bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospects and challenges of dynamic DNA nanostructures in biomedical applications
Authors: Tian Taoran , Li Yanjing , Lin Yunfeng 
Published: May 2022

AbstractThe physicochemical nature of DNA allows the assembly of highly predictable structures via several fabrication strategies, which have been applied to make breakthroughs in various fields. Moreover, DNA nanostructures are regarded as materials with excellent editability and biocompatibility for biomedical applications. The ongoing maintenance and release of new DNA structure design tools ease the work and make large and arbitrary DNA structures feasible for different applications. However, the nature of DNA nanostructures endows them with several stimulus-responsive mechanisms capable of responding to biomolecules, such as nucleic acids and proteins, as well as biophysical environmental parameters, such as temperature and pH. Via these mechanisms, stimulus-responsive dynamic DNA nanostructures have been applied in several biomedical settings, including basic research, active drug delivery, biosensor development, and tissue engineering. These applications have shown the versatility of dynamic DNA nanostructures, with unignorable merits that exceed those of their traditional counterparts, such as polymers and metal particles. However, there are stability, yield, exogenous DNA, and ethical considerations regarding their clinical translation. In this review, we first introduce the recent efforts and discoveries in DNA nanotechnology, highlighting the uses of dynamic DNA nanostructures in biomedical applications. Then, several dynamic DNA nanostructures are presented, and their typical biomedical applications, including their use as DNA aptamers, ion concentration/pH-sensitive DNA molecules, DNA nanostructures capable of strand displacement reactions, and protein-based dynamic DNA nanostructures, are discussed. Finally, the challenges regarding the biomedical applications of dynamic DNA nanostructures are discussed.
Epithelial de-differentiation triggered by co-ordinate epigenetic inactivation of the EHF and CDX1 transcription factors drives colorectal cancer progression
Authors: Luk Ian Y. , Jenkins Laura J. , Schoffer Kael L. , Ng Irvin , Tse Janson W. T. , Mouradov Dmitri , Kaczmarczyk Stanislaw , Nightingale Rebecca , Burrows Allan D. , Anderson Robin L. , Arango Diego , Dopeso Higinio , Croft Larry , Richardson Mark F. , Sieber Oliver M. , Liao Yang , Mooi Jennifer K. , Vukelic Natalia , Reehorst Camilla M. , Afshar-Sterle Shoukat , Whitehall Vicki L. J. , Fennell Lochlan , Abud Helen E. , Tebbutt Niall C. , Phillips Wayne A. , Williams David S. , Shi Wei , Mielke Lisa A. , Ernst Matthias , Dhillon Amardeep S. , Clemons Nicholas J. , Mariadason John M. 
Published: May 2022

AbstractColorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF and CDX1 in poorly-differentiated CRC cells induced extensive chromatin remodelling, transcriptional re-programming, and differentiation along the enterocytic lineage, leading to reduced growth and metastasis. Strikingly, EHF and CDX1 were also able to reprogramme non-colonic epithelial cells to express colonic differentiation markers. By contrast, inactivation of EHF and CDX1 in well-differentiated CRC cells triggered tumour de-differentiation. Mechanistically, we demonstrate that EHF physically interacts with CDX1 via its PNT domain, and that these transcription factors co-operatively drive transcription of the colonic differentiation marker, VIL1. Compound genetic deletion of Ehf and Cdx1 in the mouse colon disrupted normal colonic differentiation and significantly enhanced colorectal tumour progression. These findings thus reveal a novel mechanism driving epithelial de-differentiation and tumour progression in CRC.
A genetic engineering strategy for editing near-infrared-II fluorophores
Authors: Tian Rui , Feng Xin , Wei Long , Dai Daoguo , Ma Ying , Pan Haifeng , Ge Shengxiang , Bai Lang , Ke Chaomin , Liu Yanlin , Lang Lixin , Zhu Shoujun , Sun Haitao , Yu Yanbao , Chen Xiaoyuan 
Published: May 2022

