julilili42/papers huggingface dataset:
Evolutionary Dynamics of Treatment-Induced Resistance in Cancer Informs Understanding of Rapid Evolution in Natural Systems
2021-08-06

Rapid evolution is ubiquitous in nature. We briefly review some of this quite broadly, particularly in the context of response to anthropogenic disturbances. Nowhere is this more evident, replicated and accessible to study than in cancer. Curiously cancer has been late - relative to fisheries, antibiotic resistance, pest management and evolution in human dominated landscapes - in recognizing the need for evolutionarily informed management strategies. The speed of evolution matters. Here, we employ game-theoretic modeling to compare time to progression with continuous maximum tolerable dose to that of adaptive therapy where treatment is discontinued when the population of cancer cells gets below half of its initial size and re-administered when the cancer cells recover, forming cycles with and without treatment. We show that the success of adaptive therapy relative to continuous maximum tolerable dose therapy is much higher if the population of cancer cells is defined by two cell types (sensitive vs. resistant in a polymorphic population). Additionally, the relative increase in time to progression increases with the speed of evolution. These results hold with and without a cost of resistance in cancer cells. On the other hand, treatment-induced resistance can be modeled as a quantitative trait in a monomorphic population of cancer cells. In that case, when evolution is rapid, there is no advantage to adaptive therapy. Initial responses to therapy are blunted by the cancer cells evolving too quickly. Our study emphasizes how cancer provides a unique system for studying rapid evolutionary changes within tumor ecosystems in response to human interventions; and allows us to contrast and compare this system to other human managed or dominated systems in nature.
Pain and Associated Neuropsychiatric Symptoms in Patients Suffering from Dementia: Challenges at Different Levels and Proposal of a Conceptual Framework
2021-08-06

Old age is critically associated with multi-morbidity, chronic pain, and high risk for dementia. Recognizing and treating pain is very much dependent on language comprehension and production. Both may be impaired in dementia. Moreover, neuropsychiatric symptoms may interact with pain perception. The main aims of the present article were 1) to identify key areas for future research to elucidate the relation between pain and associated neuropsychiatric symptoms in dementia, and 2) to provide a conceptual framework for ameliorating the clinical process of recognizing, assessing, and managing pain in non-communicating patients with advanced dementia.
CXCR4 hyperactivation cooperates with TCL1 in CLL development and aggressiveness
2021-08-06

Abstract Aberrant CXCR4 activity has been implicated in lymphoma pathogenesis, disease progression, and resistance to therapies. Using a mouse model with a gain-of-function CXCR4 mutation ( CXCR4 C1013G ) that hyperactivates CXCR4 signaling, we identified CXCR4 as a crucial activator of multiple key oncogenic pathways. CXCR4 hyperactivation resulted in an expansion of transitional B1 lymphocytes, which represent the precursors of chronic lymphocytic leukemia (CLL). Indeed, CXCR4 hyperactivation led to a significant acceleration of disease onset and a more aggressive phenotype in the murine Eμ-TCL1 CLL model. Hyperactivated CXCR4 signaling cooperated with TCL1 to cause a distinct oncogenic transcriptional program in B cells, characterized by PLK1/FOXM1-associated pathways. In accordance, Eμ-TCL1;CXCR4 C1013G B cells enriched a transcriptional signature from patients with Richter’s syndrome, an aggressive transformation of CLL. Notably, MYC activation in aggressive lymphoma was associated with increased CXCR4 expression. In line with this finding, additional hyperactive CXCR4 signaling in the Eμ-Myc mouse, a model of aggressive B-cell cancer, did not impact survival. In summary, we here identify CXCR4 hyperactivation as a co-driver of an aggressive lymphoma phenotype.
Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation – development of a risk score
2021-08-06

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) - a metabolite of ethanol - in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.
On the Origin of Gap States in Molecular Semiconductors—A Combined UPS, AFM, and X-ray Diffraction Study
2021-08-06

