bluuebunny/crossref_metadata_2025 huggingface dataset:
Long- and short-ranged chiral interactions in DNA-assembled plasmonic chains
Authors: Martens Kevin , Binkowski Felix , Nguyen Linh , Hu Li , Govorov Alexander O. , Burger Sven , Liedl Tim
Published: April 2021

Circular dichroism (CD) has long been used to trace chiral molecular states and changes of protein configurations. In recent years, chiral plasmonic nanostructures have shown potential for applications ranging from pathogen sensing to novel optical materials. The plasmonic coupling of the individual elements of such metallic structures is a crucial prerequisite to obtain sizeable CD signals. We here identify and implement various coupling entities—chiral and achiral—to demonstrate chiral transfer over distances close to 100 nm. The coupling is realized by an achiral nanosphere situated between a pair of gold nanorods that are arranged far apart but in a chiral fashion using DNA origami. The transmitter particle causes a strong enhancement of the CD response, the emergence of an additional chiral feature at the resonance frequency of the nanosphere, and a redshift of the longitudinal plasmonic resonance frequency of the nanorods. Matching numerical simulations elucidate the intricate chiral optical fields in complex architectures.
High-throughput fitness screening and transcriptomics identify a role for a type IV secretion system in the pathogenesis of Crohn’s disease-associated Escherichia coli
Authors: Elhenawy Wael , Hordienko Sarah , Gould Steven , Oberc Alexander M. , Tsai Caressa N. , Hubbard Troy P. , Waldor Matthew K. , Coombes Brian K.
Published: April 2021

Adherent-invasive Escherichia coli (AIEC) are pathogenic bacteria frequently isolated from patients who have Crohn’s disease (CD). Despite the phenotypic differences between AIEC and commensal E. coli, comparative genomic approaches have been unable to differentiate these two groups, making the identification of key virulence factors a challenge. Here, we conduct a high-resolution, in vivo genetic screen to map AIEC genes required for intestinal colonization of mice. In addition, we use in vivo RNA-sequencing to define the host-associated AIEC transcriptome. We identify diverse metabolic pathways required for efficient gut colonization by AIEC and show that a type IV secretion system (T4SS) is required to form biofilms on the surface of epithelial cells, thereby promoting AIEC persistence in the gut. E. coli isolated from CD patients are enriched for a T4SS, suggesting a possible connection to disease activity. Our findings establish the T4SS as a principal AIEC colonization factor and highlight the use of genome-wide screens in decoding the infection biology of CD-associated bacteria that otherwise lack a defined genetic signature.
Dynamic upconversion multicolour editing enabled by molecule-assisted opto-electrochemical modulation
Authors: Wu Yiming , Xu Jiahui , Qin Xian , Xu Jun , Liu Xiaogang
Published: April 2021

Controlling nonlinear optical signals electrically offers many opportunities for technological developments. Lanthanide-activated nanoparticles have recently emerged as leading platforms for nonlinear upconversion of infra-red excitation within nanometric volumes. However, manipulation of upconversion emission is restricted to varying percentages of component materials, nanocrystal structure, and optical pumping conditions. Here, we report temporal modulation of anti-Stokes luminescence by coupling upconversion nanoparticles with an electrochemically responsive molecule. By electrically tailoring orbital energy levels of the molecules anchored on nanoparticle surfaces, we demonstrate reversible control of molecular absorption, resulting in dynamic colour editing of anti-Stokes luminescence at single-particle resolution. Moreover, we show that a programmable logic gate array based on opto-electrochemical modulation can be constructed to convert information-encrypted electrical signals into visible patterns with millisecond photonic readout. These findings offer insights into precise control of anti-Stokes luminescence, while enabling a host of applications from low-threshold infrared logic switches to multichannel, high-fidelity photonic circuits.
Efficient photocatalytic hydrogen peroxide generation coupled with selective benzylamine oxidation over defective ZrS3 nanobelts
Authors: Tian Zhangliu , Han Cheng , Zhao Yao , Dai Wenrui , Lian Xu , Wang Yanan , Zheng Yue , Shi Yi , Pan Xuan , Huang Zhichao , Li Hexing , Chen Wei
Published: April 2021

Photocatalytic hydrogen peroxide (H2O2) generation represents a promising approach for artificial photosynthesis. However, the sluggish half-reaction of water oxidation significantly limits the efficiency of H2O2 generation. Here, a benzylamine oxidation with more favorable thermodynamics is employed as the half-reaction to couple with H2O2 generation in water by using defective zirconium trisulfide (ZrS3) nanobelts as a photocatalyst. The ZrS3 nanobelts with disulfide (S22−) and sulfide anion (S2−) vacancies exhibit an excellent photocatalytic performance for H2O2 generation and simultaneous oxidation of benzylamine to benzonitrile with a high selectivity of >99%. More importantly, the S22− and S2− vacancies can be separately introduced into ZrS3 nanobelts in a controlled manner. The S22− vacancies are further revealed to facilitate the separation of photogenerated charge carriers. The S2− vacancies can significantly improve the electron conduction, hole extraction, and kinetics of benzylamine oxidation. As a result, the use of defective ZrS3 nanobelts yields a high production rate of 78.1 ± 1.5 and 32.0 ± 1.2 μmol h−1 for H2O2 and benzonitrile, respectively, under a simulated sunlight irradiation.
A decrease in NAD+ contributes to the loss of osteoprogenitors and bone mass with aging
Authors: Kim Ha-Neui , Ponte Filipa , Warren Aaron , Ring Rebecca , Iyer Srividhya , Han Li , Almeida Maria
Published: April 2021

