julilili42/papers huggingface dataset:
Resonant Phenomena of Sound Waves and their Expression in Physiology
2024-06-06

Music and sounds activate numerous physiological effects associated with the functioning of the autonomic nervous system and involved in the maintenance of homeostasis. As such, sound interventions can play an important role in supporting human wellbeing. Physiological responses are dependent on the sound type and frequency, as well as the spatial conditions and the presence of the subject in the acoustic environment. To arrive at a more articulate understanding of these dependencies, response of subjects (n=44) to sound reproduction of two different singing bowls with fundamental frequencies at 73 Hz and 110 Hz in spatial projection of nine different geometric shapes were monitored by acoustic and physiological measurement. Contrary to other studies, we find no discrete effects related to the sound type or frequency. Observed effects indicating focused attention, relaxation and improved homeostasis were consistently dependent on the combination of sound frequency and spatial condition. Notably, we observe that the 73 Hz stimulus induced significant changes in the Gamma band of Electroencephalography (EEG) in projection of a Tetrahedron and Cube, while the 110 Hz stimulus induced significant changes in the Theta and Beta bands for the same shapes. Discrete effects of spatial shapes were observed in the Galvanic Skin Response (GSR) of subjects. Arousal was significantly decreased during projection of a Cube, Icosahedron and Dodecahedron and significantly increased during Pyramid, Tetrahedron and Sphere, regardless of the frequency. Discrete effects of stimulus duration were observed in GSR and Electromyography (EMG) of subjects, regardless of the frequency and spatial condition. Arousal and muscle tension were significantly increased during the first 15 minutes and decreased until 40 minutes of exposure. We observe highly significant deviations in projected sound waves in the presence of a subject. The localized amplitude difference of sound waves was highly correlated to localization and power of significant changes in brain activity of subjects, while the phase shift of sound wave frequency was predictive of the frequency of brain activity. Significant expressions of Heart Rate (HR) and Heart Rate Variability (HRV) of subjects were highly correlated to the mean, variability and standard deviation of amplitude difference and phase shift of the fundamental frequency and the average across frequencies. We present a model in the form of a transfer function that accurately predicts various physiological expressions in response to sound stimuli on the basis of observed sound wave deviations. We discuss the benefits of such a model and the future work necessary to develop the model to its full predictive capacity.
Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target
2024-06-07

Abstract Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments.
HBV-related HCC development in mice is STAT3 dependent and indicates an oncogenic effect of HBx
2024-06-07

Although most HCC cases in patients with chronic HBV infection occur after a sequence of liver damage and fibrosis, a subset of patients develops HCC without any signs of advanced liver damage. We demonstrate that the expression of all viral transcripts in HBV-transgenic mice suffices to induce HCC development independent of inflammation and fibrosis. These data indicate the direct oncogenic effects of HBV and emphasize the idea of early antiviral treatment in the 'immune-tolerant' phase (HBeAg-positive chronic HBV infection).
Learning the natural history of human disease with generative transformers
2024-06-07

Abstract Decision-making in healthcare relies on the ability to understand patients’ past and current health state to predict, and ultimately change, their future course. Artificial intelligence (AI) methods promise to aid this task by learning patterns of disease progression from large corpora of health records to predict detailed outcomes for an individual. However, the potential of AI has not yet been fully investigated at scale. Here, we modify the GPT (generative pretrained transformer) architecture to model the temporal progression and competing nature of human diseases in a population scale cohort. We train this model, termed Delphi-2M, on data from 0.4 million participants of the UK Biobank and validate it using external data from 1.9 million Danish individuals with no change in parameters. Delphi-2M predicts the rates of more than 1,000 different ICD-10 coded diseases and death, conditional on each individual’s past disease history, age, sex and baseline lifestyle information, and with accuracy comparable to existing single-disease models. Delphi-2M’s generative nature also enables sampling future health trajectories at any point within an individual’s life course with outcomes across the entire disease spectrum. Sampled health trajectories provide meaningful estimates of future disease burden for up to 20 years and enable training AI models which have never seen actual data. Explainable AI methods provide insights into Delphi-2M’s predictions, revealing temporal clusters of co-morbidities within and across different disease chapters and their time-dependent consequences on the future health course. These analyses, however, also reveal that biases underlying the available training data, which in the case of the UK Biobank stem from distinct healthcare sources, are learned and highlighted. In summary, GPT-based models appear well suited for predictive and generative health-related tasks, are applicable to population scale health data sets and provide insights into the temporal dependencies of past events that shape future health, impacting our ability to obtain an instantaneous view of personalised health state.
Real-world therapy management of patients with multiple sclerosis receiving cladribine tablets beyond year 4 – Results from a German cladribine cohort
2024-06-07

