julilili42/papers huggingface dataset:
Overweight patients benefit from high tibial osteotomy to the same extent as patients with normal weights but show inferior mid‐term results
2021-02-11

Abstract Purpose The purpose of this prospective study was to analyze the impact of obesity on the clinical and radiological outcomes 6 years after open‐wedge high tibial osteotomy (HTO). Methods A total of 120 prospectively recorded patients with medial compartment osteoarthritis underwent open‐wedge HTO between 2008 and 2011. The study cohort was frequently examined over a minimum of a 6‐year follow‐up. The cohort was divided into three groups according to body mass index (BMI): normal weight patients (BMI &lt; 25 kg/m 2 ), pre‐obese patients (BMI 25–30 kg/m 2 ) and obese patients (BMI &gt; 30 kg/m 2 ). Clinical and functional outcomes (Oxford Knee Score, Hospital for Special Surgery Score, Lequesne Score, Tegner Activity Scale), subjective health‐related quality of life (SF‐36), change in mechanical limb alignment (mTFA) as well as conversion to unicompartmental or total knee arthroplasty (TKA) were evaluated. To compare clinical scoring between the groups, univariate variance analysis was applied. Changes in outcome variables over time were analyzed with dependent t tests. Results From 120 patients, 85 were followed‐up over a 6.7‐year period on average (6–11.8 years) after HTO. The mean BMI was 28.6 ± 4.6 kg/m 2 . Each group showed a significant pre‐ to postoperative increase in all recorded scores (p &lt; 0.05). In absolute terms, both mental and clinical scores of overweight patients did not reach the peak values of the normal weighted population during the period of observation. There was a conversion to TKA in 10.5% after an average of 50.1 ± 25.0 months following surgery. A total of five complications occurred without significant differences (BMI &lt; 25: n = 1, BMI 25–30: n = 2, BMI &gt; 30: n = 2; n.s.). There was a mean pre‐ to postoperative (six weeks after surgery) correction difference of 6.9° ± 3.2° (mTFA) with higher loss of correction over time in overweight patients. Conclusion In terms of clinical outcome and health‐related quality of life, overweight patients may receive a benefit from open‐wedge HTO to the same extent as patients with normal weights and show similar complication rates. However, they have inferior preoperative clinical and functional results and mid‐term results after open‐wedge HTO compared to patients with normal weights. Level of evidence Level III.
Changing Personality Traits with the Help of a Digital Personality Change Intervention
2021-02-11

Personality traits predict important life outcomes such as success in love and work life, wellbeing, health, and longevity. Given these positive relations to important outcomes, economists, policy-makers, and scientists have proposed intervening to change personality traits to promote positive life outcomes. However, non-clinical interventions to change personality traits are lacking so far in large-scale naturalistic populations. This study (N = 1,523) examined the effects of a 3- month digital personality change intervention using a randomized controlled trial (RCT) and the smartphone application PEACH (PErsonality coACH). Participants who received the intervention showed greater self-reported changes compared to participants in the waitlist control group who had to wait one month before receiving the intervention. Self-reported changes aligned with intended goals for change and were significant for those desiring to increase on a trait (d = 0.52) and for those desiring to decrease on a trait (d = -0.58). Observers such as friends, family members or intimate partners also detected significant personality changes in the desired direction for those desiring to increase on a trait (d = 0.35). Observer-reported changes for those desiring to decrease on a trait were not significant (d = -0.22). Moreover, self- and observer reported changes persisted until three months after the end of the intervention. This work provides the strongest evidence to date that normal personality traits can be changed through intervention in non-clinical samples.
Bipartite and tripartite entanglement in a Bose-Einstein acoustic black\\n hole
2021-02-11

We investigate quantum entanglement in an analogue black hole realized in the\\nflow of a Bose-Einstein condensate. The system is described by a three-mode\\nGaussian state and we construct the corresponding covariance matrix at zero and\\nfinite temperature. We study associated bipartite and tripartite entanglement\\nmeasures and discuss their experimental observation. We identify a simple\\noptical setup equivalent to the analogue Bose-Einstein black hole which\\nsuggests a new way of determining the Hawking temperature and grey-body factor\\nof the system.\\n
Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19
2021-02-11

Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.
Genetic Influence on the Peripheral Differentiation Signature of Vδ2+ γδ and CD4+ αβ T Cells in Adults
2021-02-11

