bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical investigation on the role of ZnTe back surface layer in an efficient CuInS2 thin film solar cell
Authors: Rana Mohammad Masud , Abir Ahnaf Tahmid , Nushin Syeda Samiha , Hossain Jaker
Published: October 2023

This paper presents the modeling and numerical inspection of an efficient CuInS2-based n-CdS/p-CuInS2/p+-ZnTe thin film solar cell applying the SCAPS-1D simulator. The various parameters used in the simulation have been obtained from existing literature. The optimization of the device has considered the width, doping concentration, and defect density of individual layer. The optimized standalone CuInS2 device shows an efficiency of 16.83%. Addition of ZnTe in the device gives an impressive efficiency of approximately 28.67%, having a current density, JSC of 25.58 mA cm−2, a VOC of 1.25 V, and an FF of 89.12%. The superior VOC is a result of the increased built-in potential formed at the hetero-interfaces of the device and the decrease in surface recombination velocity by back surface field effect in the ZnTe layer. The highest JSC is ascribed to the enhancement of the absorption of vis-infrared photons by back surface field (BSF) effect in the ZnTe layer. These findings demonstrate the potential for manufacturing high efficiency CuInS2-based thin film solar cells in the future.
Large fitness benefits of social nesting in a small carpenter bee
Authors: Mikát Michael , Rehan Sandra M
Published: October 2023

Facultatively social insects are an optimal model group for the study of the emergence of cooperation between individuals. Factors influencing the fitness benefits of social nesting are still debated. Nonreproductive subordinates can benefit from indirect fitness benefits due to increasing reproductive success of related individuals or direct fitness benefits due to direct future reproduction. Here, we studied the costs and benefits of social nesting in the small carpenter bee Ceratina albosticta. From demographic data and within-nest relatedness, we obtained key parameters for assessing the fitness of solitary females, social primaries, and social secondaries. C. albosticta were found to usually mate with one male and multiple mating is not common although exists at low frequencies. Social nests usually contain two females, which were found to be related (full sisters), but also some females were unrelated to each other. Patterns of parentage from microsatellite loci revealed that only one female reproduces in social nests. Our results show that relatedness, per capita brood productivity, and offspring survival strongly increase the fitness benefits of social nesting strategies. Social secondaries, when related to the social primaries, have higher inclusive fitness than solitary females, but unrelated social nesting females had no indirect fitness and much reduced inclusive fitness compared to solitary females. Interestingly, average fitness benefits of the social secondary were higher than solitary females. This study provides important empirical data on the costs and benefits of sociality in a facultatively social bee and sets the stage for future comparative studies.
HetDDI: a pre-trained heterogeneous graph neural network model for drug–drug interaction prediction
Authors: Li Zhe , Tu Xinyi , Chen Yuping , Lin Wenbin
Published: October 2023

The simultaneous use of two or more drugs due to multi-disease comorbidity continues to increase, which may cause adverse reactions between drugs that seriously threaten public health. Therefore, the prediction of drug–drug interaction (DDI) has become a hot topic not only in clinics but also in bioinformatics. In this study, we propose a novel pre-trained heterogeneous graph neural network (HGNN) model named HetDDI, which aggregates the structural information in drug molecule graphs and rich semantic information in biomedical knowledge graph to predict DDIs. In HetDDI, we first initialize the parameters of the model with different pre-training methods. Then we apply the pre-trained HGNN to learn the feature representation of drugs from multi-source heterogeneous information, which can more effectively utilize drugs’ internal structure and abundant external biomedical knowledge, thus leading to better DDI prediction. We evaluate our model on three DDI prediction tasks (binary-class, multi-class and multi-label) with three datasets and further assess its performance on three scenarios (S1, S2 and S3). The results show that the accuracy of HetDDI can achieve 98.82% in the binary-class task, 98.13% in the multi-class task and 96.66% in the multi-label one on S1, which outperforms the state-of-the-art methods by at least 2%. On S2 and S3, our method also achieves exciting performance. Furthermore, the case studies confirm that our model performs well in predicting unknown DDIs. Source codes are available at https://github.com/LinsLab/HetDDI.
Risk Factors Contributing to Crossing Professional Boundaries in the Context of COVID-19 in the Czech Republic
Authors: Dimmrothová Romana , Křivánková Martina , Navrátil Pavel , Hendrychová Vanda
Published: October 2023

Crossing professional boundaries in the context of Czech social work remains an understudied phenomenon. Additionally, the recent situation caused by the COVID-19 pandemic dramatically affected work conditions and transformed social work practice. The aim of this article is to answer the following research question: How do subjectively experienced risk factors affect the social worker in situations when professional boundaries are crossed and in the context of a pandemic situation (COVID-19)? The text is based on the theory of professional boundaries in the client–worker relationship and also includes the perspective of professional boundary crossing in social work. The key conceptual framework is ecosystem theory qualitative research carried out in two phases via in-depth semi-structured interviews in the selected locality. Each phase included informers who were active as social workers in low-threshold centres for children and youth. The text is a reflection of the influence of external factors on professional boundaries and of the internal dispositions of social workers, on the basis of which the text offers practical recommendations for social work practice in three categories: social workers at the individual level, leadership and organisations, educational institutions.
Executive Summary: Periprosthetic Joint Infection—Current Clinical Challenges
Authors: Nelson Sandra B , Pinkney Jodian A , Chen Antonia F , Tande Aaron J
Published: October 2023

