julilili42/papers huggingface dataset:
KCTD7 deficiency defines a distinct neurodegenerative disorder with a conserved autophagy‐lysosome defect
2018-10-08

Objective Several small case series identified KCTD7 mutations in patients with a rare autosomal recessive disorder designated progressive myoclonic epilepsy (EPM3) and neuronal ceroid lipofuscinosis (CLN14). Despite the name KCTD (potassium channel tetramerization domain), KCTD protein family members lack predicted channel domains. We sought to translate insight gained from yeast studies to uncover disease mechanisms associated with deficiencies in KCTD7 of unknown function. Methods Novel KCTD7 variants in new and published patients were assessed for disease causality using genetic analyses, cell‐based functional assays of patient fibroblasts and knockout yeast, and electron microscopy of patient samples. Results Patients with KCTD7 mutations can exhibit movement disorders or developmental regression before seizure onset, and are distinguished from similar disorders by an earlier age of onset. Although most published KCTD7 patient variants were excluded from a genome sequence database of normal human variations, most newly identified patient variants are present in this database, potentially challenging disease causality. However, genetic analysis and impaired biochemical interactions with cullin 3 support a causal role for patient KCTD7 variants, suggesting deleterious alleles of KCTD7 and other rare disease variants may be underestimated. Both patient‐derived fibroblasts and yeast lacking Whi2 with sequence similarity to KCTD7 have impaired autophagy consistent with brain pathology. Interpretation Biallelic KCTD7 mutations define a neurodegenerative disorder with lipofuscin and lipid droplet accumulation but without defining features of neuronal ceroid lipofuscinosis or lysosomal storage disorders. KCTD7 deficiency appears to cause an underlying autophagy‐lysosome defect conserved in yeast, thereby assigning a biological role for KCTD7. Ann Neurol 2018;84:774–788
Improved results of ACL primary repair in one‐part tears with intact synovial coverage
2018-10-08

Abstract Purpose It was the aim to assess the influence of synovial sheath disruption on early failure of primary anterior cruciate ligament (ACL) repair. It was hypothesized that more‐part ACL tears with disruption of the synovial sheath are associated with a higher risk of failure after primary ACL repair. Methods A cohort study was conducted comprising patients with primal ACL tears undergoing primary ACL repair and dynamic intraligamentary stabilization (DIS). The patients were stratified into three groups: A—one‐part rupture with intact synovial membrane ( n = 50), B—two‐part ruptures resultant to separation of the ACL into two main bundles with synovial membrane tearing ( n = 52) and C—more parts involving multilacerated ruptures with membrane disruption ( n = 22). Failure was defined as a retear or residual laxity (anterior posterior translation &gt; 5 mm compared to healthy knee). Adjustment for potential risk factors was performed using a multivariate logistic‐regression model. Results The overall failure rate was 17.7% throughout the mean follow‐up period of 2.3 ± 0.8 years. The failure rate in patients with one‐part ACL tears with an intact synovial membrane was 4% ( n = 2) (Group A), which was significantly lower than the failure rates in groups B and C, 26.9% ( n = 14) ( p = 0.001) and 27.3% ( n = 6) ( p = 0.003), respectively. Disruption of the synovial sheath in two‐ or more‐part tears was identified as an independent factor influencing treatment failure in primary ACL repair (OR 8.9; 95% CI 2.0–40.0). Conclusion The integrity of the ACL bundles and synovial sheath is a factor that influences the success of ACL repair. This needs to be considered intra‐operatively when deciding about repair. Level of evidence IV.
Combination versus monotherapy for the treatment of infections due to carbapenem-resistant Enterobacteriaceae
2018-10-08

