bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical assessment on neuronal regeneration in the injury-related microenvironment of graphene-based scaffolds
Authors: Qian Yun , Wang Xu , Song Jialin , Chen Wei , Chen Shuai , Jin Yi , Ouyang Yuanming , Yuan Wei-En , Fan Cunyi
Published: June 2021

As the application of graphene nanomaterials gets increasingly attractive in the field of tissue engineering and regenerative medicine, the long-term evaluation is necessary and urgent as to their biocompatibility and regenerative capacity in different tissue injuries, such as nerve, bone, and heart. However, it still remains controversial about the potential biological effects of graphene on neuronal activity, especially after severe nerve injuries. In this study, we establish a lengthy peripheral nerve defect rat model and investigate the potential toxicity of layered graphene-loaded polycaprolactone scaffold after implantation during 18 months in vivo. In addition, we further identify possible biologically regenerative effects of this scaffold on myelination, axonal outgrowth, and locomotor function recovery. It is confirmed that graphene-based nanomaterials exert negligible toxicity and repair large nerve defects by dual regulation of Schwann cells and astroglia in the central and peripheral nervous systems. The findings enlighten the future of graphene nanomaterial as a key type of biomaterials for clinical translation in neuronal regeneration.
Change by challenge: A common genetic basis behind childhood cognitive development and cognitive training
Authors: Sauce Bruno , Wiedenhoeft John , Judd Nicholas , Klingberg Torkel
Published: June 2021

The interplay of genetic and environmental factors behind cognitive development has preoccupied multiple fields of science and sparked heated debates over the decades. Here we tested the hypothesis that developmental genes rely heavily on cognitive challenges—as opposed to natural maturation. Starting with a polygenic score (cogPGS) that previously explained variation in cognitive performance in adults, we estimated its effect in 344 children and adolescents (mean age of 12 years old, ranging from 6 to 25) who showed changes in working memory (WM) in two distinct samples: (1) a developmental sample showing significant WM gains after 2 years of typical, age-related development, and (2) a training sample showing significant, experimentally-induced WM gains after 25 days of an intense WM training. We found that the same genetic factor, cogPGS, significantly explained the amount of WM gain in both samples. And there was no interaction of cogPGS with sample, suggesting that those genetic factors are neutral to whether the WM gains came from development or training. These results represent evidence that cognitive challenges are a central piece in the gene-environment interplay during cognitive development. We believe our study sheds new light on previous findings of interindividual differences in education (rich-get-richer and compensation effects), brain plasticity in children, and the heritability increase of intelligence across the lifespan.
Alterations in lipid profile upon uterine fibroids and its recurrence
Authors: Tonoyan Narine M. , Chagovets Vitaliy V. , Starodubtseva Natalia L. , Tokareva Alisa O. , Chingin Konstantin , Kozachenko Irena F. , Adamyan Leyla V. , Frankevich Vladimir E.
Published: June 2021

Uterine fibroids (UF) is the most common (about 70% cases) type of gynecological disease, with the recurrence rate varying from 11 to 40%. Because UF has no distinct symptomatology and is often asymptomatic, the specific and sensitive diagnosis of UF as well as the assessment for the probability of UF recurrence pose considerable challenge. The aim of this study was to characterize alterations in the lipid profile of tissues associated with the first-time diagnosed UF and recurrent uterine fibroids (RUF) and to explore the potential of mass spectrometry (MS) lipidomics analysis of blood plasma samples for the sensitive and specific determination of UF and RUF with low invasiveness of analysis. MS analysis of lipid levels in the myometrium tissues, fibroids tissues and blood plasma samples was carried out on 66 patients, including 35 patients with first-time diagnosed UF and 31 patients with RUF. The control group consisted of 15 patients who underwent surgical treatment for the intrauterine septum. Fibroids and myometrium tissue samples were analyzed using direct MS approach. Blood plasma samples were analyzed using high performance liquid chromatography hyphened with mass spectrometry (HPLC/MS). MS data were processed by discriminant analysis with projection into latent structures (OPLS-DA). Significant differences were found between the first-time UF, RUF and control group in the levels of lipids involved in the metabolism of glycerophospholipids, sphingolipids, lipids with an ether bond, triglycerides and fatty acids. Significant differences between the control group and the groups with UF and RUF were found in the blood plasma levels of cholesterol esters, triacylglycerols, (lyso) phosphatidylcholines and sphingomyelins. Significant differences between the UF and RUF groups were found in the blood plasma levels of cholesterol esters, phosphotidylcholines, sphingomyelins and triacylglycerols. Diagnostic models based on the selected differential lipids using logistic regression showed sensitivity and specificity of 88% and 86% for the diagnosis of first-time UF and 95% and 79% for RUF, accordingly. This study confirms the involvement of lipids in the pathogenesis of uterine fibroids. A diagnostically significant panel of differential lipid species has been identified for the diagnosis of UF and RUF by low-invasive blood plasma analysis. The developed diagnostic models demonstrated high potential for clinical use and further research in this direction.
Greater genetic risk for adult psychiatric diseases increases vulnerability to adverse outcome after preterm birth
Authors: Cullen Harriet , Selzam Saskia , Dimitrakopoulou Konstantina , Plomin Robert , Edwards A. David
Published: June 2021

