bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon emission from Western Siberian inland waters
Authors: Karlsson Jan , Serikova Svetlana , Vorobyev Sergey N. , Rocher-Ros Gerard , Denfeld Blaize , Pokrovsky Oleg S.
Published: February 2021

High-latitude regions play a key role in the carbon (C) cycle and climate system. An important question is the degree of mobilization and atmospheric release of vast soil C stocks, partly stored in permafrost, with amplified warming of these regions. A fraction of this C is exported to inland waters and emitted to the atmosphere, yet these losses are poorly constrained and seldom accounted for in assessments of high-latitude C balances. This is particularly relevant for Western Siberia, with its extensive peatland C stocks, which can be strongly sensitive to the ongoing changes in climate. Here we quantify C emission from inland waters, including the Ob’ River (Arctic’s largest watershed), across all permafrost zones of Western Siberia. We show that the inland water C emission is high (0.08–0.10 Pg C yr−1) and of major significance in the regional C cycle, largely exceeding (7–9 times) C export to the Arctic Ocean and reaching nearly half (35–50%) of the region’s land C uptake. This important role of C emission from inland waters highlights the need for coupled land–water studies to understand the contemporary C cycle and its response to warming.
Control of zeolite microenvironment for propene synthesis from methanol
Authors: Lin Longfei , Fan Mengtian , Sheveleva Alena M. , Han Xue , Tang Zhimou , Carter Joseph H. , da Silva Ivan , Parlett Christopher M. A. , Tuna Floriana , McInnes Eric J. L. , Sastre German , Rudić Svemir , Cavaye Hamish , Parker Stewart F. , Cheng Yongqiang , Daemen Luke L. , Ramirez-Cuesta Anibal J. , Attfield Martin P. , Liu Yueming , Tang Chiu C. , Han Buxing , Yang Sihai
Published: February 2021

Optimising the balance between propene selectivity, propene/ethene ratio and catalytic stability and unravelling the explicit mechanism on formation of the first carbon–carbon bond are challenging goals of great importance in state-of-the-art methanol-to-olefin (MTO) research. We report a strategy to finely control the nature of active sites within the pores of commercial MFI-zeolites by incorporating tantalum(V) and aluminium(III) centres into the framework. The resultant TaAlS-1 zeolite exhibits simultaneously remarkable propene selectivity (51%), propene/ethene ratio (8.3) and catalytic stability (>50 h) at full methanol conversion. In situ synchrotron X-ray powder diffraction, X-ray absorption spectroscopy and inelastic neutron scattering coupled with DFT calculations reveal that the first carbon–carbon bond is formed between an activated methanol molecule and a trimethyloxonium intermediate. The unprecedented cooperativity between tantalum(V) and Brønsted acid sites creates an optimal microenvironment for efficient conversion of methanol and thus greatly promotes the application of zeolites in the sustainable manufacturing of light olefins.
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
Authors: Muskens Ivo S. , Li Shaobo , Jackson Thomas , Elliot Natalina , Hansen Helen M. , Myint Swe Swe , Pandey Priyatama , Schraw Jeremy M. , Roy Ritu , Anguiano Joaquin , Goudevenou Katerina , Siegmund Kimberly D. , Lupo Philip J. , de Bruijn Marella F. T. R. , Walsh Kyle M. , Vyas Paresh , Ma Xiaomei , Roy Anindita , Roberts Irene , Wiemels Joseph L. , de Smith Adam J.
Published: February 2021

Down syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P < 7.67 × 10−8) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P < 0.0001). The top two differentially methylated regions overlap RUNX1 and FLI1, both important regulators of megakaryopoiesis and hematopoietic development, with significant hypermethylation at promoter regions of these two genes. Excluding Down syndrome newborns harboring preleukemic GATA1 mutations (N = 30), identified by targeted sequencing, has minimal impact on the epigenome-wide association study results. Down syndrome has profound, genome-wide effects on DNA methylation in hematopoietic cells in early life, which may contribute to the high frequency of hematological problems, including leukemia, in children with Down syndrome.
Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Authors: Bakouny Ziad , Braun David A. , Shukla Sachet A. , Pan Wenting , Gao Xin , Hou Yue , Flaifel Abdallah , Tang Stephen , Bosma-Moody Alice , He Meng Xiao , Vokes Natalie , Nyman Jackson , Xie Wanling , Nassar Amin H. , Abou Alaiwi Sarah , Flippot Ronan , Bouchard Gabrielle , Steinharter John A. , Nuzzo Pier Vitale , Ficial Miriam , Sant’Angelo Miriam , Forman Juliet , Berchuck Jacob E. , Dudani Shaan , Bi Kevin , Park Jihye , Camp Sabrina , Sticco-Ivins Maura , Hirsch Laure , Baca Sylvan C. , Wind-Rotolo Megan , Ross-Macdonald Petra , Sun Maxine , Lee Gwo-Shu Mary , Chang Steven L. , Wei Xiao X. , McGregor Bradley A. , Harshman Lauren C. , Genovese Giannicola , Ellis Leigh , Pomerantz Mark , Hirsch Michelle S. , Freedman Matthew L. , Atkins Michael B. , Wu Catherine J. , Ho Thai H. , Linehan W. Marston , McDermott David F. , Heng Daniel Y. C. , Viswanathan Srinivas R. , Signoretti Sabina , Van Allen Eliezer M. , Choueiri Toni K.
Published: February 2021

Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.
C-STABILITY an innovative modeling framework to leverage the continuous representation of organic matter
Authors: Sainte-Marie Julien , Barrandon Matthieu , Saint-André Laurent , Gelhaye Eric , Martin Francis , Derrien Delphine
Published: February 2021

The understanding of soil organic matter (SOM) dynamics has considerably advanced in recent years. It was previously assumed that most SOM consisted of recalcitrant compounds, whereas the emerging view considers SOM as a range of polymers continuously processed into smaller molecules by decomposer enzymes. Mainstreaming this new paradigm in current models is challenging because of their ill-adapted framework. We propose the C-STABILITY model to resolve this issue. Its innovative framework combines compartmental and continuous modeling approaches to accurately reproduce SOM cycling processes. C-STABILITY emphasizes the influence of substrate accessibility on SOM turnover and makes enzymatic and microbial biotransformations of substrate explicit. Theoretical simulations provide new insights on how depolymerization and decomposers ecology impact organic matter chemistry and amount during decomposition and at steady state. The flexible mathematical structure of C-STABILITY offers a promising foundation for exploring new mechanistic hypotheses and supporting the design of future experiments.
Efficacy and tolerability of bevacizumab in patients with severe Covid-19
Authors: Pang Jiaojiao , Xu Feng , Aondio Gianmarco , Li Yu , Fumagalli Alberto , Lu Ming , Valmadre Giuseppe , Wei Jie , Bian Yuan , Canesi Margherita , Damiani Giovanni , Zhang Yuan , Yu Dexin , Chen Jun , Ji Xiang , Sui Wenhai , Wang Bailu , Wu Shuo , Kovacs Attila , Revera Miriam , Wang Hao , Jing Xu , Zhang Ying , Chen Yuguo , Cao Yihai
Published: February 2021

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.
Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation
Authors: Hong Chuan , Byrne Noel J. , Zamlynny Beata , Tummala Srivanya , Xiao Li , Shipman Jennifer M. , Partridge Andrea T. , Minnick Christina , Breslin Michael J. , Rudd Michael T. , Stachel Shawn J. , Rada Vanessa L. , Kern Jeffrey C. , Armacost Kira A. , Hollingsworth Scott A. , O’Brien Julie A. , Hall Dawn L. , McDonald Terrence P. , Strickland Corey , Brooun Alexei , Soisson Stephen M. , Hollenstein Kaspar
Published: February 2021

Narcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain’s ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest effectiveness and substantial adverse effects. Agonists of the orexin receptor 2 (OX2R) have shown promise as novel therapeutics that directly target the pathophysiology of the disease. However, identification of drug-like OX2R agonists has proven difficult. Here we report cryo-electron microscopy structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist. The extended carboxy-terminal segment of the peptide reaches into the core of OX2R to stabilize an active conformation, while the small-molecule agonist binds deep inside the orthosteric pocket, making similar key interactions. Comparison with antagonist-bound OX2R suggests a molecular mechanism that rationalizes both receptor activation and inhibition. Our results enable structure-based discovery of therapeutic orexin agonists for the treatment of NT1 and other hypersomnia disorders.
Phylogenetic analyses suggest centipede venom arsenals were repeatedly stocked by horizontal gene transfer
Authors: Undheim Eivind A. B. , Jenner Ronald A.
Published: February 2021

Venoms have evolved over a hundred times in animals. Venom toxins are thought to evolve mostly by recruitment of endogenous proteins with physiological functions. Here we report phylogenetic analyses of venom proteome-annotated venom gland transcriptome data, assisted by genomic analyses, to show that centipede venoms have recruited at least five gene families from bacterial and fungal donors, involving at least eight horizontal gene transfer events. These results establish centipedes as currently the only known animals with venoms used in predation and defence that contain multiple gene families derived from horizontal gene transfer. The results also provide the first evidence for the implication of horizontal gene transfer in the evolutionary origin of venom in an animal lineage. Three of the bacterial gene families encode virulence factors, suggesting that horizontal gene transfer can provide a fast track channel for the evolution of novelty by the exaptation of bacterial weapons into animal venoms.
Genetics of nodulation in Aeschynomene evenia uncovers mechanisms of the rhizobium–legume symbiosis
Authors: Quilbé Johan , Lamy Léo , Brottier Laurent , Leleux Philippe , Fardoux Joël , Rivallan Ronan , Benichou Thomas , Guyonnet Rémi , Becana Manuel , Villar Irene , Garsmeur Olivier , Hufnagel Bárbara , Delteil Amandine , Gully Djamel , Chaintreuil Clémence , Pervent Marjorie , Cartieaux Fabienne , Bourge Mickaël , Valentin Nicolas , Martin Guillaume , Fontaine Loïc , Droc Gaëtan , Dereeper Alexis , Farmer Andrew , Libourel Cyril , Nouwen Nico , Gressent Frédéric , Mournet Pierre , D’Hont Angélique , Giraud Eric , Klopp Christophe , Arrighi Jean-François
Published: February 2021

