julilili42/papers huggingface dataset:
Efficacy and safety of adjuvant immunoadsorption in pemphigus vulgaris and pemphigus foliaceus (IA-Pem Study): a multicentre randomized controlled trial
2023-12-22

Abstract Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. Objectives To assess the clinical efficacy of IA in addition to best medical treatment (BMT). Methods We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42–72 years) comparing BMT (prednisolone 1.0 mg kg−1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan–Meier and Cox regression methods. Results The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68–2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference −1214, 95% CI −2225 to −70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). Conclusions In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.
A dynamic time‐to‐event model for prediction of acute graft‐versus‐host disease in patients after allogeneic hematopoietic stem cell transplantation
2023-12-22

Abstract Background Acute graft‐versus‐host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. Methods In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time‐dependent risk factors on the development of grades II–IV aGvHD within 100 days post‐HSCT. Results Using a dynamic longitudinal time‐to‐event model, we observed a non‐monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time‐dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II–IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo‐HSCT are associated with an increased incidence of grades II–IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II–IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. Conclusion Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time‐dependent risk factors for the prediction of aGvHD.
Education, Not Age, Linked to Narrative Comprehension
2023-12-22

Background: Understanding narratives is essential for societal participation. However, insufficient literacy or age-related cognitive changes can limit narrative comprehension and create participation barriers.Aims: This study investigates the potential of pictorial narratives to convey information beyond text and break down barriers to comprehension.Sample: A representative adult sample (N = 1487).Methods: The experimental study assessed the influences of age and education on the comprehension of textual and pictorial narratives. Participants were tested on the generation of bridging inferences, a central aspect of narrative comprehension. The narratives used were based on the "Multilingual Assessment Instrument for Narratives" (MAIN), and comprehension was measured through a task where participants identified correct and false inference statements related to missing parts of the narratives.Results: Narrative comprehension was higher within higher educated groups and stable across the measured adult age span. Comprehension was generally better for pictorial narratives than textual ones across all education and age groups. Frequentist and Bayesian analyses supported these findings, showing significant effects of education and narrative modality on comprehension but no interaction between these factors.Conclusions: The findings lay the groundwork for more effectively addressing underprivileged groups and refining theories on narrative comprehension. The results suggest that pictorial narratives could be a valuable approach to enhance comprehension and participation for individuals with literacy challenges or cognitive changes due to aging. This study also emphasizes the role of education in narrative comprehension and suggests stable comprehension abilities across the adult age span.
Postoperative RNFL-Changes after Successful Trabeculectomy: 2-Year Outcomes
2023-12-22

Abstract Background The most important tool in glaucoma therapy is to lower the intraocular pressure to slow down the apoptosis of retinal ganglion cells. Trabeculectomy (TE) is considered the gold standard in glaucoma surgery. The aim of this study was to analyse the postoperative changes in retinal nerve fibre layer (RNFL) using optical coherence tomography (OCT) after TE. Material and Methods We examined 40 patients naïve to prior glaucoma surgery retrospectively, who received a TE for medically uncontrolled primary open-angle glaucoma (POAG). Intraocular pressure (IOP), IOP-lowering medication, mean deviation of perimetry, visual acuity and peripapillary RNFL-thickness using OCT were evaluated during the first 24 month after TE. Results In total 40 eyes from 40 patients were treated with TE. Mean IOP decreased from 25.0 ± 0,9 to 13.9 ± 0.6 (p &lt; 0.01), and the mean number of IOP-lowering eye drops from 3.3 ± 0.2 to 0.5 ± 0.2 (p &lt; 0.01). Visual acuity and mean deviation in perimetry remained stable while mean global RNFL-thickness decreased from 67.8 ± 2.9 to 63.7 ± 2.9 (p &lt; 0.01) and 63.4 ± 2.9 μm (p &lt; 0.01) 12 and 24 months after TE. Conclusion The TE is an effective method to reduce the IOD and the amount of IOP-lowering medication. Nevertheless, a significant further loss in RNFL thickness was observed in the first 12 months after TE. Thus, RNFL changes seem to stabilise only after a protracted period.
Mirror exposure training for adolescents with anorexia nervosa (MIRADAN): Cognitive mechanisms of body disturbance – A study protocol
2023-12-22

