bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy
Authors: Chehelgerdi Mohammad , Chehelgerdi Matin , Khorramian-Ghahfarokhi Milad , Shafieizadeh Marjan , Mahmoudi Esmaeil , Eskandari Fatemeh , Rashidi Mohsen , Arshi Asghar , Mokhtari-Farsani Abbas 
Published: January 2024

AbstractThe CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize the field of cancer research and therapy. The ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors has opened up new possibilities for the development of more effective and personalized cancer treatments. In this review, we will discuss the different CRISPR-based strategies that have been proposed for cancer therapy, including inactivating genes that drive tumor growth, enhancing the immune response to cancer cells, repairing genetic mutations that cause cancer, and delivering cancer-killing molecules directly to tumor cells. We will also summarize the current state of preclinical studies and clinical trials of CRISPR-based cancer therapy, highlighting the most promising results and the challenges that still need to be overcome. Safety and delivery are also important challenges for CRISPR-based cancer therapy to become a viable clinical option. We will discuss the challenges and limitations that need to be overcome, such as off-target effects, safety, and delivery to the tumor site. Finally, we will provide an overview of the current challenges and opportunities in the field of CRISPR-based cancer therapy and discuss future directions for research and development. The CRISPR system has the potential to change the landscape of cancer research, and this review aims to provide an overview of the current state of the field and the challenges that need to be overcome to realize this potential.
Transcriptomic signatures of individual cell types in cerebral cavernous malformation
Authors: Li Ying , Girard Romuald , Srinath Abhinav , Cruz Diana Vera , Ciszewski Cezary , Chen Chang , Lightle Rhonda , Romanos Sharbel , Sone Je Yeong , Moore Thomas , DeBiasse Dorothy , Stadnik Agnieszka , Lee Justine J. , Shenkar Robert , Koskimäki Janne , Lopez-Ramirez Miguel A. , Marchuk Douglas A. , Ginsberg Mark H. , Kahn Mark L. , Shi Changbin , Awad Issam A. 
Published: January 2024

AbstractCerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets.
Role of cell rearrangement and related signaling pathways in the dynamic process of tip cell selection
Authors: Guo Yaru , Zhang Shihan , Wang Dandan , Heng Boon Chin , Deng Xuliang 
Published: January 2024

AbstractAngiogenesis is a complex, highly-coordinated and multi-step process of new blood vessel formation from pre-existing blood vessels. When initiated, the sprouting process is spearheaded by the specialized endothelial cells (ECs) known as tip cells, which guide the organization of accompanying stalk cells and determine the function and morphology of the finally-formed blood vessels. Recent studies indicate that the orchestration and coordination of angiogenesis involve dynamic tip cell selection, which is the competitive selection of cells to lead the angiogenic sprouts. Therefore, this review attempt to summarize the underlying mechanisms involved in tip cell specification in a dynamic manner to enable readers to gain a systemic and overall understanding of tip cell formation, involving cooperative interaction of cell rearrangement with Notch and YAP/TAZ signaling. Various mechanical and chemical signaling cues are integrated to ensure the right number of cells at the right place during angiogenesis, thereby precisely orchestrating morphogenic functions that ensure correct patterning of blood vessels.
DEL-1: a promising treatment for AMD-associated ER stress in retinal pigment epithelial cells
Authors: Kwon ChangHyuk , Cho Wonjun , Choi Sung Woo , Oh Heeseung , Abd El-Aty A. M. , Gecili Ibrahim , Jeong Ji Hoon , Jung Tae Woo 
Published: January 2024

Abstract
Background
Age-related macular degeneration (AMD) is an irreversible eye disease that can cause blurred vision. Regular exercise has been suggested as a therapeutic strategy for treating AMD, but how exercise improves AMD is not yet understood. This study investigated the protective effects of developmental endothelial locus-1 (DEL-1), a myokine upregulated during exercise, on endoplasmic reticulum (ER) stress-induced injury in retinal pigment epithelial cells.

Methods
We evaluated the levels of AMPK phosphorylation, autophagy markers, and ER stress markers in DEL-1-treated human retinal pigment epithelial cells (hRPE) using Western blotting. We also performed cell viability, caspase 3 activity assays, and autophagosome staining.

Results
Our findings showed that treatment with recombinant DEL-1 dose-dependently reduced the impairment of cell viability and caspase 3 activity in tunicamycin-treated hRPE cells. DEL-1 treatment also alleviated tunicamycin-induced ER stress markers and VEGF expression. Moreover, AMPK phosphorylation and autophagy markers were increased in hRPE cells in the presence of DEL-1. However, the effects of DEL-1 on ER stress, VEGF expression, and apoptosis in tunicamycin-treated hRPE cells were reduced by AMPK siRNA or 3-methyladenine (3-MA), an autophagy inhibitor.

