bluuebunny/crossref_metadata_2025_split huggingface dataset:
An autocatalytic CRISPR-Cas amplification effect propelled by the LNA-modified split activators for DNA sensing
Authors: Sun Ke , Pu Lei , Chen Chuan , Chen Mutian , Li Kaiju , Li Xinqiong , Li Huanqing , Geng Jia 
Published: March 2024

Abstract
CRISPR-Cas systems with dual functions offer precise sequence-based recognition and efficient catalytic cleavage of nucleic acids, making them highly promising in biosensing and diagnostic technologies. However, current methods encounter challenges of complexity, low turnover efficiency, and the necessity for sophisticated probe design. To better integrate the dual functions of Cas proteins, we proposed a novel approach called CRISPR-Cas Autocatalysis Amplification driven by LNA-modified Split Activators (CALSA) for the highly efficient detection of single-stranded DNA (ssDNA) and genomic DNA. By introducing split ssDNA activators and the site-directed trans-cleavage mediated by LNA modifications, an autocatalysis-driven positive feedback loop of nucleic acids based on the LbCas12a system was constructed. Consequently, CALSA enabled one-pot and real-time detection of genomic DNA and cell-free DNA (cfDNA) from different tumor cell lines. Notably, CALSA achieved high sensitivity, single-base specificity, and remarkably short reaction times. Due to the high programmability of nucleic acid circuits, these results highlighted the immense potential of CALSA as a powerful tool for cascade signal amplification. Moreover, the sensitivity and specificity further emphasized the value of CALSA in biosensing and diagnostics, opening avenues for future clinical applications.
Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children’s Oncology Group Study
Authors: Lulla Rishi R , Buxton Allen , Krailo Mark D , Lazow Margot A , Boue Daniel R , Leach James L , Lin Tong , Geller James I , Kumar Shiva Senthil , Nikiforova Marina N , Chandran Uma , Jogal Sachin S , Nelson Marvin D , Onar-Thomas Arzu , Haas-Kogan Daphne A , Cohen Kenneth J , Kieran Mark W , Gajjar Amar , Drissi Rachid , Pollack Ian F , Fouladi Maryam 
Published: March 2024

Abstract

Background
Outcomes for children with high-grade gliomas (HGG) remain poor. This multicenter phase II trial evaluated whether concurrent use of vorinostat or bevacizumab with focal radiotherapy (RT) improved 1-year event-free survival (EFS) compared to temozolomide in children with newly diagnosed HGG who received maintenance temozolomide and bevacizumab.

Methods
Patients ≥ 3 and &lt; 22 years with localized, non-brainstem HGG were randomized to receive RT (dose 54–59.4Gy) with vorinostat, temozolomide, or bevacizumab followed by 12 cycles of bevacizumab and temozolomide maintenance therapy.

Results
Among 90 patients randomized, the 1-year EFS for concurrent bevacizumab, vorinostat, or temozolomide with RT was 43.8% (±8.8%), 41.4% (±9.2%), and 59.3% (±9.5%), respectively, with no significant difference among treatment arms. Three- and five-year EFS for the entire cohort was 14.8% and 13.4%, respectively, with no significant EFS difference among the chemoradiotherapy arms. IDH mutations were associated with more favorable EFS (P = .03), whereas H3.3 K27M mutations (P = .0045) and alterations in PIK3CA or PTEN (P = .025) were associated with worse outcomes. Patients with telomerase- and alternative lengthening of telomeres (ALT)-negative tumors (n = 4) had an EFS of 100%, significantly greater than those with ALT or telomerase, or both (P = .002). While there was no difference in outcomes based on TERT expression, high TERC expression was associated with inferior survival independent of the telomere maintenance mechanism (P = .0012).

Conclusions
Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.
Evaluation of Three Cytomegalovirus IgG Lateral Flow Assays for Rapid Determination of CMV Serostatus
Authors: Joncas-Schronce Laurel , Ali Fatima , Pepper Gregory , Stapleton Renee D , Rubenfeld Gordon D , Boeckh Michael , Limaye Ajit P 
Published: March 2024

Abstract

Background
Cytomegalovirus (CMV) serostatus is a major determinant of CMV infection, disease risk, and transplant outcomes. Current clinical serology assays are limited by relatively slow turnaround time, design for batched testing, need for trained personnel, and/or specialized equipment. Rapid diagnostic assays in development have a role in emerging settings, such as critically ill patients, but have not been systematically evaluated.

