julilili42/papers huggingface dataset:
Investigation of Autosomal Genetic Sex Differences in Parkinson’s disease
2021-02-12

Abstract Parkinson’s disease (PD) is a complex neurodegenerative disorder. Males are on average ∼1.5 times more likely to develop PD compared to females. Over the years genome-wide association studies (GWAS) have identified numerous genetic risk factors for PD, however it is unclear whether genetics contribute to disease etiology in a sex-specific manner. In an effort to study sex-specific genetic factors associated with PD, we explored two large genetic datasets from the International Parkinson’s Disease Genomics Consortium and the UK Biobank consisting of 13,020 male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases and 90,662 female controls. We performed GWAS meta-analyses to identify distinct patterns of genetic risk contributing to disease in male versus female PD cases. In total 19 genome-wide significant regions were identified, and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWASes was identified (rg=0.877) and heritability estimates were identical between male and female PD cases (∼20%). We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus females.
Review Protocol on Numerical and Arithmetic Impairments in Alzheimer, Parkinson's Dementia and Dementia with Lewy Bodies
2021-02-12

Background: Reviews addressing numerical and arithmetic deficits in neurodegenerative dementias have been conducted about 20 years ago and mainly focus on Alzheimer’s Disease (AD). Due to the overlap of neuronal areas and circuits involved in numerical cognition with areas degenerating in neurodegenerative dementias such as Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (LBD), an updated overview on available studies is needed. The aim of the planned systematic review and meta-analysis is therefore (1) to identify the prevalence of arithmetic deficits in patients with the neurodegenerative dementias AD, PDD, and LBD compared to Elderly without neurodegenerative diseases. (2) We aim at identifying patterns of deficits in various tasks of numerical cognition (differing regarding processing depth and required cognitive representations), which differ between different dementia groups.Methods: A systematic review and meta-analysis will be conducted following PRISMA criteria. Electronic databases of published and unpublished studies will be searched for relevant articles with predefined search terms. Studies are eligible if they report comparisons of patients with AD, PDD, and/ or LBD with an elderly control group without neurodegeneration regarding an empirical measure of numerical and/ or arithmetic function. Experimental case-control designs and group studies will be included. Studies without a control group, lacking an established diagnosis, only reporting neuro-imaging data and reviews will be excluded. Original study quality will be assessed with the ROBINS-I tool. Depending on the resulting data structure, meta-analyses will be conducted with random effects models or two-level models with nested effect sizes. Subgroups of the different dementias will be analysed using meta-regression.Discussion: Results of the current review cannot only be used to update the two existing reviews from early 2000s, but also to systematize numerical and arithmetic impairments in neurodegenerative dementias in the light of both neurocognitive theories of numerical cognition and neurodegeneration. It has the potential to estimate prevalence of numerical deficits in AD, PDD, and LBD, and compare numerical symptoms between different dementia entities. These findings can support clinical diagnostic and therapeutic guideline development based on more specific information regarding impairment in the respective neurodegenerative dementia. However, our systematic review and meta-analysis relies on the quality of the original studies and the quality of available risk of bias assessments.
Dataset related to article "Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration"
2021-02-12

This record contains data related to article "Control of Complement Activation by the Long Pentraxin PTX3: Implications in Age-Related Macular Degeneration" <strong>Abstract. </strong>Dysregulation of the complement system is central to age-related macular degeneration (AMD), the leading cause of blindness in the developed world. Most of the genetic variation associated with AMD resides in complement genes, with the greatest risk associated with polymorphisms in the <em>complement factor H</em> (<em>CFH</em>) gene; factor H (FH) is the major inhibitor of the alternative pathway (AP) of complement that specifically targets C3b and the AP C3 convertase. Long pentraxin 3 (PTX3) is a soluble pattern recognition molecule that has been proposed to inhibit AP activation via recruitment of FH. Although present in the human retina, if and how PTX3 plays a role in AMD is still unclear. In this work we demonstrated the presence of PTX3 in the human vitreous and studied the PTX3-FH-C3b crosstalk and its effects on complement activation in a model of retinal pigment epithelium (RPE). RPE cells cultured in inflammatory AMD-like conditions overexpressed the PTX3 protein, and up-regulated AP activating genes. PTX3 bound RPE cells in a physiological setting, however this interaction was reduced in inflammatory conditions, whereby PTX3 had no complement-inhibiting activity on inflamed RPE. However, on non-cellular surfaces, PTX3 formed a stable ternary complex with FH and C3b that acted as a "hot spot" for complement inhibition. Our findings suggest a protective role for PTX3 in response to complement dysregulation in AMD and point to a novel mechanism of complement regulation by this pentraxin with potential implications in pathology and pharmacology of AMD.
Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma
2021-02-13

Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).
Organization of radial glia reveals growth pattern in the telencephalon of a percomorph fish Astatotilapia burtoni
2021-02-13

In the brain of teleost fish, radial glial cells are the main astroglial cell type. To understand how radial glia structures are adapting to continuous growth of the brain, we studied the astroglial cells in the telencephalon of the cichlid fish Astatotilapia burtoni in small fry to large specimens. These animals grow to a standard length of 10-12 cm in this fish species, corresponding to a more than 100-fold increase in brain volume. Focusing on the telencephalon where glial cells are arranged radially in the everted (dorsal) pallium, immunocytochemistry for glial markers revealed an aberrant pattern of radial glial fibers in the central division of the dorsal pallium (DC, i.e., DC4 and DC5). The main glial processes curved around these nuclei, especially in the posterior part of the telencephalon. This was verified in tissue-cleared brains stained for glial markers. We further analyzed the growth of radial glia by immunocytochemically applied stem cell (proliferating cell nuclear antigen [PCNA], Sox2) and differentiation marker (doublecortin) and found that these markers were expressed at the ventricular surface consistent with a stacking growth pattern. In addition, we detected doublecortin and Sox2 positive cells in deeper nuclei of DC areas. Our data suggest that radial glial cells give rise to migrating cells providing new neurons and glia to deeper pallial regions. This results in expansion of the central pallial areas and displacement of existing radial glial. In summary, we show that radial glial cells can adapt to morphological growth processes in the adult fish brain and contribute to this growth.
Drosophila Homeodomain-Interacting Protein Kinase (Hipk) Phosphorylates the Hippo/Warts Signalling Effector Yorkie
2021-02-13

Developmental growth and patterning are regulated by an interconnected signalling network of several pathways. In Drosophila, the Warts (Wts) kinase, a component of the Hippo signalling pathway, plays an essential role in regulating transcription and growth by phosphorylating its substrate Yorkie (Yki). The phosphorylation of Yki critically influences its localisation and activity as a transcriptional coactivator. In this study, we identified the homeodomain-interacting protein kinase (Hipk) as another kinase that phosphorylates Yki and mapped several sites of Yki phosphorylated by Hipk, using in vitro analysis: Ser168, Ser169/Ser172 and Ser255. These sites might provide auxiliary input for Yki regulation in vivo, as transgenic flies with mutations in these show prominent phenotypes; Hipk, therefore, represents an additional upstream regulator of Yki that works in concert with Wts.
Experimental admixture among geographically disjunct populations of an invasive plant yields a global mosaic of reproductive incompatibility and heterosis
2021-02-14

Abstract Invasive species have the ability to rapidly adapt in the new regions where they are introduced. Classic evolutionary theory predicts that the accumulation of genetic differences over time in allopatric isolation may lead to reproductive incompatibilities resulting in decreases in reproductive success and, eventually, to speciation. However, experimental evidence for this theoretical prediction in the context of invasive species is lacking. We aimed to test for the potential of allopatry to determine reproductive success of invasive plants, by experimentally admixing genotypes from six different native and non‐native regions of Centaurea solstitialis , an invasive forb for which preliminary studies have detected some degree of reproductive isolation between one native and non‐native region. We grew plants under common garden conditions and outcrossed individuals originating from different source populations in the native and introduced range to evaluate reproductive success in terms of seed to ovule ratio produced. We also assessed geographical and genetic isolation among C . solstitialis regions as a potential driving factor of reproductive success. Experimental admixture generated mixed fitness effects, including significant increases, decreases and no differences in reproductive success as compared to crosses within population (control). Centaurea solstitialis invasive populations in the Americas generated preponderantly negative fitness interactions, regardless of the pollen source, suggesting selection against immigrants and reinforcement. Other non‐native populations (Australia) as well as individuals from the native range of Spain demonstrated an increase in fitness for between‐region crosses, indicating inbreeding. These differences show an asymmetrical response to inter‐regional gene flow, but no evidence of isolation by distance. Synthesis . The speed of adaptation and the accumulation of reproductive incompatibilities among allopatric populations of invasive species might be more rapid than previously assumed. Our data show a global mosaic of reproductive outputs, showcasing an array of evolutionary processes unfolding during colonization at large biogeographical scales.
Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
2021-02-15

