julilili42/papers huggingface dataset:
Myeloid-derived suppressor cells in influenza virus-induced asthma exacerbation
2024-04-17

Myeloid-derived suppressor cells (MDSCs) are a phenotypically heterogenous group of cells that potently suppress the immune response. A growing body of evidence supports the important role of MDSCs in a variety of lung diseases, such as asthma. However, the role of MDSCs in asthma exacerbation has so far not been investigated. Here, we studied the role of MDSCs in a murine model of influenza virus-induced asthma exacerbation. BALB/c mice were exposed to house dust mite (HDM) three times a week for a total of five weeks to induce a chronic asthmatic phenotype, which was exacerbated by additional exposure to the A/Hamburg/5/2009 hemagglutinin 1 neuraminidase 1 (H1N1) influenza virus. Induction of lung inflammatory features, production of T helper (Th) 1- and Th2- associated inflammatory cytokines in the lavage fluid and an increased airway hyper-responsiveness were observed, establishing the asthma exacerbation model. The number and activity of pulmonary M-MDSCs increased in exacerbated asthmatic mice compared to non-exacerbated asthmatic mice. Furthermore, depletion of MDSCs aggravated airway hyper-responsiveness in exacerbated asthmatic mice. These findings further denote the role of MDSCs in asthma and provide some of the first evidence supporting a potential important role of MDSCs in asthma exacerbation.
The Injection of Gels Through an Intact Annulus Maintains Biomechanical Performance without Extrusion Risk
2024-04-17

For autologous-disc-derived chondrocyte transplantation (ADCT) a transglutaminase crosslinked gelatine gel and an albumin hyaluronic acid gel, crosslinked with bis-thio-polyethylene glycol, were injected through a syringe into a degenerated intervertebral disc, where they solidified in situ. This biomechanical in vitro study with lumbar bovine motion segments evaluated disc height changes, motion characteristics in a quasi-static spine loading simulators, and the potential extrusion risk of these biomaterials in a complex dynamic multi-axial loading set-up with 100,000 loading cycles. After the injection and formation of the gel in the center of the nucleus, the disc height increase was about 0.3 mm. During cyclic testing, a gradual decrease in height could be detected due to viscoelastic effects and fluid loss. No gel extrusion could be observed for all specimens during the entire test procedure. A macroscopic inspection after dissections showed an accumulation of the solidified gel in the center of the nucleus. The results demonstrate that the injection of in situ solidifying gels through the intact annulus allows for the stable maintenance of the injected gel at the target location, with high potential for use as a suitable scaffold to anchor therapeutically applied cells for disc regeneration within the treated nucleus pulposus.
Transfer of cognitive control adjustments within and between speakers
2024-04-17

Congruency effects in conflict tasks are typically larger after congruent compared to incongruent trials. This congruency sequence effect (CSE) indicates that top-down adjustments of cognitive control transfer between processing episodes, at least when controlling for bottom-up memory processes by alternating between stimulus-response (S-R) sets in confound-minimised designs. According to the control-retrieval account, cognitive control is bound to task-irrelevant context features (e.g., stimulus position or modality) and retrieved upon subsequent context feature repetitions. A confound-minimised CSE should therefore be larger when context features repeat rather than change between two trials. This study tested this prediction for a more abstract contextual stimulus feature, speaker gender. In two preregistered auditory prime-probe task experiments, participants classified colour words spoken by a female or male voice. Across both experiments, we found confound-minimised CSEs that were not reliably affected by whether the speaker gender repeated or changed. This indicates that speaker transitions have virtually no influence on the transfer of control adjustments in the absence of S-R repetitions. By contrast, when allowing for bottom-up memory processes by repeating the S-R set, CSEs were consistently larger when the speaker gender repeated compared to changed. This suggests that speaker transitions can in principle influence transfer between processing episodes. The discrepancy also held true when considering learning and test episodes separated by an intervening episode. Thus, the present findings call for a refinement of the control-retrieval account to accommodate the role of more abstract contextual stimulus features for the maintenance of memory traces in auditory conflict processing.
Spatial biases in processing mirror letters by literate subjects
2024-04-17

