bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study of posttraumatic stress disorder among childhood cancer survivors: results from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort
Authors: Lu Donghao , Sapkota Yadav , Valdimarsdóttir Unnur A. , Koenen Karestan C. , Li Nan , Leisenring Wendy M. , Gibson Todd , Wilson Carmen L. , Robison Leslie L. , Hudson Melissa M. , Armstrong Gregory T. , Krull Kevin R. , Yasui Yutaka , Bhatia Smita , Recklitis Christopher J. 
Published: August 2022

AbstractGenetic influence shapes who develops posttraumatic stress disorder (PTSD) after traumatic events. However, the genetic variants identified for PTSD may in fact be associated with traumatic exposures (e.g., interpersonal violence), which appear heritable as well. Childhood cancer survivors (CCS) are at risk for PTSD, but genetic influences affecting cancer are unlikely to overlap with those affecting PTSD. This offers a unique opportunity to identify variants specific to PTSD risk. In a genome-wide association study (GWAS), 3984 5-year survivors of childhood cancer of European-ancestry from the Childhood Cancer Survivor Study (CCSS) were evaluated for discovery and 1467 survivors from the St. Jude Lifetime (SJLIFE) cohort for replication. Childhood cancer-related PTSD symptoms were assessed using the Posttraumatic Stress Diagnostic Scale in CCSS. GWAS was performed in CCSS using logistic regression and lead markers were replicated/meta-analyzed using SJLIFE. Cross-associations of identified loci were examined between CCS and the general population. PTSD criteria were met for 671 participants in CCSS and 161 in SJLIFE. Locus 10q26.3 was significantly associated with PTSD (rs34713356, functionally mapped to ECHS1, P = 1.36 × 10–8, OR 1.57), and was replicated in SJLIFE (P = 0.047, OR 1.37). Variants in locus 6q24.3-q25.1 reached marginal significance (rs9390543, SASH1, P = 3.56 × 10–6, OR 0.75) in CCSS and significance when meta-analyzing with SJLIFE (P = 2.02 × 10–8, OR 0.75). Both loci were exclusively associated with PTSD in CCS rather than PTSD/stress-related disorders in general population (P-for-heterogeneity < 5 × 10–6). Our CCS findings support the role of genetic variation in PTSD development and may provide implications for understanding PTSD heterogeneity.
Strontium-incorporated bioceramic scaffolds for enhanced osteoporosis bone regeneration
Authors: Wu Qianju , Hu Longwei , Yan Ran , Shi Junfeng , Gu Hao , Deng Yuwei , Jiang Ruixue , Wen Jin , Jiang Xinquan 
Published: August 2022

AbstractThe restoration of bone defects caused by osteoporosis remains a challenge for surgeons. Strontium ranelate has been applied in preventative treatment approaches due to the biological functions of the trace element strontium (Sr). In this study, we aimed to fabricate bioactive scaffolds through Sr incorporation based on our previously developed modified amino-functional mesoporous bioactive glass (MBG) and to systematically investigate the bioactivity of the resulting scaffold in vitro and in vivo in an osteoporotic rat model. The results suggested that Sr-incorporated amino-functional MBG scaffolds possessed favorable biocompatibility. Moreover, with the incorporation of Sr, osteogenic and angiogenic capacities were upregulated in vitro. The in vivo results showed that the Sr-incorporated amino-functional MBG scaffolds achieved better bone regeneration and vessel formation. Furthermore, bioinformatics analysis indicated that the Sr-incorporated amino-functional MBG scaffolds could reduce reactive oxygen species levels in bone marrow mesenchymal stem cells in the osteoporotic model by activating the cAMP/PKA signaling pathway, thus playing an anti-osteoporosis role while promoting osteogenesis. This study demonstrated the feasibility of incorporating trace elements into scaffolds and provided new insights into biomaterial design for facilitating bone regeneration in the treatment of osteoporosis.
Imaging and phase-locking of non-linear spin waves
Authors: Dreyer Rouven , Schäffer Alexander F. , Bauer Hans G. , Liebing Niklas , Berakdar Jamal , Woltersdorf Georg 
Published: August 2022

