julilili42/papers huggingface dataset:
How Negative Is Negative Information
2021-09-07

Daily, we face a plenty of negative information that can profoundly affect our perception and behavior. During devastating events such as the current COVID-19 pandemic, negative messages may hinder reasoning at individual level and social decisions in the society at large. These effects vary across genders in neurotypical populations (being more evident in women) and may be even more pronounced in individuals with neuropsychiatric disorders such as depression. Here, we examine how negative information impacts reasoning on a social perception task in females with breast cancer, a life-threatening disease. Two groups of patients and two groups of matched controls ( N TO TAL = 80; median age, 50 years) accomplished a psychometrically standardized social cognition and reasoning task receiving either the standard instruction solely or additional negative information. Performance substantially dropped in patients and matched controls who received negative information compared to those who did not. Moreover, patients with negative information scored much lower not only compared with controls but also with patients without negative information. We suggest the effects of negative information are mediated by the distributed brain networks involved in affective processing and emotional memory. The findings offer novel insights on the impact of negative information on social perception and decision making during life-threatening events, fostering better understanding of its neurobiological underpinnings.
A New Integrated Tool to Calculate and Map Bilateral Asymmetry on Three-Dimensional Digital Models
2021-09-07

The observation and the quantification of asymmetry in biological structures are deeply investigated in geometric morphometrics. Patterns of asymmetry were explored in both living and fossil species. In living organisms, levels of directional and fluctuating asymmetry are informative about developmental processes and health status of the individuals. Paleontologists are primarily interested in asymmetric features introduced by the taphonomic process, as they may significantly alter the original shape of the biological remains, hampering the interpretation of morphological features which may have profound evolutionary significance. Here, we provide a new R tool that produces the numerical quantification of fluctuating and directional asymmetry and charts asymmetry directly on the specimens under study, allowing the visual inspection of the asymmetry pattern. We tested this show.asymmetry algorithm, written in the R language, on fossil and living cranial remains of the genus Homo. show.asymmetry proved successful in discriminating levels of asymmetry among sexes in Homo sapiens, to tell apart fossil from living Homo skulls, to map effectively taphonomic distortion directly on the fossil skulls, and to provide evidence that digital restoration obliterates natural asymmetry to unnaturally low levels.
At‐Most‐Hexa Meshes
2021-09-07

Abstract Volumetric polyhedral meshes are required in many applications, especially for solving partial differential equations on finite element simulations. Still, their construction bears several additional challenges compared to boundary‐based representations. Tetrahedral meshes and (pure) hex‐meshes are two popular formats in scenarios like CAD applications, offering opposite advantages and disadvantages. Hex‐meshes are more intricate to construct due to the global structure of the meshing, but feature much better regularity, alignment, are more expressive, and offer the same simulation accuracy with fewer elements. Hex‐dominant meshes, where most but not all cell elements have a hexahedral structure, constitute an attractive compromise, potentially unlocking benefits from both structures, but their generality makes their employment in downstream applications difficult. In this work, we introduce a strict subset of general hex‐dominant meshes, which we term ‘at‐most‐hexa meshes’, in which most cells are still hexahedral, but no cell has more than six boundary faces, and no face has more than four sides. We exemplify the ease of construction of at‐most‐hexa meshes by proposing a frugal and straightforward method to generate high‐quality meshes of this kind, starting directly from hulls or point clouds, for example, from a 3D scan. In contrast to existing methods for (pure) hexahedral meshing, ours does not require an intermediate parameterization of other costly pre‐computations and can start directly from surfaces or samples. We leverage a Lloyd relaxation process to exploit the synergistic effects of aligning an orientation field in a modified 3D Voronoi diagram using the norm for cubical cells. The extracted geometry incorporates regularity as well as feature alignment, following sharp edges and curved boundary surfaces. We introduce specialized operations on the three‐dimensional graph structure to enforce consistency during the relaxation. The resulting algorithm allows for an efficient evaluation with parallel algorithms on GPU hardware and completes even large reconstructions within minutes.
Decreased Autonomic Reactivity and Psychiatric Comorbidities in Neurological Patients With Medically Unexplained Sensory Symptoms: A Case-Control Study
2021-09-07

