julilili42/papers huggingface dataset:
Anti-inflammatory potential of lactic acid bacteria from southern Brazil by reducing TNF-α and increasing IL-10 synthesis: an in vitro study
2023-08-01

Abstract Aims To evaluate the adhesion capacity and anti-inflammatory activity of lactic acid bacteria (LAB) isolated from raw cow milk and artisan cheese in Southern Brazil, investigating their effect on the release of cytokines such as TNF-α and IL-10 and their influence on the activation of the p38/MAPK pathway. Methods and results Lentilactobacillus parabuchneri ML4, Lacticaseibacillus paracasei ML33, Lactiplantibacillus pentosus ML82, Lactiplantibacillus plantarum CH131, and L. paracasei CH135 demonstrated high adhesion potential in an in vitro model of the intestinal epithelium, as well as anti-inflammatory activity. After a 4-hour treatment, the strains significantly increased TNF-α levels, while a 24-hour treatment led to a significant decrease in TNF-α release. Moreover, IL-10 levels significantly increased after 24-hour and 48-hour treatments with LAB. The inhibition of p38/MAPK phosphorylation was identified as one of the mechanisms by which the L. paracasei ML33 and L. plantarum CH131 strains suppressed the production and release of TNF-α. Conclusions We identified LAB strains with potential anti-inflammatory properties that could adhere to the intestinal mucosa and alleviate the inflammatory response by reducing the production and release of TNF-α through the inhibition of the p38/MAPK pathway, while promoting the production of IL-10.
From Early Bronze Age domestic plant production to Middle Bronze Age regional exchange economy: the archaeobotanical assemblages from Tel Kabri
2023-08-01

Abstract Recent excavations at the site of Tel Kabri have brought some extraordinary findings, including the earliest wine cellar in the ancient Near East discovered in 2013. During these excavations, archaeobotanical samples were collected continuously and then processed in 2019. The archaeobotanical studies focus on the Middle Bronze Age palace in Area DW and the Early Bronze Age domestic deposits in Area L. The results confirm the different nature of the two contexts. Legumes form a large portion of the crop remains in the Early Bronze Age Area L: Lathyrus sativus (grass pea), Vicia faba var. minor (faba bean), and Lens culinaris (lentil), all showing no drought stress and similar growing conditions in terms of moisture availability, as indicated by stable carbon isotope measurements. For Area L, several wild seeds have been identified to represent weeds of cereal crops, whereas Area DW is strongly affected by small wild seeds that entered the sediments as modern contaminants. Fruit crops are present in both assemblages with Olea europaea (olive), representing the most ubiquitous taxon, and Vitis vinifera (grape), with most of its pips found mineralized. The identified remains also include cereal crops, primarily Triticum dicoccum (emmer), which appears cultivated under exceptionally dry conditions. The stable nitrogen values for emmer also raised some questions regarding the growing location and cultivation strategy. Correspondence analysis has been applied, comparing the archaeobotanical assemblages of Tel Kabri within the wider geographical and chronological Levantine context and determining their placement in sub-regional patterns.
Interdependence of plasma membrane nanoscale dynamics of a kinase and its cognate substrate underliesArabidopsisresponse to viral infection
2023-08-01

ABSTRACT Plant viruses represent a risk to agricultural production and as only a few treatments exist, it is urgent to identify resistance mechanisms and factors. In plant immunity, plasma membrane (PM)-localized proteins play an essential role in sensing the extracellular threat presented by bacteria, fungi or herbivores. Viruses are intracellular pathogens and as such the role of the plant PM in detection and resistance against viruses is often overlooked. We investigated the role of the partially PM-bound Calcium-dependent protein kinase 3 (CPK3) in viral infection and we discovered that it displayed a specific ability to hamper viral propagation over CPK isoforms that are involved in immune response to extracellular pathogens. More and more evidence support that the lateral organization of PM proteins and lipids underlies signal transduction in plants. We showed here that CPK3 diffusion in the PM is reduced upon activation as well as upon viral infection and that such immobilization depended on its substrate, Remorin (REM1.2), a scaffold protein. Furthermore, we discovered that the viral infection induced a CPK3-dependent increase of REM1.2 PM diffusion. Such interdependence was also observable regarding viral propagation. This study unveils a complex relationship between a kinase and its substrate that contrasts with the commonly described co-stabilisation upon activation while it proposes a PM-based mechanism involved in decreased sensitivity to viral infection in plants.
Association of ward-level antibiotic consumption with healthcare-associated Clostridioides difficile infections: an ecological study in five German university hospitals, 2017–2019
2023-08-01

