bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Detection Efficiency of World Wide Lightning Location Network in Southeast Asian Region
Authors: Rafi Mehdi Hasan , Holzworth Robert H. , Mostafa Md Golam 
Published: August 2024

AbstractThe detection efficiency (DE) of the World Wide Lightning Location Network (WWLLN) is evaluated in Southeast Asia by comparing WWLLN data with the Earth Network Total Lightning Network (ENTLN) data taking into account time, distance, and peak‐current parameters. The performance of WWLLN is evaluated in the months of November and December in two different years (2020–2021). These periods are selected to assess the change (if any) in DE overtime and the inclusion of new stations. The strokes between the two networks were considered matched if they fell within a time criterion of 100 µs and a location difference of 25 km. Using this criterion, 5.2 × 106 WWLLN strokes were matched with ENTLN cloud‐to‐ground (CG) lightning strokes in November‐December 2020, resulting in a DE of 32.9%. Similarly, 4.6 × 106 WWLLN strokes were found to match in November‐December 2021, yielding a DE of 36.5%. Analysis of the peak‐currents reveals that DE is lowest (<10%) for a peak‐current below ±10 kA. However, for peak‐current exceeding ±50 kA, the DE increases to ∼60%. During November‐December 2021, WWLLN reported 38.95 × 106 lightning strokes globally; amongst them, Dhaka station detected 0.5 × 106 strokes, contributing to a 1.3% increase in the global DE. Dhaka station detects most lightning strokes within 8 × 103 km, which diminishes to zero after 10 × 103 km. The Dhaka station recorded a larger number of strokes at longer detection distances during midnight (22:00–02:00) than during noon (10:00–14:00). The results signify a positive impact of the Dhaka station on WWLLN's DE during the mentioned period.
Hepcidin depending on astrocytic NEO1 ameliorates blood-brain barrier dysfunction after subarachnoid hemorrhage
Authors: Wei Boyang , Liu Wenchao , Jin Lei , Huang Yaxian , Cheng Wenping , Fan Haiyan , Su Shixing , Jin Fa , Zhang Xin , Yang Zeyu , Liang Shuyin , Li Longxiang , Wu Yu , Liu Yanchao , Duan Chuanzhi , Li Xifeng 
Published: August 2024

AbstractSubarachnoid hemorrhage (SAH) significantly compromises the blood-brain barrier (BBB) and impairs patient recovery. This study elucidates the critical role of astrocytic Neogenin-1 (NEO1) in BBB integrity post-SAH and examines the regulatory effects of hepcidin on endothelial cell (EC) function amid NEO1-mediated disruptions in iron homeostasis. Proteomic analyses of cerebrospinal fluid (CSF) from SAH patients revealed a substantial decrease in NEO1 expression, identifying it as a key factor in BBB integrity. 111 CSF proteins were significantly reduced in early SAH stages (days 1–3), with NEO1 among the most significantly altered. This dysregulation was linked to poorer patient outcomes, as indicated by a negative correlation between NEO1 levels and Modified Rankin Scale scores six months post-SAH (R = −0.4743, P < 0.0001). Experimental models further highlighted the importance of NEO1: SAH model and NEO1GFAP-Cre mice exhibited exacerbated EC dysfunction and increased BBB permeability, evidenced by significant Evans Blue retention and dextran leakage in the parietal cortex, effects that were mitigated by hepcidin administration. Our findings highlight the complex interplay between astrocytic signaling and endothelial function in SAH pathophysiology. The loss of astrocytic NEO1 led to increased EC proliferation and altered BBB structure, as confirmed by transmission electron microscopy and immunostaining for PECAM-1, indicating heightened blood vessel density in the affected cortex. Hepcidin treatment effectively reversed the EC dysfunction and BBB disruption in both NEO1-cKO mice and the SAH model, highlighting its potential as a therapeutic agent to enhance recovery and improve prognosis following SAH.
ALDH1A1 promotes immune escape of tumor cells through ZBTB7B-glycolysis pathway
Authors: Wang Mingyuan , Wang Taoli , Wang Jinjin , Yang Yuexin , Li Xi , Chen Huan , Liao Jingnan 
Published: August 2024