Up to 48% of patients with medically unexplained symptoms seen in neurological practice suffer from sensory symptoms, which could be of functional nature or secondary to psychiatric disorders. These patients show high medical care utilization causing elevated healthcare costs. Despite the high prevalence, little is known about clinical characteristics and pathophysiological mechanisms. For functional disorders such as irritable bowel syndrome, a reduction of heart rate variability (HRV) has been shown, suggesting a dysfunction of the autonomic nervous system (ANS). The aim of this study was to investigate psychological data and functional changes of the ANS in patients with medically unexplained sensory symptoms (MUSS). In this exploratory pilot study, 16 patients (11 females, 31.6 ± 11.9 years) with MUSS, who were recruited at a single tertiary neurological center, underwent a structured clinical interview (SCID) to evaluate psychiatric comorbidities. Patients and age- and sex-matched healthy volunteers filled in questionnaires, and individual sensory thresholds (perception, pain) were detected by quantitative sensory testing (QST). HRV was assessed at baseline and under three different experimental conditions (tonic pain stimulus, placebo application, cold-face test). All tests were repeated after 6–8 weeks. SCID interviews revealed clinical or subclinical diagnoses of psychiatric comorbidities for 12 patients. Questionnaires assessing somatization, depression, anxiety, and perceived stress significantly discriminated between patients with MUSS and healthy controls. While there was no difference in QST, reduced ANS reactivity was found in patients during experimental conditions, particularly with regard to vagally mediated HRV. Our pilot study of neurological patients with MUSS reveals a high prevalence of psychiatric comorbidities and provides evidence for altered ANS function. Our data thus give insight in possible underlying mechanisms for these symptoms and may open the door for a better diagnostic and therapeutic approach for these patients in the future.
From Process to Centuries: Upscaling Field‐Calibrated Models of Fluvial Bedrock Erosion
2021-09-07

Abstract Fluvial bedrock erosion formulas lack validation over space and time. We explore the performance of field‐calibrated models at the patch‐scale (&lt;1 ) and from minutes to centuries. At the hour to annual scales (in 1‐min resolution), we verify predictions using linked discharge, bedload transport and at‐a‐point erosion, together with spatial erosion from a mountain streambed. Local and spatial erosion linearly scale with bedload mass. The unit stream power model ( USP ) fails to describe erosion dynamics without a threshold for its onset. Extrapolating over the decadal scale (14 years of discharge and bedload data), scaled models predict up to 12% of erosion for two exceptional floods. Erosion predictions for a bi‐centennial discharge varied over four orders of magnitude (extrapolated from 32.5 years discharge and 16 years bedload data at 10‐min resolution). Bi‐centennial erosion predictions summing up to 1 m for bedload models versus 0.1 m for USP highlight the likely dominance of large events in setting long‐term erosion under sediment‐starved conditions.
Intraoral scanning of neonates and infants with craniofacial disorders: feasibility, scanning duration, and clinical experience
2021-09-08

Summary Objective The aim of this study was to evaluate intraoral scanning (IOS) in infants, neonates, and small children with craniofacial anomalies for its feasibility, scanning duration, and success rate. Impression taking in vulnerable patients can be potentially life-threatening, with the risk of airway obstruction and aspiration of impression material. The advantage of increasingly digitalized dentistry is demonstrated. Materials and methods IOS was captured with the Trios 3® (3Shape, Copenhagen, Denmark) intraoral scanner. The underlying disorders were divided into cleft lip and palate (CLP), Trisomy 21 (T21), Robin Sequence (RS), Treacher Collins syndrome (TC), and isolated mandibular retrognathia (MR). Scan data were analysed by scanning duration, number of images, possible correlations of these factors with the different craniofacial disorders, patient age, and relationship between first and subsequent scans. Clinical experiences with the repeated digital impressions are described. Results Patient data of 141 scans in 83 patients were analysed within an 11-month period. Patients had a median age of 137 days. Median scanning duration was 138 seconds, resulting in a median of 352 images. There was a statistically significant difference in scanning duration (P = 0.001) between infants and neonates. IOS took longest in patients with CLP (537 seconds) and shortest in T21 patients (21 seconds), although there was no statistically significant difference between aetiologies. There was no statistically significant difference between first and subsequent scans in scanning duration. In four cases the IOS had to be repeated, and one patient ultimately required conventional impression taking (all CLP patients; success rate 94%). No severe adverse events occurred. Conclusion IOS is a fast, safe, and feasible procedure for neonates, small children, and infants with craniofacial malformations. One special challenge for both technician and user was identified in patients with CLP, though implementing this new approach of digital impression taking was otherwise found to be highly successful in everyday clinical routine.
Allosteric Inhibition of Parkinson’s-Linked LRRK2 by Constrained Peptides
2021-09-08

