bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics
Authors: Bahia Ravinder K. , Hao Xiaoguang , Hassam Rozina , Cseh Orsolya , Bozek Danielle A. , Luchman H. Artee , Weiss Samuel
Published: August 2023

Histone deacetylases are important epigenetic regulators that have been reported to play essential roles in cancer stem cell functions and are promising therapeutic targets in many cancers including glioblastoma. However, the functionally relevant roles of specific histone deacetylases, in the maintenance of key self-renewal and growth characteristics of brain tumour stem cell (BTSC) sub-populations of glioblastoma, remain to be fully resolved. Here, using pharmacological inhibition and genetic loss and gain of function approaches, we identify HDAC2 as the most relevant histone deacetylase for re-organization of chromatin accessibility resulting in maintenance of BTSC growth and self-renewal properties. Furthermore, its specific interaction with the transforming growth factor-β pathway related proteins, SMAD3 and SKI, is crucial for the maintenance of tumorigenic potential in BTSCs in vitro and in orthotopic xenograft models. Inhibition of HDAC2 activity and disruption of the coordinated mechanisms regulated by the HDAC2-SMAD3-SKI axis are thus promising therapeutic approaches for targeting BTSCs.
DECIMER.ai: an open platform for automated optical chemical structure identification, segmentation and recognition in scientific publications
Authors: Rajan Kohulan , Brinkhaus Henning Otto , Agea M. Isabel , Zielesny Achim , Steinbeck Christoph
Published: August 2023

The number of publications describing chemical structures has increased steadily over the last decades. However, the majority of published chemical information is currently not available in machine-readable form in public databases. It remains a challenge to automate the process of information extraction in a way that requires less manual intervention - especially the mining of chemical structure depictions. As an open-source platform that leverages recent advancements in deep learning, computer vision, and natural language processing,DECIMER.ai(Deep lEarning for Chemical IMagE Recognition) strives to automatically segment, classify, and translate chemical structure depictions from the printed literature. The segmentation and classification tools are the only openly available packages of their kind, and the optical chemical structure recognition (OCSR) core application yields outstanding performance on all benchmark datasets. The source code, the trained models and the datasets developed in this work have been published under permissive licences. An instance of theDECIMERweb application is available athttps://decimer.ai.
SCFRMF mediates degradation of the meiosis-specific recombinase DMC1
Authors: Xu Wanyue , Yu Yue , Jing Juli , Wu Zhen , Zhang Xumin , You Chenjiang , Ma Hong , Copenhaver Gregory P. , He Yan , Wang Yingxiang
Published: August 2023

Meiotic recombination requires the specific RecA homolog DMC1 recombinase to stabilize strand exchange intermediates in most eukaryotes. Normal DMC1 levels are crucial for its function, yet the regulatory mechanisms of DMC1 stability are unknown in any organism. Here, we show that the degradation of Arabidopsis DMC1 by the 26S proteasome depends on F-box proteins RMF1/2-mediated ubiquitination. Furthermore, RMF1/2 interact with the Skp1 ortholog ASK1 to form the ubiquitin ligase complex SCFRMF1/2. Genetic analyses demonstrate that RMF1/2, ASK1 and DMC1 act in the same pathway downstream of SPO11-1 dependent meiotic DNA double strand break formation and that the proper removal of DMC1 is crucial for meiotic crossover formation. Moreover, six DMC1 lysine residues were identified as important for its ubiquitination but not its interaction with RMF1/2. Our results reveal mechanistic insights into how the stability of a key meiotic recombinase that is broadly conserved in eukaryotes is regulated.
Enantioselective organocatalytic synthesis of axially chiral aldehyde-containing styrenes via SNAr reaction-guided dynamic kinetic resolution
Authors: Guo Fengyuan , Fang Siqiang , He Jiajia , Su Zhishan , Wang Tianli
Published: August 2023

The precise and efficient construction of axially chiral scaffolds, particularly toward the aryl-alkene atropoisomers with impeccably full enantiocontrol and highly structural diversity, remains greatly challenging. Herein, we disclose an organocatalytic asymmetric nucleophilic aromatic substitution (SNAr) reaction of aldehyde-substituted styrenes involving a dynamic kinetic resolution process via a hemiacetal intermediate, offering a novel and facile way to significant axial styrene scaffolds. Upon treatment of the aldehyde-containing styrenes bearing (o-hydroxyl)aryl unit with commonly available fluoroarenes in the presence of chiral peptide-phosphonium salts, the SNAr reaction via an exquisite bridged biaryl lactol intermediate undergoes smoothly to furnish a series of axially chiral aldehyde-containing styrenes decorated with various functionalities and bioactive fragments in high stereoselectivities (up to >99% ee) and complete E/Z selectivities. These resulting structural motifs are important building blocks for the preparation of diverse functionalized axial styrenes, which have great potential as efficient and privileged chiral ligands/catalysts in asymmetric synthesis.
Sphagnum increases soil’s sequestration capacity of mineral-associated organic carbon via activating metal oxides
Authors: Zhao Yunpeng , Liu Chengzhu , Li Xingqi , Ma Lixiao , Zhai Guoqing , Feng Xiaojuan
Published: August 2023