Adaptive as well as innate immune traits are variously affected by environmental and genetic influences, but little is known about the impact of genetics on the diversity, differentiation and functionality of γδ T cells in humans. Here, we analyzed a cohort of 95 middle-aged twins from the Danish Twin Registry. The differentiation status of peripheral αβ and γδ T cells was assessed by flow cytometry based on the surface expression of CD27, CD28 and CD45RA. Our data confirm the established associations of latent cytomegalovirus (CMV) infection with an accumulation of late differentiated memory T cells in the αβ compartment as well as in the Vδ1+ γδ T cell subset. A comparison of differentiation phenotypes of γδ and αβ T cells that were not affected by CMV seropositivity identified a significant correlation of early differentiated (ED) Vδ2+ and intermediate differentiated (ID) CD4+ T cells in monozygotic (MZ), but not in dizygotic (DZ) co-twins. Thus, our data suggest a genetic influence on the differentiation of γδ and αß T cell subsets.
Faculty Opinions recommendation of Molecular basis for control of antibiotic production by a bacterial hormone.
2021-02-11

Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR3. Here we report the X-ray crystal structure of an MmfR-AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR-operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics. PMID: 33536618
Improved in vitro Efficacy of Baloxavir Marboxil Against Influenza A Virus Infection by Combination Treatment With the MEK Inhibitor ATR-002
2021-02-12

Currently, all available antiviral drugs against influenza virus (IV) that target the virus proteins directly, like Baloxavir acid (BXA), lead to viral resistance. Therefore, cellular mechanisms and factors essential for IV replication are promising antiviral targets. As IV strongly depends on the virus-induced Raf/MEK/ERK signal pathway for efficient generation of infectious progeny virions, this pathway represents an important target. We aimed to determine whether the MEK inhibitor ATR-002 (PD0184264) is able to impair replication of BXA-resistant influenza A virus (IAV) and whether a treatment combining BXA and ATR-002 improves the therapeutic efficiency in vitro . A549 cells infected with different IAV strains including BXA-resistant variants were treated with ATR-002 or BXA and the effect on virus titer reduction was determined. The synergistic effect of ATR-002 and BXA was also analyzed using different evaluation methods. The data demonstrated that ATR-002 has a significant and dose-dependent inhibitory effect on IAV replication across different strains and subtypes. IAV with the PA-I38T mutation shows resistance against BXA, but is still susceptible toward ATR-002. The combination of ATR-002 and BXA exhibited a synergistic potency reflected by low combination index values. In conclusion, we show that ATR-002 permits to counteract the limitations of BXA against BXA-resistant IAV. Moreover, the results support the use of ATR-002 (i) in a mono-therapy, as well as (ii) in a combined approach together with BXA. These findings might also apply to the treatment of infections with IAV, resistant against other direct-acting antiviral compounds.
Crystallographic analysis of temperate ice on Rhonegletscher, Swiss Alps
2021-02-12

Abstract. Crystal orientation fabric (COF) analysis provides information about the c-axis orientation of ice grains and the associated anisotropy and microstructural information about deformation and recrystallisation processes within the glacier. This information can be used to introduce modules that fully describe the microstructural anisotropy or at least direction-dependent enhancement factors for glacier modelling. The COF was studied at an ice core that was obtained from the temperate Rhonegletscher, located in the central Swiss Alps. Seven samples, extracted at depths between 2 and 79 m, were analysed with an automatic fabric analyser. The COF analysis revealed conspicuous four-maxima patterns of the c-axis orientations at all depths. Additional data, such as microstructural images, produced during the ice sample preparation process, were considered to interpret these patterns. Furthermore, repeated high-precision global navigation satellite system (GNSS) surveying allowed the local glacier flow direction to be determined. The relative movements of the individual surveying points indicated longitudinal compressive stresses parallel to the glacier flow. Finally, numerical modelling of the ice flow permitted estimation of the local stress distribution. An integrated analysis of all the data sets provided indications and suggestions for the development of the four-maxima patterns. The centroid of the four-maxima patterns of the individual core samples and the coinciding maximum eigenvector approximately align with the compressive stress directions obtained from numerical modelling with an exception for the deepest sample. The clustering of the c axes in four maxima surrounding the predominant compressive stress direction is most likely the result of a fast migration recrystallisation. This interpretation is supported by air bubble analysis of large-area scanning macroscope (LASM) images. Our results indicate that COF studies, which have so far predominantly been performed on cold ice samples from the polar regions, can also provide valuable insights into the stress and strain rate distribution within temperate glaciers.
Preserved Inhibitory Control Deficits of Overweight Participants in a Gamified Stop-Signal Task: Experimental Study of Validity
2021-02-12