The recommended three treatment scenarios in year 5 appear to be feasible in clinical practice. Treatment-free structured monitoring is the most frequently applied strategy, highly likely due to the prospect of continuing low disease activity under cladribine treatment.
Machine learning prediction of malaria vaccine efficacy based on antibody profiles
2024-06-07

Immunization through repeated direct venous inoculation of Plasmodium falciparum (Pf) sporozoites (PfSPZ) under chloroquine chemoprophylaxis, using the PfSPZ Chemoprophylaxis Vaccine (PfSPZ-CVac), induces high-level protection against controlled human malaria infection (CHMI). Humoral and cellular immunity contribute to vaccine efficacy but only limited information about the implicated Pf-specific antigens is available. Here, we examined Pf-specific antibody profiles, measured by protein arrays representing the full Pf proteome, of 40 placebo- and PfSPZ-immunized malaria-naïve volunteers from an earlier published PfSPZ-CVac dose-escalation trial. For this purpose, we both utilized and adapted supervised machine learning methods to identify predictive antibody profiles at two different time points: after immunization and before CHMI. We developed an adapted multitask support vector machine (SVM) approach and compared it to standard methods, i.e. single-task SVM, regularized logistic regression and random forests. Our results show, that the multitask SVM approach improved the classification performance to discriminate the protection status based on the underlying antibody-profiles while combining time- and dose-dependent data in the prediction model. Additionally, we developed the new f E ature di S tance ex P lainabilit Y (ESPY) method to quantify the impact of single antigens on the non-linear multitask SVM model and make it more interpretable. In conclusion, our multitask SVM model outperforms the studied standard approaches in regard of classification performance. Moreover, with our new explanation method ESPY, we were able to interpret the impact of Pf-specific antigen antibody responses that predict sterile protective immunity against CHMI after immunization. The identified Pf-specific antigens may contribute to a better understanding of immunity against human malaria and may foster vaccine development.
MRI‐ARSACS: An Imaging Index for Autosomal Recessive Spastic Ataxia of Charlevoix‐Saguenay (ARSACS) Identification Based on the Multicenter PROSPAX Study
2024-06-07

Abstract Background Autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) and hereditary spastic paraplegia type 7 (SPG7) represent the most common genotypes of spastic ataxia (SPAX). To date, their magnetic resonance imaging (MRI) features have only been described qualitatively, and a pure neuroradiological differential diagnosis between these two conditions is difficult to achieve. Objectives To test the performance of MRI measures to discriminate between ARSACS and SPG7 (as an index of common SPAX disease). Methods In this prospective multicenter study, 3D‐T1‐weighted images of 59 ARSACS (35.4 ± 10.3 years, M/F = 33/26) and 78 SPG7 (54.8 ± 10.3 years, M/F = 51/27) patients of the PROSPAX Consortium were analyzed, together with 30 controls (45.9 ± 16.9 years, M/F = 15/15). Different linear and surface measures were evaluated. A receiver operating characteristic analysis was performed, calculating area under the curve (AUC) and corresponding diagnostic accuracy parameters. Results The pons area proved to be the only metric increased exclusively in ARSACS patients ( P = 0.02). Other different measures were reduced in ARSACS and SPG7 compared with controls (all with P ≤ 0.005). A cut‐off value equal to 1.67 of the pons‐to‐superior vermis area ratio proved to have the highest AUC (0.98, diagnostic accuracy 93%, sensitivity 97%) in discriminating between ARSACS and SPG7. Conclusions Evaluation of the pons‐to‐superior vermis area ratio can discriminate ARSACS from other SPAX patients, as exemplified here by SPG7. Hence, we hereby propose this ratio as the Magnetic Resonance Index for the Assessment and Recognition of patients harboring SACS mutations (MRI‐ARSACS), a novel diagnostic tool able to identify ARSACS patients and useful for discriminating ARSACS from other SPAX patients undergoing MRI. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Buronius manfredschmidi—A new small hominid from the early late Miocene of Hammerschmiede (Bavaria, Germany)
2024-06-07

