bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender differences among Swedish COPD patients: results from the ARCTIC, a real-world retrospective cohort study
Authors: Lisspers Karin , Larsson Kjell , Janson Christer , Ställberg Björn , Tsiligianni Ioanna , Gutzwiller Florian S. , Mezzi Karen , Bjerregaard Bine Kjoeller , Jorgensen Leif , Johansson Gunnar 
Published: December 2019

AbstractThe present study aimed to generate real-world evidence regarding gender differences among chronic obstructive pulmonary disease (COPD) patients, especially as regards the diagnosis and outcomes in order to identify areas for improvement and management and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients and a matched reference population from 52 primary care centers in 2000–2014. The incidence of COPD, prevalence of asthma and other comorbidities, risk of exacerbations, mortality rate, COPD drug prescriptions, and healthcare resource utilization were analyzed. In total, 17,479 patients with COPD were included in the study. During the study period, COPD was more frequent among women (53.8%) and women with COPD experienced more exacerbations vs. men (6.66 vs. 4.66). However, the overall mortality rate was higher in men compared with women (45% vs. 38%), but no difference for mortality due to COPD was seen between genders over the study period. Women seemed to have a greater susceptibility to asthma, fractures, osteoporosis, rheumatoid arthritis, rhinitis, depression, and anxiety, but appeared less likely to have diabetes, kidney diseases, and cardiovascular diseases. Furthermore, women had a greater risk of COPD-related hospitalization and were likely to receive a significantly higher number of COPD drug prescriptions compared with men. These results support the need to reduce disease burden among women with COPD and highlight the role of healthcare professionals in primary care who should consider all these parameters in order to properly diagnose and treat women with COPD.
Mindfulness video game improves connectivity of the fronto-parietal attentional network in adolescents: A multi-modal imaging study
Authors: Patsenko Elena G. , Adluru Nagesh , Birn Rasmus M. , Stodola Diane E. , Kral Tammi R. A. , Farajian Reza , Flook Lisa , Burghy Cory A. , Steinkuehler Constance , Davidson Richard J. 
Published: December 2019

AbstractMindfulness training has been shown to improve attention and change the underlying brain substrates in adults. Most mindfulness training programs involve a myriad of techniques, and it is difficult to attribute changes to any particular aspect of the program. Here, we created a video game, Tenacity, which models a specific mindfulness technique – focused attention on one’s breathing – and assessed its potential to train an attentional network in adolescents. A combined analysis of resting state functional connectivity (rs-FC) and diffusion tensor imaging (DTI) yielded convergent results – change in communication within the left fronto-parietal network after two weeks of playing Tenacity compared to a control game. Rs-FC analysis showed greater connectivity between left dorsolateral prefrontal cortex (dlPFC) and left inferior parietal cortex (IPC) in the Tenacity group. Importantly, changes in left dlPFC – IPC rs-FC and changes in structural connectivity of the white matter tract that connects these regions –left superior longitudinal fasiculus (SLF) – were associated with changes in performance on an attention task. Finally, changes in left dlPFC – IPC rs-FC correlated with the change in left SLF structural connectivity as measured by fractional anisotropy (FA) in the Tenacity group only.
Genomic Landscape of Intramedullary Spinal Cord Gliomas
Authors: Zhang Ming , Iyer Rajiv R. , Azad Tej D. , Wang Qing , Garzon-Muvdi Tomas , Wang Joanna , Liu Ann , Burger Peter , Eberhart Charles , Rodriguez Fausto J. , Sciubba Daniel M. , Wolinsky Jean-Paul , Gokaslan Ziya , Groves Mari L. , Jallo George I. , Bettegowda Chetan 
Published: December 2019

AbstractIntramedullary spinal cord tumors (IMSCTs) are rare neoplasms that have limited treatment options and are associated with high rates of morbidity and mortality. To better understand the genetic basis of these tumors we performed whole exome sequencing on 45 tumors and matched germline DNA, including twenty-nine spinal cord ependymomas and sixteen astrocytomas. Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts (e.g. glioblastoma) did not harbor the canonical mutations associated with their intracranial counterparts. Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides the framework to begin more biologically based therapeutic strategies.
The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development
Authors: Schmidt Ewoud R. E. , Kupferman Justine V. , Stackmann Michelle , Polleux Franck 
Published: December 2019