AbstractNon-linear processes are a key feature in the emerging field of spin-wave based information processing and allow to convert uniform spin-wave excitations into propagating modes at different frequencies. Recently, the existence of non-linear magnons at half-integer multiples of the driving frequency has been predicted for Ni80Fe20 at low bias fields. However, it is an open question under which conditions such non-linear spin waves emerge coherently and how they may be used in device structures. Usually non-linear processes are explored in the small modulation regime and result in the well known three and four magnon scattering processes. Here we demonstrate and image a class of spin waves oscillating at half-integer harmonics that have only recently been proposed for the strong modulation regime. The direct imaging of these parametrically generated magnons in Ni80Fe20 elements allows to visualize their wave vectors. In addition, we demonstrate the presence of two degenerate phase states that may be selected by external phase-locking. These results open new possibilities for applications such as spin-wave sources, amplifiers and phase-encoded information processing with magnons.
KLF4 recruits SWI/SNF to increase chromatin accessibility and reprogram the endothelial enhancer landscape under laminar shear stress
Authors: Moonen Jan-Renier , Chappell James , Shi Minyi , Shinohara Tsutomu , Li Dan , Mumbach Maxwell R. , Zhang Fan , Nair Ramesh V. , Nasser Joseph , Mai Daniel H. , Taylor Shalina , Wang Lingli , Metzger Ross J. , Chang Howard Y. , Engreitz Jesse M. , Snyder Michael P. , Rabinovitch Marlene 
Published: August 2022

AbstractPhysiologic laminar shear stress (LSS) induces an endothelial gene expression profile that is vasculo-protective. In this report, we delineate how LSS mediates changes in the epigenetic landscape to promote this beneficial response. We show that under LSS, KLF4 interacts with the SWI/SNF nucleosome remodeling complex to increase accessibility at enhancer sites that promote the expression of homeostatic endothelial genes. By combining molecular and computational approaches we discover enhancers that loop to promoters of KLF4- and LSS-responsive genes that stabilize endothelial cells and suppress inflammation, such as BMPR2, SMAD5, and DUSP5. By linking enhancers to genes that they regulate under physiologic LSS, our work establishes a foundation for interpreting how non-coding DNA variants in these regions might disrupt protective gene expression to influence vascular disease.
Nucleosome-directed replication origin licensing independent of a consensus DNA sequence
Authors: Li Sai , Wasserman Michael R. , Yurieva Olga , Bai Lu , O’Donnell Michael E. , Liu Shixin 
Published: August 2022

AbstractThe numerous enzymes and cofactors involved in eukaryotic DNA replication are conserved from yeast to human, and the budding yeast Saccharomyces cerevisiae (S.c.) has been a useful model organism for these studies. However, there is a gap in our knowledge of why replication origins in higher eukaryotes do not use a consensus DNA sequence as found in S.c. Using in vitro reconstitution and single-molecule visualization, we show here that S.c. origin recognition complex (ORC) stably binds nucleosomes and that ORC-nucleosome complexes have the intrinsic ability to load the replicative helicase MCM double hexamers onto adjacent nucleosome-free DNA regardless of sequence. Furthermore, we find that Xenopus laevis nucleosomes can substitute for yeast ones in engaging with ORC. Combined with re-analyses of genome-wide ORC binding data, our results lead us to propose that the yeast origin recognition machinery contains the cryptic capacity to bind nucleosomes near a nucleosome-free region and license origins, and that this nucleosome-directed origin licensing paradigm generalizes to all eukaryotes.
Bayesian optimization with experimental failure for high-throughput materials growth
Authors: Wakabayashi Yuki K. , Otsuka Takuma , Krockenberger Yoshiharu , Sawada Hiroshi , Taniyasu Yoshitaka , Yamamoto Hideki 
Published: August 2022

AbstractA crucial problem in achieving innovative high-throughput materials growth with machine learning, such as Bayesian optimization (BO), and automation techniques has been a lack of an appropriate way to handle missing data due to experimental failures. Here, we propose a BO algorithm that complements the missing data in optimizing materials growth parameters. The proposed method provides a flexible optimization algorithm that searches a wide multi-dimensional parameter space. We demonstrate the effectiveness of the method with simulated data as well as in its implementation for actual materials growth, namely machine-learning-assisted molecular beam epitaxy (ML-MBE) of SrRuO3, which is widely used as a metallic electrode in oxide electronics. Through the exploitation and exploration in a wide three-dimensional parameter space, while complementing the missing data, we attained tensile-strained SrRuO3 film with a high residual resistivity ratio of 80.1, the highest among tensile-strained SrRuO3 films ever reported, in only 35 MBE growth runs.
Multiple heavy metals affect root response, iron plaque formation, and metal bioaccumulation of Kandelia obovata
Authors: Chai Minwei , Li Ruili , Shen Xiaoxue , Yu Lingyun , Han Jie 
Published: August 2022