Among legumes (Fabaceae) capable of nitrogen-fixing nodulation, several Aeschynomene spp. use a unique symbiotic process that is independent of Nod factors and infection threads. They are also distinctive in developing root and stem nodules with photosynthetic bradyrhizobia. Despite the significance of these symbiotic features, their understanding remains limited. To overcome such limitations, we conduct genetic studies of nodulation in Aeschynomene evenia, supported by the development of a genome sequence for A. evenia and transcriptomic resources for 10 additional Aeschynomene spp. Comparative analysis of symbiotic genes substantiates singular mechanisms in the early and late nodulation steps. A forward genetic screen also shows that AeCRK, coding a receptor-like kinase, and the symbiotic signaling genes AePOLLUX, AeCCamK, AeCYCLOPS, AeNSP2, and AeNIN are required to trigger both root and stem nodulation. This work demonstrates the utility of the A. evenia model and provides a cornerstone to unravel mechanisms underlying the rhizobium–legume symbiosis.
Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy
Authors: Yang Riyao , Sun Linlin , Li Ching-Fei , Wang Yu-Han , Yao Jun , Li Hui , Yan Meisi , Chang Wei-Chao , Hsu Jung-Mao , Cha Jong-Ho , Hsu Jennifer L. , Chou Cheng-Wei , Sun Xian , Deng Yalan , Chou Chao-Kai , Yu Dihua , Hung Mien-Chie
Published: February 2021

The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to the persistence of PD-1+TIM-3+ T cells by binding to the TIM-3 ligand galectin-9 (Gal-9) and attenuates Gal-9/TIM-3-induced cell death. Anti-Gal-9 therapy selectively expands intratumoral TIM-3+ cytotoxic CD8 T cells and immunosuppressive regulatory T cells (Treg cells). The combination of anti-Gal-9 and an agonistic antibody to the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) that depletes Treg cells induces synergistic antitumor activity. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers. Our work uncovers a function for PD-1 in exhausted T cell survival and suggests Gal-9 as a promising target for immunotherapy.
Ph2 encodes the mismatch repair protein MSH7-3D that inhibits wheat homoeologous recombination
Authors: Serra Heïdi , Svačina Radim , Baumann Ute , Whitford Ryan , Sutton Tim , Bartoš Jan , Sourdille Pierre
Published: February 2021

Meiotic recombination is a critical process for plant breeding, as it creates novel allele combinations that can be exploited for crop improvement. In wheat, a complex allohexaploid that has a diploid-like behaviour, meiotic recombination between homoeologous or alien chromosomes is suppressed through the action of several loci. Here, we report positional cloning of Pairing homoeologous 2 (Ph2) and functional validation of the wheat DNA mismatch repair protein MSH7-3D as a key inhibitor of homoeologous recombination, thus solving a half-century-old question. Similar to ph2 mutant phenotype, we show that mutating MSH7-3D induces a substantial increase in homoeologous recombination (up to 5.5 fold) in wheat-wild relative hybrids, which is also associated with a reduction in homologous recombination. These data reveal a role for MSH7-3D in meiotic stabilisation of allopolyploidy and provides an opportunity to improve wheat’s genetic diversity through alien gene introgression, a major bottleneck facing crop improvement.
Nonenzymatic polymerase-like template-directed synthesis of acyclic l-threoninol nucleic acid
Authors: Murayama Keiji , Okita Hikari , Kuriki Takumi , Asanuma Hiroyuki
Published: February 2021

Evolution of xeno nucleic acid (XNA) world essentially requires template-directed synthesis of XNA polymers. In this study, we demonstrate template-directed synthesis of an acyclic XNA, acyclicl-threoninol nucleic acid (l-aTNA), via chemical ligation mediated by N-cyanoimidazole. The ligation of an l-aTNA fragment on an l-aTNA template is significantly faster and occurs in considerably higher yield than DNA ligation. Both l-aTNA ligation on a DNA template and DNA ligation on an l-aTNA template are also observed. High efficiency ligation of trimer l-aTNA fragments to a template-bound primer is achieved. Furthermore, a pseudo primer extension reaction is demonstrated using a pool of random l-aTNA trimers as substrates. To the best of our knowledge, this is the first example of polymerase-like primer extension of XNA with all four nucleobases, generating phosphodiester bonding without any special modification. This technique paves the way for a genetic system of the l-aTNA world.
IL-22-dependent dysbiosis and mononuclear phagocyte depletion contribute to steroid-resistant gut graft-versus-host disease in mice
Authors: Song Qingxiao , Wang Xiaoning , Wu Xiwei , Kang Tae Hyuk , Qin Hanjun , Zhao Dongchang , Jenq Robert R. , van den Brink Marcel R. M. , Riggs Arthur D. , Martin Paul J. , Chen Yuan-Zhong , Zeng Defu
Published: February 2021

