julilili42/papers huggingface dataset:
Late recurrence of melanoma after 10 years – Is the course of the disease different from early recurrences?
2019-11-23

Abstract Background It is known that melanoma can metastasize and recur many years after the first diagnosis. Although predictive and prognostic factors for melanoma are well defined, there is still insufficient information about the factors affecting the recurrence period and the effect of the recurrence time to survival. Objectives This study investigates the course of melanoma to show prognostic factors comparing early and late recurrence patients. The main objective is to uncover the effect of the recurrence time on the progression of the disease. Methods In this retrospective study, late recurrence ( LR ) was defined as melanoma recurrence 10 years after the first diagnosis and early recurrence ( ER ) was defined as recurrence within 10 years. Gender, age, localization of primary tumour, time to first metastasis, survival rates, histological subtype, stage, tumour thickness, invasion level, ulceration and regression of the primary melanoma were documented. Survival curves were evaluated using the Kaplan–Meier and compared with the log‐rank test. Multivariate Cox proportional hazard models were used to identify significant independent prognostic factors for melanoma‐specific survival ( MSS ). Results A total of 1537 melanoma patients were analysed. Early metastasis was developed in 1438 patients (93.6%), and 99 patients (6.4%) developed late metastasis. Late recurrence patients were younger ( P &lt; 0.001) and had fewer ulcerated ( P = 0.005), fewer head/neck localized ( P = 0.009) and thinner ( P &lt; 0.001) melanomas than ER patients. The MSS time (mean ± SD ) was nearly identical for LR (31 ± 4.4 months 95% CI [22.3–39.7]) and ER (32 ± 1.9 months [28.3–35.7]). Multivariate regression analysis revealed male gender (hazard ratio [ HR = 1.4, P &lt; 0.001), truncal tumour localization ( HR = 1.7, P &lt; 0.001), tumour thickness ( HR = 1.4, P &lt; 0.045) and ulceration ( HR = 1.3, P &lt; 0.008) as significant independent prognostic factors for MSS . Conclusion Although ER and LR patients are found to have different clinicopathologic features, the time of the first recurrence after diagnosis do not seem to have an effect on the survival.
Impact of diagnostic methods on efficacy estimation – a proof‐of‐principle based on historical examples
2019-11-23

Abstract Introduction Accurate diagnostic methods are essential for evaluating treatment efficacy in clinical trials, including vaccine trials. Although a plethora of studies assessing novel or modified treatment options is available, clinical trials evaluating the sensitivity and specificity of diagnostic methods in compliance with the demands of drug registration trials are scarce. We assessed the accuracy of diagnostic methods in two vaccine trials conducted in 1995 and 2009 to demonstrate the impact of sensitivity and specificity on efficacy estimations. Methods We applied the sensitivity‐ and specificity‐adjusted vaccine efficacy estimator of Lachenbruch for modelling the impact of test characteristics on the outcome of the two vaccine trials by varying diagnostic specificity. Results Because of non‐ideal diagnostic sensitivity and specificity, the estimation of vaccine efficacy is compromised. We demonstrate the impact of diagnostic accuracy on efficacy estimations with increasing confidence limits. Conclusions Because sensitivity and specificity less than one have a direct impact on efficacy estimations in clinical trials, evaluation of diagnostic methods should lead to a level of evidence comparable with the efficacy assessment of novel treatment options. Furthermore, statistical methods adjusted for sensitivity and specificity of diagnostic methods should be applied for efficacy estimations, or this lack of confidence has to be taken into account when interpreting the results of trials.
Biomarkers Apo10 and TKTL1: Epitope-detection in monocytes (EDIM) as a new diagnostic approach for cholangiocellular, pancreatic and colorectal carcinoma
2019-11-24

The sensitivity of the EDIM blood test and the comparison with traditional tumor markers indicate that this new test might improve the detection of carcinomas (CCC, PC and, CRC) and might be relevant for the diagnosis of all tumor entities.
First results from the CRESST-III low-mass dark matter program
2019-11-25

