julilili42/papers huggingface dataset:
Miocene basement exhumation in the Central Alps recorded by detrital garnet geochemistry in foreland basin deposits
2019-09-20

Abstract. The Neogene evolution of the European Alps was characterized by the exhumation of crystalline basement, the so-called external crystalline massifs. Their exhumation presumably controlled the evolution of relief, distribution of drainage networks, and generation of sediment in the Central Alps. However, due to the absence of suitable proxies, the timing of their surficial exposure and thus the initiation of sediment supply from these areas are poorly constrained. The northern Alpine foreland basin preserves the Oligocene to Miocene sedimentary record of tectonic and climatic adjustments in the hinterland. This contribution analyses the provenance of 25 to 14 Myr old alluvial fan deposits by means of detrital garnet chemistry. Unusually grossular- and spessartine-rich garnet is found (1) to be a unique proxy for identifying detritus from the external crystalline massifs and (2) to occur abundantly in ca. 14 Myr old deposits of the foreland basin. In contrast to previous assumptions, we therefore propose that the external massifs were already exposed to the surface ca. 14 Myr ago.
Revealing Structure and Crystallographic Orientation of Soft Epitaxial Assembly of Nanocrystals by Grazing Incidence X-ray Scattering
2019-09-20

We study the structural coherence of a self-assembled overlayer of PbS nanocrystal (NC) superlattice onto an underlying PbS NC monolayer, which acts as a template. We explore the effect of the templating layer on the structure of the overlayer asemblies by varying interfacial strain and determine the impact of new ligands on their superlattice structure. The overlayers and templates are analyzed by grazing-incidence X-ray scattering and microscopy. We find that differences in the lattice parameters of 7.7% between the two layers are tolerated in terms of a "soft epitaxial" assembly into the body-centered tetragonal superstucture and lead to structural registry within the overlayer. Conversely, at the interface, a lattice mismatch of 24.4% is too large for soft epitaxy and invokes a change in the superlattice. Upon ligand treatment, the overlayer superlattices transform their orientation axis and the NCs orient preferentially. These results provide new insights into mitigating defects in layered, heterostructured NC assemblies.
Ongoing evolution of hepatitis B virus during viremia in patients with febrile in Central Africa
2019-09-20

Abstract Hepatitis B virus (HBV) infection remains to be a major public health issue worldwide, although there is currently a safe vaccine and effective antiviral treatments. In surveillance of infectious diseases in Gabon, HBV viremia was detected in patients with febrile. Whole‐genome sequencing was conducted to characterize the HBV strains currently circulating in Gabon and to investigate HBV genome diversity during viremia. Phylogenetic analysis revealed the existence of former subgenotype A5, which exhibits a particular pattern of distribution from several West and Central African countries to Haiti. Furthermore, sequencing analysis identified two similar HBV strains mixed in one sample, and a very rare 1‐base pair insertion in the viral precore region. This insertion caused a frameshift mutation, indicating the production of an aberrant fusion protein of the HBV x and e antigens. Our data showed that the detected HBV strain was possibly in an “evolving” state during viremia, a phase of active replication.
Targets, Tracers and Translation – Novel Radiopharmaceuticals Boost Nuclear Medicine
2019-09-20

This is the fourth Special Issue in Pharmaceuticals within the last six years dealing with aspects of radiopharmaceutical sciences. It demonstrates the significant interest and increasing relevance to ameliorate nuclear medicine imaging with PET or SPECT, and also radiotherapeutical procedures.Numerous targets and mechanisms have been identified and have been under investigation over the previous years, covering many fields of medical and clinical research. This development is well illustrated by the articles in the present issue, including 13 original research papers and one review, covering a broad range of actual research topics in the field of radiopharmaceutical sciences.
Disease progression and defects in primary hemostasis as major cause of bleeding in multiple myeloma
2019-09-21

Abstract Background and objectives In patients with multiple myeloma (MM), unexpected bleeding complications remain a major issue. Since routine coagulation parameters are often inconspicuous, diagnosis and treatment of the underlying coagulation disorders are challenging. Patients and methods In our single‐center observational study, we analyzed 164 patients with MM for coagulation disorders and bleeding complications. Results Prolonged closure times (CTs), measured by PFA‐100, were the most common, abnormal coagulation test, found in 66% of bleeding patients vs 5% in non‐bleeding, followed by qualitative defects of von Willebrand factor (VWF:CB/VWF:Ag ratios), found in 34% vs 1% in the non‐bleeding group. Increased serum free light chains (SFLC) and SFLC ratios were significantly associated with prolonged CTs and acquired von Willebrand syndrome (AVWS). Prolonged CTs and AVWS were associated with disease progression, determined by dynamics of SFLC ratios ( P &lt; .001), serum creatinine level ( P = .013), Beta‐2 microglobulin ( P = .03), LDH ( P = .016), and bone marrow infiltration ( P &lt; .001). Of note, response to myeloma therapy was frequently correlated with normalization of coagulation parameters. Conclusions Bleeding complications in MM are predominantly caused by defects in primary hemostasis and associated with disease progression. In a peri‐interventional workup, determination of CTs and VWF:CB/VWF:Ag ratios are of significant importance to assess bleeding risk.
Dermatology in Ancient Rome: Medical ingredients in Ovid's “Remedies for female faces”
2019-09-21

