bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conditional knockdown of OsMLH1 to improve plant prime editing systems without disturbing fertility in rice
Authors: Liu Xiaoshuang , Gu Dongfang , Zhang Yiru , Jiang Yingli , Xiao Zhi , Xu Rongfang , Qin Ruiying , Li Juan , Wei Pengcheng 
Published: May 2024

Abstract
Background
High-efficiency prime editing (PE) is desirable for precise genome manipulation. The activity of mammalian PE systems can be largely improved by inhibiting DNA mismatch repair by coexpressing a dominant-negative variant of MLH1. However, this strategy has not been widely used for PE optimization in plants, possibly because of its less conspicuous effects and inconsistent performance at different sites.

Results
We show that direct RNAi knockdown of OsMLH1 in an ePE5c system increases the efficiency of our most recently updated PE tool by 1.30- to 2.11-fold in stably transformed rice cells, resulting in as many as 85.42% homozygous mutants in the T0 generation. The high specificity of ePE5c is revealed by whole-genome sequencing. To overcome the partial sterility induced by OsMLH1 knockdown of ePE5c, a conditional excision system is introduced to remove the RNAi module by Cre-mediated site-specific recombination. Using a simple approach of enriching excision events, we generate 100% RNAi module-free plants in the T0 generation. The increase in efficiency due to OsMLH1 knockdown is maintained in the excised plants, whose fertility is not impaired.

Conclusions
This study provides a safe and reliable plant PE optimization strategy for improving editing efficiency without disturbing plant development via transient MMR inhibition with an excisable RNAi module of MLH1.
Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial
Authors: Bhagavan Chiranth , Glue Paul , Evans Will , Reynolds Lisa , Turner Thivya , King Chris , Russell Bruce R. , Morunga Eva , Mills Jessica Lee , Layton Geoff , Menkes David B. 
Published: May 2024

Abstract
Background
Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer.

Methods
Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first.

Discussion
This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness.

Trial registration
Trial registered on Australian New Zealand Clinical Trials Registry.
Registration number: ACTRN12619001334190p.
Date registered: 30/09/2019.
URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true
Synthesis of novel carbazole hydrazine-carbothioamide scaffold as potent antioxidant, anticancer and antimicrobial agents
Authors: Çapan İrfan , Hawash Mohammed , Qaoud Mohammed T. , Gülüm Levent , Tunoglu Ezgi Nurdan Yenilmez , Çifci Kezban Uçar , Çevrimli Bekir Sıtkı , Sert Yusuf , Servi Süleyman , Koca İrfan , Tutar Yusuf 
Published: May 2024

Abstract
Background
Carbazole-based molecules containing thiosemicarbazide functional groups are recognized for their diverse biological activities, particularly in enhancing therapeutic anticancer effects through inhibiting crucial pathways. These derivatives also exhibit noteworthy antioxidant properties.

Objectives
This study aims to synthesize, characterize, and evaluate the antioxidant and anticancer activities of 18 novel carbazole derivatives.

Methods
The radical scavenging capabilities of the compounds were assessed using the 2,2-diphenyl-1-picrylhydrazyl assay. Antiproliferative activities were evaluated on MCF-7 cancer cell lines through viability assays. Additionally, the modulation of the PI3K/Akt/mTOR pathway, apoptosis/necrosis induction, and cell cycle analysis were conducted for the most promising anticancer agents.