The CRESST experiment is a direct dark matter search which aims to measure interactions of potential dark matter particles in an Earth-bound detector. With the current stage, CRESST-III, we focus on a low energy threshold for increased sensitivity towards light dark matter particles. In this paper we describe the analysis of one detector operated in the first run of CRESST-III (05/2016–02/2018) achieving a nuclear recoil threshold of 30.1 eV. This result was obtained with a 23.6 g CaWO 4 crystal operated as a cryogenic scintillating calorimeter in the CRESST setup at the Laboratori Nazionali del Gran Sasso (LNGS). Both the primary phonon (heat) signal and the simultaneously emitted scintillation light, which is absorbed in a separate silicon-on-sapphire light absorber, are measured with highly sensitive transition edge sensors operated at ∼ 15 mK . The unique combination of these sensors with the light element oxygen present in our target yields sensitivity to dark matter particle masses as low as 160 MeV / c 2 .
Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein
2019-11-25

To discover novel genes underlying amyotrophic lateral sclerosis (ALS), we aggregated exomes from 3,864 cases and 7,839 ancestry-matched controls. We observed a significant excess of rare protein-truncating variants among ALS cases, and these variants were concentrated in constrained genes. Through gene level analyses, we replicated known ALS genes including SOD1, NEK1 and FUS. We also observed multiple distinct protein-truncating variants in a highly constrained gene, DNAJC7. The signal in DNAJC7 exceeded genome-wide significance, and immunoblotting assays showed depletion of DNAJC7 protein in fibroblasts in a patient with ALS carrying the p.Arg156Ter variant. DNAJC7 encodes a member of the heat-shock protein family, HSP40, which, along with HSP70 proteins, facilitates protein homeostasis, including folding of newly synthesized polypeptides and clearance of degraded proteins. When these processes are not regulated, misfolding and accumulation of aberrant proteins can occur and lead to protein aggregation, which is a pathological hallmark of neurodegeneration. Our results highlight DNAJC7 as a novel gene for ALS.
H.E.S.S. detection of very high-energy γ-ray emission from the quasar PKS 0736+017
2019-11-25

Context. Flat-spectrum radio-quasars (FSRQs) are rarely detected at very high energies ( E ≥ 100 GeV) due to their low-frequency-peaked spectral energy distributions. At present, only six FSRQs are known to emit very high-energy (VHE) photons, representing only 7% of the VHE extragalactic catalog, which is largely dominated by high-frequency-peaked BL Lacertae objects. Aims. Following the detection of MeV–GeV γ -ray flaring activity from the FSRQ PKS 0736+017 ( z = 0.189) with Fermi -LAT, the H.E.S.S. array of Cherenkov telescopes triggered target-of-opportunity (ToO) observations on February 18, 2015, with the goal of studying the γ -ray emission in the VHE band. Methods. H.E.S.S. ToO observations were carried out during the nights of February 18, 19, 21, and 24, 2015. Together with Fermi -LAT, the multi-wavelength coverage of the flare includes Swift observations in soft X-ray and optical-UV bands, and optical monitoring (photometry and spectro-polarimetry) by the Steward Observatory, and the ATOM, the KAIT, and the ASAS-SN telescopes. Results. VHE emission from PKS 0736+017 was detected with H.E.S.S. only during the night of February 19, 2015. Fermi -LAT data indicate the presence of a γ -ray flare, peaking at the time of the H.E.S.S. detection, with a flux doubling timescale of around six hours. The γ -ray flare was accompanied by at least a 1 mag brightening of the non-thermal optical continuum. No simultaneous observations at longer wavelengths are available for the night of the H.E.S.S. detection. The γ -ray observations with H.E.S.S. and Fermi -LAT are used to put constraints on the location of the γ -ray emitting region during the flare: it is constrained to be just outside the radius of the broad-line region r B L R with a bulk Lorentz factor Γ ≃ 20, or at the level of the radius of the dusty torus r torus with Γ ≃ 60. Conclusions. PKS 0736+017 is the seventh FSRQ known to emit VHE photons, and at z = 0.189 is the nearest so far. The location of the γ -ray emitting region during the flare can be tightly constrained thanks to opacity, variability, and collimation arguments.
WENGAN: Efficient and high quality hybrid de novo assembly of human genomes
2019-11-25