Preterm birth is an extreme environmental stress associated with an increased risk of later cognitive dysfunction and mental health problems. However, the extent to which preterm birth is modulated by genetic variation remains largely unclear. Here, we test for an interaction effect between psychiatric polygenic risk and gestational age at birth on cognition at age four. Our sample comprises 4934 unrelated individuals (2066 individuals born < 37 weeks, 918 born <  = 34 weeks). Genome-wide polygenic scores (GPS’s) were calculated for each individual for five different psychiatric pathologies: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder. Linear regression modelling was used to estimate the interaction effect between psychiatric GPS and gestational age at birth (GA) on cognitive outcome for the five psychiatric disorders. We found a significant interaction effect between Schizophrenia GPS and GA (β = 0.038 ± 0.013, p = 6.85 × 10–3) and Bipolar Disorder GPS and GA (β = 0.038 ± 0.014, p = 6.61 × 10–3) on cognitive outcome. Individuals with greater genetic risk for Schizophrenia or Bipolar Disorder are more vulnerable to the adverse effects of birth at early gestational age on brain development, as assessed by cognition at age four. Better understanding of gene-environment interactions will inform more effective risk-reducing interventions for this vulnerable population.
Genomic analysis and phylogenetic position of the complex IncC plasmid found in the Spanish monophasic clone of Salmonella enterica serovar Typhimurium
Authors: Vázquez Xenia , García Patricia , García Vanesa , de Toro María , Ladero Víctor , Heinisch Jürgen J. , Fernández Javier , Rodicio Rosaura , Rodicio M. Rosario
Published: June 2021

pUO-STmRV1 is an IncC plasmid discovered in the Spanish clone of the emergent monophasic variant of Salmonella enterica serovar Typhimurium, which has probably contributed to its epidemiological success. The sequence of the entire plasmid determined herein revealed a largely degenerated backbone with accessory DNA incorporated at four different locations. The acquired DNA constitutes more than two-thirds of the pUO-STmRV1 genome and originates from plasmids of different incompatibility groups, including IncF (such as R100 and pSLT, the virulence plasmid specific of S. Typhimurium), IncN and IncI, from the integrative element GIsul2, or from yet unknown sources. In addition to pSLT virulence genes, the plasmid carries genes conferring resistance to widely-used antibiotics and heavy metals, together with a wealth of genetic elements involved in DNA mobility. The latter comprise class 1 integrons, transposons, pseudo-transposons, and insertion sequences, strikingly with 14 copies of IS26, which could have played a crucial role in the assembly of the complex plasmid. Typing of pUO-STmRV1 revealed backbone features characteristically associated with type 1 and type 2 IncC plasmids and could therefore be regarded as a hybrid plasmid. However, a rooted phylogenetic tree based on core genes indicates that it rather belongs to an ancient lineage which diverged at an early stage from the branch leading to most extant IncC plasmids detected so far. pUO-STmRV1 may have evolved at a time when uncontrolled use of antibiotics and biocides favored the accumulation of multiple resistance genes within an IncC backbone. The resulting plasmid thus allowed the Spanish clone to withstand a wide variety of adverse conditions, while simultaneously promoting its own propagation through vertical transmission.
57Fe and 151Eu Mössbauer studies of 3d-4f spin interplay in EuFe2−xNixAs2
Authors: Komędera K. , Gatlik J. , Błachowski A. , Żukrowski J. , Rybicki D. , Delekta A. , Babij M. , Bukowski Z.
Published: June 2021

The EuFe2−xNixAs2 (with 0 ≤ x ≤ 0.4) compounds exhibiting 3d and/or 4f magnetic order were investigated by means of 57Fe and 151Eu Mössbauer spectroscopy. Additionally, results for EuNi2As2 are reported for comparison. It was found that spin-density-wave order of the Fe itinerant moments is monotonically suppressed by Ni-substitution. However, the 3d magnetic order survives at the lowest temperature up to at least x = 0.12 and it is certainly completely suppressed for x = 0.20. The Eu localized moments order regardless of the Ni concentration, but undergo a spin reorientation with increasing x from alignment parallel to the a-axis in the parent compound, toward c-axis alignment for x > 0.07. Change of the 4f spins ordering from antiferromagnetic to ferromagnetic takes place simultaneously with a disappearance of the 3d spins order what is the evidence of a strong coupling between magnetism of Eu2+ ions and the conduction electrons of [Fe2−xNixAs2]2- layers. The Fe nuclei experience the transferred hyperfine magnetic field due to the Eu2+ ordering for Ni-substituted samples with x > 0.04, while the transferred field is undetectable in EuFe2As2 and for compound with a low Ni-substitution level. It seems that the 4f ferromagnetic component arising from a tilt of the Eu2+ moments to the crystallographic c-axis leads to the transferred magnetic field at the Fe atoms. Superconductivity is not observed down to 1.8 K, although a comparison with 57Fe and 151Eu Mössbauer data for EuFe2As2-based superconductors indicates a similar magnetic structure.
Functional and structural ophthalmic imaging using noncontact multimodal photoacoustic remote sensing microscopy and optical coherence tomography
Authors: Hosseinaee Zohreh , Nima Abbasi  , Pellegrino Nicholas , Khalili Layla , Mukhangaliyeva Lyazzat , Haji Reza Parsin
Published: June 2021

