julilili42/papers huggingface dataset:
Targeting connexin hemichannels to control the inflammasome: the correlation between connexin43 and NLRP3 expression in chronic eye disease
2019-09-26

<b>Introduction</b>: Chronic inflammatory diseases, including retinal diseases that are a major cause of vision loss, are associated with activation of the nucleotide-binding domain and leucine-rich repeat containing (NLR) protein-3 (NLRP3) inflammasome pathway. In chronic disease, the inflammasome becomes self-perpetuating, indicating a common pathway in such diseases irrespective of underlying etiology, and implying a shared solution is feasible. Connexin43 hemichannels correlate directly with NLRP3 inflammasome complex assembly (shown here in models of retinal disease). Connexin43 hemichannel-mediated ATP release is proposed to be the principal activator signal for inflammasome complex assembly in primary signal-sensitized cells. Connexin hemichannel block on its own is sufficient to inhibit the inflammasome pathway. <b>Areas covered</b>: We introduce chronic retinal disease, discuss available preclinical models and examine findings from these models regarding the targeting of connexin43 hemichannels and its effects on the inflammasome. <b>Expert opinion</b>: In over 25 animal disease models, connexin hemichannel regulation has shown therapeutic benefit, and one oral connexin hemichannel blocker, tonabersat (Xiflam), is Phase II ready with safety evidence in over 1000 patients. Regulating the connexin hemichannel provides a means to move quickly into clinical trials designed to ameliorate the progression of devastating chronic diseases of the eye, but also elsewhere in the body.
Glutamate receptors and glutamatergic signalling in the peripheral nerves
2019-09-26

In the peripheral nervous system, the vast majority of axons are accommodated within the fibre bundles that constitute the peripheral nerves. Axons within the nerves are in close contact with myelinating glia, the Schwann cells that are ideally placed to respond to, and possibly shape, axonal activity. The mechanisms of intercellular communication in the peripheral nerves may involve direct contact between the cells, as well as signalling via diffusible substances. Neurotransmitter glutamate has been proposed as a candidate extracellular molecule mediating the cross-talk between cells in the peripheral nerves. Two types of experimental findings support this idea: first, glutamate has been detected in the nerves and can be released upon electrical or chemical stimulation of the nerves; second, axons and Schwann cells in the peripheral nerves express glutamate receptors. Yet, the studies providing direct experimental evidence that intercellular glutamatergic signalling takes place in the peripheral nerves during physiological or pathological conditions are largely missing. Remarkably, in the central nervous system, axons and myelinating glia are involved in glutamatergic signalling. This signalling occurs via different mechanisms, the most intriguing of which is fast synaptic communication between axons and oligodendrocyte precursor cells. Glutamate receptors and/or synaptic axon-glia signalling are involved in regulation of proliferation, migration, and differentiation of oligodendrocyte precursor cells, survival of oligodendrocytes, and re-myelination of axons after damage. Does synaptic signalling exist between axons and Schwann cells in the peripheral nerves? What is the functional role of glutamate receptors in the peripheral nerves? Is activation of glutamate receptors in the nerves beneficial or harmful during diseases? In this review, we summarise the limited information regarding glutamate release and glutamate receptors in the peripheral nerves and speculate about possible mechanisms of glutamatergic signalling in the nerves. We highlight the necessity of further research on this topic because it should help to understand the mechanisms of peripheral nervous system development and nerve regeneration during diseases.
Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro
2019-09-26

Abstract Myeloid‐derived suppressor cells (MDSCs) are key regulators of immunity that initially have been defined by their ability to potently suppress T‐cell responses. Recent studies collectively demonstrate that the suppressive activity of MDSCs is not limited to T cells, but rather affects a broad range of immune cell subsets. However, relatively few studies have assessed the impact of MDSCs on B cells, particularly in the human context. Here, we report that human monocytic MDSCs (M‐MDSCs) significantly interfere with human B‐cell proliferation and function in vitro. We further show that the inhibition occurs independent of direct cell‐contact and involves the expression of suppressive mediators such as indoleamine 2, 3‐dioxygenase (IDO), arginase‐1 (Arg1), and nitric oxide (NO). In addition, our studies demonstrate that the suppression of B cells by M‐MDSCs is paralleled by a skewing in B‐cell phenotype and gene expression signatures. M‐MDSCs induced the downregulation of key surface markers on activated B cells, including IgM, HLA‐DR, CD80, CD86, TACI, and CD95. Concurrently, M‐MDSCs but not conventional monocytes elicited alterations in the transcription of genes involved in apoptosis induction, class‐switch regulation, and B‐cell differentiation and function. In summary, this study expands our understanding of the regulatory role of M‐MDSCs for human B‐cell responses.
The Impact of CYP3A4*22 on Tacrolimus Pharmacokinetics and Outcome in Clinical Practice at a Single Kidney Transplant Center
2019-09-26

