bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-genome sequencing of multiple related individuals with type 2 diabetes reveals an atypical likely pathogenic mutation in the PAX6 gene
Authors: Boehm Bernhard O. , Kratzer Wolfgang , Bansal Vikas
Published: October 2022

Pathogenic variants in more than 14 genes have been implicated in monogenic diabetes; however, a significant fraction of individuals with young-onset diabetes and a strong family history of diabetes have unknown genetic etiology. To identify novel pathogenic alleles for monogenic diabetes, we performed whole-genome sequencing (WGS) on four related individuals with type 2 diabetes – including one individual diagnosed at the age of 31 years – that were negative for mutations in known monogenic diabetes genes. The individuals were ascertained from a large case-control study and had a multi-generation family history of diabetes. Identity-by-descent (IBD) analysis revealed that the four individuals represent two sib-pairs that are third-degree relatives. A novel missense mutation (p.P81S) in thePAX6gene was one of eight rare coding variants across the genome shared IBD by all individuals and was inherited from affected mothers in both sib-pairs. The mutation affects a highly conserved amino acid located in the paired-domain ofPAX6- a hotspot for missense mutations that cause aniridia and other eye abnormalities. However, no eye-related phenotype was observed in any individual. The well-established functional role of PAX6 in glucose-induced insulin secretion and the co-segregation of diabetes in families with aniridia provide compelling support for the pathogenicity of this mutation for diabetes. The mutation could be classified as “likely pathogenic” with a posterior probability of 0.975 according to the ACMG/AMP guidelines. This is the firstPAX6missense mutation that is likely pathogenic for autosomal-dominant adult-onset diabetes without eye abnormalities.
Behaviourally modulated hippocampal theta oscillations in the ferret persist during both locomotion and immobility
Authors: Dunn Soraya L. S. , Town Stephen M. , Bizley Jennifer K. , Bendor Daniel
Published: October 2022

Theta oscillations are a hallmark of hippocampal activity across mammals and play a critical role in many hippocampal models of memory and spatial navigation. To reconcile the cross-species differences observed in the presence and properties of theta, we recorded hippocampal local field potentials in rats and ferrets during auditory and visual localisation tasks designed to vary locomotion and sensory attention. Here, we show that theta oscillations occur during locomotion in both ferrets and rats, however during periods of immobility, theta oscillations persist in the ferret, contrasting starkly with the switch to large irregular activity (LIA) in the rat. Theta during immobility in the ferret is identified as analogous to Type 2 theta that has been observed in rodents due to its sensitivity to atropine, and is modulated by behavioural state with the strongest theta observed during reward epochs. These results demonstrate that even under similar behavioural conditions, differences exist between species in the relationship between theta and behavioural state.
ZIP1+ fibroblasts protect lung cancer against chemotherapy via connexin-43 mediated intercellular Zn2+ transfer
Authors: Ni Chen , Lou Xiaohan , Yao Xiaohan , Wang Linlin , Wan Jiajia , Duan Xixi , Liang Jialu , Zhang Kaili , Yang Yuanyuan , Zhang Li , Sun Chanjun , Li Zhenzhen , Wang Ming , Zhu Linyu , Lv Dekang , Qin Zhihai
Published: October 2022

Tumour–stroma cell interactions impact cancer progression and therapy responses. Intercellular communication between fibroblasts and cancer cells using various soluble mediators has often been reported. In this study, we find that a zinc-transporter (ZIP1) positive tumour-associated fibroblast subset is enriched after chemotherapy and directly interconnects lung cancer cells with gap junctions. Using single-cell RNA sequencing, we identify several fibroblast subpopulations, among which Zip1+ fibroblasts are highly enriched in mouse lung tumours after doxorubicin treatment. ZIP1 expression on fibroblasts enhances gap junction formation in cancer cells by upregulating connexin-43. Acting as a Zn2+ reservoir, ZIP1+ fibroblasts absorb and transfer Zn2+ to cancer cells, leading to ABCB1-mediated chemoresistance. Clinically, ZIP1high stromal fibroblasts are also associated with chemoresistance in human lung cancers. Taken together, our results reveal a mechanism by which fibroblasts interact directly with tumour cells via gap junctions and contribute to chemoresistance in lung cancer.
Ornaments are equally informative in male and female birds
Authors: Nolazco Sergio , Delhey Kaspar , Nakagawa Shinichi , Peters Anne
Published: October 2022

Female ornaments are often reduced, male-like traits. Although these were long perceived as non-functional, it is now broadly accepted that female ornaments can be adaptive. However, it is unclear whether this is as common in females as it is in males, and whether ornaments fulfil similar signalling roles. Here, we apply a bivariate meta-analysis to a large dataset of ornaments in mutually ornamented birds. As expected, female ornament expression tends to be reduced compared to males. However, ornaments are equally strongly associated with indicators of condition and aspects of reproductive success in both sexes, regardless of the degree of sexual dimorphism. Thus, we show here in a paired comparison within-and-across species, that ornaments in birds provide similar information in both sexes: more ornamented individuals are in better condition and achieve higher reproductive success. Although limited by their correlational nature, these outcomes imply that female ornaments could widely function in a similar manner as male ornaments.
Premorbid adjustment associates with cognitive and functional deficits in individuals at ultra-high risk of psychosis
Authors: Lundsgaard Julie , Kristensen Tina Dam , Wenneberg Christina , Gregersen Maja , Nordentoft Merete , Glenthøj Louise Birkedal
Published: October 2022