Age-related osteoporosis is caused by a deficit in osteoblasts, the cells that secrete bone matrix. The number of osteoblast progenitors also declines with age associated with increased markers of cell senescence. The forkhead box O (FoxO) transcription factors attenuate Wnt/β-catenin signaling and the proliferation of osteoprogenitors, thereby decreasing bone formation. The NAD+-dependent Sirtuin1 (Sirt1) deacetylates FoxOs and β-catenin in osteoblast progenitors and, thereby, increases bone mass. However, it remains unknown whether the Sirt1/FoxO/β-catenin pathway is dysregulated with age in osteoblast progenitors. We found decreased levels of NAD+ in osteoblast progenitor cultures from old mice, associated with increased acetylation of FoxO1 and markers of cell senescence. The NAD+ precursor nicotinamide riboside (NR) abrogated FoxO1 and β-catenin acetylation and several marker of cellular senescence, and increased the osteoblastogenic capacity of cells from old mice. Consistent with these effects, NR administration to C57BL/6 mice counteracted the loss of bone mass with aging. Attenuation of NAD+ levels in osteoprogenitor cultures from young mice inhibited osteoblastogenesis in a FoxO-dependent manner. In addition, mice with decreased NAD+ in cells of the osteoblast lineage lost bone mass at a young age. Together, these findings suggest that the decrease in bone formation with old age is due, at least in part, to a decrease in NAD+ and dysregulated Sirt1/FoxO/β-catenin pathway in osteoblast progenitors. NAD+ repletion, therefore, represents a rational therapeutic approach to skeletal involution.
In situ XPS investigation of the X-ray-triggered decomposition of perovskites in ultrahigh vacuum condition
Authors: Lin Wei-Chun , Lo Wei-Chun , Li Jun-Xian , Wang Yi-Kai , Tang Jui-Fu , Fong Zi-Yun
Published: April 2021

X-ray photoelectron spectroscopy (XPS) has been used to investigate the composition of perovskite films upon exposure to different environmental factors, such as moisture, heat, and UV light. However, few research studies have determined that the X-ray itself could cause damage to the perovskite crystals. In this study, the X-ray-induced degradation of CH3NH3PbI3 perovskite films was investigated via XPS within an in situ ultrahigh vacuum system. It is demonstrated that fresh methylammonium lead iodine contains Pb2+ without the initial existence of Pb0. The Pb0 signal was discovered after a few hours of soft X-ray exposure, which indicates that the CH3NH3PbI3 perovskite structure undergoes a decomposition process to form metallic Pb. In addition, the nitrogen content was found to be significantly decreasing in the first hour of X-ray exposure. The discovery of the X-ray-induced chemical state change and the volatile methylamine of perovskite crystals could be further applied as an indicator for the field of X-ray sensors or detectors.
Improving estimation of Parkinson’s disease risk—the enhanced PREDICT-PD algorithm
Authors: Bestwick Jonathan P. , Auger Stephen D. , Simonet Cristina , Rees Richard N. , Rack Daniel , Jitlal Mark , Giovannoni Gavin , Lees Andrew J. , Cuzick Jack , Schrag Anette E. , Noyce Alastair J.
Published: April 2021

We previously reported a basic algorithm to identify the risk of Parkinson’s disease (PD) using published data on risk factors and prodromal features. Using this algorithm, the PREDICT-PD study identified individuals at increased risk of PD and used tapping speed, hyposmia and REM sleep behaviour disorder (RBD) as “intermediate” markers of prodromal PD in the absence of sufficient incident cases. We have now developed and tested an enhanced algorithm which incorporates the intermediate markers into the risk model. Risk estimates were compared using the enhanced and the basic algorithm in members of the PREDICT-PD pilot cohort. The enhanced PREDICT-PD algorithm yielded a much greater range of risk estimates than the basic algorithm (93–609-fold difference between the 10th and 90th centiles vs 10–13-fold respectively). There was a greater increase in the risk of PD with increasing risk scores for the enhanced algorithm than for the basic algorithm (hazard ratios per one standard deviation increase in log risk of 2.75 [95% CI 1.68–4.50; p < 0.001] versus 1.47 [95% CI 0.86–2.51; p = 0.16] respectively). Estimates from the enhanced algorithm also correlated more closely with subclinical striatal DaT-SPECT dopamine depletion (R2 = 0.164, p = 0.005 vs R2 = 0.043, p = 0.17). Incorporating the previous intermediate markers of prodromal PD and using likelihood ratios improved the accuracy of the PREDICT-PD prediction algorithm.
School-based self-management interventions for asthma among primary school children: a systematic review
Authors: Ramdzan Siti Nurkamilla , Suhaimi Julia , Harris Katherine M. , Khoo Ee Ming , Liew Su May , Cunningham Steve , Pinnock Hilary
Published: April 2021

