bluuebunny/crossref_metadata_2025 huggingface dataset:
Fostering societal participation of marginalised people in street-outreach services in the Netherlands
Authors: Rauwerdink-Nijland Evelien , van den Dries Linda , Metz Judith , Verhoeff Arnoud , Wolf Judith
Published: June 2024

Marginalisation is a multilevel phenomenon in society depriving people from essential rights, resources, and opportunities. Street-outreach services in the Netherlands, like social street work (SSW), support these marginalised people in fostering their participation in society as an answer to their marginalised position in society. We followed 927 clients in SSW over an eight-month period. Clients filled in a questionnaire at three timepoints. We examined whether clients’ perceived belongingness, self-esteem, strengths, and informal support (outcome measures) were associated with the working relationship, over time. Results showed the establishment of a working relationship with clients at all three timepoints. An evolving working relationship was associated with an increase in clients’ perceived belongingness, self-esteem, strengths, and informal support over time. This study showed the ability of workers to establish a working relationship with clients in their living environment and underscored the necessity of establishing a working relationship in street-outreach services to foster clients’ participation in society. This study encourages policymakers to reflect on current street-outreach services, to deviate from demanding short-term and measurable results from professionals’ efforts, and to opt for a better fit between performance and financing conditions and daily practices of street-outreach services.
Overexpression of PD-L1 causes germ cell failure and infertility via CRISP1/PD-L1 interaction in mouse epididymis
Authors: Li Ting , Guo Hongmin
Published: June 2024

Spermatogenesis is a highly complex process through which mature sperms are produced, and it requires three important stages; mitosis, meiosis and sperm formation. The expression of genes regulated by transcription factors at specific stages exerts important regulatory effects on the development process of germ cells. Male mice with overexpressed programmed death ligand 1 (PD-L1) (B7 homolog1) in the testis have infertility and abnormal sperm development, thereby exhibiting severe malformation and sloughing throughout spermatid maturation and collapsed and disorganized seminiferous epithelium structure. Furthermore, PD-L1 overexpression causes overexpression of cysteine-rich secretory protein 1 (CRISP1) in the epididymis and adversely affects or precludes sperm energization, sperm-pellucida binding and sperm-oocyte fusion. These findings suggest that CRISP1 and PD-L1 can interact with each other to induce male infertility and germ-cell dissociation.
A rare case of intra-ovarian oocyte maturation
Authors: Jobson Sara , Hamel Jean-François , Mercier Annie
Published: June 2024

The intra-ovarian presence of ootids, i.e. female gametes that have completed meiosis, is considered exceptional in the animal kingdom. The present study explores the first such case to be reported in a sea cucumber (Echinodermata: Holothuroidea). In the overwhelming majority of animals, including holothuroids, oocytes (i.e. immature female gametes) that are developing in the ovary undergo a primary arrest at the prophase stage of meiosis, which may last from days to decades. In free-spawning taxa, this arrest is normally lifted only during or shortly before transit in the gonoduct, when gamete release (spawning) is imminent. However, oocytes of the holothuroid Chiridota laevis were discovered to have resumed the second meiotic division including the completion of germinal vesicle breakdown and polar-body expulsion inside the ovary, effectively reaching the ootid stage concomitantly with ovulation (i.e. escape from follicle cells) prior to spawning. The potential drivers and significance of this exceptionally rare case of full intra-ovarian oogenic maturation are discussed.
Politics of Performance/Performance of Politics
Authors: Cheng Meiling
Published: June 2024

The 2022 anti–zero Covid White Paper protests that erupted in China and its diaspora demonstrated the intertwinement of politics and performance in contemporary China. The symbolic dimensions of blank sheets of A4 paper and other performative tactics used in these demonstrations exemplify the shifting roles of performance art in the field of contemporary Chinese art.
WAKE
Authors: Carlon Jay
Published: June 2024

WAKE is a queer postcolonial ritual centering grief, healing, and solace through movement within the collective. Created by choreographer Jay Carlon with collaborator and vocalist Micaela Tobin, alongside a live electronic musical score, WAKE is a meditative performance imbued with images, sound, and objects derived from Carlon’s Filipinx heritage and dedicated to those born in the wake of US imperialism.
Rome: The Game. Creating an online course as an interactive adventure game
Authors: Moser Claudia , Thomas Christian
Published: June 2024

