julilili42/papers huggingface dataset:
Nitrogen-vacancy centers for prosthesis control
2024-01-26

A prosthesis is conventionally controlled and monitored by recording and converting the electrical signals from the muscles (electromyography) into machine-understandable signals. However, the activity of the muscle can be registered not only electrically, but also magnetically, as every electrical activity within the muscle also generates a magnetic field. This magnetomyography originates from the same ionic currents and presents comparable temporal and spectral profiles, but poses two potential advantages over electromyography: A) the intrinsic contactless nature of the measurement and b) a theoretical superiority when it comes towards the decomposition of muscle signals. MMG can be recorded contactless as the magnetic permeability of human tissue is comparable to that of empty space and thereby magnetic field is less distorted. This suggests a possible superiority of MMG for the study of muscle signal and theoretically leads (in silico) to a twofold discrimination of motor neurons of the spinal cord, when compared to electromyography. Despite these advantages, current challenges are the need for magnetic shielding and sensor size and sensitivity-which can be partly surpassed using nitrogen-vacancy diamond magnetometers. Given the circumstance that little is known for magnetomyography and prosthesis control, we performed several experiments using commercially available optically pumped magnetometer to provide a reference about current technological possibilities (e.g., sensor sensitivity); furthermore, we present a new fully-integrated nitrogen vacancy-based sensor system, which may augment and/or replace traditional biosignal interfaces to peripheral devices such exoprostheses or exoskeletons.
Age-depth model ensembles for SISAL v3 speleothem records
2024-01-27

&lt;p&gt;Depth-age model ensembles created for the SISAL database v3, in supplement to&nbsp;&lt;strong&gt;&lt;a href="https://essd.copernicus.org/preprints/essd-2023-364/" target="_blank" rel="noopener"&gt;Kaushal et al., 2024&lt;/a&gt;&lt;/strong&gt;&nbsp; and building on &lt;a href="https://www.earth-syst-sci-data-discuss.net/essd-2020-39/"&gt;Comas-Bru, Rehfeld, Roesch et al., 2020&lt;/a&gt;.&lt;/p&gt; &lt;p&gt;This upload includes ensemble data for 5 methods (interpolation, linear regression, copRa, Bchron and Bacon) created following the protocol&nbsp; in previous versions but for newly included entities in the database.&lt;/p&gt; &lt;p&gt;Each file contains a matrix with the first column giving the row number, the second the SISAL v3 sample ID, the third the depth in the speleothem (in mm), and the fourth to 2003rd column contains the 2000 age model ensemble members.&lt;/p&gt;
Distracted by a talking head? An eye tracking study on the effects of instructor presence in learning videos with animated graphic slides
2024-01-28

There are still unanswered questions concerning the optimal design of educational videos, for instance with regard to the visibility of a talking head next to the learning content. Although visible talking heads in educational videos may stimulate deeper processing, they can also distract from the visual learning content. The current eye tracking study investigated how a talking head presented next to stepwise appearing (i.e., animated) graphic-based content affected learners' eye movements, learning, and ratings (e.g., social presence). Ninety-six university students participated in the experiment. We used a within-subjects design to vary whether a talking head was present in short learning videos with narrated slides. Our results revealed that the talking head both reduced fixation duration of the overall content and fixation duration and number of fixations of newly appearing content. Further, time to first fixation of newly appearing content was delayed by the talking head. However, the talking head did not affect learning outcomes (knowledge test and picture recognition task performance) and there was no mediation by the fixation duration of the content. Additionally, learners indicated higher social presence ratings for videos including a talking head, but we observed no differences in ratings of perceived learning, satisfaction, perceived difficulty, and invested mental effort due to the talking head. The talking head strongly influenced learners' eye movements by reducing fixations of the learning content but did not cause any learning losses. We discuss implications and limitations of the findings also in view of future research.
Predictive uncertainty in deep learning–based MR image reconstruction using deep ensembles: Evaluation on the fastMRI data set
2024-01-28