The continuous improvement of long-read sequencing technologies along with the development of ad-doc algorithms has launched a new de novo assembly era that promises high-quality genomes. However, it has proven difficult to use only long reads to generate accurate genome assemblies of large, repeat-rich human genomes. To date, most of the human genomes assembled from long error-prone reads add accurate short reads to further polish the consensus quality. Here, we report the development of a novel algorithm for hybrid assembly, W ENGAN , and the de novo assembly of four human genomes using a combination of sequencing data generated on ONT PromethION, PacBio Sequel, Illumina and MGI technology. W ENGAN implements efficient algorithms that exploit the sequence information of short and long reads to tackle assembly contiguity as well as consensus quality. The resulting genome assemblies have high contiguity (contig NG50:16.67-62.06 Mb), few assembly errors (contig NGA50:10.9-45.91 Mb), good consensus quality (QV:27.79-33.61), and high gene completeness (B USCO complete: 94.6-95.1%), while consuming low computational resources (CPU hours:153-1027). In particular, the W ENGAN assembly of the haploid CHM13 sample achieved a contig NG50 of 62.06 Mb (NGA50:45.91 Mb), which surpasses the contiguity of the current human reference genome ( GRCh38 contig NG50:57.88 Mb). Providing highest quality at low computational cost, W ENGAN is an important step towards the democratization of the de novo assembly of human genomes. The W ENGAN assembler is available at https://github.com/adigenova/wengan
Is there really no place like home? Changes in the perception of domestic spaces in German picturebooks from 1945 to the present
2019-11-25

This chapter investigates the changing perceptions of domestic spaces and how it impacts on the complex concept of home in German picturebooks from 1945 until the present. The corpus consists of 38 picturebooks, with roughly five exemplars for each decade. The selection likewise considers the historical fact that Germany has been divided into two states in 1949, the Federal Republic of Germany and the German Democratic Republic, until the re-union of both states in 1990. Based on the theoretical framework of cognitive studies with an emphasis on cognitive mapping and cognitive narratology, this chapter inquires how children are introduced into the concept of home on the one hand, and how this concept is closely connected with children’s emotional, moral, and cognitive development on the other. As this concept is subject to political, social, and cultural modifications, this survey also demonstrates the impact of these changes onto the narrative and visual depiction of domestic spaces in picturebooks.
Faculty Opinions recommendation of Identification of a Functional Non-coding Variant in the GABA A Receptor α2 Subunit of the C57BL/6J Mouse Reference Genome: Major Implications for Neuroscience Research.
2019-11-25

GABA type-A (GABA-A) receptors containing the α2 subunit (GABRA2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function.Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse.Gabra2 expression varies as a function of genotype and is modulated by sequence variants in several brain structures and populations, including F2 crosses originating from C57BL/6J (B6J) and the BXD recombinant inbred family derived from B6J and DBA/2J.Here we demonstrate a global reduction of GABRA2 brain protein and mRNA in the B6J strain relative to other inbred strains, and identify and validate the causal mutation in B6J.The mutation is a single base pair deletion located in an intron adjacent to a splice acceptor site that only occurs in the B6J reference genome.The deletion became fixed in B6J between 1976 and 1991 and is now pervasive in many engineered lines, BXD strains generated after 1991, the Collaborative Cross, and the majority of consomic lines.Repair of the deletion using CRISPR-Cas9-mediated gene editing on a B6J genetic background completely restored brain levels of GABRA2 protein and mRNA.Comparison of transcript expression in hippocampus, cortex, and striatum between B6J and repaired genotypes revealed alterations in GABA-A receptor subunit expression, especially in striatum.These results
miR-212 and miR-132 Are Downregulated in Neurally Derived Plasma Exosomes of Alzheimer’s Patients
2019-11-26