Abstract Background In Roman medicine, face packs, plasters, unguents, and peelings were part of the therapy of dermatological diseases, but also served cosmetic purposes. Ancient medical textbooks inform us about the ingredients for these applications. Beyond medical literature, other genres contain information about dermatological applications. The Roman poet Ovid (43 BC–17 AD) wrote a didactic poem recording five recipes for topical applications for female faces ( Medicamina faciei femineae ). Researchers debate the relation of Ovid's poem to Roman medicine: Does the poem contain therapeutical or cosmetical information, or is it mere belles lettres ? Aims The objective of the paper is to conduct a medico‐historical classification of Ovid's poem by determining whether the ingredients of Ovid's recipes were thought to be effective by the authors of Roman medical textbooks. Methods First, translation and identification of the ingredients were carried out. Second, comparison of the ingredients' functions regarding the therapy of dermatological diseases in two important Roman medical textbooks was realized. For this purpose, several commentaries on the text of Ovid were used and a keyword search in Roman medical textbooks was performed. Results Ovid's five recipes contain 23 ingredients. All ingredients can be found in medical textbooks. We find that 14 of these ingredients serve cosmetic purposes, 17 serve the therapy of dermatological diseases, and 13 serve both. Conclusion Ovid's recipes contain drugs that were considered effective by the authors of Roman medical textbooks. These drugs were recommended both for therapeutic and cosmetic purposes by the same authors. Therefore, Ovid's didactic poem is not mere belles lettres , but contains serious medical and cosmetical information. As far as we know, it is the first Roman text that contains dermatological recipes.
An arbitrary-spectrum spatial visual stimulator for vision research
2019-09-23

Visual neuroscientists require accurate control of visual stimulation. However, few stimulator solutions simultaneously offer high spatio-temporal resolution and free control over the spectra of the light sources, because they rely on off-the-shelf technology developed for human trichromatic vision. Importantly, consumer displays fail to drive UV-shifted short wavelength-sensitive photoreceptors, which strongly contribute to visual behaviour in many animals, including mice, zebrafish and fruit flies. Moreover, many non-mammalian species feature more than three spectral photoreceptor types. Here, we present a flexible, spatial visual stimulator with up to six arbitrary spectrum chromatic channels. It combines a standard digital light processing engine with open source hard- and software that can be easily adapted to the experimentalist’s needs. We demonstrate the capability of this general visual stimulator experimentally in the in vitro mouse retinal whole-mount and the in vivo zebrafish. With this work, we intend to start a community effort of sharing and developing a common stimulator design for vision research.
Inhibition of Δ24-dehydrocholesterol reductase activates pro-resolving lipid mediator biosynthesis and inflammation resolution
2019-09-23

Significance Lipid metabolism is crucial to many (patho-)physiological processes, including inflammation. In particular, cholesterol biosynthesis has emerged as an exciting novel therapeutic target in numerous recent studies. Much is known about the early steps in cholesterol biosynthesis; however, the later steps have hitherto largely been neglected. Here, we investigated the druggability of distal cholesterol biosynthesis using a selective and potent chemical probe (SH42). This inhibition leads to the accumulation of the bioactive metabolite desmosterol, boosting the biosynthesis of polyunsaturated fatty acids (PUFA) and the downstream production of antiinflammatory mediators. Our report integrates distal cholesterol biosynthesis and its intermediate desmosterol with endogenous PUFA biosynthesis and resolution of inflammation, rendering this pathway attractive for further developments in the context of proresolving therapies.
Deep‐intronic variants in CNGB3 cause achromatopsia by pseudoexon activation
2019-09-23

Our comprehensive cohort of 1100 unrelated achromatopsia (ACHM) patients comprises a considerable number of cases (~5%) harboring only a single pathogenic variant in the major ACHM gene CNGB3. We sequenced the entire CNGB3 locus in 33 of these patients to find a second variant which eventually explained the patients' phenotype. Forty-seven intronic CNGB3 variants were identified in 28 subjects after a filtering step based on frequency and the exclusion of variants found in cis with pathogenic alleles. In a second step, in silico prediction tools were used to filter out those variants with little odds of being deleterious. This left three variants that were analyzed using heterologous splicing assays. Variant c.1663-1205G>A, found in 14 subjects, and variant c.1663-2137C>T, found in two subjects, were indeed shown to exert a splicing defect by causing pseudoexon insertion into the transcript. Subsequent screening of further unsolved CNGB3 subjects identified four additional cases harboring the c.1663-1205G>A variant which makes it the eighth most frequent CNGB3 variant in our cohort. Compound heterozygosity could be validated in ten cases. Our study demonstrates that whole gene sequencing can be a powerful approach to identify the second pathogenic allele in patients apparently harboring only one disease-causing variant.
Local surgical treatment of cutaneous squamous cell carcinoma: deficits and controversies in the literature
2019-09-23