Methods
We assessed the performance of 3 rapid lateral flow assays (LFAs) for the detection of CMV immunoglobulin (Ig)G antibodies compared with a reference commercially available CMV IgG enzyme-linked immunosorbent assay in residual serum samples from 200 consecutive adults who underwent clinical CMV serology testing. Samples with discrepant results between the LFA and reference assay were tested by a second reference assay. A subset of serum samples was assessed for interoperator variability. Operating characteristics of the QooLabs LFA were separately assessed in plasma samples.

Results
The sensitivity and specificity of the individual LFA assays using serum varied significantly: 86%/83%, 99/93%, and 57/97%, for Healgen, QNow automated reader, and nanoComposix, respectively, compared with the reference assay. Results for the QNow assay were comparable between automated and manual reads. Among a subset of 10 serum samples assessed by 5 individual operators, 44 of 50 (88%) results were concordant. Among 50 plasma samples assessed by the QooLabs LFA, the sensitivity and specificity were 72% and 96%.

Conclusions
The ease of performance, rapid turnaround time, and good operating characteristics provide the rationale for further evaluation of the Qoolabs QNow LFA in specialized settings where rapid assessment of CMV serostatus would be advantageous.
Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses
Authors: Barouch Susanna E , Chicz Taras M , Blanc Ross , Barbati Domenic R , Parker Lily J , Tong Xin , Li Wenjun , McNamara Ryan P 
Published: March 2024

Abstract

Background
The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear.

Methods
Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination.

Results
IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration.

Conclusions
These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza.
Primary Resistance to RET Inhibition in a RET Fusion-Positive Pancreatic Neuroendocrine Carcinoma
Authors: McKinley Blake J , Coston Tucker W , Starr Jason S 
Published: March 2024

Abstract
We present a 54-year-old White male with a diagnosis of stage IV pancreatic neuroendocrine carcinoma. Next-generation sequencing of the tumor/blood identified a complex tumor genome, which included a rearranged during transfection (RET) gene fusion. The patient initially received cytotoxic chemotherapy with a significant radiographic response. After 4 cycles of chemotherapy, the patient was transitioned to a clinical trial using selpercatinib, a RET inhibitor, as maintenance therapy. Unfortunately, our patient developed progression of disease at the first treatment monitoring scan. Our patient suffered primary resistance to RET-targeted therapy. Proposed mechanisms of resistance include intrinsic resistance of the nuclear receptor co-activator 4-RET fusion to RET inhibition, the RET fusion representing a passenger alteration to another tumorigenic driver pathway and/or decreased efficacy of RET inhibition after platinum-based chemotherapy. Our patient’s clinical course highlights the fact that “actionable” genomic alterations do not always equate to patient benefit.
Efficacy, Safety, and Tolerability of Tivozanib in Heavily Pretreated Patients With Advanced Clear Cell Renal Cell Carcinoma
Authors: Johns Andrew C , Campbell Matthew T , Gao Mamie , Hahn Andrew W , Lim Zita , Wang Emily , Gao Jianjun , Shah Amishi Y , Msaouel Pavlos , Tannir Nizar M 
Published: March 2024

Abstract

Background
Tivozanib has been approved as a third-line or later therapy for advanced renal cell carcinoma based on the TIVO-3 trial, which was conducted before immune checkpoint therapies (ICT), cabozantinib, and lenvatinib/everolimus became incorporated in the current sequential treatment paradigm for advanced clear cell RCC (ccRCC).

Methods
We performed a retrospective study of patients with advanced ccRCC treated with tivozanib at MD Anderson Cancer Center during 6/2021-7/2023. A blinded radiologist assessed tumor response by RECIST v1.1. We assessed overall response rate (ORR), clinical benefit rate (CBR) [percentage of all treated patients who achieved radiologic response or stable disease (SD) for ≥ 6 months], progression-free survival (PFS), overall survival (OS), and safety.

Results
Of 30 analyzed patients, 23% had performance status ≥ 2; 47% had International Metastatic RCC Database Consortium (IMDC) poor-risk disease. Median number of prior therapies was 4 (range 1-8). All patients received prior ICT, 87% cabozantinib and 60% lenvatinib ± everolimus. Of 26 evaluable patients, 2 patients had confirmed partial response (ORR 7.7%); 5 patients had SD for ≥ 6 months (CBR 23.3%). Median PFS was 3.8 months (range 0.7-13.9); median OS was 14.1 months (range 0.3-28.5). Fifteen patients (50%) had ≥ 1 treatment-related adverse event (TRAE). There were 6 grade ≥ 3 TRAEs [hypertension, congestive heart failure (3), mucositis, and GI perforation (grade 5)].