In this article, we focus on the development of Rome: The Game – a large, lower-division online course crossed-listed in the History of Art and Architecture Department and Writing Program at the University of California, Santa Barbara – that features a choose-your-own-adventure-style interactive narrative. We explore the design principles underpinning the development of this type of gamified course, the mechanics of the course itself, student experiences, and learning outcomes. Citing relevant research in several fields – such as game studies, educational psychology, and communication studies – we argue that creating an online course in the style of an interactive, narrative-driven digital game presents a model for engaging and effective active learning in an online environment – one that goes beyond conventional virtual learning to offer an innovative, active, and deeply immersive model for online teaching.
Association Between Rheumatoid Arthritis and Clonal Hematopoiesis: A Mendelian Randomization Study
Authors: Zhang Jie , Zhou Chun , Guan Shaoxing
Published: June 2024

Immunity activation and inflammation are the main characteristics of rheumatoid arthritis and clonal hematopoiesis. However, it remains unclear whether rheumatoid arthritis increase the risk of clonal hematopoiesis. Here, a Mendelian randomization (MR) analysis was conduct to explore the causal effects of rheumatoid arthritis on clonal hematopoiesis. Summary statistics data of rheumatoid arthritis (13,838 cases and 33,742 controls) and clonal hematopoiesis (10,203 cases and 173,918 controls) derived from a genomewide association study were selected to analyze. We selected inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode to evaluate the causal effect of rheumatoid arthritis on clonal hematopoiesis. The two-sample MR analysis suggested a strong causal relationship between rheumatoid arthritis and clonal hematopoiesis by inverse-variance weighted (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .039706) and weighted median (OR = 1.002311673, 95% CI [1.000110757, 1.004517433], p = .039518447) methods. No significant pleiotropy or heterogeneity was found in the sensitivity analysis. These results supported a potentially causal relationship between rheumatoid arthritis and clonal hematopoiesis, and the exposure of rheumatoid arthritis increased the risks of clonal hematopoiesis. Our findings highlight the importance of how chronic inflammation and immune activation induced rheumatoid arthritis enhances the risks of clonal hematopoiesis, and that early intervention with rheumatoid arthritis patients might reduce the clonal hematopoiesis risks in rheumatoid arthritis patients. Moreover, our study provides clues for prediction of risk factors and potential mechanisms of clonal hematopoiesis.
Influence of Microbial Activities on Fluorescent Dissolved Organic Matter in the Dark Canada Basin Waters
Authors: Sylvestre N. , Guéguen C.
Published: June 2024

The fluorescence characteristics of dissolved organic matter (DOM) were measured to determine the distribution and drivers of DOM in the dark Canada Basin waters. We studied the relationship between fluorescent DOM (FDOM) and apparent oxygen utilization (AOU) in the whole water column as well as in the main water masses (Pacific Winter Water, Atlantic halocline (AH), Atlantic water—Fram Strait and Barents Sea branches, Deep Temperature Minimum, and Canada Basin deep water). The relative water mass fractions of different water masses were estimated using a five end‐members mixing model. The distribution of water mass fractions was found to be in good agreement with the distribution based on the traditional temperature‐salinity diagram. The fractions of AH waters were linked with AOU, highlighting the significant role played by mineralization in shaping AH humic‐like levels. The slope of the relationship between in situ FDOM—AOU was greater than those reported in the other oceans worldwide. This suggests that the AH is a hot spot for microbial mineralization of humic‐like DOM. On the other hand, the relationships with the humic‐like intensities differed among the four humic‐like components in the >125 m waters, indicating distinct environmental dynamics and biogeochemical roles for each humic‐like component.
Divergent Impacts of Evapotranspiration by Plant CO2 Physiological Forcing on the Mean and Variability of Water Availability
Authors: Li Ziwei , Sun Fubao , Liu Wenbin , Wang Hong , Wang Tingting , Feng Yao , Tang Senlin
Published: June 2024

Vegetation responses to rising atmospheric CO2 levels can significantly affect water availability (defined as precipitation minus evapotranspiration (ET)). While this effect has long been recognized and assessed for the mean state, its influence on interannual variability, which is more closely associated with extreme events, has yet to be comprehensively quantified. In this study, our primary focus is to evaluate the impacts of ET by plant physiology (denoted as ETPhy) on the mean and interannual variability of water availability under elevated CO2 using multiple CO2 sensitivity experiments from the coupled model intercomparison project phase 6. We show that the contribution of vegetation physiological effects to the mean water availability varies among regions, while it consistently contributes to variability by about 33%. Considering CO2 physiological effects alone, ETPhy exerts a more significant influence on the mean state than on variability, particularly in humid regions. Consequently, ETPhy contributes less than 5% to the variability of water availability in humid regions under rising CO2, whereas it accounts for about 20% of the mean state. This distinction could be attributed to the different mechanisms governing the mean and variability of ETPhy. Specifically, evaporation from CO2 physiological forcing is the most critical contributor to the variability of ETPhy in most regions while showing minimal impacts on the mean state. Our findings identify the divergent effects of ETPhy on the mean state and interannual variability of water availability under elevated CO2, as important in future climate projections.
Third‐Order Structure Functions of Zonal Winds in the Thermosphere Using CHAMP and GOCE Observations
Authors: Poblet Facundo L. , Liu Huixin , Chau Jorge L.
Published: June 2024

