julilili42/papers huggingface dataset:
A potential dissociation between perception and production version for bounded but not unbounded number line estimation
2023-04-16

These results substantiate that the production version of bounded NLE seems to rely on proportion judgment strategies, whereas both unbounded versions and the perception version of the bounded NLE task may rely more on magnitude estimation.
Gravitational-wave imprints of compact and galactic-scale environments in extreme-mass-ratio binaries
2023-04-17

Circumambient and galactic-scale environments are intermittently present around black holes, especially those residing in active galactic nuclei. As supermassive black holes impart energy on their host galaxy, so the galactic environment affects the geodesic dynamics of solar-mass objects around supermassive black holes and subsequently the gravitational waves emitted from such nonvacuum extreme-mass-ratio binaries. Only recently an exact general-relativistic solution has been found that describes a Schwarzschild black hole immersed in a dark matter halo profile of the Hernquist type. We perform an extensive analysis generic geodesics delving in such nonvacuum spacetimes and compare our results with those obtained in vacuum Schwarzschild spacetime, as well as calculate their dominant gravitational-wave emission. Our findings indicate that the radial and polar oscillation frequency ratios, which designate resonances, descend deeper into the extreme gravity regime as the compactness of the halo increases. This translates to a gravitational redshift of nonvacuum geodesics and their resulting waveforms with respect to the vacuum ones; a phenomenon that has also been observed for ringdown signals in these setups. We calculate the maximized overlap between waveforms resulting from orbital evolutions around Schwarzschild and nonvacuum geometries and find that it decreases as the halo compactness grows, meaning that dark matter environments should be distinguishable by space-borne gravitational-wave detectors. For compact environments, we find that the apsidal precession of orbits is strongly affected due to the gravitational pull of dark matter; the orbit's axis can rotate in the opposite direction as that of the orbital motion, leading to a retrograde precession drift that depends on the halo's mass, as opposed to the typical prograde precession transpiring in vacuum and galactic-scale environments. Gravitational waves in retrograde-to-prograde orbital alterations demonstrate transient frequency phenomena around a critical nonprecessing turning point, thus they may serve as a "smoking gun" for the presence of dense dark matter environments around supermassive black holes.
Here, There, and Everywhere: Myeloid-Derived Suppressor Cells in Immunology
2023-04-17

Abstract Myeloid-derived suppressor cells (MDSCs) were initially identified in humans and mice with cancer where they profoundly suppress T cell– and NK cell–mediated antitumor immunity. Inflammation is a central feature of many pathologies and normal physiological conditions and is the dominant driving force for the accumulation and function of MDSCs. Therefore, MDSCs are present in conditions where inflammation is present. Although MDSCs are detrimental in cancer and conditions where cellular immunity is desirable, they are beneficial in settings where cellular immunity is hyperactive. Because MDSCs can be generated ex vivo, they are being exploited as therapeutic agents to reduce damaging cellular immunity. In this review, we discuss the detrimental and beneficial roles of MDSCs in disease settings such as bacterial, viral, and parasitic infections, sepsis, obesity, trauma, stress, autoimmunity, transplantation and graft-versus-host disease, and normal physiological settings, including pregnancy and neonates as well as aging. The impact of MDSCs on vaccination is also discussed.
4’-Fluorouridine mitigates lethal infection with pandemic human and highly pathogenic avian influenza viruses
2023-04-17

Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4’-Fluorouridine (4’-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium (HAE) models, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4’-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar to sub-micromolar potency in HAE cells. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4’-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4’-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1)pdm09 (pdmCa09) with 4’-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating a broad time window for effective intervention. Therapeutic oral 4’-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pdmCa09. Recoverees were protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4’-FlU and supports 4’-FlU as developmental candidate for the treatment of seasonal and pandemic influenza.
Second‐line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR)
2023-04-17