Abstract Preschool children often confuse letters with their mirror images when they try to read and write. Mirror confusion seems to occur more often in line with the direction of script (e.g., left-to-right for the Latin alphabetic script), suggesting that the processing of letter orientation and text directionality may be interrelated in preliterate age. When children go to school, mirror mistakes in writing/reading letters disappear. Here we ask whether the processing of letter shapes and text direction are still related in readers at different proficiency levels. Literate subjects – school children from the 1st and 4th grades and adults – decided under time pressure whether a displayed letter was oriented correctly or incorrectly (mirrored). We observed that reaction times were faster when a letter was oriented rightward, i.e. in line with the cultural text direction (left-to-right), but we did not find any differences between the groups. We conclude that, even if mirror mistakes disappear during primary school years, letter shapes are still processed in a close relation to the left-to-right reading direction in the Latin script.
Environmental metabolomics characterization of modern stromatolites and annotation of ibhayipeptolides
2024-04-17

Lithified layers of complex microbial mats known as microbialites are ubiquitous in the fossil record, and modern forms are increasingly identified globally. A key challenge to developing an understanding of microbialite formation and environmental role is how to investigate complex and diverse communities in situ. We selected living, layered microbialites (stromatolites) in a peritidal environment near Schoenmakerskop, Eastern Cape, South Africa to conduct a spatial survey mapping the composition and small molecule production of the microbial communities from environmental samples. Substrate core samples were collected from nine sampling stations ranging from the upper point of the freshwater inflow to the lower marine interface where tidal overtopping takes place. Substrate cores provided material for parallel analyses of microbial community diversity by 16S rRNA gene amplicon sequencing and metabolomics using LC–MS2. Species and metabolite diversities were correlated, and prominent specialized metabolites were targeted for preliminary characterization. A new series of cyclic hexadepsipeptides, named ibhayipeptolides, was most abundant in substrate cores of submerged microbialites. These results demonstrate the detection and identification of metabolites from mass-limited environmental samples and contribute knowledge about microbialite chemistry and biology, which facilitates future targeted studies of specialized metabolite function and biosynthesis.
A Minimal Metadata Schema and Its Tool to Improve the Searchableness of Research Data in Bioinformatics
2024-04-17

Bioinformatics develops methods to understand biological data and to explain biological processes. The discipline operates on huge data sets and is computationally intensive. The fast growth of the field and its specialization into many subdisciplines makes it hard to search for, find, and to keep track of scientific results relevant for one's own research. Being able to get knowledge of prior studies, and the data they rely on, is a prerequisite to further one's own research and to ensure effective progress of bioinformatics as a field. At the same time, scientists' own research and reputation benefit from the best possible searchableness of their research data. The FAIR data movement draws from this motivation. Before research data can be accessed and reused, however, it must first be found or discovered. For this purpose, the large space of highly diverse research data must be conquered, it must have a high quality of searchableness. To increase searchableness, we have devised a metadata schema to describe the entire field of bioinformatics by a small set of descriptors. Our metadata schema has been inspired by Dublin Core and aims at replicating its success in the domain of bioinformatics. The schema aims at complementing the many metadata schemes used by bioinformaticians in practice by extracting their common core, yielding to a schema that can be used across bioinformatics subdisciplines. Our minimal schema for bioinformatics metadata is complemented by a Web-based annotation tool where such metadata can be provided in an effective, time-saving, and concise manner.
Limits on the Primordial Black Holes Dark Matter with current and future missions
2024-04-17

In this proceeding we consider primordial black holes (PBHs) as a dark matter candidate. We discuss the existing limits on the fraction of the dark matter constituting of PBHs as a function of PBHs mass. The discussed limits cover almost all possible mass range with the currently only open window in g in which the PBHs can make up to 100% of the dark matter content of the universe. We present the estimates of the capabilities of the near-future instruments (Einstein Probe/WXT, SVOM/MXT) and discuss the potential of next-generation missions(Athena, THESEUS, eXTP) to probe this mass range. We discuss the targets most suitable for the PBH dark matter searches with these missions and the potential limiting factor of the systematics on the derived results.
PhantomAR: Gamified Mixed Reality System for Alleviating Phantom Limb Pain in Upper Limb Amputees – Design, Implementation, and Clinical Usability Evaluation
2024-04-17