Electronic states within the HOMO–LUMO gap of organic semiconductors play a key role in the energy level alignment of substrate–organic and organic–organic interfaces and therefore are a defining parameter for device functionality and efficiency. They are thought to result from structural defects influencing the specific environment of a molecule. Varying the substrate temperature for samples grown by molecular beam deposition, we are able to control their density. Using atomic force microscopy and X-ray scattering techniques, we can differentiate defects depending on their length scale and effective direction. Comparison of the respective defect density with the density of gap states, measured directly via ultra-low-background ultraviolet photoelectron spectroscopy, enables to correlate structural and electronic properties for different prototypical organic semiconductors. We investigate the impact of gap states on the energy level alignment and find a direct link between structural defects and the interface dipole.
On the Role of Heterojunctions of Core-Shell Heterostructures in Gas Sensing
2021-08-06

Heterostructures made from semiconducting metal oxides (SMOX) are fundamental for the development of high-performance gas sensors. Yet, despite the recognition of their importance in real applications, the understanding of the transduction mechanism either related to the heterojunction, or simply to the core and shell materials is still lacking. A better understanding of the sensing response of heterostructured nanomaterials requires the engineering of heterojunctions with well-defined core and shell layers. Here, we introduce a series of prototypes nSMOX-CNT, pSMOX-CNT, and pSMOX-nSMOX-CNT and nSMOX-pSMOX-CNT hierarchical core-shell heterostructures (CSHS) permitting us to directly relate the sensing response to the SMOX shell, or to the p-n heterojunction. The carbon nanotubes are here used as highly conductive substrates permitting to operate the devices at relatively low temperature and are not involved in the sensing response. NiO and SnO2 are selected as representative p- and n-type SMOX, respectively, and the response of a set of samples is studied toward hydrogen considered as model analyte. The n,pSMOX-CNT CSHS exhibit response related to the n,pSMOX-shell layer. On the other hand, the pSMOX-nSMOX-CNT and nSMOX-pSMOX-CNT CSHS show sensing responses, which in certain cases are governed by the heterojunctions between nSMOX and pSMOX and strongly depends on the thickness of the SMOX layers. Due to the fundamental nature of this study, these findings are important for the development of next generation gas sensing devices.
Correction: Deep Learning in the Detection of Rare Fractures – Development of a “Deep Learning Convolutional Network” Model for Detecting Acetabular Fractures
2021-08-06

Correction to: Deep Learning in the Detection of Rare Fractures – Development of a “Deep Learning Convolutional Network” Model for Detecting Acetabular FracturesZ Orthop Unfall eFirstDOI: 10.1055/a-1511-8595
Response to nitrogen and salinity in Rhizophora mangle propagules varies by maternal family and population of origin
2021-08-06

Abstract Many coastal foundation plant species thrive across a range of environmental conditions, often displaying dramatic phenotypic variation in response to environmental variation. We characterized the response of propagules from six populations of the foundation species Rhizophora mangle L. to full factorial combinations of two levels of salt (15 ppt and 45 ppt) reflecting the range of salinity measured in the field populations, and two levels of nitrogen (N; no addition and amended at approximately 3 mg N per pot each week) equivalent to comparing ambient N to a rate of addition of 75 kg per hectare per year. The response to increasing salt included significant plasticity in succulence. Propagules also showed plasticity in maximum photosynthetic rate in response to N amendment, but the responses depended on the level of salt and varied by population of origin. Generally, survival was lower in high salt and high N, but the impact varied among populations. Overall, this study revealed significant phenotypic plasticity in response to salt and N level. Propagules from different populations differed in all traits measured. Variation in phenotypic plasticity and propagule survival in R. mangle may contribute to adaptation to a complex mosaic of environmental conditions and response to climate change.
Identification of Network Promoters in a Regional and Intersectoral Health Promotion Network: A Qualitative Social Network Analysis in Southern Germany
2021-08-07

Health in all policies is a key approach to promote health and calls for cooperation between diverse levels of government and different sectors. In this paper, we analyze how a network called ‘Healthy Region Plus’ in Southern Germany addresses intersectoral cooperation at city and county levels. We aim to analyze the different roles of actors involved in the network based on the promoter model. We conducted two socio-material network mappings based on the Net-map approach by Schiffer and Hauck. The analysis followed three steps: data visualization, descriptive analysis of network properties, and interpretation of findings. Our findings reveal a complex intersectoral cooperation structure, with county and city level clusters, with network members who act as diverse power, expert, process, or relationship promoters. We also identified certain relevant sectors not to be part of the network. We discuss that the success of the network depends on the members’ active participation in and their outreach beyond the existing network, between city and county levels, and across sectors to promote health and build health-promoting structures in the region.
Secondary Analysis of a Study on Exercise Therapy in Hip Osteoarthritis: Follow-Up Data on Pain and Physical Functioning
2021-08-07

