bluuebunny/crossref_metadata_2025 huggingface dataset:
UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer
Authors: Zhu Congcong , Zhang Long , Zhao Senlin , Dai Weixing , Xu Yun , Zhang Yuqin , Zheng Hongtu , Sheng Weiqi , Xu Ye
Published: May 2021

UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall survival (OS) and recurrence-free survival (RFS) in CRC patients and is an independent risk factor for recurrence. UPF1 promotes chemoresistance to oxaliplatin in vitro and in vivo. UPF1-induced oxaliplatin resistance can be associated with interaction between zinc finger of UPF1 and Toprim of TOP2A and increasing phosphorylated TOP2A in a SMG1-dependent manner. Moreover, UPF1 maintains stemness in a TOP2A-dependent manner in CRC. Taken together, UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced chemoresistance to oxaliplatin in CRC, which may result from regulation of TOP2A activity and maintenance of stemness. Our findings could provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.
Long non-coding RNA TUG1/microRNA-187-3p/TESC axis modulates progression of pituitary adenoma via regulating the NF-κB signaling pathway
Authors: Zhang Rui , Yang Fan , Fan Haitao , Wang Haocong , Wang Qinghao , Yang Jianxin , Song Tao
Published: May 2021

The molecule mechanisms of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in human diseases have been broadly studied recently, therefore, our research aimed to assess the effect of lncRNA taurine upregulated gene 1 (TUG1)/miR-187-3p/tescalcin (TESC) axis in pituitary adenoma (PA) by regulating the nuclear factor-kappa B (NF-κB) signaling pathway. We observed that TUG1 was upregulated in PA tissues and was associated with invasion, knosp grade and tumor size. TUG1 particularly bound to miR-187-3p. TUG1 knockdown inhibited cell proliferation, invasion, migration, and epithelial–mesenchymal transition, promoted apoptosis, and regulated the expression of NF-κB p65 and inhibitor of κB (IκB)-α in PA cells lines in vitro, and also inhibited tumor growth in vivo, and these effects were reversed by miR-187-3p reduction. Similarly, miR-187-3p elevation inhibited PA cell malignant behaviors and modulated the expression of NF-κB p65 and IκB-α in PA cells, and reduced in vivo tumor growth as well. TUG1 inhibition downregulated TESC, which was targeted by miR-187-3p. In conclusion, this study suggests that TUG1 sponges miR-187-3p to affect PA development by elevating TESC and regulating the NF-κB signaling pathway.
CD36 promotes NLRP3 inflammasome activation via the mtROS pathway in renal tubular epithelial cells of diabetic kidneys
Authors: Hou Yanjuan , Wang Qian , Han Baosheng , Chen Yiliang , Qiao Xi , Wang Lihua
Published: May 2021

Tubulointerstitial inflammation plays a key role in the pathogenesis of diabetic nephropathy (DN). Interleukin-1β (IL-1β) is the key proinflammatory cytokine associated with tubulointerstitial inflammation. The NLRP3 inflammasome regulates IL-1β activation and secretion. Reactive oxygen species (ROS) represents the main mediator of NLRP3 inflammasome activation. We previously reported that CD36, a class B scavenger receptor, mediates ROS production in DN. Here, we determined whether CD36 is involved in NLRP3 inflammasome activation and explored the underlying mechanisms. We observed that high glucose induced-NLRP3 inflammasome activation mediate IL-1β secretion, caspase-1 activation, and apoptosis in HK-2 cells. In addition, the levels of CD36, NLRP3, and IL-1β expression (protein and mRNA) were all significantly increased under high glucose conditions. CD36 knockdown resulted in decreased NLRP3 activation and IL-1β secretion. CD36 knockdown or the addition of MitoTempo significantly inhibited ROS production in HK-2 cells. CD36 overexpression enhanced NLRP3 activation, which was reduced by MitoTempo. High glucose levels induced a change in the metabolism of HK-2 cells from fatty acid oxidation (FAO) to glycolysis, which promoted mitochondrial ROS (mtROS) production after 72 h. CD36 knockdown increased the level of AMP-activated protein kinase (AMPK) activity and mitochondrial FAO, which was accompanied by the inhibition of NLRP3 and IL-1β. The in vivo experimental results indicate that an inhibition of CD36 could protect diabetic db/db mice from tubulointerstitial inflammation and tubular epithelial cell apoptosis. CD36 mediates mtROS production and NLRP3 inflammasome activation in db/db mice. CD36 inhibition upregulated the level of FAO-related enzymes and AMPK activity in db/db mice. These results suggest that NLRP3 inflammasome activation is mediated by CD36 in renal tubular epithelial cells in DN, which suppresses mitochondrial FAO and stimulates mtROS production.
Quantum loop states in spin-orbital models on the honeycomb lattice
Authors: Savary Lucile
Published: May 2021