Sphagnum wetlands are global hotspots for carbon storage, conventionally attributed to the accumulation of decay-resistant litter. However, the buildup of mineral-associated organic carbon (MAOC) with relatively slow turnover has rarely been examined therein. Here, employing both large-scale comparisons across major terrestrial ecosystems and soil survey along Sphagnum gradients in distinct wetlands, we show that Sphagnum fosters a notable accumulation of metal-bound organic carbon (OC) via activating iron and aluminum (hydr)oxides in the soil. The unique phenolic and acidic metabolites of Sphagnum further strengthen metal-organic associations, leading to the dominance of metal-bound OC in soil MAOC. Importantly, in contrast with limited MAOC sequestration potentials elsewhere, MAOC increases linearly with soil OC accrual without signs of saturation in Sphagnum wetlands. These findings collectively demonstrate that Sphagnum acts as an efficient ‘rust engineer’ that largely boosts the rusty carbon sink in wetlands, potentially increasing long-term soil carbon sequestration.
Metabolic glycan labeling immobilizes dendritic cell membrane and enhances antitumor efficacy of dendritic cell vaccine
Authors: Han Joonsu , Bhatta Rimsha , Liu Yusheng , Bo Yang , Elosegui-Artola Alberto , Wang Hua
Published: August 2023

Dendritic cell (DC) vaccine was among the first FDA-approved cancer immunotherapies, but has been limited by the modest cytotoxic T lymphocyte (CTL) response and therapeutic efficacy. Here we report a facile metabolic labeling approach that enables targeted modulation of adoptively transferred DCs for developing enhanced DC vaccines. We show that metabolic glycan labeling can reduce the membrane mobility of DCs, which activates DCs and improves the antigen presentation and subsequent T cell priming property of DCs. Metabolic glycan labeling itself can enhance the antitumor efficacy of DC vaccines. In addition, the cell-surface chemical tags (e.g., azido groups) introduced via metabolic glycan labeling also enable in vivo conjugation of cytokines onto adoptively transferred DCs, which further enhances CTL response and antitumor efficacy. Our DC labeling and targeting technology provides a strategy to improve the therapeutic efficacy of DC vaccines, with minimal interference upon the clinical manufacturing process.
Adverse kidney outcomes of CDK 4/6 inhibitors for metastatic breast cancer
Authors: Hanna Paul E. , Strohbehn Ian A. , Moreno Daiana , Harden Destiny , Seethapathy Rituvanthikaa , Sawtell Rani , Wang Qiyu , Ouyang Tianqi , Katz-Agranov Nurit , Dinulos James , Wander Seth A. , Gupta Shruti , Sise Meghan E.
Published: August 2023

Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly improved overall and progression free survival of patients with metastatic breast cancer, but their effect on short and long-term kidney function is unknown. We found that early, mild estimated glomerular filtration rate (eGFR) decline was common in patients treated with CDK 4/6 inhibitors; however, severe kidney injury is rare and long-term eGFR decline is uncommon.
Probing octupolar hidden order via Janus impurities
Authors: Voleti Sreekar , Pradhan Koushik , Bhattacharjee Subhro , Saha-Dasgupta Tanusri , Paramekanti Arun
Published: August 2023

Quantum materials with non-Kramers doublets are a fascinating venue to realize multipolar hidden orders. Impurity probes which break point group symmetries, such as implanted muons or substitutional impurities, split the non-Kramers degeneracy and exhibit a Janus-faced influence in such systems: they can destroy the very order they seek to probe. Here, we explore this duality in cubic osmate double perovskites which are candidates for exoticd-orbital octupolar order competing with quadrupolar states. Using ab initio computations, Landau theory, and Monte Carlo simulations, we show that Janus impurities induce local strain fields, nucleating quadrupolar puddles and suppressing the octupolarTc. At the same time, strains mix the non-Kramers doublet with an excited magnetic triplet, creating parasitic dipole moments which directly expose the hidden octupolar order parameter. Our work unravels this Janus duality in recent impurity nuclear magnetic resonance (NMR) experiments, with important implications for uncovering hidden order in diverse multipolar materials.
JT002, a small molecule inhibitor of the NLRP3 inflammasome for the treatment of autoinflammatory disorders
Authors: Ambrus-Aikelin Geza , Takeda Katsuyuki , Joetham Anthony , Lazic Milos , Povero Davide , Santini Angelina M. , Pranadinata Rama , Johnson Casey D. , McGeough Matthew D. , Beasley Federico C. , Stansfield Ryan , McBride Christopher , Trzoss Lynnie , Hoffman Hal M. , Feldstein Ariel E. , Stafford Jeffrey A. , Veal James M. , Bain Gretchen , Gelfand Erwin W.
Published: August 2023