Conclusions
In this cohort of heavily pretreated patients with advanced ccRCC, tivozanib yielded a modest clinical benefit in a minority of patients who received prior ICT, cabozantinib, and lenvatinib ± everolimus. TRAEs were consistent with previously published reports.
Metabolic crosstalk between hydroxylated monoterpenes and salicylic acid in tomato defense response against bacteria
Authors: Pérez-Pérez Julia , Minguillón Samuel , Kabbas-Piñango Elías , Payá Celia , Campos Laura , Rodríguez-Concepción Manuel , Espinosa-Ruiz Ana , Rodrigo Ismael , Bellés José María , López-Gresa María Pilar , Lisón Purificación 
Published: March 2024

Abstract
Hydroxylated monoterpenes (HMTPs) are differentially emitted by tomato (Solanum lycopersicum) plants resisting bacterial infection. We have studied the defensive role of these volatiles in the tomato response to bacteria, whose main entrance is through stomatal apertures. Treatments with some HMTPs resulted in stomatal closure and pathogenesis-related protein 1 (PR1) induction. Particularly, α-terpineol induced stomatal closure in a salicylic acid (SA) and abscisic acid-independent manner and conferred resistance to bacteria. Interestingly, transgenic tomato plants overexpressing or silencing the monoterpene synthase MTS1, which displayed alterations in the emission of HMTPs, exhibited changes in the stomatal aperture but not in plant resistance. Measures of both 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) and SA levels revealed competition for MEcPP by the methylerythritol phosphate (MEP) pathway and SA biosynthesis activation, thus explaining the absence of resistance in transgenic plants. These results were confirmed by chemical inhibition of the MEP pathway, which alters MEcPP levels. Treatments with benzothiadiazole (BTH), a SA functional analog, conferred enhanced resistance to transgenic tomato plants overexpressing MTS1. Additionally, these MTS1 overexpressors induced PR1 gene expression and stomatal closure in neighboring plants. Our results confirm the role of HMTPs in both intra- and interplant immune signaling and reveal a metabolic crosstalk between the MEP and SA pathways in tomato plants.
Convergent evolution of parrot plumage coloration
Authors: Ke Fushi , van der Zwan Henriëtte , Poon Emily Shui Kei , Cloutier Alison , Van den Abeele Dirk , van der Sluis Rencia , Sin Simon Yung Wa 
Published: March 2024

Abstract
Parrots have remarkable plumage coloration that result in part from a unique ability to produce pigments called psittacofulvins that yield yellow to red feather colors. Little is known about the evolution of psittacofulvin-based pigmentation. Widespread color mutations of captive-bred parrots provide perfect opportunities to study the genetic basis of this trait. An earlier study on blue budgerigars, which do not possess psittacofulvins, reveals the involvement of an uncharacterized polyketide synthase (MuPKS) in yellow psittacofulvin synthesis. The blue phenotype had repeatedly appeared in different parrot species, similar to independent experimental replications allowing the study of convergent evolution and molecular mechanism of psittacofulvin-based pigmentation. Here, we investigated the genetic basis of the blue phenotypes in two species of Agapornis parrots, Fischer's lovebird (A. fischeri) and Yellow-collared lovebird (A. personatus). Using whole-genome data, we identified a single genomic region with size &lt;2 Mb to be strongly associated with the color difference between blue and wild-type (WT) birds in both species. Surprisingly, we discovered that the mutation associated with the blue Agapornis phenotype was identical to the previously described substitution causing the functional change of MuPKS in budgerigars. Together with the evidence of shared blue-associated haplotypes and signatures of a selective sweep in this genomic region in both species, we demonstrated both de novo mutation and interspecific introgression play a role in the evolution of this trait in different Agapornis species. The convergent substitution in the same gene in both lovebirds and budgerigars also indicates a strong evolutionary constraint on psittacofulvin-based coloration.
The maximum capability of a topological feature in link prediction
Authors: Ran Yijun , Xu Xiao-Ke , Jia Tao 
Published: March 2024