The search for truly quantum phases of matter is a center piece of modern research in condensed matter physics. Quantum spin liquids, which host large amounts of entanglement—an entirely quantum feature where one part of a system cannot be measured without modifying the rest—are exemplars of such phases. Here, we devise a realistic model which relies upon the well-known Haldane chain phase, i.e. the phase of spin-1 chains which host fractional excitations at their ends, akin to the hallmark excitations of quantum spin liquids. We tune our model to exactly soluble points, and find that the ground state realizes Haldane chains whose physical supports fluctuate, realizing both quantum spin liquid like and symmetry-protected topological phases. Crucially, this model is expected to describe actual materials, and we provide a detailed set of material-specific constraints which may be readily used for an experimental realization.
Synaptic FUS accumulation triggers early misregulation of synaptic RNAs in a mouse model of ALS
Authors: Sahadevan Sonu , Hembach Katharina M. , Tantardini Elena , Pérez-Berlanga Manuela , Hruska-Plochan Marian , Megat Salim , Weber Julien , Schwarz Petra , Dupuis Luc , Robinson Mark D. , De Rossi Pierre , Polymenidou Magdalini
Published: May 2021

Mutations disrupting the nuclear localization of the RNA-binding protein FUS characterize a subset of amyotrophic lateral sclerosis patients (ALS-FUS). FUS regulates nuclear RNAs, but its role at the synapse is poorly understood. Using super-resolution imaging we determined that the localization of FUS within synapses occurs predominantly near the vesicle reserve pool of presynaptic sites. Using CLIP-seq on synaptoneurosomes, we identified synaptic FUS RNA targets, encoding proteins associated with synapse organization and plasticity. Significant increase of synaptic FUS during early disease in a mouse model of ALS was accompanied by alterations in density and size of GABAergic synapses. mRNAs abnormally accumulated at the synapses of 6-month-old ALS-FUS mice were enriched for FUS targets and correlated with those depicting increased short-term mRNA stability via binding primarily on multiple exonic sites. Our study indicates that synaptic FUS accumulation in early disease leads to synaptic impairment, potentially representing an initial trigger of neurodegeneration.
Mattertronics for programmable manipulation and multiplex storage of pseudo-diamagnetic holes and label-free cells
Authors: Goudu Sandhya Rani , Kim Hyeonseol , Hu Xinghao , Lim Byeonghwa , Kim Kunwoo , Torati Sri Ramulu , Ceylan Hakan , Sheehan Devin , Sitti Metin , Kim CheolGi
Published: May 2021

Manipulating and separating single label-free cells without biomarker conjugation have attracted significant interest in the field of single-cell research, but digital circuitry control and multiplexed individual storage of single label-free cells remain a challenge. Herein, by analogy with the electrical circuitry elements and electronical holes, we develop a pseudo-diamagnetophoresis (PsD) mattertronic approach in the presence of biocompatible ferrofluids for programmable manipulation and local storage of single PsD holes and label-free cells. The PsD holes conduct along linear negative micro-magnetic patterns. Further, eclipse diode patterns similar to the electrical diode can implement directional and selective switching of different PsD holes and label-free cells based on the diode geometry. Different eclipse heights and junction gaps influence the switching efficiency of PsD holes for mattertronic circuitry manipulation and separation. Moreover, single PsD holes are stored at each potential well as in an electrical storage capacitor, preventing multiple occupancies of PsD holes in the array of individual compartments due to magnetic Coulomb-like interaction. This approach may enable the development of large programmable arrays of label-free matters with high throughput, efficiency, and reliability as multiplex cell research platforms.
RTEL1 influences the abundance and localization of TERRA RNA
Authors: Ghisays Fiorella , Garzia Aitor , Wang Hexiao , Canasto-Chibuque Claudia , Hohl Marcel , Savage Sharon A. , Tuschl Thomas , Petrini John H. J.
Published: May 2021

Telomere repeat containing RNAs (TERRAs) are a family of long non-coding RNAs transcribed from the subtelomeric regions of eukaryotic chromosomes. TERRA transcripts can form R-loops at chromosome ends; however the importance of these structures or the regulation of TERRA expression and retention in telomeric R-loops remain unclear. Here, we show that the RTEL1 (Regulator of Telomere Length 1) helicase influences the abundance and localization of TERRA in human cells. Depletion of RTEL1 leads to increased levels of TERRA RNA while reducing TERRA-containing R loops at telomeres. In vitro, RTEL1 shows a strong preference for binding G-quadruplex structures which form in TERRA. This binding is mediated by the C-terminal region of RTEL1, and is independent of the RTEL1 helicase domain. RTEL1 binding to TERRA appears to be essential for cell viability, underscoring the importance of this function. Degradation of TERRA-containing R-loops by overexpression of RNAse H1 partially recapitulates the increased TERRA levels and telomeric instability associated with RTEL1 deficiency. Collectively, these data suggest that regulation of TERRA is a key function of the RTEL1 helicase, and that loss of that function may contribute to the disease phenotypes of patients with RTEL1 mutations.
2,6-diaminopurine promotes repair of DNA lesions under prebiotic conditions
Authors: Szabla Rafał , Zdrowowicz Magdalena , Spisz Paulina , Green Nicholas J. , Stadlbauer Petr , Kruse Holger , Šponer Jiří , Rak Janusz
Published: May 2021