Background: Although there is evidence that the CYP3A4*22 variant should be considered in tacrolimus dosing in renal transplantation, its impact beyond tacrolimus dose requirements remains controversial. Methods: In a cohort of 121 kidney transplant recipients, we analyzed the CYP3A4*1B, CYP3A4*22, and CYP3A5*3 alleles and the ABCB1 variants 1236C&gt;T, 2677G&gt;T/A, and 3435C&gt;T for their impact on exposure and dose requirement. Relevant clinical outcome measures such as acute rejection within the first year after transplantation, delayed graft function, and renal function at discharge (estimated glomerular filtration rate) were evaluated. Results: Extensive metabolizer (n = 17, CYP3A4*1/*1 carriers with at least one CYP3A5*1 allele) showed significantly higher tacrolimus dose requirement (P = 0.004) compared with both intermediate metabolizer (IM, n = 93, CYP3A5*3/*3 plus CYP3A4*1/*1 or CYP3A4*22 carriers plus one CYP3A5*1 allele), and poor metabolizer (n = 11, CYP3A4*22 allele in combination with CYP3A5*3/*3) after onset of therapy. Significantly higher dose requirement was observed in CYP3A5 expressers (P = 0.046) compared with non-expressers again at onset of therapy. Using the log additive genetic model, the area under the curve for the total observation period up to 16 days was significantly associated with the CYP3A5*3 genotype (P = 3.34 × 10-4) as well as with the IM or extensive metabolizer phenotype (P = 1.54 × 10-4), even after adjustment for multiple testing. Heterozygous carriers for CYP3A4*22 showed significantly higher areas under the curve than the CYP3A4*1/*1 genotype in the second week post-transplantation (adjusted P = 0.016). Regarding clinical outcomes, acute rejection was significantly associated with human leukocyte antigen mismatch (≥3 alleles; OR = 12.14, 95% CI 1.76, 525.21, P = 0.019 after correction for multiple testing). Graft recipients from deceased donors showed higher incidende of delayed graft function (OR 7.15, 95% CI 2.23, 30.46, adjusted P = 0.0008) and a lower estimated glomerular filtration rate at discharge (P = 0.0001). Tested CYP3A4 or CYP3A5 variants did not show any effects on clinical outcome parameters. ABCB1 variants did neither impact on pharmacokinetics nor on clinical endpoints. Conclusion: At our transplantation center, both CYP3A5*3 and, to a lesser extent, CYP3A4*22 affect tacrolimus pharmacokinetics early after onset of therapy with consequences for steady-state treatment in routine clinical practice.
The Spatial Prediction of Soil Texture Fractions in Arid Regions of Iran
2019-09-26

To predict the soil texture fractions, 115 profiles were identified based on the Latin hypercube sampling technique, the horizons were sampled, and the clay, sand, and silt contents (in percentages) of soil samples were measured. Then equal-area quadratic spline depth functions were used to derive clay, sand, and silt contents at five standard soil depths (0–5, 5–15, 15–30, 30–60, and 60–100 cm). Auxiliary variables used in this study include the terrain attributes (derived from a digital elevation model), Landsat 8 image data (acquired in 2015), geomorphological map, and spectrometric data (laboratory data). Artificial neural network (ANN), regression tree (RT), and neuro-fuzzy (ANFIS) models were used to make a correlation between soil data (clay, sand, and silt) and auxiliary variables. The results of this study showed that the ANFIS model was more accurate in the prediction of the three parameters of clay, silt, and sand than ANN and RT. Moreover, the ability of ANFIS model to estimate the soil texture fractions in the surface layers was higher than the lower layers. The mean coefficient of determination (R2) values calculated by 10-fold cross validation suggested the higher prediction performance in the upper depth intervals and higher prediction error in the lower depth intervals (e.g., R2 = 0.91, concordance correlation coefficient (CCC) = 0.90, RMSE = 4.00 g kg−1 for sand of 0–5 cm depth, and R2 = 0.68, CCC = 0.60, RMSE = 8.03 g kg−1 for 60–100 cm depth). The results also showed that the most important auxiliary variables are spectrometric data, multi-resolution, valley-bottom flatness index and wetness index. Overall, it is recommended to use ANFIS models for the digital mapping of soil texture fractions in other arid regions of Iran.
Disinhibited Revenge – An fNIRS Study on Forgiveness and Cognitive Control
2019-09-26