The NLRP3 inflammasome is an intracellular, multiprotein complex that promotes the auto-catalytic activation of caspase-1 and the subsequent maturation and secretion of the pro-inflammatory cytokines, IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome has been implicated in the pathophysiology of a number of inflammatory and autoimmune diseases, including neuroinflammation, cardiovascular disease, non-alcoholic steatohepatitis, lupus nephritis and severe asthma. Here we describe the preclinical profile of JT002, a novel small molecule inhibitor of the NLRP3 inflammasome. JT002 potently reduced NLRP3-dependent proinflammatory cytokine production across a number of cellular assays and prevented pyroptosis, an inflammatory form of cell death triggered by active caspase-1. JT002 demonstrated in vivo target engagement at therapeutically relevant concentrations when orally dosed in mice and prevented body weight loss and improved inflammatory and fibrotic endpoints in a model of Muckle–Wells syndrome (MWS). In two distinct models of neutrophilic airway inflammation, JT002 treatment significantly reduced airway hyperresponsiveness and airway neutrophilia. These results provide a rationale for the therapeutic targeting of the NLRP3 inflammasome in severe asthma and point to the use of JT002 in a variety of inflammatory disorders.
Effects of progressive body-weight versus barbell back squat training on strength, hypertrophy and body fat among sedentary young women
Authors: Wei Wei , Zhu JingX , Ren Shuang , Jan Yih-Kuen , Zhang WuL , Su Ronghai , He Li
Published: August 2023

The objective of this study was to compare the effects of progressive bodyweight training and barbell back squat on muscle strength, muscluar hypertrophy, and body fat percentage in sedentary young women. Thirteen sedentary young women (aged 19.77 ± 0.83 years, height 164.91 ± 6.01) were randomly assigned to either the progressive bodyweight group (n = 6, consisting of 10 levels of movements progressing from bilateral to unilateral) or the barbell squat group (n = 7, 60–80% 1RM). Both groups underwent two training sessions per week for 6 weeks. Measurements of muscle strength (isokinetic knee extensor and flexor muscle peak torque of each leg), muscle thickness (gluteus maximus, rectus femoris, and gastrocnemius muscles), and body fat percentage were taken at baseline and post-testing. Both groups showed a significant increase in isometric peak torque of the knee extensor and flexor (p < 0.05), but there were no significant between-group differences in isometric peak torque of the knee extensor and flexor (p > 0.05) or in the mean concentric peak torque of the knee H/Q ratio (p > 0.05). Both groups also showed significant increases in muscle thickness (p < 0.05), with no significant differences in Gastrocnemius, Rectus femoris and Gluteus maximus (p > 0.05). The percentage of body fat significantly decreased in the barbell group (pre: 28.66 ± 4.58% vs post: 24.96 ± 5.91%, p = 0.044), but not in the bodyweight group (pre: 24.18 ± 4.63% vs post: 24.02 ± 4.48%, p = 0.679). Our findings indicate that while both training methods increased maximum strength and muscle mass, barbell back squat training may be more effective in reducing body fat percentage.
Rapid determination of levels of the main constituents in e-liquids by near infrared spectroscopy
Authors: Hoffmann Anaïs R. F. , Jeffery Jana , Dallin Paul , Andrews John , Brokl Michał
Published: August 2023

Use of e-cigarettes is increasing, alongside an expanding variety of devices and e-liquids. To match this growth and in line with the expanding legal and regulatory requirements applicable to manufacturers of e-cigarettes (e.g. disclosure of list of ingredients and quantities thereof in a product), rapid methods for determining levels of the main e-liquid constituents—namely, propylene glycol (PG), vegetable glycerol (VG), water and nicotine—are needed. We have assessed the ability of near infrared (NIR) spectroscopy, coupled with partial least squares (PLS) regression, to predict the levels of these constituents in e-liquid formulations. Using NIR spectral data from a large set of reference e-liquids incorporating working concentration ranges, flavourings, and other ingredients, linear calibration models were established for PG, VG, water and nicotine (predicted vs theoretical values, all R2 > 0.995). The performance of these models was then evaluated on commercial e-liquids using NIR and compared to results obtained by gas chromatography (GC). A strong correlation was observed between NIR-predicted values and measured values for PG, VG and nicotine (all R2 > 0.955). There was less consistency between predicted and GC measured values for water due to the relatively high limit of quantification (LOQ) of the GC method (2.6% w/w) versus the e-liquid content (0–18% w/w). The LOQ of the NIR method for water was 0.6% w/w, suggesting that NIR may be a more accurate method than GC to predict water concentration in e-liquids, especially at low levels (< 2.6% w/w). Collectively, although limitations of the technique have been identified, specifically for e-liquids containing compounds that might interfere with the set calibrations, our findings suggest that NIR combined with PLS regression is a suitable tool for rapid, simultaneous and high-throughput measurement of PG, VG, water and nicotine levels in most commercial e-liquids.
Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms
Authors: Dalto Juliana F. , Medina Jorge H.
Published: August 2023

The fate of memories depends mainly on two opposing forces: the mechanisms required for the storage and maintenance of memory and the mechanisms underlying forgetting, being the latter much less understood. Here, we show the effect of inhibiting the small Rho GTPase Rac1 on the fate of inhibitory avoidance memory in male rats. The immediate post-training micro-infusion of the specific Rac1 inhibitor NSC23766 (150 ng/0.5 µl/ side) into the ventral tegmental area (VTA) enhanced long-term memory at 1, 7, and 14 days after a single training. Additionally, an opposed effect occurred when the inhibitor was infused at 12 h after training while no effect was observed immediately after testing animals at 1 day. Control experiments ruled out the possibility that post-training memory enhancement was due to facilitation of memory formation since no effect was found when animals were tested at 1 h after acquisition and no memory enhancement was observed after the formation of a weak memory. Immediate post-training micro-infusion of Rac1 inhibitor into the dorsal hippocampus, or the amygdala did not affect memory. Our findings support the idea of a Rac1-dependent time-specific active forgetting mechanism in the VTA controlling the strength of a long-term aversive memory.
Statistical parametric and non-parametric control charts for monitoring residential water consumption
Authors: Bogo Allyson Belli , Henning Elisa , Kalbusch Andreza
Published: August 2023

