julilili42/papers huggingface dataset:
Escalating High-dimensional Imaging using Combinatorial Channel Multiplexing and Deep Learning
2023-09-12

Abstract Understanding tissue structure and function requires tools that quantify the expression of multiple proteins at single-cell resolution while preserving spatial information. Current imaging technologies use a separate channel for each individual protein, inherently limiting their throughput and scalability. Here, we present CombPlex (COMBinatorial multiPLEXing), a combinatorial staining platform coupled with an algorithmic framework to exponentially increase the number of proteins that can be measured from C up to 2 c − 1. In CombPlex, every protein can be imaged in several channels, and every channel contains agglomerated images of several proteins. These combinatorically-compressed images are then decompressed to individual protein-images using deep learning. We achieve accurate reconstruction when compressing the stains of twenty-two proteins to five imaging channels and demonstrate that the approach works in both fluorescence microscopy and in mass-based imaging. Combinatorial staining coupled with deep-learning decompression can escalate the number of proteins measured using any imaging modality, without the need for specialized instrumentation. Coupling CombPlex with instruments for high-dimensional imaging could pave the way to image hundreds of proteins at single-cell resolution in intact tissue sections.
Making the Transition to Text-Based Programming: The Pilot Evaluation of a Computational Thinking Intervention for Primary School Students
2023-09-12

Programming and computational thinking (CT) have become important topics in elementary education and are being implemented by national curricula, extracurricular programs, and informal learning environments. Most related research and implementation is mainly focused on block-based programming (BBP). However, BBP can lead to bad programming habits and a later transition to text-based programming (TBP) has been shown to be difficult for students, as they can lose confidence and motivation. Thus, we developed a course to facilitate the transition from BBP to TBP and foster CT while also promoting motivation and students' programming-related self-concept. We considered data from 27 fourth-grade students aged 9 to 10, who participated in the course as part of an extracurricular enrichment program. In a pre-/post-test design, we assessed CT and its cognitive correlates such as non-verbal visuospatial reasoning, verbal reasoning, arithmetic competencies as well as the student's motivation and attitude towards programming. Results indicated improved students' CT, arithmetic, and non-verbal visuospatial reasoning. Furthermore, the transition to TBP did not significantly reduce students' motivation for programming. Taken together, these findings indicate that the developed intervention may be helpful to facilitate the transition from BBP to TBP while keeping the students motivated and fostering CT.
Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky
2023-09-12

Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While we know how color information is processed in visual brain areas of primates, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of mouse natural scenes. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. This type of coloropponency in the receptive field center was not present at the level of the retinal output and, therefore, is likely computed in the cortex by integrating upstream visual signals. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of “predatory”-like dark UV-objects in noisy daylight scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species. More broadly, they support the hypothesis that visual cortex combines upstream information towards computing neuronal selectivity to behaviorally-relevant sensory features.
The Role of Additional Staining in the Assessment of the Peritoneal Regression Grading Score (PRGS) in Peritoneal Metastasis of Gastric Origin
2023-09-12

Introduction: The Peritoneal Regression Grading Score (PRGS) is a 4-tied histologic regression grading score for determining the response of peritoneal metastasis to chemotherapy. Peritoneal biopsies in every abdominal quadrant are recommended. A positive therapy response is defined as a decreasing or stable mean PRGS between 2 therapy cycles. The added value of periodic acid satin (PAS) and Ber-EP4 staining over HE staining for diagnosing PRGS1 (the absence of vital tumor cells) is unclear. Materials and Methods: A total of 339 biopsies obtained during 76 laparoscopies in 33 patients with peritoneal metastasis of gastric cancer were analyzed. Biopsies classified as PRGS 1 (no residual tumor, n=95) or indefinite (n=50) were stained with PAS, and remaining indefinite or PRGS1 cases additionally stained with BerEP4. Results: After PAS-staining tumor cells were detected in 28 out of 145 biopsies (19%), the remaining 117 biopsies were immunostained with Ber-EP4. Tumor cells were detected in 22 biopsies (19%). In total, additional staining allowed the detection of residual tumor cells in 50 out of 339 biopsies (15%) and changed the therapy response assessment in 7 out of 33 (21%) patients. Conclusions: In summary, 25% (24 out of 95) of initially tumor-free samples (PRGS1) showed residual tumor cells after additional staining with PAS and/or BerEp4. Immunohistochemistry provided important additional information (the presence of tumor cells) in 22 of all 339 biopsies (11.2%). Further staining reduced the instances of unclear diagnosis from 50 to 0 and changed the therapy response assessment in 7 out of 33 patients (21%). We recommend additional staining in PRGS1 or unclear cases.
Influence of open-source virtual-reality based gaze training on navigation performance in Retinitis pigmentosa patients in a crossover randomized controlled trial
2023-09-12

