bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐Speed Video Observations of Needles Evolving Into Negative Leaders in a Positive Cloud‐To‐Ground Lightning Flash
Authors: Wu Bin , Qi Qi , Lyu Weitao , Ma Ying , Chen Lyuwen , Lyu Fanchao , Zhang Yang , Fan Yanfeng , Rakov Vladimir A. 
Published: November 2023

AbstractHigh‐speed video records of a single‐stroke positive cloud‐to‐ground (+CG) flash were used to examine the evolution of eight needles developing more or less radially from the +CG channel. All these eight needles occurred during the later return‐stroke stage and the following continuing current stage. Six needles, after their initial extension from the lateral surface of the parent channel core, elongated via bidirectional recoil events, which are responsible for flickering, and two of them evolved into negative stepped leaders. For the latter two, the mean extension speed decreased from 5.3 × 106 to 3.4 × 105 and then to 1.3 × 105 m/s during the initial, recoil‐event, and stepping stages, respectively. The initial needle extension ranged from 70 to 320 m (N = 8), extension via recoil events from 50 to 210 m (N = 6), and extension via stepping from 810 to 1,870 m (N = 2). Compared with needles developing from leader channels, the different behavior of needle flickering, the longer length, the faster extension speed, and the higher flickering rate observed in this work may be attributed to a considerably higher current (rate of charge supply) during the return‐stroke and early continuing‐current stages of +CG flashes.
Zonal Indian Ocean Variability Drives Millennial‐Scale Precipitation Changes in Northern Madagascar
Authors: Tiger Benjamin H. , Burns Stephen , Dawson Robin R. , Scroxton Nick , Godfrey Laurie R. , Ranivoharimanana Lovasoa , Faina Peterson , McGee David 
Published: November 2023

AbstractThe low latitude Indian Ocean is warming faster than other tropical basins, and its interannual climate variability is projected to become more extreme under future emissions scenarios with substantial impacts on developing Indian Ocean rim countries. Therefore, it has become increasingly important to understand the drivers of regional precipitation in a changing climate. Here we present a new speleothem record from Anjohibe, a cave in northwest (NW) Madagascar well situated to record past changes in the Intertropical Convergence Zone (ITCZ). U‐Th ages date speleothem growth from 27 to 14 ka. δ18O, δ13C, and trace metal proxies reconstruct drier conditions during Heinrich Stadials 1 and 2, and wetter conditions during the Last Glacial Maximum and Bølling–Allerød. This is surprising considering hypotheses arguing for southward (northward) ITCZ shifts during North Atlantic cooling (warming) events, which would be expected to result in wetter (drier) conditions at Anjohibe in the Southern Hemisphere tropics. The reconstructed Indian Ocean zonal (west‐east) sea surface temperature (SST) gradient is in close agreement with hydroclimate proxies in NW Madagascar, with periods of increased precipitation correlating with relatively warmer conditions in the western Indian Ocean and cooler conditions in the eastern Indian Ocean. Such gradients could drive long‐term shifts in the strength of the Walker circulation with widespread effects on hydroclimate across East Africa. These results suggest that during abrupt millennial‐scale climate changes, it is not meridional ITCZ shifts, but the tropical Indian Ocean SST gradient and Walker circulation driving East African hydroclimate variability.
SCFβTrCP-mediated degradation of SHARP1 in triple-negative breast cancer
Authors: Enriqué Steinberg Juliana Haydeé , Rossi Fabiana Alejandra , Magliozzi Roberto , Yuniati Laurensia , Santucci Matteo , Rossi Mario , Guardavaccaro Daniele , Lauriola Angela 
Published: November 2023