The known diversity of European middle and late Miocene hominids has increased significantly during the last decades. Most of these great apes were frugivores in the broadest sense, ranging from soft fruit frugivores most like chimpanzees to hard/tough object feeders like orangutans, varying in size from larger than siamangs (over 17 kg) to larger than most chimpanzees (~60–70 kg). In contrast to the frequent sympatry of hominoids in the early-to-middle Miocene of Africa, in no European Miocene locality more than one hominid taxon has been identified. Here we describe the first case of hominid sympatry in Europe from the 11.62 Ma old Hammerschmiede HAM 5 level, best known from its excellent record of Danuvius guggenmosi . The new fossils are consistent in size with larger pliopithecoids but differ morphologically from any pliopithecoid and from Danuvius . They are also distinguished from early and middle Miocene apes, share affinities with late Miocene apes, and represent a small hitherto unknown late Miocene ape Buronius manfredschmidi . With an estimated body mass of about 10 kg it represents the smallest known hominid taxon. The relative enamel thickness of Buronius is thin and contrasts with Danuvius , whose enamel is twice as thick. The differences between Buronius and Danuvius in tooth and patellar morphology, enamel thickness and body mass are indicative of differing adaptations in each, permitting resource partitioning, in which Buronius was a more folivorous climber.
Digital Gait Outcomes for Autosomal Recessive Spastic Ataxia of Charlevoix‐Saguenay (ARSACS): Discriminative, Convergent, and Ecological Validity in a Multicenter Study (PROSPAX)
2024-06-07

Abstract Background With treatment trials on the horizon, this study aimed to identify candidate digital‐motor gait outcomes for autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS), capturable by wearable sensors with multicenter validity, and ideally also ecological validity during free walking outside laboratory settings. Methods Cross‐sectional multicenter study (four centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body‐worn sensors (Opal, APDM) in laboratory settings and free walking in public spaces. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (ie, clinical and patient relevance) validity by correlations with SPRS mobility (primary outcome) and Scale for the Assessment and Rating of Ataxia (SARA), Spastic Paraplegia Rating Scale (SPRS), and activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS‐ADL) (exploratory outcomes). Results Of 30 hypothesis‐based digital gait measures, 14 measures discriminated ARSACS patients from controls with large effect sizes (|Cliff's δ| &gt; 0.8) in laboratory settings, with strongest discrimination by measures of spatiotemporal variability Lateral Step Deviation (δ = 0.98), SPcmp (δ = 0.94), and Swing CV (δ = 0.93). Large correlations with the SPRS mobility were observed for Swing CV (Spearman's ρ = 0.84), Speed (ρ = −0.63), and Harmonic Ratio V (ρ = −0.62). During supervised free walking in a public space, 11/30 gait measures discriminated ARSACS from controls with large effect sizes. Large correlations with SPRS mobility were here observed for Swing CV (ρ = 0.78) and Speed (ρ = −0.69), without reductions in effect sizes compared with laboratory settings. Conclusions We identified a promising set of digital‐motor candidate gait outcomes for ARSACS, applicable in multicenter settings, correlating with patient‐relevant health aspects, and with high validity also outside laboratory settings, thus simulating real‐life walking with higher ecological validity. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Bird Species Knowledge and Its Antecedents in US High School Students—A Case Study from Michigan
2024-06-07

Bird identification is a necessary skill for citizen science projects, and teaching and learning about species is essential to halt the decline in biodiversity. Here, we investigated bird species knowledge in a case study of Michigan high school students using an online survey. Participants were asked to identify 21 common species, covering a wide range of orders and families. On average, high school students achieved a correct identification score of 35%. The most well-known species were the American Robin, Blue Jay, Cardinal and Turkey Vulture. We found no difference between boys and girls, but identification scores declined with increasing age. Interest was an important predictor of identification knowledge, as were activities (field trips, outings) both in and out of class. Among species traits, high knowledge of a species was positively related to the number of eBird entries (as a proxy for year-round population size), body mass (heavier species were better known) and internet presence. We suggest expanding this study to other states, and we encourage educators and teachers to improve bird knowledge through birding field trips.
Accessing self-diffusion on nanosecond time and nanometre length scales with minute kinetic resolution
2024-06-07

Neutron spectroscopy uniquely and non-destructively accesses diffusive dynamics in soft and biological matter, including for instance proteins in hydrated powders or in solution, and more generally dynamic properties of condensed matter on the molecular level. Given the limited neutron flux resulting in long counting times, it is important to optimize data acquisition for the specific question, in particular for time-resolved (kinetic) studies. The required acquisition time was recently significantly reduced by measurements of discrete energy transfers rather than quasi-continuous neutron scattering spectra on neutron backscattering spectrometers. Besides this reduction in acquisition times, smaller amounts of samples can be measured with better statistics, and most importantly, kinetically changing samples, such as aggregating or crystallizing samples, can be followed. However, given the small number of discrete energy transfers probed in this mode, established analysis frameworks for full spectra can break down. Presented here are new approaches to analyze measurements of diffusive dynamics recorded within fixed windows in energy transfer, and these are compared with the analysis of full spectra. The new approaches are tested by both modeled scattering functions and a comparative analysis of fixed energy window data and full spectra on well understood reference samples. This new approach can be employed successfully for kinetic studies of the dynamics focusing on the short-time apparent center-of-mass diffusion.
The AMATUS dataset: Arithmetic performance, Mathematics anxiety and Attitudes in primary school Teachers and University Students
2024-06-07