Abstract Background Outcome of relapsed disease of localized rhabdomyosarcoma remains poor. An individual treatment approach considering the initial systemic treatment and risk group was included in the Cooperative Weichteilsarkom Studiengruppe (CWS) Guidance. Methods Second‐line chemotherapy (sCHT) ACCTTIVE based on anthracyclines (adriamycin, carboplatin, cyclophosphamide, topotecan, vincristine, etoposide) was recommended for patients with initial low‐ (LR), standard‐ (SR), and high‐risk (HR) group after initial treatment without anthracyclines. TECC (topotecan, etoposide, carboplatin, cyclophosphamide) was recommended after initial anthracycline‐based regimen in the very high‐risk (VHR) group. Data of patients with relapse ( n = 68) registered in the European Soft Tissue Sarcoma Registry SoTiSaR (2009–2018) were retrospectively analyzed. Results Patients of initial LR ( n = 2), SR ( n = 16), HR ( n = 41), and VHR ( n = 9) group relapsed. sCHT consisted of ACCTTIVE ( n = 36), TECC ( n = 12), or other ( n = 15). Resection was performed in 40/68 (59%) patients and/or radiotherapy in 47/68 (69%). Initial risk stratification, pattern/time to relapse, and achievement of second complete remission were significant prognostic factors. Microscopically incomplete resection with additional radiotherapy was not inferior to microscopically complete resection ( p = .17). The 5‐year event‐free survival (EFS) and overall survival (OS) were 26% (±12%) and 31% (±14%). The 5‐year OS of patients with relapse of SR, HR, and VHR groups was 80% (±21%), 20% (±16%), and 13% (±23%, p = .008), respectively. Conclusion Adapted systemic treatment of relapsed disease considering the initial risk group and initial treatment is reasonable. New treatment options are needed for patients of initial HR and VHR groups.
Temporal attention
2023-04-17

Attention, that is, the ability to focus processing resources on a specific part of sensory input, is often thought of as being mainly allocated in space, toward specific objects or modalities. However, attention can also be allocated within time. Temporal attention can be induced implicitly, that is, through learning of temporal regularities between at least two events, or explicitly, by the active instruction to attend to a specific time point. Moreover, temporal attention can be induced via external rhythmic stimulation. Many studies throughout the last 120 years have shown that, irrespective of the way temporal attention is induced, it facilitates processing of upcoming events. Based on early findings measuring reaction time, researchers initially assumed that temporal attention primarily accelerates motor processing. Within the last 20 years, however, more and more evidence has emerged supporting the view that temporal attention facilitates perceptual processing. Moreover, temporal attention may even interact with other attentional domains such as spatial attention or feature-based attention. In the present article, we summarize classical as well as current findings and theoretical accounts on how temporal attention affects perceptual processing. Furthermore, we sketch current challenges and open questions in research on temporal attention.
Structural-Functional Correlates of Response to Pedunculopontine Stimulation in a Randomized Clinical Trial for Axial Symptoms of Parkinson’s Disease
2023-04-17

Background: Axial symptoms of Parkinson’s disease (PD) can be debilitating and are often refractory to conventional therapies such as dopamine replacement therapy and deep brain stimulation (DBS) of the subthalamic nuclei (STN). Objective: Evaluate the efficacy of bilateral DBS of the pedunculopontine nucleus area (PPNa) and investigate structural and physiological correlates of clinical response. Methods: A randomized, double-blind, cross-over clinical trial was employed to evaluate the efficacy of bilateral PPNa-DBS on axial symptoms. Lead positions and neuronal activity were evaluated with respect to clinical response. Connectomic cortical activation profiles were generated based on the volumes of tissue activated. Results: PPNa-DBS modestly improved ( p = 0.057) axial symptoms in the medication-off condition, with greatest positive effects on gait symptoms ( p = 0.027). Electrode placements towards the anterior commissure (ρ= 0.912; p = 0.011) or foramen caecum (ρ= 0.853; p = 0.031), near the 50% mark of the ponto-mesencephalic junction, yielded better therapeutic responses. Recording trajectories of patients with better therapeutic responses (i.e., more anterior electrode placements) had neurons with lower firing-rates ( p = 0.003) and higher burst indexes ( p = 0.007). Structural connectomic profiles implicated activation of fibers of the posterior parietal lobule which is involved in orienting behavior and locomotion. Conclusion: Bilateral PPNa-DBS influenced gait symptoms in patients with PD. Anatomical and physiological information may aid in localization of a favorable stimulation target.
ON and OFF receptive field processing in the presence of optical scattering
2023-04-17

The balance of ON/OFF pathway activation in the retina plays a role in emmetropization. A new myopia control lens design uses contrast reduction to down-regulate a hypothesized enhanced ON contrast sensitivity in myopes. The study thus examined ON/OFF receptive field processing in myopes and non-myopes and the impact of contrast reduction. A psychophysical approach was used to measure the combined retinal-cortical output in the form of low-level ON and OFF contrast sensitivity with and without contrast reduction in 22 participants. ON responses were lower than OFF responses (ON 1.25 ± 0.03 vs. OFF 1.39 ± 0.03 log(CS); p &lt; 0.0001) and myopes showed generally reduced sensitivities (myopes 1.25 ± 0.05 vs. non-myopes 1.39 ± 0.05 log(CS); p = 0.05). These findings remained unaffected by contrast reduction (p &gt; 0.05). The study suggests that perceptual differences in ON and OFF signal processing between myopes and non-myopes exist but cannot explain how contrast reduction can inhibit myopia development.
Reduce methane emission from rice paddies by man-made aerenchymatous tissues
2023-04-17