High-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments.
Electronic metal–support interaction modulates single-atom platinum catalysis for hydrogen evolution reaction
Authors: Shi Yi , Ma Zhi-Rui , Xiao Yi-Ying , Yin Yun-Chao , Huang Wen-Mao , Huang Zhi-Chao , Zheng Yun-Zhe , Mu Fang-Ya , Huang Rong , Shi Guo-Yue , Sun Yi-Yang , Xia Xing-Hua , Chen Wei
Published: May 2021

Tuning metal–support interaction has been considered as an effective approach to modulate the electronic structure and catalytic activity of supported metal catalysts. At the atomic level, the understanding of the structure–activity relationship still remains obscure in heterogeneous catalysis, such as the conversion of water (alkaline) or hydronium ions (acid) to hydrogen (hydrogen evolution reaction, HER). Here, we reveal that the fine control over the oxidation states of single-atom Pt catalysts through electronic metal–support interaction significantly modulates the catalytic activities in either acidic or alkaline HER. Combined with detailed spectroscopic and electrochemical characterizations, the structure–activity relationship is established by correlating the acidic/alkaline HER activity with the average oxidation state of single-atom Pt and the Pt–H/Pt–OH interaction. This study sheds light on the atomic-level mechanistic understanding of acidic and alkaline HER, and further provides guidelines for the rational design of high-performance single-atom catalysts.
Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology
Authors: Kargapolova Yulia , Rehimi Rizwan , Kayserili Hülya , Brühl Joanna , Sofiadis Konstantinos , Zirkel Anne , Palikyras Spiros , Mizi Athanasia , Li Yun , Yigit Gökhan , Hoischen Alexander , Frank Stefan , Russ Nicole , Trautwein Jonathan , van Bon Bregje , Gilissen Christian , Laugsch Magdalena , Gusmao Eduardo Gade , Josipovic Natasa , Altmüller Janine , Nürnberg Peter , Längst Gernot , Kaiser Frank J. , Watrin Erwan , Brunner Han , Rada-Iglesias Alvaro , Kurian Leo , Wollnik Bernd , Bouazoune Karim , Papantonis Argyris
Published: May 2021

Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. By combining genomics with functional in vivo and in vitro assays, we show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS mutation affects CHD6 protein folding and impairs its ability to recruit co-remodelers in response to DNA damage or autophagy stimulation. This leads to accumulation of DNA damage burden and senescence-like phenotypes. We therefore uncovered a molecular mechanism explaining HSS onset via chromatin control of autophagic flux and genotoxic stress surveillance.
DNA origami single crystals with Wulff shapes
Authors: Wang Yong , Dai Lizhi , Ding Zhiyuan , Ji Min , Liu Jiliang , Xing Hang , Liu Xiaoguo , Ke Yonggang , Fan Chunhai , Wang Peng , Tian Ye
Published: May 2021

DNA origami technology has proven to be an excellent tool for precisely manipulating molecules and colloidal elements in a three-dimensional manner. However, fabrication of single crystals with well-defined facets from highly programmable, complex DNA origami units is a great challenge. Here, we report the successful fabrication of DNA origami single crystals with Wulff shapes and high yield. By regulating the symmetries and binding modes of the DNA origami building blocks, the crystalline shapes can be designed and well-controlled. The single crystals are then used to induce precise growth of an ultrathin layer of silica on the edges, resulting in mechanically reinforced silica-DNA hybrid structures that preserve the details of the single crystals without distortion. The silica-infused microcrystals can be directly observed in the dry state, which allows meticulous analysis of the crystal facets and tomographic 3D reconstruction of the single crystals by high-resolution electron microscopy.
Severe T cell hyporeactivity in ventilated COVID-19 patients correlates with prolonged virus persistence and poor outcomes
Authors: Renner Kerstin , Schwittay Tobias , Chaabane Sophia , Gottschling Johanna , Müller Christine , Tiefenböck Charlotte , Salewski Jan-Niklas , Winter Frederike , Buchtler Simone , Balam Saidou , Malfertheiner Maximilian V. , Lubnow Matthias , Lunz Dirk , Graf Bernhard , Hitzenbichler Florian , Hanses Frank , Poeck Hendrik , Kreutz Marina , Orsó Evelyn , Burkhardt Ralph , Niedermair Tanja , Brochhausen Christoph , Gessner André , Salzberger Bernd , Mack Matthias
Published: May 2021

Coronavirus disease 2019 (COVID-19) can lead to pneumonia and hyperinflammation. Here we show a sensitive method to measure polyclonal T cell activation by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood. We report a clear T cell hyporeactivity in hospitalized COVID-19 patients that is pronounced in ventilated patients, associated with prolonged virus persistence and reversible with clinical recovery. COVID-19-induced T cell hyporeactivity is T cell extrinsic and caused by plasma components, independent of occasional immunosuppressive medication of the patients. Monocytes respond stronger in males than females and IL-2 partially restores T cell activation. Downstream markers of T cell hyporeactivity are also visible in fresh blood samples of ventilated patients. Based on our data we developed a score to predict fatal outcomes and identify patients that may benefit from strategies to overcome T cell hyporeactivity.
Structural basis of substrate recognition and thermal protection by a small heat shock protein
Authors: Yu Chuanyang , Leung Stephen King Pong , Zhang Wenxin , Lai Louis Tung Faat , Chan Ying Ki , Wong Man Chit , Benlekbir Samir , Cui Yong , Jiang Liwen , Lau Wilson Chun Yu
Published: May 2021