Efforts to improve the prognosis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) have suffered from poor understanding of its pathogenesis. Here we show that the pathogenesis of SR-Gut-aGVHD is associated with reduction of IFN-γ+ Th/Tc1 cells and preferential expansion of IL-17−IL-22+ Th/Tc22 cells. The IL-22 from Th/Tc22 cells causes dysbiosis in a Reg3γ-dependent manner. Transplantation of IFN-γ-deficient donor CD8+ T cells in the absence of CD4+ T cells produces a phenocopy of SR-Gut-aGVHD. IFN-γ deficiency in donor CD8+ T cells also leads to a PD-1-dependent depletion of intestinal protective CX3CR1hi mononuclear phagocytes (MNP), which also augments expansion of Tc22 cells. Supporting the dual regulation, simultaneous dysbiosis induction and depletion of CX3CR1hi MNP results in full-blown Gut-aGVHD. Our results thus provide insights into SR-Gut-aGVHD pathogenesis and suggest the potential efficacy of IL-22 antagonists and IFN-γ agonists in SR-Gut-aGVHD therapy.
Photo thermal effect graphene detector featuring 105 Gbit s−1 NRZ and 120 Gbit s−1 PAM4 direct detection
Authors: Marconi S. , Giambra M. A. , Montanaro A. , Mišeikis V. , Soresi S. , Tirelli S. , Galli P. , Buchali F. , Templ W. , Coletti C. , Sorianello V. , Romagnoli M.
Published: February 2021

One of the main challenges of next generation optical communication is to increase the available bandwidth while reducing the size, cost and power consumption of photonic integrated circuits. Graphene has been recently proposed to be integrated with silicon photonics to meet these goals because of its high mobility, fast carrier dynamics and ultra-broadband optical properties. We focus on graphene photodetectors for high speed datacom and telecom applications based on the photo-thermo-electric effect, allowing for direct optical power to voltage conversion, zero dark current, and ultra-fast operation. We report on a chemical vapour deposition graphene photodetector based on the photo-thermoelectric effect, integrated on a silicon waveguide, providing frequency response >65 GHz and optimized to be interfaced to a 50 Ω voltage amplifier for direct voltage amplification. We demonstrate a system test leading to direct detection of 105 Gbit s−1non-return to zero and 120 Gbit s−14-level pulse amplitude modulation optical signals.
Experimental quantum homomorphic encryption
Authors: Zeuner Jonas , Pitsios Ioannis , Tan Si-Hui , Sharma Aditya N. , Fitzsimons Joseph F. , Osellame Roberto , Walther Philip
Published: February 2021

Quantum computers promise not only to outperform classical machines for certain important tasks, but also to preserve privacy of computation. For example, the blind quantum computing protocol enables secure delegated quantum computation, where a client can protect the privacy of their data and algorithms from a quantum server assigned to run the computation. However, this security comes with the practical limitation that the client and server must communicate after each step of computation. A practical alternative is homomorphic encryption, which does not require any interactions, while providing quantum-enhanced data security for a variety of computations. In this scenario, the server specifies the computation to be performed, and the client provides only the input data, thus enabling secure noninteractive computation. Here, we demonstrate homomorphic-encrypted quantum computing with unitary transformations of individual qubits, as well as multi-qubit quantum walk computations using single-photon states and non-birefringent integrated optics. The client encrypts their input in the photons’ polarization state, while the server performs the computation using the path degree of freedom. Our demonstration using integrated quantum photonics underlines the applicability of homomorphic-encrypted quantum computations, and shows the potential for delegated quantum computing using photons.
The Cuban Human Brain Mapping Project, a young and middle age population-based EEG, MRI, and cognition dataset
Authors: Valdes-Sosa Pedro A. , Galan-Garcia Lidice , Bosch-Bayard Jorge , Bringas-Vega Maria L. , Aubert-Vazquez Eduardo , Rodriguez-Gil Iris , Das Samir , Madjar Cecile , Virues-Alba Trinidad , Mohades Zia , MacIntyre Leigh C. , Rogers Christine , Brown Shawn , Valdes-Urrutia Lourdes , Evans Alan C. , Valdes-Sosa Mitchell J.
Published: February 2021

The Cuban Human Brain Mapping Project (CHBMP) repository is an open multimodal neuroimaging and cognitive dataset from 282 young and middle age healthy participants (31.9 ± 9.3 years, age range 18–68 years). This dataset was acquired from 2004 to 2008 as a subset of a larger stratified random sample of 2,019 participants from La Lisa municipality in La Habana, Cuba. The exclusion criteria included the presence of disease or brain dysfunctions. Participant data that is being shared comprises i) high-density (64–120 channels) resting-state electroencephalograms (EEG), ii) magnetic resonance images (MRI), iii) psychological tests (MMSE, WAIS-III, computerized go-no go reaction time), as well as iv,) demographic information (age, gender, education, ethnicity, handedness, and weight). The EEG data contains recordings with at least 30 minutes in duration including the following conditions: eyes closed, eyes open, hyperventilation, and subsequent recovery. The MRI consists of anatomical T1 as well as diffusion-weighted (DWI) images acquired on a 1.5 Tesla system. The dataset presented here is hosted by Synapse.org and available at https://chbmp-open.loris.ca.
Limb and trunk accelerometer data collected with wearable sensors from subjects with Parkinson’s disease
Authors: Vergara-Diaz Gloria , Daneault Jean-Francois , Parisi Federico , Admati Chen , Alfonso Christina , Bertoli Matilde , Bonizzoni Edoardo , Carvalho Gabriela Ferreira , Costante Gianluca , Fabara Eric Eduardo , Fixler Naama , Golabchi Fatemah Noushin , Growdon John , Sapienza Stefano , Snyder Phil , Shpigelman Shahar , Sudarsky Lewis , Daeschler Margaret , Bataille Lauren , Sieberts Solveig K. , Omberg Larsson , Moore Steven , Bonato Paolo
Published: February 2021