Abstract Objectives To analyse the influence of antibiotic consumption on healthcare-associated healthcare onset (HAHO) Clostridioides difficile infection (CDI) in a German university hospital setting. Methods Monthly ward-level antibiotic consumption measured in DDD/100 patient days (pd) and CDI surveillance data from five university hospitals in the period 2017 through 2019 were analysed. Uni- and multivariable analyses were performed with generalized estimating equation models. Results A total of 225 wards with 7347 surveillance months and 4 036 602 pd participated. With 1184 HAHO-CDI cases, there was a median incidence density of 0.17/1000 pd (IQR 0.03–0.43) across all specialties, with substantial differences among specialties. Haematology-oncology wards showed the highest median incidence density (0.67/1000 pd, IQR 0.44–1.01), followed by medical ICUs (0.45/1000 pd, IQR 0.27–0.73) and medical general wards (0.32/1000 pd, IQR 0.18–0.53). Multivariable analysis revealed carbapenem (mostly meropenem) consumption to be the only antibiotic class associated with increased HAHO-CDI incidence density. Each carbapenem DDD/100 pd administered increased the HAHO-CDI incidence density by 1.3% [incidence rate ratio (IRR) 1.013; 95% CI 1.006–1.019]. Specialty-specific analyses showed this influence only to be valid for haematological-oncological wards. Overall, factors like ward specialty (e.g. haematology-oncology ward IRR 2.961, 95% CI 2.203–3.980) or other CDI cases on ward had a stronger influence on HAHO-CDI incidence density (e.g. community-associated CDI or unknown association case in same month IRR 1.476, 95% CI 1.242–1.755) than antibiotic consumption. Conclusions In the German university hospital setting, monthly ward-level carbapenem consumption seems to increase the HAHO-CDI incidence density predominantly on haematological-oncological wards. Furthermore, other patient-specific factors seem to be equally important to control HAHO-CDI.
Seasonal variation in the diurnal activity pattern of Eurasian blackbirds (Turdus merula) in the forest
2023-08-01

Abstract Camera traps are increasingly used to estimate the density of animals as well as their activity patterns. As camera traps allow monitoring of animals over long periods of time without disturbance, they are especially useful to observe changes in diurnal activity patterns over time. In ornithology, camera trapping is still in its infancy. To our knowledge, no study has yet investigated the activity pattern of a songbird over the full annual cycle. We used camera traps in the Rammert, a small mountainous forest area near Rottenburg in Southwest Germany to monitor the diurnal activity pattern of forest-dwelling Eurasian blackbirds ( Turdus merula ). As the activity level of animals is known to be affected by day light, we used double-anchoring transformation of day times to account for the variation in sunrise and sunset across the different seasons. By generating activity models, we investigated the pattern of blackbird activity during the four seasons of the year and compared the patterns of male and female birds, respectively. A significant difference between a unimodal activity pattern in spring and a bimodal pattern for the rest of the year was found which might be related to breeding and territorial behaviour in spring. Moreover, we observed that the activity pattern of males and females overlapped greatly but still showed some variation in the number and timing of density peaks.
Comparison of the visual discharge properties of primate superior colliculus and primary visual cortex neurons
2023-08-01