It was recently discovered that brain cells release extracellular vesicles (EV) which can pass from brain into blood. These findings raise the possibility that brain-derived EV's present in blood can be used to monitor disease processes occurring in the cerebrum. Since the levels of certain micro-RNAs (miRNAs) have been reported to be altered in Alzheimer's disease (AD) brain, we sought to assess miRNA dysregulation in AD brain tissue and to determine if these changes were reflected in neural EVs isolated from blood of subjects with AD. To this end, we employed high-content miRNA arrays to search for differences in miRNAs in RNA pools from brain tissue of AD (<i>n</i> = 5), high pathological control (HPC) (<i>n</i> = 5), or cognitively intact pathology-free controls (<i>n</i> = 5). Twelve miRNAs were altered by >1.5-fold in AD compared to controls, and six of these were also changed compared to HPCs. Analysis of hits in brain extracts from 11 AD, 7 HPCs and 9 controls revealed a similar fold difference in these six miRNAs, with three showing statistically significant group differences and one with a strong trend toward group differences. Thereafter, we focused on the four miRNAs that showed group differences and measured their content in neurally derived blood EVs isolated from 63 subjects: 16 patients with early stage dementia and a CSF Aβ42+ tau profile consistent with AD, 16 individuals with mild cognitive impairment (MCI) and an AD CSF profile, and 31 cognitively intact controls with normal CSF Aβ42+ tau levels. ROC analysis indicated that measurement of miR-132-3p in neurally-derived plasma EVs showed good sensitivity and specificity to diagnose AD, but did not effectively separate individuals with AD-MCI from controls. Moreover, when we measured the levels of a related miRNA, miR-212, we found that this miRNA was also decreased in neural EVs from AD patients compared to controls. Our results suggest that measurement of miR-132 and miR-212 in neural EVs should be further investigated as a diagnostic aid for AD and as a potential theragnostic.
Structure and decays of hidden heavy pentaquarks
2019-11-26

We study the hadronic molecular structure of hidden heavy pentaquarks - new\\nexotic states composed of charmed/bottom baryons and mesons.\\nBased on the observation of three pentaquark candidates ,\\n , and by the LHCb Collaboration we consider the\\nclassification of possible flavor partners composed of charmed baryons and\\n mesons within the hadronic molecular approach. We extend this\\nclassification to the bottom sector. Using phenomenological Lagrangians we\\nconstruct baryon-meson bound states governed by the Weinberg-Salam\\ncompositeness condition. As an application we consider strong two-body decays\\nof the new exotic states into a light baryon and or\\n mesons. Results are presented in the heavy quark limit.\\n
Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa: A Multicenter Safety Study of the OkuStim® System (TESOLA-Study)
2019-11-26

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Transcorneal electrical stimulation (TES) has been suggested as a possible treatment for retinitis pigmentosa (RP). &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To expand the safety assessment of repeated applications of an electrical current from a DTL-like electrode in patients with RP. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This single-arm open label interventional safety trial included a total of 105 RP patients from 11 European centers, who received weekly TES for 6 months on 1 eye followed by observation for another 6 months without stimulation. The primary outcome measure was safety, indicated by the frequency and severity of adverse events. Secondary measures included intraocular pressure and central retinal thickness. Visual field and visual acuity were examined using the methods available at each site. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Dry eye sensation was the most common adverse event recorded (37.5%). Serious adverse events secondary to TES were not observed. Most adverse events were mild and all resolved without sequelae. The secondary outcome measures revealed no significant or clinically relevant changes. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The present results confirm the excellent safety profile of TES. Transient dry eye symptoms were the most common adverse event.
Influence of Molybdenum Back Contact on the PID Effect for Cu(In,Ga)Se2 Solar Cells
2019-11-26

The authors investigated the effect of an applied high voltage (1 kV) across the thickness of a soda-lime glass substrate of Cu(In,Ga)Se2 (CIGS) thin-film solar cells. Two types of CIGS cells were tested, differing only in the deposition process of the molybdenum (Mo) back contact. Whilst one cell type was susceptible to potential induced degradation (PID), the other exhibited highly increased stability against PID. PID occurs for PID-susceptible cells after the transfer of a certain amount of charge through the soda-lime glass substrate when the Mo back contact of the cell operates as a cathode (negatively biased versus backside of the substrate). Capacitance–voltage and electron-beam-induced current measurements showed an enlarged space charge region expanding to the Mo back contact and a lowered doping density by a negative potential for PID-susceptible cells. Glow discharge optical emission spectroscopy (GDOES) revealed an accumulation of sodium (Na) in the solution-grown CdS buffer layer and a segregation on the surface of the ZnO:Al window layer for higher charges for PID-susceptible cells. Cells with increased PID immunity did not show an increase of Na for charges up to around 9 mC/cm2. We demonstrate that it is possible to improve the PID stability of CIGS solar cells by modification of the molybdenum back contact.
Ca2+‐independent and voltage‐dependent exocytosis in mouse chromaffin cells
2019-11-26