AbstractHuman-specific gene duplications (HSGDs) have recently emerged as key modifiers of brain development and evolution. However, the molecular mechanisms underlying the function of HSGDs remain often poorly understood. In humans, a truncated duplication of SRGAP2A led to the emergence of two human-specific paralogs: SRGAP2B and SRGAP2C. The ancestral copy SRGAP2A limits synaptic density and promotes maturation of both excitatory (E) and inhibitory (I) synapses received by cortical pyramidal neurons (PNs). SRGAP2C binds to and inhibits all known functions of SRGAP2A leading to an increase in E and I synapse density and protracted synapse maturation, traits characterizing human cortical neurons. Here, we demonstrate how the evolutionary changes that led to the emergence of SRGAP2 HSGDs generated proteins that, in neurons, are intrinsically unstable and, upon hetero-dimerization with SRGAP2A, reduce SRGAP2A levels in a proteasome-dependent manner. Moreover, we show that, despite only a few non-synonymous mutations specifically targeting arginine residues, SRGAP2C is unique compared to SRGAP2B in its ability to induce long-lasting changes in synaptic density throughout adulthood. These mutations led to the ability of SRGAP2C to inhibit SRGAP2A function and thereby contribute to the emergence of human-specific features of synaptic development during evolution.
Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27
Authors: García-Gutiérrez Lucía , Bretones Gabriel , Molina Ester , Arechaga Ignacio , Symonds Catherine , Acosta Juan C. , Blanco Rosa , Fernández Adrián , Alonso Leticia , Sicinski Piotr , Barbacid Mariano , Santamaría David , León Javier 
Published: December 2019

AbstractCell cycle stimulation is a major transforming mechanism of Myc oncoprotein. This is achieved through at least three concomitant mechanisms: upregulation of cyclins and Cdks, downregulation of the Cdk inhibitors p15 and p21 and the degradation of p27. The Myc-p27 antagonism has been shown to be relevant in human cancer. To be degraded, p27 must be phosphorylated at Thr-187 to be recognized by Skp2, a component of the ubiquitination complex. We previously described that Myc induces Skp2 expression. Here we show that not only Cdk2 but Cdk1 phosphorylates p27 at the Thr-187. Moreover, Myc induced p27 degradation in murine fibroblasts through Cdk1 activation, which was achieved by Myc-dependent cyclin A and B induction. In the absence of Cdk2, p27 phosphorylation at Thr-187 was mainly carried out by cyclin A2-Cdk1 and cyclin B1-Cdk1. We also show that Cdk1 inhibition was enough for the synthetic lethal interaction with Myc. This result is relevant because Cdk1 is the only Cdk strictly required for cell cycle and the reported synthetic lethal interaction between Cdk1 and Myc.
Boosted acceleration of protons by tailored ultra-thin foil targets
Authors: Kaymak Vural , Aktan Esin , Cerchez Mirela , Elkin Bentsian , Papenheim Marc , Prasad Rajendra , Pukhov Alexander , Scheer Hella-C. , Schroer Anna-Marie , Willi Oswald , Aurand Bastian 
Published: December 2019

AbstractWe report on a detailed experimental and numerical study on the boosted acceleration of protons from ultra-thin hemispherical targets utilizing multi-Joule short-pulse laser-systems. For a laser intensity of 1 × 1020 W/cm2 and an on-target energy of only 1.3 J with this setup a proton cut-off energy of 8.5 MeV was achieved, which is a factor of 1.8 higher compared to a flat foil target of the same thickness. While a boost of the acceleration process by additionally injected electrons was observed for sophisticated targets at high-energy laser-systems before, our studies reveal that the process can be utilized over at least two orders of magnitude in intensity and is therefore suitable for a large number of nowadays existing laser-systems. We retrieved a cut-off energy of about 6.5 MeV of proton energy per Joule of incident laser energy, which is a noticeable enhancement with respect to previous results employing this mechanism. The approach presented here has the advantage of using structure-wise simple targets and being sustainable for numerous applications and high repetition rate demands at the same time.
Heat dissipation in quasi-ballistic single-atom contacts at room temperature
Authors: Tsutsui Makusu , Chen Yu-Chang 
Published: December 2019