Results
nine compounds showed potent antioxidant activities with IC50 values lower than the positive control acarbose, with compounds 4 h and 4y exhibiting the highest potency (IC50 values of 0.73 and 0.38 µM, respectively). Furthermore, compounds 4o and 4r displayed significant anticancer effects, with IC50 values of 2.02 and 4.99 µM, respectively. Compound 4o, in particular, exhibited promising activity by targeting the PI3K/Akt/mTOR signaling pathway, inhibiting tumor survival, inducing apoptosis, and causing cell cycle arrest in MCF-7 cell lines. Furthermore, compound 4o was showed significant antimicrobial activities against S. aureus and E. coli, and antifungal effect against C. albicans. Its potential to overcome drug resistance through this pathway inhibition highlights its promise as an anticancer agent. Molecular docking simulations supported these findings, revealing favorable binding profiles and interactions within the active sites of the enzymes PI3K, AKT1, and mTOR. Moreover, assessing the druggability of the newly synthesized thiosemicarbazide derivatives demonstrated optimal physicochemical properties, further endorsing their potential as drug candidates.
Semimethylation is a feature of diffuse large B-cell lymphoma, and subgroups with poor prognosis are characterized by global hypomethylation and short telomere length
Authors: Carlund Olivia , Thörn Elina , Osterman Pia , Fors Maja , Dernstedt Andy , Forsell Mattias N. E. , Erlanson Martin , Landfors Mattias , Degerman Sofie , Hultdin Magnus 
Published: May 2024

Abstract
Background
Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL.

Results
We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n = 66), High-grade B-cell lymphoma (n = 7), Primary CNS lymphoma (n = 8), and transformation of indolent B-cell lymphoma (n = 12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15 ≤ β ≤ 0.8) with large intertumor variation and overall low hypermethylation (β > 0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (β < 0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR 6.920, 95% CI 1.499–31.943) and progression-free survival (PFS) (HR 4.923, 95% CI 1.286–18.849) in DLBCL and with worse DSS (HR 5.147, 95% CI 1.239–21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR 6.011, 95% CI 1.319–27.397) and PFS (HR 4.689, 95% CI 1.102–19.963) in LBCL treated with R-CHOP-like regimens.

Conclusion
We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs.
CaMKIIβ deregulation contributes to neuromuscular junction destabilization in Myotonic Dystrophy type I
Authors: Falcetta Denis , Quirim Sandrine , Cocchiararo Ilaria , Chabry Florent , Théodore Marine , Stiefvater Adeline , Lin Shuo , Tintignac Lionel , Ivanek Robert , Kinter Jochen , Rüegg Markus A. , Sinnreich Michael , Castets Perrine 
Published: May 2024

Abstract
Background
Myotonic Dystrophy type I (DM1) is the most common muscular dystrophy in adults. Previous reports have highlighted that neuromuscular junctions (NMJs) deteriorate in skeletal muscle from DM1 patients and mouse models thereof. However, the underlying pathomechanisms and their contribution to muscle dysfunction remain unknown.

Methods
We compared changes in NMJs and activity-dependent signalling pathways in HSALR and Mbnl1ΔE3/ΔE3 mice, two established mouse models of DM1.

Results
Muscle from DM1 mouse models showed major deregulation of calcium/calmodulin-dependent protein kinases II (CaMKIIs), which are key activity sensors regulating synaptic gene expression and acetylcholine receptor (AChR) recycling at the NMJ. Both mouse models exhibited increased fragmentation of the endplate, which preceded muscle degeneration. Endplate fragmentation was not accompanied by changes in AChR turnover at the NMJ. However, the expression of synaptic genes was up-regulated in mutant innervated muscle, together with an abnormal accumulation of histone deacetylase 4 (HDAC4), a known target of CaMKII. Interestingly, denervation-induced increase in synaptic gene expression and AChR turnover was hampered in DM1 muscle. Importantly, CaMKIIβ/βM overexpression normalized endplate fragmentation and synaptic gene expression in innervated Mbnl1ΔE3/ΔE3 muscle, but it did not restore denervation-induced synaptic gene up-regulation.

Conclusions
Our results indicate that CaMKIIβ-dependent and -independent mechanisms perturb synaptic gene regulation and muscle response to denervation in DM1 mouse models. Changes in these signalling pathways may contribute to NMJ destabilization and muscle dysfunction in DM1 patients.
Whole-genome screening for near-diagnostic genetic markers for four western European white oak species identification
Authors: Kremer Antoine , Delcamp Adline , Lesur Isabelle , Wagner Stefanie , Rellstab Christian , Guichoux Erwan , Leroy Thibault 
Published: May 2024

Abstract
Key message
Mining genome-wide DNA sequences enabled the discovery of near-diagnostic markers for species assignment in four European white oaks (Quercus petraea (Matt.) Liebl., Quercus pubescens Willd., Quercus pyrenaica Willd., and Quercus robur L.) despite their low interspecific differentiation. Near-diagnostic markers are almost fully fixed in one species and absent in the three others. As a result, only a handful of markers are needed for species identification, making this genetic assay a very promising operational taxonomic assignment procedure in research and forestry.