AbstractMultiple heavy metal pollution in mangrove wetlands is serious. Kandelia obovata seedlings were cultured in pots in which lead (Pb), zinc (Zn) and copper (Cu) were added separately and in combinations. The results showed that heavy metal stress improved the rate of root oxygen leakage, enhanced root activity, and reduced root porosity. The root under single heavy metal stress was impacted by the addition of other heavy metals, demonstrating antagonistic or synergistic effects. Iron plaque (IP) formation was improved under single Zn or Cu stress, and inhibited in binary stress of Pb + Cu. The adsorptions of IP on heavy metals in combined stress (Pb, 62–116 μg g−1; Zn, 194–207 μg g−1; Cu, 35–52 μg g−1) were higher than that in single stress (Pb, 18 μg g−1; Zn, 163 μg g−1; Cu, 22 μg g−1). K. obovata accumulated higher levels of heavy metals in root (Pb, 7–200 μg g−1; Cu, 4–78 μg g−1), compared with IP (Pb, 18–116 μg g−1; Cu, 22–52 μg g−1), stem (Pb, 3–7 μg g−1; Cu, 9–17 μg g−1), and leaf (Pb, 2–4 μg g−1; Cu, 4–7 μg g−1). Correlation analysis showed that single and binary stresses affected K. obovata, with more significant effect of trinary stress. Regression path analysis showed that multiple heavy metal stress firstly affected root, then indirectly contributed to IP formation, as well as heavy metal in IP and root; at last, heavy metal in IP directly contributed to heavy metal bioaccumulations in root.
Patient-reported symptom burden in patients with rare cancers receiving pembrolizumab in a phase II Clinical Trial
Authors: Mendoza Tito R. , Hong David S. , Peterson Christine B. , Stephen Bettzy , Dumbrava Ecaterina , Pant Shubbam , Tsimberidou Apostolia Maria , Yap Timothy Anthony , Sheshadri Ajay , Altan Mehmet , George Goldy , Castillo Lilibeth , Rodriguez Enedelia , Gong Jing , Subbiah Vivek , Janku Filip , Fu Siqing , Piha-Paul Sarina A. , Ahnert Jordi Rodon , Karp Daniel D. , Cleeland Charles , Meric-Bernstam Funda , Naing Aung 
Published: August 2022

AbstractPatients with rare solid tumors treated on early phase trials experience toxicities from their tumors and treatments. However, limited data exist to describe the detailed symptom burden suffered by these patients, particularly those with rare solid tumors treated with immunotherapy. We performed a prospective longitudinal study to capture patient-reported symptom burden. Patients completed the validated MD Anderson Symptom Inventory (MDASI)—Immunotherapy with 20 symptoms including 7 immunotherapy-specific items and 6 interference items at baseline and weekly thereafter for up to 9 weeks. Symptoms and interference were rated on 0–10 scales (0 = none or no interference, 10 = worst imaginable or complete interference). Group-based trajectory modelling determined higher and lower symptom groups. A total of 336 MDASI questionnaires were completed by 53 patients (mean age 55.4y, 53% male) with advanced rare cancers receiving pembrolizumab in a Phase II clinical trial. Symptoms reported as most severe over the course of the treatment over 9 weeks were fatigue [mean (M) = 3.8, SD = 2.3], pain (M = 3.7, SD = 2.9), disturbed sleep (M = 2.7, SD = 2.3), drowsiness (M = 2.6, SD = 2.0) and lack of appetite (M = 2.5, SD = 2.1). Pain in the abdomen (M = 2.2, SD = 2.4), rash (M = 1.1, SD = 1.8) and diarrhea (M = 0.9, SD = 1.5) were less severe. Interference with walking was rated the highest (M = 3.4, SD = 2.8) and relations with others was rated the lowest (M = 2.1, SD = 2.6). Using a composite score based on the five most severe symptoms (fatigue, pain, lack of appetite, feeling drowsy and sleep disturbance), 43% were classified into the high symptom burden group. Using a score based on immunotherapy-specific symptoms (e.g., rash, diarrhea) 33% of patients were included in the high symptom group. Symptom burden stayed relatively stable in the high- and low-symptom burden patient groups from baseline through 9 weeks. Some patients with rare malignancies experienced high symptom burden even at baseline. In patients with rare cancers, symptom trajectories stayed relatively stable over nine weeks of treatment with pembrolizumab.Trial registration: ClinicalTrials.gov identifier: NCT02721732.
Harmonisation of in-silico next-generation sequencing based methods for diagnostics and surveillance
Authors: Nunez-Garcia J. , AbuOun M. , Storey N. , Brouwer M. S. , Delgado-Blas J. F. , Mo S. S. , Ellaby N. , Veldman K. T. , Haenni M. , Châtre P. , Madec J. Y. , Hammerl J. A. , Serna C. , Getino M. , La Ragione R. , Naas T. , Telke A. A. , Glaser P. , Sunde M. , Gonzalez-Zorn B. , Ellington M. J. , Anjum M. F. 
Published: August 2022