AbstractThe primary impediment to the success of immunotherapy lies in the immune evasion orchestrated by tumors, contributing to the suboptimal overall response rates observed. Despite this recognition, the intricacies of the underlying mechanisms remain incompletely understood. Through preliminary detection of clinical patient tissues, we have found that ALDH1A1 was a key gene for the prognosis of cancer patients and tumor glycolysis. In vitro experiments and tumor formation in nude mice suggested that targeting ALDH1A1 could inhibit tumor growth. Through further analysis of xenograft tumor models in immune-normal mice and flow cytometry, we found that deficiency in ALDH1A1 could promote immune system suppression of tumors in vivo. Specifically, RNA-seq analysis, combined with qPCR and western blot, identified the transcription factor ZBTB7B as downstream of ALDH1A1. The binding sites of the transcription factor ZBTB7B on the LDHA promoter region, which is responsible for regulating the rate-limiting enzyme gene LDHA in glycolysis, were determined using luciferase reporter gene detection and Chip-qPCR, respectively. In addition, the increased SUMOylation of ZBTB7B stabilized its transcriptional activity. Further in vivo and in vitro experiments confirmed that the combination of targeting ALDH1A1 and ZBTB7B with immune checkpoint inhibitors could synergistically inhibit tumors in vivo. Finally, after conducting additional verification of patient tissue and clinical data, we have confirmed the potential translational value of targeting ALDH1A1 and ZBTB7B for tumor immunotherapy. These results emphasize the potential translational significance of targeting ALDH1A1 and ZBTB7B in the realm of tumor immunotherapy. The convergence of ALDH1A1 inhibition and immune checkpoint blockade, particularly with PD-L1/PD-1 mAb, presents a compelling avenue for curtailing tumor immune escape.
Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor
Authors: de Jonge Janeska J. , Graw Andreas , Kargas Vasileios , Batters Christopher , Montanarella Antonino F. , O’Loughlin Tom , Johnson Chloe , Arden Susan D. , Warren Alan J. , Geeves Michael A. , Kendrick-Jones John , Zaccai Nathan R. , Kröss Markus , Veigel Claudia , Buss Folma 
Published: August 2024

AbstractMyosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Motor activity control within the cell involves on/off switches, however, few examples are known of how myosins regulate speed or processivity and fine-tune their activity to a specific cellular task. Here, we describe a phosphorylation event for myosins of class VI (MYO6) in the motor domain, which accelerates its ATPase activity leading to a 4-fold increase in motor speed determined by actin-gliding assays, single molecule mechanics and stopped flow kinetics. We demonstrate that the serine/threonine kinase DYRK2 phosphorylates MYO6 at S267 in vitro. Single-molecule optical-tweezers studies at low load reveal that S267-phosphorylation results in faster nucleotide-exchange kinetics without change in the working stroke of the motor. The selective increase in stiffness of the acto-MYO6 complex when proceeding load-dependently into the nucleotide-free rigor state demonstrates that S267-phosphorylation turns MYO6 into a stronger motor. Finally, molecular dynamic simulations of the nucleotide-free motor reveal an alternative interaction network within insert-1 upon phosphorylation, suggesting a molecular mechanism, which regulates insert-1 positioning, turning the S267-phosphorylated MYO6 into a faster motor.
Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial
Authors: Balinda Henriette U. , Kelly William J. , Kaklamani Virginia G. , Lathrop Kate I. , Canola Marcela Mazo , Ghamasaee Pegah , Sareddy Gangadhara R. , Michalek Joel , Gilbert Andrea R. , Surapaneni Prathibha , Tiziani Stefano , Pandey Renu , Chiou Jennifer , Lodi Alessia , Floyd John R. , Brenner Andrew J. 
Published: August 2024

AbstractSacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM). We enrolled 25 patients aged ≥18 years diagnosed with BCBM and rGBM to receive a single intravenous dose of SG at 10 mg/kg given one day before resection and continued on days 1 and 8 of 21-day cycles following recovery. The PFS was 8 months and 2 months for BCBM and rGBM cohorts, respectively. The OS was 35.2 months and 9.5 months, respectively. Grade≥3 AE included neutropenia (28%), hypokalemia (8%), seizure (8%), thromboembolic event (8%), urinary tract infection (8%) and muscle weakness of the lower limb (8%). In post-surgical tissue, the median total SN-38 was 249.8 ng/g for BCBM and 104.5 ng/g for rGBM, thus fulfilling the primary endpoint. Biomarker analysis suggests delivery of payload by direct release at target site and that hypoxic changes do not drive indirect release. Secondary endpoint of OS was 35.2 months for the BCBM cohort and 9.5 months for rGBM. Non-planned exploratory endpoint of ORR was 38% for BCBM and 29%, respectively. Exploratory endpoint of Trop-2 expression was observed in 100% of BCBM and 78% of rGBM tumors. In conclusion, SG was found to be well tolerated with adequate penetration into intracranial tumors and promising preliminary activity within the CNS. Trial Registration: Trial (NCT03995706) enrolled at Clinical Trials.gov as Neuro/Sacituzumab Govitecan/Breast Brain Metastasis/Glioblastoma/Ph 0: https://clinicaltrials.gov/study/NCT03995706?cond=NCT03995706.
Atomic-precision control of plasmon-induced single-molecule switching in a metal–semiconductor nanojunction
Authors: Park Youngwook , Hamada Ikutaro , Hammud Adnan , Kumagai Takashi , Wolf Martin , Shiotari Akitoshi 
Published: August 2024

AbstractAtomic-scale control of photochemistry facilitates extreme miniaturisation of optoelectronic devices. Localised surface plasmons, which provide strong confinement and enhancement of electromagnetic fields at the nanoscale, secure a route to achieve sub-nanoscale reaction control. Such local plasmon-induced photochemistry has been realised only in metallic structures so far. Here we demonstrate controlled plasmon-induced single-molecule switching of peryleneanhydride on a silicon surface. Using a plasmon-resonant tip in low-temperature scanning tunnelling microscopy, we can selectively induce the dissociation of the O–Si bonds between the molecule and surface, resulting in reversible switching between two configurations within the nanojunction. The switching rate can be controlled by changing the tip height with 0.1-Å precision. Furthermore, the plasmon-induced reactivity can be modified by chemical substitution within the molecule, suggesting the importance of atomic-level design for plasmon-driven optoelectronic devices. Thus, metal–single-molecule–semiconductor junctions may serve as a prominent controllable platform beyond conventional nano-optoelectronics.
Risk of stroke in male and female patients with atrial fibrillation in a nationwide cohort
Authors: Nielsen Peter Brønnum , Brøndum Rasmus Froberg , Nøhr Anne Krogh , Overvad Thure Filskov , Lip Gregory Y. H. 
Published: August 2024

AbstractFemale sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation (AF) with comorbid prevalent stroke risk factors. Management has evolved over time towards a holistic approach that may have diminished any sex difference in AF-related stroke. In a nationwide cohort of AF patients free from oral anticoagulant treatment, we examine the time trends in stroke risk overall and in relation to risk differences between male and female patients. Here we show that among 158,982 patients with AF (median age 78 years (IQR: 71 to 85); 52% female) the 1-year thromboembolic risk was highest between 1997–2000 with a risk of 5.6% and lowest between 2013–2016 with a risk of 3.8%, declining over the last two decades. The excess stroke risk for female vs male patients has also been declining, with risk-score adjusted relative risk estimates suggesting limited sex-difference in recent years.
Integrative radiomics clustering analysis to decipher breast cancer heterogeneity and prognostic indicators through multiparametric MRI
Authors: He Yongsheng , Duan Shaofeng , Wang Wuling , Yang Hongkai , Pan Shuya , Cheng Weiqun , Xia Liang , Qi Xuan 
Published: August 2024

AbstractBreast cancer diagnosis and treatment have been revolutionized by multiparametric Magnetic Resonance Imaging (mpMRI), encompassing T2-weighted imaging (T2WI), Diffusion-weighted imaging (DWI), and Dynamic Contrast-Enhanced MRI (DCE-MRI). We conducted a retrospective analysis of mpMRI data from 194 breast cancer patients (September 2019 to October 2023). Using ‘pyradiomics’ for radiomics feature extraction and MOVICS for unsupervised clustering. Interestingly, we identified two distinct patient clusters associated with significant differences in molecular subtypes, particularly in Luminal A subtype distribution (p = 0.03), estrogen receptor (ER) (p = 0.01), progesterone receptor (PR) (p = 0.04), mean tumor size (p < 0.01), lymph node metastasis (LNM) (p = 0.01), and edema (p < 0.01). Our study emphasizes mpMRI’s potential in breast cancer by using radiomics-based cluster analysis to categorize tumors, uncovering heterogeneity, and aiding in personalized treatment strategies.
Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε
Authors: Roske Johann J. , Yeeles Joseph T. P. 
Published: August 2024