Purpose of review Combination therapy is a common strategy for treatment of multidrug resistant infections. Despite the strong twin rationales of improving efficacy and reducing resistance development, the evidence supporting this strategy remains controversial. The aims of this review are to assess the most recent studies supporting the use of combination therapy for treating infections because of carbapenem-resistant Enterobacteriaceae (CRE) and to highlight relevant areas for further research. Recent findings Evidence supporting the use of combination therapy for the treatment of CRE remains limited to in-vitro experiments and observational studies with considerable risk of bias. Very few antibiotic combinations have been tested in well designed randomized controlled trials, making it difficult to draw general conclusions for clinical practice. Summary Further studies are urgently needed to test the most promising synergistic combinations. New drugs potentially active against CRE should also to be tested in studies with adequate sample size and truly representative of the general patient population.
Sounding the alarm for right-wing #MeToo: “120 Dezibel” in Germany
2018-10-08

One hundred and twenty decibels is the standard frequency of a commercial personal pocket alarm. Such alarms, often sold in the form of key chains, are advertised as safety devices for women to det...
Macular spatial distribution of preserved autofluorescence in patients with choroideremia
2018-10-08

Background/Aims To better understand the pattern of degeneration progression in cases with choroideremia. Methods A cohort of genotypically confirmed choroideremia cases who underwent optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging was studied. Using HEYEX review software, the foveal centre was marked on FAF images under guidance of corresponding OCT images, followed by application of an ETDRS grid. The boundaries of preserved autofluorescence (AF) were manually segmented in each individual ETDRS subfield. The regional distribution of preserved AF was assessed by comparing its area among the various subfields. Results A total of 168 eyes from 84 choroideremia cases were enrolled. There was a statistically significant difference in the amount of preserved AF area between inner subfields as determined by one-way analysis of variance (F (3,668)=9.997, p&lt;0.001) and also between outer subfields (F (3,668)=8.348, p&lt;0.001). A Tukey posthoc test revealed that the preserved AF area in the nasal subfields in both the inner and outer subfields was significantly smaller compared with analogue subfields. Conclusion The asymmetric spatial distribution of preserved AF in choroideremia (corresponding to the stellate shaped nature of these regions) suggests that the progression of degeneration has directional preference.
Locating Paradise in China: Joseph Stöcklein’s Chronology (1729) in Context*
2018-10-08

This article focuses on the Chronology by the Graz Jesuit Joseph Stöcklein (1676–1732), published in 1729. Since late antiquity, intellectuals have been crafting chronological works with a view to making apparent God’s actions in the world. These attempts were primarily based on the Old Testament, which was seen as a historiographical narrative and thus counted as a record of factual truth. New chronographical insights from China, which had been reaching Europe since the beginning of the seventeenth century, contradicted this exegetical tradition, however. Whoever attempted to relate the new findings arriving from China to the Bible had no choice but to give up certain truths in order to save others. Seen in this light, the tight framework of biblical truth led directly to creative hypotheses such as Stöcklein’s Chronology, which demonstrated two main shifts in the conceptualizing of universal history: first, Stöcklein emphasized the significance of the Old Reich and therefore decentred his universal history from western Europe to (mainly) Augsburg and Nuremberg; secondly, he envisaged the Far East rather than the Middle East and Europe as the geographical centre of Christian universalism and of the beginning of universal history. One crucial step was his relocation of Paradise to the immediate vicinity of China. Discussing the manifold Buddhist, Muslim and Christian sources with which Stöcklein was playing, I argue that Stöcklein’s turned the biblical story of salvation into a Chinese story of salvation.
Radial perturbations of the scalarized Einstein-Gauss-Bonnet black holes
2018-10-09