Early diagnosis of ocular diseases improves the understanding of pathophysiology and aids in accurate monitoring and effective treatment. Advanced, multimodal ocular imaging platforms play a crucial role in visualization of ocular components and provide clinicians with a valuable tool for evaluating various eye diseases. Here, for the first time we present a non-contact, multiwavelength photoacoustic remote sensing (PARS) microscopy and swept-source optical coherence tomography (SS-OCT) for in-vivo functional and structural imaging of the eye. The system provides complementary imaging contrasts of optical absorption and optical scattering, and is used for simultaneous, non-contact, in-vivo imaging of murine eye. Results of vasculature and structural imaging as well as melanin content in the retinal pigment epithelium layer are presented. Multiwavelength PARS microscopy using Stimulated Raman scattering is applied to enable in-vivo, non-contact oxygen saturation estimation in the ocular tissue. The reported work may be a major step towards clinical translation of ophthalmic technologies and has the potential to advance the diagnosis and treatment of ocular diseases.
Relationship between gene regulation network structure and prediction accuracy in high dimensional regression
Authors: Okinaga Yuichi , Kyogoku Daisuke , Kondo Satoshi , Nagano Atsushi J. , Hirose Kei
Published: June 2021

The least absolute shrinkage and selection operator (lasso) and principal component regression (PCR) are popular methods of estimating traits from high-dimensional omics data, such as transcriptomes. The prediction accuracy of these estimation methods is highly dependent on the covariance structure, which is characterized by gene regulation networks. However, the manner in which the structure of a gene regulation network together with the sample size affects prediction accuracy has not yet been sufficiently investigated. In this study, Monte Carlo simulations are conducted to investigate the prediction accuracy for several network structures under various sample sizes. When the gene regulation network is a random graph, a sufficiently large number of observations are required to ensure good prediction accuracy with the lasso. The PCR provided poor prediction accuracy regardless of the sample size. However, a real gene regulation network is likely to exhibit a scale-free structure. In such cases, the simulation indicates that a relatively small number of observations, such as$$N=300$$N=300, is sufficient to allow the accurate prediction of traits from a transcriptome with the lasso.
KAUST Metagenomic Analysis Platform (KMAP), enabling access to massive analytics of re-annotated metagenomic data
Authors: Alam Intikhab , Kamau Allan Anthony , Ngugi David Kamanda , Gojobori Takashi , Duarte Carlos M. , Bajic Vladimir B.
Published: June 2021

Exponential rise of metagenomics sequencing is delivering massive functional environmental genomics data. However, this also generates a procedural bottleneck for on-going re-analysis as reference databases grow and methods improve, and analyses need be updated for consistency, which require access to increasingly demanding bioinformatic and computational resources. Here, we present the KAUST Metagenomic Analysis Platform (KMAP), a new integrated open web-based tool for the comprehensive exploration of shotgun metagenomic data. We illustrate the capacities KMAP provides through the re-assembly of ~ 27,000 public metagenomic samples captured in ~ 450 studies sampled across ~ 77 diverse habitats. A small subset of these metagenomic assemblies is used in this pilot study grouped into 36 new habitat-specific gene catalogs, all based on full-length (complete) genes. Extensive taxonomic and gene annotations are stored in Gene Information Tables (GITs), a simple tractable data integration format useful for analysis through command line or for database management. KMAP pilot study provides the exploration and comparison of microbial GITs across different habitats with over 275 million genes. KMAP access to data and analyses is available at https://www.cbrc.kaust.edu.sa/aamg/kmap.start.
Use of antimicrobials and antimicrobial resistance in Nepal: a nationwide survey
Authors: Rijal Komal Raj , Banjara Megha Raj , Dhungel Binod , Kafle Samarpan , Gautam Kedar , Ghimire Bindu , Ghimire Prabina , Dhungel Samriddh , Adhikari Nabaraj , Shrestha Upendra Thapa , Sunuwar Dev Ram , Adhikari Bipin , Ghimire Prakash
Published: June 2021

