julilili42/papers huggingface dataset:
DNA methylation signature for the assessment of metastatic risk in primary renal cell cancer.
2017-02-20

516 Background: Transition from localized renal cell cancer (RCC) to metastatic disease is associated with an immense mortality. Beside clinicopathological risk estimation, a molecular prediction of metastatic risk from primary cancers with a sufficient diagnostic accuracy is not available. We biometrically identified a candidate metastasis associated methylation signature (MAMS) in a genome-wide in silico DNA methylation analysis of TCGA data and carried out a double evaluation study using tissues from localized RCC, primary metastatic RCC, and distant metastases. Methods: Candidate MAMS was identified by genome-wide random forest analyses of TCGA methylation level 3 data aiming for classification of 230 primary RCC without distant metastases and 52 metastasized tumors. Forty-nine pyrosequencing and/or quantitative methylation specific PCR analyses were established for a total of 20 candidate methylated loci. For evaluation of MAMS, DNA was isolated and bisulfite converted from the primary RCC tissue cohort (n=187) as well as 99 distant metastases. Localized RCCs consisted of 92 pT1a/b tumors (clear cell, 73; papillary, 16; chromophobe, 2; not classified, 1) without lymph node or distant metastases. RCC samples of primary metastatic disease were obtained from 31 patients. Results: Single candidate loci showed specific hypermethylation when metastatic tissues were compared to primary RCC samples. Random forest analysis showed that MAMS including nine methylation loci achieved a sensitivity of 93% and a specificity of 89% (AUC 0.95) for differentiation of localized RCC and metastases (chi square, p = 3.4*10 -29 ). Positive, negative likelihood, and diagnostic odds ratios were 8.6, 0.08, and 108. Using this random forest model for prediction of primary RCCs associated with distant or lymph node metastases revealed a sensitivity of 58% and specificity of 94% (AUC 0.84, p = 1.0*10 -9 ). Positive, negative likelihood, and diagnostic odds ratios were 9.2, 0.45, and 20.5. Conclusions: A negative MAMS test result retrospectively reduced the probability of metastasis 15-fold in the localized disease cohort, suggesting a prospective evaluation for a possible clinical translation of MAMS in handling RCC patients.
Dissecting the genomic landscape of metastatic bladder cancer using circulating tumor DNA.
2017-02-20

378 Background: To date, only limited data are available on genomic alterations present in metastatic lesions of patients with metastatic urothelial carcinoma (mUC). The constant release of cell free DNA (cfDNA) from tumor cells into the peripheral blood stream may provide a valuable source for detection of cancer associated somatic copy number variations and mutations. The aim of this project was to evaluate the feasibility of detecting clinically relevant genomic alterations in mUC by next-generation sequencing (NGS) of circulating cfDNA. Methods: Peripheral blood (20ml) was collected from 15 patients with mUC before chemotherapy. Plasma cfDNA was isolated using the QIAAmp Circulating Nucleic Acid Kit. Germline control DNA was extracted from peripheral blood mononuclear cells (PBMCs) using the DNEasy Kit (Qiagen). We performed deep (&gt;500X) targeted DNA sequencing on cfDNA and germline DNA using a custom NimbleGen SeqCap EZ Choice Library and Illumina sequencers. Our custom panel included 50 bladder cancer-relevant genes, including key tumor suppressors (e.g. TP53, RB1, CDKN2A), cell cycle drivers (e.g. CCND1, CCNE1), DNA repair genes (e.g. ATM, BAP1, ERCC2), PI3K pathway genes (e.g. PIK3CA, PTEN, AKT1), and other oncogenic pathways (e.g. RAS/RAF, EGFR, ERBB2, PPARG, FGFR3). Results: Somatic mutations and/or copy number changes were detected in 14/15 samples, with a median variant allele frequency &gt;5%. The overall mutational landscape was highly consistent with bladder cancer, including mutations in TP53 and ARID1A (and other chromatin modifiers), as well as hotspot activating mutations in PIK3CA. Typical copy number changes, including focal amplifications of ERBB2, KRAS, and CCNE1 were detected. We identified complex gene rearrangements, including an activating FGFR3 fusion in one case. Extended analyses with a larger patient population are currently pending. Conclusions: Non-invasive characterization of genomic changes in peripheral blood of patients with mUC using NGS of plasma cfDNA is feasible in a high proportion of patients. Analysis of cfDNA might therefore provide an improved understanding of genomic changes in mUC and could be developed as a biomarker to help guide the use of targeted therapies.
Development of hydrogels for regenerative engineering
2017-02-21