A Cochrane review of school-based asthma interventions (combining all ages) found improved health outcomes. Self-management skills, however, vary according to age. We assessed effectiveness of primary school-based self-management interventions and identified components associated with successful programmes in children aged 6–12 years. We updated the Cochrane search (March 2020) and included the Global Health database. Two reviewers screened, assessed risk-of-bias and extracted data. We included 23 studies (10,682 participants); four at low risk-of-bias. Twelve studies reported at least one positive result for an outcome of interest. All 12 positive studies reported parental involvement in the intervention, compared to two-thirds of ineffective studies. In 10 of the 12 positive studies, parental involvement was substantial (e.g. attending sessions; phone/video communication) rather than being provided with written information. School-based self-management intervention can improve health outcomes and substantial parental involvement in school-based programmes seemed important for positive outcomes among primary school children.
Triacylglycerols are preferentially oxidized over free fatty acids in heated soybean oil
Authors: Shen Qing , Zhang Zhichao , Emami Shiva , Chen Jianchu , Leite Nobrega de Moura Bell Juliana Maria , Taha Ameer Y.
Published: April 2021

In oil, free fatty acids (FFAs) are thought to be the preferred substrate for lipid oxidation although triacylglycerols (TAGs) are the predominant lipid class. We determined the preferential oxidation substrate (TAGs versus FFAs) in soybean oil heated at 100 °C for 24 h, after validating a method for quantifying esterified and free lipid oxidation products (i.e., oxylipins) with mass-spectrometry. Reaction velocities and turnover (velocity per unit substrate) of FFA, and free and TAG-bound (esterified) oxylipins were determined. FFA hydrolysis rate and turnover were orders of magnitude greater (16-4217 fold) than that of esterified and free oxylipin formation. The velocity and turnover of TAG-bound oxylipins was significantly greater than free oxylipins by 282- and 3-fold, respectively. The results suggest that during heating, TAGs are preferentially oxidized over FFAs, despite the rapid hydrolysis and availability of individual FFAs as substrates for oxidation. TAG-bound oxylipins may serve as better markers of lipid oxidation.
Control of endothelial quiescence by FOXO-regulated metabolites
Authors: Andrade Jorge , Shi Chenyue , Costa Ana S. H. , Choi Jeongwoon , Kim Jaeryung , Doddaballapur Anuradha , Sugino Toshiya , Ong Yu Ting , Castro Marco , Zimmermann Barbara , Kaulich Manuel , Guenther Stefan , Wilhelm Kerstin , Kubota Yoshiaki , Braun Thomas , Koh Gou Young , Grosso Ana Rita , Frezza Christian , Potente Michael
Published: April 2021

Endothelial cells (ECs) adapt their metabolism to enable the growth of new blood vessels, but little is known how ECs regulate metabolism to adopt a quiescent state. Here, we show that the metabolite S-2-hydroxyglutarate (S-2HG) plays a crucial role in the regulation of endothelial quiescence. We find that S-2HG is produced in ECs after activation of the transcription factor forkhead box O1 (FOXO1), where it limits cell cycle progression, metabolic activity and vascular expansion. FOXO1 stimulates S-2HG production by inhibiting the mitochondrial enzyme 2-oxoglutarate dehydrogenase. This inhibition relies on branched-chain amino acid catabolites such as 3-methyl-2-oxovalerate, which increase in ECs with activated FOXO1. Treatment of ECs with 3-methyl-2-oxovalerate elicits S-2HG production and suppresses proliferation, causing vascular rarefaction in mice. Our findings identify a metabolic programme that promotes the acquisition of a quiescent endothelial state and highlight the role of metabolites as signalling molecules in the endothelium.
Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning
Authors: Ing-Simmons Elizabeth , Vaid Roshan , Bing Xin Yang , Levine Michael , Mannervik Mattias , Vaquerizas Juan M.
Published: April 2021

The relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression. Here, using the dorsoventral patterning of theDrosophila melanogasterembryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.
Suppression of TGF-β1 signaling by Matrigel via FAK signaling in cultured human trabecular meshwork cells
Authors: Zhang Yuan , Tseng Scheffer C. G. , Zhu Ying-Ting
Published: April 2021

The trabecular meshwork (TM) is composed of TM cells and beams of the extracellular matrix, together contributing to aqueous humor (AH) outflow resistance. Herein, we validated that our culture system on 2D Matrigel expressed putative TM markers and myocilin, of which the latter was upregulated by dexamethasone. Continuous passage of these cells on 2D Matrigel resulted in a gradual loss of expression of these markers. However, such a loss was restored by seeding cells in 3D Matrigel where expression of TM markers was further upregulated upon continuous passage. In contrast, TM cells seeded on fibronectin, collagen I/IV, or laminin lost expression of these markers and turned into myofibroblasts with expression of αSMA, which were dose-dependently upregulated by TGF-β1/TGF-β2. TM cells in 3D Matrigel also expressed TGF-β1/TGF-β3 despite challenge of TGF-β1. The maintenance of TM phenotype by 3D Matrigel was linked to inhibition of canonical TGF-β signaling and activation of pFAK-pSrc-pP190RhoGAP-P120RasGAP signaling. These findings indicate that basement membrane matrix with low rigidity plays an active role in maintaining TM phenotype in the presence of TGF-β1 and shed light on its physiological role. Furthermore, abnormal matrices may perpetuate the pathological TM phenotype when the level of TGF-β2 is elevated in glaucoma patients.
Electron tunneling between vibrating atoms in a copper nano-filament
Authors: Al-Mamun Mohammad , Orlowski Marius
Published: April 2021