Summary The prognostic impact of primary excision in the treatment of cutaneous squamous cell carcinoma depends on certain tumor characteristics (risk factors), the surgical approach chosen and the subsequent histological examination. For the development of the AWMF (Association of Scientific Medical Societies in Germany) guidelines for squamous cell carcinoma, the most conclusive guidelines available were evaluated using the DELBI tool (German Instrument for the Methodological Appraisal of Guidelines). These were the Scottish and Canadian guidelines as well as the joint guidelines published by EDF, EADO and EORTC. The primary literature on the aforementioned topics that was used for these guidelines included 49 studies and 9 reviews. None of the studies had a prospective, randomized design; 19 studies contained prospective data; 30 studies provided retrospective data. Overall, the results were heterogeneous. Not only were there discrepancies in terms of the validity of the various risk factors for locoregional disease progression – such as dedifferentiation, desmoplasia and perineural invasion – but also with respect to tumor thickness and surgical consequences. Differences were also found regarding the histological processing method used. In general, there are two such methods: conventional histology (bread loaf technique) and complete histological assessment of excision margins. The latter was found to be associated both with low recurrence rates and low metastatic rates, possibly due to the fact that patients treated with the latter method had lower‐risk tumors. Publications on bread loaf histology lacked precise information as to how the tissue was actually processed. Likewise, there was a lack of usable data in terms of the surgical margins used in the primary excision. Conclusion : The current literature is inconsistent and insufficient with regard to the various prognostic factors and the surgical approach to cutaneous squamous cell carcinoma.
Clinical Impact of the TCF7L2 Gene rs7903146 Type 2 Diabetes Mellitus Risk Polymorphism in Women with Gestational Diabetes Mellitus: Impaired Glycemic Control and Increased Need of Insulin Therapy
2019-09-23

Abstract Background The single nucleotide polymorphism in TCF7L2 rs7903146 is associated with an increased risk of type 2 diabetes mellitus and gestational diabetes mellitus. Mechanisms by which this mutation acts, and its impact on the clinical course of the diseases remain unclear. Here we investigated the clinical impact of the T risk allele in women with gestational diabetes mellitus. Methods We genotyped the C/T polymorphism in 164 Caucasian women with GDM (German n=114; Greek n=50). The impact of the T allele on the results of the 75g oral-glucose-tolerance-test, and on the required therapy (diet/lifestyle or insulin) was investigated. Results During oral-glucose-tolerance-test, women harboring the T allele displayed significantly higher glucose values at 60 min (p=0.034) and were more likely to require insulin therapy even after adjusting for confounders, such as BMI and age. Conclusion These results provide evidence that the T risk allele in TCF7L2 rs7903146 is associated with failure in early postprandial glycemic control and requirement of insulin therapy in women with gestational diabetes mellitus, even after adjusting for confounding factors such BMI and age.
Artefact and ablation performance of an MR-conditional high-power microwave system in bovine livers: an ex vivo study
2019-09-23

Abstract Background We evaluated a magnetic resonance (MR)-conditional high-power microwave ablation system. Methods An ex vivo 1.5-T evaluation was conducted by varying the sequence (T1-weighted volume interpolated breath-hold examination, T1w-VIBE; T1-weighted fast low-angle shot, T1w-FLASH; T2-weighted turbo spin-echo, T2w-TSE), applicator angulation to B 0 ( A -to- B 0 ), slice orientation, and encoding direction. Tip location error (TLE) and artefact diameters were measured, and influence of imaging parameters was assessed with analysis of variance and post hoc testing. Twenty-four ex vivo ablations were conducted in three bovine livers at 80 W and 120 W. Ablation durations were 5, 10, and 15 min. Ablation zones were compared for short-axis diameter (SAD), volume, and sphericity index (SI) with unpaired t test. Results The artefact pattern was similar for all sequences. The shaft artefact (4.4 ± 2.9 mm, mean ± standard deviation) was dependent on the sequence ( p = 0.012) and the A -to- B 0 ( p &lt; 0.001); the largest shaft diameter was measured with T1w-FLASH (6.3 ± 3.4 mm) and with perpendicular A -to- B 0 (6.7 ± 2.4 mm). The tip artefact (1.6 ± 0.7 mm) was dependent on A -to- B 0 ( p = 0.001); TLE was -2.6 ± 1.0 mm. Ablation results at the maximum setting (15 min, 120 W) were SAD = 42.0 ± 1.41 mm; volume = 56.78 ± 3.08 cm 3 , SI = 0.68 ± 0.05. In all ablations, SI ranged 0.68–0.75 with the smallest SI at 15 min and 120 W ( p = 0.048). Conclusion The system produced sufficiently large ablation zones and the artefact was appropriate for MR-guided interventions.
Kv1 potassium channels control action potential firing of putative GABAergic deep cerebellar nuclear neurons
2019-09-23