Small heat shock proteins (sHsps) bind unfolding proteins, thereby playing a pivotal role in the maintenance of proteostasis in virtually all living organisms. Structural elucidation of sHsp-substrate complexes has been hampered by the transient and heterogeneous nature of their interactions, and the precise mechanisms underlying substrate recognition, promiscuity, and chaperone activity of sHsps remain unclear. Here we show the formation of a stable complex between Arabidopsis thaliana plastid sHsp, Hsp21, and its natural substrate 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) under heat stress, and report cryo-electron microscopy structures of Hsp21, DXPS and Hsp21-DXPS complex at near-atomic resolution. Monomeric Hsp21 binds across the dimer interface of DXPS and engages in multivalent interactions by recognizing highly dynamic structural elements in DXPS. Hsp21 partly unfolds its central α-crystallin domain to facilitate binding of DXPS, which preserves a native-like structure. This mode of interaction suggests a mechanism of sHsps anti-aggregation activity towards a broad range of substrates.
Accurate and scalable graph neural network force field and molecular dynamics with direct force architecture
Authors: Park Cheol Woo , Kornbluth Mordechai , Vandermause Jonathan , Wolverton Chris , Kozinsky Boris , Mailoa Jonathan P.
Published: May 2021

Recently, machine learning (ML) has been used to address the computational cost that has been limiting ab initio molecular dynamics (AIMD). Here, we present GNNFF, a graph neural network framework to directly predict atomic forces from automatically extracted features of the local atomic environment that are translationally-invariant, but rotationally-covariant to the coordinate of the atoms. We demonstrate that GNNFF not only achieves high performance in terms of force prediction accuracy and computational speed on various materials systems, but also accurately predicts the forces of a large MD system after being trained on forces obtained from a smaller system. Finally, we use our framework to perform an MD simulation of Li7P3S11, a superionic conductor, and show that resulting Li diffusion coefficient is within 14% of that obtained directly from AIMD. The high performance exhibited by GNNFF can be easily generalized to study atomistic level dynamics of other material systems.
Optimal provable robustness of quantum classification via quantum hypothesis testing
Authors: Weber Maurice , Liu Nana , Li Bo , Zhang Ce , Zhao Zhikuan
Published: May 2021

Quantum machine learning models have the potential to offer speedups and better predictive accuracy compared to their classical counterparts. However, these quantum algorithms, like their classical counterparts, have been shown to also be vulnerable to input perturbations, in particular for classification problems. These can arise either from noisy implementations or, as a worst-case type of noise, adversarial attacks. In order to develop defense mechanisms and to better understand the reliability of these algorithms, it is crucial to understand their robustness properties in the presence of natural noise sources or adversarial manipulation. From the observation that measurements involved in quantum classification algorithms are naturally probabilistic, we uncover and formalize a fundamental link between binary quantum hypothesis testing and provably robust quantum classification. This link leads to a tight robustness condition that puts constraints on the amount of noise a classifier can tolerate, independent of whether the noise source is natural or adversarial. Based on this result, we develop practical protocols to optimally certify robustness. Finally, since this is a robustness condition against worst-case types of noise, our result naturally extends to scenarios where the noise source is known. Thus, we also provide a framework to study the reliability of quantum classification protocols beyond the adversarial, worst-case noise scenarios.
Probing the interplay between lattice dynamics and short-range magnetic correlations in CuGeO3 with femtosecond RIXS
Authors: Paris E. , Nicholson C. W. , Johnston S. , Tseng Y. , Rumo M. , Coslovich G. , Zohar S. , Lin M. F. , Strocov V. N. , Saint-Martin R. , Revcolevschi A. , Kemper A. , Schlotter W. , Dakovski G. L. , Monney C. , Schmitt T.
Published: May 2021

Investigations of magnetically ordered phases on the femtosecond timescale have provided significant insights into the influence of charge and lattice degrees of freedom on the magnetic sub-system. However, short-range magnetic correlations occurring in the absence of long-range order, for example in spin-frustrated systems, are inaccessible to many ultrafast techniques. Here, we show how time-resolved resonant inelastic X-ray scattering (trRIXS) is capable of probing such short-ranged magnetic dynamics in a charge-transfer insulator through the detection of a Zhang–Rice singlet exciton. Utilizing trRIXS measurements at the O K-edge, and in combination with model calculations, we probe the short-range spin correlations in the frustrated spin chain material CuGeO3 following photo-excitation, revealing a strong coupling between the local lattice and spin sub-systems.
Inflammatory profile of induced sputum composition in systemic sclerosis and comparison with healthy volunteers
Authors: Jacquerie P. , Henket M. , André B. , Moermans C. , de Seny D. , Gester F. , Louis R. , Malaise M. , Guiot J.
Published: May 2021

Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease specially in case of interstitial lung disease (SSc-ILD). The aim of our study was to evaluate the potential utility of dosing in the induced sputum (IS) and to compare their levels in SSc-ILD and SSc-nonILD patients, as well as in healthy volunteers (HV). IS and sera values were also compared. In a prospective cross-sectional analysis, we studied the IS and serum provided from 25 SSc patients, 15 SSc-nonILD and 10 SSc-ILD, compared to 25 HV. We analyzed sputum cell composition and quantified in the supernatant and corresponding serum by commercially available immunoassays: IGFBP-1, IGFBP-2, IGFBP-3, TGF-β, IL-8, TNF-α, YKL-40, MMP-7 and MMP-9. Lung function was studied by the determination of FEV-1 (%), FVC (%), DLCO (%) and KCO (%). The IS of SSc patients had a lower weight than HV (p<0.05, p<0.01) without any significant difference with regard to the cellularity. IGFBP-1 (p < 0.0001), TGF-β (p < 0.05), IL-8 (p < 0.05), YKL-40 (p < 0.0001) and MMP-7 (p < 0.01) levels were increased in the IS of SSc patients compared to HV. Only IL-8 serum levels (p < 0.001) were increased in SSc patients compared to HV. Neither in IS nor in serum were observed differences between SSc-ILD and SSc-nonILD patients. Correlations were observed between IS IL-8 levels and FEV-1 (%) (r =  = − 0.53, p < 0.01), FVC (%) (r = − 0.51, p < 0.01) and annualized ∆KCO (%) (r = 0.57, p < 0.05), between IS TGF-β levels and annualized ∆FEV-1 (%) (r =  = − 0.57, p < 0.05), between IS IGFBP-2 levels and annualized ∆KCO (%) (r = 0.56, p < 0.05). Our study showed that SSc patients exhibit raised IS levels of IGFBP-1, TGF-β, IL-8, YKL-40 and MMP-7, molecules known to be involved in lung remodeling and fibrotic process, without any significant difference between SSc-ILD and SSc-nonILD patients. IL-8, TGF-β and IGFBP-2 are correlated with lung function in SSc patients which emphasize clinical relevance. IS analysis represents a new approach to understand lung inflammatory process in SSc patients. A longitudinal study is needed to evaluate their pathophysiological relevance.
Fully integrated ultra-sensitive electronic nose based on organic field-effect transistors
Authors: Anisimov Daniil S. , Chekusova Victoria P. , Trul Askold A. , Abramov Anton A. , Borshchev Oleg V. , Agina Elena V. , Ponomarenko Sergey A.
Published: May 2021

Modern solid-state gas sensors approaching ppb-level limit of detection open new perspectives for process control, environmental monitoring and exhaled breath analysis. Organic field-effect transistors (OFETs) are especially promising for gas sensing due to their outstanding sensitivities, low cost and small power consumption. However, they suffer of poor selectivity, requiring development of cross-selective arrays to distinguish analytes, and environmental instability, especially in humid air. Here we present the first fully integrated OFET-based electronic nose with the whole sensor array located on a single substrate. It features down to 30 ppb limit of detection provided by monolayer thick active layers and operates in air with up to 95% relative humidity. By means of principal component analysis, it is able to discriminate toxic air pollutants and monitor meat product freshness. The approach presented paves the way for developing affordable air sensing networks for the Internet of Things.
β-Galactosidase is a target enzyme for detecting peritoneal metastasis of gastric cancer
Authors: Kubo Hidemasa , Murayama Yasutoshi , Ogawa Soichiro , Matsumoto Tatsuya , Yubakami Masayuki , Ohashi Takuma , Kubota Takeshi , Okamoto Kazuma , Kamiya Mako , Urano Yasuteru , Otsuji Eigo
Published: May 2021

Diagnosis of peritoneal metastasis in gastric cancer (GC) is essential for determining appropriate therapeutic strategies and avoiding non-essential laparotomy or gastrectomy. Recently, a variety of activatable fluorescence probes that can detect enzyme activities have been developed for cancer imaging. The aim of this study was to identify the key enzyme involved in peritoneal metastasis in GC. The enzymatic activity of gamma-glutamyl transpeptidase, dipeptidyl peptidase IV, and β-galactosidase (β-Gal) was assessed in lysates prepared from preserved human GC (n = 89) and normal peritoneal (NP; n = 20) samples. β-Gal activity was significantly higher in the human GC samples than in NP samples, whereas no differences were observed in the activities of the other enzymes. Therefore, we used SPiDER-βGal, a fluorescent probe that can be activated by β-Gal, for imaging GC cell lines, peritoneal metastasis in a mouse model, and fresh human resected GC samples (n = 13). All cell lines showed fluorescence after applying SPiDER-βGal, and metastatic nodules in the mice gradually developed high fluorescence that could be visualized with SPiDER-βGal. The human GC samples showed significantly higher fluorescence than NP samples. β-Gal is a useful target enzyme for fluorescence imaging of peritoneal metastasis in GC.
Self-reported symptoms of arm lymphedema and health-related quality of life among female breast cancer survivors
Authors: Togawa Kayo , Ma Huiyan , Smith Ashley Wilder , Neuhouser Marian L. , George Stephanie M. , Baumgartner Kathy B. , McTiernan Anne , Baumgartner Richard , Ballard Rachel M. , Bernstein Leslie
Published: May 2021