The adoption of strategies for monitoring water consumption is essential for water resources management, contributing to the promotion of the sustainability in the water sector. Statistical process control (SPC) charts, which are widely used in the industrial sector, are statistical methods developed to improve the quality of products and processes. The application of this method has reached other areas over the last decades and has recently been identified as an option for environmental monitoring. In this context, the application of SPC charts emerges as an option for water consumption monitoring, whether in a building or an urban scale. Thus, this article aims to analyze the application of statistical process control charts in the monitoring of water consumption of two housing compounds in Joinville, southern Brazil. The methodological procedures include the use of the Shewhart and the EWMA control charts in addition to the non-parametric alternative, the EWMA-SN, assessing the effectiveness of these techniques in detecting water leaks in residential apartment buildings. The data sets, obtained through a telemetry metering system from the water utility, represent a period of 243 days. The results show that control charts are a powerful tool in identifying changes in water consumption patterns, with the EWMA chart flagging the leaks sooner.
Carbon dioxide reduction by photosynthesis undetectable even during phytoplankton blooms in two lakes
Authors: Münzner Karla , Langenheder Silke , Weyhenmeyer Gesa A. , Csitári Bianka , Lindström Eva S.
Published: August 2023

Lakes located in the boreal region are generally supersaturated with carbon dioxide (CO2), which emerges from inflowing inorganic carbon from the surrounding watershed and from mineralization of allochthonous organic carbon. While these CO2 sources gained a lot of attention, processes that reduce the amount of CO2 have been less studied. We therefore examined the CO2 reduction capacity during times of phytoplankton blooms. We investigated partial pressure of CO2 (pCO2) in two lakes at times of blooms dominated by the cyanobacterium Gloeotrichia echinulata (Erken, Sweden) or by the nuisance alga Gonyostomum semen (Erssjön, Sweden) during two years. Our results showed that pCO2 and phytoplankton densities remained unrelated in the two lakes even during blooms. We suggest that physical factors, such as wind-induced water column mixing and import of inorganic carbon via inflowing waters suppressed the phytoplankton signal on pCO2. These results advance our understanding of carbon cycling in lakes and highlight the importance of detailed lake studies for more precise estimates of local, regional and global carbon budgets.
Importance of optimal rewiring guided by 3-dimensional optical frequency domain imaging during double-kissing culotte stenting demonstrated through a novel bench model
Authors: Okamura Takayuki , Iwasaki Kiyotaka , Lu Hongze , Zhu Xiaodong , Fujimura Tatsuhiro , Kitaba Norika , Murakami Keisuke , Nakamura Ryota , Mitsui Haruki , Tsuboko Yusuke , Miyazaki Yousuke , Matsuyama Tetsuya
Published: August 2023

The usefulness of optical frequency domain imaging (OFDI) guidance on two-stenting at left main bifurcation has not been evaluated. Here, we used a novel bench model to investigate whether pre-defined optimal rewiring with OFDI-guidance decreases acute incomplete stent apposition (ISA) at the left main bifurcation segment. A novel bench simulation system was developed to simulate the foreshortening and overlapping of daughter vessels as well as left main bifurcation motion under fluoroscopy. Double-kissing (DK) culotte stenting was performed using the novel bench model under fluoroscopy with or without OFDI-guidance. In the OFDI-guidance group, if the guidewire did not pass through the pre-defined optimal cell according to the 3-dimensional OFDI, additional attempts of rewiring into the jailed side branch were performed. The success rate of optimal jailed side branch rewiring after implantation of the first and second stent under OFDI-guidance was significantly higher than that under only angio-guidance. After completion of the DK-culotte stenting, the incidence and volume of ISA at the bifurcation segment in the OFDI-guidance group was significantly lower than that in the angio-guidance group. Online 3-dimensional OFDI-guided DK-culotte stenting according to a pre-defined optimal rewiring point might be superior to only angio-guided rewiring for reducing ISA at the bifurcation.
Advances in methylation analysis of liquid biopsy in early cancer detection of colorectal and lung cancer
Authors: Kwon Hyuk-Jung , Shin Sun Hye , Kim Hyun Ho , Min Na Young , Lim YuGyeong , Joo Tae-woon , Lee Kyoung Joo , Jeong Min-Seon , Kim Hyojung , Yun Seon-young , Kim YoonHee , Park Dabin , Joo Joungsu , Bae Jin-Sik , Lee Sunghoon , Jeong Byeong-Ho , Lee Kyungjong , Lee Hayemin , Kim Hong Kwan , Kim Kyongchol , Um Sang-Won , An Changhyeok , Lee Min Seob
Published: August 2023

Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I–IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I–IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I–IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis.

Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT 04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509. Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr, https://who.init/ictrp. Healthy control samples were retrospectively registered.
Endothelial CD34 expression and regulation of immune cell response in-vitro
Authors: Arakelian Lousineh , Lion Julien , Churlaud Guillaume , Bargui Rezlene , Thierry Briac , Mutabazi Evelyne , Bruneval Patrick , Alberdi Antonio José , Doliger Christelle , Veyssiere Maëva , Larghero Jérôme , Mooney Nuala
Published: August 2023

Endothelial cells cover the lining of different blood vessels and lymph nodes, and have major functions including the transport of blood, vessel homeostasis, inflammatory responses, control of transendothelial migration of circulating cells into the tissues, and formation of new blood vessels. Therefore, understanding these cells is of major interest. The morphological features, phenotype and function of endothelial cells varies according to the vascular bed examined. The sialomucin, CD34, is widely used as an endothelial marker. However, CD34 is differentially expressed on endothelial cells in different organs and in pathological conditions. Little is known about regulation of endothelial CD34 expression or function. Expression of CD34 is also strongly regulated in-vitro in endothelial cell models, including human umbilical vein endothelial cells (HUVEC) and endothelial colony forming cells (ECFC). We have therefore analysed the expression and function of CD34 by comparing CD34high and CD34low endothelial cell subpopulations. Transcriptomic analysis showed that CD34 gene and protein expressions are highly correlated, that CD34high cells proliferate less but express higher levels of IL-33 and Angiopoietin 2, compared with CD34low cells. Higher secretion levels of IL-33 and Angiopoietin 2 by CD34high HUVECs was confirmed by ELISA. Finally, when endothelial cells were allowed to interact with peripheral blood mononuclear cells, CD34high endothelial cells activated stronger proliferation of regulatory T lymphocytes (Tregs) compared to CD34low cells whereas expansion of other CD4+-T cell subsets was equivalent. These results suggest that CD34 expression by endothelial cells in-vitro associates with their ability to proliferate and with an immunogenic ability that favours the tolerogenic response.
Summer rain and wet soil rather than management affect the distribution of a toxic plant in production grasslands
Authors: Wagner Thomas C. , Laumer Michael , Kuhn Gisbert , Mayer Franziska , Gehring Klaus , Krieger Marie-Therese , Kollmann Johannes , Albrecht Harald
Published: August 2023

In the northern forelands of the Alps, farmers report an increase ofJacobaea aquaticain production grasslands. Due to its toxicity, the species affects grassland productivity and calls for costly control measures. We are investigating the extent to which management practices or climatic factors are responsible for the increase of the species and how the situation will change due to climate change. We tested for effects of management intensity, fertilization, agri-environmental measures, and soil disturbance, and modeled the occurrence of the species under rcp4.5 and rcp8.5 scenarios. The main determinants of the occurrence of the species are soil type and summer rainfall. A high risk is associated with wet soils and > 400 mm of rain between June and August; an influence of the management-related factors could not be detected. Under the climate-change scenarios, the overall distribution decreases and shifts to the wetter alpine regions. Thus, the current increase is rather a shift in the occurrence of the species due to the altered precipitation situation. Under future climatic conditions, the species will decline and retreat to higher regions in the Alps. This will decrease the risk of forage contamination for production grassland in the lowlands.
Comparison of typical Thai and Hungarian personality profiles using the Zuckerman–Kuhlman–Aluja Personality Questionnaire
Authors: Kövi Zsuzsanna , Wongpakaran Tinakon , Wongpakaran Nahathai , Zábó Virág , Birkás Béla , Mirnics Zsuzsanna
Published: August 2023

The aim of our study was to compare typical Thai and Hungarian personality profiles of the Zuckerman–Kuhlman–Aluja Personality Questionnaire (ZKA-PQ). 672 Thai and 647 Hungarian were included in our study. The distribution of age, gender and education level were matched. The ZKA-PQ was administered that measures Aggression, Extraversion, Activity, Sensation Seeking and Neuroticism. We tested reliability, the structural invariance and analyzed aggregated mean profiles for cultures as well as typical profiles by cluster analyses. Reliability of factors were acceptable in both cultures, but some facets (especially AC3 Restlessness) showed low reliability. The global Tucker’s coefficient of congruence (TCC) for cross-cultural factorial invariance was 95. We have also run a Multigroup Confirmatory Factor Analysis, but fit indices were not adequate. Cross-cultural neural network invariance was not met either. Hungarians scored significantly higher on Extraversion, Sensation Seeking, Aggression and Activity. Cluster-analyses revealed six typical profiles: Introverted impulsive, Reserved, Resilients, Overcontrolled, Aggressive impulsive and Positive sensation seeker. Majority of first two clusters were Thai respondents, majority for last two clusters were Hungarians. In sum, there were some cross-cultural congruence in factor structure, but strict invariance was not fulfilled. Comparison of mean profiles remain tentative, but cluster analysis revealed cross-cultural differences in typical profiles.
Development of an artificial intelligence bacteremia prediction model and evaluation of its impact on physician predictions focusing on uncertainty
Authors: Choi Dong Hyun , Lim Min Hyuk , Kim Ki Hong , Shin Sang Do , Hong Ki Jeong , Kim Sungwan
Published: August 2023