Background Gamification in mental health could increase training adherence, motivation, and transfer effects, but the external validity of gamified tasks is unclear. This study documents that gamified task variants can show preserved associations between markers of behavioral deficits and health-related variables. We draw on the inhibitory control deficit in overweight populations to investigate effects of gamification on performance measures in a web-based experimental task. Objective This study tested whether associations between inhibitory control and overweight were preserved in a gamified stop-signal task (SST). Methods Two versions of an adaptive SST were developed and tested in an online experiment. Participants (n=111) were randomized to 1 of the 2 task variants and completed a series of questionnaires along with either the gamified SST or a conventional SST. To maximize its possible effects on participants’ inhibitory control, the gamified SST included multiple game elements in addition to the task itself and the stimuli. Both variants drew on the identical core mechanics, but the gamified variant included an additional narrative, graphical theme, scoring system with visual and emotional feedback, and the presence of a companion character. In both tasks, food and neutral low-poly stimuli were classified based on their color tone (go trials), but responses were withheld in 25% of the trials (stop trials). Mean go reaction times and stop-signal reaction times (SSRT) were analyzed as measures of performance and inhibitory control. Results Participants in the gamified SST had longer reaction times (803 [SD 179] ms vs 607 [SD 90] ms) and worse inhibitory control (SSRT 383 [SD 109] ms vs 297 [SD 45] ms). The association of BMI with inhibitory control was relatively small (r=.155, 95% CI .013-.290). Overweight participants had longer reaction times (752 [SD 217] ms vs 672 [SD 137] ms) and SSRTs (363 [SD 116] ms vs 326 [SD 77] ms). Gamification did not interact with the effect of overweight on mean performance or inhibitory control. There were no effects of gamification on mood and user experience, despite a negative effect on perceived efficiency. Conclusions The detrimental effects of heightened BMI on inhibitory control were preserved in a gamified version of the SST. Overall, the effects of overweight were smaller than in previously published web-based and laboratory studies. Gamification elements can impact behavioral performance, but gamified tasks can still assess inhibitory control deficits. Although our results are promising, according validations may differ for other types of behavior, gamification, and health variables.
Exact theory for the Rezzolla-Zhidenko metric and self-consistent calculation of quasinormal modes
2021-02-12

A covariant, scalar-tensor gravity is constructed such that the static, spherically symmetric Rezzolla-Zhidenko metric is an exact solution to the theory. The equations describing gravitational perturbations of this spacetime, which represents a generic black hole possessing an arbitrary number of hairs, can then be derived. This allows for a self-consistent study of the associated quasinormal modes. It is shown that mode spectra are tied to not only the non-Einstein parameters in the metric but also to those that appear at the level of the action, and that different branches of the exact theory can, in some cases, predict significantly different oscillation frequencies and damping times. For choices which make the theory appear more like general relativity in some precise sense, we find that a nontrivial Rezzolla-Zhidenko parameter space is permissible under current constraints on fundamental ringdown modes observed by Advanced LIGO.
Importance of diagnostics and risk of secondary malignancies in primary cutaneous lymphomas
2021-02-12

Summary Background and Objectives Primary cutaneous lymphomas (PCL) often strongly differ in clinical behavior and prognosis from systemic lymphomas of the same histopathologic type. The aim of the study was to investigate the distribution of PCL subtypes, the average time from disease manifestation to diagnosis, the importance of diagnostic procedures, the occurrence of secondary malignancies and the different treatment modalities. Patients and Methods Retrospective analysis of 152 patients with PCL examined at the Department of Dermatology of the University Hospital Tübingen from 2010–2012. Results 105 patients with CTCL (69.1 %) and 47 patients with CBCL (30.9 %) were included. The average time from disease manifestation to diagnosis was four years. The most common diagnosed lymphoma was mycosis fungoides (MF) (47.4 %). First‐line therapies here include phototherapy only (psoralen‐UV‐A [PUVA], n = 48; UVB 311 nm, n = 7) or combination therapies primarily phototherapy with systemic retinoids (n = 18). Most frequent second‐line therapy was interferon (INF)‐α plus PUVA (n = 15). The outcome was favorable (45.2 % remission, 28.6 % stable disease, 22.6 % progressive disease). Malignant comorbidities were observed more frequently compared to a healthy control group. Conclusions The diagnosis of lymphoma often takes several years. The value of staging procedures is still low and the treatment modalities for MF in earlier stages are mainly based on phototherapy.
Associations Between Abstract Concepts: Investigating the Relationship Between Deictic Time and Valence
2021-02-12