AbstractTriple-negative breast cancer (TNBC) is a subtype of breast cancer associated with metastasis, high recurrence rate, and poor survival. The basic helix-loop-helix transcription factor SHARP1 (Split and Hairy-related Protein 1) has been identified as a suppressor of the metastatic behavior of TNBC. SHARP1 blocks the invasive phenotype of TNBC by inhibiting hypoxia-inducible factors and its loss correlates with poor survival of breast cancer patients. Here, we show that SHARP1 is an unstable protein that is targeted for proteasomal degradation by the E3 ubiquitin ligase complex SCFβTrCP. SHARP1 recruits βTrCP via a phosphodegron encompassing Ser240 and Glu245 which are required for SHARP1 ubiquitylation and degradation. Furthermore, mice injected with TNBC cells expressing the non-degradable SHARP1(S240A/E245A) mutant display reduced tumor growth and increased tumor-free survival. Our study suggests that targeting the βTrCP-dependent degradation of SHARP1 represents a therapeutic strategy in TNBC.
Prediction on X-ray output of free electron laser based on artificial neural networks
Authors: Li Kenan , Zhou Guanqun , Liu Yanwei , Wu Juhao , Lin Ming-fu , Cheng Xinxin , Lutman Alberto A. , Seaberg Matthew , Smith Howard , Kakhandiki Pranav A. , Sakdinawat Anne 
Published: November 2023

AbstractKnowledge of x-ray free electron lasers’ (XFELs) pulse characteristics delivered to a sample is crucial for ensuring high-quality x-rays for scientific experiments. XFELs’ self-amplified spontaneous emission process causes spatial and spectral variations in x-ray pulses entering a sample, which leads to measurement uncertainties for experiments relying on multiple XFEL pulses. Accurate in-situ measurements of x-ray wavefront and energy spectrum incident upon a sample poses challenges. Here we address this by developing a virtual diagnostics framework using an artificial neural network (ANN) to predict x-ray photon beam properties from electron beam properties. We recorded XFEL electron parameters while adjusting the accelerator’s configurations and measured the resulting x-ray wavefront and energy spectrum shot-to-shot. Training the ANN with this data enables effective prediction of single-shot or average x-ray beam output based on XFEL undulator and electron parameters. This demonstrates the potential of utilizing ANNs for virtual diagnostics linking XFEL electron and photon beam properties.
Themis2 regulates natural killer cell memory function and formation
Authors: Nabekura Tsukasa , Deborah Elfira Amalia , Tahara Saeko , Arai Yuya , Love Paul E. , Kako Koichiro , Fukamizu Akiyoshi , Muratani Masafumi , Shibuya Akira 
Published: November 2023

AbstractImmunological memory is a hallmark of the adaptive immune system. Although natural killer (NK) cells are innate immune cells important for the immediate host defence, they can differentiate into memory NK cells. The molecular mechanisms controlling this differentiation are yet to be fully elucidated. Here we identify the scaffold protein Themis2 as a critical regulator of memory NK cell differentiation and function. Themis2-deficient NK cells expressing Ly49H, an activating NK receptor for the mouse cytomegalovirus (MCMV) antigen m157, show enhanced differentiation into memory NK cells and augment host protection against MCMV infection. Themis2 inhibits the effector function of NK cells after stimulation of Ly49H and multiple activating NK receptors, though not specific to memory NK cells. Mechanistically, Themis2 suppresses Ly49H signalling by attenuating ZAP70/Syk phosphorylation, and it also translocates to the nucleus, where it promotes Zfp740-mediated repression to regulate the persistence of memory NK cells. Zfp740 deficiency increases the number of memory NK cells and enhances the effector function of memory NK cells, which further supports the relevance of the Themis2-Zfp740 pathway. In conclusion, our study shows that Themis2 quantitatively and qualitatively regulates NK cell memory formation.
Reactivity of complex communities can be more important than stability
Authors: Yang Yuguang , Coyte Katharine Z. , Foster Kevin R. , Li Aming 
Published: November 2023

AbstractUnderstanding stability—whether a community will eventually return to its original state after a perturbation—is a major focus in the study of various complex systems, particularly complex ecosystems. Here, we challenge this focus, showing that short-term dynamics can be a better predictor of outcomes for complex ecosystems. Using random matrix theory, we study how complex ecosystems behave immediately after small perturbations. Our analyses show that many communities are expected to be ‘reactive’, whereby some perturbations will be amplified initially and generate a response that is directly opposite to that predicted by typical stability measures. In particular, we find reactivity is prevalent for complex communities of mixed interactions and for structured communities, which are both expected to be common in nature. Finally, we show that reactivity can be a better predictor of extinction risk than stability, particularly when communities face frequent perturbations, as is increasingly common. Our results suggest that, alongside stability, reactivity is a fundamental measure for assessing ecosystem health.
Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter
Authors: Tang Qingyu , Sinclair Matt , Hasdemir Hale S. , Stein Richard A. , Karakas Erkan , Tajkhorshid Emad , Mchaourab Hassane S. 
Published: November 2023

