bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy
Authors: Karges Johannes , Kuang Shi , Maschietto Federica , Blacque Olivier , Ciofini Ilaria , Chao Hui , Gasser Gilles
Published: June 2020

The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E′)-4,4′-bisstyryl-2,2′-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.
Behavior-dependent directional tuning in the human visual-navigation network
Authors: Nau Matthias , Navarro Schröder Tobias , Frey Markus , Doeller Christian F.
Published: June 2020

The brain derives cognitive maps from sensory experience that guide memory formation and behavior. Despite extensive efforts, it still remains unclear how the underlying population activity unfolds during spatial navigation and how it relates to memory performance. To examine these processes, we combined 7T-fMRI with a kernel-based encoding model of virtual navigation to map world-centered directional tuning across the human cortex. First, we present an in-depth analysis of directional tuning in visual, retrosplenial, parahippocampal and medial temporal cortices. Second, we show that tuning strength, width and topology of this directional code during memory-guided navigation depend on successful encoding of the environment. Finally, we show that participants’ locomotory state influences this tuning in sensory and mnemonic regions such as the hippocampus. We demonstrate a direct link between neural population tuning and human cognition, where high-level memory processing interacts with network-wide visuospatial coding in the service of behavior.
Tracking down the molecular architecture of the synaptonemal complex by expansion microscopy
Authors: Zwettler Fabian U. , Spindler Marie-Christin , Reinhard Sebastian , Klein Teresa , Kurz Andreas , Benavente Ricardo , Sauer Markus
Published: June 2020

The synaptonemal complex (SC) is a meiosis-specific nuclear multiprotein complex that is essential for proper synapsis, recombination and segregation of homologous chromosomes. We combined structured illumination microscopy (SIM) with different expansion microscopy (ExM) protocols including U-ExM, proExM, and magnified analysis of the proteome (MAP) to investigate the molecular organization of the SC. Comparison with structural data obtained by single-molecule localization microscopy of unexpanded SCs allowed us to investigate ultrastructure preservation of expanded SCs. For image analysis, we developed an automatic image processing software that enabled unbiased comparison of structural properties pre- and post-expansion. Here, MAP-SIM provided the best results and enabled reliable three-color super-resolution microscopy of the SCs of a whole set of chromosomes in a spermatocyte with 20–30 nm spatial resolution. Our data demonstrate that post-expansion labeling by MAP-SIM improves immunolabeling efficiency and allowed us thus to unravel previously hidden details of the molecular organization of SCs.
Representation of molecular structures with persistent homology for machine learning applications in chemistry
Authors: Townsend Jacob , Micucci Cassie Putman , Hymel John H. , Maroulas Vasileios , Vogiatzis Konstantinos D.
Published: June 2020

Machine learning and high-throughput computational screening have been valuable tools in accelerated first-principles screening for the discovery of the next generation of functionalized molecules and materials. The application of machine learning for chemical applications requires the conversion of molecular structures to a machine-readable format known as a molecular representation. The choice of such representations impacts the performance and outcomes of chemical machine learning methods. Herein, we present a new concise molecular representation derived from persistent homology, an applied branch of mathematics. We have demonstrated its applicability in a high-throughput computational screening of a large molecular database (GDB-9) with more than 133,000 organic molecules. Our target is to identify novel molecules that selectively interact with CO2. The methodology and performance of the novel molecular fingerprinting method is presented and the new chemically-driven persistence image representation is used to screen the GDB-9 database to suggest molecules and/or functional groups with enhanced properties.
Tumor invasion in draining lymph nodes is associated with Treg accumulation in breast cancer patients
Authors: Núñez Nicolas Gonzalo , Tosello Boari Jimena , Ramos Rodrigo Nalio , Richer Wilfrid , Cagnard Nicolas , Anderfuhren Cyrill Dimitri , Niborski Leticia Laura , Bigot Jeremy , Meseure Didier , De La Rochere Philippe , Milder Maud , Viel Sophie , Loirat Delphine , Pérol Louis , Vincent-Salomon Anne , Sastre-Garau Xavier , Burkhard Becher , Sedlik Christine , Lantz Olivier , Amigorena Sebastian , Piaggio Eliane
Published: June 2020

Tumor-draining lymph node (TDLN) invasion by metastatic cells in breast cancer correlates with poor prognosis and is associated with local immunosuppression, which can be partly mediated by regulatory T cells (Tregs). Here, we study Tregs from matched tumor-invaded and non-invaded TDLNs, and breast tumors. We observe that Treg frequencies increase with nodal invasion, and that Tregs express higher levels of co-inhibitory/stimulatory receptors than effector cells. Also, while Tregs show conserved suppressive function in TDLN and tumor, conventional T cells (Tconvs) in TDLNs proliferate and produce Th1-inflammatory cytokines, but are dysfunctional in the tumor. We describe a common transcriptomic signature shared by Tregs from tumors and nodes, including CD80, which is significantly associated with poor patient survival. TCR RNA-sequencing analysis indicates trafficking between TDLNs and tumors and ongoing Tconv/Treg conversion. Overall, TDLN Tregs are functional and express a distinct pattern of druggable co-receptors, highlighting their potential as targets for cancer immunotherapy.
Cavity piezo-mechanics for superconducting-nanophotonic quantum interface
Authors: Han Xu , Fu Wei , Zhong Changchun , Zou Chang-Ling , Xu Yuntao , Sayem Ayed Al , Xu Mingrui , Wang Sihao , Cheng Risheng , Jiang Liang , Tang Hong X.
Published: June 2020