Prediction of bacteremia is a clinically important but challenging task. An artificial intelligence (AI) model has the potential to facilitate early bacteremia prediction, aiding emergency department (ED) physicians in making timely decisions and reducing unnecessary medical costs. In this study, we developed and externally validated a Bayesian neural network-based AI bacteremia prediction model (AI-BPM). We also evaluated its impact on physician predictive performance considering both AI and physician uncertainties using historical patient data. A retrospective cohort of 15,362 adult patients with blood cultures performed in the ED was used to develop the AI-BPM. The AI-BPM used structured and unstructured text data acquired during the early stage of ED visit, and provided both the point estimate and 95% confidence interval (CI) of its predictions. High AI-BPM uncertainty was defined as when the predetermined bacteremia risk threshold (5%) was included in the 95% CI of the AI-BPM prediction, and low AI-BPM uncertainty was when it was not included. In the temporal validation dataset (N = 8,188), the AI-BPM achieved area under the receiver operating characteristic curve (AUC) of 0.754 (95% CI 0.737–0.771), sensitivity of 0.917 (95% CI 0.897–0.934), and specificity of 0.340 (95% CI 0.330–0.351). In the external validation dataset (N = 7,029), the AI-BPM’s AUC was 0.738 (95% CI 0.722–0.755), sensitivity was 0.927 (95% CI 0.909–0.942), and specificity was 0.319 (95% CI 0.307–0.330). The AUC of the post-AI physicians predictions (0.703, 95% CI 0.654–0.753) was significantly improved compared with that of the pre-AI predictions (0.639, 95% CI 0.585–0.693; p-value < 0.001) in the sampled dataset (N = 1,000). The AI-BPM especially improved the predictive performance of physicians in cases with high physician uncertainty (low subjective confidence) and low AI-BPM uncertainty. Our results suggest that the uncertainty of both the AI model and physicians should be considered for successful AI model implementation.
Time-dependent variations in BK polyomavirus genome from kidney transplant recipients with persistent viremia
Authors: Mineeva-Sangwo Olga , Van Loon Elisabet , Andrei Graciela , Kuypers Dirk , Naesens Maarten , Snoeck Robert
Published: August 2023

BK polyomavirus (BKPyV) is a human DNA virus that resides latent in the host’s renal tissue. Reactivation occurs occasionally and in case of kidney transplantation, it can lead to polyomavirus-associated nephropathy (PVAN). Due to the lack of specific antivirals for BKPyV and despite the risk of allograft rejection, reduction of immunosuppression remains the main approach for treating PVAN. Current data suggests that mutations can accumulate over time in the major capsid protein VP1 and can lead to neutralization escape in kidney transplant recipients. Herein, we show that mutations occur throughout the entire BKPyV genome, including in VP1. Changes were identified by per-patient comparison of viral genome sequences obtained in samples from 32 kidney recipients with persistent viremia collected at different post-transplant time-points. Amino acid changes were observed in both earlier and later post-transplant samples, although some of them were only found in later samples. Changes in VP1 mainly consisted in the introduction of a new amino acid. A switch back to the conservative amino acid was also observed. This should be considered in future approaches for treating BKPyV infection in kidney transplant recipients.
Paleoenvironmental changes in the coastal zone of the northwest South China Sea during the last 13 kyr
Authors: Liang Dingyong , Wu Shuzhuang , Xu Guoqiang , Xia Changjian , Gao Fanglei , Lin Yihua , Du Juan , Jia Liyun
Published: August 2023

Marine sediments in coastal zones serve as valuable archives for understanding the history of silicate chemical weathering and summer monsoon rainfall in source areas, providing insights into terrigenous climate and environmental evolution. In this study, we investigated the grain size, clay minerals, and geochemistry of sediments retrieved from core KZK01 in the coastal zone of the northwest South China Sea during the past 13 thousand years before present (kyr BP). Our findings demonstrated that the illite crystallinity index served as a reliable proxy for assessing the intensity of chemical weathering in the source area. Moreover, it distinctly recorded significant climatic events such as the Younger Dryas and Bond events during the Holocene. The dominant driver of the regional East Asian summer monsoon was identified as summer solar radiation in the Northern Hemisphere at low latitudes. Cold climate events exhibited global consistency, potentially influenced by the presence of ice sheets at high latitudes. Lastly, our records revealed a distinct transition at 9.0 kyr, highlighting significant impacts of the Qiongzhou Strait and sea level rise on regional climate dynamics.
Biological sex is associated with heterogeneous responses to IL-6 receptor inhibitor treatment in COVID-19—A retrospective cohort study
Authors: Stein Dan F. , Foley Conor , Byott Matt , Nastouli Eleni , Ambler Gareth , Arulkumaran Nishkantha
Published: August 2023