Although the mathematics anxiety-performance link has been extensively studied, its interplay with other emotional and attitude constructs is still unclear. The present dataset includes measures of mathematics anxiety and arithmetic performance alongside different types of anxiety (i.e., state, test, general anxiety and neuroticism), attitudes towards mathematics (i.e., mathematics self-concept, mathematics self-efficacy and mathematics-gender stereotype endorsement), and math-unrelated constructs among university students (N = 848) and primary school teachers (N = 258) from Germany and Belgium. The data is accessible in the Open Science Framework (https://osf.io/gszpb/).
Clinical and radiological outcome following trauma-related reverse shoulder arthroplasty
2024-06-07

Abstract Background Reverse shoulder arthroplasty (RSA) is a frequently used therapy for complex proximal humeral fractures and posttraumatic disorders. The present study’s purpose was to assess the clinical and radiological outcome of primary and secondary RSA, and to analyze the impact of refixation of the greater tuberosity (GT). Patients and methods 28 patients with primary fracture RSA and 18 patients with RSA due to posttraumatic disorders were examined with a mean clinical follow-up of 2.5 ± 1.73 years. Operative details and radiographs were retrospectively reviewed. Additional analyses were performed for healed and non-healed GT in primary RSA. Results Patients with fracture RSA had higher Constant-Murley score (CMS) than secondary RSA without reaching significance ( p = 0.104). No significant difference was present for the quality of life measured by the Short Form 36 (SF 36) and the range of motion. In primary RSA, 78.6% GT healed anatomically. Compared to non-healed GT, patients with healed GT had a significantly higher CMS ( p = 0.011), external rotation ( p = 0.026) and forward flexion ( p = 0.083), whereas DASH score was lower without a significant difference ( p = 0.268). SF 36 showed no significant difference. Patients with healed GT had a more neutral glenoid version ( p = 0.009). Conclusion Superior range of motion and clinical outcome scores were present for anatomically healed GT. Therefore, refixation of the tuberosities is recommended. Secondary RSA can result in inferior results compared to primary RSA, so patients need to be adequately informed.
XEN45 gel stent in the treatment of pigmentary glaucoma: A two-year follow-up
2024-06-07

Purpose To investigate safety and efficacy of the XEN gel stent in patients with pigmentary glaucoma (PG). Methods A retrospective analysis of 26 eyes of 19 patients with PG undergoing XEN gel stent implantation was performed. Best-corrected visual acuity, intraocular pressure (IOP), and number of antiglaucoma medications were analyzed preoperatively, and at 2 weeks and 3, 6, 12, and 24 months after surgery. Success, needling, and complications were analyzed. Complete success was defined as an IOP reduction of &gt;20% and achieving a target IOP of ≤18, ≤15, or ≤12 mmHg without antiglaucoma medication. Qualified success was indicated if the IOP target was reached with or without medication. Results Mean IOP decreased significantly from 27.6 ± 14.3 (standard deviation, SD) mmHg to 14.3 ± 4.6 mmHg after one year ( p &lt; 0.001) and 15.1 ± 2.7 mmHg ( p &lt; 0.001) after two years. The median number of hypotensive drugs declined significantly from 4 (range: 3–5) to 0 (0–2) and 0 (0–3) after one and two years, respectively. After two years, complete success with an IOP of ≤18 mmHg and ≤15 mmHg was achieved in 73.1% and 61.5%, respectively. Half of the eyes required needling after a median time of 8 months (0.5–34 months). No sight-threatening complications were observed. Conclusion The XEN gel stent is a safe and effective surgical treatment option for PG. Needling is an important part of the procedure and should be communicated preoperatively to the patients.
Regulation of the DLC3 tumor suppressor by a novel phosphoswitch
2024-06-07

Deleted in liver cancer 3 (DLC3) is a Rho GTPase-activating protein (RhoGAP) that plays a crucial role in maintaining adherens junction integrity and coordinating polarized vesicle transport by modulating Rho activity at the plasma membrane and endomembranes. By employing bioinformatical sequence analysis, <i>in vitro</i> experiments, and <i>in cellulo</i> assays we here identified a polybasic region (PBR) in DLC3 that facilitates the association of the protein with cellular membranes. Within the PBR, we mapped two serines whose phosphorylation can alter the electrostatic character of the region. Consequently, phosphomimetic mutations of these sites impaired the membrane association of DLC3. Furthermore, we found a new PBR-dependent localization of DLC3 at the midbody region, where the protein locally controlled Rho activity. Here, the phosphorylation-dependent regulation of DLC3 appeared to be required for proper cytokinesis. Our work thus provides a novel mechanism for spatiotemporal termination of Rho signaling by the RhoGAP protein DLC3.