bluuebunny/crossref_metadata_2025_split huggingface dataset:
RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair
Authors: Xiao Yanxuan , Li Jingyi , Liao Xiaoyu , He Yumin , He Tao , Yang Cuiping , Jiang Lu , Jeon So Mi , Lee Jong-Ho , Chen Yongbin , Liu Rui , Chen Qianming 
Published: February 2022

AbstractExposure to radiation causes DNA damage; hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1 (RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination (HR) repair but not nonhomologous end-joining (NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase (cGAS) to release cGAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29 (SGF29), which subsequently enables cGAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1 (PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains cGAS K491me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of cGAS that is essential for the regulation of ionizing radiation-elicited HR repair.
SF3B4 promotes ovarian cancer progression by regulating alternative splicing of RAD52
Authors: Diao Yuchao , Li Yingwei , Wang Zixiang , Wang Shourong , Li Peng , Kong Beihua 
Published: February 2022

AbstractMany studies have proven that splicing factors are crucial for human malignant tumor development. However, as a classical splicing factor, the expression of SF3B4 is not clear, and its biological function needs to be further clarified in ovarian cancer (OC). We determined that SF3B4 was obviously upregulated and its high expression was associated with poor prognosis in OC patients. In vitro and in vivo assays suggested that SF3B4 overexpression promoted OC cell proliferation and mobility, and downregulation of SF3B4 had the opposite effect. Further studies found that miR-509–3p decreased SF3B4 mRNA expression by binding to the 3’ -UTR of SF3B4 directly. Importantly, we revealed that RAD52 was a potential target of SF3B4 through alternative splicing events analysis. Loss of SF3B4 led to decreased expression of RAD52, owing to intron 8 retention and generation of premature termination codons. Moreover, decreased expression of RAD52 partially counteracted the tumor-promoting effect of SF3B4 overexpression. In conclusion, our results suggested that SF3B4, negatively regulated by miR-509–3p, promoted OC progression through effective splicing of RAD52. Therefore, SF3B4 may be a promising biomarker and effective therapeutic target for OC.
Cellular fractionation reveals transcriptome responses of human fibroblasts to UV-C irradiation
Authors: Liu Jiena , Wu Zhenzhen , He Jin , Wang Yuming 
Published: February 2022

AbstractWhile cells activate a multifaceted DNA damage response to remove transcription-blocking DNA lesions, mechanisms to regulate genome-wide reduction of RNA synthesis and the paradoxical continuous loading of RNAP II at initiation sites are still poorly understood. Uncovering how dramatic changes to the transcriptional program contribute to TC-NER (transcription-coupled nucleotide excision repair) is important in DNA repair research. However, the functional significance of transcriptome dynamics and the mechanisms of chromatin attachment for thousands of unstudied human lncRNAs remain unclear. To address these questions, we examined UV-induced gene expression regulation in human fibroblasts by performing RNA-seq with fractionated chromatin-associated and cytoplasmic transcripts. This approach allowed us to separate the synthesis of nascent transcripts from the accumulation of mature RNAs. In addition to documenting the subcellular locations of coding transcripts, our results also provide a high-resolution view of the transcription activities of noncoding RNAs in response to cellular stress. At the same time, the data showed that vast majority of genes exhibit large changes in chromatin-associated nascent transcripts without corresponding changes in cytoplasmic mRNA levels. Distinct from protein-coding genes that transcripts with shorter length prefer to be recovered first, repression of lncRNA transcription after UV exposure is inactivated first on noncoding transcripts with longer length. This work provides an updated framework for cellular RNA organization in response to stress and may provide useful information in understanding how cells respond to transcription-blocking DNA damage.
M1 macrophage-derived exosomes and their key molecule lncRNA HOTTIP suppress head and neck squamous cell carcinoma progression by upregulating the TLR5/NF-κB pathway
Authors: Jiang Huaili , Zhou Lei , Shen Na , Ning Xianhui , Wu Daquan , Jiang Kanglun , Huang Xinsheng 
Published: February 2022