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.
Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion
2021-02-15

Abstract Background Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood. Methods Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) v. a sham control condition on mood after the exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design) using linear mixed-effects and hierarchical Bayesian analyses of mood ratings. Results We found that 90 min of either left-sided or right-sided taVNS improved positive mood [ b = 5.11, 95% credible interval, CI (1.39–9.01), 9.6% improvement relative to the mood intercept, BF 10 = 7.69, p LME = 0.017], yet only during the post-stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation [ r = −0.42, 95% CI (−0.58 to −0.21), BF 10 = 249]. Conclusions We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to the reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.
Potential origin of the state-dependent high-energy tail in the black hole microquasar Cygnus X-1 as seen with INTEGRAL
2021-02-15

Context. 0.1–10 MeV observations of the black hole microquasar Cygnus X-1 have shown the presence of a spectral feature in the form of a power law in addition to the standard black body (0.1–10 keV) and Comptonization (10–200 keV) components observed by INTEGRAL in several black-hole X-ray binaries. This so-called “high-energy tail” was recently shown to be strong in the hard spectral state of Cygnus X-1, and, in this system, has been interpreted as the high-energy part of the emission from a compact jet. Aims. This result was nevertheless obtained from a data set largely dominated by hard state observations. In the soft state, only upper limits on the presence and hence the potential parameters of a high-energy tail could be derived. Using an extended data set, we aim to obtain better constraints on the properties of this spectral component in both states. Methods. We make use of data obtained from about 15 years of observations with the INTEGRAL satellite. The data set is separated into the different states and we analyze stacked state-resolved spectra obtained from the X-ray monitors, the gamma-ray imager, and the gamma-ray spectrometer (SPI) onboard. Results. A high-energy component is detected in both states, confirming its earlier detection in the hard state and its suspected presence in the soft state with INTEGRAL, as seen in a much smaller SPI data set. We first characterize the high-energy tail components in the two states through a model-independent, phenomenological analysis. We then apply physical models based on hybrid Comptonization ( eqpair and belm ). The spectra are well modeled in all cases, with a similar goodness of the fits. While in the semi-phenomenological approach the high-energy tail has similar indices in both states, the fits with the physical models seem to indicate slightly different properties. Based on this approach, we discuss the potential origins of the high-energy components in both the soft and hard states, and favor an interpretation where the high-energy component is due to a compact jet in the hard state and hybrid Comptonization in either a magnetized or nonmagnetized corona in the soft state.
Structured Reporting in the Characterization of Renal Cysts by Contrast-Enhanced Ultrasound (CEUS) Using the Bosniak Classification System—Improvement of Report Quality and Interdisciplinary Communication
2021-02-15

Background: This study aims to evaluate the potential benefits of structured reporting (SR) compared to conventional free-text reporting (FTR) in contrast-enhanced ultrasound (CEUS) of cystic renal lesions, based on the Bosniak classification. Methods: Fifty patients with cystic renal lesions who underwent CEUS were included in this single-center study. FTR created in clinical routine were compared to SR retrospectively generated by using a structured reporting template. Two experienced urologists evaluated the reports regarding integrity, effort for information extraction, linguistic quality, and overall quality. Results: The required information could easily be extracted by the reviewers in 100% of SR vs. 82% of FTR (p &lt; 0.001). The reviewers trusted the information given by SR significantly more with a mean of 5.99 vs. 5.52 for FTR (p &lt; 0.001). SR significantly improved the linguistic quality (6.0 for SR vs. 5.68 for FTR (p &lt; 0.001)) and the overall report quality (5.98 for SR vs. 5.58 for FTR (p &lt; 0.001)). Conclusions: SR significantly increases the quality of radiologic reports in CEUS examinations of cystic renal lesions compared to conventional FTR and represents a promising approach to facilitate interdisciplinary communication in the future.
Data for "Magnetoencephalographic Signatures of Conscious Processing Before Birth"
2021-02-15

&lt;p&gt;Data uploaded here belongs to the manuscript "Magnetoencephalographic Signatures of Conscious Processing Before Birth" (https://www.biorxiv.org/content/10.1101/2020.10.27.357129v1). It contains an overview over the study participants and processed MEG data, used for the analysis described in the manuscript. The content of the folder is further described in a README text file. The methods section of the manuscript contains further necessary information. For more information or any clarification or additional data/code, please contact the author. &lt;/p&gt;
Frontispiece: Pushing the Limits of Acene Chemistry: The Recent Surge of Large Acenes
2021-02-15