We use multi‐year observations of cross‐track winds (u) from the CHAllenging Minisatellite Payload (CHAMP) and the Gravity Field and Steady State Ocean Circulation Explorer (GOCE) to calculate third‐order structure functions in the thermosphere as a function of horizontal separation (s). They are computed using the mean (〈δu3〉) and the median and implemented over non‐polar satellite paths in both hemispheres. On height averages, 〈δu3〉 is shown to scale with s2 for s ≃ 80–1,000 km, in agreement with equivalent estimates in the lower atmosphere from aircraft observations. Conversely, follows an s3 power law for almost the whole s range, consistent with the two‐dimensional turbulence scaling law for a direct enstrophy cascade. These scaling laws appear independent of winds in distinct atmospheric regions. Furthermore, the functions are predominantly positive, indicating a preferential cyclonic motion for the wind.
Intensification and Poleward Shift of Compound Wind and Precipitation Extremes in a Warmer Climate
Authors: Li Delei , Zscheischler Jakob , Chen Yang , Yin Baoshu , Feng Jianlong , Freund Mandy , Qi Jifeng , Zhu Yuchao , Bevacqua Emanuele
Published: June 2024

Compound wind and precipitation extremes (CWPEs) can severely impact natural and socioeconomic systems. However, our understanding of CWPE future changes, drivers, and uncertainties under a warmer climate is limited. Here, by analyzing the event both on oceans and landmasses via state‐of‐the‐art climate model simulations, we reveal a poleward shift of CWPE occurrences by the late 21st century, with notable increases at latitudes exceeding 50° in both hemispheres and decreases in the subtropics around 25°. CWPE intensification occurs across approximately 90% of global landmasses, and is most pronounced under a high‐emission scenario. Most changes in CWPE frequency and intensity (about 70% and 80%, respectively) stem from changes in precipitation extremes. We further identify large uncertainties in CWPE changes, which can be understood at the regional level by considering climate model differences in trends of CWPE drivers. These results provide insights into understanding CWPE changes under a warmer climate, aiding robust regional adaptation strategy development.
Neuron type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct
Authors: Kim Ra Gyung , Cho Jongwook , Park Ji-Young , Kim Young Ro , Lee Min-Cheol , Kim Hyoung-Ihl
Published: June 2024

Cortical neuromodulation (CNM) is widely used to promote recovery after stroke. Despite the beneficial results of CNM, the roles played by different neuron types in the effects of current CNM techniques are unable to be differentiated. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to poststroke recovery. We transduced the sensory-parietal cortex (SPC) of rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons resulted in significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed a significant reduction in cortical diaschisis and activation of the corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in the stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that the plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could improve poststroke outcomes.
O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts
Authors: Very Ninon , Boulet Clémence , Gheeraert Céline , Berthier Alexandre , Johanns Manuel , Bou Saleh Mohamed , Guille Loïc , Bray Fabrice , Strub Jean-Marc , Bobowski-Gerard Marie , Zummo Francesco P. , Vallez Emmanuelle , Molendi-Coste Olivier , Woitrain Eloise , Cianférani Sarah , Montaigne David , Ntandja-Wandji Line Carolle , Dubuquoy Laurent , Dubois-Chevalier Julie , Staels Bart , Lefebvre Philippe , Eeckhoute Jérôme
Published: June 2024

Tissue injury causes activation of mesenchymal lineage cells into wound-repairing myofibroblasts (MFs), whose uncontrolled activity ultimately leads to fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, we report that the metabolic sensor post-translational modification O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) is increased and required for myofibroblastic activation. Inhibition of protein O-GlcNAcylation impairs archetypal myofibloblast cellular activities including extracellular matrix gene expression and collagen secretion/deposition as defined in vitro and using ex vivo and in vivo murine liver injury models. Mechanistically, a multi-omics approach combining proteomic, epigenomic, and transcriptomic data mining revealed that O-GlcNAcylation controls the MF transcriptional program by targeting the transcription factors Basonuclin 2 (BNC2) and TEA domain transcription factor 4 (TEAD4) together with the Yes-associated protein 1 (YAP1) co-activator. Indeed, inhibition of protein O-GlcNAcylation impedes their stability leading to decreased functionality of the BNC2/TEAD4/YAP1 complex towards promoting activation of the MF transcriptional regulatory landscape. We found that this involves O-GlcNAcylation of BNC2 at Thr455 and Ser490 and of TEAD4 at Ser69 and Ser99. Altogether, this study unravels protein O-GlcNAcylation as a key determinant of myofibroblastic activation and identifies its inhibition as an avenue to intervene with fibrogenic processes.
Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila
Authors: Pilesi Eleonora , Tesoriere Giulia , Ferriero Angelo , Mascolo Elisa , Liguori Francesco , Argirò Luca , Angioli Chiara , Tramonti Angela , Contestabile Roberto , Volontè Cinzia , Vernì Fiammetta
Published: June 2024

Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5’-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign RasV12 tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgllPNPO gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating RasV12 and downregulating Discs-large (Dlg) gene. Moreover, we found that RasV12 eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding RasV12 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in RasV12DlgRNAi 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.
Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency
Authors: Goehring Liana , Keegan Sarah , Lahiri Sudipta , Xia Wenxin , Kong Michael , Jimenez-Sainz Judit , Gupta Dipika , Drapkin Ronny , Jensen Ryan B. , Smith Duncan J. , Rothenberg Eli , Fenyö David , Huang Tony T.
Published: June 2024

BRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of head-on transcription-replication conflicts (HO-TRCs). Using Okazaki-fragment sequencing (Ok-seq) and computational analysis, we identified origins (dormant origins) that are activated near the transcription termination sites (TTS) of highly expressed, long genes in response to replication stress. Dormant origins are a source for HO-TRCs, and drug treatments that inhibit dormant origin firing led to a reduction in HO-TRCs, R-loop formation, and DNA damage. Using super-resolution microscopy, we showed that HO-TRC events track with elongating RNA polymerase II, but not with transcription initiation. Importantly, RNase H2 is recruited to sites of HO-TRCs in a BRCA2-dependent manner to help alleviate toxic R-loops associated with HO-TRCs. Collectively, our results provide a mechanistic basis for how BRCA2 shields against genomic instability by preventing HO-TRCs through both direct and indirect means occurring at predetermined genomic sites based on the pre-cancer transcriptome.
Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status
Authors: Wearn Alfie , Tremblay Stéfanie A. , Tardif Christine L. , Leppert Ilana R. , Gauthier Claudine J. , Baracchini Giulia , Hughes Colleen , Hewan Patrick , Tremblay-Mercier Jennifer , Rosa-Neto Pedro , Poirier Judes , Villeneuve Sylvia , Schmitz Taylor W. , Turner Gary R. , Spreng R. Nathan ,   PREVENT-AD Research Group
Published: June 2024

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer’s disease (AD). They project broadly throughout the brain’s white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD. Using multiparametric quantitative magnetic resonance imaging we observed two covariance patterns between IdC and white matter microstructure in 133 cognitively unimpaired older adults (age 67.9 ± 5.3 years) with familial risk for AD. IdC integrity related to 1) whole-brain neurite density, and 2) neurite orientation dispersion in white matter tracts known to be affected early in AD. Pattern 2 was associated with CSF concentration of phosphorylated-tau, indicating AD specificity. Apolipoprotein-E4 carriers expressed both patterns more strongly than non-carriers. IdC microstructure variation is reflected in white matter, particularly in AD-affected tracts, highlighting an early mechanism of pathological development.
IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice
Authors: Muckenhuber Moritz , Mengrelis Konstantinos , Weijler Anna Marianne , Steiner Romy , Kainz Verena , Buresch Marlena , Regele Heinz , Derdak Sophia , Kubetz Anna , Wekerle Thomas
Published: June 2024

The efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with ATG allowed CTLA4-Ig therapy to achieve long-term, rejection-free heart allograft survival. This beneficial effect was abolished upon Treg depletion. Combining ATG with IL-6 blockade prevents costimulation blockade-resistant rejection, thereby eliminating a major impediment to clinical use of costimulation blockers in transplantation.
Recovery of europium from E-waste using redox active tetrathiotungstate ligands
Authors: Perrin Marie A. , Dutheil Paul , Wörle Michael , Mougel Victor
Published: June 2024

