julilili42/papers huggingface dataset:
Prognostic relevance of high pretreatment CA125 levels in primary serous ovarian cancer
2020-11-12

The objective of the present study was to analyze the prognostic relevance of pretreatment serum CA125 ≥500 U/ml and its role as a non-invasive factor for estimating optimal cytoreduction (≤1 cm) in primary serous ovarian cancer. Clinicopathological parameters and CA125 levels prior to primary cytoreductive surgery were retrospectively evaluated in all 261 consecutive patients with primary epithelial ovarian cancer from a single centre. Inclusion criteria were existing preoperative CA125 level, serous ovarian cancer and performed full primary treatment (surgery/platinum-based chemotherapy). A total of 136 patients met the criteria. Among them, 74 patients had CA125 ≥500 U/ml. The other 62 patients that met the aforementioned criteria and had CA125 <500 U/ml were defined as controls. The present study tested cut-off CA125 values to detect subgroups affecting prognosis. The goal was to evaluate patients with optimal cytoreduction (R≤1 cm). Univariate analyses were performed with PASW to identify clinicopathological parameters associated with the pretreatment CA125 level. For survival analyses, a cut-off-value of CA125 ≥500 U/ml was used to identify the association between preoperative CA125 levels, resection status and prognosis. To test significant differences between examined groups, Student's t-test and the Mann-Whitney test were used. P<0.05 was considered to indicate a statistically significant difference. Significantly worse prognosis in terms of overall survival (P=0.023) and progression-free survival (P=0.011) was detected in the CA125 ≥500 U/ml group of optimally cytoreduced patients compared with in the CA125 <500 U/ml group. The complete cytoreduction rate was higher in CA125 <500 U/ml (33.9%) vs. CA125 ≥500 U/ml (21.6%). A CA125 level >1,404 U/ml had a higher rate of suboptimal cytoreduction (32.4%) compared with lower CA125 levels. A pretreatment CA125 level ≥500 U/ml had significantly worse prognostic impact after optimal cytoreduction compared with CA125 <500 U/ml. The higher the CA125 level the higher the suboptimal cytoreduction rate. Patients with CA125 ≥500 U/ml may be candidates for an initial laparoscopic approach to specify resectability and to determine how to proceed. Overall, CA125 levels appear to be helpful in predicting suboptimal cytoreductive surgery for patients with primary ovarian cancer, but should be interpreted together with clinical and radiologic findings. This may improve defining the optimal treatment strategy in these patients.
Neural Tissue Degeneration in Rosenthal’s Canal and Its Impact on Electrical Stimulation of the Auditory Nerve by Cochlear Implants: An Image-Based Modeling Study
2020-11-12

Sensorineural deafness is caused by the loss of peripheral neural input to the auditory nerve, which may result from peripheral neural degeneration and/or a loss of inner hair cells. Provided spiral ganglion cells and their central processes are patent, cochlear implants can be used to electrically stimulate the auditory nerve to facilitate hearing in the deaf or severely hard-of-hearing. Neural degeneration is a crucial impediment to the functional success of a cochlear implant. The present, first-of-its-kind two-dimensional finite-element model investigates how the depletion of neural tissues might alter the electrically induced transmembrane potential of spiral ganglion neurons. The study suggests that even as little as 10% of neural tissue degeneration could lead to a disproportionate change in the stimulation profile of the auditory nerve. This result implies that apart from encapsulation layer formation around the cochlear implant electrode, tissue degeneration could also be an essential reason for the apparent inconsistencies in the functionality of cochlear implants.
Effects of tDCS on Tactile Perception Depend on Tactile Expertise in Both Musicians and Non-Musicians
2020-11-12

Brain plasticity in the somatosensory cortex and tactile performance can be facilitated by brain stimulation. Here, we investigated the effects of transcranial direct current stimulation (tDCS) on tactile perception in musicians and non-musicians to elucidate how tDCS-effects might depend on tactile expertise. On three separate days, 17 semi-professional musicians (e.g., piano or violin players) and 16 non-musicians aged 18–27 years received 15 min of 1 mA anodal (a-tDCS), cathodal (c-tDCS) or sham tDCS in a pseudorandomized design. Pre and post tDCS, tactile sensitivity (Touch Detection Task; TDT) and discrimination performance (Grating Orientation Task; GOT) were assessed. For further analysis, the weekly hours of instrument-playing and computer-typing were combined into a “tactile experience” variable. For GOT, but not TDT, a significant group effect at baseline was revealed with musicians performing better than non-musicians. TDT thresholds were significantly reduced after a-tDCS but not c-tDCS or sham stimulation. While both musicians’ and non-musicians’ performance improved after anodal stimulation, neither musical nor tactile expertise was directly associated with the magnitude of this improvement. Low performers in TDT with high tactile experience profited most from a-tDCS. We conclude that tactile expertise may facilitate somatosensory cortical plasticity and tactile learning in low performers.
Report on 2010.07838v1
2020-11-12

