julilili42/papers huggingface dataset:
Is a single portal venous phase in contrast-enhanced CT sufficient to detect metastases or recurrence in clear cell renal cell carcinoma? – a single-center retrospective study
2022-01-21

Abstract Background This study aims at describing the imaging features of the metastatic presentation of clear cell renal cell carcinoma (ccRCC) in arterial (AP) and portal venous phase (PVP) of contrast-enhanced-computed-tomography (CECT) during clinical follow-up (FU) and to evaluate the necessity of a dual phase approach for metastasis detection. Methods We identified a total of 584 patients that were diagnosed with ccRCC between January 2016 and April 2020. Inclusion criteria were histologically proven ccRCC with metastatic spread, proven by histology or interim follow-up of at least 2 years and follow-up CT examination with AP and PVP CECT including thorax/abdomen and pelvis. Exclusion criteria were defined by missing or incomplete CT-scans or lack of sufficient follow-up. CT studies of 43 patients with histologically proven ccRCCs were analyzed in retrospect. AP and PVP images were analyzed by two radiologists for metastases, two additional independent radiologists analyzed PVP images only. A 5-point Likert scale was used to evaluate the likelihood off the presence of metastasis. Imaging patterns of the metastases were analyzed visually. Results 43 patients (16 female; mean age: 67±10 years) with recurrent ccRCC and metastatic disease were included. Three imaging patterns were observed (solid, heterogeneous or cystic metastases), which rarely exhibited calcifications (2%). All metastases showed hyperenhancement in AP and PVP. Inter-reader agreement was substantial (Fleiss’ κ 0.6–0.8, p &lt;0.001). No significant differences in sensitivity or specificity between readers (AP and PVP images vs. PVP images only) were present (79.4-85.2%, 97.1-99.6%, p ≥ 0.05). The area under the receiver-operating-characteristic (ROC) curve was between 0.901and 0.922 for all four radiologists. Conclusions Similar rates for detection, sensitivity and specificity of metastasis and local recurrence in ccRCC were observed irrespective of using a dual-phase protocol with AP and PVP or a single PVP protocol only. Thus, a single-phase examination of PVP can be sufficient for experienced radiologists to detect metastatic disease in the follow-up of ccRCC patients.
Long-Term Leaching Behavior of Organic and Inorganic Pollutants after Wet Processing of Solid Waste Materials
2022-01-23

The recycling of mineral materials is a sustainable and economical approach for reducing solid waste and saving primary resources. However, their reuse may pose potential risks of groundwater contamination, which may result from the leaching of organic and inorganic substances into water that percolates the solid waste. In this study, column leaching tests were used to investigate the short- and long-term leaching behavior of “salts”, “metals”, and organic pollutants such as PAHs and herbicides from different grain size fractions of construction &amp; demolition waste (CDW) and railway ballast (RB) after a novel treatment process. Specifically, silt, sand and gravel fractions obtained after a sequential crushing, sieving, and washing process (“wet-processing”) of very heterogeneous input materials are compared with respect to residual contamination, potentially limiting their recycling. Concentrations in solid fractions and aqueous leachate were evaluated according to threshold values for groundwater protection to identify relevant substances and to classify materials obtained for recycling purposes according to limit values. For that, the upcoming German recycling degree was applied for the first time. Very good agreement was observed between short and extensive column tests, demonstrating that concentrations at L/S 2 ratios are suitable for quality control of recycling materials. Different solutes showed a characteristic leaching behavior such as the rapid decrease in “salts”, e.g., SO42− and Cl−, from all solid fractions, and a slower decrease in metals and PAHs in the sand and silt fractions. Only the gravel fraction, however, showed concentrations of potential pollutants low enough for an unlimited re-use as recycling material in open technical applications. Sand fractions may only be re-used as recycling material in isolated or semi-isolated scenarios. Leaching from heterogeneous input materials proved harder to predict for all compounds. Overall, column leaching tests proved useful for (i) initial characterization of the mineral recycling materials, and (ii) continuous internal (factory control) and external quality control within the upcoming German recycling decree. Results from such studies may be used to optimize the treatment of mixed solid waste since they provide rapid insight in residual pollution of material fractions and their leaching behavior.
Amacrine cells differentially balance zebrafish colour circuits in the central and peripheral retina
2022-01-23