Recently a new class of scalarized black holes in Einstein-Gauss-Bonnet (EGB)\\ntheories was discovered. What is special for these black hole solutions is that\\nthe scalarization is not due to the presence of matter, but {it is induced} by\\nthe curvature of spacetime itself. Moreover, more than one branch of scalarized\\nsolutions can bifurcate from the Schwarzschild branch, and these scalarized\\nbranches are characterized by the number of nodes of the scalar field. The next\\nstep is to consider the linear stability of these solutions, which is\\nparticularly important due to the fact that the Schwarzschild black holes lose\\nstability at the first point of bifurcation. Therefore we here study in detail\\nthe radial perturbations of the scalarized EGB black holes. The results show\\nthat all branches with a nontrivial scalar field with one or more nodes are\\nunstable. The stability of the solutions on the fundamental branch, whose\\nscalar field has no radial nodes, depends on the particular choice of the\\ncoupling function between the scalar field and the Gauss-Bonnet invariant. We\\nconsider two particular cases based on the previous studies of the background\\nsolutions. If this coupling has the form used in \\\\cite{Doneva:2017bvd} the\\nfundamental branch of solutions is stable, except for very small masses. In the\\ncase of a coupling function quadratic in the scalar field \\\\cite{Silva:2017uqg},\\nthough, the whole fundamental branch is unstable.\\n
Experimental Evidence of Functional Group-Dependent Effects of Tree Diversity on Soil Fungi in Subtropical Forests
2018-10-09

Deconvoluting the relative contributions made by specific biotic and abiotic drivers to soil fungal community compositions facilitates predictions about the functional responses of ecosystems to environmental changes, such as losses of plant diversity, but it is hindered by the complex interactions involved. Experimental assembly of tree species allows separation of the respective effects of plant community composition (biotic components) and soil properties (abiotic components), enabling much greater statistical power than can be achieved in observational studies. We therefore analyzed these contributions by assessing, via pyrotag sequencing of the internal transcribed spacer (ITS2) rDNA region, fungal communities in young subtropical forest plots included in a large experiment on the effects of tree species richness. Spatial variables and soil properties were the main drivers of soil fungal alpha and beta-diversity, implying strong early-stage environmental filtering and dispersal limitation. Tree related variables, such as tree community composition, significantly affected arbuscular mycorrhizal and pathogen fungal community structure, while differences in tree host species and host abundance affected ectomycorrhizal fungal community composition. At this early stage of the experiment, only a limited amount of carbon inputs (rhizodeposits and leaf litter) was being provided to the ecosystem due to the size of the tree saplings, and persisting legacy effects were observed. We thus expect to find increasing tree related effects on fungal community composition as forest development proceeds.
Application of Experimental Polystyrene Partition Constants and Diffusion Coefficients to Predict the Sorption of Neutral Organic Chemicals to Multiwell Plates in in Vivo and in Vitro Bioassays
2018-10-09

Sorption to the polystyrene (PS) of multiwell plates can affect the exposure to organic chemicals over time in in vitro and in vivo bioassays. Experimentally determined diffusion coefficients in PS ( D<sub>PS</sub>) were in a narrow range of 1.25 to 8.0 · 10<sup>-16</sup> m<sup>2</sup> s<sup>-1</sup> and PS-water partition constants ( K<sub>PS/w</sub>) ranged from 0.04 to 5.10 log-units for 22 neutral organic chemicals. A kinetic model, which explicitly accounts for diffusion in the plastic, was applied to predict the depletion of neutral organic chemicals from different bioassay media by sorption to various multiwell plate formats. For chemicals with log K<sub>ow</sub> > 3, the medium concentrations decreased rapidly and considerably in the fish embryo toxicity assay but medium concentrations remained relatively constant in the cell-based bioassays with medium containing 10% fetal bovine serum (FBS), emphasizing the ability of the protein- and lipid-rich medium to compensate for losses by multiwell plate sorption. The PS sorption data may serve not only for exposure assessment in bioassays but also to model the contaminant uptake by and release from plastic packaging material and the chemical transport by PS particles in the environment.
Facilitation from an intraspecific perspective – stress tolerance determines facilitative effect and response in plants
2018-10-09