AbstractThe second near-infrared (NIR-II) window is a fundamental modality for deep-tissue in vivo imaging. However, it is challenging to synthesize NIR-II probes with high quantum yields (QYs), good biocompatibility, satisfactory pharmacokinetics, and tunable biological properties. Conventional long-wavelength probes, such as inorganic probes (which often contain heavy metal atoms in their scaffolds) and organic dyes (which contain large π-conjugated groups), exhibit poor biosafety, low QYs, and/or uncontrollable pharmacokinetic properties. Herein, we present a bioengineering strategy that can replace the conventional chemical synthesis methods for generating NIR-II contrast agents. We use a genetic engineering technique to obtain a series of albumin fragments and recombinant proteins containing one or multiple domains that form covalent bonds with chloro-containing cyanine dyes. These albumin variants protect the inserted dyes and remarkably enhance their brightness. The albumin variants can also be genetically edited to develop size-tunable complexes with precisely tailored pharmacokinetics. The proteins can also be conjugated to biofunctional molecules without impacting the complexed dyes. This combination of albumin mutants and clinically-used cyanine dyes can help widen the clinical application prospects of NIR-II fluorophores.
Kinetically restrained oxygen reduction to hydrogen peroxide with nearly 100% selectivity
Authors: Chen Jinxing , Ma Qian , Zheng Xiliang , Fang Youxing , Wang Jin , Dong Shaojun 
Published: May 2022

AbstractHydrogen peroxide has been synthesized mainly through the electrocatalytic and photocatalytic oxygen reduction reaction in recent years. Herein, we synthesize a single-atom rhodium catalyst (Rh1/NC) to mimic the properties of flavoenzymes for the synthesis of hydrogen peroxide under mild conditions. Rh1/NC dehydrogenates various substrates and catalyzes the reduction of oxygen to hydrogen peroxide. The maximum hydrogen peroxide production rate is 0.48 mol gcatalyst−1 h−1 in the phosphorous acid aerobic oxidation reaction. We find that the selectivity of oxygen reduction to hydrogen peroxide can reach 100%. This is because a single catalytic site of Rh1/NC can only catalyze the removal of two electrons per substrate molecule; thus, the subsequent oxygen can only obtain two electrons to reduce to hydrogen peroxide through the typical two-electron pathway. Similarly, due to the restriction of substrate dehydrogenation, the hydrogen peroxide selectivity in commercial Pt/C-catalyzed enzymatic reactions can be found to reach 75%, which is 30 times higher than that in electrocatalytic oxygen reduction reactions.
Effectiveness of CoronaVac in children 3–5 years of age during the SARS-CoV-2 Omicron outbreak in Chile
Authors: Jara Alejandro , Undurraga Eduardo A. , Zubizarreta José R. , González Cecilia , Acevedo Johanna , Pizarro Alejandra , Vergara Verónica , Soto-Marchant Mario , Gilabert Rosario , Flores Juan Carlos , Suárez Pamela , Leighton Paulina , Eguiguren Pablo , Ríos Juan Carlos , Fernandez Jorge , García-Escorza Heriberto , Araos Rafael 
Published: May 2022

AbstractThe outbreak of the B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron) has caused an unprecedented number of Coronavirus Disease 2019 (COVID-19) cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but, to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3–5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of Sinovac’s inactivated SARS-CoV-2 vaccine (CoronaVac). We used inverse probability-weighted survival regression models to estimate hazard ratios of symptomatic COVID-19, hospitalization and admission to an intensive care unit (ICU) for children with complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between 6 December 2021 and 26 February 2022, during the Omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95% confidence interval (CI), 36.5–39.9) against symptomatic COVID-19, 64.6% (95% CI, 49.6–75.2) against hospitalization and 69.0% (95% CI, 18.6–88.2) against ICU admission. The effectiveness against symptomatic COVID-19 was modest; however, protection against severe disease was high. These results support vaccination of children aged 3–5 years to prevent severe illness and associated complications and highlight the importance of maintaining layered protections against SARS-CoV-2 infection.
A Fetal Brain magnetic resonance Acquisition Numerical phantom (FaBiAN)
Authors: Lajous Hélène , Roy Christopher W. , Hilbert Tom , de Dumast Priscille , Tourbier Sébastien , Alemán-Gómez Yasser , Yerly Jérôme , Yu Thomas , Kebiri Hamza , Payette Kelly , Ledoux Jean-Baptiste , Meuli Reto , Hagmann Patric , Jakab Andras , Dunet Vincent , Koob Mériam , Kober Tobias , Stuber Matthias , Bach Cuadra Meritxell 
Published: May 2022

AbstractAccurate characterization of in utero human brain maturation is critical as it involves complex and interconnected structural and functional processes that may influence health later in life. Magnetic resonance imaging is a powerful tool to investigate equivocal neurological patterns during fetal development. However, the number of acquisitions of satisfactory quality available in this cohort of sensitive subjects remains scarce, thus hindering the validation of advanced image processing techniques. Numerical phantoms can mitigate these limitations by providing a controlled environment with a known ground truth. In this work, we present FaBiAN, an open-source Fetal Brain magnetic resonance Acquisition Numerical phantom that simulates clinical T2-weighted fast spin echo sequences of the fetal brain. This unique tool is based on a general, flexible and realistic setup that includes stochastic fetal movements, thus providing images of the fetal brain throughout maturation comparable to clinical acquisitions. We demonstrate its value to evaluate the robustness and optimize the accuracy of an algorithm for super-resolution fetal brain magnetic resonance imaging from simulated motion-corrupted 2D low-resolution series compared to a synthetic high-resolution reference volume. We also show that the images generated can complement clinical datasets to support data-intensive deep learning methods for fetal brain tissue segmentation.
A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients
Authors: Jung Seoyeon , Kim Jaeyeon , Park Jin Hoo , Kim Ki-Yeol , Kim Hyung Jun , Park Wonse 
Published: May 2022