AbstractDuring chromosome replication, the nascent leading strand is synthesized by DNA polymerase epsilon (Pol ε), which associates with the sliding clamp processivity factor proliferating cell nuclear antigen (PCNA) to form a processive holoenzyme. For high-fidelity DNA synthesis, Pol ε relies on nucleotide selectivity and its proofreading ability to detect and excise a misincorporated nucleotide. Here, we present cryo-electron microscopy (cryo-EM) structures of human Pol ε in complex with PCNA, DNA and an incoming nucleotide, revealing how Pol ε associates with PCNA through its PCNA-interacting peptide box and additional unique features of its catalytic domain. Furthermore, by solving a series of cryo-EM structures of Pol ε at a mismatch-containing DNA, we elucidate how Pol ε senses and edits a misincorporated nucleotide. Our structures delineate steps along an intramolecular switching mechanism between polymerase and exonuclease activities, providing the basis for a proofreading mechanism in B-family replicative polymerases.
Intuitive moral bias favors the religiously faithful
Authors: Dayer Alex , Aswamenakul Chanuwas , Turner Matthew A. , Nicolay Scott , Wang Emily , Shurik Katherine , Holbrook Colin 
Published: August 2024

AbstractBelief in powerful supernatural agents that enforce moral norms has been theoretically linked with cooperative altruism and prosociality. Correspondingly, prior research reveals an implicit association between atheism and extreme antisociality (e.g., serial murder). However, findings centered on associations between lack of faith and moral transgression do not directly address the hypothesized conceptual association between religious belief and prosociality. Accordingly, we conducted two pre-registered experiments depicting a “serial helper” to assess biases related to extraordinary helpfulness, mirroring designs depicting a serial killer used in prior cross-cultural work. In both a predominantly religious society (the U.S., Study 1) and a predominantly secular society (New Zealand, Study 2), we successfully replicated previous research linking atheism with transgression, and obtained evidence for a substantially stronger conceptual association between religiosity and virtue. The results suggest that stereotypes linking religiosity with prosociality are both real and global in scale.
Utilization of RESOLV with polymer to produce prazosin hydrochloride nanoparticles and optimization of the process parameters
Authors: Ansari Eslam , Honarvar Bizhan , Sajadian Seyed Ali , Arab Aboosadi Zahra , Azizi Mehdi 
Published: August 2024

AbstractIn this study, rapid expansion of a supercritical solution into a Liquid Solvent (RESOLV) was used for the first time to produce pharmaceutical nanoparticles of Prazosin hydrochloride (PRH). The Taguchi method (robust design) was utilized to design the experiments and ensure obtaining the optimal process conditions. The pressure (15–25 MPa), temperature (308–328 K) and nozzle diameter (300–700 μm) effects on the morphology and size distribution of the resulting particles were also examined. The size of the particles decreased from about 40 μm to the range of (252–418 nm). FTIR, DLS, FESEM, XRD, DSC were used to characterize the primary and processed PRH particles. According to DSC investigations, RESOLV-produced PRH showed lower crystallinity than original PRH.
Monitoring of nanoplasmonics-assisted deuterium production in a polymer seeded with resonant Au nanorods using in situ femtosecond laser induced breakdown spectroscopy
Authors: Kroó N. , Aladi M. , Kedves M. , Ráczkevi B. , Kumari A. , Rácz P. , Veres M. , Galbács G. , Csernai L. P. , Biró T. S. 
Published: August 2024