Hybrid quantum systems are essential for the realization of distributed quantum networks. In particular, piezo-mechanics operating at typical superconducting qubit frequencies features low thermal excitations, and offers an appealing platform to bridge superconducting quantum processors and optical telecommunication channels. However, integrating superconducting and optomechanical elements at cryogenic temperatures with sufficiently strong interactions remains a tremendous challenge. Here, we report an integrated superconducting cavity piezo-optomechanical platform where 10 GHz phonons are resonantly coupled with photons in a superconducting cavity and a nanophotonic cavity at the same time. Taking advantage of the large piezo-mechanical cooperativity (Cem ~7) and the enhanced optomechanical coupling boosted by a pulsed optical pump, we demonstrate coherent interactions at cryogenic temperatures via the observation of efficient microwave-optical photon conversion. This hybrid interface makes a substantial step towards quantum communication at large scale, as well as novel explorations in microwave-optical photon entanglement and quantum sensing mediated by gigahertz phonons.
Generative adversarial networks (GAN) based efficient sampling of chemical composition space for inverse design of inorganic materials
Authors: Dan Yabo , Zhao Yong , Li Xiang , Li Shaobo , Hu Ming , Hu Jianjun
Published: June 2020

A major challenge in materials design is how to efficiently search the vast chemical design space to find the materials with desired properties. One effective strategy is to develop sampling algorithms that can exploit both explicit chemical knowledge and implicit composition rules embodied in the large materials database. Here, we propose a generative machine learning model (MatGAN) based on a generative adversarial network (GAN) for efficient generation of new hypothetical inorganic materials. Trained with materials from the ICSD database, our GAN model can generate hypothetical materials not existing in the training dataset, reaching a novelty of 92.53% when generating 2 million samples. The percentage of chemically valid (charge-neutral and electronegativity-balanced) samples out of all generated ones reaches 84.5% when generated by our GAN trained with such samples screened from ICSD, even though no such chemical rules are explicitly enforced in our GAN model, indicating its capability to learn implicit chemical composition rules to form compounds. Our algorithm is expected to be used to greatly expand the range of the design space for inverse design and large-scale computational screening of inorganic materials.
Building a PubMed knowledge graph
Authors: Xu Jian , Kim Sunkyu , Song Min , Jeong Minbyul , Kim Donghyeon , Kang Jaewoo , Rousseau Justin F. , Li Xin , Xu Weijia , Torvik Vetle I. , Bu Yi , Chen Chongyan , Ebeid Islam Akef , Li Daifeng , Ding Ying
Published: June 2020

PubMed® is an essential resource for the medical domain, but useful concepts are either difficult to extract or are ambiguous, which has significantly hindered knowledge discovery. To address this issue, we constructed a PubMed knowledge graph (PKG) by extracting bio-entities from 29 million PubMed abstracts, disambiguating author names, integrating funding data through the National Institutes of Health (NIH) ExPORTER, collecting affiliation history and educational background of authors from ORCID®, and identifying fine-grained affiliation data from MapAffil. Through the integration of these credible multi-source data, we could create connections among the bio-entities, authors, articles, affiliations, and funding. Data validation revealed that the BioBERT deep learning method of bio-entity extraction significantly outperformed the state-of-the-art models based on the F1 score (by 0.51%), with the author name disambiguation (AND) achieving an F1 score of 98.09%. PKG can trigger broader innovations, not only enabling us to measure scholarly impact, knowledge usage, and knowledge transfer, but also assisting us in profiling authors and organizations based on their connections with bio-entities.
Life Course Trajectories of Maternal Cardiovascular Risk Factors according to Offspring Birthweight: The HUNT Study
Authors: Horn Julie , Haug Eirin B. , Markovitz Amanda R. , Fraser Abigail , Vatten Lars J. , Romundstad Pål R. , Rich-Edwards Janet W. , Åsvold Bjørn O.
Published: June 2020

Women with small or large for gestational age offspring are at increased risk of cardiovascular disease later in life. How their cardiovascular risk factors develop across the life course is incompletely known. We linked data from the population-based HUNT Study (1984–2008) and the Medical Birth Registry of Norway (1967–2012) for 22,487 women. Mixed effect models were used to compare cardiovascular risk factor trajectories for women according to first offspring birthweight for gestational age. Women with small for gestational age (SGA) offspring had 1–2 mmHg higher systolic and diastolic blood pressure across the life course, but lower measures of adiposity, compared to women with offspring who were appropriate for gestational age (AGA). In contrast, women with large for gestational age (LGA) offspring had higher measures of adiposity, ~0.1 mmol/l higher non-HDL cholesterol and triglycerides and 0.2 mmol/l higher non-fasting glucose, compared with mothers of AGA offspring. These differences were broadly stable from prior to first pregnancy until 60 years of age. Our findings point to different cardiovascular risk profiles in mothers of SGA versus LGA offspring, where giving birth to SGA offspring might primarily reflect adverse maternal vascular health whereas LGA offspring might reflect the mother’s metabolic health.
Validation of four-dimensional flow cardiovascular magnetic resonance for aortic stenosis assessment
Authors: Archer Gareth T. , Elhawaz Alaa , Barker Natasha , Fidock Benjamin , Rothman Alexander , van der Geest R. J. , Hose Rod , Briffa Norman , Hall Ian R. , Grech Ever , Bissell Malenka , Al-Mohammad Abdallah , Treibel Thomas A. , Swift Andrew J. , Wild James M. , Garg Pankaj
Published: June 2020