Abstract Methane is the second most important greenhouse gas after carbon dioxide, and 8–11% is emitted from paddy fields. Methanogenic microbial processes in water-saturated soils can be alleviated through the oxygenation of soils, which may hamper methane production and emissions in paddies. Here, by mimicking O 2 release from rice roots, we report the use of man-made (i.e., silicone tube-based) aerenchymatous tissues (MAT) to continuously release O 2 to abate methane emission from paddies. High O 2 -releasing rates (such as 5 kg O 2 /ha/d) can be easily achieved by adjusting MAT density (e.g., 0.2 m 2 tube/m 2 soil) and its inner air pressure (e.g., 25 kPa). Following deployment, MAT significantly increased soil redox potential (from -150 mV to -88.6 mV) and induced active iron redox cycling. This decreased the availability of organic substrates of methanogens and therefore dramatically reduced their abundance (-25.1% active mcrA gene). We quantified the decrease in methane emission both in mesocosms and paddy field trials and found in both setups that ~ 50% of methane emission was reduced. Moreover, we showed that the performance of MAT can be further improved by simply increasing the air pressure in MAT (e.g., -74.2% methane emission at 200 kPa air pressure). This work provides a powerful and sustainable method for mitigating methane emission from rice paddies. Graphical Abstract
Characterization of Potent ABCG2 Inhibitor Derived from Chromone: From the Mechanism of Inhibition to Human Extracellular Vesicles for Drug Delivery
2023-04-17

Inhibition of ABC transporters is a promising approach to overcome multidrug resistance in cancer. Herein, we report the characterization of a potent ABCG2 inhibitor, namely, chromone 4a (C4a). Molecular docking and in vitro assays using ABCG2 and P-glycoprotein (P-gp) expressing membrane vesicles of insect cells revealed that C4a interacts with both transporters, while showing selectivity toward ABCG2 using cell-based transport assays. C4a inhibited the ABCG2-mediated efflux of different substrates and molecular dynamic simulations demonstrated that C4a binds in the Ko143-binding pocket. Liposomes and extracellular vesicles (EVs) of Giardia intestinalis and human blood were used to successfully bypass the poor water solubility and delivery of C4a as assessed by inhibition of the ABCG2 function. Human blood EVs also promoted delivery of the well-known P-gp inhibitor, elacridar. Here, for the first time, we demonstrated the potential use of plasma circulating EVs for drug delivery of hydrophobic drugs targeting membrane proteins.
Isotopic niche modelling of the Pondaung mammal fauna (middle Eocene, Myanmar) shows microhabitat differences. Insights into paleoecology and early anthropoid primate habitats
2023-04-17

The late Middle Eocene Pondaung Fm. is a window to understand the environment and ecosystem dynamics of a past greenhouse world and the paleoenvironments where modern mammal clades such as anthropoid primates originated. Previous studies focused on the overall climate and vegetation of this Eocene habitat and provided first evidence for an early monsoon onset before the orogenesis of the Himalayan-Tibetan range. Here, we wanted to investigate how the mammal fauna used this habitat and which different ecological niches and microhabitats they occupied. We analyzed the carbonate fraction of dental enamel of a fossil mammal assemblage from various localities of the Pondaung Fm. in Myanmar. Bayesian niche modelling of the δ 13 C and δ 18 O values allowed us to quantify aspects of the ecological core niches occupied by these taxa, to calculate niche overlap and to use these data to infer directional competition potential in this mammal assemblage. Furthermore, comparison of different areas of the Pondaung Fm. revealed two different microhabitats whose distribution is consistent with existing vegetation models. Most primate taxa were found in both described environments, which gives a first indication about their ecological flexibility.
Tissue-based absolute quantification using large-scale TMT and LFQ experiments
2023-04-17