Single neutral atoms trapped in optical tweezers and laser-coupled to Rydberg states provide a fast and flexible platform to generate configurable atomic arrays for quantum simulation.The platform is especially suited to study quantum spin systems in various geometries.However, for experiments requiring continuous trapping, inhomogeneous light shifts induced by the trapping potential and temperature broadening impose severe limitations.Here we show how Raman sideband cooling allows one to overcome those limitations, thus, preparing the stage for Rydberg dressing in tweezer arrays.
Fluid biomarkers in frontotemporal dementia: past, present and future
2020-11-13

The frontotemporal dementia (FTD) spectrum of neurodegenerative disorders includes a heterogeneous group of conditions. However, following on from a series of important molecular studies in the early 2000s, major advances have now been made in the understanding of the pathological and genetic underpinnings of the disease. In turn, alongside the development of novel methodologies for measuring proteins and other molecules in biological fluids, the last 10 years have seen a huge increase in biomarker studies within FTD. This recent past has focused on attempting to develop markers that will help differentiate FTD from other dementias (particularly Alzheimer’s disease (AD)), as well as from non-neurodegenerative conditions such as primary psychiatric disorders. While cerebrospinal fluid, and more recently blood, markers of AD have been successfully developed, specific markers identifying primary tauopathies or TDP-43 proteinopathies are still lacking. More focus at the moment has been on non-specific markers of neurodegeneration, and in particular, multiple studies of neurofilament light chain have highlighted its importance as a diagnostic, prognostic and staging marker of FTD. As clinical trials get under way in specific genetic forms of FTD, measures of progranulin and dipeptide repeat proteins in biofluids have become important potential measures of therapeutic response. However, understanding of whether drugs restore cellular function will also be important, and studies of key pathophysiological processes, including neuroinflammation, lysosomal function and synaptic health, are also now becoming more common. There is much still to learn in the fluid biomarker field in FTD, but the creation of large multinational cohorts is facilitating better powered studies and will pave the way for larger omics studies, including proteomics, metabolomics and lipidomics, as well as investigations of multimodal biomarker combinations across fluids, brain imaging and other domains. Here we provide an overview of the past, present and future of fluid biomarkers within the FTD field.
Effects as capabilities: effect handlers and lightweight effect polymorphism
2020-11-13

Effect handlers have recently gained popularity amongst programming language researchers. Existing type- and effect systems for effect handlers are often complicated and potentially hinder a wide-spread adoption. We present the language Effekt with the goal to close the gap between research languages with effect handlers and languages for working programmers. The design of Effekt revolves around a different view of effects and effect types. Traditionally, effect types express which side effects a computation might have. In Effekt, effect types express which capabilities a computation requires from its context. While this new point in the design space of effect systems impedes reasoning about purity, we demonstrate that it simplifies the treatment of effect polymorphism and the related issues of effect parametricity and effect encapsulation. To guarantee effect safety, we separate functions from values and treat all functions as second-class. We define the semantics of Effekt as a translation to System Xi, a calculus in explicit capability-passing style.
Stability of the Cauchy horizon in accelerating black-hole spacetimes
2020-11-13

The extendibility of spacetime and the existence of weak solutions to the\\nEinstein field equations beyond Cauchy horizons, is a crucial ingredient to\\nexamine the limits of General Relativity. Strong Cosmic Censorship serves as a\\nfirewall for gravitation by demanding inextendibility of spacetime beyond the\\nCauchy horizon. For asymptotically flat spacetimes, the predominance of the\\nblueshift instability and the subsequent formation of a mass-inflation\\nsingularity at the Cauchy horizon have, so far, substantiated the conjecture.\\nAccelerating black holes, described by the metric, are exact solutions of\\nthe field equations without a cosmological constant, which possess an\\nacceleration horizon with similar causal properties to the cosmological horizon\\nof de Sitter spacetime. Here, by considering linear scalar field perturbations,\\nwe provide numerical evidence for the stability of the Cauchy horizon of\\ncharged accelerating black holes. In particular, we show that the stability of\\nCauchy horizons in accelerating charged black holes is connected to quasinormal\\nmodes, we discuss the regularity requirement for which weak solutions to the\\nfield equations exist at the Cauchy horizon and show that Strong Cosmic\\nCensorship may be violated near extremality.\\n
Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
2020-11-13

Abstract Objectives Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA. Methods We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status. Results ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P &amp;lt; 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P &amp;lt; 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients. Conclusion PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.
Geoarchaeological investigation of occupation deposits in Blombos Cave in South Africa indicate changes in site use and settlement dynamics in the southern Cape during MIS 5b-4
2020-11-13