Nepal suffers from high burden of antimicrobial resistance (AMR) due to inappropriate use of antibiotics. The main objective of this study was to explore knowledge, attitude and practices of antibiotics uses among patients, healthcare workers, laboratories, drug sellers and farmers in eight districts of Nepal. A cross-sectional survey was conducted between April and July 2017. A total of 516 individuals participated in a face-to-face interview that included clinicians, private drug dispensers, patients, laboratories, public health centers/hospitals and, livestock and poultry farmers. Out of 516 respondents, 62.8% (324/516) were patients, 16.9% (87/516) were clinicians, 6.4% (33/516) were private drug dispensers. A significant proportion of patients (42.9%; 139/324) thought that fever could be treated with antibiotics. Majority (79%; 256/324) of the patients purchased antibiotics over the counter. The knowledge of antibiotics used among patients increased proportionately with the level of education: literate only [AOR = 1.4 (95% Cl = 0.6–4.4)], versus secondary education (8–10 grade) [AOR = 1.8 (95% Cl = 1.0–3.4)]. Adult patients were more aware of antibiotic resistance. Use of antibiotics over the counter was found high in this study. Knowledge, attitude and practice related to antibiotic among respondents showed significant gaps and need an urgent effort to mitigate such practice.
Mortality of surgically treated 80-year-old or older intracranial meningioma patients in comparison to matched general population
Authors: Rautalin Ilari , Schwartz Christoph , Niemelä Mika , Korja Miikka
Published: June 2021

Population aging is likely increasing the number of surgically treated very old (≥ 80–year-old) intracranial meningioma (IM) patients. Since there is little data on mortality in this patient group, we studied whether survival of surgically treated very old IM patients differs from survival of a matched general population. We retrospectively identified 83 consecutive very old IM patients (median age 83 years; 69% women) operated between 2010 and 2018. During the first postoperative year, operated IM patients suffered 2.5 times higher mortality as compared to age- and sex-matched general population but no annual survival difference occurred thereafter. Regarding cumulative estimates, no excess mortality was detected after the second postoperative year. Of the patient who were and who were not able to live at home preoperatively, 78% and 42% lived at home within 3 months, respectively. Preoperative loss of capability to live at home associated with a less frequent return to home [odds ratio (95% confidence interval) 0.21 (0.06–0.67)]. Operated very old IM patients had short-term excess mortality but similar cumulative survival as the matched general population. Moreover, most patients returned home soon after surgery.
Synthesis, photocatalytic and antidiabetic properties of ZnO/PVA nanoparticles
Authors: EL-Dafrawy Shady M. , Tarek Mahmoud , Samra Salem , Hassan Shawky M.
Published: June 2021

A series of ZnO and ZnO/poly(vinyl alcohol) (PVA) catalysts were prepared using sol–gel method. An X-ray diffraction analysis confirmed the existence of the wurtzite ZnO phase, and scanning electron microscopy (SEM) observation revealed the formation of spherical ZnO and ZnO/PVA nanoparticles. The decomposition of methylene blue (MB) and methyl orange (MO) induced by the synthesized pure ZnO and ZnO/PVA nanoparticles was studied under ultraviolet–visible irradiation. Among the catalysts evaluated, ZnO/5PVA was the most active in the decomposition of MB, whereas ZnO/7PVA was the most active catalyst in the decomposition of MO. Moreover, an investigation of the biological activity of pure ZnO and ZnO/PVA indicated that ZnO/5PVA exhibited the best performance in lowering the glucose level in diabetic rats.
Analysis of the impact of three phthalates on the freshwater gastropod Physella acuta at the transcriptional level
Authors: Prieto-Amador Marina , Caballero Patricia , Martínez-Guitarte José-Luis
Published: June 2021

Plastic pollution is one of the leading environmental problems. Phthalates are widely used plastic additives released into the environment. Although the effects of phthalates on vertebrates have been extensively studied, there is a knowledge gap regarding their effects on invertebrates. This work analyzes the impact of three phthalates, diethyl phthalate (DEP), benzyl butyl phthalate (BBP), and bis-(2-ethylhexyl) phthalate (DEHP), on the gastropod Physella acuta at the molecular level to establish the putative pathways involved in its response to them. By real-time PCR, we obtained the expression profile of 30 genes in animals exposed for 1 week to 0.1, 10, and 1000 μg/L of each phthalate. The genes cover DNA repair, detoxification, apoptosis, oxidative and stress responses, immunity, energy reserves, and lipid transport. The results show that while DEP and DEHP did not alter the mRNA levels, BBP modulated almost all the analyzed genes. It can be concluded that the impact of BBP is extensive at the molecular level. However, it cannot be dismissed that the increase in transcriptional activity is a general response due to this compound’s well-known role as an endocrine disruptor. Additional research is needed to elucidate the differences observed in the impact of these compounds on the gastropod P. acuta.
Portable rotating grating stimulation for anisometropic amblyopia with 6 months training
Authors: Yeh Wen-Hsiu , Lai Li-Ju , Chang Da-Wei , Lin Wei-Sin , Lin Guan-Ming , Shaw Fu-Zen
Published: June 2021