Rare-earth elements (REEs) are critical to our modern economy, yet their mining from natural ores bears a profound environmental impact. Traditional separation techniques are chemical and energy-intensive because their chemical similarities make REEs very challenging to purify, requiring multiple extraction steps to achieve high purity products. This emphasizes the need for sustainable and straightforward separation methods. Here we introduce a strategy for the direct separation of europium (Eu) from complex mixtures under ambient conditions, leveraging on the redox non innocence of purely inorganic tungsten tetrathiolate (WS42−) ligands. The recovery of Eu is achieved upon reduction of Eu(III) to a Eu(II) coordination polymer, driven by an induced internal electron transfer from the tetrathiotungstate ligand. Applying this strategy to unconventional feedstock such as spent energy-saving lamps allows selective europium recovery with separation factors over 1000 and recovery efficiency as high as 99% without pre-treatment of the waste.
Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
Authors: Salihovic Samira , Nyström Niklas , Mathisen Charlotte Bache-Wiig , Kruse Robert , Olbjørn Christine , Andersen Svend , Noble Alexandra J. , Dorn-Rasmussen Maria , Bazov Igor , Perminow Gøri , Opheim Randi , Detlie Trond Espen , Huppertz-Hauss Gert , Hedin Charlotte R. H. , Carlson Marie , Öhman Lena , Magnusson Maria K. , Keita Åsa V. , Söderholm Johan D. , D’Amato Mauro , Orešič Matej , Wewer Vibeke , Satsangi Jack , Lindqvist Carl Mårten , Burisch Johan , Uhlig Holm H. , Repsilber Dirk , Hyötyläinen Tuulia , Høivik Marte Lie , Halfvarson Jonas
Published: June 2024

Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.
Observation of nonlinear response and Onsager regression in a photon Bose-Einstein condensate
Authors: Sazhin Alexander , Gladilin Vladimir N. , Erglis Andris , Hellmann Göran , Vewinger Frank , Weitz Martin , Wouters Michiel , Schmitt Julian
Published: June 2024

The quantum regression theorem states that the correlations of a system at two different times are governed by the same equations of motion as the single-time averages. This provides a powerful framework for the investigation of the intrinsic microscopic behaviour of physical systems by studying their macroscopic response to a controlled external perturbation. Here we experimentally demonstrate that the two-time particle number correlations in a photon Bose-Einstein condensate inside a dye-filled microcavity exhibit the same dynamics as the response of the condensate to a sudden perturbation of the dye molecule bath. This confirms the regression theorem for a quantum gas, and, moreover, demonstrates it in an unconventional form where the perturbation acts on the bath and only the condensate response is monitored. For strong perturbations, we observe nonlinear relaxation dynamics which our microscopic theory relates to the equilibrium fluctuations, thereby extending the regression theorem beyond the regime of linear response.
Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice
Authors: Mao Xiaotian , Larsen Sabina Birgitte , Zachariassen Line Sidsel Fisker , Brunse Anders , Adamberg Signe , Mejia Josue Leonardo Castro , Larsen Frej , Adamberg Kaarel , Nielsen Dennis Sandris , Hansen Axel Kornerup , Hansen Camilla Hartmann Friis , Rasmussen Torben Sølbeck
Published: June 2024

Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.
Novel temperatures are already widespread beneath the world’s tropical forest canopies
Authors: Trew Brittany T. , Edwards David P. , Lees Alexander C. , Klinges David H. , Early Regan , Svátek Martin , Plichta Roman , Matula Radim , Okello Joseph , Niessner Armin , Barthel Matti , Six Johan , Maeda Eduardo E. , Barlow Jos , do Nascimento Rodrigo Oliveria , Berenguer Erika , Ferreira Joice , Sallo-Bravo Jhonatan , Maclean Ilya M. D.
Published: June 2024

Tropical forest biodiversity is potentially at high risk from climate change, but most species reside within or below the canopy, where they are buffered from extreme temperatures. Here, by modelling the hourly below-canopy climate conditions of 300,000 tropical forest locations globally between 1990 and 2019, we show that recent small increases in below-canopy temperature (<1 °C) have led to highly novel temperature regimes across most of the tropics. This is the case even within contiguous forest, suggesting that tropical forests are sensitive to climate change. However, across the globe, some forest areas have experienced relatively non-novel temperature regimes and thus serve as important climate refugia that require urgent protection and restoration. This pantropical analysis of changes in below-canopy climatic conditions challenges the prevailing notion that tropical forest canopies reduce the severity of climate change impacts.
Fractional dynamics study: analytical solutions of modified Kordeweg-de Vries equation and coupled Burger’s equations using Aboodh transform
Authors: Iqbal Naveed , Hussain Shah , Hamza Amjad E. , Abdullah Ali , Mohammed Wael W. , Yar Mohammad
Published: June 2024