The primate superior colliculus (SC) receives substantial cortical visual inputs, including from the primary visual cortex (V1). However, there is currently no detailed neurophysiological comparison of visual response properties in the SC and V1. Here, we recorded from 107 V1 neurons and 70 SC neurons in one male rhesus macaque monkey. Of these, 107 V1 and 52 SC neurons were recorded simultaneously. The V1 neurons were all from the lower visual field representation (~6-10 deg eccentricity); some SC neurons (18) were from the upper visual field representation, but the rest were matched in visual response field (RF) location with the V1 recordings. Behaviorally, the monkey fixated, and we presented gabor gratings of various spatial frequencies and orientations for 300 ms over a gray background. The gratings were sized to approximately fill the SC visual RF’s, which we mapped (along with the V1 RF’s) using an earlier behavioral task. RF mapping was performed using small white spots appearing over a gray background during fixation. V1 neurons had significantly smaller RF sizes than SC neurons. V1 neurons also responded to stimulus onsets consistently earlier than simultaneously recorded SC neurons, and V1 neurons exhibited offset responses (at stimulus removal at the end of a trial) more robustly than SC neurons. SC neurons, on the other hand, had higher baseline activity. In terms of feature tuning, SC orientation tuning widths were significantly bigger than in V1, suggesting weaker orientation selectivity. Spatial frequency tuning widths were more similar, but SC neurons preferred lower spatial frequencies in general. Interestingly, coarse-to-fine processing, evidenced by the temporal profile of responses to different spatial frequencies, was substantially more prominent in the SC. These results demonstrate that the SC does not merely inherit V1 response properties, but is functionally specialized, perhaps to best exploit its proximity to the motor periphery.
Investigating Fatigue and Its Relationship to Quality of Life and Pruritus in Cutaneous T-Cell Lymphoma
2023-08-01

Cancer-related fatigue as a morbid state of physical, emotional, and mental exhaustion influencing everyday life is an important yet poorly investigated symptom in patients with cutaneous T-cell lymphomas. The aim of this study was to evaluate the prevalence of and the association between pruritus, quality of life, and fatigue in patients with cutaneous T-cell lymphomas. Mycosis fungoides and Sézary syndrome patients were invited to complete the Functional Assessment of Cancer Therapy-General (FACT-G) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) subscale questionnaire. Pruritus was assessed using the peak pruritus numeric rating scale. Half of the 38 recruited patients reported fatigue. 13 patients (34%) suffered from severe fatigue. The median (interquartile range) FACIT-Fatigue subscale score was 35.5 (25.75–43). The advanced disease stage was associated with more severe fatigue and a poorer quality of life. The FACIT-Fatigue subscale score was significantly correlated with quality of life (r = 0.8 and <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>P</a:mi> </a:math> &lt; 0.0001). More than 80% of patients reported pruritus. There was no correlation between pruritus and fatigue (r = −0.19 and <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> </c:math> = 0.26). All in all, fatigue is a common symptom of cutaneous T-cell lymphomas in early and advanced stage disease and has a strongly negative effect on cutaneous T-cell lymphoma patients’ quality of life.
FusionVAC22_01: A phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion
2023-08-01

The DNAJB1-PRKACA fusion transcript was identified as the oncogenic driver of tumor pathogenesis in fibrolamellar hepatocellular carcinoma (FL-HCC) as well as in other tumor entities, comprising oncocytic neoplasms of pancreas and bile duct, thus representing a broad target for novel treatment in multiple cancer entities. In preclinical work, we showed that the DNAJB1-PRKACA fusion protein is a source for naturally presented immunogenic neoepitopes and can be actively targeted by T-cell-based immunotherapy (Bauer et al. Nat. Commun., 2022). The DNAJB1-PRKACA fusion-derived neoepitope FusionVAC-22 is a 22mer peptide in silico predicted to bind to 1,290 different HLA class II alleles that contains 13 embedded HLA class I alleles that cover 96.6% and 93.8% of the European and world population with at least one HLA allotype, respectively. Application of FusionVAC-22-based peptide vaccines, adjuvanted with the TLR1/2 agonist XS15 and Montanide ISA51 VG, in two FL-HCC patients was well tolerated without systemic side effects and an induction of a T-cell response six weeks after the second vaccination was observed in both patients. In the first patient specific T cells persisted in peripheral blood and were accompanied by relapse-free survival of the patient until now 27 months post vaccination (Bauer et al. Nat. Commun., 2022). The second patient with metastasized disease was treated in combination with an Immune Checkpoint Inhibitor (ICI). Of note, increased side effects at vaccination site as well as immune related events were not observed in this patient. Most importantly, until now the second patient showed stable disease for 8 months after vaccination. Based on these promising data, we established a Phase I open label, multicentric clinical trial (EU-CT Number 2022-502869-17-00) evaluating the immunogenicity along with safety and toxicity, as well as first signs of efficacy of the FusionVAC-22 based peptide vaccine, combined with an ICI (anti-PD-L1), in 20 patients with locally advanced or metastatic FL-HCC or other malignant disease with proven presence of the DNAJB1-PRKACA fusion transcript.
Prospects for annihilating dark matter from M31 and M33 observations with the Cherenkov Telescope Array
2023-08-01