AbstractExosomes serve as a crucial mode of communication between tumor-associated macrophages (TAMs) and cancer cells. This study attempted to explore the function of M1-derived exosomes and clarify their specific mechanism in head and neck squamous cell carcinoma (HNSCC). Moreover, the functional roles of M1-derived exosomes and their key molecule long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) in HNSCC were investigated by conducting a series of in vitro and in vivo experiments. The dual-luciferase test was utilized to clarify the binding capacities between HOTTIP/mRNA and miRNAs. Accordingly, HOTTIP was found to be upregulated in M1-derived exosomes. Meanwhile, the in vitro experiments indicated that M1 exosomes suppressed proliferation, migration and invasion but induced apoptosis of cancer cells. This function was noted to be enhanced by HOTTIP-overexpressed M1 exosomes but was weakened by HOTTIP-knockdown ones, indicating that HOTTIP serves as a key molecule in M1 exosomes. Therefore, the function of HOTTIP in cancer cells was explored, for which overexpression of HOTTIP was found to inhibit proliferation, migration and invasion but induced apoptosis of cancer cells in vitro. A mechanism study further showed that M1 exosomes and HOTTIP activated the TLR5/NF-κB signaling pathway by competitively sponging miR-19a-3p and miR-19b-3p. Furthermore, cancer cells expressing HOTTIP were noted to induce the polarization of both local M1 and M2 macrophages; however, M1 exosomes were observed to reprogram local TAMs into M1 macrophages. More importantly, both cancer cells expressing HOTTIP and M1 exosomes reeducated circulating monocytes to express the M1 phenotype. The corresponding data demonstrated that the M1 exosomal lncRNA HOTTIP suppresses HNSCC progression by upregulating the TLR5/NF-κB signaling pathway through competitively sponging miR-19a-3p and miR-19b-3p. In particular, M1 exosomes and HOTTIP induce the polarization of M1 in circulating monocytes, thus providing novel insight into HNSCC immunotherapy.
Aberrantly expressed Wnt5a in nurse-like cells drives resistance to Venetoclax in chronic lymphocytic leukemia
Authors: Guo Yao , Pei Hanzhong , Lu Bo , Zhang Dengyang , Zhao Yuming , Wu Fuqun , Sun Honghua , Huang Junbin , Li Peng , Yi Chenju , Zhu Chengming , Pan Yihang , Wu Shunjie , Chen Chun , Xu Xiaojun , Chen Yun 
Published: February 2022

AbstractChronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic B lymphocytes with high levels of Wnt5a in the plasma. Currently, the cell source of Wnt5a remains controversial. The receptor of Wnt5a is ROR1, whose expression is associated with disease progression and resistance to venetoclax, a BCL-2 inhibitor approved for the treatment of CLL. In this study, we found that the levels of Wnt5a in the plasma of CLL patients were positively correlated with absolute monocyte counts, but not lymphocyte counts. We cultured monocyte-derived nurse-like cells (NLCs) from patients with CLL, and detected Wnt5a expressed in NLCs. Flow cytometry and transwell assays showed that the antibody neutralizing Wnt5a inhibited the enhanced survival and migration in CLL cells co-cultured with NLCs. Furthermore, we performed a drug screening with CLL cells cultured with or without NLCs with a library containing 133 FDA-approved oncology drugs by using high-throughput flow cytometry. We observed a significant resistance to venetoclax in CLL cells co-cultured with NLCs. Immunoblot revealed the activation of NF-κB with enhanced expression of MCL-1 and BCL-XL in CLL cells co-cultured with NLCs. Neutralizing Wnt5a or blocking NF-κB pathway significantly decreased the expression of MCL-1 and BCL-XL, which leads to enhanced sensitivity to venetoclax in CLL cells co-cultured with NLCs. In conclusion, our data showed that NLCs could be one of the sources of Wnt5a detected in patients with CLL, and Wnt5a-induced NF-κB activation in the CLL microenvironment results in resistance to venetoclax in CLL cells.
Inter-element miscibility driven stabilization of ordered pseudo-binary alloy
Authors: Matsumoto Kenshi , Sato Ryota , Tatetsu Yasutomi , Takahata Ryo , Yamazoe Seiji , Yamauchi Miho , Inagaki Yuji , Horibe Yoichi , Kudo Masaki , Toriyama Takaaki , Auchi Mitsunari , Haruta Mitsutaka , Kurata Hiroki , Teranishi Toshiharu 
Published: February 2022