Abstract The aim of regenerative engineering is to restore complex tissues and biological systems through convergence in the fields of advanced biomaterials, stem cell science, and developmental biology. Hydrogels are one of the most attractive biomaterials for regenerative engineering, since they can be engineered into tissue mimetic 3D scaffolds to support cell growth due to their similarity to native extracellular matrix. Advanced nano‐ and micro‐technologies have dramatically increased the ability to control properties and functionalities of hydrogel materials by facilitating biomimetic fabrication of more sophisticated compositions and architectures, thus extending our understanding of cell‐matrix interactions at the nanoscale. With this perspective, this review discusses the most commonly used hydrogel materials and their fabrication strategies for regenerative engineering. We highlight the physical, chemical, and functional modulation of hydrogels to design and engineer biomimetic tissues based on recent achievements in nano‐ and micro‐technologies. In addition, current hydrogel‐based regenerative engineering strategies for treating multiple tissues, such as musculoskeletal, nervous and cardiac tissue, are also covered in this review. The interaction of multiple disciplines including materials science, cell biology, and chemistry, will further play an important role in the design of functional hydrogels for the regeneration of complex tissues.
Disappearing giants: a review of threats to freshwater megafauna
2017-02-21

Charismatic megafauna species may act as both flagship and umbrella species. They influence local environments and biotas, determine related ecosystem processes and functions, and are associated with high levels of biodiversity. However, the intrinsic characteristics of megafauna species including long lifespan, large body size, sparseness and/or rarity, late maturity, and low fecundity, as well as high market value, make them very prone to extinction. Up to now, scientific interest and conservation efforts have mainly focused on terrestrial and marine megafauna, while freshwater species have received comparatively little attention, despite evidence suggesting that freshwaters are losing species faster than marine or terrestrial realms. The high susceptibility of freshwater megafauna to multiple threats, coupled with immense human pressure on freshwater ecosystems, places freshwater megafauna amongst the most threatened species globally. The main threats include overexploitation, dam construction, habitat degradation, pollution, and species invasion. These threats increase mortality, decrease productivity, and reduce fitness, causing the decline of populations and the extinction of freshwater megafauna species. Given the essential ecological and biological roles of freshwater megafauna, further research should focus on their distribution patterns, extinction risks, and population dynamics, thereby improving the knowledge base for conservation planning. Finally, freshwater megafauna‐based conservation strategies may raise public awareness for freshwater conservation and therefore benefit a broader range of freshwater species and functions. WIREs Water 2017, 4:e1208. doi: 10.1002/wat2.1208 This article is categorized under: Water and Life &gt; Conservation, Management, and Awareness Water and Life &gt; Nature of Freshwater Ecosystems Water and Life &gt; Stresses and Pressures on Ecosystems
Systematic review of the oncological and functional outcomes of pelvic organ‐preserving radical cystectomy ( RC ) compared with standard RC in women who undergo curative surgery and orthotopic neobladder substitution for bladder cancer
2017-02-21