COVID-19 is associated with higher inflammatory markers, illness severity and mortality in males compared to females. Differences in immune responses to COVID-19 may underpin sex- specific outcome differences. We hypothesised that anti-IL-6 receptor monoclonal antibodies are associated with heterogenous treatment effects between male and female patients. We conducted a retrospective cohort study assessing the interaction between biological sex and anti-IL-6 receptor antibody treatment with respect to hospital mortality or progression of respiratory failure. We used a Cox proportional hazards regression model to adjust for age, ethnicity, steroid use, baseline C-reactive protein, and COVID-19 variant. We included 1274 patients, of which 58% were male and 15% received anti-IL-6 receptor antibodies. There was a significant interaction between sex and anti-IL-6 receptor antibody use on progression to respiratory failure or death (p = 0.05). For patients who did not receive anti-IL-6 receptor antibodies, the risk of death was slightly higher in males (HR = 1.13 (0.72–1.79)), whereas in patients who did receive anti-IL-6 receptor antibodies, the risk was lower in males (HR = 0.65 (0.32–1.33)). There was a heterogenous treatment effect with anti-IL-6 receptor antibodies between males and females; with anti-IL-6 receptor antibody use having a greater benefit in preventing progression to respiratory failure or death in males (p = 0.05).
Machine learning‑based prediction of survival prognosis in esophageal squamous cell carcinoma
Authors: Zhang Kaijiong , Ye Bo , Wu Lichun , Ni Sujiao , Li Yang , Wang Qifeng , Zhang Peng , Wang Dongsheng
Published: August 2023

The current prognostic tools for esophageal squamous cell carcinoma (ESCC) lack the necessary accuracy to facilitate individualized patient management strategies. To address this issue, this study was conducted to develop a machine learning (ML) prediction model for ESCC patients' survival management. Six ML approaches, including Rpart, Elastic Net, GBM, Random Forest, GLMboost, and the machine learning-extended CoxPH method, were employed to develop risk prediction models. The model was trained on a dataset of 1954 ESCC patients with 27 clinical features and validated on a dataset of 487 ESCC patients. The discriminative performance of the models was assessed using the concordance index (C-index). The best performing model was used for risk stratification and clinical evaluation. The study found that N stage, T stage, surgical margin, tumor grade, tumor length, sex, MPV, AST, FIB, and Mg are the important feature for ESCC patients’ survival. The machine learning-extended CoxPH model, Elastic Net, and Random Forest had similar performance in predicting the mortality risk of ESCC patients, and outperformed GBM, GLMboost, and Rpart. The risk scores derived from the CoxPH model effectively stratified ESCC patients into low-, intermediate-, and high-risk groups with distinctly different 3-year overall survival (OS) probabilities of 80.8%, 58.2%, and 29.5%, respectively. This risk stratification was also observed in the validation cohort. Furthermore, the risk model demonstrated greater discriminative ability and net benefit than the AJCC8th stage, suggesting its potential as a prognostic tool for predicting survival events and guiding clinical decision-making. The classical algorithm of the CoxPH method was also found to be sufficiently good for interpretive studies.
Hog1-mediated stress tolerance in the pathogenic fungus Trichosporon asahii
Authors: Matsumoto Yasuhiko , Sugiyama Yu , Nagamachi Tae , Yoshikawa Asami , Sugita Takashi
Published: August 2023

Trichosporon asahii is an opportunistic pathogenic fungus that causes severe and sometimes fatal infections in immunocompromised patients. Hog1, a mitogen-activated protein kinase, regulates the stress resistance of some pathogenic fungi, however its role in T. asahii has not been investigated. Here, we demonstrated that the hog1 gene-deficient T. asahii mutant is sensitive to high temperature, cell membrane stress, oxidative stress, and antifungal drugs. Growth of the hog1 gene-deficient T. asahii mutant was delayed at 40 °C. The hog1 gene-deficient T. asahii mutant also exhibited sensitivity to sodium dodecyl sulfate, hydrogen peroxide, menadione, methyl methanesulfonate, UV exposure, and antifungal drugs such as amphotericin B under a glucose-rich condition. Under a glucose-restricted condition, the hog1 gene-deficient mutant exhibited sensitivity to NaCl and KCl. The virulence of the hog1 gene-deficient mutant against silkworms was attenuated. Moreover, the viability of the hog1 gene-deficient mutant decreased in the silkworm hemolymph. These phenotypes were restored by re-introducing the hog1 gene into the gene-deficient mutant. Our findings suggest that Hog1 plays a critical role in regulating cellular stress responses in T. asahii.
A task-unified network with transformer and spatial–temporal convolution for left ventricular quantification
Authors: Li Dapeng , Peng Yanjun , Sun Jindong , Guo Yanfei
Published: August 2023

Quantification of the cardiac function is vital for diagnosing and curing the cardiovascular diseases. Left ventricular function measurement is the most commonly used measure to evaluate the function of cardiac in clinical practice, how to improve the accuracy of left ventricular quantitative assessment results has always been the subject of research by medical researchers. Although considerable efforts have been put forward to measure the left ventricle (LV) automatically using deep learning methods, the accurate quantification is yet a challenge work as a result of the changeable anatomy structure of heart in the systolic diastolic cycle. Besides, most methods used direct regression method which lacks of visual based analysis. In this work, a deep learning segmentation and regression task-unified network with transformer and spatial–temporal convolution is proposed to segment and quantify the LV simultaneously. The segmentation module leverages a U-Net like 3D Transformer model to predict the contour of three anatomy structures, while the regression module learns spatial–temporal representations from the original images and the reconstruct feature map from segmentation path to estimate the finally desired quantification metrics. Furthermore, we employ a joint task loss function to train the two module networks. Our framework is evaluated on the MICCAI 2017 Left Ventricle Full Quantification Challenge dataset. The results of experiments demonstrate the effectiveness of our framework, which achieves competitive cardiac quantification metric results and at the same time produces visualized segmentation results that are conducive to later analysis.
Socioeconomic and environmental determinants of foot and mouth disease incidence: an ecological, cross-sectional study across Iran using spatial modeling
Authors: Nazari Ashani Mahdi , Alesheikh Ali Asghar , Neisani Samani Zeinab , Lotfata Aynaz , Bayat Sayeh , Alipour Siamak , Hoseini Benyamin
Published: August 2023