<sec xmlns="http://www.ncbi.nlm.nih.gov/JATS1"> <title>Background</title> Anorexia Nervosa (AN) is a severe mental illness, which typically develops in adolescence and, if left untreated, often becomes chronic. Body dissatisfaction is a core characteristic of AN. Mirror exposure (ME) is an effective therapeutic technique to tackle body dissatisfaction in adult patients with eating disorders, but there is limited evidence for the effects of ME in adolescence. One potential mechanism underlying effects of ME on body dissatisfaction is change in body-related attention bias. However, this mechanism remains to be empirically tested. Accordingly, the aim of the current study is twofold: primarily, we aim to test if ME can reduce body dissatisfaction and associated symptoms in adolescent patients with AN. Additionally, we aim to investigate whether change in biased body-related attention due to ME is a possible mechanism of action. </sec> <sec xmlns="http://www.ncbi.nlm.nih.gov/JATS1"> <title>Method</title> Adolescent patients with AN are randomized to either 12 sessions of ME (3 ME-sessions/week) or wait-list within four weeks. Main outcomes include body dissatisfaction and associated symptoms of AN. Moreover, body-related attention bias is assessed at baseline and post-treatment by means of eye-tracking with two paradigms. Further, process variables are collected weekly. In addition, 12 weeks after end of the study, the acceptability of the ME is assessed. </sec> <sec xmlns="http://www.ncbi.nlm.nih.gov/JATS1"> <title>Discussion</title> The main aim of the study is to evaluate high-frequency and high-intense ME for treating body dissatisfaction in adolescents with AN. In addition, we would like to clarify whether change in attentional bias for body stimuli is a mechanism underlying change in body dissatisfaction due to ME. </sec>
Individualisation in cognitive skills training: essential or superfluous? Examining the effectiveness of an adaptive game for training executive functions in young adults
2023-12-22

Significant resources have been allocated to the development of training programmes designed to enhance executive functions. Recently, digital games have emerged as a promising tool for this purpose. However, the impact of adaptive games, which adjust game difficulty based on the player’s performance, on trained and untrained executive functions (i.e., near and far transfer) remains to be investigated. In the present study, 59 young adults participated in an executive function game designed to improve shifting abilities for a total duration of 120 minutes, distributed over four consecutive days. The differential effects of both an adaptive and a non-adaptive game version on shifting (i.e., near transfer), and updating and inhibition (i.e., far transfer) were examined. The findings indicated that while near and far transfer effects were identified, there were no discernible variations in training outcomes between the two game versions. The present study thus contributes to the expansion of the evidence base in the field of executive function games.
Predictors of Survival in Friedreich's Ataxia: A Prospective Cohort Study
2023-12-23

ABSTRACT Background Friedreich's ataxia (FA) is a rare multisystemic disorder which can cause premature death. Objectives To investigate predictors of survival in FA. Methods Within a prospective registry established by the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS; ClinicalTrials.gov identifier NCT02069509) we enrolled genetically confirmed FA patients at 11 tertiary centers and followed them in yearly intervals. We investigated overall survival applying the Kaplan–Meier method, life tables, and log‐rank test. We explored prognostic factors applying Cox proportional hazards regression and subsequently built a risk score which was assessed for discrimination and calibration performance. Results Between September 2010 and March 2017, we enrolled 631 FA patients. Median age at inclusion was 31 (range, 6–76) years. Until December 2022, 44 patients died and 119 terminated the study for other reasons. The 10‐year cumulative survival rate was 87%. In a multivariable analysis, the disability stage (hazard ratio [HR] 1.51, 95% CI 1.08–2.12, P = 0.02), history of arrhythmic disorder (HR 2.93, 95% CI 1.34–6.39, P = 0.007), and diabetes mellitus (HR 2.31, 95% CI 1.05–5.10, P = 0.04) were independent predictors of survival. GAA repeat lengths did not improve the survival model. A risk score built on the previously described factors plus the presence of left ventricular systolic dysfunction at echocardiography enabled identification of four trajectories to prognosticate up to 10‐year survival (log‐rank test P &lt; 0.001). Conclusions Arrhythmias, progressive neurological disability, and diabetes mellitus influence the overall survival in FA. We built a survival prognostic score which identifies patients meriting closer surveillance and who may benefit from early invasive cardiac monitoring and therapy. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
SPIRO – the automated Petri plate imaging platform designed by biologists, for biologists
2023-12-23