Leucine-Rich Repeat Kinase 2 (LRRK2) is a large, multidomain protein with dual kinase and GTPase function that is commonly mutated in both familial and idiopathic Parkinson's Disease (PD). While dimerization of LRRK2 is commonly detected in PD models, it remains unclear whether inhibition of dimerization can regulate catalytic activity and pathogenesis. Here, we show constrained peptides that are cell-penetrant, bind LRRK2, and inhibit LRRK2 activation by downregulating dimerization. We further show that inhibited dimerization decreases kinase activity and inhibits ROS production and PD-linked apoptosis in primary cortical neurons. While many ATP-competitive LRRK2 inhibitors induce toxicity and mislocalization of the protein in cells, these constrained peptides were found to not affect LRRK2 localization. The ability of these peptides to inhibit pathogenic LRRK2 kinase activity suggests that disruption of dimerization may serve as a new allosteric strategy to downregulate PD-related signaling pathways.
Job Satisfaction and Chronic Stress of General Practitioners and Their Teams: Baseline Data of a Cluster-Randomised Trial (IMPROVEjob)
2021-09-08

Background: A high prevalence of poor job satisfaction and high chronic stress is documented for general practitioners (GPs) and non-physician practice staff from various countries. The reasons are multifactorial and include deficits in leadership, communication and workflows. This publicly funded study evaluates the effectiveness of the newly developed participatory, interdisciplinary, and multimodal IMPROVEjob intervention on improving job satisfaction among GPs and practice personnel. Here, we report the baseline characteristics of the participating GPs and practice assistants, focusing on job satisfaction and perceived chronic stress. Methods: The IMPROVEjob study was performed as a cluster-randomised, controlled trial (cRCT) with German GP practices in the North Rhine Region. The IMPROVEjob intervention comprised two leadership workshops (one for practice leaders only; a second for leaders and practice assistants), a toolbox with supplemental printed and online material, and a nine-month implementation phase supported by IMPROVEjob facilitators. The intervention addressed issues of leadership, communication, and work processes. During study nurse visits, participants completed questionnaires at baseline and after nine months follow up. The primary outcome was the change in job satisfaction as measured by the respective scale of the validated German version of the Copenhagen Psychosocial Questionnaire (German COPSOQ, version 2018). Perceived chronic stress was measured using the Trier Inventory of Chronic Stress (TICS- SSCS). Results: Recruitment of 60 practices was successful: 21 were solo, 39 were group practices. At baseline, n = 84 practice owners, n = 28 employed physicians and n = 254 practice assistants were included. The mean age of all participants was 44.4 (SD = 12.8). At baseline, the job satisfaction score in the total sample was 74.19 of 100 (±14.45) and the perceived chronic stress score was 19.04 of 48 (±8.78). Practice assistants had a significantly lower job satisfaction than practice owners (p &lt; 0.05) and employed physicians (p &lt; 0.05). In the regression analysis, perceived chronic stress was negatively associated with job satisfaction (b= −0.606, SE b = 0.082, p &lt; 0.001, ICC = 0.10). Discussion: The degree of job satisfaction was similar to those in other medical professionals published in studies, while perceived chronic stress was markedly higher compared to the general German population. These findings confirm the need for interventions to improve psychological wellbeing in GP practice personnel.
Serum interferon-α2 measured by single-molecule array associates with systemic disease manifestations in Sjögren’s syndrome
2021-09-08

Abstract Objectives Type I IFN (IFN-I) activation is a prominent feature of primary SS (pSS), SLE and SSc. Ultrasensitive single-molecule array (Simoa) technology has facilitated the measurement of subfemtomolar concentrations of IFNs. Here we aimed to measure IFN-α2 in serum from pSS, SLE and SSc using a Simoa immunoassay and correlate these levels to blood IFN-stimulated gene (ISG) expression and disease activity. Methods Serum IFN-α2 was measured in patients with pSS (n = 85 and n = 110), SLE (n = 24) and SSc (n = 23) and healthy controls (HCs; n = 68) using an IFN-α Simoa assay on an HD-X analyser. IFN-I pathway activation was additionally determined from serum by an IFN-I reporter assay and paired samples of whole blood ISG expression of IFI44, IFI44L, IFIT1, IFIT3 and MxA by RT-PCR or myxovirus resistance protein 1 (MxA) protein ELISA. Results Serum IFN-α2 levels were elevated in pSS (median 61.3 fg/ml) compared with HCs (median ≤5 fg/ml, P &amp;lt; 0.001) and SSc (median 11.6 fg/ml, P = 0.043), lower compared with SLE (median 313.5 fg/ml, P = 0.068) and positively correlated with blood ISG expression (r = 0.66–0.94, P &amp;lt; 0.001). Comparable to MxA ELISA [area under the curve (AUC) 0.93], IFN-α2 measurement using Simoa identified pSS with high ISG expression (AUC 0.90) with 80–93% specificity and 71–84% sensitivity. Blinded validation in an independent pSS cohort yielded a comparable accuracy. Multiple regression indicated independent associations of autoantibodies, IgG, HCQ treatment, cutaneous disease and a history of extraglandular manifestations with serum IFN-α2 concentrations in pSS. Conclusion Simoa serum IFN-α2 reflects blood ISG expression in pSS, SLE and SSc. In light of IFN-targeting treatments, Simoa could potentially be applied for patient stratification or retrospective analysis of historical cohorts.
A revised analysis of ferrihydrite at liquid helium temperature using Mössbauer spectroscopy
2021-09-08