Conclusions
Our study suggests that DEL-1, a myokine, may have potential as a treatment strategy for AMD by attenuating ER stress-induced injury in retinal pigment epithelial cells.
Circ_0006640 transferred by bone marrow-mesenchymal stem cell-exosomes suppresses lipopolysaccharide-induced apoptotic, inflammatory and oxidative injury in spinal cord injury
Authors: Yang Dan , Wei Haitang , Sheng Yang , Peng Tao , Zhao Qiang , Xie Liang , Yang Jun 
Published: January 2024

Abstract
Background
Emerging proofs have shown that differentially expressed circular RNAs (circRNAs) are closely associated with the pathophysiological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-exosomes have been demonstrated to possess favorable therapeutic effects in diseases. Herein, this work aimed to investigate the action of circ_0006640 transferred by MSC-exosomes functional recovery after SCI.

Methods
SCI animal models were established by spinal cord contusion surgery in mice and lipopolysaccharide (LPS)-stimulated mouse microglial cell line BV2. Levels of genes and proteins were detected by qRT-PCR and Western blot. Properties of BV2 cells were characterized using CCK-8 assay, flow cytometry and ELISA analysis. The oxidative stress was evaluated. Dual-luciferase reporter assay was used for verifying the binding between miR-382-5p and circ_0006640 or IGF-1 (Insulin-like Growth Factor 1). Exosome separation was conducted by using the commercial kit.

Results
Circ_0006640 expression was lower in SCI mice and LPS-induced microglial cells. Circ_0006640 overexpression protected microglial cells from LPS-induced apoptotic, inflammatory and oxidative injury. Mechanistically, circ_0006640 directly sponged miR-382-5p, which targeted IGF-1. MiR-382-5p was increased, while IGF-1 was decreased in SCI mice and LPS-induced microglial cells. Knockdown of miR-382-5p suppressed apoptosis, inflammation and oxidative stress in LPS-induced microglial cells, which were reversed by IGF-1 deficiency. Moreover, miR-382-5p up-regulation abolished the protective functions of circ_0006640 in LPS-induced microglial cells. Additionally, circ_0006640 was packaged into MSC-exosomes and could be transferred by exosomes. Exosomal circ_0006640 also had protective effects on microglial cells via miR-382-5p/IGF-1 axis.

Conclusion
Circ_0006640 transferred by BMSC-exosomes suppressed LPS-induced apoptotic, inflammatory and oxidative injury via miR-382-5p/IGF-1 axis, indicating a new insight into the clinical application of exosomal circRNA-based therapeutic in the function recovery after SCI.
Male with an apparently normal phenotype carrying a BRCA1 exon 20 duplication in trans to a BRCA1 frameshift variant
Authors: Block Ines , Mateu-Regué Àngels , Do Thi Tuyet Nhu , Miceikaite Ieva , Sdogati Daniel , Larsen Martin J. , Hao Qin , Nielsen Henriette Roed , Boonen Susanne E. , Skytte Anne-Bine , Jensen Uffe Birk , Høffding Louise K. , De Nicolo Arcangela , Viel Alessandra , Tudini Emma , Parsons Michael T. , Hansen Thomas V. O. , Rossing Maria , Kruse Torben A. , Spurdle Amanda B. , Thomassen Mads 
Published: January 2024

Abstract
Background
Reports of dual carriers of pathogenic BRCA1 variants in trans are extremely rare, and so far, most individuals have been associated with a Fanconi Anemia-like phenotype.

Methods
We identified two families with a BRCA1 in-frame exon 20 duplication (Ex20dup). In one male individual, the variant was in trans with the BRCA1 frameshift variant c.2475delC p.(Asp825Glufs*21). We performed splicing analysis and used a transcription activation domain (TAD) assay to assess the functional impact of Ex20dup. We collected pedigrees and mapped the breakpoints of the duplication by long- and short-read genome sequencing. In addition, we performed a mitomycin C (MMC) assay from the dual carrier using cultured lymphoblastoid cells.

Results
Genome sequencing and RNA analysis revealed the BRCA1 exon 20 duplication to be in tandem. The duplication was expressed without skipping any one of the two exon 20 copies, resulting in a lack of wild-type transcripts from this allele. TAD assay indicated that the Ex20dup variant has a functional level similar to the well-known moderate penetrant pathogenic BRCA1 variant c.5096G > A p.(Arg1699Gln). MMC assay of the dual carrier indicated a slightly impaired chromosomal repair ability.