SUMMARY In vertebrate vision, the feature-extracting circuits of the inner retina are driven by photoreceptors whose outputs are already pre-processed. In zebrafish, for example, outer retinal circuits split “colour” from “greyscale” information across all four cone-photoreceptor types. How does the inner retina process this incoming spectral information while also combining cone-signals to shape new greyscale functions? We address this question by imaging the light driven responses of amacrine cells (ACs) and bipolar cells (BCs) in larval zebrafish, in the presence and pharmacological absence of inner retinal inhibition. We find that amacrine cells exert distinct effects on greyscale processing depending on retinal region, as well as contributing to the generation of colour opponency in the central retina. However, in the peripheral retina amacrine cells enhanced opponency in some bipolar cells while at the same time suppressing pre-existing opponency in others, such that the net change in the number of colour-opponent units was essentially zero. To achieve this ‘dynamic balance’ ACs counteracted intrinsic colour opponency of BCs via the On-channel. Consistent with these observations, Off-stratifying ACs were exclusively achromatic, while all colour opponent ACs stratified in the On-sublamina. This study reveals that the central and peripheral retina of larval zebrafish employ fundamentally distinct inhibitory circuits to control the interaction between greyscale- and colour-processing. Differential actions on the On- and Off-channels control the transmission of colour-opponent signals in the periphery.
Microbiome profiling reveals that Pseudomonas antagonises parasitic nodule colonisation of cheater rhizobia in Lotus
2022-01-24

Summary Nodule microbiota are dominated by symbiotic nitrogen‐fixing rhizobia, however, other non‐rhizobial bacteria also colonise this niche. Although many of these bacteria harbour plant‐growth‐promoting functions, it is not clear whether these less abundant nodule colonisers impact root–nodule symbiosis. We assessed the relationship between the nodule microbiome and nodulation as influenced by the soil microbiome, by using a metabarcoding approach to characterise the communities inside nodules of healthy and starved Lotus species. A machine learning algorithm and network analyses were used to identify nodule bacteria of interest, which were re‐inoculated onto plants in controlled conditions to observe their potential functionality. The nodule microbiome of all tested species differed according to inoculum, but only that of Lotus burttii varied with plant health. Amplicon sequence variants representative of Pseudomonas species were the most indicative non‐rhizobial signatures inside healthy L. burttii nodules and negatively correlated with Rhizobium sequences. A representative Pseudomonas isolate co‐colonised nodules infected with a beneficial Mesorhizobium , but not with an ineffective Rhizobium isolate and another even reduced the number of ineffective nodules induced on Lotus japonicus . Our results show that nodule endophytes influence the overall outcome of the root–nodule symbiosis, albeit in a plant host‐specific manner.
Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders
2022-01-24

Significance Loss-of-function mutations in MECP2 cause the neurological disorder Rett syndrome (RTT), but the precise molecular mechanism driving pathogenesis remains unclear. Using an unbiased approach to identify proteins that interact with MeCP2, we identified the transcription factor 20 (TCF20) complex and discovered that RTT-causing mutations in MECP2 disrupt this interaction. Using biochemical, morphological, behavioral, and transcriptional studies, we examined the importance of this interaction for brain function and found that the TCF20 complex plays a direct role in MeCP2-dependent gene regulation and modifies MECP2 -induced synaptic and behavioral deficits. Our data uncovered a previously unknown molecular aspect of MeCP2 function and revealed a converging molecular mechanism, whereby mutations of genes encoding several subunits in the same complex contribute to shared neurological symptoms.
Real‐Life Turning Movements Capture Subtle Longitudinal and Preataxic Changes in Cerebellar Ataxia
2022-01-24