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35–64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value < 0.0001). No difference was observed for perceived mental health (P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values < 0.05). Treatment targeting specific lymphedema-related symptoms in addition to size/volume reduction may improve some aspects of HRQoL among affected women.
The impact of improved data quality on the prevalence estimates of anthropometric measures using DHS datasets in India
Authors: Harkare Harsh Vivek , Corsi Daniel J. , Kim Rockli , Vollmer Sebastian , Subramanian S. V.
Published: May 2021

The importance of data quality to correctly determine prevalence estimates of child anthropometric failures has been a contentious issue among policymakers and researchers. Our research objective was to ascertain the impact of improved DHS data quality on the prevalence estimates of stunting, wasting, and underweight. The study also looks for the drivers of data quality. Using five data quality indicators based on age, sex, anthropometric measurements, and normality distribution, we arrive at two datasets of differential data quality and their estimates of anthropometric failures. For this purpose, we use the 2005–2006 and 2015–2016 NFHS data covering 311,182 observations from India. The prevalence estimates of stunting and underweight were virtually unchanged after the application of quality checks. The estimate of wasting had fallen 2 percentage points, indicating an overestimation of the true prevalence. However, this differential impact on the estimate of wasting was driven by the flagging procedure’s sensitivity and was in accordance with empirical evidence from existing literature. We found DHS data quality to be of sufficiently high quality for the prevalence estimates of stunting and underweight, to not change significantly after further improving the data quality. The differential estimate of wasting is attributable to the sensitivity of the flagging procedure.
Interacting with virtual objects via embodied avatar hands reduces pain intensity and diverts attention
Authors: Hoffman Hunter G.
Published: May 2021

The current study introduces a new paradigm for exploring cognitive factors in pain. Interacting with virtual objects via embodied avatar hands increased the illusion of “being there” in the virtual world, increased VR analgesia for acute pain, and reduced accuracy on an attention demanding task. Twenty-four healthy volunteer college students participated in this within-subject randomized crossover design study. During Phase 1, each participant received brief thermal pain stimuli during interactive embodied avatar VR vs. passive VR (no avatar and no interactivity), VR treatment order randomized. After each pain stimulus, participants provided subjective 0–10 ratings of pain. Compared to the passive VR condition, during the interactive avatar VR, participants reported significant reductions in (1) worst pain, (2) pain unpleasantness, (3) time thinking about pain and (4). they had significantly more fun during the pain stimulus (p = .000 for each). During Phase 2, participants performed a divided attention task in each of the two VR conditions. Participants made significantly more errors on the divided attention task during the interactive avatar VR condition, compared to passive VR, implicating an attention mechanism for how virtual reality reduces pain and helping understand how VR influences pain perception.

Trial registration: NCT04245475. Date of registration: 29/01/2020.
A nickel phosphide nanoalloy catalyst for the C-3 alkylation of oxindoles with alcohols
Authors: Fujita Shu , Imagawa Kohei , Yamaguchi Sho , Yamasaki Jun , Yamazoe Seiji , Mizugaki Tomoo , Mitsudome Takato
Published: May 2021

Although transition metal phosphides are well studied as electrocatalysts and hydrotreating catalysts, the application of metal phosphides in organic synthesis is rare, and cooperative catalysis between metal phosphides and supports remains unexplored. Herein, we report that a cerium dioxide-supported nickel phosphide nanoalloy (nano-Ni2P/CeO2) efficiently promoted the C-3 alkylation of oxindoles with alcohols without any additives through the borrowing hydrogen methodology. Oxindoles were alkylated with various alcohols to provide the corresponding C-3 alkylated oxindoles in high yields. This is the first catalytic system for the C-3 alkylation of oxindoles with alcohols using a non-precious metal-based heterogeneous catalyst. The catalytic activity of nano-Ni2P/CeO2was comparable to that reported for precious metal-based catalysts. Moreover, nano-Ni2P/CeO2was easily recoverable and reusable without any significant loss of activity. Control experiments revealed that the Ni2P nanoalloy and the CeO2support functioned cooperatively, leading to a high catalytic performance.
Hydrologic variation influences stream fish assemblage dynamics through flow regime and drought
Authors: Magoulick Daniel D. , Dekar Matthew P. , Hodges Shawn W. , Scott Mandy K. , Rabalais Michael R. , Bare Christopher M.
Published: May 2021