Abstract Motivation People living with tunnel vision caused by Retinitis pigmentosa (RP) oftentimes face challenges navigating and avoiding obstacles due to a severely decreased Visual Field. Previous studies have shown that gaze training – guided tasks to encourage specific gaze behavior – help improve visual performance in patients with limited Visual Field. We propose a Virtual-Reality based, at-home gaze training – to the best of our knowledge the first of its kind – to increase effective eye movements and navigation performance of RP patients in a real-world obstacle course. Methods A group of RP patients (n=8) participated in a study consisting of two 4-week-phases, both carried out by the same patient group in randomized order: In the ‘training phase’, participants carried out a Virtual-Reality gaze training for 30 minutes per day; In the ‘control phase’, no training occurred. Before and after each phase, participants were tasked to move through a randomized real-world obstacle course. Navigation performance in the obstacle course as well as eye-tracking data during the trials were evaluated. The study is registered at the German Clinical Trials Register (DRKS) with the ID DRKS00032628. Results On average, the time required to move through the obstacle course decreased by 17.0% after the training phase ( p &lt; 0.001), the number of collisions decreased by 50.0% ( p &lt; 0.001) and the average visual area observed by participants increased by 4.41% ( p &lt; 0.001). In comparison, after the control phase, the time required to move through the obstacle course was found to have decreased by 5.9% ( p = 0.003), collisions decreased by 10.4% ( p = 0.609) and the observed visual area increased by 2.06% ( p = 0.0835). Conclusion The performance increase over the training phase significantly surpasses the natural learning effect found in the control phase, suggesting that Virtual-Reality based gaze training can improve real-world navigation performance and effective gaze movements of patients with RP. The training is available as work-in-progress open-source software.
Collective PV-RCNN: A Novel Fusion Technique using Collective Detections for Enhanced Local LiDAR-Based Perception
2023-09-12

Comprehensive perception of the environment is crucial for the safe operation of autonomous vehicles. However, the perception capabilities of autonomous vehicles are limited due to occlusions, limited sensor ranges, or environmental influences. Collective Perception (CP) aims to mitigate these problems by enabling the exchange of information between vehicles. A major challenge in CP is the fusion of the exchanged information. Due to the enormous bandwidth requirement of early fusion approaches and the interchangeability issues of intermediate fusion approaches, only the late fusion of shared detections is practical. Current late fusion approaches neglect valuable information for local detection, this is why we propose a novel fusion method to fuse the detections of cooperative vehicles within the local LiDAR-based detection pipeline. Therefore, we present Collective PV-RCNN (CPV-RCNN), which extends the PV-RCNN++ framework to fuse collective detections. Code is available at https://github.com/ekut-es
From Intellectual Investment Trait Theory to Dynamic Intellectual Investment Trait and State Theory: Theory Development, Methodological Advancement, and Empirical Illustration
2023-09-12

This paper introduces Dynamic Intellectual Investment Trait and State Theory, which (a) centers on dynamic within-person reciprocal relationships between cognitive performance states and intellectual investment personality states, (b) integrates within-person dynamics and developmental trajectories in cognitive abilities and intellectual investment traits, and (c) is embedded in a continuous-time framework. Aligning personality theories with statistical models, we discuss the most appropriate model for testing Dynamic Intellectual Investment Trait and State Theory: a continuous-time growth curve model that combines dynamics and trends. We apply the continuous-time growth curve model in an empirical illustration involving 204 German adults who were assessed roughly 100 times on cognitive abilities (working memory) and intellectual investment personality (interest).
Capturing Types
2023-09-13

Type systems usually characterize the shape of values but not their free variables. However, many desirable safety properties could be guaranteed if one knew the free variables captured by values. We describe CC &lt; :◻ , a calculus where such captured variables are succinctly represented in types, and show it can be used to safely implement effects and effect polymorphism via scoped capabilities. We discuss how the decision to track captured variables guides key aspects of the calculus, and show that CC &lt; :◻ admits simple and intuitive types for common data structures and their typical usage patterns. We demonstrate how these ideas can be used to guide the implementation of capture checking in a practical programming language.
Synergistic relationships between the age of soil organic matter, Fe speciation, and aggregate stability in an arable Luvisol
2023-09-13