Premorbid social and academic adjustment are important predictors of cognitive and functional performance in schizophrenia. Whether this relationship is also present in individuals at ultra-high risk (UHR) for psychosis is the focus of the present study. Using baseline data from a randomised clinical trial (N = 146) this study investigated associations between premorbid adjustment and neuro- and social cognition and functioning in UHR individuals aged 18–40 years. Patients were evaluated with the Premorbid Adjustment Scale (PAS) comprising a social and an academic domain. Using validated measures neurocognition was assessed in the domains of processing speed, executive function, attention, verbal learning and memory, visual learning and memory, and working memory along with estimated IQ. Social cognitive domains assessed were theory of mind, emotion recognition, and attributional bias. Functional assessment comprised the domains of social- and role functioning, functional capacity, and quality of life. Linear regression analyses revealed poor premorbid academic adjustment to be associated with poorer performance in processing speed, working memory, attention, full scale IQ, and verbal IQ. Poor premorbid social adjustment was associated with theory of mind deficits. Additionally, both premorbid adjustment domains were associated with social- and role functioning and quality of life. Corroborating evidence from schizophrenia samples, our findings indicate poor premorbid adjustment to correlate with deficits in specific cognitive and functional domains in UHR states. Early premorbid adjustment difficulties may therefore indicate a poor cognitive and functional trajectory associated with significant impairments in early and established psychotic disorders suggesting targets for primary intervention.
Comparisons of resting-state brain activity between insomnia and schizophrenia: a coordinate-based meta-analysis
Authors: Gao Ziyang , Xiao Yuan , Zhang Ye , Zhu Fei , Tao Bo , Tang Xiangdong , Lui Su
Published: October 2022

Growing evidence shows that insomnia is closely associated with schizophrenia (SCZ), but the neural mechanism under the association remains unclear. A direct comparison of the patterns of resting-state brain activities would help understand the above question. Using meta-analytic approach, 11 studies of insomnia vs. healthy controls (HC) and 39 studies of SCZ vs. HC were included to illuminate the common and distinct patterns between insomnia and SCZ. Results showed that SCZ and insomnia shared increased resting-state brain activities in frontolimbic structures including the right medial prefrontal gyrus (mPFC) and left parahippocampal gyrus. SCZ additionally revealed greater increased activities in subcortical areas including bilateral putamen, caudate and right insula and greater decreased activities in precentral gyrus and orbitofrontal gyrus. Our study reveals both shared and distinct activation patterns in SCZ and insomnia, which may provide novel insights for understanding the neural basis of the two disorders and enlighten the possibility of the development of treatment strategies for insomnia in SCZ in the future.
A highway vehicle routing dataset during the 2019 Kincade Fire evacuation
Authors: Xu Yiming , Zhao Xilei , Lovreglio Ruggiero , Kuligowski Erica , Nilsson Daniel , Cova Thomas J. , Yan Xiang
Published: October 2022

As the threat of wildfire increases, it is imperative to enhance the understanding of household evacuation behavior and movements. Mobile GPS data provide a unique opportunity for studying evacuation routing behavior with high ecological validity, but there are little publicly available data. We generated a highway vehicle routing dataset derived from GPS trajectories generated by mobile devices (e.g., smartphones) in Sonoma County, California during the 2019 Kincade Fire that started on October 23, 2019. This dataset contains 21,160 highway vehicle routing records within Sonoma County from October 16, 2019 to November 13, 2019. The quality of the dataset is validated by checking trajectories and average travel speeds. The potential use of this dataset lies in analyzing and modeling evacuee route choice behavior, estimating traffic conditions during the evacuation, and validating wildfire evacuation simulation models.
Size-fractionated microbiome observed during an eight-month long sampling in Jiaozhou Bay and the Yellow Sea
Authors: Tao Jianchang , Wang Wenxiu , Weissman JL , Zhang Yongyu , Chen Songze , Zhu Yuanqing , Zhang Chuanlun , Hou Shengwei
Published: October 2022

Jiaozhou Bay is a typical semi-enclosed bay with a temperate climate imposed by strong anthropogenic influence. To investigate microbial biodiversity and ecosystem services in this highly dynamic coastal environment, we conducted a monthly microbial survey spanning eight months at two stations in the bay and the open Yellow Sea starting in April 2015. This report provides a comprehensive inventory of amplicon sequences and environmental microbial genomes from this survey. In total, 2,543 amplicon sequence variants were obtained with monthly relative abundance profiles in three size fractions (>2.7 μm, 2.7–0.7 μm, and 0.7–0.22 μm). Shotgun metagenomes yielded 915 high-quality metagenome-assembled genomes with ≥50% completeness and ≤5% contamination. These environmental genomes comprise 27 bacterial and 5 archaeal phyla. We expect this comprehensive dataset will facilitate a better understanding of coastal microbial ecology.
Comparative performance assessment of deep learning based image steganography techniques
Authors: Himthani Varsha , Dhaka Vijaypal Singh , Kaur Manjit , Rani Geeta , Oza Meet , Lee Heung-No
Published: October 2022