AbstractAn infinite number of crystal structures in a multicomponent alloy with a specific atomic ratio can be devised, although only thermodynamically-stable phases can be formed. Here, we experimentally show the first example of a layer-structured pseudo-binary alloy, theoretically called Z3-FePd3. This Z3 structure is achieved by adding a small amount of In, which is immiscible with Fe but miscible with Pd and consists of an alternate L10 (CuAu-type)-PdFePd trilayer and Pd–In ordered alloy monolayer along the c axis. First-principles calculations strongly support that the specific inter-element miscibility of In atoms stabilizes the thermodynamically-unstable Z3-FePd3 phase without significantly changing the original density of states of the Z3-FePd3 phase. Our results demonstrate that the specific inter-element miscibility can switch stable structures and manipulate the material nature with a slight composition change.
Modeling comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India
Authors: Du Zhanwei , Wang Lin , Pandey Abhishek , Lim Wey Wen , Chinazzi Matteo , Piontti Ana Pastore y. , Lau Eric H. Y. , Wu Peng , Malani Anup , Cobey Sarah , Cowling Benjamin J. 
Published: February 2022

AbstractGiven global Coronavirus Disease 2019 (COVID-19) vaccine shortages and inequity of vaccine distributions, fractionation of vaccine doses might be an effective strategy for reducing public health and economic burden, notwithstanding the emergence of new variants of concern. In this study, we developed a multi-scale model incorporating population-level transmission and individual-level vaccination to estimate the costs of hospitalization and vaccination and the economic benefits of reducing COVID-19 deaths due to dose-fractionation strategies in India. We used large-scale survey data of the willingness to pay together with data of vaccine and hospital admission costs to build the model. We found that fractional doses of vaccines could be an economically viable vaccination strategy compared to alternatives of either full-dose vaccination or no vaccination. Dose-sparing strategies could save a large number of lives, even with the emergence of new variants with higher transmissibility.
Domestic dogs (Canis familiaris) grieve over the loss of a conspecific
Authors: Uccheddu Stefania , Ronconi Lucia , Albertini Mariangela , Coren Stanley , Da Graça Pereira Gonçalo , De Cataldo Loriana , Haverbeke Anouck , Mills Daniel Simon , Pierantoni Ludovica , Riemer Stefanie , Testoni Ines , Pirrone Federica 
Published: February 2022