Abstract Background Knowledge of soil aggregate formation and stability is essential, as this is important for maintaining soil functions. Aims This study aimed to investigate the influence of organic matter (OM), the content of pedogenic iron (Fe) (oxyhydr)oxides, and aggregate size on the stability of aggregates in arable soil. Methods To this end, the Ap and Bt horizons of a Luvisol were sampled after 14 years of bare fallow, and the results were compared with a control field that had been permanently cropped. Results In the Ap horizon, bare fallow decreased the median diameter of the 53–250 μm size fraction by 26%. Simultaneously, the mass of the 20–53 μm size fraction increased by 65%, indicating reduced stability—particularly of larger soil microaggregates—due to the lack of input of fresh OM. The range of 14 carbon ( 14 C) fraction of modern C (F 14 C) under bare fallow was between 0.50 and 0.90, and thus lower than the cropped site (F 14 C between 0.75 and 1.01), which is particularly pronounced in the smallest size fraction, indicating the presence of older C. This higher stability and the reduced C turnover in &lt;20 μm aggregates is probably also due to having the highest content of poorly crystalline Fe (oxy)hydroxides, compared to the other size fractions, which act as a cementing agent. Colloid transport from the Ap to the Bt horizon was observed under bare fallow treatment. Conclusions The lack of input of OM decreased the stability of microaggregates and led to a release of mobile colloids, the transport of which can initiate elemental fluxes with as‐yet unknown environmental consequences.
Ancient origin of the rod bipolar cell pathway in the vertebrate retina
2023-09-13

ABSTRACT Vertebrates rely on rod photoreceptors for vision in low-light conditions 1 . Mammals have a specialized downstream circuit for rod signaling called the primary rod pathway, which comprises specific cell types and wiring patterns that are thought to be unique to this lineage 2–6 . Thus, it has been long assumed that the primary rod pathway evolved in mammals 3, 5–7 . Here, we challenge this view by demonstrating that the mammalian primary rod pathway is conserved in zebrafish, which diverged from extant mammals ∼400 million years ago. Using single-cell RNA-sequencing, we identified two bipolar cell (BC) types in zebrafish that are related to mammalian rod BCs (RBCs) of the primary rod pathway. By combining electrophysiology, histology, and ultrastructural reconstruction of the zebrafish RBCs, we found that, like mammalian RBCs 8 , both zebrafish RBC types connect with all rods and red-cones in their dendritic territory, and provide output largely onto amacrine cells. The wiring pattern of the amacrine cells post-synaptic to one RBC type is strikingly similar to that of mammalian RBCs. This suggests that the cell types and circuit design of the primary rod pathway may have emerged before the divergence of teleost fish and amniotes (mammals, bird, reptiles). The second RBC type in zebrafish, which forms separate pathways from the first RBC type, is either lost in mammals or emerged in fish to serve yet unknown roles. Highlights - Zebrafish have two rod bipolar cell types (RBC1/2). - Synaptic connectivity of RBC1 resembles that of the mammalian RBCs. - The primary rod pathway therefore probably evolved more than 400 million years ago. - The second zebrafish RBC type, RBC2, forms a separate pathway from RBC1.
Live imaging of microglia during sleeping sickness reveals early and heterogeneous inflammatory responses
2023-09-13

Introduction Invasion of the central nervous system (CNS) is the most serious consequence of Trypanosoma brucei infection, which causes sleeping sickness. Recent experimental data have revealed some more insights into the disease during the meningoencephalitic stage. However, detailed cellular processes befalling the CNS during the disease are poorly understood. Methods To further address this issue, we implanted a cranial window on the cortex of B6.129P2(Cg)- Cx3cr1 tm1Litt /J mice, infected them with Trypanosoma brucei expressing RFP via intraperitoneal injection, and monitored microglial cells and parasites longitudinally over 30 days using in vivo 2-photon imaging. We correlated the observed changes with histological analyses to evaluate the recruitment of peripheral immune cells. Results and discussion We uncovered an early involvement of microglia that precedes invasion of the CNS by the parasite. We accomplished a detailed characterization of the progressive sequence of events that correlates with microglial morphological changes and microgliosis. Our findings unveiled a heterogeneous microglial response in places of initial homeostatic disruption near brain barriers and pointed out an exceptional capability of microglia to hamper parasite proliferation inside the brain. We also found early signs of inflammation in the meninges, which synchronize with the microglial response. Moreover, we observed a massive infiltration of peripheral immune cells into the parenchyma as a signature in the final disease stage. Overall, our study provides new insights into the host-pathogen immune interactions in the meningeal and parenchymal compartments of the neocortex.
Characterizing brain stage-dependent pupil dynamics based on lateral hypothalamic activity
2023-09-13