Increasing data infringement while transmission and storage have become an apprehension for the data owners. Even the digital images transmitted over the network or stored at servers are prone to unauthorized access. However, several image steganography techniques were proposed in the literature for hiding a secret image by embedding it into cover media. But the low embedding capacity and poor reconstruction quality of images are significant limitations of these techniques. To overcome these limitations, deep learning-based image steganography techniques are proposed in the literature. Convolutional neural network (CNN) based U-Net encoder has gained significant research attention in the literature. However, its performance efficacy as compared to other CNN based encoders like V-Net and U-Net++ is not implemented for image steganography. In this paper, V-Net and U-Net++ encoders are implemented for image steganography. A comparative performance assessment of U-Net, V-Net, and U-Net++ architectures are carried out. These architectures are employed to hide the secret image into the cover image. Further, a unique, robust, and standard decoder for all architectures is designed to extract the secret image from the cover image. Based on the experimental results, it is identified that U-Net architecture outperforms the other two architectures as it reports high embedding capacity and provides better quality stego and reconstructed secret images.
Clinical factors and dopamine transporter availability for the prediction of outcomes after globus pallidus deep brain stimulation in Parkinson’s disease
Authors: Lee Seung Hyun , Kim Mina , Lee Jooyoung , Kim Jae-Woo , Kim Mi Sun , Jo Sungyang , Jeon Sang Ryong , Chung Sun Ju
Published: October 2022

We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson’s disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [18F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson’s Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD.
Humoral and cellular immune response over 9 months of mRNA-1273, BNT162b2 and ChAdOx1 vaccination in a University Hospital in Spain
Authors: Fernández-Ciriza Leire , González Álvaro , del Pozo José Luis , Fernández-Montero Alejandro , Carmona-Torre Francisco , Carlos Silvia , Sarasa María del Mar , Reina Gabriel
Published: October 2022

Scarce data have been reported about cellular immunity and longevity for different COVID-19 vaccination schedules. We carried out a prospective study enrolling 709 healthcare workers receiving two doses of mRNA-1273, BNT162b2, ChAdOx1, ChAdOx1/BNT162b2 or ChAdOx1 single dose to compare humoral and cellular immunogenicity across 9 months. Higher SARS-CoV-2 spike antibody levels were observed among individuals with hybrid immunity with one dose of any vaccine in comparison to uninfected individuals receiving two doses (mRNA-1273: 20,145 vs 4295 U/mL; BNT162b2: 15,659 vs 1959 U/mL; ChAdOx1: 5344 vs 2230 U/mL), except for ChAdOx1/BNT162b2 heterologous schedule (12,380 U/mL). Naturally infected individuals did not increase substantially the titers after the second dose and showed higher levels throughout the 9 months follow-up. The mean elimination half-life of antibodies among COVID-19 naïve participants was 98, 111, 60 and 36 days, for mRNA-1273, BNT162b2, ChAdOx1/ChAdOx1 and ChAdOx1/BNT162b2, respectively. Cellular immunity was preserved in 96%, 98%, 88% and 92% of uninfected individuals who received mRNA-1273, BNT162b2, ChAdOx1/ChAdOx1 and ChAdOx1/BNT162b2 after 6/9 months. Individuals with specific T cells showed robust long lasting protection, especially when m-RNA based vaccines are inoculated. These data may influence the validity of the vaccination passport and the need for booster vaccinations.
Comprehensive immunophenotypic analysis reveals the pathological involvement of Th17 cells in Graves' disease
Authors: Torimoto Keiichi , Okada Yosuke , Nakayamada Shingo , Kubo Satoshi , Kurozumi Akira , Narisawa Manabu , Tanaka Yoshiya
Published: October 2022

Graves' disease (GD) is an organ-specific autoimmune disease, but there are a few studies that have evaluated how immunophenotypes are related to clinical symptoms and intractable pathology, or the effects of treatment on immunophenotypes. We performed peripheral blood immunophenotyping in GD. We assessed the proportion of functional subsets of T helper cells (such as Th1, Th17, Treg and Tfh cells), B cells (Naïve, IgM memory, Class-switched, IgD−CD27− double negative and Plasmablasts cells), Monocytes, Dendritic cells and NK cells, and evaluated the relationship of immunophenotypes with clinical indices, disease activity, risk of relapse, and changes in immunophenotypes after treatment with antithyroid drugs. The activated Th17 cells, activated T follicular helper (Tfh) cells, and IgD−CD27− double-negative B cells were higher in newly onset GD compared with healthy participants. Th17 cells were associated with thyroid autoantibodies, thyroid function, thyroid enlargement, and Graves' Recurrent Events After Therapy (GREAT) score; while double-negative B cells were associated with thyroid autoantibodies. Treatment with antithyroid drugs decreased the activated Tfh cells in parallel with the improvement in thyroid function. However, activated Th17 cells were not associated with clinical improvement and remained unchanged. Peripheral blood immunophenotyping identified the differential involvement of T and B cell subsets in the pathogenesis of GD. Abnormalities in the differentiation of Th17, Tfh, and double-negative B cells reflected the clinical pathology associated with autoantibody production and excess thyroid hormones. And Th17 cells are significantly associated with the marker for resistance to treatment. These results suggest the involvement of Th17 cell activation in the intractable pathology associated with potential immune abnormalities in GD.