The management of patients with aortic stenosis (AS) crucially depends on accurate diagnosis. The main aim of this study were to validate the four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR) methods for AS assessment. Eighteen patients with clinically severe AS were recruited. All patients had pre-valve intervention 6MWT, echocardiography and CMR with 4D flow. Of these, ten patients had a surgical valve replacement, and eight patients had successful transcatheter aortic valve implantation (TAVI). TAVI patients had invasive pressure gradient assessments. A repeat assessment was performed at 3–4 months to assess the remodelling response. The peak pressure gradient by 4D flow was comparable to an invasive pressure gradient (54 ± 26 mmHG vs 50 ± 34 mmHg, P = 0.67). However, Doppler yielded significantly higher pressure gradient compared to invasive assessment (61 ± 32 mmHG vs 50 ± 34 mmHg, P = 0.0002). 6MWT was associated with 4D flow CMR derived pressure gradient (r = −0.45, P = 0.01) and EOA (r = 0.54, P < 0.01) but only with Doppler EOA (r = 0.45, P = 0.01). Left ventricular mass regression was better associated with 4D flow derived pressure gradient change (r = 0.64, P = 0.04). 4D flow CMR offers an alternative method for non-invasive assessment of AS. In addition, 4D flow derived valve metrics have a superior association to prognostically relevant 6MWT and LV mass regression than echocardiography.
Numerical evaluation of spray position for improved nasal drug delivery
Authors: Basu Saikat , Holbrook Landon T. , Kudlaty Kathryn , Fasanmade Olulade , Wu Jihong , Burke Alyssa , Langworthy Benjamin W. , Farzal Zainab , Mamdani Mohammed , Bennett William D. , Fine Jason P. , Senior Brent A. , Zanation Adam M. , Ebert Charles S. , Kimple Adam J. , Thorp Brian D. , Frank-Ito Dennis O. , Garcia Guilherme J. M. , Kimbell Julia S.
Published: June 2020

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.
Computational translation of drug effects from animal experiments to human ventricular myocytes
Authors: Tveito Aslak , Jæger Karoline Horgmo , Maleckar Mary M. , Giles Wayne R. , Wall Samuel
Published: June 2020

Using animal cells and tissues as precise measuring devices for developing new drugs presents a long-standing challenge for the pharmaceutical industry. Despite the very significant resources that continue to be dedicated to animal testing of new compounds, only qualitative results can be obtained. This often results in both false positives and false negatives. Here, we show how the effect of drugs applied to animal ventricular myocytes can be translated, quantitatively, to estimate a number of different effects of the same drug on human cardiomyocytes. We illustrate and validate our methodology by translating, from animal to human, the effect of dofetilide applied to dog cardiomyocytes, the effect of E-4031 applied to zebrafish cardiomyocytes, and, finally, the effect of sotalol applied to rabbit cardiomyocytes. In all cases, the accuracy of our quantitative estimates are demonstrated. Our computations reveal that, in principle, electrophysiological data from testing using animal ventricular myocytes, can give precise, quantitative estimates of the effect of new compounds on human cardiomyocytes.
Mucus layer modeling of human colonoids during infection with enteroaggragative E. coli
Authors: Liu Lixia , Saitz-Rojas Waleska , Smith Rachel , Gonyar Laura , In Julie G. , Kovbasnjuk Olga , Zachos Nicholas C. , Donowitz Mark , Nataro James P. , Ruiz-Perez Fernando
Published: June 2020

EAEC is a common cause of diarrheal illness worldwide. Pathogenesis is believed to occur in the ileum and colon, where the bacteria adhere and form a robust aggregating biofilm. Among the multiple virulence factors produced by EAEC, the Pic serine protease has been implicated in bacterial colonization by virtue of its mucinolytic activity. Hence, a potential role of Pic in mucus barrier disruption during EAEC infection has been long postulated. In this study, we used human colonoids comprising goblet cells and a thick mucin barrier as an intestinal model to investigate Pic’s roles during infection with EAEC. We demonstrated the ability of purified Pic, but not a protease defective Pic mutant to degrade MUC2. Western blot and confocal microscopy analysis revealed degradation of the MUC2 layer in colonoids infected with EAEC, but not with its isogenic EAECpic mutant. Wild-type and MUC2-knockdown colonoids infected with EAEC strains exposed a differential biofilm distribution, greater penetration of the mucus layer and increased colonization of the colonic epithelium by Wild-type EAEC than its isogenic Pic mutant. Higher secretion of pro-inflammatory cytokines was seen in colonoids infected with EAEC than EAECpic. Although commensal E. coli expressing Pic degraded MUC2, it did not show improved mucus layer penetration or colonization of the colonic epithelium. Our study demonstrates a role of Pic in MUC2 barrier disruption in the human intestine and shows that colonoids are a reliable system to study the interaction of pathogens with the mucus layer.
Plasma metabolome and cognitive skills in Down syndrome
Authors: Antonaros Francesca , Ghini Veronica , Pulina Francesca , Ramacieri Giuseppe , Cicchini Elena , Mannini Elisa , Martelli Anna , Feliciello Agnese , Lanfranchi Silvia , Onnivello Sara , Vianello Renzo , Locatelli Chiara , Cocchi Guido , Pelleri Maria Chiara , Vitale Lorenza , Strippoli Pierluigi , Luchinat Claudio , Turano Paola , Piovesan Allison , Caracausi Maria
Published: June 2020