Nanowires, atomic point contacts, and chains of atoms are one-dimensional nanostructures, which display size-dependent quantum effects in electrical and thermal conductivity. In this work a Cu nanofilament of a defined resistance and formed between a Cu and Pt electrode is heated remotely in a controlled way. Depending on the robustness of the conductive filament and the amount of heat transferred several resistance-changing effects are observed. In case of sufficiently fragile nanofilament exhibiting electrical quantum conductance effects and moderate heating applied to it, a dramatic increase of resistance is observed just after the completion of the heating cycle. However, when the filament is allowed to cool off, a spontaneous restoration of the originally set resistance of the filament is observed within less than couple tens of seconds. When the filament is sufficiently fragile or the heating too excessive, the filament is permanently ruptured, resulting in a high resistance of the cell. In contrast, for robust, low resistance filaments, the remote heating does not affect the resistance. The spontaneous restoration of the initial resistance value is explained by electron tunneling between neighboring vibrating Cu atoms. As the vibrations of the Cu atoms subside during the cooling off period, the electron tunneling between the Cu atoms becomes more likely. At elevated temperatures, the average tunneling distance increases, leading to a sharp decrease of the tunneling probability and, consequently, to a sharp increase in transient resistance.
Transcriptome analysis of human dermal fibroblasts following red light phototherapy
Authors: Austin Evan , Koo Eugene , Merleev Alexander , Torre Denis , Marusina Alina , Luxardi Guillaume , Mamalis Andrew , Isseroff Roslyn Rivkah , Ma’ayan Avi , Maverakis Emanual , Jagdeo Jared
Published: April 2021

Fibrosis occurs when collagen deposition and fibroblast proliferation replace healthy tissue. Red light (RL) may improve skin fibrosis via photobiomodulation, the process by which photosensitive chromophores in cells absorb visible or near-infrared light and undergo photophysical reactions. Our previous research demonstrated that high fluence RL reduces fibroblast proliferation, collagen deposition, and migration. Despite the identification of several cellular mechanisms underpinning RL phototherapy, little is known about the transcriptional changes that lead to anti-fibrotic cellular responses. Herein, RNA sequencing was performed on human dermal fibroblasts treated with RL phototherapy. Pathway enrichment and transcription factor analysis revealed regulation of extracellular matrices, proliferation, and cellular responses to oxygen-containing compounds following RL phototherapy. Specifically, RL phototherapy increased the expression ofMMP1, which codes for matrix metalloproteinase-1 (MMP-1) and is responsible for remodeling extracellular collagen. Differential regulation ofMMP1was confirmed with RT-qPCR and ELISA. Additionally, RL upregulatedPRSS35,which has not been previously associated with skin activity, but has known anti-fibrotic functions. Our results suggest that RL may benefit patients by altering fibrotic gene expression.
Flow virometry for process monitoring of live virus vaccines-lessons learned from ERVEBO
Authors: Ricci Geoffri , Minsker Kevin , Kapish Austin , Osborn James , Ha Sha , Davide Joseph , Califano Joseph P. , Sehlin Darrell , Rustandi Richard R. , Dick Lawrence W. , Vlasak Josef , Culp Timothy D. , Baudy Andreas , Bell Edward , Mukherjee Malini
Published: April 2021

Direct at line monitoring of live virus particles in commercial manufacturing of vaccines is challenging due to their small size. Detection of malformed or damaged virions with reduced potency is rate-limited by release potency assays with long turnaround times. Thus, preempting batch failures caused by out of specification potency results is almost impossible. Much needed are in-process tools that can monitor and detect compromised viral particles in live-virus vaccines (LVVs) manufacturing based on changes in their biophysical properties to provide timely measures to rectify process stresses leading to such damage. Using ERVEBO, MSD’s Ebola virus vaccine as an example, here we describe a flow virometry assay that can quickly detect damaged virus particles and provide mechanistic insight into process parameters contributing to the damage. Furthermore, we describe a 24-h high throughput infectivity assay that can be used to correlate damaged particles directly to loss in viral infectivity (potency) in-process. Collectively, we provide a set of innovative tools to enable rapid process development, process monitoring, and control strategy implementation in large scale LVV manufacturing.
Salmonella Typhi and Salmonella Paratyphi prevalence, antimicrobial susceptibility profile and factors associated with enteric fever infection in Bahir Dar, Ethiopia
Authors: Amsalu Tadele , Genet Chalachew , Adem Siraj Yesuf
Published: April 2021