Abstract Pupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain dynamic stages can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and whole-brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional magnetic resonance imaging (fMRI) data showed various correlations to pupil dynamics across trials that span negative, null, and positive correlation values, demonstrating brain state-dependent coupling features. Our results indicate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, suggesting a role of the latter in brain dynamic stage regulation.
Metadata Schema for the German Human Genome-Phenome Archive
2023-09-13

&amp;lt;p&amp;gt;This White Paper summarizes the development of the German Human Genome-Phenome Archive (GHGA) Metadata Model and describes the modeling framework in detail. Further, it elaborates on implemented ontologies,&amp;nbsp;data privacy considerations and alignment with other (inter-) national consortia.&amp;lt;/p&amp;gt;
Relapsing TIPIC Syndrome after Administration of an mRNA-Based COVID-19 Vaccine
2023-09-13

Reported vascular complications following mRNA-based COVID-19 vaccines are consisting of myocarditis, cerebral venous thrombosis, cerebral vascular thrombosis, and vaccine-induced thrombocytopenia. Here, we describe a case of a 49-year-old woman with left-sided pain above the middle common carotid artery (carotidynia) starting a few days after her second vaccination with an mRNA-based COVID-19 vaccine (Spikevax). Imaging was indicative of transient perivascular inflammation of the carotid artery (TIPIC) syndrome. The diagnostic workup for other immunologically mediated diseases was negative. The inflammation subsided after a course of prednisone and aspirin, and clinical symptoms vanished, but later mildly relapsed in the context of a viral upper respiratory tract infection other than SARS-CoV-2. Carotidynia because of TIPIC syndrome may present as an immunogenic side effect of the newly developed mRNA-based vaccinations against COVID-19. TIPIC syndrome should be considered in new-onset neck pain after vaccination.
Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors
2023-09-13

Abstract Bivalent molecules consisting of groups connected through bridging linkers often exhibit strong target binding and unique biological effects. However, developing bivalent inhibitors with the desired activity is challenging due to the dual motif architecture of these molecules and the variability that can be introduced through differing linker structures and geometries. We report a set of alternatively linked bivalent EGFR inhibitors that simultaneously occupy the ATP substrate and allosteric pockets. Crystal structures show that initial and redesigned linkers bridging a trisubstituted imidazole ATP-site inhibitor and dibenzodiazepinone allosteric-site inhibitor proved successful in spanning these sites. The re-engineered linker yielded a compound that exhibited significantly higher potency (~60 pM) against the drug-resistant EGFR L858R/T790M and L858R/T790M/C797S, which was superadditive as compared with the parent molecules. The enhanced potency is attributed to factors stemming from the linker connection to the allosteric-site group and informs strategies to engineer linkers in bivalent agent design.
Development of chronic kidney disease after major surgery
2023-09-13

<title>Abstract</title> Purpose Chronic kidney disease (CKD) is a significant health care burden worldwide. However, little is known about its development after major surgery. Methods We conducted an international prospective, observational, multi-center study in 30 countries among patients undergoing major surgery. The primary study endpoint was the incidence of CKD (defined as new onset CKD with an eGFR &lt; 60ml/min/1.73m<sup>2</sup> at day 90). Secondary endpoints included the relationship between early postoperative-AKI (within 72h after major surgery) and development of postoperative CKD, the identification of risk factors for CKD, and the rate and risk factors for CKD progression in patients with pre-existing CKD. Results We studied 9,510 patients without pre-existing CKD. Of these, 940 (9.9%) developed CKD with 34.2% experiencing an episode of early postoperative-AKI. CKD rates significantly increased with the severity of early AKI (19.1% KDIGO1, 24.5% KDIGO2, 34.3% KDIGO3; <italic>P</italic> &lt; 0.001) and duration (15.5% transient vs 38.3% persistent AKI; <italic>P</italic> &lt; 0.001). Independent risk factors for CKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for CKD of 2.64 (95%-CI 2.21–3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90 as defined. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. Conclusion One in ten major surgery patients developed postoperative CKD, most of them without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration was associated with an increased rate of CKD with early postoperative-AKI being a major independent risk factor for CKD. Clinical trial number: The study was registered at ClinicalTrials.gov (NCT04165369).
GRFolres: A code for modified gravity simulations in strong gravity
2023-09-13

GRFolres is an open-source code for performing simulations in modified theories of gravity, based on the publicly available 3+1D numerical relativity code GRChombo. Note: Submitted for review in the Journal of Open Source Software; Comments welcome; The code can be found at https://github.com/GRChombo/GRFolres