Trisomy 21 (Down syndrome, DS) is the main human genetic cause of intellectual disability (ID). Lejeune hypothesized that DS could be considered a metabolic disease, and we found that subjects with DS have a specific plasma and urinary metabolomic profile. In this work we confirmed the alteration of mitochondrial metabolism in DS and also investigated if metabolite levels are related to cognitive aspects of DS. We analyzed the metabolomic profiles of plasma samples from 129 subjects with DS and 46 healthy control (CTRL) subjects by 1H Nuclear Magnetic Resonance (NMR). Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to 94% accuracy) between the two groups. The univariate analysis revealed a significant alteration in 7 metabolites out of 28 assigned unambiguously. Correlations among the metabolite levels in DS and CTRL groups were separately investigated and statistically significant relationships appeared. On the contrary, statistically significant correlations among the NMR-detectable part of DS plasma metabolome and the different intelligence quotient ranges obtained by Griffiths-III or WPPSI-III tests were not found. Even if metabolic imbalance provides a clear discrimination between DS and CTRL groups, it appears that the investigated metabolomic profiles cannot be associated with the degree of ID.
Overexpression of PGC-1α influences the mitochondrial unfolded protein response (mtUPR) induced by MPP+ in human SH-SY5Y neuroblastoma cells
Authors: Cai Yousheng , Shen Hui , Weng Huidan , Wang Yingqing , Cai Guoen , Chen Xiaochun , Ye Qinyong
Published: June 2020

Parkinson’s disease (PD) is a common dyskinesia disease, the mitochondrial unfolded protein response (mtUPR) may be directly or indirectly involved in the occurrence and development of PD, although the exact mechanism is unclear. We established a dopaminergic neuronal-like cell model of PD, by overexpression of PGC-1α to detect evaluate the expression of proteases and molecular chaperones of involved in the mtUPR, as well as the expression of PGC-1α and LRPPRC, illustrated the distribution of LRPPRC. Remarkably, the mtUPR activation reached maximal at 24 h after MPP+ treatment in SH-SY5Y cells, which the protein and transcription levels of the proteases and molecular chaperones reached maximal. The proteases and molecular chaperones were significantly increased when overexpressed PGC-1α, which indicated that PGC-1α overexpression activated the mtUPR, and PGC-1α had a protective effect on SH-SY5Y cells. The expression levels of PGC-1α and LRPPRC were significantly improved in the PGC-1α overexpression groups. LRPPRC was markedly reduced in the nucleus, suggesting that PGC-1α overexpression may play a protective role to the mitochondria through LRPPRC. Our finding indicates that overexpression of PGC-1α may activate mtUPR, reducing the oxidative stress injury induced by MPP+ through LRPPRC signaling, thus maintain mitochondrial homeostasis.
Effect of donor age and 3D-cultivation on osteogenic differentiation capacity of adipose-derived mesenchymal stem cells
Authors: Payr Stephan , Schuseil Tim , Unger Marina , Seeliger Claudine , Tiefenboeck Thomas , Balmayor Elizabeth R. , van Griensven Martijn
Published: June 2020

Background and Purpose:Age and co-morbidities compromise healing tendencies of traumatic fractures in geriatric patients. Non-healing fractures may need regenerative medicine techniques involving autologous mesenchymal stem cells (MSCs). Donor age may affect the viability and differentiation capacity of MSCs. We investigated age-related differences in adipose-derived MSCs (AMSCs) concerning osteogenic potential in 2D and 3D cultivation.Materials and Methods:AMSCs were harvested from young (mean age: 37.5 ± 8.6 years) and old (mean age: 75.8 ± 9.2 years) patients. Cells were induced to osteogenic differentiation and cultivated in 2D and 3D for 14 days. Alkaline phosphatase (ALP) activity, mineralization and gene expression were investigated.Results:ALP activity revealed highest levels in 3D of old AMSCs after 14 days. ALP expression showed significant rises in old vs. young cells in 2D (p = 0.0024). Osteoprotegerin revealed the highest levels in old AMSCs in 2D. Highest osteocalcin levels presented in young cells compared to old cells in 2D (p = 0.0258) and young cells in 3D (p = 0.0014).Conclusion:3D arrangement of old AMSCs without growth factors is not ensuring superior osteogenesisin vitro. AMSCs, especially cells from older patients, reveal higher osteogenic potential in 2D than in 3D. 3D arrangement favors osteogenic potential of young cells.
Comparison between Surgical Outcomes of LASIK with and without Laser Asymmetric Keratectomy to Avoid Conventional Laser Refractive Surgery Adverse Effects
Authors: Min Ji Sang , Min Byung Moo
Published: June 2020