Over the last several decades, periprosthetic joint infection (PJI) has been increasing in incidence and is occurring in more complex patients. While there have been advances in both surgical and medical treatment strategies, there remain important gaps in our understanding. Here, we share our current approaches to the diagnosis and management of PJI, focusing on frequent clinical challenges and collaborative interdisciplinary care. The more detailed review including diagnosis, surgical considerations, and a detailed antimicrobial discussion is presented in the online version.
Clinical Testing Guidance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis in Patients With Community-Acquired Pneumonia for Primary and Urgent Care Providers
Authors: Smith Dallas J , Free Rebecca J , Thompson George R , Baddley John W , Pappas Peter G , Benedict Kaitlin , Gold Jeremy A W ,   Endemic Mycoses Diagnostic Algorithm Subject Matter Expert Group, Andes David , Bradsher Robert W , Ebell Mark H , Spec Andrej , Bahr Nathan C , Kauffman Carol A , Mott Timothy , Saccente Michael , Blair Janis E , Galgiani John , Johnson Royce H , Rutherford Richard , Tushla Lisa A , Chiller Tom , Jackson Brendan R , Toda Mitsuru
Published: October 2023

Coccidioidomycosis, histoplasmosis, and blastomycosis are underrecognized and frequently misdiagnosed fungal infections that can clinically resemble bacterial and viral community-acquired pneumonia. This guidance is intended to help outpatient clinicians test for these fungal diseases in patients with community-acquired pneumonia to reduce misdiagnoses, unnecessary antibacterial use, and poor outcomes.
Effect of music therapy intervention on anxiety and pain during percutaneous renal biopsy: a randomized controlled trial
Authors: Giordano Filippo , Mitrotti Adele , Losurdo Antonia , Esposito Flavia , Granata Antonio , Pesino Alessandra , Rossini Michele , Natale Patrizia , Dileo Vincenzo , Fiorentino Marco , Gesualdo Loreto
Published: October 2023

Background

Percutaneous renal biopsy (PRB) may subject patients to emotional distress and pain before and during the biopsy. The aim of this study was to evaluate the effects of complementary/non-pharmacological interventions such as music therapy (MT) on anxiety, pain and satisfaction in renal patients undergoing PRB.

Methods

A prospective, single-centre, single-blind, randomized controlled two-arm trial was conducted. Patients ≥18 years of age, hospitalized at the Nephrology, Dialysis and Transplantation Unit (Bari, Italy) and scheduled for PRB were screened. Participants were assigned to standard treatment (CG) or to the music therapy (MT) intervention group. Participants in the MT group received standard care and an MT intervention by a certified music therapist qualified in guided imagery and music. The CG patients received the standard of care. MT and CG patients were subjected to identical measurements (pre/post) of the parameters in the State Trait Anxiety Inventory Y1 (STAI-Y1), visual analogue scale for pain (VAS-P) and satisfaction (VAS-S) and heart rate variability.

Results

A statistically significant difference in the anxiety scores after PRB between MT and CG patients (STAI-Y1 35.4 ± 6.2 versus 42.9 ± 9.0) was observed. MT also had strong and significant effects on VAS-P compared with CG (5.0 ± 1.4 versus 6.3 ± 1.3, respectively; P < .001) and VAS-S (7.8 ± 1.0 versus 6.0 ± 0.9, respectively; P < .001). Decreased activity of the sympathetic nervous system and increased activity of the parasympathetic nervous system was observed after PRB in the MT group.

Conclusion

Our study supports the use of MT to mitigate the psychological anxiety, pain and sympathetic activation associated with PRB.
Chromosome-level assembly and annotation of the Xyrichtys novacula (Linnaeus, 1758) genome
Authors: Cruz Fernando , Gómez-Garrido Jèssica , Gut Marta , Alioto Tyler S , Pons Joan , Alós Josep , Barcelo-Serra Margarida
Published: October 2023

The pearly razorfish (Xyrichtys novacula), commonly known as raor in the Balearic Islands, is a wrasse within the family Labridae. This fish species has particular biological and socio-cultural characteristics making it an ideal model organism in the fields of behavioural ecology, molecular ecology and conservation biology. In this study, we present the first annotated chromosome-level assembly for this species. Sequencing involved a combination of long reads with Oxford Nanopore Technologies, Illumina paired-end short reads (2 × 151 bp), Hi-C and RNA-seq from different tissues. The nuclear genome assembly has a scaffold N50 of 34.33 Mb, a total assembly span of 775.53 Mb and 99.63% of the sequence assembled into 24 superscaffolds, consistent with its known karyotype. Quality metrics revealed a consensus accuracy (QV) of 42.92 and gene completeness > 98%. The genome annotation resulted in 26,690 protein-coding genes and 12,737 non-coding transcripts. The coding regions encoded 39,613 unique protein products, 93% of them with assigned function. Overall, the publication of the X. novacula’s reference genome will broaden the scope and impact of genomic research conducted on this iconic and colourful species.
Echo Chambers: Social Learning under Unobserved Heterogeneity
Authors: Williams Cole
Published: October 2023