<title>Abstract</title> Background: Phantom limb pain (PLP) is a restrictive condition in which patients perceive pain in a limb that is no longer present, greatly reducing their quality of life. Mirror Therapy, wherein patients observe a mirror reflection of their intact limb, has demonstrated efficacy in alleviating PLP. However, its unilateral and seated nature presents limitations. To address these constraints while still reducing PLP, and evaluating the impact of different virtual limb representations (anthropomorphic vs. non-anthropomorphic) on the user's sense of ownership, agency, and embodiment, PhantomAR was developed. Leveraging wearable first-person augmented reality (AR) technology, PhantomAR extends traditional Mirror Therapy by enabling users to move freely and engage in bimanual tasks. <bold>Methods:</bold> The assistive mixed reality game application PhantomAR was deployed on the Microsoft HoloLens 2 and augmented the user’s residual limb by superimposing a virtual arm or tentacle that was controlled via residual muscles on their stump using an EMG electrode array. This setup allowed patients to engage in a first-person perspective and manipulate virtual objects with both the healthy and augmented limbs, free from the confines of a seated position. The study enrolled 10 able-bodied individuals and 8 individuals with unilateral, transradial amputation. All amputees experienced PLP. The usability of the PhantomAR application was evaluated using the System Usability Scale (SUS) and a user-centric survey. Additionally, the Game Experience was assessed on a 5-point Likert questionnaire (GEQ). Participants rated their phantom sensations using the Numerical Rating Scale and McGill Pain Questionnaire before, during, and after interaction with PhantomAR. The embodiment and agency of the virtual superimposed arm were evaluated with an altered Prosthesis Embodiment Scale. The study protocol included two sessions of 30 minutes each, during which participants experienced PhantomAR. <bold>Results:</bold> Participants (n=18) rated PhantomAR highly usable (SUS m=90.8%, SD=6.88). Feedback on the Game Experience Questionnaire was overwhelmingly positive, showing high immersion (m=4.46, SD=0.08) and positive affect (m=4.97, SD=0.05). PLP (n=8) significantly decreased post-intervention (NRS and McGill Pain Questionnaire, p&lt;.001). Skin temperature in the residual limb increased significantly post-intervention (p&lt;.01) but did not correlate with PLP (r=-0.08, p=0.83). Tentacle overlay yielded mixed ownership but high agency ratings. <bold>Conclusion:</bold> PhantomAR leverages extended reality to significantly reduce Phantom Limb Pain, enhance user engagement, and alter perceptions of ownership and agency of their augmented limb through dynamic, full-body interactions.
Testing General Relativity with Black Hole X-Ray Data and ABHModels
2024-04-17

The past 10 years have seen tremendous progress in our capability of testing General Relativity in the strong field regime with black hole observations. 10 years ago, the theory of General Relativity was almost completely unexplored in the strong field regime. Today, we have gravitational wave data of the coalescence of stellar-mass black holes, radio images of the supermassive black holes SgrA and M87 , and high-quality X-ray data of stellar-mass black holes in X-ray binaries and supermassive black holes in active galactic nuclei. In this manuscript, we will review current efforts to test General Relativity with black hole X-ray data and we will provide a detailed description of the public codes available on ABHModels.
Induction of NK cell reactivity against acute myeloid leukemia by Fc-optimized CD276 (B7-H3) antibody
2024-04-18

Abstract Acute myeloid leukemia (AML) remains a therapeutic challenge despite recent therapeutic advances. Although monoclonal antibodies (mAbs) engaging natural killer (NK) cells via antibody-dependent cellular cytotoxicity (ADCC) hold promise in cancer therapy, almost none have received clinical approval for AML, so far. Recently, CD276 (B7-H3) has emerged as a promising target for AML immunotherapy, due to its high expression on leukemic blasts of AML patients. Here, we present the preclinical development of the Fc-optimized CD276 mAb 8H8_SDIE with enhanced CD16 affinity. We demonstrate that 8H8_SDIE specifically binds to CD276 on AML cell lines and primary AML cells and induces pronounced NK cell activation and degranulation as measured by CD69, CD25, and CD107a. Secretion of IFNγ, TNF, granzyme B, granulysin, and perforin, which mediate NK cell effector functions, was induced by 8H8_SDIE. A pronounced target cell-restricted lysis of AML cell lines and primary AML cells was observed in cytotoxicity assays using 8H8_SDIE. Finally, xenograft models with 8H8_SDIE did not cause off-target immune activation and effectively inhibited leukemia growth in vivo. We here present a novel attractive immunotherapeutic compound that potently induces anti-leukemic NK cell reactivity in vitro and in vivo as treatment option for AML.
Concept and feasibility of the Augsburg Longitudinal Plasma Study (ALPS) – a prospective trial for comprehensive liquid biopsy-based longitudinal monitoring of solid cancer patients
2024-04-18