Enteric fever (EF) is caused by Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi (S. Paratyphi) causing significant health problems in developing countries including Ethiopia. Thus present study aimed to determine prevalence and antimicrobial resistance profile of S. Typhi and S. Paratyphi among EF suspected patients at Felege-Hiwot comprehensive specialized hospital, Bahir Dar, Ethiopia. Hospital based cross-sectional study was conducted from March-to-May 2020. Totally, 150 patients were included conveniently. Data were collected using questionnaires by face-to-face interview. Concurrently, venous blood and stool specimens were collected and processed following standard bacteriological technique. Antimicrobial susceptibility test (AST) was performed by disc diffusion method. Logistic regression was performed to identify factors associated with EF infection. The study indicated 5.3% EF prevalence where S. Typhi accounted 75%. S. Typhi and S. Paratyphi isolates were 100% sensitive to cephalosporins but at least 83.3% showed resistance against chloramphenicol and tetracycline. At least 66.7% of isolates were multidrug resistance (MDR). Using well water for drinking (AOR = 6.22, CI 1.4–27.5) and previous EF history (AOR = 10.74, CI 2.01–55.9) were significantly associated with EF infection. Thus high bacterial prevalence and MDR isolates was observed. Therefore, health professionals should consider AST and use antibiotics with cautions for EF patient management.
Neuroimaging of depression with diffuse optical tomography during repetitive transcranial magnetic stimulation
Authors: Jiang Shixie , Huang Jingyu , Yang Hao , Wagoner Ryan , Kozel F. Andrew , Currier Glenn , Jiang Huabei
Published: April 2021

Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for depression; however, its potential has likely been hindered due to non-optimized targeting, unclear ideal stimulation parameters, and lack of information regarding how the brain is physiologically responding during and after stimulation. While neuroimaging is ideal for obtaining such critical information, existing modalities have been limited due to poor resolutions, along with significant noise interference from the electromagnetic spectrum. In this study, we used a novel diffuse optical tomography (DOT) device in order to advance our understanding of the neurophysiological effects of rTMS in depression. Healthy and depressed subjects aged 18–70 were recruited. Treatment parameters were standardized with targeting of the left dorsolateral prefrontal cortex with a magnetic field intensity of 100% of motor threshold, pulse frequency of 10 per second, a 4 s stimulation time and a 26 s rest time. DOT imaging was simultaneously acquired from the contralateral dorsolateral prefrontal cortex. Six healthy and seven depressed subjects were included for final analysis. Hemoglobin changes and volumetric three-dimensional activation patterns were successfully captured. Depressed subjects were observed to have a delayed and less robust response to rTMS with a decreased volume of activation compared to healthy subjects. In this first-in-human study, we demonstrated the ability of DOT to safely and reliably capture and compare cortical response patterns to rTMS in depressed and healthy subjects. We introduced this emerging optical functional imaging modality as a novel approach to investigating targeting, new treatment parameters, and physiological effects of rTMS in depression.
Comparison of penetrating femtosecond laser-assisted astigmatic keratotomy and toric intraocular lens implantation for correction of astigmatism in cataract surgery
Authors: Noh Hoon , Yoo Young-Sik , Shin Kyoung Yoon , Lim Dong Hui , Chung Tae-Young
Published: April 2021

This study tried to compare the clinical outcomes of femtosecond laser-assisted astigmatic keratotomy (FSAK) and toric intraocular lens (IOL) implantation for astigmatism correction and identify factors affecting the efficacy of FSAK and toric IOL implantation in astigmatism correction. This retrospective case series comprised patients with corneal astigmatism ranging between 0.5 D and 4.5 D. Patients underwent FSAK or toric IOL implantation for cataract treatment and correction of astigmatism at the Samsung Medical Center, a tertiary surgical center, between April 2016 and December 2018. All patients underwent examination before and at three months after the surgery for comparative evaluation of refractive astigmatism, corneal high order aberrations and irregularity index. The astigmatism correction was analyzed by the Alpins method. Subgroup analysis of preoperative factors was based on the extent of target-induced astigmatism (TIA), the degree of astigmatism, and astigmatism classification based on topography. Thirty-one eyes underwent toric IOL implantation and 35 eyes underwent FSAK. The refractive astigmatism was significantly decreased in both toric IOL (P = 0.000) and FSAK group (P = 0.003). The correction index (CI) of refractive astigmatism was 0.84 ± 0.39 in the toric IOL and 0.71 ± 0.60 in the FSAK group. There was no difference between the two groups (P = 0.337). The CI of the FSAK group was significantly lower than in the toric IOL group when TIA was more than 1.5 D (P = 0.006), when correcting against-the-rule (P = 0.017), and limbus-to-limbus astigmatism (P = 0.008). In conclusion, toric IOL implantation is an effective and safe procedure for correcting preoperative astigmatism in cataract surgery in the short-term observation.
Multimodal synergisms in host stimuli drive landing response in malaria mosquitoes
Authors: Carnaghi Manuela , Belmain Steven R. , Hopkins Richard J. , Hawkes Frances M.
Published: April 2021