Summary Plant–plant interactions are reciprocal and include effects on and response to neighbours. Distinct traits confer competitive effect and response ability, but how specific traits determine effect and response in facilitative interactions has not been studied experimentally. We utilized the model species Arabidopsis thaliana to test for trait dependence of facilitative interactions. Salt‐sensitive (sos) mutants or salt‐tolerant wild‐types were exposed to an experimental salinity gradient with and without intraspecific neighbours and the intensity of plant–plant interactions was measured for three performance variables. We tested whether salt tolerance can predict facilitative effect and response and whether a tradeoff exists between competitive ability and tolerance to stress. Interactions shifted very clearly from negative to positive with increasing stress. Salt‐sensitive genotypes were less negatively affected by competition but more dependent on facilitation than were wild‐types, indicating a tradeoff between competitive ability and stress tolerance. Surprisingly, sensitive genotypes imposed stronger facilitative effects, despite being much smaller under stress, probably because they retrieved more salt from the soil. Stress tolerance defined facilitative effect and response via distinct mechanisms. We advocate more controlled experiments with model species to advance our understanding of the trait dependence of biotic interactions and their consequences for community organization.
The Benefit of Combining Neuronal Feedback and Feed-Forward Control for Robustness in Step Down Perturbations of Simulated Human Walking Depends on the Muscle Function
2018-10-09

It is often assumed that the spinal control of human locomotion combines feed-forward central pattern generation with sensory feedback via muscle reflexes. However, the actual contribution of each component to the generation and stabilization of gait is not well understood, as direct experimental evidence for either is difficult to obtain. We here investigate the relative contribution of the two components to gait stability in a simulation model of human walking. Specifically, we hypothesize that a simple linear combination of feedback and feed-forward control at the level of the spinal cord improves the reaction to unexpected step down perturbations. In previous work, we found preliminary evidence supporting this hypothesis when studying a very reduced model of rebounding behaviors. In the present work, we investigate if the evidence extends to a more realistic model of human walking. We revisit a model that has previously been published and relies on spinal feedback control to generate walking. We extend the control of this model with a feed-forward muscle activation pattern. The feed-forward pattern is recorded from the unperturbed feedback control output. We find that the improvement in the robustness of the walking model with respect to step down perturbations depends on the ratio between the two strategies and on the muscle to which they are applied. The results suggest that combining feed-forward and feedback control is not guaranteed to improve locomotion, as the beneficial effects are dependent on the muscle and its function during walking.
Online peer consulting for health professionals
2018-10-09

Summary Background Many health care professionals specialise in particular medical fields. Nevertheless, they often encounter patients with other indications for which they have only limited experience. In such situations it is helpful to consult colleagues who have specialised in the respective areas. The Internet provides the opportunity to connect with other specialists that can be used for peer consulting. We argue that health professionals should learn to make use of online peer consulting during vocational training. Methods We used an open‐source platform that provided the opportunity to chat and upload documents. We recruited 45 first‐year physiotherapy students as participants. The training for online peer consulting was integrated into courses where students were taught basic principles of gait analysis and learned how to document the findings of their examinations. Subsequently, the students evaluated the course and the online collaboration. Findings Students were highly motivated to use the online platform and perceived the online peer consulting and the atmosphere of collaboration on the platform to be very positive. In addition, students had a significant increase in content knowledge and were more confident in their own knowledge than they were before the online peer consulting. Discussion It seems appropriate to provide training for giving and gathering online peer feedback. This opportunity, provided at an early stage of training, could help prepare students for continuing co‐operative exchange in their professional lives. Health care professionals should learn how to gather information from colleagues and how to provide adequate feedback
Retrosigmoid Transmeatal Endoscope-Assisted Approach in Semi-Sitting Position for Resection of Vestibular Schwannoma: 2-D operative Video
2018-10-09

We present a case of a mid-sized vestibular schwannoma (T3b according to the Hannover classification) that was resected through a retrosigmoid transmeatal approach in semi-sitting position under endoscopic assistance. The patient is a 52-year-old male with acute loss of functional hearing on the right side. Audiometry confirmed a loss of up to 60 dB and lost speech discrimination, there were no associated symptoms such as tinnitus or vertigo. This 2D video demonstrates positioning, OR set-up, anatomical and surgical nuances of the skull base approach and the operative technique for microdissection of the tumor from the critical neurovascular structures, especially the facial and cochlear nerves. A gross total resection was achieved and the patient discharged home after four days with unaltered function of the facial nerve (HB I). At one year follow up there was no indication of residual or recurrence. In summary, the retrosigmoid transmeatal approach is an important and powerful tool in the armamentarium for the microsurgical management of all kinds of vestibular schwannomas. Provided the necessary anesthesiological precautions and intraoperative procedures the semi-sitting position is safe and effective. If needed, the approach can be complemented by the use of an endoscope for visualization of the distal internal auditory canal. The link to the video can be found at: https://youtu.be/pPKT4_5nIn0.
Mitochondrial Morphology, Function and Homeostasis Are Impaired by Expression of an N-terminal Calpain Cleavage Fragment of Ataxin-3
2018-10-10