ABSTRACT The Kv1 voltage-gated potassium channels (kv1.1-1.8) display characteristic low-threshold activation ranges what enables their role in regulating diverse aspects of neuronal function, such as the action potential (AP) threshold and waveform, and thereby influence neuronal excitability or synaptic transmission. Kv1 channels are highly expressed in the cerebellar cortex and nuclei and mutations of human Kv1 genes are associated to episodic forms of ataxia (EAT-1). Besides the well-established role of Kv1 channels in regulating the basket-Purkinje cells inhibitory synapses of cerebellar cortex, cerebellar Kv1 channels regulate the principal deep cerebellar nuclear neurons activity (DCNs). DCNs however, include as well different groups of GABAergic cells that project locally to target principal DCNs, or to the inferior-olive or recurrently to the cerebellar cortex, but whether their function is controlled by Kv1 channels remains unclear. Here, using cerebellar slices from the GAD67-GFP line mice to identify putative GABAergic-DCNs and specific Kv1 channel blockers (dendrotoxins-alpha/I/K (DTXs)) we provide evidence that putative GABAergic-DCNs spontaneous and evoked activity is controlled by Kv1 currents. DTXs shifted in the hyperpolarizing direction the voltage threshold of spontaneous APs in GABAergic-DCNs, increased GABAergic-DCNs spontaneous firing rate and decreased these neurons ability to fire repetitively action potentials at high frequency. Moreover, in spontaneously silent putative nucleo-cortical DCNs, DTXs application induced depolarization and tonic firing. These results strongly suggest that Kv1 channels regulate GABAergic-DCNs activity and thereby can control previously unrecognized aspects of cerebellar function.
Intelligence, Diplomacy, Entertainment: Catherine II’s Son Tours Europe Incognito
2019-09-23

From September 1781 to November 1782 Grand Duke Paul Petrovich, in the company of his wife, Grand Duchess Mariia Feodorovna, visited the major royal courts of Europe under the pseudonym “Comte &amp; Comtesse du Nord.” By emphasizing the ceremonial meanings of high-status incognito tour, this article addresses the seemingly paradoxical relationship between the private status public visibility of the traveling Russian court analyzes the narratives about it in the European press in other documentary accounts related to the tour.
On Zwickyism
2019-09-23

Novel Research in Sciences On Zwickyism Otto E Rossler* Faculty of Science, University of Tuebingen, Auf der Morgenstelle 8, Germany *Corresponding author: Otto E Rossler, Faculty of Science, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany Submission: September 19, 2019; Published: September 23, 2019 Volume2 Issue2September 23, 2019
Dominant mutations in mtDNA maintenance gene SSBP1 cause optic atrophy and foveopathy
2019-09-24

Mutations in genes encoding components of the mitochondrial DNA (mtDNA) replication machinery cause mtDNA depletion syndromes (MDSs), which associate ocular features with severe neurological syndromes. Here, we identified heterozygous missense mutations in single-strand binding protein 1 (SSBP1) in 5 unrelated families, leading to the R38Q and R107Q amino acid changes in the mitochondrial single-stranded DNA-binding protein, a crucial protein involved in mtDNA replication. All affected individuals presented optic atrophy, associated with foveopathy in half of the cases. To uncover the structural features underlying SSBP1 mutations, we determined a revised SSBP1 crystal structure. Structural analysis suggested that both mutations affect dimer interactions and presumably distort the DNA-binding region. Using patient fibroblasts, we validated that the R38Q variant destabilizes SSBP1 dimer/tetramer formation, affects mtDNA replication, and induces mtDNA depletion. Our study showing that mutations in SSBP1 cause a form of dominant optic atrophy frequently accompanied with foveopathy brings insights into mtDNA maintenance disorders.
Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses
2019-09-24

Abstract Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. To identify novel loci, we performed a genome-wide association study (GWAS) including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status and tumor grade. We identified 32 novel susceptibility loci ( P &lt;5.0×10 -8 ), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate &lt;0.05). Five loci showed associations ( P &lt;0.05) in opposite directions between luminal- and non-luminal subtypes. In-silico analyses showed these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 37.6% for triple-negative and 54.2% for luminal A-like disease. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.