AbstractBehavioural reactions towards a dead conspecific have been observed rarely in wild canids and there is no documented scientific evidence of grief in pet dogs. A quantitative analysis of grief-related responses in both dogs and owners was conducted, using the validated online Mourning Dog Questionnaire. The survey was completed by 426 Italian adults who had owned at least two dogs, one of whom died while the other was still alive. This research aims to explore whether, how and what a dog may experience over the loss of a companion dog. Multiple logistic regression indicates that both a friendly or parental relationship between two dogs but also the fact that dogs used to share food and the owner’s grief and anger are principal predictors of negative behavioural changes. According to dog owners’ answers, the surviving dog after the death of the companion dog changed both in terms of activities (“playing”, “sleeping”, and “eating”) and emotions (fearfulness), which occurred as a function of the quality of the relationship between the two animals. By contrast, the time the two dogs had spent together had no effect on the behaviours of surviving dog. Owner perceptions about their dog’s reactions and emotions were not related to the memory or suffering of the event that tended to diminish over time. These findings indicate that a dog may show grief-related behavioural and emotional patterns when a close conspecific dies, with aspects of the latter possibly related to the owner’s emotional status.
Improving the efficiency and effectiveness of an industrial SARS-CoV-2 diagnostic facility
Authors: Douthwaite Julie A. , Brown Christopher A. , Ferdinand John R. , Sharma Rahul , Elliott Jane , Taylor Molly A. , Malintan Nancy T. , Duvoisin Hannah , Hill Thomas , Delpuech Oona , Orton Alexandra L. , Pitt Haidee , Kuenzi Fred , Fish Simon , Nicholls David J. , Cuthbert Anna , Richards Ian , Ratcliffe Giles , Upadhyay Abhishek , Marklew Abigail , Hewitt Craig , Ross-Thriepland Douglas , Brankin Christopher , Chodorge Matthieu , Browne Gareth , Mander Palwinder K. , DeWildt Ruud M. , Weaver Shane , Smee Penny A. , van Kempen Joost , Bartlett Jon G. , Allen Paula M. , Koppe Emma L. , Ashby Charlotte A. , Phipps Julian D. , Mehta Nalini , Brierley David J. , Tew David G. , Leveridge Melanie V. , Baddeley Stuart M. , Goodfellow Ian G. , Green Clive , Abell Chris , Neely Andy , Waddell Ian , Rees Steve , Maxwell Patrick H. , Pangalos Menelas N. , Howes Rob , Clark Roger 
Published: February 2022

AbstractOn 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories.
Design and implementation of compact dual-band conformal antenna for leadless cardiac pacemaker system
Authors: Sharma Deepti , Kanaujia Binod Kumar , Kaim Vikrant , Mittra Raj , Arya Ravi Kumar , Matekovits Ladislau 
Published: February 2022

AbstractThe leadless cardiac pacemaker is a pioneering device for heart patients. Its rising success requires the design of compact implantable antennas. In this paper, we describe a circularly polarized Hilbert curve inspired loop antenna. The proposed antenna works in the WMTS (Wireless Medical Telemetry Services) 1.4 GHz and ISM (Industrial, Scientific, and Medical) 2.45 GHz bands. High dielectric constant material Rogers RT/Duroid 6010 LM ($${\epsilon }_{r}$$

ϵ
r

=10) and fractal geometry helps to design the antenna with a small footprint of 9.1 mm3 (6 mm × 6 mm × 0.254 mm). The designed antenna has a conformal shape that fits inside a leadless pacemaker’s capsule is surrounded by IC models and battery, which are tightly packed in the device enclosure. Subsequently, the integrated prototype is simulated deep inside at the center of the multi-layer canonical heart model. To verify experimentally, we have put dummy electronics (IC and battery) inside the 3D printed pacemaker’s capsule and surfaced the fabricated conformal antenna around the inner curved body of the TCP (Transcatheter Pacing) capsule. Furthermore, we have tested the TCP capsule by inserting it in a ballistic gel phantom and minced pork. The measured impedance bandwidths at 1.4 GHz and 2.45 GHz are 250 MHz and 430 MHz, whereas measured gains are − 33.2 dBi, and − 28.5 dBi, respectively.
Unsupervised topological learning approach of crystal nucleation
Authors: Becker Sébastien , Devijver Emilie , Molinier Rémi , Jakse Noël 
Published: February 2022