SUMMARY Phenotyping of model organisms grown on Petri plates is often carried out manually, despite the procedures being time‐consuming and laborious. The main reason for this is the limited availability of automated phenotyping facilities, whereas constructing a custom automated solution can be a daunting task for biologists. Here, we describe SPIRO, the Smart Plate Imaging Robot, an automated platform that acquires time‐lapse photographs of up to four vertically oriented Petri plates in a single experiment, corresponding to 192 seedlings for a typical root growth assay and up to 2500 seeds for a germination assay. SPIRO is catered specifically to biologists' needs, requiring no engineering or programming expertise for assembly and operation. Its small footprint is optimized for standard incubators, the inbuilt green LED enables imaging under dark conditions, and remote control provides access to the data without interfering with sample growth. SPIRO's excellent image quality is suitable for automated image processing, which we demonstrate on the example of seed germination and root growth assays. Furthermore, the robot can be easily customized for specific uses, as all information about SPIRO is released under open‐source licenses. Importantly, uninterrupted imaging allows considerably more precise assessment of seed germination parameters and root growth rates compared with manual assays. Moreover, SPIRO enables previously technically challenging assays such as phenotyping in the dark. We illustrate the benefits of SPIRO in proof‐of‐concept experiments which yielded a novel insight on the interplay between autophagy, nitrogen sensing, and photoblastic response.
Dissecting the Complexities of Learning With Infinite Hidden Markov Models
2023-12-23

Abstract Learning to exploit the contingencies of a complex experiment is not an easy task for animals. Individuals learn in an idiosyncratic manner, revising their approaches multiple times as they are shaped, or shape themselves, and potentially end up with different strategies. Their long-run learning curves are therefore a tantalizing target for the sort of individualized quantitative characterizations that sophisticated modelling can provide. However, any such model requires a flexible and extensible structure which can capture radically new behaviours as well as slow changes in existing ones. To this end, we suggest a dynamic input-output infinite hidden semi-Markov model, whose latent states are associated with specific components of behaviour. This model includes an infinite number of potential states and so has the capacity to describe substantially new behaviours by unearthing extra states; while dynamics in the model allow it to capture more modest adaptations to existing behaviours. We individually fit the model to data collected from more than 100 mice as they learned a contrast detection task over tens of sessions and around fifteen thousand trials each. Despite large individual differences, we found that most animals progressed through three major stages of learning, the transitions between which were marked by distinct additions to task understanding. We furthermore showed that marked changes in behaviour are much more likely to occur at the very beginning of sessions, i.e. after a period of rest, and that response biases in earlier stages are not predictive of biases later on in this task.
Biallelic NUDT2 variants defective in mRNA decapping cause a neurodevelopmental disease
2023-12-23

Abstract Dysfunctional RNA processing caused by genetic defects in RNA processing enzymes has a profound impact on the nervous system, resulting in neurodevelopmental conditions. We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay and gait disturbance. In some patients peripheral neuropathy, corpus callosum abnormalities and progressive basal ganglia deposits were present. The disorder is associated with rare variants in NUDT2, a mRNA decapping and Ap4A hydrolysing enzyme, including novel missense and in-frame deletion variants. We show that these NUDT2 variants lead to a marked loss of enzymatic activity, strongly implicating loss of NUDT2 function as the cause of the disorder. NUDT2-deficient patient fibroblasts exhibit a markedly altered transcriptome, accompanied by changes in mRNA half-life and stability. Amongst the most up-regulated mRNAs in NUDT2-deficient cells, we identified host response and interferon-responsive genes. Importantly, add-back experiments using an Ap4A hydrolase defective in mRNA decapping highlighted loss of NUDT2 decapping as the activity implicated in altered mRNA homeostasis. Our results confirm that reduction or loss of NUDT2 hydrolase activity is associated with a neurological disease, highlighting the importance of a physiologically balanced mRNA processing machinery for neuronal development and homeostasis.
Developmental epileptic encephalopathy in DLG4‐related synaptopathy
2023-12-23