AbstractWe report on evaluations of local heating in Au single-atom chains at room temperature. We performed onsite thermometry of atomic-scale Au junctions under applied sinusoidal voltage of variable amplitudes. The AC approach enabled to preclude electromigration effects for characterizing the influence of energy dissipations on the lifetime. We elucidated nonlinear increase in the effective temperature of the current-carrying single-atom chains with the voltage amplitudes, which was attributed to subtle interplay between electron-phonon scattering and electron-mediated thermal transport in the quasi-ballistic conductor. We also found that only 0.2% of the electric power contributed to local heating while the majority was consumed at the diffusive bank. The present findings can be used for thermal management of future integrated nanoelectronics.
Long-term impact of oral surgery with or without amoxicillin on the oral microbiome-A prospective cohort study
Authors: Menon R. K. , Gomez A. , Brandt B. W. , Leung Y. Y. , Gopinath D. , Watt R. M. , Crielaard W. , Nelson K. E , Botelho M. G. 
Published: December 2019

AbstractRoutine postoperative antibiotic prophylaxis is not recommended for third molar extractions. However, amoxicillin still continues to be used customarily in several clinical practices worldwide to prevent infections. A prospective cohort study was conducted in cohorts who underwent third molar extractions with (group EA, n = 20) or without (group E, n = 20) amoxicillin (250 mg three times daily for 5 days). Further, a control group without amoxicillin and extractions (group C, n = 17) was included. Salivary samples were collected at baseline, 1-, 2-, 3-, 4-weeks and 3 months to assess the bacterial shift and antibiotic resistance gene changes employing 16S rRNA gene sequencing (Illumina-Miseq) and quantitative polymerase chain reaction. A further 6-month follow-up was performed for groups E and EA. Seven operational taxonomic units reported a significant change from baseline to 3 months for group EA (adjusted p < 0.05). No significant change in relative abundance of bacteria and β-lactamase resistance genes (TEM-1) was observed over 6 months for any group (adjusted p > 0.05). In conclusion, the salivary microbiome is resilient to an antibiotic challenge by a low-dose regimen of amoxicillin. Further studies evaluating the effect of routinely used higher dose regimens of amoxicillin on gram-negative bacteria and antibiotic resistance genes are warranted.
Rectal Cancer Invasiveness: Whole-Lesion Diffusion-Weighted Imaging (DWI) Histogram Analysis by Comparison of Reduced Field-of-View and Conventional DWI Techniques
Authors: Peng Yang , Tang Hao , Hu Xuemei , Shen Yaqi , Kamel Ihab , Li Zhen , Hu Daoyu 
Published: December 2019

AbstractTo explore the role of whole-lesion histogram analysis of apparent diffusion coefficient (ADC) for discriminating between T stages of rectal carcinoma by comparison of reduced field-of-view (FOV) and conventional DWI techniques. 102 patients with rectal cancer were enrolled in this retrospective study. All patients received preoperative MR scan at 3 T, including reduced and full FOV DWI sequences. Histogram parameters from two DWI methods were calculated and correlated with histological T stage of rectal cancer. The diagnostic performance of individual parameter for differentiating stage pT1-2 and pT3-4 tumors from both DWI techniques was assessed by receiver operating characteristic curve analysis. There were significant differences for the parameters of ADCmean, 50th, 75th, 90th, 95th percentiles, skewness and kurtosis of both DWI sequences in patients with pT1-2 as compared to those with pT3-4 tumors (P < 0.05), in addition to parameters including ADCmin (P = 0.015) and 25th percentile (P = 0.006) from rFOV DWI. Correlations were noted between T staging and above histogram parameters from rFOV DWI (r: −0.741–0.682) and fFOV DWI (r: −0.449–0.449), besides parameters of ADCmin (0.370) and 25th percentile (−0.425) from rFOV DWI. The AUCs of 75th and 90th percentiles from rFOV DWI were significantly higher than that from fFOV DWI (P = 0.0410 and P = 0.0208). The whole-lesion histogram analysis based on rFOV DWI was overall more advantageous than the one based on fFOV DWI in differentiating T staging of rectal cancer and the 90th percentile ADC from rFOV DWI was the value with the highest AUC (0.932).
Quantum scale biomimicry of low dimensional growth: An unusual complex amorphous precursor route to TiO2 band confinement by shape adaptive biopolymer-like flexibility for energy applications
Authors: Choi Dahyun , Sonkaria Sanjiv , Fox Stephen J. , Poudel Shivraj , Kim Sung-yong , Kang Suhee , Kim Seheon , Verma Chandra , Ahn Sung Hoon , Lee Caroline Sunyong , Khare Varsha 
Published: December 2019