Treatment of grating stimulation has been used in amblyopia for decades, but high dropout rate and inconvenience for daily practice occur in previous studies. We developed a home-based portable system with rotating grating stimulation on a tablet. Thirty anisometropic amblyopic children were randomly allocated into the control or Grating group. They drew contour of the picture under patch of a better eye for 6 months. Best-corrected visual acuity (BCVA), grating acuity (GA), and contrast sensitivity (CS) were assessed at the baseline, 1st, 2nd, 3rd, and 6th months of training. All participants completed the 6-month training. Patched eyes of both groups exhibited no difference. Trained eyes of the control group had significantly slight improvement in BCVA and GA. In particular, the Grating group exhibited significantly higher BCVA, GA, and CS compared with those of the control group at the 3rd and 6th months of training. Moreover, percentage of the Grating group with great improvement (BCVA ≥ 0.3 or CS ≥ 0.3) was significantly larger than those of the control group at the 3rd or 6th months of training. The portable grating stimulation system demonstrates its trainability by no dropout and effectiveness by significant improvements in all assessments through a well experimental design.

Trial Registration: ClinicalTrials.gov NCT04213066, registered 30/12/2019, https://clinicaltrials.gov/ct2/show/NCT04213066.
Author Correction: Comparable antibacterial effects and action mechanisms of silver and iron oxide nanoparticles on Escherichia coli and Salmonella typhimurium
Authors: Gabrielyan Lilit , Badalyan Hamlet , Gevorgyan Vladimir , Trchounian Armen
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
An analysis of pre-season risk factors for low back injury in high-school baseball pitchers: a prospective study
Authors: Nakase Kurumi , Shitara Hitoshi , Tajika Tsuyoshi , Kuboi Takuro , Ichinose Tsuyoshi , Sasaki Tsuyoshi , Hamano Noritaka , Endo Fumitaka , Kamiyama Masataka , Miyamoto Ryosuke , Yamamoto Atsushi , Kobayashi Tsutomu , Takagishi Kenji , Chikuda Hirotaka
Published: June 2021

Pitching motion requires whole-body coordination; therefore, poor control of the lower extremities, pelvis and trunk may cause shoulder and elbow injuries. However, few studies have described the relationship between the shoulder joint function and low back injury in high-school baseball pitchers. A total of 128 healthy high school pitchers underwent pre-season medical checkups, where their shoulder range of motion and shoulder strength were measured. The participants completed a self-recorded daily questionnaire regarding the presence of low back pain. Pitchers were divided into injured and non-injured groups. Low back injury was observed in 13 participants (13.4%). In the injured group, horizontal adduction on the dominant shoulder was significantly less than in the non-injured group. A logistic regression analysis showed that horizontal adduction on the dominant side was a significant independent risk factor for low back injury during the season. It is important to recognize that restriction of the shoulder function not only causes shoulder and elbow injuries but can also risk low back injury.
Fine scale analysis of malaria incidence in under-5: hierarchical Bayesian spatio-temporal modelling of routinely collected malaria data between 2012–2018 in Cameroon
Authors: Danwang Celestin , Khalil Élie , Achu Dorothy , Ateba Marcelin , Abomabo Moïse , Souopgui Jacob , De Keukeleire Mathilde , Robert Annie
Published: June 2021

The current study aims to provide a fine-scale spatiotemporal estimate of malaria incidence among Cameroonian under-5, and to determine its associated environmental factors, to set up preventive interventions that are adapted to each health district of Cameroon. Routine data on symptomatic malaria in children under-5 collected in health facilities, between 2012 and 2018 were used. The trend of malaria cases was assessed by the Mann–Kendall (M–K) test. A time series decomposition was applied to malaria incidence to extract the seasonal component. Malaria risk was estimated by the standardised incidence ratio (SIR) and smoothed by a hierarchical Bayesian spatiotemporal model. In total, 4,052,216 cases of malaria were diagnosed between 2012 and 2018. There was a gradual increase per year, from 369,178 in 2012 to 652,661 in 2018. After adjusting the data for completeness, the national incidence ranged from 489‰ in 2012 to 603‰ in 2018, with an upward trend (M–K test p-value < 0.001). At the regional level, an upward trend was observed in Adamaoua, Centre without Yaoundé, East, and South regions. There was a positive spatial autocorrelation of the number of malaria incident-cases per district per year as suggested by the Moran’s I test (statistic range between 0.11 and 0.53). The crude SIR showed a heterogeneous malaria risk with values ranging from 0.00 to 8.90, meaning that some health districts have a risk 8.9 times higher than the national annual level. The incidence and risk of malaria among under-5 in Cameroon are heterogeneous and vary significantly across health districts and seasons. It is crucial to adapt malaria prevention measures to the specificities of each health district, in order to reduce its burden in health districts where the trend is upward.
Exposure to air pollution and renal function
Authors: Kuźma Łukasz , Małyszko Jolanta , Bachórzewska-Gajewska Hanna , Kralisz Paweł , Dobrzycki Sławomir
Published: June 2021