Abstract The archaeological assemblage recovered from the Middle Stone Age (MSA) levels in Blombos Cave, South Africa, is central to our understanding of the development of early modern humans. Here, we demonstrate that the cultural and technological innovations inferred from the Blombos Cave MSA record also correlate with significant shifts in site use and occupational intensity. Through a comprehensive geoarchaeological investigation of three MSA occupation phases, we identified distinct diachronic trends in the frequency of visits and the modes of occupation. During the earliest phases (ca. 88–82 ka), humans inhabited the cave for more extended periods, but cave visits were not frequent. During the later phases (ca. 77–72 ka), the cave was more regularly visited but for shorter periods each time. We argue that these changes in local occupational intensity, which also coincide with shifts in vegetation, sea levels, and subsistence, can best be explained by broader changes in hunter-gatherer mobility strategies and occupation patterns. Fundamental changes in regional settlement dynamics during Marine Oxygen Isotope Stages 5b-4 would have significantly affected the nature and frequency of social interaction within and between prehistoric populations living in the southern Cape, a scenario that ultimately may explain some of the social and technological advances that occurred there during this time frame.
Human Dopaminergic Neurons Lacking PINK1 Exhibit Disrupted Dopamine Metabolism Related to Vitamin B6 Co-Factors
2020-11-13

PINK1 loss-of-function mutations cause early onset Parkinson disease. PINK1-Parkin mediated mitophagy has been well studied, but the relevance of the endogenous process in the brain is debated. Here, the absence of PINK1 in human dopaminergic neurons inhibits ionophore-induced mitophagy and reduces mitochondrial membrane potential. Compensatory, mitochondrial renewal maintains mitochondrial morphology and protects the respiratory chain. This is paralleled by metabolic changes, including inhibition of the TCA cycle enzyme <i>m</i>Aconitase, accumulation of NAD<sup>+</sup>, and metabolite depletion. Loss of PINK1 disrupts dopamine metabolism by critically affecting its synthesis and uptake. The mechanism involves steering of key amino acids toward energy production rather than neurotransmitter metabolism and involves cofactors related to the vitamin B6 salvage pathway identified using unbiased multi-omics approaches. We propose that reduction of mitochondrial membrane potential that cannot be controlled by PINK1 signaling initiates metabolic compensation that has neurometabolic consequences relevant to Parkinson disease.
Building Event-Based Ad Hoc Properties: On the Interpretation of Adjectival Passives
2020-11-13

The paper develops a new perspective on the semantics and pragmatics of adjectival passives that focuses on their characteristic context dependency. Adjectival passives are analyzed as a flexible grammatical means of creating a potentially new ad hoc property based on the verbal event by which the subject referent is categorized according to contextually salient goals. The post state vs. target state ambiguity of adjectival passives is accounted for by deriving the two readings from a semantically underspecified representation that requires the pragmatic machinery to infer a suitable contextual instantiation.
Bi-allelic truncating mutations in VWA1 cause neuromyopathy
2020-11-13

Abstract The von Willebrand Factor A domain containing 1 protein, encoded by VWA1, is an extracellular matrix protein expressed in muscle and peripheral nerve. It interacts with collagen VI and perlecan, two proteins that are affected in hereditary neuromuscular disorders. Lack of VWA1 is known to compromise peripheral nerves in a Vwa1 knock-out mouse model. Exome sequencing led us to identify bi-allelic loss of function variants in VWA1 as the molecular cause underlying a so far genetically undefined neuromuscular disorder. We detected six different truncating variants in 15 affected individuals from six families of German, Arabic, and Roma descent. Disease manifested in childhood or adulthood with proximal and distal muscle weakness predominantly of the lower limbs. Myopathological and neurophysiological findings were indicative of combined neurogenic and myopathic pathology. Early childhood foot deformity was frequent, but no sensory signs were observed. Our findings establish VWA1 as a new disease gene confidently implicated in this autosomal recessive neuromyopathic condition presenting with child-/adult-onset muscle weakness as a key clinical feature.
Selective Brain Hypothermia in Acute Ischemic Stroke: Reperfusion Without Reperfusion Injury
2020-11-13