This study compared one-year postoperative outcomes of laser refractive surgery combined with laser asymmetric keratectomy (LAK) and laser in situ keratomileusis (LASIK)for myopia correction in middle-aged patients (aged 40–49 years) with a total corneal thickness deviation (summed across four directions) ≥ 80 microns. The control group (n = 26; 52 eyes) underwent LASIK; the comparison group (n = 26; 52 eyes) underwent combined laser refractive surgery and LAK. Age, spherical equivalence, uncorrected visual acuity (near and far), corneal irregularity on the Orbscan map, sum of corneal thickness deviations in four directions, corneal thickness distribution, distance between the maximum posterior elevation (best-fit sphere; BFS) and visual axis, and postoperative blurring scores were analysed retrospectively between the groups. Both groups had similar preoperative findings. Postoperatively, the sum of corneal thickness deviations in four directions (p = 0.000), distance between maximum posterior elevation (BFS) and visual axis (p = 0.003),blurring score (p = 0.001), and corneal irregularity in the 3.0 and 5.0 mm zones on the Orbscan map (p = 0.033 and p < 0.0001, respectively) were significantly lower in the comparison group (p = 0.000). LAK reduced total corneal thickness deviation, improved corneal symmetry, and reduced blurring scores significantly, one-year postoperatively. LAK could resolve shortcomings of LASIK, producing better surgical outcomes.
Glycogen as an advantageous polymer carrier in cancer theranostics: Straightforward in vivo evidence
Authors: Gálisová Andrea , Jirátová Markéta , Rabyk Mariia , Sticová Eva , Hájek Milan , Hrubý Martin , Jirák Daniel
Published: June 2020

As a natural polysaccharide polymer, glycogen possesses suitable properties for use as a nanoparticle carrier in cancer theranostics. Not only it is inherently biocompatible, it can also be easily chemically modified with various moieties. Synthetic glycogen conjugates can passively accumulate in tumours due to enhanced permeability of tumour vessels and limited lymphatic drainage (the EPR effect). For this study, we developed and examined a glycogen-based carrier containing a gadolinium chelate and near-infrared fluorescent dye. Our aim was to monitor biodistribution and accumulation in tumour-bearing rats using magnetic resonance and fluorescence imaging. Our data clearly show that these conjugates possess suitable imaging and tumour-targeting properties, and are safe under both in vitro and in vivo conditions. Additional modification of glycogen polymers with poly(2-alkyl-2-oxazolines) led to a reduction in the elimination rate and lower uptake in internal organs (lower whole-body background: 45% and 27% lower MRI signals of oxazoline-based conjugates in the liver and kidneys, respectively compared to the unmodified version). Our results highlight the potential of multimodal glycogen-based nanopolymers as a carrier for drug delivery systems in tumour diagnosis and treatment.
Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction
Authors: Ahmed Ibrahim , Tucci Felicia A. , Aflalo Aure , Smith Kenneth G. C. , Bashford-Rogers Rachael J. M.
Published: June 2020

The ability to accurately characterize DNA variant proportions using PCR amplification is key to many genetic studies, including studying tumor heterogeneity, 16S microbiome, viral and immune receptor sequencing. We develop a novel generalizable ultrasensitive amplicon barcoding approach that significantly reduces the inflation/deflation of DNA variant proportions due to PCR amplification biases and sequencing errors. This method was applied to immune receptor sequencing, where it significantly improves the quality and estimation of diversity of the resulting library.
Gabapentin-induced drug-seeking-like behavior: a potential role for the dopaminergic system
Authors: Althobaiti Yusuf S. , Alghorabi Amal , Alshehri Fahad S. , Baothman Bandar , Almalki Atiah H. , Alsaab Hashem O. , Alsanie Walaa , Gaber Ahmed , Almalki Hussam , Alghamdi Abdulrahman S. , Basfer Ahmad , Althobaiti Sultan , Hardy Ana Maria Gregio , Shah Zahoor A.
Published: June 2020

Drugs of abuse represent a growing public health crisis. Accumulating evidence indicates that gabapentin (GBP), a prescription drug, is prone to misuse, abuse, withdrawal, and dependence. Commonly, drugs of abuse modulate the dopaminergic system to induce addiction. In this study, we used the conditioned place preference (CPP) model to investigate the involvement of the dopamine 1 (D1) receptor on the reward and reinforcement behavior of GBP. Under a CPP paradigm, male BALB/c mice were intraperitoneally injected either saline or 100, 200, or 300 mg/kg of GBP and confined to the injection-paired chamber for 30 min. In the pre-conditioning phase, mice were conditioned for 3 days, and baseline data were collected. In the conditioning phase, mice were given once-daily alternating injections of either GBP or saline for 8 days and subsequently assessed in a post-conditioning test. Injections of 300 mg/kg of GBP significantly increased the time spent in the drug-paired chamber compared to the saline-paired chamber. However, lower doses of GBP (100 and 200 mg/kg) showed no effect. Pre-treatment with SKF-83566, a D1 receptor antagonist, attenuated GBP-induced CPP. Thus, for the first time, we show that GBP can induce CPP through a dopaminergic-dependent mechanism.
PEGylated lipid nanocarrier for enhancing photodynamic therapy of skin carcinoma using curcumin: in-vitro/in-vivo studies and histopathological examination
Authors: Abdel Fadeel Doaa A. , Kamel Rabab , Fadel Maha
Published: June 2020