Acenes are a fundamental class of organic π conjugated aromatic compounds. Due to the linear annulation of benzene building blocks, they acquire high reactivity with increasing lengths that limited their experimental accessibility for a long time. The Review by C. Tönshoff and H. F. Bettinger on page 3193 summarizes recent synthetic, spectroscopic, and computational progress on acene molecules that significantly enhanced the understanding of this fascinating class of compounds.
Radiocarbon dates associated to Neolithic contexts (ca. 5900 – 2000 cal BC) from the northwestern Mediterranean Arch to the High Rhine area
2021-02-15

This database is a compilation of radiocarbon dates associated with the process of arrival, development and consolidation of the first farming communities that settled between the north-western Mediterranean Arch and the High Rhine area approximately between 5900 and 2000 cal BC., covering a large geographical area previously out of the main focus of <sup>14</sup>C data compilations. The database includes dates from scientific publications and it incorporates several fields for evaluating the quality and the reliability of the available samples. It overall provides 3690 radiocarbon dates that allow the scientific community to build chronological models that can be combined with other proxies such as spatial location, type of sample or chronocultural phase.
Data for "Magnetoencephalographic Signatures of Conscious Processing Before Birth"
2021-02-15

Data uploaded here belongs to the manuscript "Magnetoencephalographic Signatures of Conscious Processing Before Birth" (Moser, J., Schleger, F., Weiss, M., Sippel, K., Semeia, L., & Preissl, H. (2021). Magnetoencephalographic signatures of conscious processing before birth. Developmental cognitive neuroscience, 49, 100964). It contains an overview over the study participants and processed MEG data, used for the analysis described in the manuscript. The content of the folder is further described in a README text file. The methods section of the manuscript contains further necessary information. Additional code can be found on Github: https://github.com/moser297/fMEG_data_processing/tree/main/Code_DCN_2021_fetal. For more information or any clarification or additional data/code, please contact the author.
Tandem Lesions in Anterior Circulation Stroke
2021-02-16

Background and Purpose: Tandem lesions in the anterior circulation account for up to 30% of all large vessel occlusion strokes. The optimal periprocedural approach in these lesions is still a matter of debate. Methods: Data from the German Stroke Registry—Endovascular Treatment between June 2015 and December 2019 were analyzed. The German Stroke Registry—Endovascular Treatment is an academic, independent, prospective, multicenter, observational registry study with 25 participating stroke centers from all over Germany enrolling consecutive mechanical thrombectomy patients. Tandem lesions were defined as a combination of a relevant extracranial internal carotid artery (ICA) pathology (ipsilateral stenosis &gt;70% or occlusion) and concomitant intracranial large vessel occlusion. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b-3. The modified Rankin Scale score of 0 to 2 at 3 months indicated good outcome. The aim of this study was to investigate the safety and efficacy of different technical strategies in tandem lesions. Results: Out of 6635 patients, 874 (13.2%) presented with tandem lesions. Of these, 607 (69.5%) underwent acute treatment of the extracranial ICA. Acute treatment of the extracranial ICA lesion led to a higher probability of successful reperfusion (odds ratio, 40.63 [95% CI, 30.03–70.06]) compared with patients who did not undergo acute treatment of the extracranial ICA lesion and was associated with good clinical outcome (39.5% versus 29.3%, P &lt;0.001) and a lower rate of mortality (17.1% versus 27.1%, P &lt;0.001) at 3 months. Further significant predictors of successful reperfusion were age (odds ratio, 0.98 [95% CI, 0.96–0.99]; P =0.035) and intravenous thrombolysis (odds ratio, 10.58 [95% CI, 10.04–20.4]; P =0.033). Intracranial-first approach (n=227) compared with extracranial-first approach (n=267) resulted in a shorter time to flow restoration (53.5 versus 72.0 minutes, P &lt;0.001) and a higher nonsignificant probability of good outcome (45.8% versus 33.0%, P =0.24) without differences in periprocedural complications. Conclusions: In tandem lesions in the anterior circulation, acute treatment of the extracranial ICA lesion is associated with better clinical outcome and lower mortality. The intracranial-first approach might provide advantages.