Hydrologic variation can play a major role in structuring stream fish assemblages and relationships between hydrology and biology are likely to be influenced by flow regime. We hypothesized that more variable flow regimes would have lower and more variable species richness, higher species turnover and lower assemblage stability, and greater abiotic environment-fish relationships than more stable flow regimes. We sampled habitats (pool, run, and riffle) in three Runoff/Intermittent Flashy streams (highly variable flow regime) and three Groundwater Flashy streams (less variable flow regime) seasonally (spring, early summer, summer and autumn) in 2002 (drought year) and 2003 (wet year). We used backpack electrofishing and three-pass removal techniques to estimate fish species richness, abundance and density. Fish species richness and abundance remained relatively stable within streams and across seasons, but densities changed substantially as a result of decreased habitat volume. Mixed model analysis showed weak response variable-habitat relationships with strong season effects in 2002, and stronger habitat relationships and no season effect in 2003, and flow regime was not important in structuring these relationships. Seasonal fish species turnover was significantly greater in 2002 than 2003, but did not differ between flow regimes. Fish assemblage stability was significantly lower in Runoff/Intermittent Flashy than Groundwater Flashy streams in 2002, but did not differ between flow regimes in 2003. Redundancy analysis showed fish species densities were well separated by flow regime in both years. Periodic and opportunistic species were characteristic of Runoff/Intermittent Flashy streams, whereas mainly equilibrium species were characteristic of Groundwater Flashy streams. We found that spatial and temporal variation in hydrology had a strong influence on fish assemblage dynamics in Ozark streams with lower assemblage stability and greater fluctuations in density in more hydrologically variable streams and years. Understanding relationships between fish assemblage structure and hydrologic variation is vital for conservation of fish biodiversity. Future work should consider addressing how alteration of hydrologic variation will affect biotic assemblages.
Using data linkage for national surveillance of clinical quality indicators for dementia care among Australian aged care users
Authors: Cations Monica , Lang Catherine , Ward Stephanie A. , Caughey Gillian E. , Crotty Maria , Whitehead Craig , Ahern Susannah , Maddison John , Inacio Maria C.
Published: May 2021

Care quality has important implications for people with dementia. We examined trends and geographical variation of four clinical quality indicators (CQIs) in Australia. This retrospective cohort study included all people with dementia using Australian government-subsidised aged care in 2008–2016 (n = 373,695). Quality indicator data were derived from linked national aged care, health, and pharmaceutical datasets. Negative binomial regression modelling assessed trends in CQI performance over time (2011–2016) and funnel plots examined geographical variation in performance. The incidence rate of antipsychotic medicine dispensing decreased slightly from 1.17/1000 person-days to 1.07/1000 person-days (adjusted incidence rate ratio (aIRR) = 0.98, 95%CI 0.98–0.99). Cholinesterase inhibitors and memantine dispensing did not change (aIRR = 1.02, 95%CI 1.00–1.04), while exposure to high sedative load increased slightly from 1.39/1000 person-days to 1.44/1000 person-days (aIRR = 1.01, 95%CI 1.00–1.01). Dementia and delirium-related hospitalisations increased slightly from 0.17/1000 person-days to 0.18/1000 person-days (aIRR = 1.02, 95%CI 1.01–1.03). There was marked variation in cholinesterase inhibitor and memantine dispensing by geographical area (0–41%). There has been little change in four indicators of dementia care quality in Australian aged care users over time. Cholinesterase inhibitor and memantine dispensing varied substantially by geographical region. Existing strategies to improve national performance on these indicators appear to be insufficient, despite the significant impact of these indicators on outcomes for people with dementia.
Differential mast cell numbers and characteristics in human tuberculosis pulmonary lesions
Authors: Garcia-Rodriguez Karen Magdalena , Bini Estela Isabel , Gamboa-Domínguez Armando , Espitia-Pinzón Clara Inés , Huerta-Yepez Sara , Bulfone-Paus Silvia , Hernández-Pando Rogelio
Published: May 2021

Tuberculosis (TB) is still a major worldwide health threat and primarily a lung disease. The innate immune response againstMycobacterium tuberculosis(Mtb) is orchestrated by dendritic cells, macrophages, neutrophils, natural killer cells and apparently mast cells (MCs). MCs are located at mucosal sites including the lungs and contribute in host-defence against pathogens, but little is known about their role duringMtbinfection. This study investigates the location and characteristics of MCs in TB lesions to assess their contribution to TB pathology. To this purpose, number, location and phenotype of MCs was studied in 11 necropsies of pulmonary TB and 3 necropsies of non-TB infected lungs that were used as controls. MCs were localised at pneumonic areas, in the granuloma periphery and particularly abundant in fibrotic tissue. Furthermore, MCs displayed intracellularMtband IL-17A and TGF-β immunostaining. These findings were validated by analysing, post-mortem lung tissue microarrays from 44 individuals with pulmonary TB and 25 control subjects. In affected lungs, increased numbers of MCs expressing intracellularly both tryptase and chymase were found at fibrotic sites. Altogether, our data suggest that MCs are recruited at the inflammatory site and that actively produce immune mediators such as proteases and TGF-β that may be contributing to late fibrosis in TB lesions.
Development﻿ of fully automated anterior chamber cell analysis based on image software
Authors: Kang Tae Seen , Lee Yeongseop , Lee Seongjin , Kim Kyonghoon , Lee Woong-sub , Lee Woohyuk , Kim Jin Hyun , Han Yong Seop
Published: May 2021