People are often more influenced by opinions similar to their own and even seek information from those with whom they expect to most agree—behaviours often attributed to irrational biases. In this paper, I argue that these behaviours can be understood within the context of rational social learning by accounting for the presence of unobserved heterogeneity in preferences or priors. Individuals display local learning by placing greater weight on opinions that are closer to their own. When individuals choose whom to learn from, local learning leads to the development of echo chambers.
Evolutionarily labile dispersal behavior and discontinuous habitats enhance population differentiation in island versus continentally distributed swallows
Authors: Broyles Grant G , Myers Brian M , Friedman Nicholas R , Gawin Dency F , Mohd-Taib Farah S , Sahlan Penigran G M , Seneviratne Sampath S , de Silva N Chamalka G , Lekamlage Thilini T M , Hund Amanda K , Scordato Elizabeth S C
Published: October 2023

The causes of population divergence in vagile groups remain a paradox in evolutionary biology: dispersive species should be able to colonize new areas, a prerequisite for allopatric speciation, but dispersal also facilitates gene flow, which erodes population differentiation. Strong dispersal ability has been suggested to enhance divergence in patchy habitats and inhibit divergence in continuous landscapes, but empirical support for this hypothesis is lacking. Here we compared patterns of population divergence in a dispersive clade of swallows distributed across both patchy and continuous habitats. The Pacific Swallow (Hirundo tahitica) has an insular distribution throughout Southeast Asia and the Pacific, while its sister species, the Welcome Swallow (H. neoxena), has a continental distribution in Australia. We used whole-genome data to demonstrate strong genetic structure and limited introgression among insular populations, but not among continental populations. Demographic models show that historic changes in habitat connectivity have contributed to population structure within the clade. Swallows appear to exhibit evolutionarily labile dispersal behavior in which they reduce dispersal propensity after island colonization despite retaining strong flight ability. Our data support the hypothesis that fragmented habitats enhance population differentiation in vagile groups, and suggest that labile dispersal behavior is a key mechanism underlying this pattern.
A novel synthetic inhibitor of polyamine utilization in Streptomyces coelicolor
Authors: Krysenko Sergii , Lopez Maria , Meyners Christian , Purder Patrick L , Zinser Alina , Hausch Felix , Wohlleben Wolfgang
Published: October 2023

In this work, we present the first inhibitor of GlnA2Sc, a gamma-glutamylpolyamine synthetase, which allows Streptomyces coelicolor to detoxify high concentrations of polyamines and to utilize them as a carbon or nitrogen source. GlnA2 belongs to the class of glutamine synthetase-like (GS-like) enzymes that catalyze the glutamylation of different nitrogen-containing compounds. Whereas a number of inhibitors for GS are known, none of them are known to inhibit GlnA2. In this work, PPU268, an inhibitor for GlnA2 is presented that is structurally derived from the prototypic GS inhibitor—methionine sulfoximine (MSO). It combines two features: the binding mechanism of MSO and the amine substrate specificity of GlnA2Sc. This inhibitor is a novel compound to block the polyamine utilization in bacteria resulting in the inability to detoxify polyamines. This may offer a possibility to develop novel therapeutic strategies to combat actinobacterial human pathogens that encounter polyamines in the course of the infection processes.
Beyond Inflammaging: The Impact of Immune System Aging on Age-Related Muscle Decline, Results From the InCHIANTI Study
Authors: Pellegrino Raffaello , Paganelli Roberto , Di Iorio Angelo , Bandinelli Stefania , Moretti Antimo , Iolascon Giovanni , Sparvieri Eleonora , Tarantino Domiziano , Tanaka Toshiko , Ferrucci Luigi
Published: October 2023

Aging is characterized by chronic low-level inflammation and is associated with geriatric syndromes such as sarcopenia and frailty. Our aim was to evaluate the longitudinal variation of muscle area, muscle quality, and muscle strength, relative to the variation of leukocyte-derived markers, and to assess the presence of a pathway of associations among derived leukocyte ratios, and the components of muscle health. The InCHIANTI is a longitudinal cohort study of aging that began in 1998 with follow-up visits every 3 years. Out of the 1 453 participants enrolled at baseline, this study includes 1 179 participants with complete data. Muscle strength was assessed by hand grip strength test, whereas muscle density and fat area were considered as indirect markers of muscle quality, derived from peripheral quantitative computed tomography of the calf. Muscle area was associated with neutrophil-to-lymphocyte ratio (NL-ratio), age, gender, comorbidities, and body mass index (BMI). Muscle density variation over time was inversely associated with age, comorbidities, and BMI, while being positively associated with monocyte-to-lymphocyte ratio (ML-ratio) and male gender. Fat area was inversely associated with age, interleukine-6 (IL-6), male gender, and NL-ratio, while being positively associated with ML-ratio, comorbidities, and BMI. Handgrip strength decreased with age, IL-6 levels, comorbidities, and NL-ratio, but increased with ML-ratio, being male, and having a higher BMI. In a path-analysis model, ML-ratio positively correlates with muscle mass, density, and strength, while NL-ratio only correlates inversely with muscle mass and density. NL-ratio and ML-ratio are associated with aging and may be implicated in age-related mechanisms that affect body composition and muscle strength. These ratios may represent a link between aging of the immune system and decline of muscle health with aging. However, further studies are needed to identify their usefulness for early detection of sarcopenia, myosteatosis, and frailty in the older adult.
Imaging upper mantle anisotropy with traveltime and splitting intensity observations from teleseismic shear waves: insights from tomographic reconstructions of subduction simulations
Authors: VanderBeek Brandon P , Bue Rosalia Lo , Rappisi Francesco , Faccenda Manuele
Published: October 2023