The use of (PEG)-grafted materials has a positive impact on drug delivery. In this study we designed PEGylated lipid nanocarriers (PLN) loaded with curcumin (Cur) to target skin cancer by photodynamic therapy. Cur is a polyphenolic compound having vast biological effects masked due to its low aqueous solubility. PLN were prepared using Tefose 1500 with different surfactants. PLN3, containing Tween 80, had the smallest particle size (167.60 ± 15.12 nm), Z = − 26.91 mV and, attained the highest drug release (Q24 = 75.02 ± 4.61% and Q48 = 98.25 ± 6.89%). TEM showed spherical, well-separated nanoparticles. The dark and photo-cytotoxicity study on a human skin cancer cell line (A431) revealed that, at all tested concentrations, the viability of cells treated with PLN3 was significantly lower than those treated by Cur suspension and, it decreased upon irradiation by blue light (410 nm). The amount of Cur extracted from the skin of mice treated by PLN3 was twice that of mice treated by aqueous drug suspension, this was confirmed by the increase in fluorescence intensity measured by confocal laser microscopy. Histopathological studies showed that PLN3 could extend Cur effect to deeper skin layers, especially after irradiation. This study highlights the possible efficacy of curcumin-loaded PEGylated lipidic nanoparticles to combat skin cancer by photodynamic therapy.
Prevalence and incidence of visual impairment in patients with proliferative diabetic retinopathy in India
Authors: Khan Rehana , Chandra Shruti , Rajalakshmi Ramachandran , Rani Padmaja Kumari , Anantharaman Giridhar , Sen Alok , Desai Abhishek , Roy Rupak , Natarajan Sundaram , Chen Lanin , Chawla Gajendra , Behera Umesh Chandra , Gopal Lingam , Gurudas Sarega , Sivaprasad Sobha , Raman Rajiv
Published: June 2020

To provide the real-world outcomes of people with proliferative diabetic retinopathy (PDR) in India and highlight opportunities for improvement of their disease status and to evaluate their visual acuity (VA) status. A multicenter retrospective study in which ten centers in India with established vitreoretinal services for over 10 years were invited to provide long-term data on PDR. This study population were of Indian nationality. Patients with a diagnosis of type 1 or 2 diabetes with a clinical diagnosis of active PDR in any or both eyes, who had long term follow-up for up to 10 years were included. Baseline data collected included age, sex, duration of diabetes, source of referral and best-corrected visual acuity, diabetic retinopathy status in both eyes. Available follow-up data on VA were collected at 6 months post baseline, 5 years and 10 years within a ± 3 months window. Evaluating the presenting VA of people with PDR, short-term outcomes at 6 months and the incidence of visual impairment (VI) at 5 and 10 years are the main outcome of the study. Data was available for 516, 424 and 455 patients at baseline, 5 years and 10 years respectively. Gender and duration of diabetes did not have statistically significant effect on VI outcomes. Eyes receiving treatment early in the disease course (i.e. baseline VA ≥ 6/12) had significantly better VA outcomes at 10 years versus eyes treated at a later stage (i.e. baseline VA < 6/12) (p = <0.0001). On comparing eyes with stable treated PDR and persistent PDR at end of 10 year follow up, a significantly higher percentage of eyes in the stable treated group maintained VA of ≥ 6/12 (55.1% vs. 24.2%) (p = < 0.0001), indicating persistent disease activity due to inadequate treatment results in worse VA outcomes. We found no trend in VI or blindness with increasing levels of age at both 5- and 10-year time points (p > 0.05). The age standardized incidence for VI was 11.10% (95% CI 8.1, 14.2) and for blindness was found to be 7.7% (95% CI 5.2, 10.3). Our results suggest that despite robust recent clinical trial results showing that pan retinal photocoagulation is an excellent treatment for PDR, people with diabetes in India need to be made aware of annual screening and treatment of their eyes to avoid vision impairment and blindness.
The impact of climate change and glacier mass loss on the hydrology in the Mont-Blanc massif
Authors: Laurent Léa , Buoncristiani Jean-François , Pohl Benjamin , Zekollari Harry , Farinotti Daniel , Huss Matthias , Mugnier Jean-Louis , Pergaud Julien
Published: June 2020

The Mont-Blanc massif, being iconic with its large glaciers and peaks of over 4,000 m, will experience a sharp increase in summer temperatures during the twenty-first century. By 2100, the impact of climate change on the cryosphere and hydrosphere in the Alps is expected to lead to a decrease in annual river discharge. In this work, we modelled the twenty-first century evolution of runoff in the Arve river, downstream of Mont-Blanc’s French side. For the first time for this region, we have forced a hydrological model with output from an ice-dynamical glacier model and 16 downscaled climate projections, under RCP4.5 and RCP8.5 scenarios. By 2100, under RCP8.5 (high-emission scenario), the winter discharge of the Arve river remains low but is expected to increase by 80% when compared to the beginning of the century. By contrast, the summer season, currently the most important discharge period, will be marked by a runoff decrease of approximately 40%. These changes are almost similar according to a scenario with a lower warming (RCP4.5) and are mostly driven by glacier retreat. These shifts will have significant downstream impacts on water quantity and quality, affecting hydroelectric generation, agriculture, forestry, tourism and aquatic ecosystems.
Arthropod entombment in weathering-formed opal: new horizons for recording life in rocks
Authors: Chauviré Boris , Houadria Mickal , Donini Aline , Berger Brian T. , Rondeau Benjamin , Kritsky Gene , Lhuissier Pierre
Published: June 2020

Animal fossils preserved in various geological materials, such as limestone, claystone, or amber, provide detailed information on extinct species that is indispensable for retracing the evolution of terrestrial life. Here, we present the first record of an animal fossil preserved in opal formed by weathering with such high-resolution details that even individual cuticle hairs are observed. The fossil consists of the exoskeleton of a nymphal insect belonging to the order Hemiptera and either the family Tettigarctidae or the Cicadidae. This identification is based on anatomical details such as the tibial and femoral morphology of the forelegs. The exoskeleton of the insect was primarily zeolitized during the alteration of the host rocks and later sealed in opal deposited by silica-rich fluids derived from the continental weathering of the volcanic host rocks. Organic matter is preserved in the form of amorphous carbon. This finding makes opal formed by rocks weathering a new, complementary source of animal fossils, offering new prospects for the search for ancient life in the early history of Earth and possibly other terrestrial planets such as Mars, where weathering-formed opal occurs.
A site-moiety map and virtual screening approach for discovery of novel 5-LOX inhibitors
Authors: Hsu Kai-Cheng , HuangFu Wei-Chun , Lin Tony Eight , Chao Min-Wu , Sung Tzu-Ying , Chen Yi-Ying , Pan Shiow-Lin , Lee Jih-Chin , Tzou Shey-Cherng , Sun Chung-Ming , Yang Jinn-Moon
Published: June 2020