Abstract M31 and M33 are the closest spiral galaxies and the largest members (together with the Milky Way) of the Local group, which makes them interesting targets for indirect dark matter searches. In this paper we present studies of the expected sensitivity of the Cherenkov Telescope Array (CTA) to an annihilation signal from weakly interacting massive particles from M31 and M33. We show that a 100 h long observation campaign will allow CTA to probe annihilation cross-sections up to 〈 συ 〉 ≈ 5·10 -25 cm 3 s -1 for the τ + τ - annihilation channel (for M31, at a DM mass of 0.3 TeV), improving the current limits derived by HAWC by up to an order of magnitude. We present an estimate of the expected CTA sensitivity, by also taking into account the contributions of the astrophysical background and other possible sources of systematic uncertainty. We also show that CTA might be able to detect the extended emission from the bulge of M31, detected at lower energies by the Fermi /LAT.
Diffusion coefficients of linear trimer particles
2023-08-01

We study the diffusive behavior of linear trimer particles via numerical calculations. First, we utilize hydrodynamic bead-shell calculations to compute the microscopic diffusion coefficients for different particle aspect ratios. These values are then used to obtain continuous empirical formulas for said coefficients. As an application example for the empirical formulas, we perform Brownian dynamics simulations of monolayers consisting of a linear trimer surrounded by colloidal spheres. Here, we obtain empirical formulas for the corresponding long-time diffusion coefficients of the trimer. By comparing our data for the microscopic and long-time diffusion coefficients with known results for spherocylinders, we find that the diffusive behavior of both particle geometries is approximately identical. Based on this observation, we introduce simplified equations for the microscopic diffusion coefficients that can be used for arbitrary short rods that are spheres at the minimum aspect ratios. The calculated equations for the diffusion coefficients can be applied to various further numerical and experimental studies utilizing linear trimer particles.
Extreme mass-ratio inspirals into black holes surrounded by scalar clouds
2023-08-01

We study extreme mass-ratio binary systems in which a stellar mass compact object spirals into a supermassive black hole surrounded by a scalar cloud. Scalar clouds can form through superradiant instabilities of massive scalar fields around spinning black holes and can also serve as a proxy for dark matter halos. Our framework is fully relativistic and assumes that the impact of the cloud on the geometry can be treated perturbatively. As a proof of concept, here we consider a point particle in circular, equatorial motion around a non-spinning black hole surrounded either by a spherically symmetric or a dipolar non-axisymmetric scalar cloud, but the framework can in principle be generalized to generic black hole spins and scalar cloud geometries. We compute the leading-order power lost by the point particle due to scalar radiation and show that, in some regimes, it can dominate over gravitational-wave emission. We confirm the presence of striking signatures due to the presence of a scalar cloud that had been predicted using Newtonian approximations, such as resonances that can give rise to sinking and floating orbits, as well as "sharp features" in the power lost by the particle at given orbital radii. Finally, for a spherically symmetric scalar cloud, we also compute the leading-order corrections to the black-hole geometry and to the gravitational-wave energy flux, focusing only on axial metric perturbations for the latter. We find that, for non-compact clouds, the corrections to the (axial) gravitational-wave fluxes at high frequencies can be understood in terms of a gravitational-redshift effect, in agreement with previous works.
P780: G-CSF THERAPY IN EUROPEAN PATIENTS WITH SHWACHMAN-DIAMOND SYNDROME
2023-08-01