AbstractHere we used cryo-electron microscopy (cryo-EM), double electron-electron resonance spectroscopy (DEER), and molecular dynamics (MD) simulations, to capture and characterize ATP- and substrate-bound inward-facing (IF) and occluded (OC) conformational states of the heterodimeric ATP binding cassette (ABC) multidrug exporter BmrCD in lipid nanodiscs. Supported by DEER analysis, the structures reveal that ATP-powered isomerization entails changes in the relative symmetry of the BmrC and BmrD subunits that propagates from the transmembrane domain to the nucleotide binding domain. The structures uncover asymmetric substrate and Mg2+ binding which we hypothesize are required for triggering ATP hydrolysis preferentially in one of the nucleotide-binding sites. MD simulations demonstrate that multiple lipid molecules differentially bind the IF versus the OC conformation thus establishing that lipid interactions modulate BmrCD energy landscape. Our findings are framed in a model that highlights the role of asymmetric conformations in the ATP-coupled transport with general implications to the mechanism of ABC transporters.
Lanthanum modulated reaction pacemakers on a single catalytic nanoparticle
Authors: Raab Maximilian , Zeininger Johannes , Suchorski Yuri , Genest Alexander , Weigl Carla , Rupprechter Günther 
Published: November 2023

AbstractPromoters are important in catalysis, but the atomistic details of their function and particularly their role in reaction instabilities such as kinetic phase transitions and oscillations are often unknown. Employing hydrogen oxidation as probe reaction, a Rh nanotip for mimicking a single Rh nanoparticle and field electron microscopy for in situ monitoring, we demonstrate a La-mediated local catalytic effect. The oscillatory mode of the reaction provides a tool for studying the interplay between different types of reaction pacemakers, i.e., specific local surface atomic configurations that initiate kinetic transitions. The presence of La shifts the bistable reaction states, changes the oscillation pattern and deactivates one of two pacemaker types for the La-free surface. The observed effects originate from the La-enhanced oxygen activation on the catalyst. The experimental observations are corroborated by micro-kinetic model simulations comprising a system of 25 coupled oscillators.
Multipole engineering by displacement resonance: a new degree of freedom of Mie resonance
Authors: Tang Yu-Lung , Yen Te-Hsin , Nishida Kentaro , Li Chien-Hsuan , Chen Yu-Chieh , Zhang Tianyue , Pai Chi-Kang , Chen Kuo-Ping , Li Xiangping , Takahara Junichi , Chu Shi-Wei 
Published: November 2023

AbstractThe canonical studies on Mie scattering unravel strong electric/magnetic optical responses in nanostructures, laying foundation for emerging meta-photonic applications. Conventionally, the morphology-sensitive resonances hinge on the normalized frequency, i.e. particle size over wavelength, but non-paraxial incidence symmetry is overlooked. Here, through confocal reflection microscopy with a tight focus scanning over silicon nanostructures, the scattering point spread functions unveil distinctive spatial patterns featuring that linear scattering efficiency is maximal when the focus is misaligned. The underlying physical mechanism is the excitation of higher-order multipolar modes, not accessible by plane wave irradiation, via displacement resonance, which showcases a significant reduction of nonlinear response threshold, sign flip in all-optical switching, and spatial resolution enhancement. Our result fundamentally extends the century-old light scattering theory, and suggests new dimensions to tailor Mie resonances.
Symptomatic, functional and quality of life measures of remission in 194 outpatients with schizophrenia followed naturalistically in a 6-month, non-interventional study of aripiprazole once-monthly
Authors: Correll Christoph U. , Brieden Andreas , Janetzky Wolfgang 
Published: November 2023