The ability to reconcile is a key factor for a cooperative and successful life. Among the many factors that have an impact on how people negotiate social contracts, poor cognitive control (which is inversely linked to impulsivity) may exert negative effects on forgiveness. To investigate the neurobiological basis of this proposition, subjects with high vs. low impulsivity scores completed an ultimatum game (UG) and a dictator game (DG). First, the participants played an UG where they had to accept or reject offers from fair or unfair opponents. Afterward, the roles changed, and a DG was played. Here, subjects had the opportunity to forgive or take revenge on unfair opponents by the allocation of a fair/unfair amount of money. During this task, activity of the dorsolateral prefrontal cortex (DLPFC) was assessed <i>via</i> functional near-infrared spectroscopy (fNIRS). Highly impulsive subjects were significantly more revenge-seeking than individuals with a low impulsivity. This behavioral difference was reflected in the activation pattern of the left DLPFC, where higher activation in trials with unfair opponents was found, but only in the highly impulsive group. This result is discussed as an indicator of more revenge-driven behavior in highly impulsive individuals, since activity in the left DLPFC is associated with retaliation.
Solid‐State Phosphorescence of A2[W6I14] with A = PPN, PPh4
2019-09-26

Hybrid organic‐inorganic cluster compounds A 2 [W 6 I 14 ] with A = Ph 4 P, PPN were prepared by cation exchange reactions from Cs 2 [W 6 I 14 ] with a corresponding organic halide; and a purification method for A 2 [W 6 I 14 ] compounds by column chromatography is introduced. Crystal structures of compounds were solved and refined based on single‐crystal X‐ray diffraction data. Photoluminescence properties of the new A 2 [W 6 I 14 ] compounds reveal orange to deep‐red emission on excitation between 300 and 500 nm. (PPN) 2 [W 6 I 14 ] is an exception among compounds with the [W 6 I 14 ] 2– ion, showing a solid‐state phosphorescence with a quantum yield (φ P ) in the order of 40 %.
Why Collectivity? On the Problematization of Documentary Perspectives on Teaching
2019-09-26

Die dokumentarische Methode, die als Milieuforschungsmethode am Gegenstand der Freundschafts- und Freizeitgruppe entwickelt wurde, hat sich inzwischen in verschiedensten Gegenstandsfeldern in der Erziehungswissenschaft etabliert. In diesem Beitrag werden kritische Anfragen an die vollumfangliche Passung zwischen dokumentarischer Methode und dem Gegenstand Unterricht gestellt. Dies wird am Beispiel des systematischen Auseinanderfallens von SchulerInnen- und LehrerInnenhabitus und damit dem Fehlen eines gemeinsam geteilten Orientierungsrahmens im Unterricht thematisiert. Meine an diesem Spezialproblem und der gefundenen Losung entwickelte These ist, dass Unterricht mit der Methode durch das Primat und damit die Suche nach dem Konjunktiven, die trotz des Fehlens eines gemeinsamen Orientierungsrahmens aufrechterhalten wird, tendenziell harmonisierend beobachtet wird. Als Folge konnen Komplexitatsdimensionen aus dem Blick geraten. In meinem Beitrag zeichne ich die empirischen und theoretischen Folgen dieses Primats der Konjunktion nach und begrunde die These, dass zu einer umfanglicheren Erfassung der Komplexitat von Unterricht eine Verschiebung im Primat und eine Erweiterung um andere Prinzipien der Sozialitat notwendig sind. Ich behandele somit die grundlegende Frage, ob und wenn ja welche Grenzen der Expansion der dokumentarischen Methode durch ihre methodologischen Annahmen gesetzt sind.
Temperate Phages of Staphylococcus aureus
2019-09-27

ABSTRACT Most Staphylococcus aureus isolates carry multiple bacteriophages in their genome, which provide the pathogen with traits important for niche adaptation. Such temperate S. aureus phages often encode a variety of accessory factors that influence virulence, immune evasion and host preference of the bacterial lysogen. Moreover, transducing phages are primary vehicles for horizontal gene transfer. Wall teichoic acid (WTA) acts as a common phage receptor for staphylococcal phages and structural variations of WTA govern phage-host specificity thereby shaping gene transfer across clonal lineages and even species. Thus, bacteriophages are central for the success of S. aureus as a human pathogen.
UVA Photoprotective Activity of Brown Macroalgae Sargassum cristafolium
2019-09-27