Abstract Objective The postsynaptic density protein of excitatory neurons PSD‐95 is encoded by discs large MAGUK scaffold protein 4 ( DLG4 ), de novo pathogenic variants of which lead to DLG4 ‐related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4 ‐related synaptopathy. Methods We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video‐polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician. Results A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow‐wave sleep (ESES)/developmental epileptic encephalopathy with spike–wave activation during sleep (DEE‐SWAS) was diagnosed in &gt;25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE‐SWAS, as well as some who did not. We could not identify a clear genotype–phenotype relationship even between individuals with the same DLG4 variants. Significance Our study shows that a subgroup of individuals with DLG4 ‐related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE‐SWAS. Our study confirms DEE as part of the DLG4 ‐related phenotypic spectrum. Occurrence of ESES/DEE‐SWAS in DLG4 ‐related synaptopathy requires proper investigation with sleep EEG.
Individual and averaged power density spectra of X-ray bursts from SGR J1935+2154: quasi-periodic oscillation search and slopes
2023-12-23

ABSTRACT The study of quasi-periodic oscillations (QPOs) and power density spectra (PDSs) continuum properties can help shed light on the still elusive emission physics of magnetars and as a window into the interiors of neutron stars using asteroseismology. In this work, we employ a PDS method to search for the QPOs in the hundreds of X-ray bursts from SGR J1935+2154 observed by Insight-HXMT, GECAM, and Fermi/GBM from 2014 July to 2022 January. Although no definitive QPO signal (significance &amp;gt;3 σ) is detected in individual bursts or the averaged periodogram of the bursts grouped by duration, we identify several bursts exhibiting features at ∼40 Hz, attributed to the the proximity intervals between adjacent pulses and consistent with that reported in the X-ray burst associated with FRB 200428. We investigate the PDS continuum properties and find that the distribution of the PDS slope in the simple power-law model peaks at ∼2.5, which is consistent with other magnetars but higher than 5/3 commonly seen in gamma-ray bursts. Besides, the distribution of the break frequency in the broken power-law model peaks at ∼60 Hz. Finally, we report that the power-law index of PDS has an anti-correlation and power-law dependence on the burst duration as well as the minimum variation time-scale.
Discerning state estimation and sensory gating, two presumptive predictive signals in mouse barrel cortex
2023-12-23

Abstract The brain is assumed to contain distinctive predictive systems ranging from sensorimotor to cognitive functions. Here we report the successful functional delineation of two different presumptive predictive systems on the neuronal level, state estimation (SE) and sensory gating (SG), which both attenuate sensory flow during movement. Studying neuronal sensorimotor responses throughout the depth of primary somatosensory cortex in mice trained on a whisker reach task, SE appeared as a learned attenuation of tactile signal flow, due to a suppressive predictive signal, precisely at the time of an experimental sensory consequence. In contrast, SG was observable during a much longer interval after onset of the motor command. Both phenomena are internal, presumptively predictive signals, as blockade of the reafference did not affect them. We speculate that SG may be related to cognitive signals monitoring goals of movements, while SE likely is the expression of the classical notion of the reafference principle.
‘To Live a Peaceful Life’: African American Defectors in the German Democratic Republic
2023-12-23

Abstract In this article I follow the paths of six African Americans who defected from the US Army stationed in West Germany in the early 1950s and applied for political asylum in the German Democratic Republic. Their reasons for moving to and staying in East Germany are my point of departure, in order to gain an understanding of how they made sense of the Cold War divide based on their experiences of racism. The perceptions of the six African Americans are contrasted with the reactions of the Stasi, illustrating how those working to defend the policies and politics of the governing Socialist Unity Party of Germany located race and racism in their conceptualization of political asylum. The article then focuses on the lives of the six defectors in East Germany over a period of roughly four decades. I argue that questions of race/racism were closely linked to questions of (violated) intimacy and settledness, both for the African American defectors and for the Stasi. Zooming in on the intimate allows me to reconfigure the broader context, providing a glimpse into how race and racism shaped the Cold War geography as well as how this geography changed in light of decolonization.