Abstract Aim It is widely accepted that the exocytosis of synaptic and secretory vesicles is triggered by Ca 2+ entry through voltage‐dependent Ca 2+ channels. However, there is evidence of an alternative mode of exocytosis induced by membrane depolarization but lacking Ca 2+ current and intracellular Ca 2+ increase. In this work we investigated if such a mechanism contributes to secretory vesicle exocytosis in mouse chromaffin cells. Methods Exocytosis was evaluated by patch‐clamp membrane capacitance measurements, carbon fibre amperometry and TIRF. Cytosolic Ca 2+ was estimated using epifluorescence microscopy and fluo‐8 (salt form). Results Cells stimulated by brief depolatizations in absence of extracellular Ca +2 show moderate but consistent exocytosis, even in presence of high cytosolic BAPTA concentration and pharmacological inhibition of Ca +2 release from intracellular stores. This exocytosis is tightly dependent on membrane potential, is inhibited by neurotoxin Bont‐B (cleaves the v‐SNARE synaptobrevin), is very fast (saturates with time constant &lt;10 ms), it is followed by a fast endocytosis sensitive to the application of an anti‐dynamin monoclonal antibody, and recovers after depletion in &lt;5 s. Finally, this exocytosis was inhibited by: (i) ω‐agatoxin IVA (blocks P/Q‐type Ca 2+ channel gating), (ii) in cells from knock‐out P/Q‐type Ca 2+ channel mice, and (iii) transfection of free synprint peptide (interferes in P/Q channel‐exocytic proteins association). Conclusion We demonstrated that Ca 2+ ‐independent and voltage‐dependent exocytosis is present in chromaffin cells. This process is tightly coupled to membrane depolarization, and is able to support secretion during action potentials at low basal rates. P/Q‐type Ca 2+ channels can operate as voltage sensors of this process.
Manipulating Attributes of Natural Scenes via Hallucination
2019-11-26

In this study, we explore building a two-stage framework for enabling users to directly manipulate high-level attributes of a natural scene. The key to our approach is a deep generative network that can hallucinate images of a scene as if they were taken in a different season (e.g., during winter), weather condition (e.g., on a cloudy day), or at a different time of the day (e.g., at sunset). Once the scene is hallucinated with the given attributes, the corresponding look is then transferred to the input image while preserving the semantic details intact, giving a photo-realistic manipulation result. As the proposed framework hallucinates what the scene will look like, it does not require any reference style image as commonly utilized in most of the appearance or style transfer approaches. Moreover, it allows to simultaneously manipulate a given scene according to a diverse set of transient attributes within a single model, eliminating the need of training multiple networks per each translation task. Our comprehensive set of qualitative and quantitative results demonstrates the effectiveness of our approach against the competing methods.
Evaluation of the Atellica COAG 360 coagulation analyzer in a central laboratory of a maximum care hospital
2019-11-26

Abstract Introduction Fully‐automated coagulation analyzers are key components of a high‐throughput central laboratory. The novel Atellica COAG 360 (Siemens Healthineers) is a high‐volume coagulation analyzer approved for hemostasis diagnostics. The aim of the study was to evaluate the analytical performance of this coagulation analyzer in a central laboratory. Methods Intra (n = 10)‐ and inter (n = 20)‐assay precision of the Atellica COAG 360 was determined using commercially available control samples. Patient samples (n = 74‐104) were used for comparison analyses with the Sysmex CS ‐5100 (Siemens Healthineers). Effects of visual interferences on coagulation testing were assessed and the sample throughput rate of the Atellica COAG 360 was determined. Results Intra‐ and inter‐assay precision of the Atellica COAG 360 showed coefficient of variations ( CV s) &lt; 5% for most of the coagulation parameters comparable to CV s of the Sysmex CS ‐5100. Passing‐Bablok and Bland‐Altman analyses revealed high correlation and good agreement between both coagulation analyzers in determination of coagulation parameters. Results of coagulation measurements determined in optically abnormal samples were comparable between the Atellica COAG 360 and the Sysmex CS ‐5100 and were confirmed by mechanical measurements on a ST art Max (Stago Diagnostics) coagulation analyzer. A sample throughput rate of about 190 tests per hour in a routine setting including five coagulation parameters was determined for the Atellica COAG 360 integrated in a total laboratory automation system. Conclusion The Atellica COAG 360 provides high analytical performance as high‐throughput analyzer for routine and specific coagulation parameters and is suitable to be connected to a total laboratory automation.