AbstractImprovements in cost and speed of next generation sequencing (NGS) have provided a new pathway for delivering disease diagnosis, molecular typing, and detection of antimicrobial resistance (AMR). Numerous published methods and protocols exist, but a lack of harmonisation has hampered meaningful comparisons between results produced by different methods/protocols vital for global genomic diagnostics and surveillance. As an exemplar, this study evaluated the sensitivity and specificity of five well-established in-silico AMR detection software where the genotype results produced from running a panel of 436 Escherichia coli were compared to their AMR phenotypes, with the latter used as gold-standard. The pipelines exploited previously known genotype–phenotype associations. No significant differences in software performance were observed. As a consequence, efforts to harmonise AMR predictions from sequence data should focus on: (1) establishing universal minimum to assess performance thresholds (e.g. a control isolate panel, minimum sensitivity/specificity thresholds); (2) standardising AMR gene identifiers in reference databases and gene nomenclature; (3) producing consistent genotype/phenotype correlations. The study also revealed limitations of in-silico technology on detecting resistance to certain antimicrobials due to lack of specific fine-tuning options in bioinformatics tool or a lack of representation of resistance mechanisms in reference databases. Lastly, we noted user friendliness of tools was also an important consideration. Therefore, our recommendations are timely for widespread standardisation of bioinformatics for genomic diagnostics and surveillance globally.
Computational modelling of γ-H2AX foci formation in human cells induced by alpha particle exposure
Authors: Abu Shqair Ali , Lee Ui-Seob , Kim Eun-Hee 
Published: August 2022

AbstractIn cellular experiments, radiation-induced DNA damage can be quantified by counting the number of γ-H2AX foci in cell nucleus by using an immunofluorescence microscope. Quantification of DNA damage carries uncertainty, not only due to lack of full understanding the biological processes but also limitations in measurement techniques. The causes of limited certainty include the possibility of expressing foci in varying sizes responding individual DSBs and the overlapping of foci on the two-dimensional (2D) immunofluorescence microscopy image of γ-H2AX foci, especially when produced due to high-LET radiation exposure. There have been discussions on those limitations, but no successful studies to overcome them. In this paper, a practical modelling has been developed to simulate the occurrences of double-strand breaks (DSBs) and the formations of γ-H2AX foci in response to individual DSB formations, in cell nucleus due to exposure to alpha particles. Cell irradiation and DSB production were simulated using a user-written code that utilizes Geant4-DNA physics models. A C +  + code was used to simulate the formation γ-H2AX foci, which were spatially correlated to the loci of DBSs, and to calculate the number of individual foci from the observed 2D image of the cell nucleus containing the overlapping γ-H2AX foci. The average size of focal images was larger from alpha particle exposure than that from X-ray exposure, whereas the number of separate focal images were comparable except at doses up to 0.5 Gy. About 40% of separate focal images consisted of overlapping γ-H2AX foci at 1 Gy of alpha particle exposure. The foci overlapping ratios were obtained by simulation for individual size groups of focal images at varying doses. The size distributions of foci at varying doses were determined with experimentally obtained separate focal images. The correction factor for foci number was calculated using the foci overlapping ratio and foci size distribution, which are specific to dose from alpha particle exposure. The number of individual foci formations induced by applying the correction factor to the experimentally observed number of focal images better reflected the quality of alpha particles in causing DNA damage. Consequently, the conventional γ-H2AX assay can be better implemented by employing this computational modelling of γ-H2AX foci formation.
Characterization of anti-proliferative and anti-oxidant effects of nano-sized vesicles from Brassica oleracea L. (Broccoli)
Authors: Hossain Md Niamat , De Leo Vincenzo , Tamborra Rosanna , Laselva Onofrio , Ingrosso Chiara , Daniello Valeria , Catucci Lucia , Losito Ilario , Sollitto Francesco , Loizzi Domenico , Conese Massimo , Di Gioia Sante 
Published: August 2022