Abstract
Networks offer a powerful approach to modeling complex systems by representing the underlying set of pairwise interactions. Link prediction is the task that predicts links of a network that are not directly visible, with profound applications in biological, social, and other complex systems. Despite intensive utilization of the topological feature in this task, it is unclear to what extent a feature can be leveraged to infer missing links. Here, we aim to unveil the capability of a topological feature in link prediction by identifying its prediction performance upper bound. We introduce a theoretical framework that is compatible with different indexes to gauge the feature, different prediction approaches to utilize the feature, and different metrics to quantify the prediction performance. The maximum capability of a topological feature follows a simple yet theoretically validated expression, which only depends on the extent to which the feature is held in missing and nonexistent links. Because a family of indexes based on the same feature shares the same upper bound, the potential of all others can be estimated from one single index. Furthermore, a feature’s capability is lifted in the supervised prediction, which can be mathematically quantified, allowing us to estimate the benefit of applying machine learning algorithms. The universality of the pattern uncovered is empirically verified by 550 structurally diverse networks. The findings have applications in feature and method selection, and shed light on network characteristics that make a topological feature effective in link prediction.
Lattice Realization of the Axial U(1) Noninvertible Symmetry
Authors: Honda Yamato , Morikawa Okuto , Onoda Soma , Suzuki Hiroshi 
Published: March 2024

Abstract
In U(1) lattice gauge theory with compact U(1) variables, we construct the symmetry operator, i.e. the topological defect, for the axial U(1) noninvertible symmetry. This requires a lattice formulation of chiral gauge theory with an anomalous matter content and we employ the lattice formulation on the basis of the Ginsparg–Wilson relation. The invariance of the symmetry operator under the gauge transformation of the gauge field on the defect is realized, imitating the prescription by Karasik in continuum theory, by integrating the lattice Chern–Simons term on the defect over smooth lattice gauge transformations. The projection operator for allowed magnetic fluxes on the defect then emerges with lattice regularization. The resulting symmetry operator is manifestly invariant under lattice gauge transformations. In an appendix, we give another way of constructing the symmetry operator on the basis of a 3D $\mathbb {Z}_N$ topological quantum field theory, the level-N BF theory on the lattice.
MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases
Authors: Wu Changqiang , Chen Wei , Yan Shuang , Zhong Jie , Du Liang , Yang Chenwu , Pu Yu , Li Yang , Lin Jiafu , Zeng Mei , Zhang Xiaoming 
Published: March 2024

Abstract
Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven to be an effective local treatment modality but incompetent against metastases. Hence, the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a magnetic resonance imaging (MRI)-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with a programmed cell death 1 (PD-1) inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser. In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32°C to 60.7°C in 5 min. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided PTT/PDT results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.
The spectacle of automation and status aspirations: adoption of automated metro systems around the world, 2000–2020
Authors: Kang Youbin , Kim Jungmyung 
Published: March 2024

Abstract
Automation’s extensive impact on the labor market and economy is well recognized, but the underlying motivations for its adoption remain understudied. To address this gap, we analyze an original dataset covering 1276 cities across 148 countries, using event history analysis to examine the adoption of automated metro systems. Our research suggests that city governments are driven by status competition in their decisions to automate subway systems. We find that high-status cities are more likely to adopt automation. However, this trend diminishes when cities are preparing to host a mega-event such as the Olympics, indicating that lower-status cities use these events as opportunities to adopt automation technologies. Our finding reveals that status-driven aspirations, manifesting in the spectacle of automation, are a significant motivator for adopting automated technologies, prompting further investigation into the socio-economic factors influencing automation and the symbolic importance of technological advancement across various economic sectors.
Spindle-slow wave coupling and problem-solving skills: impact of age
Authors: Baena Daniel , Toor Balmeet , van den Berg Nicholas H , Ray Laura B , Fogel Stuart M 
Published: March 2024

Abstract
We examined how aging affects the role of sleep in the consolidation of newly learned cognitive strategies. Forty healthy young adults (20–35 years) and 30 healthy older adults (60–85 years) were included. Participants were trained on the Tower of Hanoi (ToH) task, then, half of each age group were assigned to either the 90-minute nap condition, or stayed awake, before retesting. The temporal co-occurrence between slow waves (SW) and sleep spindles (SP) during non-rapid eye movement sleep was examined as a function of age in relation to memory consolidation of problem-solving skills. We found that despite intact learning, older adults derived a reduced benefit of sleep for problem-solving skills relative to younger adults. As expected, the percentage of coupled spindles was lower in older compared to younger individuals from control to testing sessions. Furthermore, coupled spindles in young adults were more strongly coupled to the SW upstate compared to older individuals. Coupled spindles in older individuals were lower in amplitude (mean area under the curve; μV) compared to the young group. Lastly, there was a significant relationship between offline gains in accuracy on the ToH and percent change of spindles coupled to the upstate of the slow wave in older, but not younger adults. Multiple regression revealed that age accounted for differences in offline gains in accuracy, as did spindle coupling during the upstate. These results suggest that with aging, spindle-slow wave coupling decreases. However, the degree of the preservation of coupling with age correlates with the extent of problem-solving skill consolidation during sleep.