Anophelesmosquitoes transmit malaria, which affects one-fifth of the world population. A comprehensive understanding of mosquito behaviour is essential for the development of novel tools for vector control and surveillance. Despite abundant research on mosquito behaviour, little is known on the stimuli that drive malaria vectors during the landing phase of host-seeking. Using behavioural assays with a multimodal step approach we quantified both the individual and the combined effect of three host-associated stimuli in eliciting landing inAnopheles coluzziifemales. We demonstrated that visual, olfactory and thermal sensory stimuli interact synergistically to increase the landing response. Furthermore, if considering only the final outcome (i.e. landing response), our insect model can bypass the absence of either a thermal or a visual stimulus, provided that at least one of these is presented simultaneously with the olfactory stimuli, suggesting that landing is the result of a flexible but accurate stimuli integration. These results have important implications for the development of mosquito control and surveillance tools.
Muscle allele-specific expression QTLs may affect meat quality traits in Bos indicus
Authors: Bruscadin Jennifer Jessica , de Souza Marcela Maria , de Oliveira Karina Santos , Rocha Marina Ibelli Pereira , Afonso Juliana , Cardoso Tainã Figueiredo , Zerlotini Adhemar , Coutinho Luiz Lehmann , Niciura Simone Cristina Méo , de Almeida Regitano Luciana Correia
Published: April 2021

Single nucleotide polymorphisms (SNPs) located in transcript sequences showing allele-specific expression (ASE SNPs) were previously identified in the Longissimus thoracis muscle of a Nelore (Bos indicus) population consisting of 190 steers. Given that the allele-specific expression pattern may result from cis-regulatory SNPs, called allele-specific expression quantitative trait loci (aseQTLs), in this study, we searched for aseQTLs in a window of 1 Mb upstream and downstream from each ASE SNP. After this initial analysis, aiming to investigate variants with a potential regulatory role, we further screened our aseQTL data for sequence similarity with transcription factor binding sites and microRNA (miRNA) binding sites. These aseQTLs were overlapped with methylation data from reduced representation bisulfite sequencing (RRBS) obtained from 12 animals of the same population. We identified 1134 aseQTLs associated with 126 different ASE SNPs. For 215 aseQTLs, one allele potentially affected the affinity of a muscle-expressed transcription factor to its binding site. 162 aseQTLs were predicted to affect 149 miRNA binding sites, from which 114 miRNAs were expressed in muscle. Also, 16 aseQTLs were methylated in our population. Integration of aseQTL with GWAS data revealed enrichment for traits such as meat tenderness, ribeye area, and intramuscular fat . To our knowledge, this is the first report of aseQTLs identification in bovine muscle. Our findings indicate that various cis-regulatory and epigenetic mechanisms can affect multiple variants to modulate the allelic expression. Some of the potential regulatory variants described here were associated with the expression pattern of genes related to interesting phenotypes for livestock. Thus, these variants might be useful for the comprehension of the genetic control of these phenotypes.
Environmental chemicals in dog testes reflect their geographical source and may be associated with altered pathology
Authors: Sumner Rebecca N. , Byers Andrew , Zhang Zulin , Agerholm Jorgen S. , Lindh Lena , England Gary C. W. , Lea Richard G.
Published: April 2021

In humans and dogs, a temporal decline in semen quality and increased incidence of testicular cancer is hypothesised to be associated with exposure to anthropogenic chemicals, particularly during fetal development. Human studies suggest that differential exposures to environmental chemicals may be associated with geographical differences in male reproductive health. Here we investigate testicular chemical profiles and pathologies in dogs residing in the UK [West Midlands (WM), East Midlands (EM), South East (SE)], Denmark (Copenhagen) and Finland (Vantaa). Testes, surplus from routine castrations, contained region specific differences in relative concentrations of diethylhexyl phthalate (DEHP), polybrominated diphenyl ethers (PBDE) and polychlorinated biphenyls (PCB). Relative to UK regions, testes from dogs living in Finland and Denmark had higher concentrations of PBDE and lower concentrations of DEHP and PCBs. Regional differences in the UK in PCB concentrations were also observed. Dog testes from Finland had fewer pathologies, reduced testicular area stained for Sertoli and germ cells and evidence of reduced cellular proliferation. Since the geographical differences in testis pathologies in dogs parallel reports of regional differences in human testicular cancer, we postulate that this may reflect chemical effects within the testis and that this may be related to environmental influences on male reproductive function.
Insights into extrinsic foot muscle activation during a 75 min run using T2 mapping
Authors: Bratke Grischa , Willwacher Steffen , Siedek Florian , Maintz David , Mählich Daniela , Weiss Kilian , Hickethier Tilman , Brüggemann Gert-Peter
Published: April 2021

The extrinsic foot muscles are essentially for controlling the movement path but our knowledge of their behavior during prolonged running is still very limited. Therefore, this study analyzed the time-course of muscle activation using T2 mapping during 75 min of running. In this prospective study, 19 recreational active runners completed 75 min of treadmill running at a constant speed. Interleaved T2 mapping sequences were acquired and segmented at timepoints 0, 2.5, 5, 10, 15, 45, and 75 min. ANOVA for repeated measurements followed by a Tukey post hoc test and Pearson correlation between running speed and initial signal increase at 2.5 min were calculated. All muscles showed a significant signal increase between baseline and 2.5 min (e.g. medial gastrocnemius: + 15.48%; p < 0.01). This was followed by a plateau phase till 15 min for all but the extensor digitorum longus muscle and a significant decrease at 45 or 75 min for all muscles (all p < 0.05). Correlation between running speed and signal increase was negative for all muscles and significant for both gastrocnemii (e.g. medial: r =  − 0.57, p = 0.0104) and soleus (r =  − 0.47, p = 0.0412). The decrease of relaxation times times in the later running phases was less pronounced for faster runners (≥ 10 km/h). T2 relaxation times do not only decrease after cessation of exercise but already during prolonged running. The lesser initial increase and later decrease in faster runners may indicate training induced changes.
Impact of water–rock interaction on the pore structures of red-bed soft rock
Authors: Zhou Meiling , Li Jianlin , Luo Zuosen , Sun Jianbin , Xu Feng , Jiang Qiao , Deng Huafeng
Published: April 2021