Context
Identifying species in the European white oak complex has been a long-standing concern in taxonomy, evolution, forest research, and management. Quercus petraea (Matt.) Liebl., Q. robur L., Q. pubescens Willd., and Q. pyrenaica Willd. are part of this species complex in western temperate Europe and hybridize in mixed stands, challenging species identification.

Aims
Our aim was to identify near-diagnostic single-nucleotide polymorphisms (SNPs) for each of the four species that are suitable for routine use and rapid diagnosis in research and applied forestry.

Methods
We first scanned existing whole-genome and target-capture data sets in a reduced number of samples (training set) to identify candidate diagnostic SNPs, i.e., genomic positions being characterized by a reference allele in one species and by the alternative allele in all other species. Allele frequencies of the candidates SNPs were then explored in a larger, range-wide sample of populations in each species (validation step).

Results
We found a subset of 38 SNPs (10 for Q. petraea, 7 for Q. pubescens, 9 for Q. pyrenaica, and 12 for Q. robur) that showed near-diagnostic features across their species distribution ranges with Q. pyrenaica and Q. pubescens exhibiting the highest (0.876) and lowest (0.747) diagnosticity, respectively.

Conclusions
We provide a new, efficient, and reliable molecular tool for the identification of the species Q. petraea, Q. robur, Q. pubescens, and Q. pyrenaica, which can be used as a routine tool in forest research and management. This study highlights the resolution offered by whole-genome sequencing data to design near-diagnostic marker sets for taxonomic assignment, even for species complexes with relatively low differentiation.
The relationship between food selectivity and stature in pediatric patients with avoidant-restrictive food intake disorder – an electronic medical record review
Authors: Proctor Kaitlin B. , Mansoura Maryam , Rodrick Eugene , Volkert Valerie , Sharp William G. , Kindler Joseph M. 
Published: May 2024

Abstract
Background
We aimed to characterize stature in pediatric patients with avoidant/restrictive food intake disorder (ARFID), including associations between body size and nutrient intake and height.

Methods
We conducted a secondary analysis of pre-treatment data from 60 patients diagnosed with ARFID that were collected from the electronic medical record. Anthropometric measurements were converted to age- and sex-specific Z-scores using pediatric CDC growth charts. Spearman correlations were performed to test the relationship between height and weight/BMI Z-scores as well as height Z-score and diet variables.

Results
On average, height (-0.35 ± 1.38), weight (-0.58 ± 1.56), and BMI (-0.56 ± 1.48) Z-scores tended to be lower than what would be expected in a generally healthy pediatric population. Percent of individuals with height, weight, or BMI Z-score < -2.0 was 8%, 20%, and 17%, respectively. BMI (P < 0.05) and weight (P < 0.05) were positively associated with height Z-score. Further, intake of some nutrients (e.g., calcium, vitamin D) correlated positively with height Z-score (all P < 0.05).

Conclusions
The cross-sectional relationships reported in this study suggest that in children with ARFID, body weight and consumption of bone-augmenting nutrients such as calcium and vitamin D correlated with height. A thorough understanding of the clinical manifestations of malnutrition and longitudinal effects of restrictive eating in patients with ARFID is critical.
Body evaluation in men: the role of body weight dissatisfaction in appearance evaluation, eating, and muscle dysmorphia psychopathology
Authors: Dal Brun David , Pescarini Elena , Calonaci Sofia , Bonello Elisa , Meneguzzo Paolo 
Published: May 2024

Abstract
Background
Body image dissatisfaction is a significant concern among men, influencing appearance evaluation, eating behaviors, and muscle dysmorphia psychopathology. However, research on these correlations is notably deficient in men, largely because body image concerns are unevenly distributed between genders. Therefore, this study aims to assess the various dimensions of concerns about body image in men and explore their associations with characteristics such as sexual orientation.

