, for the first time, that a lens loaded-cavity can be transformed into a lens-loaded dynamic aperture by introducing a mechanically controlled mode-mixing mechanism inside the cavity. This work also proposes a way of optimizing this lens-loaded dynamic aperture by exploiting the mode mixing mechanism governed by a machine learning-assisted evolutionary algorithm. The concept is verified by a series of extensive simulations of the dynamic aperture states obtained via the machine learning-assisted evolutionary optimization technique. The simulation results show a 25$$\%$$%improvement in the conditioning for the DoA estimation using the proposed technique.
Classification and reconstruction of spatially overlapping phase images using diffractive optical networks
Authors: Mengu Deniz , Veli Muhammed , Rivenson Yair , Ozcan Aydogan 
Published: May 2022

AbstractDiffractive optical networks unify wave optics and deep learning to all-optically compute a given machine learning or computational imaging task as the light propagates from the input to the output plane. Here, we report the design of diffractive optical networks for the classification and reconstruction of spatially overlapping, phase-encoded objects. When two different phase-only objects spatially overlap, the individual object functions are perturbed since their phase patterns are summed up. The retrieval of the underlying phase images from solely the overlapping phase distribution presents a challenging problem, the solution of which is generally not unique. We show that through a task-specific training process, passive diffractive optical networks composed of successive transmissive layers can all-optically and simultaneously classify two different randomly-selected, spatially overlapping phase images at the input. After trained with ~ 550 million unique combinations of phase-encoded handwritten digits from the MNIST dataset, our blind testing results reveal that the diffractive optical network achieves an accuracy of > 85.8% for all-optical classification of two overlapping phase images of new handwritten digits. In addition to all-optical classification of overlapping phase objects, we also demonstrate the reconstruction of these phase images based on a shallow electronic neural network that uses the highly compressed output of the diffractive optical network as its input (with e.g., ~ 20–65 times less number of pixels) to rapidly reconstruct both of the phase images, despite their spatial overlap and related phase ambiguity. The presented phase image classification and reconstruction framework might find applications in e.g., computational imaging, microscopy and quantitative phase imaging fields.