Abstract Short-range-ordered Fe(III) minerals such as ferrihydrite (Fh) are ubiquitous in the environment, are key players in biogeochemical cycling, and sorb trace elements and nutrients. As such, it is important to be able to identify the presence of such minerals in natural samples. Fh is commonly observed to be X-ray amorphous and cannot be easily analyzed using X-ray diffraction, meaning that spectroscopic methods such as X-ray absorption or 57Fe Mössbauer spectroscopy (MBS) are necessary for accurate identification and quantification. Despite decades of research into Fh using MBS, there is a discrepancy in the literature about the exact parameters applicable to the mineral when measured at liquid helium temperature. Fh is frequently fitted with either one, two, or three hyperfine sextets with little interpretation applied to the meaning of each, which is problematic as a one sextet model does not account for the asymmetric lineshape frequently observed for Fh. Here, we address inconsistencies in the fitting of Fh and provide a more standardized approach to its identification by MBS. We present a systematic comparison of different fitting methods, notably based on Lorentzian and Voigt functions. We suggest that the most suitable approach to fitting pure Fh at liquid helium temperature is with two sextets (A and B) fitted using an extended Voigt-based function with the ability to apply probability distributions to each hyperfine parameter. 2-line Fh: A (δ = 0.49 mm/s; ε = 0.00 mm/s; Bhf = 50.1 T) and B (δ = 0.42 mm/s; ε = –0.01 mm/s; Bhf = 46.8 T) 6-line Fh: A (δ = 0.50 mm/s; ε = –0.03 mm/s; Bhf = 50.2 T) and B (δ = 0.40 mm/s; ε = –0.05 mm/s; Bhf = 47.1 T). We interpret the two sextets to be due to either differences in the coordination environment of iron, i.e., in tetrahedral or octahedral sites, the presence of a disordered surface phase, or a combination of both. We hope that provoking a discussion on the use of MBS for Fh will help develop a greater understanding of this mineral, and other short-range ordered iron minerals, which are so important in environmental processes.
Fatal late-onset CAR T-cell–mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma
2021-09-08

Abstract Treatment with CD19-directed (CAR) T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune effector cell–associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30% to 40% of patients treated with axicabtagene-ciloleucel (axi-cel), usually within the first 4 weeks after administration of the dose and usually responding well to steroids. We describe a case of progressive central neurotoxicity occurring 9 months after axi-cel infusion in a patient with r/r LBCL who had undergone a prior allogeneic hematopoietic cell transplant. Despite extensive systemic and intrathecal immunosuppression, neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T-cell DNA copy numbers and elevated levels of interleukin-1 (IL-1) and IL-6 were found in the cerebral spinal fluid as clinical symptoms emerged, and CAR T-cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected, devastating, late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.
De novo missense variants in FBXO11 alter its protein expression and subcellular localization
2021-09-08

Abstract Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant constructs in HEK293 and HeLa cells. We found that the majority of missense variants resulted in subcellular mislocalization and/or reduced FBXO11 protein expression levels. For instance, variants located in the nuclear localization signal and the N-terminal F-Box domain lead to altered subcellular localization with exclusion from the nucleus or the formation of cytoplasmic aggregates and to reduced protein levels in western blot. In contrast, variants localized in the C-terminal Zn-finger UBR domain lead to an accumulation in the cytoplasm without alteration of protein levels. Together with the mutational data, our functional results suggest that most missense variants likely lead to a loss of the original FBXO11 function and thereby highlight haploinsufficiency as the most likely disease mechanism for FBXO11-associated NDDs.