The physical and mechanical properties of the reservoir bank slope are affected by the water–rock interaction. However, few studies considered the impact of long-term water–rock interaction on the evolution law of mesostructure. Therefore, in this study, the water–rock interaction test was conducted on a slightly weathered red-bed soft rock from the Three Gorges Reservoir area, considering the fluctuation in the reservoir water level. The corresponding pore structure parameters were measured and analyzed based on a scanning electron microscope (SEM) and digital image processing technology. The study showed that: (1) The pore size has been gradually increased, while the number of pores was increased initially and then decreased. Within 12 cycles, the maximum and average pore radius of the rock specimens was increased by 101.02% and 43.32%, respectively, and the porosity has been increased by 26.59%, whereas the number of pores decreased by 22.65%. This indicates the effect of water–rock interaction on the propagation of pores. (2) The pores were changed from oblate to slender by the water–rock interaction. The shape factor was decreased by about 15.79% within 12 cycles. In the meantime, the fractal dimension was increased from 1.20 to 1.28, and more complex structures of pores were observed. (3) The porosity evolution model for the red-bed soft rock was established based on the curve fitting technique. The results can be used as a reference to conceptualize the mesostructure damage of rocks under water–rock interaction.
Cost-effectiveness of CYP2C19 genotyping to guide antiplatelet therapy for acute minor stroke and high-risk transient ischemic attack
Authors: Cai Zeling , Cai De , Wang Ruiwen , Wang Heng , Yu Ze , Gao Fei , Liu Yuansheng , Kang Yingbo , Wu Zhuomin
Published: April 2021

Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin within 48 h of acute minor strokes and transient ischemic attacks (TIAs) has been indicated to effectively reduce the rate of recurrent strokes. However, the efficacy of clopidogrel has been shown to be affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. Patients carrying loss-of-function alleles (LoFAs) at a low risk of recurrence (ESRS < 3) cannot benefit from clopidogrel plus aspirin at all and may have an increased bleeding risk. In order to optimize antiplatelet therapy for these patients and avoid the waste of medical resources, it is important to identify the subgroups that genuinely benefit from DAPT with clopidogrel plus aspirin through CYP2C19 genotyping. This study sought to assess the cost-effectiveness of CYP2C19 genotyping to guide drug therapy for acute minor strokes or high-risk TIAs in China. A decision tree and Markov model were constructed to evaluate the cost-effectiveness of CYP2C19 genotyping. We used a healthcare payer perspective, and the primary outcomes included quality-adjusted life years (QALYs), costs and the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to evaluate the robustness of the results. CYP2C19 genotyping resulted in a lifetime gain of 0.031 QALYs at an additional cost of CNY 420.13 (US$ 59.85), yielding an ICER of CNY 13,552.74 (US$ 1930.59) per QALY gained. Probabilistic sensitivity analysis showed that genetic testing was more cost-effective in 95.7% of the simulations at the willingness-to-pay threshold of CNY 72,100 (GDP per capita, US$ 10,300) per QALY. Therefore, CYP2C19 genotyping to guide antiplatelet therapy for acute minor strokes and high-risk TIAs is highly cost-effective in China.
Evaluation of organ glucose metabolism by 18F-FDG accumulation with insulin loading in aged mice compared with young normal mice
Authors: Zhao Jingmin , Tan Chengbo , Imai Ryota , Ukon Naoyuki , Shimoyama Saki , Maejima Yuko , Omiya Yuji , Takahashi Kazuhiro , Ito Hiroshi , Nan Guangxian , Zhao Songji , Shimomura Kenju
Published: April 2021

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-d-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.
Head movement differs for positive and negative emotions in video recordings of sitting individuals
Authors: Behnke Maciej , Bianchi-Berthouze Nadia , Kaczmarek Lukasz D.
Published: April 2021

Individuals tend to approach positive stimuli and avoid negative stimuli. Furthermore, emotions influence whether individuals freeze or move more. These two kinds of motivated behavior refer to the approach/avoidance behavior and behavioral freezing/activation. Previous studies examined (e.g., using forced platforms) whether individuals' behavior depends on stimulus' valence; however, the results were mixed. Thus, we aimed to test whether emotions' effects on spontaneous whole-body behavior of standing individuals also occur in the seated position. We used a computer vision method to measure the head sway in video recordings that offers ease of use, replicability, and unobtrusiveness for the seated research participant. We analyzed behavior recorded in the laboratory during emotion manipulations across five studies totaling 932 participants. We observed that individuals leaned more forward and moved more when watching positive stimuli than when watching negative stimuli. However, individuals did not behave differently when watching positive or negative stimuli than in the neutral condition. Our results indicate that head movements extracted from seated individuals' video recordings can be useful in detecting robust differences in emotional behavior (positive vs. negative emotions).
Hospitalization rates for complications due to systemic therapy in the United States
Authors: Saxena Anshul , Rubens Muni , Ramamoorthy Venkataraghavan , Tonse Raees , Veledar Emir , McGranaghan Peter , Sundil Subrina , Chuong Michael D. , Hall Matthew D. , Odia Yazmin , Mehta Minesh P. , Kotecha Rupesh
Published: April 2021