Foot-and-mouth disease (FMD) is a highly contagious animal disease caused by a ribonucleic acid (RNA) virus, with significant economic costs and uneven distribution across Asia, Africa, and South America. While spatial analysis and modeling of FMD are still in their early stages, this research aimed to identify socio-environmental determinants of FMD incidence in Iran at the provincial level by studying 135 outbreaks reported between March 21, 2017, and March 21, 2018. We obtained 46 potential socio-environmental determinants and selected four variables, including percentage of population, precipitation in January, percentage of sheep, and percentage of goats, to be used in spatial regression models to estimate variation in spatial heterogeneity. In our analysis, we employed global models, namely ordinary least squares (OLS), spatial error model (SEM), and spatial lag model (SLM), as well as local models, including geographically weighted regression (GWR) and multiscale geographically weighted regression (MGWR). The MGWR model yielded the highest adjusted $${R}^{2}$$

R

2

of 90%, outperforming the other local and global models. Using local models to map the effects of environmental determinants (such as the percentage of sheep and precipitation) on the spatial variability of FMD incidence provides decision-makers with helpful information for targeted interventions. Our findings advocate for multiscale and multidisciplinary policies to reduce FMD incidence.
The effectiveness of isometric protocols using an external load or voluntary effort on jump height enhancement in trained females
Authors: Koźlenia Dawid , Domaradzki Jarosław
Published: August 2023

This study aimed to examine the effectiveness of isometric post-activation performance enhancement protocols using an external load (EXL) or voluntary effort (VE) on jump height (JH) in trained females divided into EXL (n = 15), VE (n = 14), and control (CON; n = 12) groups. JH was assessed using countermovement jumps at baseline and the third, fifth, seventh, and ninth minutes after the protocols. The EXL performed three sets of back squats with a 70%-repetition maximum load for four seconds, with one-minute breaks. The VE performed three sets of pushing against an immovable bar in the back squat position for five seconds, with one-minute breaks. The CON group ran on a treadmill at 6 km/h for four minutes. A RM-ANOVA showed a significant interaction for group-time (p < 0.01). The EXL protocol provided JH improvement at the third minute compared to baseline (p = 0.01), though it decreased in subsequent minutes (p < 0.05). JH declined in the VE group at the third and fifth minutes (p < 0.05), then peaked, surpassing baseline, after nine minutes (p = 0.04). No significant differences were found between the protocols in the relative effect (best—baseline) (p = 0.09), though the EXL group appeared to gain more (effect size [ES] = 0.76). Both protocols improved JH, but caution is required due to peak performance time and potential JH reduction.
El Niño and La Niña asymmetry in short-term predictability on springtime initial condition
Authors: Chen Hui , Jin Yishuai , Shen Xingchen , Lin Xiaopei , Hu Ruikun
Published: August 2023

El Niño-Southern Oscillation (ENSO) asymmetry in predictability on springtime initial condition remains unclear. From the perspective of the spring predictability barrier (SPB), this paper investigates the ENSO asymmetry in SPB and explores the potential factors that may lead to this asymmetry. Both the observation and 29 Coupled Model Intercomparison Project Phase 6 (CMIP6) models show that the spring sea surface temperature (SST) persistence is significantly higher in El Niño years than that in La Niña years, and the SPB intensity is stronger in La Niña years than that in El Niño years. Through the recharge oscillator model, observation and CMIP6 models, we demonstrate that the nonlinear wind stress response to SST anomalies in spring is the main cause of the asymmetric SPB intensity. By the mixed-layer heat budget of the tropical Pacific in the spring, we further identify that a stronger response of zonal wind stress in El Niño events can cause a stronger zonal advection feedback, which finally leads to a weaker SPB and enhances the predictability of El Niño. In contrast, the cooling SST in the spring only leads to weak easterly anomalies, the zonal advection feedback is relatively weaker, thus SPB is stronger and the predictability of La Niña is lower. From the perspective of SPB, we suggest that El Niño is more predictable than La Niña.
Possible factors for the recent changes in frequency of central Indian Summer Monsoon precipitation extremes during 2005–2020
Authors: Bajrang C. , Attada Raju , Goswami B. N.
Published: August 2023

The transitions of short-term trends of Indian Summer Monsoon daily precipitation extremes remain poorly understood. Here, we show a short-term declination of temporal frequency of monsoonal precipitation extremes over Central India for the last 15 years starting from 2005 to 2020 while the low and moderate events show increasing trends. The possible dynamical and thermodynamical factors for the observed decline in precipitation extremes include depletion in moisture transport to Central India via cross-equatorial flow and the low-level Somali jet, caused by reduced evaporation from the regional moisture sources. In addition, the vertical gradient of the moist static energy exhibits favorable conditions for increased lower atmospheric stability, supporting the declining trends. Lastly, the Atlantic Zonal Mode seems to be a potential large-scale climate driver for the less frequent central Indian extreme rainfall events during 2005–2020.