Air pollution contributes to the premature death of approximately 428,000 citizens of Europe every year. The adverse effects of air pollution can be observed in respiratory, circulatory systems but also in renal function. We decide to investigate the hypothesis indicating that we can observe not only long- but also short-term impact of air pollution on kidney function. We used linear, log-linear, and logistic regression models to assess the association between renal function and NO2, SO2, and PMs. Results are reported as beta (β) coefficients and odds ratios (OR) for an increase in interquartile range (IQR) concentration. 3554 patients (median age 66, men 53.2%) were included into final analysis. Chronic kidney disease (CKD) was diagnosed in 21.5%. The odds of CKD increased with increase in annual concentration of PM2.5 (OR for IQR increase = 1.07; 95% CI 1.01–1.15, P = 0.037) and NO2 (OR for IQR increase = 1.05; 95% CI 1.01–1.10, P = 0.047). The IQR increase in weekly PM2.5 concentration was associated with 2% reduction in expected eGFR (β = 0.02, 95% CI − 0.03; − 0.01). Medium- and short-term exposure to elevated air pollution levels was associated with a decrease in eGFR and development CKD. The main pollutants affecting the kidneys were PM2.5 and NO2.
Dynamic patterns of DNA methylation in the normal prostate epithelial differentiation program are targets of aberrant methylation in prostate cancer
Authors: Long Mark D. , Dhiman Vineet K. , Affronti Hayley C. , Hu Qiang , Liu Song , Smiraglia Dominic J.
Published: June 2021

Understanding the epigenetic control of normal differentiation programs might yield principal information about critical regulatory states that are disturbed in cancer. We utilized the established non-malignant HPr1-AR prostate epithelial cell model that upon androgen exposure commits to a luminal cell differentiation trajectory from that of a basal-like state. We profile the dynamic transcriptome associated with this transition at multiple time points (0 h, 1 h, 24 h, 96 h), and confirm that expression patterns are strongly indicative of a progressive basal to luminal cell differentiation program based on human expression signatures. Furthermore, we establish dynamic patterns of DNA methylation associated with this program by use of whole genome bisulfite sequencing (WGBS). Expression patterns associated with androgen induced luminal cell differentiation were found to have significantly elevated DNA methylation dynamics. Shifts in methylation profiles were strongly associated with Polycomb repressed regions and to promoters associated with bivalency, and strongly enriched for binding motifs of AR and MYC. Importantly, we found that dynamic DNA methylation patterns observed in the normal luminal cell differentiation program were significant targets of aberrant methylation in prostate cancer. These findings suggest that the normal dynamics of DNA methylation in luminal differentiation contribute to the aberrant methylation patterns in prostate cancer.
Biosorption of Cu2+, Pb2+, Cd2+ and their mixture from aqueous solutions by Michelia figo sawdust
Authors: Long Mingzhong , Jiang Hong , Li Xiaona
Published: June 2021

The study aimed at investigating copper, lead, and cadmium removal from both single and mixed metal solutions byMichelia figo(Lour.) Spreng. wood sawdust treated with 0.5 mol l−1NaOH for four hours. In order to evaluate the effects of each factor and interactions between factors on metal ion biosorption, a 23factorial experimental design was applied. FTIR results showed that the metal ions would bind to the hydroxyl and carboxyl groups ofM. figowood sawdust biomass. The main effects and interactions of three factors pH (3 and 5), initial metal ion concentration (C0, 0.157 and 1.574 mmol L−1), and dosage of biomass (D, 4 and 10 g L−1) at two levels were analyzed. The most significant variable regarding Cu2+and Pb2+biosorption was initial metal iron concentration. For Cd2+, pH was found to be the most significant factor. The maximum removal efficiencies were 94.12 and 100% for Cu2+and Cd2+, respectively, at conditions of (+ 1, − 1, + 1): pH 5, initial metal concentration 0.157 mmol L−1and dosage of biomass 10 g L−1, while 96.39% for Pb2+at conditions of (− 1, − 1, + 1): pH 3, initial metal concentration 0.157 mmol L−1and dosage of biomass 10 g L−1. There were some interactions between factors: pH*C0andC0*Dfor Cu2+, pH*C0, pH*DandC0*Dfor Pb2+, pH*C0andC0*Dfor Cd2+. Biosorption from a multi metal system showed that the presence of Cu2+and Cd2+had no significant influence on the Pb2+removal, while Pb2+in solution significantly decreased the removal efficiencies of the other two metals.
Risk factors for the severity of Guillain-Barré syndrome and predictors of short-term prognosis of severe Guillain-Barré syndrome
Authors: Wen Puyuan , Wang Lisha , Liu Hong , Gong Li , Ji Han , Wu Hongliang , Chu Wenzheng
Published: June 2021