The aim of this study was to estimate the trends and burdens associated with systemic therapy-related hospitalizations, using nationally representative data. National Inpatient Sample data from 2005 to 2016 was used to identify systemic therapy-related complications using ICD-9 and ICD-10 external causes-of-injury codes. The primary outcome was hospitalization rates, while secondary outcomes were cost and in-hospital mortality. Overall, there were 443,222,223 hospitalizations during the study period, of which 2,419,722 were due to complications of systemic therapy. The average annual percentage change of these hospitalizations was 8.1%, compared to − 0.5% for general hospitalizations. The three most common causes for hospitalization were anemia (12.8%), neutropenia (10.8%), and sepsis (7.8%). Hospitalization rates had the highest relative increases for sepsis (1.9-fold) and acute kidney injury (1.6-fold), and the highest relative decrease for dehydration (0.21-fold) and fever of unknown origin (0.35-fold). Complications with the highest total charges were anemia ($4.6 billion), neutropenia ($3.0 billion), and sepsis ($2.5 billion). The leading causes of in-hospital mortality associated with systemic therapy were sepsis (15.8%), pneumonia (7.6%), and acute kidney injury (7.0%). Promoting initiatives such as rule OP-35, improving access to and providing coordinated care, developing systems leading to early identification and management of symptoms, and expanding urgent care access, can decrease these hospitalizations and the burden they carry on the healthcare system.
Assessment of genetic diversity and structure of Bambara groundnut [Vigna subterranea (L.) verdc.] landraces in South Africa
Authors: Minnaar-Ontong Adré , Gerrano Abe S. , Labuschagne Maryke T.
Published: April 2021

With its drought tolerant and protein-rich properties, Bambara groundnut [Vigna subterranea (L.) Verdc.], an indigenous African legume crop can contribute immensely to food security. This miracle crop is used as food and for the enhancement of soil fertility in South Africa. Knowledge on the genetic diversity and structure among the Bambara groundnut landraces can pave the way for the effective use and cultivation of this crop in southern Africa, especially South Africa. The aim of this study was to assess the genetic diversity and structure among Bambara groundnut landraces collected across South Africa and compared to a limited number of accessions from southern Africa using SSR markers. Seventy-eight Bambara groundnut accessions were genotyped using 19 Bambara specific SSR markers. SSR loci explored in this study, were all polymorphic. A total of 127 alleles were detected with a mean of 6.7 alleles per locus. Allele diversity and frequency among genotypes varied from 0.21 to 0.85 with an average of 0.62 per locus. Genetic variation as described by the analysis of molecular variance indicated higher genetic diversity (92%) within landraces than between (8%) different landraces. Population structure analysis showed that three subpopulations existed, and most of the South African accessions were restricted to one subpopulation, indicating that Bambara landraces has the ability to form unique haplotypes in different environments. Information harnessed in this study is helpful for further use in breeding programs for crop improvement.
Author Correction: VHS, US3 and UL13 viral tegument proteins are required for Herpes Simplex Virus-Induced modification of protein kinase R
Authors: Pennisi Rosamaria , Musarra-Pizzo Maria , Lei Zhixiang , Zhou Grace Guoying , Sciortino Maria Teresa
Published: April 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Physical properties of porphyrin-based crystalline metal‒organic frameworks
Authors: Rajasree Sreehari Surendran , Li Xinlin , Deria Pravas
Published: April 2021

Metal‒organic frameworks (MOFs) are widely studied molecular assemblies that have demonstrated promise for a range of potential applications. Given the unique and well-established photophysical and electrochemical properties of porphyrins, porphyrin-based MOFs are emerging as promising candidates for energy harvesting and conversion applications. Here we discuss the physical properties of porphyrin-based MOFs, highlighting the evolution of various optical and electronic features as a function of their modular framework structures and compositional variations.
Control of nuclear dynamics in the benzene cation by electronic wavepacket composition
Authors: Tran Thierry , Worth Graham A. , Robb Michael A.
Published: April 2021

The study of coupled electron-nuclear dynamics driven by coherent superpositions of electronic states is now possible in attosecond science experiments. The objective is to understand the electronic control of chemical reactivity. In this work we report coherent 8-state non-adiabatic electron-nuclear dynamics simulations of the benzene radical cation. The computations were inspired by the extreme ultraviolet (XUV) experimental results in which all 8 electronic states were prepared with significant population. Our objective was to study the nuclear dynamics using various bespoke coherent electronic state superpositions as initial conditions in the Quantum-Ehrenfest method. The original XUV measurements were supported by Multi-configuration time-dependent Hartree (MCTDH) simulations, which suggested a model of successive passage through conical intersections. The present computations support a complementary model where non-adiabatic events are seen far from a conical intersection and are controlled by electron dynamics involving non-adjacent adiabatic states. It proves to be possible to identify two superpositions that can be linked with two possible fragmentation paths.