Conclusions
This is the first reported case where two BRCA1 variants with demonstrated functional impact are identified in trans in a male patient with an apparently normal clinical phenotype and no BRCA1-associated cancer. The results pinpoint a minimum necessary BRCA1 protein activity to avoid a Fanconi Anemia-like phenotype in compound heterozygous status and yet still predispose carriers to hormone-related cancers. These findings urge caution when counseling families regarding potential Fanconi Anemia risk. Furthermore, prudence should be taken when classifying individual variants as benign based on co-occurrence in trans with well-established pathogenic variants.
Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial)
Authors: Zapata-Arriaza Elena , Medina-Rodríguez Manuel , Moniche Álvarez Francisco , de Albóniga-Chindurza Asier , Aguilar-Pérez Marta , Ainz-Gómez Leire , Baena-Palomino Pablo , Zamora Aynara , Pardo-Galiana Blanca , Delgado-Acosta Fernando , Valverde Moyano Roberto , Jiménez-Gómez Elvira , Bravo Rey Isabel , Oteros Fernández Rafael , Escudero-Martínez Irene , Vielba-Gomez Isabel , Morales Caba Lluis , Díaz Pérez Jose , García Molina Estefania , Mosteiro Sonia , Castellanos Rodrigo María del Mar , Amaya Pascasio Laura , Hidalgo Carlos , Freijo Guerrero María del Mar , González Díaz Eva , Ramírez Moreno Jose María , Fernández Prudencio Luis , Terceño Izaga Mikel , Bashir Viturro Saima , Gamero-García Miguel Ángel , Jiménez Jorge Silvia , Rosso Fernández Clara , Montaner Joan , González García Alejandro 
Published: January 2024

Abstract
Rationale
In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated.

Aims
To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL.

Sample size estimates
Two hundred forty patients will be enrolled, 120 in every treatment arm.

Methods and design
A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months.

Study outcomes
Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage.

Discussion
This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL.

Trial registration
The trial is registered as NCT05225961. February, 7th, 2022.
miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer’s disease
Authors: Han Sang-Won , Pyun Jung-Min , Bice Paula J. , Bennett David A. , Saykin Andrew J. , Kim Sang Yun , Park Young Ho , Nho Kwangsik 
Published: January 2024

AbstractBackgroundAlzheimer’s dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers.MethodsWe performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA profiles from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) (N= 702) as a discovery dataset. We performed association analysis of hub miRNAs with AD, its neuropathology markers, and cognition. After selecting target genes of the hub miRNAs, we performed association analysis of the hub miRNAs with their target genes and then performed pathway-based enrichment analysis. For replication, we performed a consensus miRNA co-expression network analysis using the ROS/MAP dataset and an independent dataset (N= 16) from the Gene Expression Omnibus (GEO). Furthermore, we performed a machine learning approach to assess the performance of hub miRNAs for AD classification.ResultsNetwork analysis identified a glucose metabolism pathway-enriched module (M3) as significantly associated with AD and cognition. Five hub miRNAs (miR-129-5p, miR-433, miR-1260, miR-200a, and miR-221) of M3 had significant associations with AD clinical and/or pathologic traits, with miR129-5p by far the strongest across all phenotypes. Gene-set enrichment analysis of target genes associated with their corresponding hub miRNAs identified significantly enriched biological pathways including ErbB, AMPK, MAPK, and mTOR signaling pathways. Consensus network analysis identified two AD-associated consensus network modules and two hub miRNAs (miR-129-5p and miR-221). Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, andAPOEε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs.ConclusionsIntegrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers.
Average effective subcarrier-domain sparse representation approach for target information estimation in CP-OFDM-based passive bistatic radar
Authors: Zhao Zhixin , Gong Yanghang , Zhou Huilin , Cao Yulong 
Published: January 2024

AbstractAlthough some existing sparse representation (SR) methods are robust for target detection in passive bistatic radar (PBR), they still face the challenges of high computational complexity and poor detection performance for extremely low-signal-to-clutter ratio (SCR) target. So, an average effective subcarrier (AES)-domain sparse representation approach is investigated in this paper. Firstly, the AES-based SR model is proposed to solve the problem of high computational complexity, which is established by utilizing the sparseness of the orthogonal frequency-division multiplexing (OFDM) with cyclic prefix (CP) signals in each effective subcarrier domain. Then, considering the difficulty of detecting extremely low-SCR targets, clutter cancellation is implemented by the SR-based optimization model. Two AES-S algorithms, namely AES-S-based clutter cancellation in the time domain (AES-S-T) and AES-S-based clutter cancellation in the subcarrier domain (AES-S-C), are proposed, and the computational complexity is further reduced. Finally, extensive simulation and experimental results illustrate that the proposed algorithms have good detection performance and low computational complexity in PBR detection scene.
Beyond correlates: the social gradient in childhood overweight
Authors: Hermeling Lina , Steinacker Jürgen M. , Kobel Susanne 
Published: January 2024

Abstract
Background
Health (in)equity has a high priority on research and policy agendas. Even though it is known that inequalities in overweight prevalence accumulate with age and are already existent among children below the age of six, research on this topic is scarce. In this young age group, parents play an important role in preventing overweight and associated adverse consequences. This study examines the magnitude of parental misclassification of child weight status and its correlates, focussing on the factors that determine social status and equity.