Abstract Background Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints that capture change in ataxia severity in patients' real life. Objectives This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real‐life turning movements that are sensitive for changes both longitudinally and at the preataxic stage. Methods Combined cross‐sectional (n = 30) and longitudinal (n = 14, 1‐year interval) observational study in degenerative cerebellar disease (including eight preataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body‐worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real‐life movements. Results Measures that quantified dynamic balance during turning—lateral velocity change (LVC) and outward acceleration—but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life (effect size δ = 0.68), with LVC also differentiating preataxic against healthy subjects (δ = 0.53). LVC was highly correlated with clinical ataxia severity (scale for the assessment and rating of ataxia [SARA] score, effect size ρ = 0.79) and patient reported balance confidence (activity‐specific balance confidence scale [ABC] score, ρ = 0.66). Moreover, LVC in real life—but not general turning measures or the SARA score—allowed detecting significant longitudinal change in 1‐year follow‐up with high effect size ( r prb = 0.66). Conclusions Measures of turning allow capturing specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers, even in the highly treatment‐relevant early stages of degenerative cerebellar disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Linear projection‐based chemical exchange saturation transfer parameter estimation
2022-01-24

Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B 0 and B 1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z‐spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection‐based multiparametric CEST evaluation method is introduced that offers fast B 0 and B 1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation‐based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1‐regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1‐regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8‐fold reduction of scan time. Similar observations as for the 7‐T data can be made for data from a clinical 3‐T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1‐regularization (“CEST‐LASSO”) constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.
Aquaporin-4 expression in the human choroid plexus
2022-01-24

Abstract The choroid plexus (CP) consists of specialized ependymal cells and underlying blood vessels and stroma producing the bulk of the cerebrospinal fluid (CSF). CP epithelial cells are considered the site of the internal blood-cerebrospinal fluid barrier, show epithelial characteristics (basal lamina, tight junctions), and express aquaporin-1 (AQP1) apically. In this study, we analyzed the expression of aquaporins in the human CP using immunofluorescence and qPCR. As previously reported, AQP1 was expressed apically in CP epithelial cells. Surprisingly, and previously unknown, many cells in the CP epithelium were also positive for aquaporin-4 (AQP4), normally restricted to ventricle-lining ependymal cells and astrocytes in the brain. Expression of AQP1 and AQP4 was found in the CP of all eight body donors investigated (3 males, 5 females; age 74–91). These results were confirmed by qPCR, and by electron microscopy detecting orthogonal arrays of particles. To find out whether AQP4 expression correlated with the expression pattern of relevant transport-related proteins we also investigated expression of NKCC1, and Na/K-ATPase. Immunostaining with NKCC1 was similar to AQP1 and revealed no particular pattern related to AQP4. Co-staining of AQP4 and Na/K-ATPase indicated a trend for an inverse correlation of their expression. We hypothesized that AQP4 expression in the CP was caused by age-related changes. To address this, we investigated mouse brains from young (2 months), adult (12 months) and old (30 months) mice. We found a significant increase of AQP4 on the mRNA level in old mice compared to young and adult animals. Taken together, we provide evidence for AQP4 expression in the CP of the aging brain which likely contributes to the water flow through the CP epithelium and CSF production. In two alternative hypotheses, we discuss this as a beneficial compensatory, or a detrimental mechanism influencing the previously observed CSF changes during aging.
Transitions in subduction zone properties align with long-term topographic growth (Cascadia, USA)
2022-01-24

Simple mechanical models of the earthquake cycle assume that interseismic elastic deformation is recovered during earthquakes, closing the strain budget of steady and episodic slip on the deep and shallow subduction interfaces, respectively. However, elevated topography in the forearc high requires that some deformation is not recovered over each elastic cycle. Here, we compare constraints on deformation over decadal to million-year timescales to disentangle contributions from elastic (recoverable) and inelastic (unrecoverable) deformation within the Olympic Mountains of the Cascadia Subduction Zone. Over timescales of 103 – 106 yrs, elevated topography, permanent deformation, and denudation (from thermochronometry and cosmogenic nuclide data) accumulate in an area adjacent, but not identical, to the maximum in geodetically observed reduced vertical velocity and surface upwarping over tens of years. The domains of geodetic and geomorphic maximum uplift occur over a 20-60 km wide zone overlying the up-dip limits of the zone of conditional frictional stability at the subduction interface. We attribute geologic-scale orogenesis, accumulation of topography and advection of rocks in the active orogen to unrecoverable deformation as stress is relayed up-dip through parts of the subduction interface and dissipated in the overriding plate.
Bioorthogonal click chemistry-based labelling of proteins in living neuronal cell lines and primary neurons
2022-01-24