In acute ischemic stroke, early recanalization of the occluded artery is crucial for best outcome to be achieved. Recanalization aims at restoring blood flow to the ischemic tissue (reperfusion) and is achieved with pharmacological thrombolytic drugs, endovascular thrombectomy (EVT) devices, or both. The introduction of modern endovascular devices has led to tremendous anatomical and clinical success with rates of substantial reperfusion exceeding 80% and proven clinical benefit in patients with anterior circulation large vessel occlusions (LVOs). However, not every successful reperfusion procedure leads to the desired clinical outcome. In fact, the rate of non-disabled outcome at 3 months with current EVT treatment is ~1 out of 4. A constraint upon better outcomes is that reperfusion, though resolving ischemic stress, may not restore the anatomic structures and metabolic functions of ischemic tissue to their baseline states. In fact, ischemia triggers a complex cascade of destructive mechanisms that can sometimes be exacerbated rather than alleviated by reperfusion therapy. Such reperfusion injury may cause infarct progression, intracranial hemorrhage, and unfavorable outcome. Therapeutic hypothermia has been shown to have a favorable impact on the molecular elaboration of ischemic injury, but systemic hypothermia is limited by slow speed of attaining target temperatures and clinical complications. A novel approach is endovascular delivery of hypothermia to cool the affected brain tissue selectively and rapidly with tight local temperature control, features not available with systemic hypothermia devices. In this perspective article, we discuss the possible benefits of adjunctive selective endovascular brain hypothermia during interventional stroke treatment.
A theory for the emergence of neocortical network architecture
2020-11-13

Developmental programs that guide neurons and their neurites into specific subvolumes of the mammalian neocortex give rise to lifelong constraints for the formation of synaptic connections. To what degree do these constraints affect cortical wiring diagrams? Here we introduce an inverse modeling approach to show how cortical networks would appear if they were solely due to the spatial distributions of neurons and neurites. We find that neurite packing density and morphological diversity will inevitably translate into non-random pairwise and higher-order connectivity statistics. More importantly, we show that these non-random wiring properties are not arbitrary, but instead reflect the specific structural organization of the underlying neuropil. Our predictions are consistent with the empirically observed wiring specificity from subcellular to network scales. Thus, independent from learning and genetically encoded wiring rules, many of the properties that define the neocortex’ characteristic network architecture may emerge as a result of neuron and neurite development.
Review on the Compositional Variation of Eudialyte-Group Minerals in the Ilímaussaq Complex (South Greenland)
2020-11-13

We review the compositional variation of eudialyte-group minerals (EGM) from the Ilímaussaq complex in South Greenland. Investigated samples cover all major rock units and associated pegmatites and aplites. The whole data set (&gt;3000 analyses from &gt;250 samples) exhibits variable XMn (0.1–0.5), REE (0.2–1.7 apfu), Nb (0.1–0.4), and Cl contents (0.4–1.6 apfu). Most EGM compositions are Na-rich (13–15 apfu), while deviations to Na-rich but also to Na-poor compositions occur because of a combination of primary features (peralkalinity, water activity) and secondary alteration. During magma evolution, REE contents in EGM cores generally increase and reach their highest contents in the most evolved rock units of the complex. This points to the moderate compatibility of REE in EGM and a bulk D (cEGM/cmelt) value of &lt;1 during magma differentiation. Chlorine contents in EGM cores continuously decrease, and are lowest at the rims of individual crystals, suggesting a continuous decrease of Cl activity in the magmas by large-scale EGM and sodalite extraction during the orthomagmatic stage and water enrichment during the late-magmatic stage. The overall variations of XMn across stratigraphy are only minor and likely influenced by the co-crystallization of sodic pyroxene and amphibole (c.f. aegirine, arfvedsonite) and local phase proportions. Similarly, Nb and Ti contents are influenced by co-crystallizing aenigmatite, rinkite, and others. Their presence buffers Ti and Nb contents to rather constant and low values, while their absence may cause variable enrichment on a local scale. Very low Sr contents (&lt;0.1 apfu) in magmatic EGM from Ilímaussaq are related to the basaltic nature of the parental magmas of the complex, as large-scale plagioclase fractionation occurred prior to the formation of the Ilímaussaq magmas, effectively removing Sr from the system. This is in line with very strong negative Eu anomalies in EGM from Ilímaussaq. Consistently, Sr contents in EGM from alkaline complexes, for which foiditic parental magmas are assumed, are much higher and, in such cases, negative Eu anomalies are generally absent.
Comparison in Turkish: A Rediscovery of the Phrasal Comparative
2020-11-13

This paper argues that clausal comparatives are completely unattested in Turkish and thus verifies the need for a genuinely phrasal analysis of comparison constructions in this language. It develops such a syntactic and semantic analysis that differs considerably from ‘standard’ analyses commonly suggested for languages like English and also shows that this phrasal analysis derives the correct predictions for the scopal behaviour of quantified DPs and the comparative operator. It furthermore argues that phrasal comparatives are the ‘basic’ and potentially universal type of comparatives, in contrast to what has been hypothesised previously, and speculates on how this phrasal analysis might even be applied to solve problems for analysis with English comparatives.