Teleseismic traveltime tomography remains one of the most popular methods for obtaining images of Earth’s upper mantle. However, despite extensive evidence for an elastically anisotropic mantle, the isotropic assumption remains commonplace in such imaging studies. This can result in significant model artefacts which in turn may yield misguided inferences regarding mantle dynamics. The nature of anisotropy-induced apparent velocity anomalies has been well-documented in P-wave imaging and various strategies have been proposed to constrain both isotropic and anisotropic heterogeneity from these data. In contrast, few studies have explored the consequences for shear wave tomography and no practical framework for the anisotropic inversion of S-wave delays exists. Here, we propose a new method for constraining arbitrarily oriented hexagonal anisotropy using both traveltime and splitting intensity observations from direct S phases. Our approach accounts for polarization and finite-frequency effects and allows for isotropic starting models. The imaging method is validated through the tomographic analysis of a realistic synthetic dataset produced from waveform simulations through a geodynamic model of subduction. Results illustrate that neglecting anisotropy produces distortions in slab geometry and the appearance of sub- and supraslab low-velocity zones. Anisotropic inversions remove these artefacts while also constraining geodynamically relevant fabric properties including dip.
Towards the usage of quarry blasts as an active seismic source for subsurface characterization and imaging
Authors: Li Peiyao , Nakata Nori , Kolawole Folarin , Carpenter Brett M , Qiu Hongrui
Published: October 2023

Active or man-made seismic sources are often used to delineate subsurface geological structures via seismic imaging techniques. Although conventional controlled seismic sources have provided high-resolution subsurface images, the high cost of data acquisition necessitates improved use of cheaper alternative seismic sources for subsurface imaging, such as traffic noise, quarry blasts and earthquakes. Here, we explore the potential use of quarry blasts as an active seismic source for subsurface imaging. The goal of our study is to demonstrate the utility of quarry blasts as seismic sources for investigating subsurface structure with a field experiment in Mill Creek, southern Oklahoma. We deployed a 7455-m-long receiver line of 72 receivers (105 m spacing) extending away from a quarry, with a recording time of 28 d. We analyse similarities between blasts, wave types, origin time and excitation location of quarry blasts, which is important information for using such signal as an active source. Given a relative homogeneous geological condition in the study area, we could not observe clear reflected waves. However, the use of P- and S-wave velocities led to the delineation of a major basement damage zone in the study area, which further demonstrates the viability of quarry blasts as a useful seismic source for subsurface geological imaging.
The intersection of HIF-1α, O-GlcNAc, and skeletal muscle loss in chronic obstructive pulmonary disease
Authors: Sekar Jinendiran , Attaway Amy H
Published: October 2023

Sarcopenia, defined as the loss of muscle mass and strength, is a major cause of morbidity and mortality in COPD (chronic obstructive pulmonary disease) patients. However, the molecular mechanisms that cause sarcopenia remain to be determined. In this review, we will highlight the unique molecular and metabolic perturbations that occur in the skeletal muscle of COPD patients in response to hypoxia, and emphasize important areas of future research. In particular, the mechanisms related to the glycolytic shift that occurs in skeletal muscle in response to hypoxia may occur via a hypoxia-inducible factor 1-alpha (HIF-1α)-mediated mechanism. Upregulated glycolysis in skeletal muscle promotes a unique post-translational glycosylation of proteins known as O-GlcNAcylation, which further shifts metabolism toward glycolysis. Molecular changes in the skeletal muscle of COPD patients are associated with fiber-type shifting from Type I (oxidative) muscle fibers to Type II (glycolytic) muscle fibers. The metabolic shift toward glycolysis caused by HIF-1α and O-GlcNAc modified proteins suggests a potential cause for sarcopenia in COPD, which is an emerging area of future research.
Intratracheal recurrence of thymoma 7 years after complete resection
Authors: Fukuyama Kaoru , Funakoshi Yasunobu
Published: October 2023

A 66-year-old woman with a massive anterior mediastinal tumour was diagnosed with type B2 thymoma. After 2 courses of chemotherapy, extended thymectomy and partial resection of the lung and large vessels were performed, and the tumour was completely resected. The patient received no postoperative therapy. Seven years after the surgery, follow-up chest computed tomography showed a papillary soft tissue tumour in the trachea almost obstructing the airway. Intratracheal tumour resection was performed under rigid bronchoscopy, and the pathological diagnosis of intratracheal recurrence of thymoma was made. The patient received postoperative radiotherapy and has remained alive without disease progression 9 months after the second operation.
The Clinical and Economic Burden of Antibiotic Use in Pediatric Patients With Varicella Infection: A Retrospective Cohort Analysis of Real-World Data in England
Authors: Kujawski Stephanie A , Banks Victoria , Casey Caroline S , Drysdale Simon B , Patel Amisha , Massey Olivia , Holbrook Tim , Pawaskar Manjiri
Published: October 2023

Background

Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England.