Alterations in mitochondrial morphology and function have been linked to neurodegenerative diseases, including Parkinson disease, Alzheimer disease and Huntington disease. Metabolic defects, resulting from dysfunctional mitochondria, have been reported in patients and respective animal models of all those diseases. Spinocerebellar Ataxia Type 3 (SCA3), another neurodegenerative disorder, also presents with metabolic defects and loss of body weight in early disease stages although the possible role of mitochondrial dysfunction in SCA3 pathology is still to be determined. Interestingly, the SCA3 disease protein ataxin-3, which is predominantly localized in cytoplasm and nucleus, has also been associated with mitochondria in both its mutant and wildtype form. This observation provides an interesting link to a potential mitochondrial involvement of mutant ataxin-3 in SCA3 pathogenesis. Furthermore, proteolytic cleavage of ataxin-3 has been shown to produce toxic fragments and even overexpression of artificially truncated forms of ataxin-3 resulted in mitochondria deficits. Therefore, we analyzed the repercussions of expressing a naturally occurring N-terminal cleavage fragment of ataxin-3 and the influence of an endogenous expression of the S256 cleavage fragment <i>in vitro</i> and <i>in vivo</i>. In our study, expression of a fragment derived from calpain cleavage induced mitochondrial fragmentation and cristae alterations leading to a significantly decreased capacity of mitochondrial respiration and contributing to an increased susceptibility to apoptosis. Furthermore, analyzing mitophagy revealed activation of autophagy in the early pathogenesis with reduced lysosomal activity. In conclusion, our findings indicate that cleavage of ataxin-3 by calpains results in fragments which interfere with mitochondrial function and mitochondrial degradation processes.
The MIS5 Pietersburg at ‘28’ Bushman Rock Shelter, Limpopo Province, South Africa
2018-10-10

In the past few decades, a diverse array of research has emphasized the precocity of technically advanced and symbolic practices occurring during the southern African Middle Stone Age. However, uncertainties regarding the regional chrono-cultural framework constrain models and identification of the cultural and ecological mechanisms triggering the development of such early innovative behaviours. Here, we present new results and a refined chronology for the Pietersburg, a techno-complex initially defined in the late 1920's, which has disappeared from the literature since the 1980's. We base our revision of this techno-complex on ongoing excavations at Bushman Rock Shelter (BRS) in Limpopo Province, South Africa, where two Pietersburg phases (an upper phase called '21' and a lower phase called '28') are recognized. Our analysis focuses on the '28' phase, characterized by a knapping strategy based on Levallois and semi-prismatic laminar reduction systems and typified by the presence of end-scrapers. Luminescence chronology provides two sets of ages for the upper and lower Pietersburg of BRS, dated respectively to 73±6ka and 75±6ka on quartz and to 91±10ka and 97±10ka on feldspar, firmly positioning this industry within MIS5. Comparisons with other published lithic assemblages show technological differences between the Pietersburg from BRS and other southern African MIS5 traditions, especially those from the Western and Eastern Cape. We argue that, at least for part of MIS5, human populations in South Africa were regionally differentiated, a process that most likely impacted the way groups were territorially and socially organized. Nonetheless, comparisons between MIS5 assemblages also indicate some typological similarities, suggesting some degree of connection between human groups, which shared similar innovations but manipulated them in different ways. We pay particular attention to the end-scrapers from BRS, which represent thus far the earliest documented wide adoption of such tool-type and provide further evidence for the innovative processes characterizing southern Africa from the MIS5 onwards.