Context Pelvic organ‐preserving radical cystectomy ( POPRC ) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical cystectomy ( RC ). Objective To determine the effect of POPRC on sexual, oncological and urinary outcomes compared with RC in women who undergo standard curative surgery and orthotopic neobladder substitution for bladder cancer. Evidence acquisition Medline, Embase, Cochrane controlled trials databases and clinicaltrial.gov were systematically searched for all relevant publications. Women with bladder cancer who underwent POPRC or standard RC and orthotopic neobladder substitution with curative intent were included. Prospective and retrospective comparative studies and single‐arm case series were included. The primary outcomes were sexual function at 6–12 months after surgery and oncological outcomes including disease recurrence and overall survival ( OS ) at &gt;2 years. Secondary outcomes included urinary continence at 6–12 months. Risk of bias (RoB) assessment was performed using standard Cochrane review methodology including additional domains based on confounder assessment. Evidence synthesis The searches yielded 11 941 discrete articles, of which 15 articles reporting on 15 studies recruiting a total of 874 patients were eligible for inclusion. Three papers had a matched‐pair study design and the rest of the studies were mainly small, retrospective case series. Sexual outcomes were reported in seven studies with 167/194 patients (86%) having resumed sexual activity within 6 months postoperatively, with median (range) patients’ sexual satisfaction score of 88.5 (80–100)%. Survival outcomes were reported in seven studies on 197 patients, with a mean follow‐up of between 12 and 132 months. At 3 and 5 years, cancer‐specific survival was 70–100% and OS was 65–100%. In all, 11 studies reported continence outcomes. Overall, the daytime and night‐time continence rates were 58–100% and 42–100%, respectively. Overall, the self‐catheterisation rate was 9.5–78%. Due to poor reporting and large heterogeneity between studies, instead of subgroup‐analysis, a narrative synthesis approach was used. The overall RoB was high across all studies. Conclusion For well‐selected patients, POPRC with orthotopic neobladder may potentially be comparable to standard RC for oncological outcomes, whilst improving sexual and urinary function outcomes. However, in women undergoing RC , oncological and functional data regarding POPRC remain immature and require further evaluation in a prospective comparative setting.
Maximum mass limit of neutron stars in scalar-tensor gravity
2017-02-21

The maximum mass limits of neutron stars in scalar-tensor gravity is\\ndiscussed and compared with the limits set by general relativity. The limit is\\nparametrized with respect to the combination of the nuclear saturation\\nparameters and the maximum sound velocity in the core. It is shown that, for\\nsmaller values of the sound velocity in the core, the maximum mass limit of the\\nscalarized neutron stars is larger than that of in general relativity. However,\\nfor stiff equations of state with sound velocity higher than of the\\nvelocity of light, the maximum mass limit in general relativity is larger than\\nthat of in scalar-tensor gravity. The results suggest that future observations\\nof massive neutron stars, may constrain the maximum sound velocity as well as\\nthe coupling parameter in scalar-tensor gravity.\\n
Low Prevalence of Substandard and Falsified Antimalarial and Antibiotic Medicines in Public and Faith-Based Health Facilities of Southern Malawi
2017-02-21

Substandard and falsified antimalarial and antibiotic medicines represent a serious problem for public health, especially in low- and middle-income countries. However, information on the prevalence of poor-quality medicines is limited. In the present study, samples of six antimalarial and six antibiotic medicines were collected from 31 health facilities and drug outlets in southern Malawi. Random sampling was used in the selection of health facilities. For sample collection, an overt approach was used in licensed facilities, and a mystery shopper approach in nonlicensed outlets. One hundred and fifty-five samples were analyzed by visual and physical examination and by rapid prescreening tests, that is, disintegration testing and thin-layer chromatography using the GPHF-Minilab. Fifty-six of the samples were analyzed according to pharmacopeial monographs in a World Health Organization-prequalified quality control laboratory. Seven out-of-specification medicines were identified. One sample was classified as falsified, lacking the declared active ingredients, and containing other active ingredients instead. Three samples were classified as substandard with extreme deviations from the pharmacopeial standards, and three further samples as substandard with nonextreme deviations. Of the substandard medicines, three failed in dissolution testing, two in the assay for the content of the active pharmaceutical ingredient, and one failed in both dissolution testing and assay. Six of the seven out-of-specification medicines were from private facilities. Only one out-of-specification medicine was found within the samples from public and faith-based health facilities. Although the observed presence of substandard and falsified medicines in Malawi requires action, their low prevalence in public and faith-based health facilities is encouraging.
The Palatal Interpterygoid Vacuities of Temnospondyls and the Implications for the Associated Eye‐ and Jaw Musculature
2017-02-21