The immune system works in conjunction with inflammation. Excessive inflammation underlies various human diseases, such as asthma, diabetes and heart disease. Previous studies found that 5-lipoxygenase (5-LOX) plays a crucial role in metabolizing arachidonic acid into inflammatory mediators and is a potential therapeutic target. In this study, we performed an in silico approach to establish a site-moiety map (SiMMap) to screen for new 5-LOX inhibitors. The map is composed of several anchors that contain key residues, moiety preferences, and their interaction types (i.e., electrostatic (E), hydrogen-bonding (H), and van der Waals (V) interactions) within the catalytic site. In total, we identified one EH, one H, and five V anchors, within the 5-LOX catalytic site. Based on the SiMMap, three 5-LOX inhibitors (YS1, YS2, and YS3) were identified. An enzyme-based assay validated inhibitory activity of YS1, YS2, and YS3 against 5-LOX with an IC50 value of 2.7, 4.2, and 5.3 μM, respectively. All three inhibitors significantly decrease LPS-induced TNF-α and IL-6 production, which suggests its potential use an anti-inflammatory agent. In addition, the identified 5-LOX inhibitors contain a novel scaffold. The discovery of these inhibitors presents an opportunity for designing specific anti-inflammatory drugs.
Three visual working memory representations simultaneously control attention
Authors: King Michael J. , Macnamara Brooke N.
Published: June 2020

How many items can we store in visual working memory while simultaneously conducting a visual search? Previous research has proposed that during concurrent visual search, only one visual working memory representation can be activated to directly influence attention. This previous research suggests that other visual working memory representations are “accessory items”, which have little direct influence on attention. However, recent findings provided evidence that not one, but two visual working memory representations can capture attention and interfere with concurrent visual search. We successfully replicate these findings, and further test whether the capacity of visual working memory during visual search extends to not two, but three representations that influence attention directly. We find evidence that three visual working memory representations can simultaneously control attention.
Publisher Correction: Deep neural networks for automated detection of marine mammal species
Authors: Shiu Yu , Palmer K. J. , Roch Marie A. , Fleishman Erica , Liu Xiaobai , Nosal Eva-Marie , Helble Tyler , Cholewiak Danielle , Gillespie Douglas , Klinck Holger
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: (−)-Epigallocatechin-3-gallate (EGCG) attenuates salt-induced hypertension and renal injury in Dahl salt-sensitive rats
Authors: Luo Dan , Xu Jianping , Chen Xuejiao , Zhu Xu , Liu Shuang , Li Jie , Xu Xinting , Ma Xiao , Zhao Jinhua , Ji Xu
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Stabilization of SIRT7 deacetylase by viral oncoprotein HBx leads to inhibition of growth restrictive RPS7 gene and facilitates cellular transformation
Authors: Pandey Vijaya , Kumar Vijay
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A portable point-of-care testing system to diagnose lung cancer through the detection of exosomal miRNA in urine and saliva
Authors: Zhou Ping , Lu Fei , Wang Jianbo , Wang Kaiye , Liu Bo , Li Na , Tang Bo
Published: June 2020

A low-cost, easy-to-operate, highly sensitive and effective lung cancer diagnostic kit (LCDK) was developed, and can realize non-invasive detection of early-, middle- and late-stage lung cancers using clinical salivary and urine samples.
In situ detection of intracellular tissue transglutaminase based on aggregation-induced emission
Authors: Wu Yafeng , Gao Yaqiong , Su Juan , Chen Zixuan , Liu Songqin
Published: June 2020

Aggregation-induced emission (AIE) nanoprobes were developed for in situ imaging and real-time monitoring of intracellular tissue transglutaminase (TG2).
Benzenebistriazole-strapped calix[4]pyrrole: a neutral anion receptor with CH and NH donor groups that exhibits high sulfate binding affinity and selectivity in aqueous solutions
Authors: He Ying-Chun , Yan Yan-Mei , Tong Hong-Bo , Ren Zhen-Xing , Wang Jun-Hong , Zhang Yong-Bin , Chao Jian-Bin , Wang Meng-Liang
Published: June 2020

Benzenebistriazole-strapped calix[4]pyrrole with high binding affinity and selectivity for sulfate in an aqueous solution has been synthesized.
Cocrystallization of 5-fluorouracil and l-phenylalanine: the first zwitterionic cocrystal of 5-fluorouracil with amino acid exhibiting perfect in vitro/vivo pharmaceutical properties
Authors: Wang Lin-Lin , Wang Ling-Yang , Yu Yue-Ming , Li Yan-Tuan , Wu Zhi-Yong , Yan Cui-Wei
Published: June 2020