The study examines the using of Aboodh residual power series method and the Aboodh transform iteration method (ATIM) to analyze modified Korteweg-de Vries equation (mKdV) beside coupled Burger’s equations in the framework of the Caputo operator. These sets of equations represent the non-linear wave description for various physical systems. Through APM and ATIM, the solution for the coupled Burger’s equations and the mKdV equation get accurate dynamics information that will reveal the nature of their interactions. Using mathematically proven techniques and computational simulations, the developed methods’ efficiency and reliability are illustrated in the complex behaviors of these nonlinear wave equations, so that we can gain deeper insights into their complex dynamics. The research is aimed at an increase of the knowledge about the fractional calculus utilization for nonlinear wave motion and it also provides analytical tools for an analysis of wave acting in different scientific and engineering areas.
Effects of bone surface topography and chemistry on macrophage polarization
Authors: Özcolak Birgün , Erenay Berkay , Odabaş Sedat , Jandt Klaus D. , Garipcan Bora
Published: June 2024

Surface structure plays a crucial role in determining cell behavior on biomaterials, influencing cell adhesion, proliferation, differentiation, as well as immune cells and macrophage polarization. While grooves and ridges stimulate M2 polarization and pits and bumps promote M1 polarization, these structures do not accurately mimic the real bone surface. Consequently, the impact of mimicking bone surface topography on macrophage polarization remains unknown. Understanding the synergistic sequential roles of M1 and M2 macrophages in osteoimmunomodulation is crucial for effective bone tissue engineering. Thus, exploring the impact of bone surface microstructure mimicking biomaterials on macrophage polarization is critical. In this study, we aimed to sequentially activate M1 and M2 macrophages using Poly-l-Lactic acid (PLA) membranes with bone surface topographical features mimicked through the soft lithography technique. To mimic the bone surface topography, a bovine femur was used as a model surface, and the membranes were further modified with collagen type-I and hydroxyapatite to mimic the bone surface microenvironment. To determine the effect of these biomaterials on macrophage polarization, we conducted experimental analysis that contained estimating cytokine release profiles and characterizing cell morphology. Our results demonstrated the potential of the hydroxyapatite-deposited bone surface-mimicked PLA membranes to trigger sequential and synergistic M1 and M2 macrophage polarizations, suggesting their ability to achieve osteoimmunomodulatory macrophage polarization for bone tissue engineering applications. Although further experimental studies are required to completely investigate the osteoimmunomodulatory effects of these biomaterials, our results provide valuable insights into the potential advantages of biomaterials that mimic the complex microenvironment of bone surfaces.
Comparative assessment of differently randomized accelerated particle swarm optimization and squirrel search algorithms for selective harmonics elimination problem
Authors: Tariq Muhammad Ayyaz , Fakhar Muhammad Salman , Abbas Ghulam , Kashif Syed Abdul Rahman , Rehman Ateeq Ur , Ouahada Khmaies , Hamam Habib
Published: June 2024

A random initialization of the search particles is a strong argument in favor of the deployment of nature-inspired metaheuristic algorithms when the knowledge of a good initial guess is lacked. This article analyses the impact of the type of randomization on the working of algorithms and the acquired solutions. In this study, five different types of randomizations are applied to the Accelerated Particle Swarm Optimization (APSO) and Squirrel Search Algorithm (SSA) during the initializations and proceedings of the search particles for selective harmonics elimination (SHE). The types of randomizations include exponential, normal, Rayleigh, uniform, and Weibull characteristics. The statistical analysis shows that the type of randomization does impact the working of optimization algorithms and the fittest value of the objective function.
Stability of asymmetric Schwarzschild–Rindler–de Sitter thin shell wormhole
Authors: Eid A. , Alkaoud A. , Khader M. M. , Bakry M. A.
Published: June 2024

The paper examines the dynamics of asymmetric thin shell wormholes that connect two distinct spacetimes using the cut and paste technique. The focus is on analyzing the linear stability of these wormholes by considering radial perturbations and utilizing the modified generalized Chaplygin gas equation of state. The specific case of an asymmetric wormhole connecting Schwarzschild–Rindler spacetime to Schwarzschild–Rindler–de Sitter space–time is analyzed using this formalism. Our investigation uncovers the existence of both stable and unstable regions, which are contingent upon the appropriate selection of various parameters within the metric spacetime and equation of state. Additionally, we determine that stability regions exist as a consequence of the square speed of sound. By increasing the value of the cosmological constant, the stability region is expanded. Furthermore, the stability regions are augmented by the influence of Rindler parameters, while the stability regions are also affected by adjustments in the equation of state parameters, leading to their enlargement.
Epidemiological trends, antifungal drug susceptibility and SQLE point mutations in etiologic species of human dermatophytosis in Al-Diwaneyah, Iraq
Authors: Mahmood Hussein R. , Shams-Ghahfarokhi Masoomeh , Salehi Zahra , Razzaghi-Abyaneh Mehdi
Published: June 2024