We evaluated the short- and longer-term effects of exercise therapy in hip osteoarthritis patients (OA) at baseline, three, six, and 12 months in a randomized setting, followed by a non-randomized setting. The primary randomized intervention (E = exercise, P = placebo–ultrasound, C = control) was followed by a voluntary three-month exercise therapy for P and C (renamed P-E, C-E). Participants randomized to E were not offered treatment again (E-C). Effect sizes (ES; 95% CI) were calculated for within-group effects across time for bodily pain (SF-36) and WOMAC pain, function, and stiffness. ANCOVAs of post-treatment scores were used for group comparison after the group-specific exercise intervention phase. Exercise adherence was assessed and related to post-treatment scores of clinical outcomes. Data of 115 participants of the RCT eligible for follow-up and completing exercise therapy were included into our analyses. Small to medium beneficial long-term effects of cumulative interventional effects, including exercise training, persisted in all groups. Group E-C (n = 49) showed significant 12 months vs. baseline within-group ES in all outcomes (ES 0.39–0.59) except stiffness. Findings were less prominent for exercise therapy in a non-randomized setting (C-E, P-E, both n = 33). Differences are partially explained by adherence rates, highlighting the relevance of therapy compliance strategies. Short-term between-group differences (ANCOVAs) only showed statistically significant differences for WOMAC function between P-E and E-C in favor of E-C (6.4 (95% CI 1.6–11.2; score range 0–100)).
Absolute Geist or Self-Loving God?
2021-08-07

Given recent naturalist readings of Hegel’s metaphysics and Spinoza’s rather widespread reputation as being the most consistent rationalist, the question arises in what sense Hegel can be called a ‘Spinozist’. An analysis of Hegel’s notion of philosophy reveals that despite Hegel’s and Spinoza’s common commitment to the notion that philosophy is “the self-comprehension of universal and unconditioned truth”, Hegel thinks that Spinoza’s substance-based account renders the finite philosophers entirely explicable in terms of universal truth’s self-causing and thus undermines individual autonomy. In contrast, Hegel’s commitment to concept-metaphysics is supposed to enable him to argue that individual philosophers still exert control over their thought and remain autonomous in their acts of channeling truth. Hegel thus aims to retain Kant’s allegedly anti-spinozistic commitment to individual autonomy by grounding his notion of philosophy on concept- rather than substance-metaphysics.
Introduction
2021-08-07

In 1817, Hegel published a condensed articulation of his basic philosophical commitments, designed to help make his notoriously difficult lectures a bit easier to follow. He titled this compendium the Encyclopedia of the Philosophical Sciences in Basic Outline and, for the rest of his life, made consistent use of it in his classes, constantly amending it until its last, more detailed version was published in 1830. That Hegel called this text an “encyclopedia” was as bold a choice as it was strange. For on the one hand, it of course suggests that Hegel saw his own knowledge and system of philosophy as encyclopedic. But on the other hand, the text also bears no structural resemblance to any other encyclopedia.
The Effect of Probiotics on Quality of Life, Depression and Anxiety in Patients with Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis
2021-08-08

Background: Functional gastrointestinal disorders such as irritable bowel syndrome (IBS) report clinical improvement following probiotic therapy, but whether psychiatric comorbidity and quality-of-life in IBS improves directly or in directly is unknown. This meta-analysis synthesized the evidence regarding the effects of probiotics on quality of life (QoL), anxiety and depression in IBS. Methods: The review was executed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the databases PubMed, Web of Science and Cochrane Library. For QoL, the data were meta-analyzed, and for anxiety and depression a qualitative analysis was performed. Results: Thirty-five placebo-controlled studies were included of which 11 were eligible for meta-analysis. QoL improved with probiotic and placebo similarly, with the probiotic interventions slightly superior (mean QoL difference—0.36 (95% CI: 0.07, 0.64); p = 0.01). Anxiety and depression were similar between placebo and probiotic groups following therapy. Conclusion: For IBS, probiotic therapy improved QoL, but had no effects on anxiety and depression. However, the applied probiotics were not developed for selective effects on psyche and the brain. Therefore, it remains to be shown whether or not patients with IBS would benefit from second generation probiotics developed for these central effects (psychobiotics).
Autologous human immunocompetent white adipose tissue-on-chip
2021-08-08