Guillain-Barré syndrome (GBS) is a neurological disorder characterized by paralysis. Identifying the severity, appropriate therapeutic method, and prognosis of GBS at an early stage is highly important. This study aimed to investigate the modifiable risk factors for the severity of GBS and consequent need for mechanical ventilation (MV) and to identify clinical predictive factors for poor short-term outcomes of severe GBS. 155 GBS patients who were admitted to the Affiliated Yantai Yuhuangding Hospital of Qingdao University during 2014–2020 were enrolled. Demographic, clinical, therapeutic and evolutionary data were collected and were then analyzed using univariate and multivariate regression analyses. Our analytic data demonstrated that the significant clinical predictors of severe GBS were recent history of surgery, older age, cranial nerve impairment, and elevated levels of liver enzymes (p < 0.05). Furthermore, autonomic dysfunction, lower Medical Research Council (MRC) score at nadir, and elevated levels of liver enzymes were significantly associated with MV for severe GBS (p < 0.05), and lower MRC score at nadir and autonomic dysfunction remained significant predictors of MV in severe GBS (p < 0.05). Lastly, recent history of surgery, lower MRC score at admission and at nadir, requirement for MV, and pneumonia during hospitalization were significantly associated with the short-term outcome of severe GBS and that lower MRC score at admission and need for MV were confirmed to be predictors of poor short-term prognosis (p < 0.05). Of note, this study suggested that recent history of surgery is a predictor of severity in GBS patients and is associated with the poor short-term prognosis of severe GBS.
Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey
Authors: Shimamura Munehisa , Kaikita Koichi , Nakagami Hironori , Kawano Tomohiro , Ju Nan , Hayashi Hiroki , Nakamaru Ryo , Yoshida Shota , Sasaki Tsutomu , Mochizuki Hideki , Tsujita Kenichi , Morishita Ryuichi
Published: June 2021

In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund’s adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.
Publisher Correction: Linking landscape-scale conservation to regional and continental outcomes for a migratory species
Authors: Mattsson B. J. , Devries J. H. , Dubovsky J. A. , Semmens D. , Thogmartin W. E. , Derbridge J. J. , Lopez-Hoffman L.
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Simultaneous absolute quantification and sequencing of fish environmental DNA in a mesocosm by quantitative sequencing technique
Authors: Hoshino Tatsuhiko , Nakao Ryohei , Doi Hideyuki , Minamoto Toshifumi
Published: June 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification
Authors: Hollis Robert L. , Stanley Barbara , Thomson John P. , Churchman Michael , Croy Ian , Rye Tzyvia , Bartos Clare , Nussey Fiona , Mackean Melanie , Meynert Alison M. , Semple Colin A. , Gourley Charlie , Herrington C. Simon
Published: June 2021

Endometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.
Comparison of bias and resolvability in single-cell and single-transcript methods
Authors: Rammohan Jayan , Lund Steven P. , Alperovich Nina , Paralanov Vanya , Strychalski Elizabeth A. , Ross David
Published: June 2021

Single-cell and single-transcript measurement methods have elevated our ability to understand and engineer biological systems. However, defining and comparing performance between methods remains a challenge, in part due to the confounding effects of experimental variability. Here, we propose a generalizable framework for performing multiple methods in parallel using split samples, so that experimental variability is shared between methods. We demonstrate the utility of this framework by performing 12 different methods in parallel to measure the same underlying reference system for cellular response. We compare method performance using quantitative evaluations of bias and resolvability. We attribute differences in method performance to steps along the measurement process such as sample preparation, signal detection, and choice of measurand. Finally, we demonstrate how this framework can be used to benchmark different methods for single-transcript detection. The framework we present here provides a practical way to compare performance of any methods.
Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor
Authors: Dowsett Joseph , Ferkingstad Egil , Rasmussen Line Jee Hartmann , Thørner Lise Wegner , Magnússon Magnús K. , Sugden Karen , Thorleifsson Gudmar , Frigge Mike , Burgdorf Kristoffer Sølvsten , Ostrowski Sisse Rye , Sørensen Erik , Erikstrup Christian , Pedersen Ole Birger , Hansen Thomas Folkmann , Banasik Karina , Brunak Søren ,   DBDS Genomic Consortium,   Denmark, Andersen Steffen , Jemec Gregor , Jennum Poul , Nielsen Rene Kasper , Nyegaard Mette , Paarup Helene Martina , Petersen Mikkel , Werge Thomas ,   Iceland, Gudbjartsson Daniel , Stefansson Kari , Þorsteinsdóttir Unnur , Tragante Vinicius , Lund Sigrun Helga , Stefansdottir Lilja , Gunnarson Bjarni , Poulton Richie , Arseneault Louise , Caspi Avshalom , Moffitt Terrie E. , Gudbjartsson Daníel , Eugen-Olsen Jesper , Stefánsson Hreinn , Stefánsson Kári , Ullum Henrik
Published: June 2021

Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR’s potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation.
Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis
Authors: Saeki Kohei , Chang Gregory , Kanaya Noriko , Wu Xiwei , Wang Jinhui , Bernal Lauren , Ha Desiree , Neuhausen Susan L. , Chen Shiuan
Published: June 2021