Methods

Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics data sets. The study included patients <18 years old with varicella diagnosed during 2014–2018 and 3-month follow-up available. We determined varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3 months after diagnosis.

Results

We identified 114 578 children with a primary varicella diagnosis. Of these, 7.7% (n = 8814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1% [n = 3271]). In all, 25.9% (n = 29 706 of 114 578) were prescribed antibiotics. A higher proportion of patients with complications than without complications were prescribed antibiotics (64.3% [n = 5668 of 8814] vs 22.7% [n = 24 038 of 105 764]). Mean annualized varicella-related costs were £2 231 481 for the study cohort. Overall, antibiotic prescriptions cost approximately £262 007.

Conclusions

This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs.
Growth of alfalfa in the presence of metabolites from a dark septate endophyte strain Alternaria sp. 17463 cultured with a nonionic surfactant and emulsifier
Authors: Tan Hai , Bi Yinli , Zhang Shishuang , Wang Shuhui
Published: October 2023

Aim

Dark septate endophytes (DSE) were widely used in the agriculture and ecological restoration. The objective of this work was to assess the effect of culture media nonionic surfactant and emulsifier on the biomass and metabolites of DSE strain Alternaria sp. 17463.

Methods and results

Changes in the composition of DSE metabolites following the addition of Tween 80 during liquid culture of a DSE fungus were analyzed and used in growth tests of alfalfa.

Shaking flask fermentation was carried out and the surfactant was fed to the fungus during the fermentation. The residual sugar content and pH declined significantly in the medium and the biomass of DSE increased by 7.27% over controls with no surfactant. Metabolomic analysis showed that adding the surfactant significantly increased the content of 63 metabolites (P < 0.05). These include lipids and lipid-like molecules, organooxygen compounds, amino acids and organic acids, and flavonoids. Enrichment analysis of metabolic pathways indicates that surfactant addition promoted carbohydrate metabolism and amino acid synthesis. A plant hydroponic experiment indicated that these changes in metabolites altered the root structure of alfalfa seedlings. They also promoted significant increases in root length and root surface area, and increased alfalfa total biomass by 50.2%.

Conclusions

The addition of the surfactant promoted sugar utilization by the DSE fungus and increased the synthesis of lipids and amino acids, resulting in the ability of the fungal metabolites to change root structure and promote plant growth.
Induction of Skin Allograft Chimerism by Pharmacological Mobilization of Endogenous Bone Marrow-Derived Stem Cells
Authors: Ahmadi Ali R , Wesson Russell N , Huang Jinny , Harmon John , Burdick James F , Cameron Andrew M , Sun Zhaoli
Published: October 2023

Skin substitutes including allografts remain a standard therapeutic approach to promote healing of both acute and chronic large wounds. However, none have resulted in the regrowth of lost and damaged tissues and scarless wound healing. Here, we demonstrate skin allograft chimerism and repair through the mobilization of endogenous bone marrow-derived stem and immune cells in rats and swine. We show that pharmacological mobilization of bone marrow stem cells and immune cells into the circulation promotes host repopulation of skin allografts and restoration of the skin’s normal architecture without scarring and minimal contracture. When skin allografts from DA rats are transplanted into GFP transgenic Lewis recipients with a combination of AMD3100 and low-dose FK506 (AF) therapy, host-derived GFP-positive cells repopulate and/or regenerate cellular components of skin grafts including epidermis and hair follicles and the grafts become donor-host chimeric skin. Using AF combination therapy, burn wounds with skin allografts were healed by newly regenerated chimeric skin with epidermal appendages and pigmentation and without contracture in swine.
Effects of lysine deacetylase inhibitor treatment on LPS responses of alveolar-like macrophages
Authors: Russo Sara , Kwiatkowski Marcel , Wolters Justina C , Gerding Albert , Hermans Jos , Govorukhina Natalia , Bischoff Rainer , Melgert Barbro N
Published: October 2023