Abstract Purpose To estimate pixel‐wise predictive uncertainty for deep learning–based MR image reconstruction and to examine the impact of domain shifts and architecture robustness. Methods Uncertainty prediction could provide a measure for robustness of deep learning (DL)–based MR image reconstruction from undersampled data. DL methods bear the risk of inducing reconstruction errors like in‐painting of unrealistic structures or missing pathologies. These errors may be obscured by visual realism of DL reconstruction and thus remain undiscovered. Furthermore, most methods are task‐agnostic and not well calibrated to domain shifts. We propose a strategy that estimates aleatoric (data) and epistemic (model) uncertainty, which entails training a deep ensemble (epistemic) with nonnegative log‐likelihood (aleatoric) loss in addition to the conventional applied losses terms. The proposed procedure can be paired with any DL reconstruction, enabling investigations of their predictive uncertainties on a pixel level. Five different architectures were investigated on the fastMRI database. The impact on the examined uncertainty of in‐distributional and out‐of‐distributional data with changes to undersampling pattern, imaging contrast, imaging orientation, anatomy, and pathology were explored. Results Predictive uncertainty could be captured and showed good correlation to normalized mean squared error. Uncertainty was primarily focused along the aliased anatomies and on hyperintense and hypointense regions. The proposed uncertainty measure was able to detect disease prevalence shifts. Distinct predictive uncertainty patterns were observed for changing network architectures. Conclusion The proposed approach enables aleatoric and epistemic uncertainty prediction for DL‐based MR reconstruction with an interpretable examination on a pixel level.
Sustained Extracellular Electrical Stimulation Modulates the Permeability of Gap Junctions in rd1 Mouse Retina with Photoreceptor Degeneration
2024-01-28

Neurons build vast gap junction-coupled networks (GJ-nets) that are permeable to ions or small molecules, enabling lateral signaling. Herein, we investigate (1) the effect of blinding diseases on GJ-nets in mouse retinas and (2) the impact of electrical stimulation on GJ permeability. GJ permeability was traced in the acute retinal explants of blind retinal degeneration 1 (rd1) mice using the GJ tracer neurobiotin. The tracer was introduced via the edge cut method into the GJ-net, and its spread was visualized in histological preparations (fluorescent tagged) using microscopy. Sustained stimulation was applied to modulate GJ permeability using a single large electrode. Our findings are: (1) The blind rd1 retinas displayed extensive intercellular coupling via open GJs. Three GJ-nets were identified: horizontal, amacrine, and ganglion cell networks. (2) Sustained stimulation significantly diminished the tracer spread through the GJs in all the cell layers, as occurs with pharmaceutical inhibition with carbenoxolone. We concluded that the GJ-nets of rd1 retinas remain coupled and functional after blinding disease and that their permeability is regulatable by sustained stimulation. These findings are essential for understanding molecular signaling in diseases over coupled networks and therapeutic approaches using electrical implants, such as eliciting visual sensations or suppressing cortical seizures.
Frequency shifts of free water signals from compact bone: Simulations and measurements using a UTE‐FID sequence
2024-01-28

Abstract Purpose Free water in cortical bone is either contained in nearly cylindrical structures (mainly Haversian canals oriented parallel to the bone axis) or in more spherically shaped pores (lacunae). Those cavities have been reported to crucially influence bone quality and mechanical stability. Susceptibility differences between bone and water can lead to water frequency shifts dependent on the geometric characteristics. The purpose of this study is to calculate and measure the frequency distribution of the water signal in MRI in dependence of the microscopic bone geometry. Methods Finite element modeling and analytical approaches were performed to characterize the free water components of bone. The previously introduced UTE‐FID technique providing spatially resolved FID‐spectra was used to measure the frequency distribution pixel‐wise for different orientations of the bone axis. Results The frequency difference between free water in spherical pores and in canals parallel to B 0 amounts up to approximately 100 Hz at 3T. Simulated resonance frequencies showed good agreement with the findings in UTE‐FID spectra. The intensity ratio of the two signal components (parallel canals and spherical pores) was found to vary between periosteal and endosteal regions. Conclusion Spatially resolved UTE‐FID examinations allow the determination of the frequency distribution of signals from free water in cortical bone. This frequency distribution indicates the composition of the signal contributions from nearly spherical cavities and cylindrical canals which allows for further characterization of bone structure and status.
Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial.
2024-01-29