The first zwitterionic cocrystal of 5-fluorouracil with amino acid has been prepared and its structure and in vitro/vivo properties have been systematically studied.
Facile surface improvement of LaCoO3 perovskite with high activity and water resistance towards toluene oxidation: Ca substitution and citric acid etching
Authors: Chen Hanlin , Wei Gaoling , Liang Xiaoliang , Liu Peng , Xi Yunfei , Zhu Jianxi
Published: June 2020

We employ two facile modification methods, i.e., Ca substitution and citric acid etching, to further improve the catalytic activity of LaCoO3 perovskite towards toluene oxidation.
Tris-pyridylmethylamine (TPMA) complexes functionalized with persistent nitronyl nitroxide organic radicals
Authors: Badetti Elena , Lloveras Vega , Scaramuzzo Francesca Anna , Wurst Klaus , Veciana Jaume , Vidal-Gancedo José , Licini Giulia , Zonta Cristiano
Published: June 2020

The chance to have persistent organic radicals in combination with metals has attracted much interest since it offers the possibility of having new functional molecules with multiple open-shell elements.
Barriers to handpump serviceability in Malawi: life-cycle costing for sustainable service delivery
Authors: Truslove Jonathan P. , Coulson Andrea B. , Mbalame Emma , Kalin Robert M.
Published: June 2020

Life-cycle assessment model and regression analysis identifies drivers that negatively impact the lifecycle of community Afridev handpumps under various tariff scenarios for rural community water supply.
Effect of cooking, 24 h cold storage, microwave reheating, and particle size on in vitro starch digestibility of dry and fresh pasta
Authors: Cañas Silvia , Perez-Moral Natalia , Edwards Cathrina H.
Published: June 2020

The aim of this study was to investigate the effect of preparation method and particle size on digestion of starch in fresh and dry pasta types.
Two-step conversion of Kraft lignin to nylon precursors under mild conditions
Authors: Zhou Hui , Wang Hsin , Perras Frédéric A. , Naik Pranjali , Pruski Marek , Sadow Aaron D. , Slowing Igor I.
Published: June 2020

Treatment of Kraft lignin, massive byproduct of pulping industry, with dilute aqueous base followed by catalytic hydrogenation of the extracted monomers at ambient pressure yields KA oil, the precursor of high demand nylon polymer.
Chemically controlled shape-morphing of elastic sheets
Authors: Manna Raj Kumar , Shklyaev Oleg E. , Stone Howard A. , Balazs Anna C.
Published: June 2020

A catalyst-coated 2D elastic sheet that generates controllable fluid flows can self-morph into multiple 3D structures in fluid-filled microchambers.
Highly efficient removal of Cr(vi) ions from wastewater by the pomegranate-like magnetic hybrid nano-adsorbent of polydopamine and Fe3O4 nanoparticles
Authors: Li Jikang , Chen Sheng , Xiao Hongyan , Yao Guo , Gu Yingchun , Yang Qin , Yan Bin
Published: June 2020

Fe3O4 nanoparticles have attracted extensive attention for solving Cr(vi) pollution because they can effectively reduce Cr(vi) to the less toxic and less soluble Cr(iii)-containing species.
A new fluorone-based bridging ligand for discrete and polymeric assemblies including Mo and W based [4+4] metallocycles
Authors: Sutton Ashley L. , Abrahams Brendan F. , Hudson Timothy A. , Robson Richard
Published: June 2020

The synthesis of a planar, trianionic, redox-active ligand is described, which is able to bridge metal centres and form [4+4] square anionic metallocycles.
Free-standing SiO2/TiO2–MoS2 composite nanofibrous membranes as nanoadsorbents for efficient Pb(ii) removal
Authors: Mercante Luiza A. , Andre Rafaela S. , Schneider Rodrigo , Mattoso Luiz H. C. , Correa Daniel S.
Published: June 2020

The practical utility of a hybrid material based on flexible free-standing ceramic nanofibers functionalized with MoS2 for heavy metal removal.
Preparation of monodisperse ferrous nanoparticles embedded in carbon aerogels via in situ solid phase polymerization for electrocatalytic oxygen reduction
Authors: Hong Wei , Feng Xin , Tan Lianqiao , Guo Aiming , Lu Bing , Li Jing , Wei Zidong
Published: June 2020

Core–shell structured materials constructed by using Fe/Fe3C cores and nitrogen doped carbon shells represent a type of promising non-precious oxygen reduction reaction (ORR) catalyst due to well-established active sites at the interface positions.
Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature
Authors: Leach Adam , Smyth Peter , Ferguson Laura , Steven John , Greene Michelle K. , Branco Cristina M. , McCann Aidan P. , Porter Andrew , Barelle Caroline J. , Scott Christopher J.
Published: June 2020

Anti-DLL4 VNAR targeted nanoparticles – a novel targeting ligand towards an under-investigated target.
Electron–phonon scattering and excitonic effects in T-carbon
Authors: Bu Xiangtian , Wang Shudong
Published: June 2020

Through first-principles calculations combining many-body perturbation theory, we investigate electron–phonon scattering and optical properties including the excitonic effects of T-carbon.
Facile synthesis of TiO2/Ag3PO4 composites with co-exposed high-energy facets for efficient photodegradation of rhodamine B solution under visible light irradiation
Authors: Du Yi-en , Li Wanxi , Bai Yang , Huangfu Zewen , Wang Weijin , Chai Ruidong , Chen Changdong , Yang Xiaojing , Feng Qi
Published: June 2020

TiO2/Ag3PO4 composites with co-exposed {101}, {010}/{100}, {001} and [111]-facets were successfully synthesized by combining hydrothermal and ion-exchange methods.