Macrophages are key immune cells that can adapt their metabolic phenotype in response to different stimuli. Lysine deacetylases are important enzymes regulating inflammatory gene expression and lysine deacetylase inhibitors have been shown to exert anti-inflammatory effects in models of chronic obstructive pulmonary disease. We hypothesized that these anti-inflammatory effects may be associated with metabolic changes in macrophages. To validate this hypothesis, we used an unbiased and a targeted proteomic approach to investigate metabolic enzymes, as well as liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry, to quantify metabolites in combination with the measurement of functional parameters in primary murine alveolar-like macrophages after lipopolysaccharide-induced activation in the presence or absence of lysine deacetylase inhibition. We found that lysine deacetylase inhibition resulted in reduced production of inflammatory mediators such as tumor necrosis factor α and interleukin 1β. However, only minor changes in macrophage metabolism were observed, as only one of the lysine deacetylase inhibitors slightly increased mitochondrial respiration while no changes in metabolite levels were seen. However, lysine deacetylase inhibition specifically enhanced expression of proteins involved in ubiquitination, which may be a driver of the anti-inflammatory effects of lysine deacetylase inhibitors. Our data illustrate that a multiomics approach provides novel insights into how macrophages interact with cues from their environment. More detailed studies investigating ubiquitination as a potential driver of lysine deacetylase inhibition will help developing novel anti-inflammatory drugs for difficult-to-treat diseases such as chronic obstructive pulmonary disease.
Minkowski functionals of CMB polarization intensity with pynkowski: theory and application to Planck and future data
Authors: Carones Alessandro , CarrónDuque Javier , Marinucci Domenico , Migliaccio Marina , Vittorio Nicola
Published: October 2023

The angular power spectrum of the cosmic microwave background (CMB) anisotropies is a key tool to study the Universe. However, it is blind to the presence of non-Gaussianities and deviations from statistical isotropy, which can be detected with other statistics such as Minkowski functionals (MFs). These tools have been applied to CMB temperature and E-mode anisotropies with no detection of deviations from Gaussianity and isotropy. In this work, we extend the MF formalism to the CMB polarization intensity, P2 = Q2 + U2. We use the Gaussian kinematic formula to derive the theoretical predictions of MFs for Gaussian isotropic fields. We develop a software that computes MFs on P2healpix maps and apply it to simulations to verify the robustness of both theory and methodology. We then estimate MFs of P2 maps from Planck, both in pixel space and needlet domain, comparing them with realistic simulations that include CMB and instrumental noise residuals. We find no significant deviations from Gaussianity or isotropy in Planck CMB polarization intensity. However, MFs could play an important role in the analysis of CMB polarization measurements from upcoming experiments with improved sensitivity. Therefore, we forecast the ability of MFs applied to P2 maps to detect much fainter non-Gaussian anisotropic signals than with Planck data for two future complementary experiments: the LiteBIRD satellite and the ground-based Simons Observatory. We publicly release the software to compute MFs in arbitrary scalar healpix maps as a fully documented python package called pynkowski.
Rapidly rotating massive Population III stars: a solution for high carbon enrichment in CEMP-no stars
Authors: Jeena S K , Banerjee Projjwal , Chiaki Gen , Heger Alexander
Published: October 2023

Very metal-poor stars that have [Fe/H] < −2 and that are enhanced in C relative to Fe ([C/Fe] > +0.7) but have no enhancement of heavy elements ([Ba/Fe] < 0) are known as carbon-enhanced metal-poor (CEMP-no) stars. These stars are thought to be produced from a gas that was polluted by the supernova (SN) ejecta of the very first generation (Population III) massive stars. The very high enrichment of C (A(C) ≳ 6) observed in many of the CEMP-no stars is difficult to explain by current models of SN explosions from massive Population III stars when a reasonable dilution of the SN ejecta, which is consistent with detailed simulation of metal mixing in minihaloes, is adopted. We explore rapidly rotating Population III stars that undergo efficient mixing and reach a quasi-chemically homogeneous (QCH) state. We find that QCH stars can eject large amounts of C in the wind and that the resulting dilution of the wind ejecta in the interstellar medium can lead to a C enrichment of A(C) ≲ 7.75. The core of QCH stars can produce up to an order of magnitude of more C than non-rotating progenitors of similar mass and the resulting SN can lead to a C enrichment of A(C) ≲ 7. Our rapidly rotating massive Population III stars cover almost the entire range of A(C) observed in CEMP-no stars and are a promising site for explaining the high C enhancement in the early Galaxy. Our work indicates that a substantial fraction of Population III stars were likely rapid rotators.
The rotational excitation of the water isotopologues by molecular hydrogen
Authors: Faure A , Żółtowski M , Wiesenfeld L , Lique F , Bergeat A
Published: October 2023

We present cross-sections and rate coefficients for rotational transitions in the water isotopologues D2O, H$_2^{18}$O, and HDO induced by collisions with para-H2(j2 = 0) and ortho-H2(j2 = 1). Quantum scattering calculations are performed at the full close-coupling level with the isotopic variants of an accurate full-dimensional H2O−H2 interaction potential. The D2O, H$_2^{18}$O, and HDO cross-sections are compared to the corresponding cross-sections for H2O. Large isotopic effects are observed in the case of D2O and HDO, in particular for collisions with p-H2(j2 = 0), while the 18O isotopic substitution is found to be negligible. Rate coefficients are provided for rotational transitions among all para-D2O, ortho-D2O, and HDO levels with internal energy below 300 cm−1 and for kinetic temperatures in the range 5–300 K. Non-LTE radiative transfer calculations show that the HDO 225.9 GHz and H$_2^{18}$O 203.4 GHz transitions recently detected with ALMA in the young proto-planetary disc V883 Ori should be inverted (weak masers) in a large fraction of the disc.
Main-sequence companions to white dwarfs – II. The age–activity–rotation relation from a sample of Gaia common proper motion pairs
Authors: Rebassa-Mansergas A , Maldonado J , Raddi R , Torres S , Hoskin M , Cunningham T , Hollands M A , Ren J , Gänsicke B T , Tremblay P-E , Camisassa M
Published: October 2023