362 Background: N+C demonstrated superior progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in patients (pts) with previously untreated aRCC in the primary analysis of the phase 3 CheckMate 9ER trial (18.1 mo median follow-up). N+C maintained efficacy benefits vs S with 44.0 mo median follow-up. Here, we report updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety with extended follow-up. Methods: Pts with aRCC were randomized to N 240 mg every 2 weeks + C 40 mg QD vs S 50 mg QD (4 weeks of 6-week cycles) until disease progression or unacceptable toxicity, with up to 2 y of N. The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Overall, 323 pts were randomized to N+C and 328 to S (ITT). With 55.6 mo median (48.1 mo min.) follow-up for OS, median PFS was 16.4 vs 8.4 mo (hazard ratio [HR] 0.58, 95% CI 0.49-0.70) and median OS was 46.5 vs 36.0 mo (HR 0.77, 95% CI 0.63-0.95) with N+C vs S. ORR (95% CI) was 55.7% (50.1-61.2) vs 27.7% (23.0-32.9); 13.6% vs 4.6% of pts achieved complete response (CR); 6.5% vs 13.7% had progressive disease (PD), respectively. Median (range) time to response (TTR) was 2.8 (1.0-22.2) vs 4.3 (1.7-30.4) mo for N+C vs S, and median (95% CI) duration of response (DOR) was 22.0 (18.0-25.2) vs 15.2 (10.9-19.3) mo. Efficacy by IMDC favorable (FAV) and intermediate/poor (I/P) risk groups is reported in the Table. Among all treated pts (320 pts each arm), any-grade (grade ≥ 3) treatment-related adverse events (TRAEs) occurred in 97.5% (67.5%) vs 93.1% (55.3%) with N+C vs S. Any-grade TRAEs led to discontinuation of N or C in 28.1% of pts (N only, 10.0%; C only, 10.3%; N+C simultaneously, 6.6%; N+C sequentially, 1.3%) and of S in 10.9% of pts. Additional analyses in subgroups of clinical interest will be presented. Conclusions: With 55.6 mo median follow-up, N+C continues to maintain meaningful long-term efficacy benefits over S. No new safety concerns were identified. These results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . [Table: see text]
Non-canonical G protein signaling
2024-01-29

The original paradigm of classical - also referred to as canonical - cellular signal transduction of heterotrimeric G proteins (G protein) is defined by a hierarchical, orthograde interaction of three players: the agonist-activated G protein-coupled receptor (GPCR), which activates the transducing G protein, that in turn regulates its intracellular effectors. This receptor-transducer-effector concept was extended by the identification of regulators and adapters such as the regulators of G protein signaling (RGS), receptor kinases like βARK, or GPCR-interacting arrestin adapters that are integrated into this canonical signaling process at different levels to enable fine-tuning. Finally, the identification of atypical signaling mechanisms of classical regulators, together with the discovery of novel modulators, added a new and fascinating dimension to the cellular G protein signal transduction. This heterogeneous group of accessory G protein modulators was coined "activators of G protein signaling" (AGS) proteins and plays distinct roles in canonical and non-canonical G protein signaling pathways. AGS proteins contribute to the control of essential cellular functions such as cell development and division, intracellular transport processes, secretion, autophagy or cell movements. As such, they are involved in numerous biological processes that are crucial for diseases, like diabetes mellitus, cancer, and stroke, which represent major health burdens. Although the identification of a large number of non-canonical G protein signaling pathways has broadened the spectrum of this cellular communication system, their underlying mechanisms, functions, and biological effects are poorly understood. In this review, we highlight and discuss atypical G protein-dependent signaling mechanisms with a focus on inhibitory G proteins (G<sub>i</sub>) involved in canonical and non-canonical signal transduction, review recent developments and open questions, address the potential of new approaches for targeted pharmacological interventions.
Occurrence of NECTIN4 amplification in solid tumors and enfortumab vedotin response in metastatic urothelial cancer.
2024-01-29

673 Background: The anti-NECTIN4 antibody-drug conjugate (ADC) enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains are frequent genomic events in mUC leading to NECTIN4 amplifications. Here, we aimed to evaluate the potential of NECTIN4 amplification as a genomic biomarker to predict EV response in patients with mUC. Methods: We established a NECTIN4-specific fluorescence in-situ hybridization (FISH) assay to assess NECTIN4 copy number variations (CNVs) in a multicenter EV-treated mUC patient cohort (UC-EV, N=77), and CNV data were correlated with membranous NECTIN4 protein expression (H-score) assessed via immunohistochemistry, EV treatment responses and outcomes. Next, we conducted a pan-cancer analysis of the The Cancer Genome Atlas (TCGA) datasets, comprising 10,712 patients across 32 cancer types, to investigate the relationship between NECTIN4 CNV, mRNA expression (RNAseq) and protein levels (RPPA) across entities. Results: In TCGA cohorts, NECTIN4 amplification occurs frequently across different solid cancer types, especially in 15-20% of bladder cancers (17% in TCGA-BLCA), as well as 5-10% in breast cancer (TCGA-BRCA) and lung adenocarcinoma (TCGA-LUAD). We confirmed the amplification frequency in our UC-EV cohort (18%). NECTIN4 amplification is significantly associated with both increased NECTIN4 mRNA expression (e.g., TCGA-BLCA, BRCA, LUAD) and membranous NECTIN4 protein expression (UC-EV), and represents a stable genomic alteration during metastatic progression. In the UC-EV cohort, all patients with NECTIN4 amplification (N=14) responded to EV. In multivariable Cox adjusted for age and sex, NECTIN4 amplifications led to a 93% risk reduction for death compared to a NECTIN4non-amplified status (HR=0.07, 95%-CI 0.01–0.53; P&lt;0.001). Conclusions: Our study highlights the value of NECTIN4 amplifications to predict EV responses in patients with mUC. NECTIN4 amplifications occur frequently in different cancer types and therefore have the potential to be a novel tumor-agnostic genomic biomarker that enables tailored NECTIN4-targeted therapies in various entities.
European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (3) postoperative imaging
2024-01-29