AbstractAn important goal in the treatment of patients with schizophrenia is remission in various domains, i.e., of symptoms, psychosocial functioning and subjective well-being. We undertook a post hoc analysis of pre-stabilized outpatients with schizophrenia and complete outcome data who had been enrolled in a 6-month non-interventional study of aripiprazole once-monthly (AOM) at 75 German sites. Key outcomes were (i) symptomatic remission (cross-sectional Andreasen et al. criteria (≤mild positive and negative key symptoms on the Brief Psychiatric Rating Scale (BPRS))); (ii) functional remission (Global Assessment of Functioning (GAF) scale score >70), and (iii) subjective well-being remission (WHO-5 scale score ≥13) at week 24. Of 242 enrolled patients, 194 (80.2%) (age = 43.9 ± 15.3 years; 51.5% male, illness duration = 14.0 ± 12.0 years) with complete data were analyzed. While 61.3% of the patients achieved symptomatic remission and 76.8% achieved remission regarding subjective well-being, only 24.7% achieved psychosocial functioning remission at 6 months. Remission rates were similar for men and women and across strata of disease duration with, on average, less remission in patients with longer illness duration. Correlations of improvements on the BPRS and GAF were weak, with the weakest correlation between the BPRS depressive mood item and the GAF scale, but similarly high correlation between BPRS subscales or the BPRS depressive mood item and subjective well-being. These findings suggest that while treatment with AOM can lead to symptomatic remission and remission regarding subjective well-being, additional interventions such as psychosocial therapy or supported employment and education may be necessary to achieve functional remission.
A systematic review and meta-analysis on the ocular characteristics in children and adolescents with neurodevelopmental disorders
Authors: Dastamooz Sima , Tham Clement C. Y. , Yam Jason C. S. , Li Minghui , Wong Stephen H. S. , Sit Cindy H. P. 
Published: November 2023

AbstractTo conduct a systematic review and meta-analysis of the association between children and adolescents with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) and ocular characteristics. Systematic review with meta-analysis. Six databases (PubMed, Scopus, APA PsycInfo, Embase, EBSCOhost, and Cochrane library) were selected for a systematic literature search from database inception to July 2022. The observational studies assessing and reporting at least one outcome regarding ocular characteristics in children and adolescents with ADHD or ASD aged 6–17 were included. Studies in languages other than English, studies of adult or elderly human populations, and animal studies were excluded. The results were analyzed following the PRISMA guideline 2020. The findings of 15 studies, including 433 participants with ADHD, 253 participants with ASD, and 514 participants with typical development (TD), revealed that there were no significant differences in retinal nerve fiber layer, ganglion cell complex, and macular thickness between the ADHD group and the TD group. In subgroup analysis, significant differences in inferior ganglion cell (MD = − 3.19; 95% CI = [− 6.06, − 0.31], p = 0.03) and nasal macular thickness (MD = 5.88; 95% CI = [− 0.01, 11.76], p = 0.05) were detected between the ADHD group and the TD group. A significant difference in pupillary light reflex (PLR) was also observed between the ASD group and the TD group (MD = 29.7; 95% CI = [18.79, 40.63], p < 0.001). Existing evidence suggests a possible association between children and adolescents with ADHD or ASD and ocular characteristics. Given the limited number of studies, further research on a larger cohort is necessary to claim a possible diagnosis of ADHD or ASD through ocular characteristics.
Macular vessel density in central retinal artery occlusion with retinal arterial cannulation
Authors: Soga Naoki , Tanaka Shin , Inoue Maiko , Inoue Tatsuya , Hayashi Atsushi , de Juan Eugene , Kadonosono Kazuaki 
Published: November 2023