AbstractDenosumab has been suggested as a first-line therapy for osteoporotic patients. However, a standardized protocol for the prevention of denosumab induced medication-related osteonecrosis of the jaw (MRONJ) has not yet been established. The purpose of this study was to report denosumab induced MRONJ cases, and investigate the factors affecting the occurrence of MRONJ in patients who underwent denosumab and invasive dental treatment (especially tooth extraction) between October 2016 and March 2020. Four of the 98 patients developed MRONJ before and after tooth extraction. The participants were divided into two groups: receiving only denosumab (n = 51) and receiving bisphosphonate as first treatment and denosumab as second treatment (n = 47). There was no significant difference between groups in the occurrence of MRONJ and factors affecting MRONJ. Two out of 4 patients developed MRONJ regardless of invasive treatment after denosumab administration and proceeded with extraction; one patient developed MRONJ after denosumab administration and extraction. The other patient underwent a tooth extraction without osteoporosis treatment, and non-identified MRONJ developed after denosumab administration. MRONJ cases reported in this study show that MRONJ can develop as chronic inflammation without invasive dental treatment; therefore, implementing preventive dental treatment before initiating denosumab treatment is necessary to reduce the occurrence of MRONJ.
Bio-actuated microvalve in microfluidics using sensing and actuating function of Mimosa pudica
Authors: Aishan Yusufu , Funano Shun-ichi , Sato Asako , Ito Yuri , Ota Nobutoshi , Yalikun Yaxiaer , Tanaka Yo 
Published: May 2022

AbstractBio-actuators and sensors are increasingly employed in microscale devices for numerous applications. Unlike other artificial devices actuated by living cells or tissues, here we introduce a microvalve system actuated by the stimuli-responsive action plant,Mimosa pudica(sleepy plant). This system realizes the control of the valve to open and close by dropping and recovering responses ofMimosa pudicabranch upon external physical stimulations. The results showed that one matured single uncutMimosa pudicabranch produced average force of 15.82 ± 0.7 mN. This force was sufficient for actuating and keeping the valve open for 8.46 ± 1.33 min in a stimulation-recovering cycle of 30 min. Additionally, two separately cutMimosa pudicabranches were able to keep the valve open for 2.28 ± 0.63 min in a stimulating-recovering cycle of 20min. The pressure resistance and the response time of the valve were 4.2 kPa and 1.4 s, respectively. This demonstration of plant-microfluidics integration encourages exploiting more applications of microfluidic platforms that involve plant science and plant energy harvesting.
Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors
Authors: Iraji Aida , Shareghi-Brojeni Diba , Mojtabavi Somayeh , Faramarzi Mohammad Ali , Akbarzadeh Tahmineh , Saeedi Mina 
Published: May 2022

AbstractIn this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with Ki = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔHm°) and entropy (ΔSm°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.
Multiagent off-screen behavior prediction in football
Authors: Omidshafiei Shayegan , Hennes Daniel , Garnelo Marta , Wang Zhe , Recasens Adria , Tarassov Eugene , Yang Yi , Elie Romuald , Connor Jerome T. , Muller Paul , Mackraz Natalie , Cao Kris , Moreno Pol , Sprechmann Pablo , Hassabis Demis , Graham Ian , Spearman William , Heess Nicolas , Tuyls Karl 
Published: May 2022