Dermatophytes show a wide geographic distribution and are the main causative agents of skin fungal infections in many regions of the world. Recently, their resistance to antifungal drugs has led to an obstacle to effective treatment. To address the lack of dermatophytosis data in Iraq, this study was designed to investigate the distribution and prevalence of dermatophytes in the human population and single point mutations in squalene epoxidase gene (SQLE) of terbinafine resistant isolates. The identification of 102 dermatophytes isolated from clinical human dermatophytosis was performed through morphological and microscopic characteristics followed by molecular analysis based on ITS and TEF-1α sequencing. Phylogeny was achieved through RAxML analysis. CLSI M38-A2 protocol was used to assess antifungal susceptibility of the isolates to four major antifungal drugs. Additionally, the presence of point mutations in SQLE gene, which are responsible for terbinafine resistance was investigated. Tinea corporis was the most prevalent clinical manifestation accounting for 37.24% of examined cases of dermatophytosis. Based on ITS, T. indotineae (50.98%), T. mentagrophytes (19.61%), and M. canis (29.41%) was identified as an etiologic species. T. indotineae and T. mentagrophytes strains were identified as T. interdigitale based on TEF-1α. Terbinafine showed the highest efficacy among the tested antifungal drugs. T. indotineae and T. mentagrophytes showed the highest resistance to antifungal drugs with MICs of 2–4 and 4 μg/mL, while M. canis was the most susceptible species. Three of T. indotineae isolates showed mutations in SQLE gene Phe397Leu substitution. A non-previously described point mutation, Phe311Leu was identified in T. indotineae and mutations Lys276Asn, Phe397Leu and Leu419Phe were diagnosed in T. mentagrophytes XVII. The results of mutation analysis showed that Phe397Leu was a destabilizing mutation; protein stability has decreased with variations in pH, and point mutations affected the interatomic interaction, resulting in bond disruption. These results could help to control the progression of disease effectively and make decisions regarding the selection of appropriate drugs for dermatophyte infections.
Unsupervised underwater shipwreck detection in side-scan sonar images based on domain-adaptive techniques
Authors: Wei Chengwei , Bai Yunfei , Liu Chang , Zhu Yuhe , Wang Caiju , Li Xiaomao
Published: June 2024

Underwater object detection based on side-scan sonar (SSS) suffers from a lack of finely annotated data. This study aims to avoid the laborious task of annotation by achieving unsupervised underwater object detection through domain-adaptive object detection (DAOD). In DAOD, there exists a conflict between feature transferability and discriminability, suppressing the detection performance. To address this challenge, a domain collaborative bridging detector (DCBD) including intra-domain consistency constraint (IDCC) and domain collaborative bridging (DCB), is proposed. On one hand, previous static domain labels in adversarial-based methods hinder the domain discriminator from discerning subtle intra-domain discrepancies, thus decreasing feature transferability. IDCC addresses this by introducing contrastive learning to refine intra-domain similarity. On the other hand, DAOD encourages the feature extractor to extract domain-invariant features, overlooking potential discriminative signals embedded within domain attributes. DCB addresses this by complementing domain-invariant features with domain-relevant information, thereby bolstering feature discriminability. The feasibility of DCBD is validated using unlabeled underwater shipwrecks as a case study. Experiments show that our method achieves accuracy comparable to fully supervised methods in unsupervised SSS detection (92.16% AP50 and 98.50% recall), and achieves 52.6% AP50 on the famous benchmark dataset Foggy Cityscapes, exceeding the original state-of-the-art by 4.5%.
Research on spatial carving method of glutenite reservoir based on opacity voxel imaging
Authors: Zhao Hu , Zhang Zhong-wei , Yang Hong-wei , Wei Guo-hua
Published: June 2024