AbstractIn this in vitro study, we test our hypothesis that Broccoli-derived vesicles (BDVs), combining the anti-oxidant properties of their components and the advantages of their structure, can influence the metabolic activity of different cancer cell lines. BDVs were isolated from homogenized fresh broccoli (Brassica oleracea L.) using a sucrose gradient ultracentrifugation method and were characterized in terms of physical properties, such as particle size, morphology, and surface charge by transmission electron microscopy (TEM) and laser doppler electrophoresis (LDE). Glucosinolates content was assessed by RPLC–ESI–MS analysis. Three different human cancer cell lines (colorectal adenocarcinoma Caco-2, lung adenocarcinoma NCI-H441 and neuroblastoma SHSY5Y) were evaluated for metabolic activity by the MTT assay, uptake by fluorescence and confocal microscopy, and anti-oxidant activity by a fluorimetric assay detecting intracellular reactive oxygen species (ROS). Three bands were obtained with average size measured by TEM based size distribution analysis of 52 nm (Band 1), 70 nm (Band 2), and 82 nm (Band 3). Glucobrassicin, glucoraphanin and neoglucobrassicin were found mostly concentrated in Band 1. BDVs affected the metabolic activity of different cancer cell lines in a dose dependent manner compared with untreated cells. Overall, Band 2 and 3 were more toxic than Band 1 irrespective of the cell lines. BDVs were taken up by cells in a dose- and time-dependent manner. Pre-incubation of cells with BDVs resulted in a significant decrease in ROS production in Caco-2 and NCI-H441 stimulated with hydrogen peroxide and SHSY5Y treated with 6-hydroxydopamine, with all three Bands. Our findings open to the possibility to find a novel “green” approach for cancer treatment, focused on using vesicles from broccoli, although a more in-depth characterization of bioactive molecules is warranted.
Understanding the mechanism of Nb-MXene bioremediation with green microalgae
Authors: Jakubczak Michał , Bury Dominika , Purbayanto Muhammad Abiyyu Kenichi , Wójcik Anna , Moszczyńska Dorota , Prenger Kaitlyn , Naguib Michael , Jastrzębska Agnieszka Maria 
Published: August 2022

AbstractRapidly developing nanotechnologies and their integration in daily applications may threaten the natural environment. While green methods of decomposing organic pollutants have reached maturity, remediation of inorganic crystalline contaminants is major problem due to their low biotransformation susceptibility and the lack of understanding of material surface-organism interactions. Herein, we have used model inorganic 2D Nb-based MXenes coupled with a facile shape parameters analysis approach to track the mechanism of bioremediating 2D ceramic nanomaterials with green microalgae Raphidocelis subcapitata. We have found that microalgae decomposed the Nb-based MXenes due to surface-related physicochemical interactions. Initially, single and few-layered MXene nanoflakes attached to microalgae surfaces, which slightly reduced algal growth. But with prolonged surface interaction, the microalgae oxidized MXene nanoflakes and further decomposed them into NbO and Nb2O5. Since these oxides were nontoxic to microalgal cells, they consumed Nb-oxide nanoparticles by an uptake mechanism thus enabling further microalgae recovery after 72 h of water treatment. The uptake-associated nutritional effects were also reflected by cells’ increased size, smoothed shape and changed growth rates. Based on these findings, we conclude that short- and long-term presence of Nb-based MXenes in freshwater ecosystems might cause only negligible environmental effects. Notably, by using 2D nanomaterials as a model system, we show evidence of the possibility of tracking even fine material shape transformations. In general, this study answers an important fundamental question about the surface interaction-associated processes that drive the mechanism of 2D nanomaterials’ bioremediation as well as provides the fundamental basis for further short- and long-term investigations on the environmental effects of inorganic crystalline nanomaterials.