AbstractCrystallization via an amorphous pathway is often preferred by biologically driven processes enabling living species to better regulate activation energies to crystal formation that are intrinsically linked to shape and size of dynamically evolving morphologies. Templated ordering of 3-dimensional space around amorphous embedded non-equilibrium phases at heterogeneous polymer─metal interfaces signify important routes for the genesis of low-dimensional materials under stress-induced polymer confinement. We report the surface induced catalytic loss of P=O ligands to bond activated aromatization of C−C C=C and Ti=N resulting in confinement of porphyrin-TiO2 within polymer nanocages via particle attachment. Restricted growth nucleation of TiO2 to the quantum scale (≤2 nm) is synthetically assisted by nitrogen, phosphine and hydrocarbon polymer chemistry via self-assembly. Here, the amorphous arrest phase of TiO2 is reminiscent of biogenic amorphous crystal growth patterns and polymer coordination has both a chemical and biomimetic significance arising from quantum scale confinement which is atomically challenging. The relative ease in adaptability of non-equilibrium phases renders host structures more shape compliant to congruent guests increasing the possibility of geometrical confinement. Here, we provide evidence for synthetic biomimicry akin to bio-polymerization mechanisms to steer disorder-to-order transitions via solvent plasticization-like behaviour. This challenges the rationale of quantum driven confinement processes by conventional processes. Further, we show the change in optoelectronic properties under quantum confinement is intrinsically related to size that affects their optical absorption band energy range in DSSC.
Transcranial direct current stimulation (tDCS) over vmPFC modulates interactions between reward and emotion in delay discounting
Authors: Manuel Aurélie L. , Murray Nicholas W. G. , Piguet Olivier 
Published: December 2019

AbstractDelay discounting requires computing trade-offs between immediate-small rewards and later-larger rewards. Negative and positive emotions shift decisions towards more or less impulsive responses, respectively. Models have conceptualized this trade-off by describing an interplay between “emotional” and “rational” processes, with the former involved during immediate choices and relying on the ventromedial prefrontal cortex (vmPFC), and the latter involved in long-term choices and relying on the dorsolateral prefrontal cortex (dlPFC). Whether stimulation of the vmPFC modulates emotion-induced delay discounting remains unclear. We applied tDCS over the vmPFC in 20 healthy individuals during a delay discounting task following an emotional (positive, negative) or neutral induction. Our results showed that cathodal tDCS increased impulsivity after positive emotions in high impulsivity trials. For low impulsivity trials, anodal tDCS decreased impulsivity following neutral induction compared with emotional induction. Our findings demonstrate that the vmPFC integrates reward and emotion most prominently in situations of increased impulsivity, whereas when higher cognitive control is required the vmPFC appears to be less engaged, possibly due to recruitment of the dlPFC. Understanding how stimulation and emotion influence decision-making at the behavioural and neural levels holds promise to develop interventions to reduce impulsivity.
Formalin-induced and neuropathic pain altered time estimation in a temporal bisection task in rats
Authors: Liu Xinhe , Wang Ning , Wang Jinyan , Luo Fei 
Published: December 2019