Optical coherence tomography (OCT) is a noninvasive method that can quickly and accurately examine the eye at the cellular level. Several studies have used OCT for analysis of anterior chamber cells. However, these studies have several limitations. This study was performed to supplement existing reports of automated analysis of anterior chamber cell images using spectral domain OCT (SD-OCT) and to compare this method with the Standardization of Uveitis Nomenclature (SUN) grading system. We analyzed 2398 anterior segment SD-OCT images from 34 patients using code written in Python. Cell density, size, and eccentricity were measured automatically. Increases in SUN grade were associated with significant cell density increases at all stages (p < 0.001). Significant differences were observed in eccentricity in uveitis, post-surgical inflammation, and vitreous hemorrhage (p < 0.001). Anterior segment SD-OCT is reliable, fast, and accurate means of anterior chamber cell analysis. This method showed a strong correlation with the SUN grade system. Also, eccentricity could be helpful as a supplementary evaluation tool.
Evidence of anticipatory immune and hormonal responses to predation risk in an echinoderm
Authors: Hamel Jean-François , Jobson Sara , Caulier Guillaume , Mercier Annie
Published: May 2021

Recent efforts have been devoted to the link between responses to non-physical stressors and immune states in animals, mostly using human and other vertebrate models. Despite evolutionary relevance, comparatively limited work on the appraisal of predation risk and aspects of cognitive ecology and ecoimmunology has been carried out in non-chordate animals. The present study explored the capacity of holothuroid echinoderms to display an immune response to both reactive and anticipatory predatory stressors. Experimental trials and a mix of behavioural, cellular and hormonal markers were used, with a focus on coelomocytes (analogues of mammalian leukocytes), which are the main components of the echinoderm innate immunity. Findings suggest that holothuroids can not only appraise threatening cues (i.e. scent of a predator or alarm signals from injured conspecifics) but prepare themselves immunologically, presumably to cope more efficiently with potential future injuries. The responses share features with recently defined central emotional states and wane after prolonged stress in a manner akin to habituation, which are traits that have rarely been shown in non-vertebrates, and never in echinoderms. Because echinoderms sit alongside chordates in the deuterostome clade, such findings offer unique insights into the adaptive value and evolution of stress responses in animals.
Spermine mediated improvements on stomatal features, growth, grain filling and yield of rice under differing water availability
Authors: Berahim Zulkarami , Dorairaj Deivaseeno , Omar Mohamad Husni , Saud Halimi Mohd , Ismail Mohd Razi
Published: May 2021

Rice which belongs to the grass family is vulnerable to water stress. As water resources get limited, the productivity of rice is affected especially in granaries located at drought prone areas. It would be even worse in granaries located in drought prone areas such as KADA that receives the lowest rainfall in Malaysia. Spermine (SPM), a polyamine compound that is found ubiquitiosly in plants is involved in adaptation of biotic and abiotic stresses. The effect of SPM on growth,grain filling and yield of rice at three main granaries namely, IADA BLS, MADA and KADA representing unlimited water, limited water and water stress conditions respectively, were tested during the main season. Additinally, the growth enhancer was also tested during off season at KADA. Spermine increased plant height, number of tillers per hill and chlorophyll content in all three granaries. Application of SPM improved yield by 38, 29 and 20% in MADA, KADA and IADA BLS, respectively. Harvest index showed 2.6, 6 and 16% increases at IADA BLS, KADA and MADA, respectively in SPM treated plants as compared to untreated. Except for KADA which showed a reduction in yield at 2.54 tha−1, SPM improved yield at MADA, 7.21 tha−1 and IADA BLS, 9.13 tha−1 as compared to the average yield at these respective granaries. In the second trial, SPM increased the yield to 7.0 and 6.4 tha−1 during main and off seasons, respectively, indicating that it was significantly higher than control and the average yield reported by KADA. The yield of SPM treatments improved by 25 and 33% with an increment of farmer’s income at main and off seasons, respectively. Stomatal width was significantly higher than control at 11.89 µm. In conclusion, irrespective of the tested granaries and rice variety, spermine mediated plots displayed increment in grain yield.
Longitudinal profiling of the burn patient cutaneous and gastrointestinal microbiota: a pilot study
Authors: Lima Kelly M. , Davis Ryan R. , Liu Stephenie Y. , Greenhalgh David G. , Tran Nam K.
Published: May 2021

Sepsis is a leading cause of morbidity and mortality in patients that have sustained a severe burn injury. Early detection and treatment of infections improves outcomes and understanding changes in the host microbiome following injury and during treatment may aid in burn care. The loss of functional barriers, systemic inflammation, and commensal community perturbations all contribute to a burn patient’s increased risk of infection. We sampled 10 burn patients to evaluate cutaneous microbial populations on the burn wound and corresponding spared skin on days 0, 3, 7, 14, 21, and 28 post-intensive care unit admission. In addition, skin samples were paired with perianal and rectal locations to evaluate changes in the burn patient gut microbiome following injury and treatment. We found significant (P = 0.011) reduction in alpha diversity on the burn wound compared to spared skin throughout the sampling period as well as reduction in common skin commensal bacteria such as Propionibacterium acnes and Staphylococcus epidermitis. Compared to healthy volunteers (n = 18), the burn patient spared skin also exhibited a significant reduction in alpha diversity (P = 0.001). Treatments such as systemic or topical antibiotic administration, skin grafting, and nutritional formulations also impact diversity and community composition at the sampling locations. When evaluating each subject individually, an increase in relative abundance of taxa isolated clinically by bacterial culture could be seen in 5/9 infections detected among the burn patient cohort.