ABSTRACT A diagnostic feature of temnospondyls is the presence of an open palate with large interpterygoid vacuities, unlike the closed palate of most other early tetrapods, in which the vacuities are either slit‐like or completely absent. Attachment sites on neurocranium and palatal bones in temnospondyls allow the reconstruction of a powerful m. retractor bulbi and a large, sheet‐like m. levator bulbi that formed the elastic floor of the orbit. This muscle arrangement indicates that temnospondyls were able to retract the eyeballs through the interpterygoid vacuities into the buccal cavity, like extant frogs and salamanders. In contrast, attachment sites on palate and neurocranium suggest a rather sauropsid‐like arrangement of these muscles in stem‐tetrapods and stem‐amniotes. However, the anteriorly enlarged, huge interpterygoid vacuities of long‐snouted stereospondyls suggest that eye retraction was not the only function of the vacuities here, since the eye‐muscles filled only the posterior part of the vacuities. We propose an association of the vacuities in temnospondyls with a long, preorbital part of the m. adductor mandibulae internus (AMIa). The trochlea‐like, anterior edge of the adductor chamber suggests that a tendon of the AMIa was redirected in an anteromedial direction in the preorbital skull and dorsal to the pterygoids. This tendon then unfolded into a wide aponeurosis bearing the flattened AMIa that filled almost the complete interpterygoid vacuities anterior to the orbits. Our muscle reconstructions permit comprehensive insights to the comparative soft tissue anatomy of early tetrapods and provide the basis for a biomechanic analysis of biting performances in the future. Anat Rec, 300:1240–1269, 2017. © 2017 Wiley Periodicals, Inc.
Characterization of a novel signal transducer element intrinsic to class IIIa/b adenylate cyclases and guanylate cyclases
2017-02-21

Adenylate cyclases (ACs) are signaling proteins that produce the second messenger cAMP. Class III ACs comprise four groups (class IIIa–d) of which class IIIa and IIIb ACs have been identified in bacteria and eukaryotes. Many class IIIa ACs are anchored to membranes via hexahelical domains. In eukaryotic ACs, membrane anchors are well conserved, suggesting that this region possesses important functional characteristics that are as yet unknown. To address this question, we replaced the hexahelical membrane anchor of the mycobacterial AC Rv1625c with the hexahelical quorum‐sensing receptor from Legionella , LqsS. Using this chimera, we identified a novel 19‐amino‐acid cyclase transducer element (CTE) located N‐terminally to the catalytic domain that links receptor stimulation to effector activation. Coupling of the receptor to the AC was possible at several positions distal to the membrane exit, resulting in stimulatory or inhibitory responses to the ligand Legionella autoinducer‐1. In contrast, on the AC effector side functional coupling was only successful when starting with the CTE. Bioinformatics approaches established that distinct CTEs are widely present in class IIIa and IIIb ACs and in vertebrate guanylate cyclases. The data suggest that membrane‐delimited receiver domains transduce regulatory signals to the downstream catalytic domains in an engineered AC model system. This may suggest a previously unknown mechanism for cellular cAMP regulation.
Suspicion of respiratory tract infection with multidrug-resistant Enterobacteriaceae: epidemiology and risk factors from a Paediatric Intensive Care Unit
2017-02-21

This study shows that critically-ill children with tracheal Enterobacteriaceae infection are at risk of carrying MDR isolates. Prior use of antibiotics for ≥ 7 days significantly increased the risk of finding MDR organisms in ventilated PICU patients with suspected infection. Our results imply that early identification of patients at risk, rapid microbiological diagnostics and tailored antibiotic therapy are essential to improve management of critically ill children infected with Enterobacteriaceae.
Sleep Enhances Recognition Memory for Conspecifics as Bound into Spatial Context
2017-02-21