Relative and absolute intensity-based protein quantification across cell lines, tissue atlases, and tumour datasets is increasingly available in public datasets. These atlases enable researchers to explore fundamental biological questions, such as protein existence, expression location, quantity, and correlation with RNA expression. Most studies provide MS1 feature-based label-free quantitative (LFQ) datasets; however, growing numbers of isobaric tandem mass tags (TMT) datasets remain unexplored. Here, we compare traditional intensity-based absolute quantification (iBAQ) proteome abundance ranking to an analogous method using reporter ion proteome abundance ranking with data from an experiment where LFQ and TMT were measured on the same samples. This new TMT method substitutes reporter ion intensities for MS1 feature intensities in the iBAQ framework. Additionally, we compared LFQ-iBAQ values to TMT-iBAQ values from two independent large-scale tissue atlas datasets (one LFQ and one TMT) using robust bottom-up proteomic identification, normalisation, and quantitation workflows.
Predictability Associated With Reduction in Phonetic Signals Without Semantics—The Case of Glossolalia
2023-04-17

Glossolalia can be regarded as an instance of speech production in which practitioners produce syllables in seemingly random sequences. However, a closer inspection of glossalalia’s statistical properties reveals that sequences show a Zipfian pattern similar to natural languages, with some syllables being more probable than others. It is well established that statistical properties of sequences are implicitly learned, and that these statistical properties correlate with changes in kinematic and speech behavior. For speech, this means that more predictable items are phonetically shorter. Accordingly, we hypothesized for glossolalia that if practitioners have learned a serial pattern in glossolalia in the same manner as in natural languages, its statistical properties should correlate with its phonetic characteristics. Our hypothesis was supported. We find significantly shorter syllables associated with higher syllable probabilities in glossolalia. We discuss this finding in relation to theories about the sources of probability-related changes in the speech signal.
Gene augmentation of LCA5-associated Leber congenital amaurosis ameliorates bulge region defects of the photoreceptor ciliary axoneme
2023-04-18

Leber congenital amaurosis (LCA) is a group of inherited retinal diseases characterized by early-onset, rapid loss of photoreceptor cells. Despite the discovery of a growing number of genes associated with this disease, the molecular mechanisms of photoreceptor cell degeneration of most LCA subtypes remain poorly understood. Here, using retina-specific affinity proteomics combined with ultrastructure expansion microscopy, we reveal the structural and molecular defects underlying LCA type 5 (LCA5) with nanoscale resolution. We show that LCA5-encoded lebercilin, together with retinitis pigmentosa 1 protein (RP1) and the intraflagellar transport (IFT) proteins IFT81 and IFT88, localized at the bulge region of the photoreceptor outer segment (OS), a region crucial for OS membrane disc formation. Next, we demonstrate that mutant mice deficient in lebercilin exhibited early axonemal defects at the bulge region and the distal OS, accompanied by reduced levels of RP1 and IFT proteins, affecting membrane disc formation and presumably leading to photoreceptor death. Finally, adeno-associated virus-based LCA5 gene augmentation partially restored the bulge region, preserved OS axoneme structure and membrane disc formation, and resulted in photoreceptor cell survival. Our approach thus provides a next level of assessment of retinal (gene) therapy efficacy at the molecular level.
Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts
2023-04-18

Abstract INTRODUCTION It remains unclear whether functional brain networks are consistently altered in individuals with subjective cognitive decline (SCD) of diverse ethnic and cultural backgrounds and whether the network alterations are associated with an amyloid burden. METHODS Cross‐sectional resting‐state functional magnetic resonance imaging connectivity (FC) and amyloid‐positron emission tomography (PET) data from the Chinese Sino Longitudinal Study on Cognitive Decline and German DZNE Longitudinal Cognitive Impairment and Dementia cohorts were analyzed. RESULTS Limbic FC, particularly hippocampal connectivity with right insula, was consistently higher in SCD than in controls, and correlated with SCD‐plus features. Smaller SCD subcohorts with PET showed inconsistent amyloid positivity rates and FC–amyloid associations across cohorts. DISCUSSION Our results suggest an early adaptation of the limbic network in SCD, which may reflect increased awareness of cognitive decline, irrespective of amyloid pathology. Different amyloid positivity rates may indicate a heterogeneous underlying etiology in Eastern and Western SCD cohorts when applying current research criteria. Future studies should identify culture‐specific features to enrich preclinical Alzheimer's disease in non‐Western populations. Highlights Common limbic hyperconnectivity across Chinese and German subjective cognitive decline (SCD) cohorts was observed. Limbic hyperconnectivity may reflect awareness of cognition, irrespective of amyloid load. Further cross‐cultural harmonization of SCD regarding Alzheimer's disease pathology is required.