AbstractTime perception is an important ability that is related closely to humans’ and animals’ daily activities. It can be distorted by various emotional states. In human studies, experimental pain has been shown to prolong the perception of time. However, related animal studies are lacking. In this study, we used a temporal bisection task to investigate how acute inflammatory pain (induced by hind-paw formalin injection) and chronic neuropathic pain [induced by spinal nerve ligation (SNL)] affected time perception in rats. Rats were trained to recognize “short” (1200-ms) and “long” (2400-ms) anchor-duration pure tones and were rewarded for corresponding lever presses. During testing, rats perceived a series of intermediate-duration and anchor-duration pure tones, and selected levers corresponding to the “short” and “long” tones. After formalin injection, rats gave more “long” lever-press responses than after saline injection. The point of subjective equality after formalin injection also increased, suggesting that formalin-induced acute pain extended time perception. In contrast, rats that had undergone SNL gave fewer “long” lever-press responses compared with the sham surgery group. This animal study suggests that formalin-induced pain and neuropathic pain may have different effects on time perception.
A change in the zinc ion concentration reflects the maturation of insulin-producing cells generated from adipose-derived mesenchymal stem cells
Authors: Ohta Shogo , Ikemoto Tetsuya , Wada Yuma , Saito Yu , Yamada Shinichiro , Imura Satoru , Morine Yuji , Shimada Mitsuo 
Published: December 2019

AbstractThe generation of insulin-producing cells (IPCs) from pluripotent stem cells could be a breakthrough treatment for type 1 diabetes. However, development of new techniques is needed to exclude immature cells for clinical application. Dithizone staining is used to evaluate IPCs by detecting zinc. We hypothesised that zinc ion (Zn2+) dynamics reflect the IPC maturation status. Human adipose-derived stem cells were differentiated into IPCs by our two-step protocol using two-dimensional (2D) or 3D culture. The stimulation indexes of 2D -and 3D-cultured IPCs on day 21 were 1.21 and 3.64 (P < 0.05), respectively. The 3D-cultured IPCs were stained with dithizone during culture, and its intensity calculated by ImageJ reached the peak on day 17 (P < 0.05). Blood glucose levels of streptozotocin-induced diabetic nude mice were normalised (4/4,100%) after transplantation of 96 3D-cultured IPCs. Zn2+ concentration changes in the medium of 3D cultures had a negative value in the early period and a large positive value in the latter period. This study suggests that Zn2+ dynamics based on our observations and staining of zinc transporters have critical roles in the differentiation of IPCs, and that their measurement might be useful to evaluate IPC maturation as a non-destructive method.
Transcriptional correlates of the pathological phenotype in a Huntington’s disease mouse model
Authors: Gallardo-Orihuela Andrea , Hervás-Corpión Irati , Hierro-Bujalance Carmen , Sanchez-Sotano Daniel , Jiménez-Gómez Gema , Mora-López Francisco , Campos-Caro Antonio , Garcia-Alloza Monica , Valor Luis M. 
Published: December 2019

AbstractHuntington disease (HD) is a fatal neurodegenerative disorder without a cure that is caused by an aberrant expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene. Although a negative correlation between the number of CAG repeats and the age of disease onset is established, additional factors may contribute to the high heterogeneity of the complex manifestation of symptoms among patients. This variability is also observed in mouse models, even under controlled genetic and environmental conditions. To better understand this phenomenon, we analysed the R6/1 strain in search of potential correlates between pathological motor/cognitive phenotypical traits and transcriptional alterations. HD-related genes (e.g., Penk, Plk5, Itpka), despite being downregulated across the examined brain areas (the prefrontal cortex, striatum, hippocampus and cerebellum), exhibited tissue-specific correlations with particular phenotypical traits that were attributable to the contribution of the brain region to that trait (e.g., striatum and rotarod performance, cerebellum and feet clasping). Focusing on the striatum, we determined that the transcriptional dysregulation associated with HD was partially exacerbated in mice that showed poor overall phenotypical scores, especially in genes with relevant roles in striatal functioning (e.g., Pde10a, Drd1, Drd2, Ppp1r1b). However, we also observed transcripts associated with relatively better outcomes, such as Nfya (CCAAT-binding transcription factor NF-Y subunit A) plus others related to neuronal development, apoptosis and differentiation. In this study, we demonstrated that altered brain transcription can be related to the manifestation of HD-like symptoms in mouse models and that this can be extrapolated to the highly heterogeneous population of HD patients.