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. Dyskinesia and motor fluctuations are complications of PD medications. An objective measure of on/off time with/without dyskinesia has been sought for some time because it would facilitate the titration of medications. The objective of the dataset herein presented is to assess if wearable sensor data can be used to generate accurate estimates of limb-specific symptom severity. Nineteen subjects with PD experiencing motor fluctuations were asked to wear a total of five wearable sensors on both forearms and shanks, as well as on the lower back. Accelerometer data was collected for four days, including two laboratory visits lasting 3 to 4 hours each while the remainder of the time was spent at home and in the community. During the laboratory visits, subjects performed a battery of motor tasks while clinicians rated limb-specific symptom severity. At home, subjects were instructed to use a smartphone app that guided the periodic performance of a set of motor tasks.
Mobility, exposure, and epidemiological timelines of COVID-19 infections in China outside Hubei province
Authors: Liu Xiao Fan , Xu Xiao-Ke , Wu Ye
Published: February 2021

The 2019 coronavirus disease (COVID-19) is pseudonymously linked to more than 100 million cases in the world as of January 2021. High-quality data are needed but lacking in the understanding of and fighting against COVID-19. We provide a complete and updating hand-coded line-list dataset containing detailed information of the cases in China and outside the epicenter in Hubei province. The data are extracted from public disclosures by local health authorities, starting from January 19. This dataset contains a very rich set of features for the characterization of COVID-19’s epidemiological properties, including individual cases’ demographic information, travel history, potential virus exposure scenario, contacts with known infections, and timelines of symptom onset, quarantine, infection confirmation, and hospitalization. These cases can be considered the baseline COVID-19 transmissibility under extreme mitigation measures, and therefore, a reference for comparative scientific investigation and public policymaking.
Indication of high lipid content in epithelial-mesenchymal transitions of breast tissues
Authors: Sabtu Siti Norbaini , Sani S. F. Abdul , Looi L. M. , Chiew S. F. , Pathmanathan Dharini , Bradley D. A. , Osman Z.
Published: February 2021

The epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression and metastasis. Study of metabolic changes during the EMT process is important in seeking to understand the biochemical changes associated with cancer progression, not least in scoping for therapeutic strategies aimed at targeting EMT. Due to the potential for high sensitivity and specificity, Raman spectroscopy was used here to study the metabolic changes associated with EMT in human breast cancer tissue. For Raman spectroscopy measurements, tissue from 23 patients were collected, comprising non-lesional, EMT and non-EMT formalin-fixed and paraffin embedded breast cancer samples. Analysis was made in the fingerprint Raman spectra region (600–1800 cm−1) best associated with cancer progression biochemical changes in lipid, protein and nucleic acids. The ANOVA test followed by the Tukey’s multiple comparisons test were conducted to see if there existed differences between non-lesional, EMT and non-EMT breast tissue for Raman spectroscopy measurements. Results revealed that significant differences were evident in terms of intensity between the non-lesional and EMT samples, as well as the EMT and non-EMT samples. Multivariate analysis involving independent component analysis, Principal component analysis and non-negative least square were used to analyse the Raman spectra data. The results show significant differences between EMT and non-EMT cancers in lipid, protein, and nucleic acids. This study demonstrated the capability of Raman spectroscopy supported by multivariate analysis in analysing metabolic changes in EMT breast cancer tissue.
A general procedure to measure the pacing of body movements timed to music and metronome in younger and older adults
Authors: Rose Dawn , Ott Laurent , Guérin Ségolène M. R. , Annett Lucy E. , Lovatt Peter , Delevoye-Turrell Yvonne N.
Published: February 2021

Finger-tapping tasks are classically used to investigate sensorimotor synchronization in relation to neutral auditory cues, such as metronomes. However, music is more commonly associated with an entrained bodily response, such as toe tapping, or dancing. Here we report an experimental procedure that was designed to bridge the gap between timing and intervention studies by directly comparing the effects of metronome and musical cue types on motor timing abilities across the three naturalistic voluntary actions of finger tapping, toe tapping, and stepping on the spot as a simplified case of whole body movement. Both pacing cues were presented at slow, medium, and fast tempi. The findings suggested that the task of stepping on the spot enabled better timing performances than tapping both in younger and older adults (75+). Timing performances followed an inverse U shape with best performances observed in the medium tempi that were set close to the spontaneous motor tempo in each movement type. Finally, music provided an entrainment effect in addition to pace setting that enabled better motor timing and greater stability than classically reported using a metronome. By applying time-stamp analyses to kinetic data, we demonstrate that tapping and stepping engage different timing modes. This work details the importance of translational research for a better understanding of motor timing. It offers a simple procedure that strengthens the validity of applying academic work and contributes in knowledge towards a wide range of therapeutic interventions.
Mapping of affordability levels for photovoltaic-based electricity generation in the solar belt of sub-Saharan Africa, East Asia and South Asia
Authors: Szabó Sándor , Pinedo Pascua Irene , Puig Daniel , Moner-Girona Magda , Negre Mario , Huld Thomas , Mulugetta Yacob , Kougias Ioannis , Szabó László , Kammen Daniel
Published: February 2021