The glutenite reservoir in an exploration area in eastern China is well-developed and holds significant exploration potential as an important oil and gas alternative layer. However, due to the influence of sedimentary characteristics, the glutenite reservoir exhibits strong lateral heterogeneity, significant vertical thickness variations, and low accuracy in reservoir space characterization, which affects the reasonable and effective deployment of development wells. Seismic data contains the three-dimensional spatial characteristics of geological bodies, but how to design a suitable transfer function to extract the nonlinear relationship between seismic data and reservoirs is crucial. At present, the transfer functions are concentrated in low-dimensional or high-dimensional fixed mathematical models, which cannot accurately describe the nonlinear relationship between seismic data and complex reservoirs, resulting in low spatial description accuracy of complex reservoirs. In this regard, this paper first utilizes a fusion method based on probability kernel to fuse seismic attributes such as wave impedance, effective bandwidth, and composite envelope difference. This provide a more intuitive reflection of the distribution characteristics of glutenite reservoirs. Moreover, a hybrid nonlinear transfer function is established to transform the fused attribute cube into an opaque attribute cube. Finally, the illumination model and ray casting method are used to perform voxel imaging of the glutenite reservoirs, brighten the detailed characteristics of reservoir space, and then form a set of methods for ' brightening reservoirs and darkening non-reservoirs ', which improves the spatial engraving accuracy of glutenite reservoirs.
Integrated PBPK-EO modeling of osimertinib to predict plasma concentrations and intracranial EGFR engagement in patients with brain metastases
Authors: Liang Feng , Zhang Yimei , Xue Qian , Zhang Xiaoling
Published: June 2024

The purpose of this study was to develop and validate a physiologically based pharmacokinetic (PBPK) model combined with an EGFR occupancy (EO) model for osimertinib (OSI) to predict plasma trough concentration (Ctrough) and the intracranial time-course of EGFR (T790M and L858R mutants) engagement in patient populations. The PBPK model was also used to investigate the key factors affecting OSI pharmacokinetics (PK) and intracranial EGFR engagement, analyze resistance to the target mutation C797S, and determine optimal dosing regimens when used alone and in drug-drug interactions (DDIs). A population PBPK-EO model of OSI was developed using physicochemical, biochemical, binding kinetic, and physiological properties, and then validated using nine clinical PK studies, observed EO study, and two clinical DDI studies. The PBPK-EO model demonstrated good consistency with observed data, with most prediction-to-observation ratios falling within the range of 0.7 to 1.3 for plasma AUC, Cmax, Ctrough and intracranial free concentration. The simulated time-course of C797S occupancy by the PBPK model was much lower than T790M and L858R occupancy, providing an explanation for OSI on-target resistance to the C797S mutation. The PBPK model identified ABCB1 CLint,u, albumin level, and EGFR expression as key factors affecting plasma Ctrough and intracranial EO for OSI. Additionally, PBPK-EO simulations indicated that the optimal dosing regimen for OSI in patients with brain metastases is either 80 mg once daily (OD) or 160 mg OD, or 40 mg or 80 mg twice daily (BID). When used concomitantly with CYP enzyme perpetrators, the PBPK-EO model suggested appropriate dosing regimens of 80 mg OD with fluvoxamine (FLUV) itraconazole (ITR) or fluvoxamine (FLUC) for co-administration and an increase to 160 mg OD with rifampicin (RIF) or efavirenz (EFA). In conclusion, the PBPK-EO model has been shown to be capable of simulating the pharmacokinetic concentration–time profiles and the time-course of EGFR engagement for OSI, as well as determining the optimum dosing in various clinical situations.
Consistency in climate change impact reports among indigenous peoples and local communities depends on site contexts
Authors: Schunko Christoph , Álvarez-Fernández Santiago , Benyei Petra , Calvet-Mir Laura , Junqueira André B. , Li Xiaoyue , Porcuna-Ferrer Anna , Schlingmann Anna , Attoh Emmanuel M. N. A. N. , Carmona Rosario , Chengula Fasco , Fernández-Llamazares Álvaro , Singh Priyatma , Torrents-Ticó Miquel , Reyes-García Victoria
Published: June 2024

Indigenous Peoples and local communities are heavily affected by climatic changes. Investigating local understandings of climate change impacts, and their patterned distribution, is essential to effectively support monitoring and adaptation strategies. In this study, we aimed to understand the consistency in climate change impact reports and factors influencing consistency at site and individual levels. We conducted cross-cultural research among iTaukei (Fiji), Dagomba (Ghana), fisherfolks (Tanzania), Tsimane’ (Bolivia), Bassari (Senegal), ribeirinhos (Brazil), Mapuche (Chile), Mongolian (China), Tibetan (China) and Daasanach (Kenya) communities using semi-structured interviews, focus groups, and surveys among 1860 individuals. We found that cross-culturally more than two-thirds of individual reports of climate change impacts match site-confirmed reports. Consistency in reports is higher for changes related to pastoralism than crop production and wild plant gathering. Individual’s experience with nature, Indigenous and local knowledge, and local family roots are not significantly associated with consistency across sites, but site-specific associations are prevalent. Despite high average consistency among sites, there is considerable variation caused by site-specific factors, including livelihood activities, socio-cultural settings, and environmental conditions. Site contexts and related consistency in climate change impact reports need to be taken into account for climate change monitoring and adaptation planning.