Magnetic activity and rotation are related to the age of low-mass main-sequence stars. To further constrain these relations, we study a sample of 574 main-sequence stars members of common proper motion pairs with white dwarfs, identified thanks to Gaia astrometry. We use the white dwarfs as age indicators, while the activity indexes and rotational velocities are obtained from the main-sequence companions using standard procedures. We find that stars older than 5 Gyr do not display H α nor Ca ii H&K emission unless they are fast rotators due to tidal locking from the presence of unseen companions and that the rotational velocities tend to decrease over time, thus supporting the so-called gyrochronology. However, we also find moderately old stars (≃2–6 Gyr) that are active presumably because they rotate faster than they should for their given ages. This indicates that they may be suffering from weakened magnetic braking or that they possibly evolved through wind accretion processes in the past. The activity fractions that we measure for all stars younger than 5 Gyr range between ≃10 and 40 per cent. This is line with the expectations, since our sample is composed of F, G, K, and early M stars, which are thought to have short (<2 Gyr) activity lifetimes. Finally, we observe that the H α fractional luminosities and the $R^{\prime }_\mathrm{HK}$ indexes for our sample of (slowly rotating) stars show a spread (−4 >log(LH α/Lbol); log($R^{\prime }_\mathrm{HK}$) > −5) typically found in inactive M stars or weakly active/inactive F, G, K stars.
Differentiated Zn(II) binding affinities in animal, plant, and bacterial metallothioneins define their zinc buffering capacity at physiological pZn
Authors: Mosna Karolina , Jurczak Kinga , Krężel Artur
Published: October 2023

Metallothioneins (MTs) are small, Cys-rich proteins present in various but not all organisms, from bacteria to humans. They participate in zinc and copper metabolism, toxic metals detoxification, and protection against reactive species. Structurally, they contain one or multiple domains, capable of binding a variable number of metal ions. For experimental convenience, biochemical characterization of MTs is mainly performed on Cd(II)-loaded proteins, frequently omitting or limiting Zn(II) binding features and related functions. Here, by choosing 10 MTs with relatively well-characterized structures from animals, plants, and bacteria, we focused on poorly investigated Zn(II)-to-protein affinities, stability–structure relations, and the speciation of individual complexes. For that purpose, MTs were characterized in terms of stoichiometry, pH-dependent Zn(II) binding, and competition with chromogenic and fluorescent probes. To shed more light on protein folding and its relation with Zn(II) affinity, reactivity of variously Zn(II)-loaded MTs was studied by (5,5ʹ-dithiobis(2-nitrobenzoic acid) oxidation in the presence of mild chelators. The results show that animal and plant MTs, despite their architectural differences, demonstrate the same affinities to Zn(II), varying from nano- to low picomolar range. Bacterial MTs bind Zn(II) more tightly but, importantly, with different affinities from low picomolar to low femtomolar range. The presence of weak, moderate, and tight zinc sites is related to the folding mechanisms and internal electrostatic interactions. Differentiated affinities of all MTs define their zinc buffering capacity required for Zn(II) donation and acceptance at various free Zn(II) concentrations (pZn levels). The data demonstrate critical roles of individual Zn(II)-depleted MT species in zinc buffering processes.
Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study
Authors: Pecci Federica , Cantini Luca , Cognigni Valeria , Perrone Fabiana , Mazzaschi Giulia , Agostinelli Veronica , Mentrasti Giulia , Favari Elda , Maffezzoli Michele , Cortellini Alessio , Rossi Francesca , Chiariotti Rebecca , Venanzi Francesco Maria , Lo Russo Giuseppe , Galli Giulia , Proto Claudia , Ganzinelli Monica , Tronconi Francesca , Morgese Francesca , Campolucci Carla , Moretti Marco , Vignini Arianna , Tiseo Marcello , Minari Roberta , Rocchi Marco Luigi Bruno , Buti Sebastiano , Berardi Rossana
Published: October 2023

Background

Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed.

Materials and Methods

We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes.

Results

At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a “LIPID score” identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS.

Conclusions

We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs.
Harnessing Deep Learning to Analyze Cryptic Morphological Variability of Marchantia polymorpha
Authors: Tomizawa Yoko , Minamino Naoki , Shimokawa Eita , Kawamura Shogo , Komatsu Aino , Hiwatashi Takuma , Nishihama Ryuichi , Ueda Takashi , Kohchi Takayuki , Kondo Yohei
Published: October 2023