Lack of access to modern forms of energy hampers efforts to reduce poverty. The provision of electricity to off-grid communities is therefore a long-standing developmental goal. Yet, many off-grid electrification projects neglect mid- and long-term operation and maintenance costs. When this is the case, electricity services are unlikely to be affordable to the communities that are the project’s primary target. Here we show that, compared with diesel-powered electricity generation systems, solar photovoltaic systems are more affordable to no less than 36% of the unelectrified populations in East Asia, South Asia, and sub-Saharan Africa. We do so by developing geo-referenced estimates of affordability at a high level of resolution (1 km2). The analysis illustrates the differences in affordability that may be found at the subnational level, which underscores that electrification investments should be informed by subnational data.
Diagnostic and prognostic value of 99mTc-MAA SPECT/CT for treatment planning of 90Y-resin microsphere radioembolization for hepatocellular carcinoma: comparison with planar image
Authors: Son Mai Hong , Ha Le Ngoc , Bang Mai Hong , Bae Sungwoo , Giang Dinh Truong , Thinh Nguyen Tien , Paeng Jin Chul
Published: February 2021

99mTc-macroaggregated albumin (MAA) imaging is performed before transarterial radioembolization (TARE), in which SPECT/CT is presumed more precise than planar image. However, additive role of SPECT/CT has not been well established. Thirty-four consecutive hepatocellular carcinoma patients of intermediate and advanced stages who underwent 90Y-microsphere TARE were recruited. On pre-treatment planning scan using 99mTc-MAA, image characteristics and absorbed dose for target tumors calculated by partition model methods were estimated on planar image and SPECT/CT, respectively. The measurements were repeated on post-treatment 90Y PET/CT, as the reference standard. Treatment response was assessed and predictive values of image parameters were analyzed. The image characteristics including heterogeneity, necrosis and thrombosis uptake were better delineated on SPECT/CT than planar scan. The agreement and correlation of TNr between SPECT/CT and PET/CT were stronger than those between planar scan and PET/CT. Tumor dose estimated on 99mTc-MAA SPECT/CT was more effective than planar image for prediction of treatment response, with cutoff value 125 Gy (sensitivity of 86% and specificity of 75%). In conclusion, 99mTc-MAA SPECT/CT is more closely correlated with post-treatment 90Y PET/CT, and is more effective for predicting treatment response than planar scan. SPECT/CT is superior to planar image in simulation before 90Y TARE.
Interchangeability of light and virtual microscopy for histopathological evaluation of prostate cancer
Authors: Zelic Renata , Giunchi Francesca , Lianas Luca , Mascia Cecilia , Zanetti Gianluigi , Andrén Ove , Fridfeldt Jonna , Carlsson Jessica , Davidsson Sabina , Molinaro Luca , Vincent Per Henrik , Richiardi Lorenzo , Akre Olof , Fiorentino Michelangelo , Pettersson Andreas
Published: February 2021

Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998–2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen’s kappa and Bland and Altman’s limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.
Genetic ancestry plays a central role in population pharmacogenomics
Authors: Yang Hsin-Chou , Chen Chia-Wei , Lin Yu-Ting , Chu Shih-Kai
Published: February 2021

Recent studies have pointed out the essential role of genetic ancestry in population pharmacogenetics. In this study, we analyzed the whole-genome sequencing data from The 1000 Genomes Project (Phase 3) and the pharmacogenetic information from Drug Bank, PharmGKB, PharmaADME, and Biotransformation. Here we show that ancestry-informative markers are enriched in pharmacogenetic loci, suggesting that trans-ancestry differentiation must be carefully considered in population pharmacogenetics studies. Ancestry-informative pharmacogenetic loci are located in both protein-coding and non-protein-coding regions, illustrating that a whole-genome analysis is necessary for an unbiased examination over pharmacogenetic loci. Finally, those ancestry-informative pharmacogenetic loci that target multiple drugs are often a functional variant, which reflects their importance in biological functions and pathways. In summary, we develop an efficient algorithm for an ultrahigh-dimensional principal component analysis. We create genetic catalogs of ancestry-informative markers and genes. We explore pharmacogenetic patterns and establish a high-accuracy prediction panel of genetic ancestry. Moreover, we construct a genetic ancestry pharmacogenomic database Genetic Ancestry PhD (http://hcyang.stat.sinica.edu.tw/databases/genetic_ancestry_phd/).
GardeninA confers neuroprotection against environmental toxin in a Drosophila model of Parkinson’s disease
Authors: Maitra Urmila , Harding Thomas , Liang Qiaoli , Ciesla Lukasz
Published: February 2021

Parkinson’s disease is an age-associated neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons from the midbrain. Epidemiological studies have implicated exposures to environmental toxins like the herbicide paraquat as major contributors to Parkinson’s disease etiology in both mammalian and invertebrate models. We have employed a paraquat-induced Parkinson’s disease model in Drosophila as an inexpensive in vivo platform to screen therapeutics from natural products. We have identified the polymethoxyflavonoid, GardeninA, with neuroprotective potential against paraquat-induced parkinsonian symptoms involving reduced survival, mobility defects, and loss of dopaminergic neurons. GardeninA-mediated neuroprotection is not solely dependent on its antioxidant activities but also involves modulation of the neuroinflammatory and cellular death responses. Furthermore, we have successfully shown GardeninA bioavailability in the fly heads after oral administration using ultra-performance liquid chromatography and mass spectrometry. Our findings reveal a molecular mechanistic insight into GardeninA-mediated neuroprotection against environmental toxin-induced Parkinson’s disease pathogenesis for novel therapeutic intervention.
Sexual excitation induces courtship ultrasonic vocalizations and cataplexy-like behavior in orexin neuron-ablated male mice
Authors: Kuwaki Tomoyuki , Kanno Kouta
Published: February 2021