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Shwachman- Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure (BMF), exocrine pancreatic dysfunction, and a varying degree of congenital abnormalities including the skeleton, liver, heart and immune system. Neutropenia is the most common hematological finding. SDS patients have a predisposition to myeloid malignancies and an increased risk for severe cytopenias. G-CSF therapy in SDS patients has always been discussed controversially. Parents and doctors are afraid to induce secondary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in SDS patients by G-CSF treatment. Aims: Here we report on the safety and effectiveness of G-CSF therapy in our cohort of SDS patients. Methods: We have analyzed data on 176 European patients with the clinical diagnosis of Shwachman- Diamond Syndrome (SDS) collected by Severe Chronic Neutropenia International Registry (SCNIR). Results: Patient characteristics: 176 SDS patients (85 female, 91 male) with a median age at last follow up of 9.59 years (range 0.95 – 45.54 years). 141 patients are alive, 11 patients are expired, 23 patients are lost to follow-up. Causes of death were MDS/AML (n=4), transplant related mortality (n=5), infection (n=2). The median age at clinical SDS diagnosis is 1.75 years (range 0 -23.62 years). Mutations in the SBDS gene were detected in 90% of patients with the majority of patients (67%) harboring the common compound heterozygous mutations 258 + 2T>C + 183_184TA>CT. Overall, G-CSF therapy was given to 62 of 176 of patients (35%) either short term (< 1year), long term (>1 year) or only interventional (e.g. during infections). Complete data on G-CSF therapy and course of CBCs before and on therapy was available in 121 patients. Therefore, our analysis focusses on this cohort of 121 patients. In the first reported CBC 88 patients showed neutropenia with an absolute neutrophil count (ANC) below 1500/μl. 39 of 121 received G-CSF therapy: interventional in 2, less than 1 year in 8 and long term (>1 year) in 25 patients. The duration was not reported in 4 patients. In the long-term G-CSF group the median age at start of therapy was 2.45 years (0.05 - 21.97 years) with a median dose of 2.0 μg/kg/day (0.3-5 μg/kg/day) and a median duration of 2.7 years (1.00- 13.6 years). All patients showed an increase in the ANC with the initiation of therapy. No patient was reported to be a non-responder to G-CSF therapy. In the cohort of 121 SDS patients 11 patients were reported to develop MDS/AML. Only 2 patients were on long term G-CSF therapy at the time of MDS/AML diagnosis. Summary/Conclusion: Only a third of SDS patients received G-CSF therapy despite more patients being neutropenic. All patients treated had a good response to G-CSF therapy with an increase in their ANCs Only small daily doses were needed to reach this goal. The majority of SDS patients who developed MDS/AML were not on G-CSF therapy at the time of MDS/AML diagnosis. Keywords: G-CSF, Neutropenia, Bone marrow failure
Reply to the comment on ‘Limitations in evaluating COVID-19 protective face masks using open circuit spirometry systems: respiratory measurement mask introduces bias in breathing pressure and perceived respiratory effort’
2023-08-01

Abstract Marek and colleagues have written a commentary on our paper (Seibt et al 2023) in which they point out some methodological inconsistencies and flaws. In our response, we first address the objective of our study so that the specific responses to Marek’s criticism are placed in the proper context. In Seibt et al (2023) we investigated whether additional respiratory measurement masks used to evaluate protective face masks influence the outcomes. The physiological effect of protective masks was not the target in our study, neither at rest nor during exercise. Subsequently, we address the criticisms of Marek et al point by point. With our study and this detailed response to Marek et al (2023)), we hope to support researchers in choosing the adequate methodological approach for evaluating the effects of protective face masks on human physiology.
A Structurally Flexible Halide Solid Electrolyte with High Ionic Conductivity and Air Processability (Adv. Energy Mater. 30/2023)
2023-08-01

All-Solid-State Batteries In article number 2300982, Guruprakash Karkera, Maximilian Fichtner, and co-workers report high ionic mobility in cesium tin chloride perovskites, highlighting their application as solid electrolytes in all-solid-state batteries. The vacancy mediated ionic conduction (depicted in the cover image) is facilitated by flexible structural building blocks, Sn/InCl6 octahedra, which contribute to significant air-humidity tolerance, structural revivability of the material, in-demand properties for commercialization of all-solid-state batteries.