Clinical trial registration: #UMIN000017726 (Date: June 1st, 2015).
Lack of ITS sequence homogenization in Erysimum species (Brassicaceae) with different ploidy levels
Authors: Osuna-Mascaró Carolina , de Casas Rafael Rubio , Berbel Modesto , Gómez José M. , Perfectti Francisco
Published: October 2022

The internal transcribed spacers (ITS) exhibit concerted evolution by the fast homogenization of these sequences at the intragenomic level. However, the rate and extension of this process are unclear and might be conditioned by the number and divergence of the different ITS copies. In some cases, such as hybrid species and polyploids, ITS sequence homogenization appears incomplete, resulting in multiple haplotypes within the same organism. Here, we studied the dynamics of concerted evolution in 85 individuals of seven plant species of the genus Erysimum (Brassicaceae) with multiple ploidy levels. We estimated the rate of concerted evolution and the degree of sequence homogenization separately for ITS1 and ITS2 and whether these varied with ploidy. Our results showed incomplete sequence homogenization, especially for polyploid samples, indicating a lack of concerted evolution in these taxa. Homogenization was usually higher in ITS2 than in ITS1, suggesting that concerted evolution operates more efficiently on the former. Furthermore, the hybrid origin of several species appears to contribute to the maintenance of high haplotype diversity, regardless of the level of ploidy. These findings indicate that sequence homogenization of ITS is a dynamic and complex process that might result in varying intra- and inter-genomic diversity levels.
Clinical determinants and prognostic significance of hypocapnia in acute heart failure
Authors: Garus Mateusz , Zdanowicz Agata , Fudim Marat , Zymliński Robert , Niewiński Piotr , Paleczny Bartłomiej , Rosiek-Biegus Marta , Iwanek Gracjan , Ponikowski Piotr , Biegus Jan
Published: October 2022

The aim of this research was to examine the prevalence of hyperventilation (defined by pCO2 value) among acute heart failure (AHF) patients and to link it with potential triggers and prognosis. All patients underwent dyspnea severity assessment and capillary blood examination on hospital admission and during hospitalization. Out of 241 AHF patients, 57(24%) were assigned to low pCO2 group (pCO2 ≤ 30 mmHg) and 184 (76%) to normal pCO2 group (pCO2 > 30 mmHg). Low pCO2 group had significantly lower HCO3- (22.3 ± 3.4 vs 24.7 ± 2.9 mmol/L, p < 0.0001) and significantly higher lactate level (2.53 ± 1.6 vs 2.14 ± 0.97 mmol/L, p = 0.03). No differences between groups were observed in respect to the following potential triggers of hyperventilation: hypoxia (sO2 92.5 ± 5.2 vs 92 ± 5.6% p = 0.57), infection (CRP 10.5[4.9–26.4]vs 7.15[3.45–17.35] mg/L, p = 0.47), dyspnea severity (7.8 ± 2.3vs 8.0 ± 2.3 points, p = 0.59) and pulmonary congestion (82.5 vs 89.1%, p = 0.19), respectively. Low pCO2 value was related to an increased 4-year all-cause mortality hazard ratio (HR) (95% CI) 2.2 (1.3–3.6); p = 0.002 and risk of death and of rehospitalization for HF, HR (95% CI) 2.0 (1.3–3.0); p = 0.002. Hyperventilation is relatively frequent in AHF and is related to poor prognosis. Low pCO2 was not contingent on expected potential triggers of dyspnea but rather on tissue hypoperfusion.
Comparison of the effectiveness of thiamethoxam and its main metabolite clothianidin after foliar spraying and root irrigation to control Myzus persicae on peach
Authors: Tian Fajun , Qiao Chengkui , Wang Caixia , Pang Tao , Guo Linlin , Li Jun , Pang Rongli , Liu Hui , Xie Hanzhong
Published: October 2022

The green peach aphid, Myzus persicae, is one of the most economically important pests in peach-growing areas around the world. In many countries, the application of insecticides is the main method to control and reduce the population of M. persicae. In this study, we investigated the effects and persistence of thiamethoxam against M. persicae by foliar spraying and root irrigation. The residues of thiamethoxam and clothianidin in peach were determined to assess food safety. The results showed that thiamethoxam treatment significantly reduced the population of M. persicae through foliar spraying and root irrigation. And the persistence of root irrigation on M. persicae was significantly longer than that of spraying. Thiamethoxam and clothianidin were absorbed by the roots, transported to other parts of the plant, and concentrated in the leaves, especially new leaves. The final residues of thiamethoxam and clothianidin in peaches were below the maximum residue limit (MRLs). These results suggested that thiamethoxam is more effective in M. persicae control through root irrigation than foliar spraying. The persistence of root irrigation on M. persicae was significantly longer than that of spraying. These results shed some light upon the control of M. persicae by root irrigation of thiamethoxam.
Kinetics of microbial and photochemical degradation of aflatoxin B1 in a sandy loam and clay soil
Authors: Albert Julius , Muñoz Katherine
Published: October 2022