Methods
Preschool children’s weight and height was measured objectively. Parents gave information on their socioeconomic background. Family education was dichotomised into tertiary and non-tertiary educational level, according to CASMIN. Binary logistic regression, adjusted for parental BMI, was applied to detect odds of childhood overweight.

Results
Data on family educational level and anthropometrics were available from 643 children (4.5 ± 0.82 years, 52.7% male) and their parents of which 46.5% (n = 299) had a tertiary educational background. The groups (tertiary vs. non-tertiary educational level) differ significantly in overweight prevalence (3.7% vs. 11.9%, p ≤ 0.001). Odds of overweight were two times higher in children with non-tertiary educational background (OR: 2.123, CI: 1.010–4.461, p < 0.05), adjusted for parental BMI.

Conclusion
Children from families with low educational background have an elevated risk of overweight, already at a very young age. Education in general (not explicitly health education) seems to play a tremendous role in the prevention of overweight and obesity and should therefore be implied in policies enhancing health equity.

Trial registration
DRKS-ID: DRKS00010089.
Passivation remediation of weakly alkaline Cd-contaminated soils using combined treatments of biochar and sepiolite
Authors: Zhang Yuxin , Gao Shan , Jia Hongtao , Sun Tao , Zheng Shunan , Wu Shihang , Sun Yuebing 
Published: January 2024

Abstract
Background
Cadmium (Cd) pollution in agricultural soils has become a priority environmental concern globally. A reasonable application of passivators is critical to address the problem. In this study, we examined the remediation effects of rice husk biochar (rBC) and sepiolite (Sep) as single and combined (rBC + Sep) treatments on Cd pollution in a weakly alkaline soil using three maize cultivars (Liyu 16, Zhengdan 958, and Sanbei 218) as test crops. We also explained the mechanisms involved in the remediation effects.

Results
The pseudo-second-order kinetic equation and Langmuir model could well describe the adsorption process of rBC + Sep for Cd2+. Compared with the control treatment (CK), soil available Cd concentration decreased by 29.51–36.34% under rBC + Sep treatment (p< 0.05) and the Cd concentrations in maize grains of Liyu 16, Zhengdan 958, and Sanbei 218 decreased by 38.08–47.85%, 37.25–45.61%, and 33.96–46.15%, respectively (p< 0.05). Following passivation treatment, soil available Cd concentration decreased and gradually changed from the exchangeable and carbonate binding forms to the Fe/Mn oxide and residual forms. The bioconcentration factors of Liyu 16 (0.05–0.09) and Sanbei 218 (0.05–0.09) were lower than those of Zhengdan 958 (0.07–0.13). In addition, rBC +Sep treatment increased soil pH and soil electrical conductivity, but the differences were not significant (p> 0.05).

Conclusions
The application of 0.2% rBC + 0.5% Sep composite passivation material to weakly alkaline Cd-contaminated soil can effectively reduce the Cd concentration of soil and maize.
Food insecurity among female farmers in rural West Sleman, Indonesia
Authors: Samputra Palupi Lindiasari , Antriyandarti Ernoiz 
Published: January 2024

Abstract
Background
Farmers, especially females, face the risk of food insecurity for their families. It would be interesting to examine the efforts made by female farmers who experience food insecurity due to the indirect impacts of COVID-19. This study aims to determine how female farmers deal with food insecurity risks in West Sleman. Data on food insecurity experiences are processed with Winstep software and the Rasch model. Ordinal logistic regression analysis calculates the probability of food insecurity for female farmers depending on their traits and the mitigation strategies they adopt.

Results
The findings of this research show that agricultural laborers (42.3%) are the most numerous type of female farmer, followed by land-owning farmers (40.4%) and land-tenants farmers (17.3%). Although more than 50% of the three types of farmers are food secure, laborers have a higher percentage of moderate-to-severe food insecurity (23%) than land owners (14%) and land tenants (11%). Factors that influence the occurrence of food insecurity are not using the home yard, which is physically accessible to grow food, having an agricultural income of less than IDR 500 thousand, and a house asset value of less than IDR 100 million.

Conclusions
Coping strategies for mitigating the risk of food insecurity start from within the family by prioritizing food spending, living frugally, growing food crops in your yard, committing full-time to farming, and avoiding dependence on government assistance. Then, optimizing and strengthening the community.