Abstract Objectives Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution. Methods The Augsburg Longitudinal Plasma Study (ALPS) is a prospective trial for patients with metastatic cancer that comprises sequential collection of LBx samples, tumor tissue, radiological imaging data, clinical information and patient-reported outcomes. Peripheral blood plasma is collected based on the individual patient’s staging intervals and LBx-derived ctDNA analyses are performed using CAncer Personalized Profiling sequencing (CAPP-seq). Results From April 2021 to October 2023, 419 patients have been enrolled. A total of 1,293 LBx samples were collected, 419 samples (100 %) at the beginning of the study and an average of 3 (range 1–12) during the 30-month follow-up period of the current interim analysis. 380 tissue biopsy (TBx) samples (90.7 %) were available at baseline and 39.6 % had ≥1 TBx samples at follow-up. Lung cancer patients are most prevalent in ALPS (n=147), followed by colorectal (n=38), prostate (n=31) and gastroesophageal cancer (n=28). On average, 12.0 ng/mL plasma cell-free DNA (cfDNA) could be isolated. First CAPP-seq analyses in 60 patients comprised 110 samples and demonstrated a detection sensitivity of 0.1 %. Conclusions The first interim analysis of ALPS confirms feasibility for comprehensive longitudinal evaluation of LBx and demonstrates suitability for ctDNA evaluation.
Import tariffs and transport prices
2024-04-18

Abstract This paper discusses how import tariffs interact with transport prices in episodes of trade liberalization. We develop a model of a transport industry that operates under imperfect competition and economies of scale. Double marginalization due to market power reduces the effects of trade liberalization, while a larger trade volume may support them due to economies of scale. We use a large data set of maritime transport data and combine them with tariff data to find that economies of scale beat market power: a decline in the tariff implies a decline in freight rates.
Beyond visual integration: sensitivity of the temporal-parietal junction for objects, places, and faces
2024-04-18

Abstract One important role of the TPJ is the contribution to perception of the global gist in hierarchically organized stimuli where individual elements create a global visual percept. However, the link between clinical findings in simultanagnosia and neuroimaging in healthy subjects is missing for real-world global stimuli, like visual scenes. It is well-known that hierarchical, global stimuli activate TPJ regions and that simultanagnosia patients show deficits during the recognition of hierarchical stimuli and real-world visual scenes. However, the role of the TPJ in real-world scene processing is entirely unexplored. In the present study, we first localized TPJ regions significantly responding to the global gist of hierarchical stimuli and then investigated the responses to visual scenes, as well as single objects and faces as control stimuli. All three stimulus classes evoked significantly positive univariate responses in the previously localized TPJ regions. In a multivariate analysis, we were able to demonstrate that voxel patterns of the TPJ were classified significantly above chance level for all three stimulus classes. These results demonstrate a significant involvement of the TPJ in processing of complex visual stimuli that is not restricted to visual scenes and that the TPJ is sensitive to different classes of visual stimuli with a specific signature of neuronal activations.
Lesions in a songbird vocal circuit increase variability in song syntax
2024-04-18

Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches ( Lonchura striata domestica ). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points , where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases , where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.
Reactivation strength during cued recall is modulated by graph distance within cognitive maps
2024-04-18

Abstract Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8-minute consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic (MEG) recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.
OneFlowTraX: a user-friendly software for super-resolution analysis of single-molecule dynamics and nanoscale organization
2024-04-19

Super-resolution microscopy (SRM) approaches revolutionize cell biology by providing insights into the nanoscale organization and dynamics of macromolecular assemblies and single molecules in living cells. A major hurdle limiting SRM democratization is post-acquisition data analysis which is often complex and time-consuming. Here, we present OneFlowTraX, a user-friendly and open-source software dedicated to the analysis of single-molecule localization microscopy (SMLM) approaches such as single-particle tracking photoactivated localization microscopy (sptPALM). Through an intuitive graphical user interface, OneFlowTraX provides an automated all-in-one solution for single-molecule localization, tracking, as well as mobility and clustering analyses. OneFlowTraX allows the extraction of diffusion and clustering parameters of millions of molecules in a few minutes. Finally, OneFlowTraX greatly simplifies data management following the FAIR (Findable, Accessible, Interoperable, Reusable) principles. We provide a detailed step-by-step manual and guidelines to assess the quality of single-molecule analyses. Applying different fluorophores including mEos3.2, PA-GFP, and PATagRFP, we exemplarily used OneFlowTraX to analyze the dynamics of plant plasma membrane-localized proteins including an aquaporin, the brassinosteroid receptor Brassinosteroid Insensitive 1 (BRI1) and the Receptor-Like Protein 44 (RLP44).