In a 28-days experiment, we investigated the dissipation of aflatoxin B1 (AFB1) (0.5–500 $${\upmu }\text {g}\,\text {kg}^{-1}$$

μ
g

kg

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1

) by microbial (MD) and photodegradation (PD) in two contrasting soils (sandy loam and clay). Sterile incubation in darkness served as control (C). AFB1 was degraded in all scenarios according to simple first-order kinetics with 50% dissipation times of 20–32 (PD), 19–48 (MD), and 56–65 days (C), respectively. Dissipation rates were significantly lower ($$\text {p}<0.001$$

p
<
0.001

) in the clay soil than in the sandy loam soil, likely due to photoquenching and strong binding of AFB1 by clay minerals and humic substances. In the sandy loam, dissipation rate of MD decreased in function of initial AFB1 concentration, probably due to toxic effects on degrading microbes. In contrast, in the clay soil the dissipation rate increased with increasing concentration up to 250 $$\upmu \text {g}\,\text {kg}^{-1}$$

μ
g

kg

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1

, followed by a sharp decrease at 500 $$\upmu \text {g}\,\text {kg}^{-1}$$

μ
g

kg

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1

, indicating an effect of soil texture on the bioavailability of AFB1 to soil microbes. AFB2a was identified as a transformation product in all scenarios. These results confirm the function of soil for AFB1 degradation, which is modulated by abiotic and biotic processes, soil characteristics and initial AFB1 concentration.
Unsupervised recognition of components from the interaction of BSA with Fe cluster in different conditions utilizing 2D fluorescence spectroscopy
Authors: Kompany-Zareh Mohsen , Akbarian Somayyeh , Najafpour Mohammad Mahdi
Published: October 2022

The excitation-emission fluorescence spectroscopy combined with three-way analysis was applied for discriminating the pure BSA and BSA/Fe3O(OAc)6ClO4 (Fe) using unsupervised classification methods. Herein, the interaction of bovine serum albumin (BSA) and Fe clusters as an artificial enzyme is studied by extracting the intrinsic excitation-emission (EEM) fluorescence of BSA. The conformation of BSA changes with pH, temperature, and Fe concentration. Three-way fluorescence data were recorded for BSA and BSA/Fe during different days. The obtained results showed that the Fe clusters cause changes in the structure of BSA conformation as a function of pH, temperature, and Fe concentration. Also, the denaturation pathway of the BSA molecule is significantly different in the presence of Fe clusters. Both techniques of PARAFAC and PCA were used in the excitation-emission fluorescence matrices (EEM) of solutions at three different pH (5.0, 7.0, and 9.0) and temperatures (15.0, 25.0, and 35.0 °C) values. Also, we reported the results of the change in concentrations of Fe (4.0, 6.0, and 8.0 mg) using these methods. These three amino acids (tyrosine, tryptophan, and phenylalanine) indicate all datasets and their similarities and differences. The spectral differences were more remarkable in different pH values compared to different temperatures. Also, we could distinguish between the groups of protein samples properly in different concentrations of Fe using low-cost EEM spectral images and PARAFAC.
Spontaneous activity patterns in human motor cortex replay evoked activity patterns for hand movements
Authors: Livne Tomer , Kim DoHyun , Metcalf Nicholas V. , Zhang Lu , Pini Lorenzo , Shulman Gordon L. , Corbetta Maurizio
Published: October 2022

Spontaneous brain activity, measured with resting state fMRI (R-fMRI), is correlated among regions that are co-activated by behavioral tasks. It is unclear, however, whether spatial patterns of spontaneous activity within a cortical region correspond to spatial patterns of activity evoked by specific stimuli, actions, or mental states. The current study investigated the hypothesis that spontaneous activity in motor cortex represents motor patterns commonly occurring in daily life. To test this hypothesis 15 healthy participants were scanned while performing four different hand movements. Three movements (Grip, Extend, Pinch) were ecological involving grip and grasp hand movements; one control movement involving the rotation of the wrist was not ecological and infrequent (Shake). They were also scanned at rest before and after the execution of the motor tasks (resting-state scans). Using the task data, we identified movement-specific patterns in the primary motor cortex. These task-defined patterns were compared to resting-state patterns in the same motor region. We also performed a control analysis within the primary visual cortex. We found that spontaneous activity patterns in the primary motor cortex were more like task patterns for ecological than control movements. In contrast, there was no difference between ecological and control hand movements in the primary visual area. These findings provide evidence that spontaneous activity in human motor cortex forms fine-scale, patterned representations associated with behaviors that frequently occur in daily life.
Flood impacts on urban road connectivity in southern China
Authors: Zhou Ruitao , Zheng Hang , Liu Yueyi , Xie Guanti , Wan Wenhua
Published: October 2022