AbstractIn this brief report, we present laser induced breakdown spectroscopy (LIBS) evidence of deuterium (D) production in a 3:1 urethane dimethacrylate (UDMA) and triethylene glycol dimethacrylate (TEGDMA) polymer doped with resonant gold nanorods, induced by intense, 40 fs laser pulses. The in situ recorded LIBS spectra revealed that the D/(2D + H) increased to 4–8% in the polymer samples in selected events. The extent of transmutation was found to linearly increase with the laser pulse energy (intensity) between 2 and 25 mJ (up to 3 × 1017W/cm2). The observed effect is attributed only to the field enhancing effects due to excited localized surface plasmons on the gold nanoparticles.
Effects of pacing strategy on metabolic responses to 2-min intense exercise in Thoroughbred horses
Authors: Takahashi Kenya , Mukai Kazutaka , Ebisuda Yusaku , Sugiyama Fumi , Yoshida Toshinobu , Hatta Hideo , Kitaoka Yu 
Published: August 2024

AbstractEvidence suggests that positive pacing strategy improves exercise performance and fatigue tolerance in athletic events lasting 1–5 min. This study investigated muscle metabolic responses to positive and negative pacing strategies in Thoroughbred horses. Eight Thoroughbred horses performed 2 min treadmill running using positive (1 min at 110% maximal O2 uptake [V̇O2max], followed by 1 min at 90% V̇O2max) and negative (1 min at 90% V̇O2max, followed by 1 min at 110% V̇O2max) pacing strategies. The arterial-mixed venous O2 difference did not significantly differ between the two strategies. Plasma lactate levels increased toward 2 min, with significantly higher concentrations during positive pacing than during negative pacing. Muscle glycogen level was significantly lower at 1 and 2 min of positive pacing than those of negative pacing. Metabolomic analysis showed that the sum of glycolytic intermediates increased during the first half of positive pacing and the second half of negative pacing. Regardless of pacing strategy, the sum of tricarboxylic acid cycle metabolites increased during the first half but remained unchanged thereafter. Our data suggest that positive pacing strategy is likely to activate glycolytic metabolism to a greater extent compared to negative pacing, even though the total workload is identical.
Evaluating multimodal AI in medical diagnostics
Authors: Kaczmarczyk Robert , Wilhelm Theresa Isabelle , Martin Ron , Roos Jonas 
Published: August 2024

AbstractThis study evaluates multimodal AI models’ accuracy and responsiveness in answering NEJM Image Challenge questions, juxtaposed with human collective intelligence, underscoring AI’s potential and current limitations in clinical diagnostics. Anthropic’s Claude 3 family demonstrated the highest accuracy among the evaluated AI models, surpassing the average human accuracy, while collective human decision-making outperformed all AI models. GPT-4 Vision Preview exhibited selectivity, responding more to easier questions with smaller images and longer questions.
Designing Cultural Adaptations of Caregiver-Implemented Interventions for Latinx Caregivers of Children Who Use Augmentative and Alternative Communication: Key Considerations
Authors: Soto Gloria , Vega Jennifer 
Published: August 2024

Purpose:
Caregivers play a critical role in their children's development and serve as their primary communication partners. Family interactions provide the most naturally occurring opportunities for children with complex communication needs to learn language in the context of family routines. A growing body of research suggests that caregivers can effectively support their children's use of augmentative and alternative communication (AAC) systems when provided with appropriate training and coaching through caregiver-implemented interventions (CIIs). However, the efficacy of these interventions remains untested among culturally and linguistically diverse caregivers. Given the increasing diversity in the United States, there is a pressing need to develop CIIs that align with the cultural and linguistic preferences of diverse families.

Method:
Using the Ecological Validity Framework and the Checklist for Cultural Adaptations, this tutorial explores considerations for culturally adapting caregiver-implemented AAC interventions for Latinx caregivers of children with AAC needs. The aim is to ensure that interventions are relevant, meaningful, and respectful of cultural and linguistic practices. Through carefully crafted cultural adaptations, interventions can achieve greater acceptance by caregivers.

Results and Discussion:
This tutorial suggests a series of cultural adaptations to ensure accessibility, sustainability, and success of caregiver-implemented AAC interventions for Latinx caregivers of children with AAC needs. By incorporating cultural and linguistic considerations into the intervention design, we can enhance its acceptability among Latinx caregivers. This, in turn, can lead to improved outcomes in AAC implementation within the home environment.