The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained by single-cell RNA sequencing, which covers most lifetime stages. Our results indicate a putative trajectory that originates from embryonic mammary stem cells which differentiates into three epithelial lineages (basal, luminal hormone-sensing, and luminal alveolar), presumably arising from unipotent progenitors in postnatal glands. The lineage-specific genes infer cells of origin of breast cancer using The Cancer Genome Atlas data and single-cell RNA sequencing of human breast cancer, as well as the association of gland reorganization to different breast cancer subtypes. This comprehensive mammary cell gene expression atlas (https://mouse-mammary-epithelium-integrated.cells.ucsc.edu) presents insights into the impact of the internal and external stimuli on the mammary epithelium at an advanced resolution.
Systemic GLP-1R agonist treatment reverses mouse glial and neurovascular cell transcriptomic aging signatures in a genome-wide manner
Authors: Li Zhongqi , Chen Xinyi , Vong Joaquim S. L. , Zhao Lei , Huang Junzhe , Yan Leo Y. C. , Ip Bonaventure , Wing Yun Kwok , Lai Hei-Ming , Mok Vincent C. T. , Ko Ho
Published: June 2021

Pharmacological reversal of brain aging is a long-sought yet challenging strategy for the prevention and treatment of age-related neurodegeneration, due to the diverse cell types and complex cellular pathways impacted by the aging process. Here, we report the genome-wide reversal of transcriptomic aging signatures in multiple major brain cell types, including glial and mural cells, by systemic glucagon-like peptide-1 receptor (GLP-1R) agonist (GLP-1RA) treatment. The age-related expression changes reversed by GLP-1RA encompass both shared and cell type-specific functional pathways that are implicated in aging and neurodegeneration. Concomitantly, Alzheimer’s disease (AD)-associated transcriptomic signature in microglia that arises from aging is reduced. These results show the feasibility of reversing brain aging by pharmacological means, provide mechanistic insights into the neurological benefits of GLP-1RAs, and imply that GLP-1R agonism may be a generally applicable pharmacological intervention for patients at risk of age-related neurodegeneration.
Simulating molecules on a cloud-based 5-qubit IBM-Q universal quantum computer
Authors: Leontica S. , Tennie F. , Farrow T.
Published: June 2021

Simulating the behaviour of complex quantum systems is impossible on classical supercomputers due to the exponential scaling of the number of quantum states with the number of particles in the simulated system. Quantum computers aim to break through this limit by using one quantum system to simulate another quantum system. Although in their infancy, they are a promising tool for applied fields seeking to simulate quantum interactions in complex atomic and molecular structures. Here, we show an efficient technique for transpiling the unitary evolution of quantum systems into the language of universal quantum computation using the IBM quantum computer and show that it is a viable tool for compiling near-term quantum simulation algorithms. We develop code that decomposes arbitrary 3-qubit gates and implement it in a quantum simulation first for a linear ordered chain to highlight the generality of the approach, and second, for a complex molecule. We choose the Fenna-Matthews-Olsen (FMO) photosynthetic protein because it has a well characterised Hamiltonian and presents a complex dissipative system coupled to a noisy environment that helps to improve the efficiency of energy transport. The method can be implemented in a broad range of molecular and other simulation settings.
Effect of chemically induced permittivity changes on the plasmonic properties of metal nanoparticles
Authors: Saito Noboru , Ryuzaki Sou , Tsuji Yuta , Noguchi Yutaka , Matsuda Rintaro , Wang Pangpang , Tanaka Daisuke , Arima Yusuke , Okamoto Koichi , Yoshizawa Kazunari , Tamada Kaoru
Published: June 2021

Understanding chemical effects on the plasmonic properties of a metal nanomaterial due to the surface molecules on that metal is of great importance in the field of plasmonics and these effects have yet to be completely elucidated. Here, we report mechanisms of the chemically induced change in the electronic state at the metal-ligand interface of silver nanoparticles due to the ligand molecules, and the effect of this change on the plasmonic properties of those nanoparticles. It was found that changes in the electron density of states at the metal-ligand interface cause alterations in the induced and permanent dipole moments, and eventually to the permittivity at the interface, when the wave function near the Fermi level is localized at the interface. These alterations play a key role in determining the plasmonic properties of silver nanoparticles. The present findings provide a more precise understanding of the interconnection between the electronic states at the metal-organic interface and the plasmonic properties of the metal.
Universal colorful staining of cancer tissues and normal tissues for histological diagnosis
Authors: Li Jin-Mei , Wang Ke-Rang
Published: June 2021

Colorful staining of human tissue sections based on staining withPMI-Manor co-staining withPMI-Manand eosin was developed, which showed unique colorful staining in different nuclei and exhibited good morphology contrast.
Bonding of C1 fragments on metal nanoclusters: a search for methane conversion catalysts with swarm intelligence
Authors: Hori Mikiya , Tsuji Yuta , Yoshizawa Kazunari
Published: June 2021

By using swarm intelligence, it is revealed that Cu nanoclusters are potential candidates as catalysts for direct methane conversion.