Abstract Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In the era of ‘diabesity’ and due to its central role for metabolic and endocrine processes, adipose tissue (specifically white adipose tissue; WAT) has become a target of high interest for therapeutic strategies. To gain insights in cellular and molecular mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models since in vitro studies on human WAT are challenging due to the large size, buoyancy, and fragility of mature white adipocytes. Leveraging the Organ-on-Chip technology, we introduce a next-generation microphysiological in vitro model of human WAT based on a tailored microfluidic platform featuring vasculature-like perfusion. The platform integrates a 3D tissue comprising all major WAT-associated cellular components in an autologous manner, including not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells featuring tissue-resident innate immune cells, specifically adipose tissue macrophages. This microphysiological tissue model recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. The combination of all individual cell types with extra cellular matrix-like hydrogels in a precisely controllable bottom-up approach enables the generation of a multitude of replicates from the same donors circumventing issues of inter-donor variability and paving the way for personalized medicine. Moreover, it allows to adjust the model’s degree of complexity to fit a specific purpose via a flexible mix- and-match approach with different cell component modules. This novel WAT-on-chip system constitutes a human-based, autologous and immunocompetent in vitro model of adipose tissue that recapitulates almost full tissue heterogeneity. In the future, the new WAT-on-chip model can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.
The Pediatric Precision Oncology INFORM Registry: Clinical Outcome and Benefit for Patients with Very High-Evidence Targets
2021-08-09

Abstract INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days [95% confidence interval (CI), 99–not applicable], compared with 117 days (95% CI, 106–143; P = 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases. Significance: The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes. See related commentary by Eggermont et al., p. 2677 . This article is highlighted in the In This Issue feature, p. 2659
Reading Covered Faces
2021-08-09

Abstract Covering faces with masks, due to mandatory pandemic safety regulations, we can no longer rely on the habitual daily-life information. This may be thought-provoking for healthy people, but particularly challenging for individuals with neuropsychiatric and neurodevelopmental conditions. Au fait research on reading covered faces reveals that: 1) wearing masks hampers facial affect recognition, though it leaves reliable inferring basic emotional expressions; 2) by buffering facial affect, masks lead to narrowing of emotional spectrum and dampen veridical evaluation of counterparts; 3) masks may affect perceived face attractiveness; 4) covered (either by masks or other veils) faces have a certain signal function introducing perceptual biases and prejudices; 5) reading covered faces is gender- and age-specific, being more challenging for males and more variable even in healthy aging; 6) the hampering effects of masks on social cognition occur over the globe; and 7) reading covered faces is likely to be supported by the large-scale assemblies of the neural circuits far beyond the social brain. Challenges and limitations of ongoing research and parallels to the Reading the Mind in the Eyes Test are assessed. Clarification of how masks affect face reading in the real world, where we deal with dynamic faces and have entrée to additional valuable social signals such as body language, as well as the specificity of neural networks underlying reading covered faces calls for further tailored research.
Disks in close binary stars
2021-08-09

Context. Close binaries ( a bin ≤ 20 au) are known to harbor planets, yet planet formation is unlikely to succeed in such systems. Studying the dynamics of disks in close binaries can help to understand how those planets could have formed. Aims. We study the impact that numerical and physical parameters have on the dynamics of disks in close binaries. We use the γ -Cephei system as an example and focus on disk quantities such as disk eccentricity and the precession rate as indicators for the dynamical state of the disks. Methods. We simulate disks in close binaries by performing two-dimensional radiative hydrodynamical simulations using a modified version of the FARGO code. First, we perform a parameter study for different numerical parameters to confirm that our results are robust. In the second part, we study the effects of different masses and different viscosities on the disks’ dynamics. Results. Previous studies on radiative disks in close binaries used too low resolutions and too small simulation domains, which impacted the disk’s dynamics. We find that radiative disks in close binaries, after an initialization phase, become eccentric with mean eccentricities between 0.06 and 0.27 and display a slow retrograde precession with periods ranging from 4−40 T bin which depends quadratically on the disk’s mean aspect ratio. In general, the disks show a coherent, rigid precession which can be broken, however, by changes in the opacity law reducing the overall eccentricity of the disk.