Sunscreens today contain several synthetic UV (Ultraviolet) filter molecules to protect the skin epidermis from UV radiation damage. However, these molecules may create several negative effects on human skin. Due to this condition, there is an increase in the development of natural products to replace uses of these synthetic chemicals. Brown macroalgae Sargassum has been recently studied for its photoprotective activities. The purpose of this study is to investigate photoprotective activity of one of most abundant Sargassum species in Lombok coast; Sargassum cristaefolium. Spectrophotometry analysis with UV-VIS revealed the UV spectra absorbing capability of Sargassum cristaefolium (SC) in the UVA spectrum range (314–400 nm). Furthermore, spectrometry analyses with LC-MS revealed the existence of UV absorbing compound MAA-palythene. In correlation, SC ethanol extracts also demonstrate that it could protect DNA from UVA irradiation as analyzed in vitro in HeLa cell model. The effects of SC on UVA exposed-dorsal mice skin have also shown interesting results, as mice pretreated with SC before UVA exposure showed protective activity on the epidermal integrity similar as positive control. Whereas, UV exposed mice without SC or commercial products resulted in increased epidermal thickness, which is the common parameter of skin photoaging. In addition, pretreated mice with SC also show protective effects in the formation of collagen connective tissues. Overall, current results show promising photoprotective activity of SC against UV radiation. More advanced investigations of SC as a potential photoprotective agent would be reasonable for development of macroalgae-based natural skin protection products.
Multidisciplinary long‐term care and modern surgical treatment of congenital melanocytic nevi – recommendations by the CMN surgery network
2019-09-27

Summary In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German‐speaking countries with extensive experience in long‐term care and surgical treatment of children and adults with CMN (CMN surgery network, “Netzwerk Nävuschirurgie”, NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi‐stage procedure. Today, the long‐term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of “removal at any cost” no longer holds. Potential treatment‐related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus‐based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion.
odMLtables: A User-Friendly Approach for Managing Metadata of Neurophysiological Experiments
2019-09-27

An essential aspect of scientific reproducibility is a coherent and complete acquisition of metadata along with the actual data of an experiment. The high degree of complexity and heterogeneity of neuroscience experiments requires a rigorous management of the associated metadata. The odML framework represents a solution to organize and store complex metadata digitally in a hierarchical format that is both human and machine readable. However, this hierarchical representation of metadata is difficult to handle when metadata entries need to be collected and edited manually during the daily routines of a laboratory. With odMLtables, we present an open-source software solution that enables users to collect, manipulate, visualize, and store metadata in tabular representations (in xls or csv format) by providing functionality to convert these tabular collections to the hierarchically structured metadata format odML, and to either extract or merge subsets of a complex metadata collection. With this, odMLtables bridges the gap between handling metadata in an intuitive way that integrates well with daily lab routines and commonly used software products on the one hand, and the implementation of a complete, well-defined metadata collection for the experiment in a standardized format on the other hand. We demonstrate usage scenarios of the odMLtables tools in common lab routines in the context of metadata acquisition and management, and show how the tool can assist in exploring published datasets that provide metadata in the odML format.
68Ga-PSMA-PET/CT-directed IGRT/SBRT for oligometastases of recurrent prostate cancer after initial surgery
2019-09-27

<b>Background:</b> We evaluated efficacy and toxicity of <sup>68</sup>Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery.<b>Methods:</b> Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five <sup>68</sup>Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03.<b>Results:</b> A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. <sup>68</sup>Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control (<i>n</i> = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient.<b>Conclusions:</b> Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of <sup>68</sup>Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.
Single-cell RNA-Sequencing in Neuroscience
2019-09-27

Summary Technical innovations in the last decade have allowed to sequence transcriptomes of single cells. Single-cell RNA-sequencing (scRNA-seq) has since then opened the window to a deeper understanding of cellular identity and is becoming a widely used method in molecular biology. In neuroscience, scRNA-seq has broad applications, for example in determining cellular diversity in different brain regions and in revealing transcriptomic variations across brain disorders. The method consists of several steps: isolation and lysis of single cells, reverse transcription of RNAs, amplification of cDNAs, and next-generation sequencing. The large datasets can subsequently be analysed using different bioinformatic tools to deduce biological meaning. Current developments aim to integrate scRNA-seq into cellular network analysis through multimodal analysis, spatial localisation and perturbation experiments, in order to understand brain physiology and pathology.
Public Childcare Expansion and Changing Gender Ideologies of Parents in Germany
2019-09-27

This study investigates whether the expansion of public childcare in Germany has been associated with an individual-level change in parents’ gender ideologies. We extend the literature by developing and testing a theoretical framework of the short-term impact of family policy institutions on attitude change over the life course. The analysis links the German Family Panel pair-fam (2008 to 2015) with administrative records on childcare provision at county-level and applies fixed-effects panel models. Our findings show that the childcare expansion has been associated with moderate changes towards less traditional gender ideologies only among mothers in West Germany and mostly so among mothers without a college degree. Surprisingly, in East Germany, we found tentative evidence of more traditional gender ideologies among mothers without a college degree as the childcare reform unfolded. The results provide evidence that policy reforms may alter gender ideologies also in the short-term over the life course.