Cataplexy is triggered by laughter in humans and palatable food in mice. To further evaluate mice’s cataplexy, we examined courtship behavior in orexin neuron-ablated mice (ORX-AB), one of the animal models of narcolepsy/cataplexy. Wild-type female mice were placed into the home cage of male ORX-AB and cataplexy-like behavior was observed along with ultrasonic vocalizations (USVs), also known as the “love song”. ORX-AB with a female encounter showed cataplexy-like behavior both during the dark and light periods, whereas ORX-AB with chocolate predominantly showed it during the dark period. During the light period observation, more than 85% of cataplexy-like bouts were preceded by USVs. A strong positive correlation was observed between the number of USVs and cataplexy-like bouts. Cataplexy-like behavior in narcoleptic mice is a good behavioral measure to study the brain mechanisms behind positive emotion because they can be induced by different kinds of positive stimuli, including chocolate and female courtship.
Nano-vault architecture mitigates stress in silicon-based anodes for lithium-ion batteries
Authors: Haro Marta , Kumar Pawan , Zhao Junlei , Koutsogiannis Panagiotis , Porkovich Alexander James , Ziadi Zakaria , Bouloumis Theodoros , Singh Vidyadhar , Juarez-Perez Emilio J. , Toulkeridou Evropi , Nordlund Kai , Djurabekova Flyura , Sowwan Mukhles , Grammatikopoulos Panagiotis
Published: February 2021

Nanomaterials undergoing cyclic swelling-deswelling benefit from inner void spaces that help accommodate significant volumetric changes. Such flexibility, however, typically comes at a price of reduced mechanical stability, which leads to component deterioration and, eventually, failure. Here, we identify an optimised building block for silicon-based lithium-ion battery (LIB) anodes, fabricate it with a ligand- and effluent-free cluster beam deposition method, and investigate its robustness by atomistic computer simulations. A columnar amorphous-silicon film was grown on a tantalum-nanoparticle scaffold due to its shadowing effect. PeakForce quantitative nanomechanical mapping revealed a critical change in mechanical behaviour when columns touched forming a vaulted structure. The resulting maximisation of measured elastic modulus (~120 GPa) is ascribed to arch action, a well-known civil engineering concept. The vaulted nanostructure displays a sealed surface resistant to deformation that results in reduced electrode-electrolyte interface and increased Coulombic efficiency. More importantly, its vertical repetition in a double-layered aqueduct-like structure improves both the capacity retention and Coulombic efficiency of the LIB.
Self-assembly and guest-induced disassembly of triply interlocked [2]catenanes
Authors: Zhang Ying-Ying , Qiu Feng-Yi , Shi Hua-Tian , Yu Weibin
Published: February 2021

Two triply interlocked [2]catenanes and one simple metallacage were constructed by tuning the widths of the organometallic dinuclear building blocks, and the interlocked architectures were disassembled by large aromatic molecules.
Size-selective synthesis of platinum nanoparticles on transition-metal dichalcogenides for the hydrogen evolution reaction
Authors: Mei Liang , Gao Xiaoping , Gao Zhan , Zhang Qingyong , Yu Xinge , Rogach Andrey L. , Zeng Zhiyuan
Published: February 2021

Pt-MoS2 composites are fabricated via growing tunable Pt nanoparticles size (NPs, 2–6 nm) on single-layer MoS2 nanosheets. Which have shown excellent performance for hydrogen evolution reaction (HER) with the Pt NPs exhibiting a volcano-type size effect toward mass activity due to the synergistic effects between the Pt NPs and MoS2.
Structure factor lineshape model gives approximate nanoscale size of polar aggregates in the ionic liquid N-methyl-N-propylpyrrolidinium bis(trifluoromethylsulfonyl)imide
Authors: Wheeler Ralph A. , Dalbey Emily E.
Published: February 2021

Fitting X-ray structure factor lineshapes from experiment or simulation quantifies the nanoscale range of charge alternation in the title compound.
Systematic cluster growth: a structure search method for transition metal clusters
Authors: Rodríguez-Kessler Peter L. , Rodríguez-Domínguez Adán R. , Muñoz-Castro Alvaro
Published: February 2021

The systematic cluster growth (SCG) method is a biased structure search strategy based on a seeding process for investigating the structural evolution and growth pattern of transition metal clusters.
Computational study on the mechanism of hydroboration of CO2 catalysed by POCOP pincer nickel thiolate complexes: concerted catalysis and hydride transfer by a shuttle
Authors: Ma Nana , Tu Chenhao , Xu Qingli , Guo Wenyue , Zhang Jie , Zhang Guisheng
Published: February 2021