Abstract Background Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of postoperative complications. So far, limited data is available regarding the best radiologic approach to monitor children after liver transplantation. Objective To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phases. This paper reports the responses related to postoperative imaging. Materials and methods An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. Results All sites commence ultrasound (US) monitoring within 24 h after liver transplantation. Monitoring frequency varies across sites, ranging from every 8 h to 72 h in early, and from daily to sporadic use in late postoperative phases. Predefined US protocols are used by 73% of sites. This commonly includes gray scale, color Doppler, and quantitative flow assessment. Alternative flow imaging techniques, contrast-enhanced US, and elastography are applied at 31.8%, 18.2%, and 63.6% of sites, respectively. Computed tomography is performed at 86.4% of sites when clarification is needed. Magnetic resonance imaging is used for selected cases at 36.4% of sites, mainly for assessment of biliary abnormalities or when blood tests are abnormal. Conclusion Diagnostic imaging is extensively used for postoperative surveillance of children after liver transplantation. While US is generally prioritized, substantial differences were noted in US protocol, timing, and monitoring frequency. The study highlights potential areas for future optimization and standardization of imaging, essential for conducting multicenter studies.
High-dimensional in situ proteomics imaging to assess γδ T cells in spatial biology
2024-01-29

Abstract This study presents a high-dimensional immunohistochemistry approach to assess human γδ T cell subsets in their native tissue microenvironments at spatial resolution, a hitherto unmet scientific goal due to the lack of established antibodies and required technology. We report an integrated approach based on multiplexed imaging and bioinformatic analysis to identify γδ T cells, characterize their phenotypes, and analyze the composition of their microenvironment. Twenty-eight γδ T cell microenvironments were identified in tissue samples from fresh frozen human colon and colorectal cancer where interaction partners of the immune system, but also cancer cells were discovered in close proximity to γδ T cells, visualizing their potential contributions to cancer immunosurveillance. While this proof-of-principle study demonstrates the potential of this cutting-edge technology to assess γδ T cell heterogeneity and to investigate their microenvironment, future comprehensive studies are warranted to associate phenotypes and microenvironment profiles with features such as relevant clinical characteristics.
Safety and efficacy of enfortumab vedotin in patients with metastatic/locally advanced urothelial cancer: Real-world evidence from a European database.
2024-01-29

553 Background: Enfortumab vedotin (EV) is an antibody drug conjugate targeting Nectin-4. It was approved by EMA/FDA in patients (pts) with metastatic/ locally advanced urothelial cancer post platinum and immune check point inhibitors following the results of the EV-301 trial. We report updated efficacy and safety data of EV in a large European cohort of real-world pts (GUARDIANS consortium) treated in hospitals and private practices. Methods: Retrospective data were collected from 25 German and Swiss hospitals and private practices for pts who received EV. Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Objective responses were evaluated by local investigators according to Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: Weidentified 188 pts (32.4% female) with a median age of 66 yrs (range 31-89; 22.3% &gt;/= 75 yrs). Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2/3-4/unknown in 36/39/11/3/11%. EV was administered in the fourth or later line in 43% of pts. Overall response rate (ORR) was 46.3% (partial remission: 42.0%, complete response 4.3%), disease control rate was 58.0%. Median OS (mOS) was 12.0 months (mo) (95% confidence interval 9.65-14.35) and median PFS (mPFS) was 7.0 mo (95% confidence interval 5.43-8.57). Any-grade AEs were observed in 71% and CTCAE grade ≥3 AEs in 32% of pts. Most common AEs were peripheral sensory neuropathy (33.5% any grade), skin toxicity (24.5%) and fatigue (22.9%). In pts &gt;/= 75 yrs, females, and pts treated in &gt;/=4 th line mOS, mPFS, ORR, and toxicities were comparable to younger and male counterparts and pts treated in &lt;4th line, respectively. Limitations are retrospective design and short follow-up. Conclusions: Anti-tumor activity of EV in real-world pts including difficult-to-treat subgroups is comparable to the results of the pivotal EV-301 trial. No new safety signals were observed.