Social memory refers to the fundamental ability of social species to recognize their conspecifics in quite different contexts. Sleep has been shown to benefit consolidation, especially of hippocampus-dependent episodic memory whereas effects of sleep on social memory are less well studied. Here, we examined the effect of sleep on memory for conspecifics in rats. To discriminate interactions between the consolidation of social memory and of spatial context during sleep, adult Long Evans rats performed on a social discrimination task in a radial arm maze. The Learning phase comprised three 10-min sampling sessions in which the rats explored a juvenile rat presented at a different arm of the maze in each session. Then the rats were allowed to sleep (<i>n</i> = 18) or stayed awake (<i>n</i> = 18) for 120 min. During the following 10-min Test phase, the familiar juvenile rat (of the Learning phase) was presented along with a novel juvenile rat, each rat at an opposite arm of the maze. Significant social recognition memory, as indicated by preferential exploration of the novel over the familiar conspecific, occurred only after post-learning sleep, but not after wakefulness. Sleep, compared with wakefulness, significantly enhanced social recognition during the first minute of the Test phase. However, memory expression depended on the spatial configuration: Significant social recognition memory emerged only after sleep when the rat encountered the novel conspecific at a place different from that of the familiar juvenile in the last sampling session before sleep. Though unspecific retrieval-related effects cannot entirely be excluded, our findings suggest that sleep, rather than independently enhancing social and spatial aspects of memory, consolidates social memory by acting on an episodic representation that binds the memory of the conspecific together with the spatial context in which it was recently encountered.
CerebroMatic: A Versatile Toolbox for Spline-Based MRI Template Creation
2017-02-22

Brain image spatial normalization and tissue segmentation rely on prior tissue probability maps. Appropriately selecting these tissue maps becomes particularly important when investigating "unusual" populations, such as young children or elderly subjects. When creating such priors, the disadvantage of applying more deformation must be weighed against the benefit of achieving a crisper image. We have previously suggested that statistically modeling demographic variables, instead of simply averaging images, is advantageous. Both aspects (more vs. less deformation and modeling vs. averaging) were explored here. We used imaging data from 1914 subjects, aged 13 months to 75 years, and employed multivariate adaptive regression splines to model the effects of age, field strength, gender, and data quality. Within the spm/cat12 framework, we compared an affine-only with a low- and a high-dimensional warping approach. As expected, more deformation on the individual level results in lower group dissimilarity. Consequently, effects of age in particular are less apparent in the resulting tissue maps when using a more extensive deformation scheme. Using statistically-described parameters, high-quality tissue probability maps could be generated for the whole age range; they are consistently closer to a gold standard than conventionally-generated priors based on 25, 50, or 100 subjects. Distinct effects of field strength, gender, and data quality were seen. We conclude that an extensive matching for generating tissue priors may model much of the variability inherent in the dataset which is then not contained in the resulting priors. Further, the statistical description of relevant parameters (using regression splines) allows for the generation of high-quality tissue probability maps while controlling for known confounds. The resulting CerebroMatic toolbox is available for download at http://irc.cchmc.org/software/cerebromatic.php.
A high-speed brain-computer interface (BCI) using dry EEG electrodes
2017-02-22

Recently, brain-computer interfaces (BCIs) based on visual evoked potentials (VEPs) have been shown to achieve remarkable communication speeds. As they use electroencephalography (EEG) as non-invasive method for recording neural signals, the application of gel-based EEG is time-consuming and cumbersome. In order to achieve a more user-friendly system, this work explores the usability of dry EEG electrodes with a VEP-based BCI. While the results show a high variability between subjects, they also show that communication speeds of more than 100 bit/min are possible using dry EEG electrodes. To reduce performance variability and deal with the lower signal-to-noise ratio of the dry EEG electrodes, an averaging method and a dynamic stopping method were introduced to the BCI system. Those changes were shown to improve performance significantly, leading to an average classification accuracy of 76% with an average communication speed of 46 bit/min, which is equivalent to a writing speed of 8.8 error-free letters per minute. Although the BCI system works substantially better with gel-based EEG, dry EEG electrodes are more user-friendly and still allow high-speed BCI communication.