Effective measures to improve road accessibility during storms are required as traffic congestion caused by storm floods increasingly constrains the efficiency of urban commuting. However, flood impacts on urban road connectivity are not yet well assessed due to inaccurate simulation of flood processes in urban areas where high-resolution data for drainage networks and gauged hydrological data are insufficient. Thus, this study assesses flood impacts on road network connectivity in an urban area of southern China through joint modeling of 1-D hydrodynamic processes in drainage networks and 2-D flood inundation processes on roads using MIKE Urban and MIKE 21. High-resolution DEM images of 5 m and a drainage network of 5635 pipelines were used for urban hydrological simulation. Flood depths were gauged for model calibration and validation by recruited volunteers in the context of citizen science. The results show that road network connectivity decreases as rainfall increases. More than 40% of road connectivity is lost in the study area when a 1-in-100-year return period rainfall occurs. The study results can help to inform more adaptive strategies for local flood control. The study methods are also applicable to improving urban hydrological modeling in broader regions.
Applying genomic approaches to delineate conservation strategies using the freshwater mussel Margaritifera margaritifera in the Iberian Peninsula as a model
Authors: Perea S. , Mendes S. L. , Sousa-Santos C. , Ondina P. , Amaro R. , Castro J. , San-Miguel E. , Lima C. S. , Garcia M. , Velasquez V. , Garcia-Roves P. , Fernández D. , Araujo R. , Sousa V. C. , Reis J.
Published: October 2022

Effective conservation actions to counteract the current decline of populations and species require a deep knowledge on their genetic structure. We used Single Nucleotide Polymorphisms (SNPs) to infer the population structure of the highly threatened freshwater pearl mussel Margaritifera margaritifera in the Iberian Peninsula. A total of 130 individuals were collected from 26 locations belonging to 16 basins. We obtained 31,692 SNPs through Genotyping by Sequencing (GBS) and used this dataset to infer population structure. Genetic diversity given as observed heterozygosity was low. Pairwise FST comparisons revealed low levels of genetic differentiation among geographically close populations. Up to 3 major genetic lineages were determined: Atlantic, Cantabrian and Douro. This structure suggests a close co-evolutionary process with brown trout (Salmo trutta), the primordial fish host of this mussel in the studied area. Some sub-basins showed some genetic structuring, whereas in others no intrapopulation differentiation was found. Our results confirm that genetic conservation units do not match individual basins, and that knowledge about the genetic structure is necessary before planning recovery plans that may involve relocation or restocking. The same reasoning should be applied to strictly freshwater species that are sessile or have restricted dispersal abilities and are currently imperiled worldwide.
Calcium dobesilate reduces SARS-CoV-2 entry into endothelial cells by inhibiting virus binding to heparan sulfate
Authors: Kiyan Yulia , Schultalbers Anna , Chernobrivaia Ekaterina , Tkachuk Sergey , Rong Song , Shushakova Nelli , Haller Hermann
Published: October 2022

Recent reports demonstrate that SARS-CoV-2 utilizes cell surface heparan sulfate as an attachment factor to facilitate the initial interaction with host cells. Heparan sulfate interacts with the receptor binding domain of SARS-CoV-2 spike glycoprotein, and blocking this interaction can decrease cell infection. We and others reported recently that the family of compounds of 2,5-dihydroxyphenylic acid interferes with the binding of the positively charged groove in growth factor molecules to negatively charged cell surface heparan sulfate. We hypothesized that Calcium Dobesilate (CaD)—calcium salt of 2,5-dihydroxyphenylic acid—may also interfere with the binding of SARS-CoV-2 spike protein to heparan sulfate. Using lentiviral SARS-CoV-2 spike protein pseudotyped particles we show that CaD could significantly reduce pseudovirus uptake into endothelial cells. On the contrary, CaD did not affect cell infection with VSVG-expressing lentivirus. CaD could also prevent retention of SARS-CoV-2 spike protein in ex vivo perfused mouse kidney. Using microfluidic culture of endothelial cells under flow, we show that CaD prevents spike protein interaction with heparan sulfate glycocalyx. Since CaD has no adverse side effects and is approved in humans for other medical indications, our findings can rapidly translate into clinical studies.
A real-time rural domestic garbage detection algorithm with an improved YOLOv5s network model
Authors: Jiang Xiangkui , Hu Haochang , Qin Yuemei , Hu Yihui , Ding Rui
Published: October 2022

An increasing number of researchers are using deep learning technology to classify and process garbage in rural areas, and have achieved certain results. However, the existing garbage detection models still have problems such as high complexity, missed detection of small targets, low detection accuracy and poor real-time performance. To address these issues, we train a model and apply it to garbage classification and detection in rural areas. In general, we propose an attention combination mechanism based on the YOLOv5 algorithm to build a better backbone network structure, add a new small object detection layer in the head network to enhance the model's ability to detect small objects, adopt the CIoU loss function to optimize the output prediction bounding box, and choose the Adam optimization algorithm to train the model. Our proposed YOLOv5s-CSS model detects a single garbage image in 0.021 s with a detection accuracy of 96.4%. Compared with the YOLOv5 algorithm and the classic detection algorithm, the improved algorithm has better detection speed and detection accuracy. At the same time, the complexity of the network model is reduced to a certain extent, which can meet the requirements of real-time detection of rural domestic garbage.
Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa
Authors: Haines Robbie R. , Putsathit Papanin , Hammer Katherine A. , Tai Anna S.
Published: October 2022

Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a β-lactam antibiotic with a β-lactamase inhibitor. New β-lactam/β-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and ceftolozane-tazobactam (C/T) against MDR CFPA (n = 20). The MIC90 of I-R, CZA, and C/T was 64/4, 32/4, and 16/8 (all µg/mL), respectively. The susceptibility of isolates to imipenem was not significantly improved with the addition of relebactam (p = 0.68). However, susceptibility to ceftazidime was significantly improved with the addition of avibactam (p < 0.01), and the susceptibility to C/T was improved compared to piperacillin/tazobactam (p < 0.05) These data provide in vitro evidence that I-R may not be any more effective than imipenem monotherapy against MDR CFPA. The pattern of susceptibility observed for CZA and C/T in the current study was similar to data previously reported for non-CF-associated MDR P. aeruginosa.
The effect of short-term refrigeration on platelet responsiveness
Authors: Kobsar Anna , Koehnlechner Karina , Klingler Philipp , Niklaus Marius , Zeller-Hahn Julia , Koessler Angela , Weber Katja , Boeck Markus , Koessler Juergen
Published: October 2022

Storage of platelet concentrates (PC) at cold temperature (CT) is discussed as an alternative to the current standard of storage at room temperature (RT). Recently, we could show that cold-induced attenuation of inhibitory signaling is an important mechanism promoting platelet reactivity. For developing strategies in blood banking, it is required to elucidate the time-dependent onset of facilitated platelet activation. Thus, freshly prepared platelet-rich-plasma (PRP) was stored for 1 and 2 h at CT (2–6 °C) or at RT (20–24 °C), followed by subsequent comparative analysis. Compared to RT, basal and induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation levels were decreased under CT within 1 h by approximately 20%, determined by Western blot analysis and flow cytometry. Concomitantly, ADP- and collagen-induced threshold aggregation values were enhanced by up to 30–40%. Furthermore, platelet-covered areas on collagen-coated slides and aggregate formation under flow conditions were increased after storage at CT, in addition to induced activation markers. In conclusion, a time period of 1–2 h for refrigeration is sufficient to induce an attenuation of inhibitory signaling, accompanied with an enhancement of platelet responsiveness. Short-term refrigeration may be considered as a rational approach to obtain PC with higher functional reactivity for the treatment of hemorrhage.
Nicotinamide adenine dinucleotide reduced (NADH) is a natural UV filter of certain bird lens
Authors: Osik Nataliya A. , Zelentsova Ekaterina A. , Sharshov Kirill A. , Tsentalovich Yuri P.
Published: October 2022

In this work, we for the first time report the identification of UV filters in the bird eye lens. We found that lenses of some raptors (black kite, common buzzard) and waterfowl (birds from Podicipedidae family) contain unusually high levels of reduced nicotinamide adenine dinucleotide (NADH)—a compound with high absorption in the UV-A range with a maximum at 340 nm. The lens metabolome of these birds also features an extremely low [NAD +]/[NADH] ratio. Chemometric analysis demonstrates that the differences between the metabolomic compositions of lenses with low and high NADH abundances should be attributed to the taxonomic features of bird species rather to the influence of the low [NAD +]/[NADH] ratio. We attributed this observation to the low metabolic activity in lens fiber cells, which make up the bulk of the lens tissue. Photochemical measurements show that properties of NADH as a UV filter are as good as that of UV filters in the human lens, including strong absorption in the UV-A spectral region, high photostability under both aerobic and anaerobic conditions, low yields of triplet state, fluorescence, and radicals under irradiation. Lenticular UV filters protect the retina and the lens from photo-induced damages and improve the visual acuity by reducing chromatic aberrations; therefore, the results obtained contribute to our understanding of the extremely high acuity of the raptor vision.
Molecular dynamics on quantum annealers
Authors: Gaidai Igor , Babikov Dmitri , Teplukhin Alexander , Kendrick Brian K. , Mniszewski Susan M. , Zhang Yu , Tretiak Sergei , Dub Pavel A.
Published: October 2022

In this work we demonstrate a practical prospect of using quantum annealers for simulation of molecular dynamics. A methodology developed for this goal, dubbed Quantum Differential Equations (QDE), is applied to propagate classical trajectories for the vibration of the hydrogen molecule in several regimes: nearly harmonic, highly anharmonic, and dissociative motion. The results obtained using the D-Wave 2000Q quantum annealer are all consistent and quickly converge to the analytical reference solution. Several alternative strategies for such calculations are explored and it was found that the most accurate results and the best efficiency are obtained by combining the quantum annealer with classical post-processing (greedy algorithm). Importantly, the QDE framework developed here is entirely general and can be applied to solve any system of first-order ordinary nonlinear differential equations using a quantum annealer.
Impact of anticoagulants on the clinical outcomes of colonic diverticular bleeding comparing warfarin and direct oral anticoagulants
Authors: Chang Li-sa , Nishida Tsutomu , Hosokawa Kana , Fujii Yoshifumi , Osugi Naoto , Sugimoto Aya , Mukai Kaori , Nakamatsu Dai , Matsumoto Kengo , Hayashi Shiro , Yamamoto Masashi , Inada Masami
Published: October 2022