<title>Abstract</title> Developments in microscopy techniques have brought about a demand for new protein labelling methods. Labelling tags should be small and ideally compatible with live-cell imaging. An elegant protein labelling technique that fulfils these criteria is based on genetic code expansion and bioorthogonal click chemistry. Genetic code expansion allows incorporation of clickable UAAs into proteins of interest which are subsequently directly labelled with small fluorescent dyes using click chemistry. While previous work has mainly focused on easy-to-transfect standard cell lines, recent publications have described applications of this technology in primary neurons. Here, we report a detailed protocol for transfections and bioorthogonal click chemistry-based labelling of intracellular proteins in living primary neurons.
Of predators and new men: how ideology matters in constructing military masculinities
2022-01-24

Abstract There is a growing literature on variations of military masculinities in armed groups which focuses mainly, but not exclusively, on Leftist guerrilla groups. Although these empirical studies deal with military masculinities in highly ideologized contexts, it remains theoretically and conceptually unclear how exactly ideology and masculinity constructions are interrelated. Drawing inspiration from civil war literature, I make the theoretical argument that ideology matters in the form of the military masculinity an armed group seeks to construct. I build on the concept of hegemonic masculinity, highlighting its practice-theoretical implications of which the notion of background knowledge is of particular interest. Here, I locate configurations of masculinity as well as ideology. Conceptualizing armed groups as total institutions, ideology, first, shapes the form of the institution and, secondly, is itself conveyed to combatants via socializing practices. It is via these same socialization processes that not only masculinities are carefully constructed but that these gender constructions are thoroughly shaped by ideological thought. My theoretical argument allows for a more nuanced explanation of ideology and military masculinities and, thus, further adds to broader Feminist debates about their variation. At the end, I illustrate the added value of my theoretical argument with empirical notes on the Salvadoran Frente Farabundo Martí de la Liberación Nacional (FMLN).
Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants
2022-01-25

PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
The longitudinal interplay of personality and school experiences in adolescence
2022-01-25

The school environment is one key developmental context that is assumed to shape individual characteristics during adolescence. However, little is known about which school experiences are central to personality change or whether school experiences and personality co-shape each other over time. We address this gap by examining the longitudinal interplay between seven school experiences in the three domains of achievement, social relationships, and well-being, and the Big Five personality traits at four measurement points from fifth to eighth grade. By using data from the German TRAIN study ( N = 3,473, M ageT1 = 11.1 years, 45% female), we estimated bivariate latent growth curve models and cross-lagged panel models to illustrate this longitudinal interplay. Results demonstrated correlated change between school experiences and personality with differentiated patterns for achievement variables and a general longitudinal interplay with the social relationship and well-being variables. Furthermore, we found cross-lagged effects in both directions, although there were more effects of personality on school experiences. The most consistent predictor of school experiences was conscientiousness, whereas well-being in school in particular was related to personality change 1 year later. We integrate our findings into the current picture of personality development in adolescence and the role of school-related environmental factors.
Assessing K+ ions and K+ channel functions in cancer cell metabolism using fluorescent biosensors
2022-01-25

Cancer represents a leading cause of death worldwide. Hence, a better understanding of the molecular mechanisms causing and propelling the disease is of utmost importance. Several cancer entities are associated with altered K<sup>+</sup> channel expression which is frequently decisive for malignancy and disease outcome. The impact of such oncogenic K<sup>+</sup> channels on cell patho-/physiology and homeostasis and their roles in different subcellular compartments is, however, far from being understood. A refined method to simultaneously investigate metabolic and ionic signaling events on the level of individual cells and their organelles represent genetically encoded fluorescent biosensors, that allow a high-resolution investigation of compartmentalized metabolite or ion dynamics in a non-invasive manner. This feature of these probes makes them versatile tools to visualize and understand subcellular consequences of aberrant K<sup>+</sup> channel expression and activity in K<sup>+</sup> channel related cancer research.