The concerted catalysis and hydride shuttle mechanism for pincer nickel thiolate catalysed hydroboration of CO2 was established by DFT computations.
Characterization of inhalation exposure to gaseous elemental mercury during artisanal gold mining and e-waste recycling through combined stationary and personal passive sampling
Authors: Snow Melanie A. , Darko Godfred , Gyamfi Opoku , Ansah Eugene , Breivik Knut , Hoang Christopher , Lei Ying Duan , Wania Frank
Published: February 2021

Stationary and personal passive sampling provides complementary information on the inhalation exposure to gaseous elemental mercury among Norwegian e-waste workers, and Ghanaian artisanal gold miners and community members.
Puerarin suppresses inflammation and ECM degradation through Nrf2/HO-1 axis in chondrocytes and alleviates pain symptom in osteoarthritic mice
Authors: Chen Ximiao , Huang Chongan , Sun Haiqiu , Hong Haofeng , Jin Jie , Bei Chaoyong , Lu Zhongqiu , Zhang Xiaolei
Published: February 2021

Puerarin suppresses the NF-κB signaling pathway by activating the Nrf2/HO-1 axis, thereby inhibiting IL-1β-induced inflammation and ECM degradation in Osteoarthritis.
Nano-bismuth sulfide based dispersive micro-solid phase extraction combined with energy dispersive X-ray fluorescence spectrometry for determination of mercury ions in waters
Authors: Pytlakowska Katarzyna , Malicka Ewa , Talik Ewa , Gągor Anna
Published: February 2021

Nano-Bi2S3 as a solid sorbent for ultra-sound assisted dispersive micro-solid phase extraction of Hg(ii) ions from surface and sea waters prior to EDXRF determination.
Additive manufacturing of multielectrode arrays for biotechnological applications
Authors: Edwards Amelia V. , Hann Christopher , Ivill Henry , Leeson Hanna , Tymczyszyn Larysa , Cummings Damian M. , Ashton Mark D. , Harper Garry R. , Spencer Diane T. , Low Wan Li , Rajeev Kiron , Martin-Hirsch Pierre , Edwards Frances A. , Hardy John G. , Rennie Allan E. W. , Cheneler David
Published: February 2021

Multielectrode arrays (MEAs) are electrical devices that transduce (record/deliver) cellular voltage signals.
Anion effects on the properties of OIPC/PVDF composites
Authors: Nti Frederick , Greene George W. , Zhu Haijin , Howlett Patrick C. , Forsyth Maria , Wang Xiaoen
Published: February 2021

Ion dynamics enhancements derived from anion–polymer interactions are proposed in organic ionic plastic crystal–poly(vinylidene fluoride)composite electrolytes.
Design of thermoresponsive hydrogels by controlling the chemistry and imprinting of drug molecules within the hydrogel for enhanced loading and smart delivery of drugs
Authors: Park Sang-Yu , Kim Seong Yeol , Kang Ji-Hye , Kim Han-Sem , Shin Ueon Sang
Published: February 2021

Thermoresponsive and molecularly imprinted hydrogels were synthesized by radical polymerization with molecular imprinting using three types of drug templates.
Hydrous cobalt–iridium oxide two-dimensional nanoframes: insights into activity and stability of bimetallic acidic oxygen evolution electrocatalysts
Authors: Ying Yuanfang , Godínez Salomón Jose Fernando , Lartundo-Rojas Luis , Moreno Ashley , Meyer Robert , Damin Craig A. , Rhodes Christopher P.
Published: February 2021

Hydrous cobalt–iridium oxide two-dimensional nanoframes consist of interconnected Co–Ir alloy domains within an unsupported, carbon-free, porous nanostructure and exhibit a higher oxygen evolution activity and similar stability compared to IrO2.
Single-layer polymeric tetraoxa[8]circulene modified by s-block metals: toward stable spin qubits and novel superconductors
Authors: Begunovich Lyudmila V. , Kuklin Artem V. , Baryshnikov Gleb V. , Valiev Rashid R. , Ågren Hans
Published: February 2021

Tetraoxa[8]circulene based 2D COFs doped with s-block metals possess metallic properties. Doping with Ca results in superconductivity and an open-shell singlet ground state composed of two doublets.
Process modelling and life cycle assessment coupled with experimental work to shape the future sustainable production of chemicals and fuels
Authors: Ioannou Iasonas , D'Angelo Sebastiano Carlo , Galán-Martín Ángel , Pozo Carlos , Pérez-Ramírez Javier , Guillén-Gosálbez Gonzalo
Published: February 2021

The quest for a sustainable chemical industry poses significant challenges, which could be addressed by bridging the gap between experimental research and industrial production with computational tools.
Acoustic cavitation rheometry
Authors: Mancia Lauren , Yang Jin , Spratt Jean-Sebastien , Sukovich Jonathan R. , Xu Zhen , Colonius Tim , Franck Christian , Johnsen Eric
Published: February 2021

Acoustic cavitation generated via high-amplitude ultrasound is used to characterize the high strain-rate mechanical properties of agarose hydrogels.
A reactive peptide interface for site-selective cysteine bioconjugation
Authors: Tuang Suan , Dieppa-Matos Diomedes , Zhang Chi , Shugrue Christopher R. , Dai Peng , Loas Andrei , Pentelute Bradley L.
Published: February 2021

A nine-residue cysteine-based reactive peptide interface enables rapid site-selective modification of proteins in water.