AbstractTo characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included. Optical coherent tomography angiography (OCTA)-based macular vessel density and visual acuity were examined. The dynamic ranged-based normalized rates of vessel density was compared within each group at the first visit to the clinic and 7 days after the onset. Macular vessel density in cannulation group was significantly better at 7 days after the onset than that at the first visit (3.73 ± 3.02 mm−1 vs. 7.89 ± 1.02 mm−1, P = 0.0001), while there wasn’t significant improvement of macular vessel density in standard treatment group at 7 days after the onset (2.13 ± 1.62 mm−1 vs. 2.89 ± 0.22 mm−1, P = 0.067). At one month after the onset, mean LogMAR visual acuity in CRAO eyes with cannulation significantly improved compared with that at the first visit after the onset (1.678 vs. 0.979, P = 0.00012). Macular vessel density loss in CRAO eyes was improved by retinal arterial cannulation. Early intervention of retinal arterial cannulation is useful for minimizing visual impairment in CRAO eyes.
Engineering and design of promising T-cell-based multi-epitope vaccine candidates against leishmaniasis
Authors: Basmenj Esmaeil Roohparvar , Arastonejad Mahshid , Mamizadeh Mina , Alem Mahsa , KhalatbariLimaki Mahdi , Ghiabi Shadan , Khamesipour Ali , Majidiani Hamidreza , Shams Morteza , Irannejad Hamid 
Published: November 2023

AbstractCutaneous leishmaniasis (CL) is a very common parasitic infection in subtropical areas worldwide. Throughout decades, there have been challenges in vaccine design and vaccination against CL. The present study introduced novel T-cell-based vaccine candidates containing IFN-γ Inducing epitopic fragments from Leishmania major (L. major) glycoprotein 46 (gp46), cathepsin L-like and B-like proteases, histone H2A, glucose-regulated protein 78 (grp78) and stress-inducible protein 1 (STI-1). For this aim, top-ranked human leukocyte antigen (HLA)-specific, IFN-γ Inducing, antigenic, CD4+ and CD8+ binders were highlighted. Four vaccine candidates were generated using different spacers (AAY, GPGPG, GDGDG) and adjuvants (RS-09 peptide, human IFN-γ, a combination of both, Mycobacterium tuberculosis Resuscitation promoting factor E (RpfE)). Based on the immune simulation profile, those with RS-09 peptide (Leish-App) and RpfE (Leish-Rpf) elicited robust immune responses and their tertiary structure were further refined. Also, molecular docking of the selected vaccine models with the human toll-like receptor 4 showed proper interactions, particularly for Leish-App, for which molecular dynamics simulations showed a stable connection with TLR-4. Upon codon optimization, both models were finally ligated into the pET28a( +) vector. In conclusion, two potent multi-epitope vaccine candidates were designed against CL and evaluated using comprehensive in silico methods, while further wet experiments are, also, recommended.
Identification of a cholesterol metabolism-related prognostic signature for multiple myeloma
Authors: Zhao Na , Qu Chunxia , Yang Yan , Li Huihui , Li Yueyue , Zhu Hongbo , Long Zhiguo 
Published: November 2023

AbstractMultiple myeloma (MM) is a prevalent hematological malignancy that poses significant challenges for treatment. Dysregulated cholesterol metabolism has been linked to tumorigenesis, disease progression, and therapy resistance. However, the correlation between cholesterol metabolism-related genes (CMGs) and the prognosis of MM remains unclear. Univariate Cox regression analysis and LASSO Cox regression analysis were applied to construct an overall survival-related signature based on the Gene Expression Omnibus database. The signature was validated using three external datasets. Enrichment analysis and immune analysis were performed between two risk groups. Furthermore, an optimal nomogram was established for clinical application, and its performance was assessed by the calibration curve and C-index. A total of 6 CMGs were selected to establish the prognostic signature, including ANXA2, CHKA, NSDHL, PMVK, SCAP and SQLE. The prognostic signature demonstrated good prognostic performance and correlated with several important clinical parameters, including number of transplants, International Staging System, albumin, beta2-Microglobulin and lactate dehydrogenase levels. The function analysis and immune analysis revealed that the metabolic pathways and immunologic status were associated with risk score. The nomogram incorporating the signature along with other clinical characteristics was constructed and the discrimination was verified by the calibration curve and C-index. Our findings indicated the potential prognostic connotation of cholesterol metabolism in MM. The development and validation of the prognostic signature is expected to aid in predicting prognosis and guiding precision treatment for MM.