Recently, direct oral anticoagulants (DOACs) have been widely used as antithrombotic agents to replace warfarin, but their clinical impact in patients with gastrointestinal bleeding is unclear. We compared the effects of warfarin and DOACs on the outcomes of patients with colonic diverticular bleeding. The patients were divided into warfarin and DOAC groups. We compared the clinical outcomes and the effect of the DOAC dosing and examined any readmissions due to colonic diverticular bleeding within 1 year. A total of 95 events (warfarin group: n = 43 and DOAC group: n = 52) were included. Compared with the warfarin group, the DOAC group was significantly older, had a lower rate of concomitant antiplatelet agents, and a shorter hospital stay, but no significant differences were found in the other clinical outcomes. Thirty-seven patients (71.2%) in the DOAC group had appropriate dosing, whereas 15 patients (28.9%) had an inappropriate dose. The patients with overdose or contraindications had significantly lower minimum hemoglobin levels. In the univariate analysis, prior hospitalization for colonic diverticular bleeding was a significant predictor of readmission. Compared with warfarin, patients with colonic diverticular bleeding treated with DOACs were older and had shorter hospital stays, and the inappropriate use of DOACs may worsen outcomes.
Application of the 2-deoxyglucose scaffold as a new chiral probe for elucidation of the absolute configuration of secondary alcohols
Authors: Trocka Alicja , Szwarc-Karabyka Katarzyna , Makowiec Sławomir , Laskowski Tomasz
Published: October 2022

Herein, we present the application of 2-deoxy-d-glucose derivatives as chiral probes for elucidation of the absolute configuration of chiral secondary alcohols. The probes are attached to the studied molecules via glycosylation reaction and the resulting products are examined by a set of standard 2D NMR experiments. The absolute configuration of an oxymethine carbon atom binding the probe is established on a basis of a set of diagnostic dipolar couplings (NOEs/ROEs). These correlations may be considered diagnostic due to a pronounced lack of conformational freedom of the formed glycosidic linkage. While the chance for an observation of the diagnostic signals is the highest when the resulting glycoside in an α-anomer. 2-deoxy-d-glucose was selected as a probe of choice since is it known to strongly prefer the formation of α-glycosides
Lumbar spine intervertebral disc gene delivery of BMPs induces anterior spine fusion in lewis rats
Authors: Cunningham Matthew E. , Kelly Natalie H. , Rawlins Bernard A. , Boachie-Adjei Oheneba , van der Meulen Marjolein C. H. , Hidaka Chisa
Published: October 2022

Minimally invasive techniques and biological autograft alternatives such as the bone morphogenetic proteins (BMPs) can reduce morbidity associated with spinal fusions. This study was a proof-of-concept for gene-therapy-mediated anterior spine fusion that could be adapted to percutaneous technique for clinical use. Isogeneic bone marrow stromal cells genetically programmed to express b-galactosidase (LACZ, a marker gene), BMP2, BMP7, a mixture of BMP2 and BMP7 infected cells (homodimers, HM), or BMP2/7 heterodimers (HT) were implanted into the discs between lumbar vertebrae 4 and 5 (L4/5) and L5/6 of male Lewis rats. Spine stiffening was monitored at 4, 8 and 12 weeks using noninvasive-induced angular displacement (NIAD) testing. At 12 weeks isolated spines were assessed for fusion and bone formation by palpation, biomechanical testing [four-point bending stiffness, moment to failure in extension, and in vitro angular displacement (IVAD)], faxitron x-rays, microCT, and histology. Progressive loss of NIAD occurred in only the HT group (p < 0.001), and biomechanical tests correlated with the NIAD results. Significant fusion occurred only in the HT group (94% of animals with one or both levels) as assessed by palpation (p < 0.001), which predicted HT bone production assessed by faxitron (p ≤ 0.001) or microCT (p < 0.023). Intervertebral bridging bone was consistently observed only in HT-treated specimens. Induced bone was located anterior and lateral to the disc space, with no bone formation noted within the disc. Percutaneous anterior spine fusions may be possible clinically, but induction of bone inside the disc space remains a challenge.
Luminous, relativistic, directional electron bunches from an intense laser driven grating plasma
Authors: Lad Amit D. , Mishima Y. , Singh Prashant Kumar , Li Boyuan , Adak Amitava , Chatterjee Gourab , Brijesh P. , Dalui Malay , Inoue M. , Jha J. , Tata Sheroy , Trivikram M. , Krishnamurthy M. , Chen Min , Sheng Z. M. , Tanaka K. A. , Kumar G. Ravindra , Habara H.
Published: October 2022

Bright, energetic, and directional electron bunches are generated through efficient energy transfer of relativistic intense (~ 1019 W/cm2), 30 femtosecond, 800 nm high contrast laser pulses to grating targets (500 lines/mm and 1000 lines/mm), under surface plasmon resonance (SPR) conditions. Bi-directional relativistic electron bunches (at 40° and 150°) are observed exiting from the 500 lines/mm grating target at the SPR conditions. The surface plasmon excited grating target enhances the electron flux and temperature by factor of 6.0 and 3.6, respectively, compared to that of the plane substrate. Particle-in-Cell simulations indicate that fast electrons are emitted in different directions at different stages of the laser interaction, which are related to the resultant surface magnetic field evolution. This study suggests that the SPR mechanism can be used to generate multiple, bright, ultrafast relativistic electron bunches for a variety of applications.