AbstractIn multiagent worlds, several decision-making individuals interact while adhering to the dynamics constraints imposed by the environment. These interactions, combined with the potential stochasticity of the agents’ dynamic behaviors, make such systems complex and interesting to study from a decision-making perspective. Significant research has been conducted on learning models for forward-direction estimation of agent behaviors, for example, pedestrian predictions used for collision-avoidance in self-driving cars. In many settings, only sporadic observations of agents may be available in a given trajectory sequence. In football, subsets of players may come in and out of view of broadcast video footage, while unobserved players continue to interact off-screen. In this paper, we study the problem of multiagent time-series imputation in the context of human football play, where available past and future observations of subsets of agents are used to estimate missing observations for other agents. Our approach, called the Graph Imputer, uses past and future information in combination with graph networks and variational autoencoders to enable learning of a distribution of imputed trajectories. We demonstrate our approach on multiagent settings involving players that are partially-observable, using the Graph Imputer to predict the behaviors of off-screen players. To quantitatively evaluate the approach, we conduct experiments on football matches with ground truth trajectory data, using a camera module to simulate the off-screen player state estimation setting. We subsequently use our approach for downstream football analytics under partial observability using the well-established framework of pitch control, which traditionally relies on fully observed data. We illustrate that our method outperforms several state-of-the-art approaches, including those hand-crafted for football, across all considered metrics.
Ultrathin picoscale white light interferometer
Authors: Dahiya Sunil , Tyagi Akansha , Mandal Ankur , Pfeifer Thomas , Singh Kamal P. 
Published: May 2022

AbstractWhite light interferometry is a well established technique with diverse precision applications, however, the conventional interferometers such as Michelson, Mach-Zehnder or Linnik are large in size, demand tedious alignment for obtaining white light fringes, require noise-isolation techniques to achieve sub-nanometric stability and importantly, exhibit unbalanced dispersion causing uncertainty in absolute zero delay reference. Here, we demonstrate an ultrathin white light interferometer enabling picometer resolution by exploiting the wavefront division of a broadband incoherent light beam after transmission through a pair of micrometer thin identical glass plates. Spatial overlap between the two diffracted split wavefronts readily produce high-contrast and stable white light fringes, with unambiguous reference to absolute zero path-delay position. The colored fringes evolve when one of the ultrathin plates is rotated to tune the interferometer with picometric resolution over tens of μm range. Our theoretical analysis validates formation of fringes and highlights self-calibration of the interferometer for picoscale measurements. We demonstrate measurement of coherence length of several broadband incoherent sources as small as a few micrometer with picoscale resolution. Furthermore, we propose a versatile double-pass configuration using the ultrathin interferometer enabling a sample cavity for additional applications in probing dynamical properties of matter.
NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59
Authors: Son Sung Wook , Cho Eunho , Cho Hanbyoul , Woo Seon Rang , Lee Hyo-Jung , Oh Se Jin , Kim Suyeon , Kim Jae-Hoon , Chung Eun Joo , Chung Joon-Yong , Kim Min Gyu , Song Kwon-Ho , Kim Tae Woo 
Published: May 2022

AbstractCancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG+ tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure triggered cross-resistance of tumor cells to the complement system, a part of the innate immune system. In this process, NANOG upregulated the membrane-bound complement regulatory protein (mCRP) CD59 through promoter occupancy, thereby contributing to the resistance of tumor cells against complement-dependent cytotoxicity (CDC). Notably, targeting of NANOG sensitized the immune-refractory tumor cells to trastuzumab-mediated CDC. Collectively, our results revealed a possible mechanism through which selection imposed by T-cell based immunotherapy triggered complement-resistant phenotypes in the tumor microenvironment (TME), by establishing a firm molecular link between NANOG and CD59 in immune-edited tumor cells. We believe these results hold important implications for the clinical application of CDC-mediated therapeutic antibody.
Identification of nontuberculous mycobacteria isolated from household showerheads of patients with nontuberculous mycobacteria
Authors: Choi Ji Yeon , Sim Bo Ra , Park Youngmok , Yong Seung Hyun , Shin Sung Jae , Kang Young Ae 
Published: May 2022

AbstractThis study aimed to examine whether nontuberculous mycobacteria (NTM) inside household showerheads are identical to those in patients with NTM-pulmonary disease (PD) since household water is one of the potential NTM sources. Samples were obtained from 32 household showerheads of patients with NTM-PD recruited through the Pulmonary Outpatient Department at the Severance Hospital between October 2018 and October 2019. All isolates from patients with NTM-PD were diagnosed using a reverse-hybridization line probe assay based on the ropB gene. To determine the mycobacterial compositions, the washing fluids were collected and investigated using multiplex polymerase chain reaction assay and NTM culture; suspected microbial isolates in these fluids and culture were identified using sequencing analysis of 16S rRNA gene. NTM species causing the PD in the patients were Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, and M. fortuitum complex. The mycobacteria isolated from the showerhead were M. lentiflavum, M. gordonae, M. triplex, M. phocaicum, M. mucogenicum, M. florentinum, M. gilvum, M. llatzerense, and M. peregrinum. However, the species identified in the showerheads did not match those of the patients. Despite NTM species in the showerheads, clinical implications in the main pathogenesis associated with the disease in the patients studied were not elucidated.