The present study examines whether deictic time and valence are mentally associated, with a link between future and positive valence and a link between past and negative valence. We employed a novel paradigm, the two-choice-sentence-completion paradigm, to address this issue. Participants were presented with an initial sentence fragment that referred to an event that was either located in time (future or past) or of different valence (positive or negative). Participants chose between two completion phrases. When the given dimension in the initial fragment was time, the two completion phrase alternatives differed in valence (positive vs. negative). However, when the given dimension in the initial fragment was valence, the two completion phrase alternatives differed in time (future vs. past). As expected, participants chose completion phrases consistent with the proposed association between time and valence. Additional analyses involving individual differences concerning optimism/pessimism revealed that this association is particularly pronounced for people with an optimistic attitude.
Steady state by recycling prevents premature collapse of protoplanetary atmospheres
2021-02-12

Context. In recent years, space missions such as Kepler and TESS have discovered many close-in planets with significant atmospheres consisting of hydrogen and helium: mini-Neptunes. This indicates that these planets formed early in gas-rich disks while avoiding the runaway gas accretion that would otherwise have turned them into hot-Jupiters. A solution is to invoke a long Kelvin-Helmholtz contraction (or cooling) timescale, but it has also been suggested that thermodynamical cooling can be prevented by hydrodynamical planet atmosphere-disk recycling. Aims. We investigate the efficacy of the recycling hypothesis in preventing the collapse of the atmosphere, check for the existence of a steady state configuration, and determine the final atmospheric mass to core mass ratio. Methods. We use three-dimensional radiation-hydrodynamic simulations to model the formation of planetary proto-atmospheres. Equations are solved in a local frame centered on the planet. Results. Ignoring small oscillations that average to zero over time, the simulations converge to a steady state where the velocity field of the gas becomes constant in time. In a steady state, the energy loss by radiative cooling is fully compensated by the recycling of the low entropy gas in the planetary atmosphere with high entropy gas from the circumstellar disk. Conclusions. For close-in planets, recycling naturally halts the cooling of planetary proto-atmospheres, preventing them from contracting toward the runaway regime and collapsing into gas giants.
Role of Tactile Noise in the Control of Digit Normal Force
2021-02-12

Whenever we grasp and lift an object, our tactile system provides important information on the contact location and the force exerted on our skin. The human brain integrates signals from multiple sites for a coherent representation of object shape, inertia, weight, and other material properties. It is still an open question whether the control of grasp force occurs at the level of individual fingers or whether it is also influenced by the control and the signals from the other fingers of the same hand. In this work, we approached this question by asking participants to lift, transport, and replace a sensorized object, using three- and four-digit grasp. Tactile input was altered by covering participant's fingertips with a rubber thimble, which reduced the reliability of the tactile sensory input. In different experimental conditions, we covered between one and three fingers opposing the thumb. Normal forces at each finger and the thumb were recorded while grasping and holding the object, with and without the thimble. Consistently with previous studies, reducing tactile sensitivity increased the overall grasping force. The gasping force increased in the covered finger, whereas it did not change from baseline in the remaining bare fingers (except the thumb for equilibrium constraints). Digit placement and object tilt were not systematically affected by rubber thimble conditions. Our results suggest that, in each finger opposing thumb, digit normal force is controlled locally in response to the applied tactile perturbation.
Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients
2021-02-12

<title>Abstract</title> Cancer patients, in particular patients with hematological malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses in unexposed and SARS-CoV-2-infected cancer patients to characterize SARS-CoV‐2 immunity and to identify immunological parameters contributing to COVID-19 outcome. Unexposed patients with hematological malignancies presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4<sup>+</sup> T cell responses and signs of T cell exhaustion when compared to solid tumor patients and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between COVID-19 cancer patients and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T cell responses were profoundly reduced in cancer patients, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T cell immunity as determinant for dismal outcome of COVID-19 in cancer patients.