AbstractNucleation phenomena commonly observed in our every day life are of fundamental, technological and societal importance in many areas, but some of their most intimate mechanisms remain however to be unravelled. Crystal nucleation, the early stages where the liquid-to-solid transition occurs upon undercooling, initiates at the atomic level on nanometre length and sub-picoseconds time scales and involves complex multidimensional mechanisms with local symmetry breaking that can hardly be observed experimentally in the very details. To reveal their structural features in simulations without a priori, an unsupervised learning approach founded on topological descriptors loaned from persistent homology concepts is proposed. Applied here to monatomic metals, it shows that both translational and orientational ordering always come into play simultaneously as a result of the strong bonding when homogeneous nucleation starts in regions with low five-fold symmetry. It also reveals the specificity of the nucleation pathways depending on the element considered, with features beyond the hypothesis of Classical Nucleation Theory.
Cycling area can be a confounder and effect modifier of the association between helmet use and cyclists’ risk of death after a crash
Authors: Molina-Soberanes Daniel , Martínez-Ruiz Virginia , Gordo Daniel Águila , Martín-delosReyes Luis Miguel , Rivera-Izquierdo Mario , Lardelli-Claret Pablo 
Published: February 2022

AbstractThe effect of helmet use on reducing the risk of death in cyclists appears to be distorted by some variables (potential confounders, effect modifiers, or both). Our aim was to provide evidence for or against the hypothesis that cycling area may act as a confounder and effect modifier of the association between helmet use and risk of death of cyclists involved in road crashes. Data were analysed for 24,605 cyclists involved in road crashes in Spain. A multiple imputation procedure was used to mitigate the effect of missing values. We used multilevel Poisson regression with province as the group level to estimate the crude association between helmet use and risk of death, and also three adjusted analyses: (1) for cycling area only, (2) for the remaining variables which may act as confounders, and (3) for all variables. Incidence–density ratios (IDR) and their 95% confidence intervals were calculated. Crude IDR was 1.10, but stratifying by cycling area disclosed a protective, differential effect of helmet use: IDR = 0.67 in urban areas, IDR = 0.34 on open roads. Adjusting for all variables except cycling area yielded similar results in both strata, albeit with a smaller difference between them. Adjusting for cycling area only yielded a strong association (IDR = 0.42), which was slightly lower in the adjusted analysis for all variables (IDR = 0.45). Cycling area can act as a confounder and also appears to act as an effect modifier (albeit to a lesser extent) of the risk of cyclists’ death after a crash.
KEu2In3B12S13: a novel type of thioborate featuring B12S12 cluster and unique In6S6 12-membered ring
Authors: Han Shan-Shan , Xu Qian-Ting , Liu Wenlong , Guo Sheng-Ping 
Published: February 2022

A novel thioborate KEu2In3B12S13 features {[In3B12S30]32–}∞ polyanionic framework built by B12S12 clusters and [In6S6]6+ 12-membered rings. Its structural chemistry, optical/magnetic properties, and theoretical calculations are studied.
Conceptual Framework Behind the Development of a Level of Confidence Tool: The Pediatric Videofluoroscopic Swallow Study Value Scale
Authors: Smith Leann Schow , Barkmeier-Kraemer Julie M. 
Published: February 2022

Purpose:The videofluoroscopic swallow study (VFSS) is the most commonly used instrumental procedure for evaluating swallowing in pediatric populations suspected of having dysphagia. Assessment and interpretation of a VFSS in pediatric populations is frequently challenged by testing-specific factors that can raise concerns regarding the representativeness of swallow events observed during testing compared to daily feeding/swallowing physiology. When VFSS findings do not represent typical swallowing patterns, treatment recommendations can result in suboptimal outcomes. To address this current challenge to pediatric VFSS interpretation and associated treatment recommendations, the pediatric VFSS Value Scale (pVFSS Value Scale) was developed within a tertiary regional pediatric medical center. This clinical focus article summarizes the initial scale development phases and resulting conceptual framework for rating clinical testing factors that influence a clinician's level of confidence regarding pediatric VFSS findings. Future goals for scientific evaluation and clinical utilization of this new rating scale are also reported.Conclusions:The pVFSS Value Scale was developed to assist clinicians with interpretation of pediatric VFSS assessment outcomes and to efficiently communicate factors influencing impressions and treatment recommendations with team members and caregivers. This clinical concept article summarizes potential uses of this tool to inform treatment planning as well as future clinical research to evaluate its psychometrics and clinical utility.