Characterizing phenotypes is a fundamental aspect of biological sciences, although it can be challenging due to various factors. For instance, the liverwort Marchantia polymorpha is a model system for plant biology and exhibits morphological variability, making it difficult to identify and quantify distinct phenotypic features using objective measures. To address this issue, we utilized a deep-learning-based image classifier that can handle plant images directly without manual extraction of phenotypic features and analyzed pictures of M. polymorpha. This dioicous plant species exhibits morphological differences between male and female wild accessions at an early stage of gemmaling growth, although it remains elusive whether the differences are attributable to sex chromosomes. To isolate the effects of sex chromosomes from autosomal polymorphisms, we established a male and female set of recombinant inbred lines (RILs) from a set of male and female wild accessions. We then trained deep learning models to classify the sexes of the RILs and the wild accessions. Our results showed that the trained classifiers accurately classified male and female gemmalings of wild accessions in the first week of growth, confirming the intuition of researchers in a reproducible and objective manner. In contrast, the RILs were less distinguishable, indicating that the differences between the parental wild accessions arose from autosomal variations. Furthermore, we validated our trained models by an ‘eXplainable AI’ technique that highlights image regions relevant to the classification. Our findings demonstrate that the classifier-based approach provides a powerful tool for analyzing plant species that lack standardized phenotyping metrics.
The RPT2a–MET1 axis regulates TERMINAL FLOWER1 to control inflorescence meristem indeterminacy in Arabidopsis
Authors: Yao Wang Jinsong , Wang Yi Peng , Peng Jing , Yin Pei Pei , Gao Hengbin , Xu Li , Laux Thomas , Zhang Xian Sheng , Su Ying Hua
Published: October 2023

Plant inflorescence architecture is determined by inflorescence meristem (IM) activity and controlled by genetic mechanisms associated with environmental factors. In Arabidopsis (Arabidopsis thaliana), TERMINAL FLOWER1 (TFL1) is expressed in the IM and is required to maintain indeterminate growth, whereas LEAFY (LFY) is expressed in the floral meristems (FMs) formed at the periphery of the IM and is required to activate determinate floral development. Here, we address how Arabidopsis indeterminate inflorescence growth is determined. We show that the 26S proteasome subunit REGULATORY PARTICLE AAA-ATPASE 2a (RPT2a) is required to maintain the indeterminate inflorescence architecture in Arabidopsis. rpt2a mutants display reduced TFL1 expression levels and ectopic LFY expression in the IM and develop a determinate zigzag-shaped inflorescence. We further found that RPT2a promotes DNA METHYLTRANSFERASE1 degradation, leading to DNA hypomethylation upstream of TFL1 and high TFL1 expression levels in the wild-type IM. Overall, our work reveals that proteolytic input into the epigenetic regulation of TFL1 expression directs inflorescence architecture in Arabidopsis, adding an additional layer to stem cell regulation.
Quantum electrodynamics on the lattice and numerical perturbative computation of g − 2
Authors: Kitano Ryuichiro , Takaura Hiromasa
Published: October 2023

We compute the electron g factor to the $\mathcal {O}(\alpha ^5)$ order on the lattice in quenched quantum electrodynamics (QED). We first study finite volume (FV) corrections in various infrared regularization methods to discuss which regularization is optimal for our purpose. We find that in QEDL the FV correction to the effective mass can have different parametric dependences depending on the size of Euclidean time t and match the ‘naive on-shell result’ only at the very large t region, t ≫ L. We adopt finite photon mass regularization to suppress FV effects exponentially and also discuss our strategy for selecting simulation parameters and the order of extrapolations to efficiently obtain the g factor. We perform lattice simulation using small lattices to test the feasibility of our calculation strategy. This study can be regarded as an intermediate step toward giving the five-loop coefficient independently of preceding studies.
Therapy with JAK inhibitors or bDMARDs and the risk of cardiovascular events in the Dutch rheumatoid arthritis population
Authors: Popa Calin D , Opdam Merel A A , den Broeder Nathan , van Ballegooijen Hanne , Mulder Kelly , van de Wiel Kayleigh M , van Herwaarden Noortje , Wientjes Maike H M , den Broeder Alfons A
Published: October 2023

Objective

Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients with an unfavourable cardiovascular risk profile. We aimed to compare the incidences in cardiovascular events between JAKi and biologic DMARDs (bDMARDs) in a large population of RA patients.

Methods

RA patients starting a new bDMARD or JAKi between 1 August 2018 and 31 January 2022 have been selected from IQVIA’s Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome was a cardiovascular event, defined as the start of platelet aggregation inhibitors during the study period. The incidence densities of cardiovascular events were compared between JAKi and bDMARDs using multilevel Poisson regression, adjusted for exposure time and confounders.

Results

The number of unique patients included was 15 191, with 28 481 patient-years on treatment with either JAKi (2373) or bDMARDs (26 108). Most patients were female (72%) and median age was 62 years. We found 36 cardiovascular events (1.52 events/100 patient-years) during therapy with JAKi and 383 events (1.47 events/100 patient-years) during therapy with bDMARDs, resulting in an adjusted incidence rate ratio (IRR) of 0.99 for JAKi compared with bDMARDs (95% CI: 0.70, 1.41). Sub-analyses in patients >65 years, by sex, or separately for tofacitinib and baricitinib, yielded similar results.

Conclusion

In a large Dutch general RA population, the risk of cardiovascular events seems not to be different between JAKi users and those using bDMARDs, although a small increase in higher risk patients cannot be excluded.