Methods
A cross-sectional study was conducted with 251 adult men from fitness centers in the Veneto Region, Italy. Participants completed self-report questionnaires, including the Eating Attitudes Test (EAT-26), the Appearance Schemas Inventory-Revised (ASI-R), and the Muscle Dysmorphic Disorder Inventory (MDDI). Body weight perception and dissatisfaction were evaluated using a Figure Rating Scale (FRS) with 12 male biometric silhouettes.

Results
Participants were divided into three subgroups based on the experienced levels of body weight dissatisfaction: those who rated a smaller body (BWsmaller), those who rated a larger body (BWlarger) more highly relative to their own estimated body size, and those who reported implicit neutrality with their current weight (BWneu). BWsmaller participants reported higher levels of eating-related concern, while BWlarger participants exhibited higher levels of muscle dysmorphia. Additionally, the BWlarger group showed the highest degree of quantitative perceptual underestimation of their body weight. Sexual orientation was found to have an impact on body weight dissatisfaction, with bisexual men more likely to desire an increase in weight and gay men more likely to desire a decrease.

Conclusions
Body weight dissatisfaction significantly impacts appearance evaluation, eating behaviors, and muscle dysmorphia psychopathology in males. Tailored interventions that consider individual differences can support the well-being of men. The study provides useful insight into male body image issues, warranting further exploration to inform effective interventions and promote positive body image and mental health in this population.
Study methodology impacts density-dependent dispersal observations: a systematic review
Authors: Jreidini Nathalie , Green David M. 
Published: May 2024

AbstractThe relationship between animal dispersal and conspecific density has been explored in various study systems but results in terms of both the magnitude and the direction of density dependence are inconsistent. We conducted a thorough review of the literature (2000–2023) and found k = 97 empirical studies of birds, fishes, herpetofauna (amphibians and reptiles), invertebrates, or mammals that had tested for a correlation between conspecific density and animal dispersal. We extracted categorical variables for taxonomic group, sex, age, migratory behavior, study design, dispersal metric, density metric and variable type, as well as temporal and spatial scale, to test each of their correlation with the effect of density on dispersal (Pearson’s r) using linear regressions and multilevel mixed-effect modelling. We found certain biases in the published literature, highlighting that the impact of conspecific density on dispersal is not as widespread as it is thought to be. We also found no predominant trend for density-dependent dispersal across taxonomic groups. Instead, results show that the scale and metrics of empirical observations significantly affected analytical results, and heterogeneity measures were high within taxonomic groups. Therefore, the direction and magnitude of the interaction between density and dispersal in empirical studies could partially be attributed to the data collection method involved. We suggest that the contradictory observations for density-dependent dispersal could be explained by dispersal-dependent density, where density is driven by movement instead, and urge researchers to either test this interaction when applicable or consider this perspective when reporting results.
HCA-DAN: hierarchical class-aware domain adaptive network for gastric tumor segmentation in 3D CT images
Authors: Yuan Ning , Zhang Yongtao , Lv Kuan , Liu Yiyao , Yang Aocai , Hu Pianpian , Yu Hongwei , Han Xiaowei , Guo Xing , Li Junfeng , Wang Tianfu , Lei Baiying , Ma Guolin 
Published: May 2024

Abstract
Background
Accurate segmentation of gastric tumors from CT scans provides useful image information for guiding the diagnosis and treatment of gastric cancer. However, automated gastric tumor segmentation from 3D CT images faces several challenges. The large variation of anisotropic spatial resolution limits the ability of 3D convolutional neural networks (CNNs) to learn features from different views. The background texture of gastric tumor is complex, and its size, shape and intensity distribution are highly variable, which makes it more difficult for deep learning methods to capture the boundary. In particular, while multi-center datasets increase sample size and representation ability, they suffer from inter-center heterogeneity.

Methods
In this study, we propose a new cross-center 3D tumor segmentation method named Hierarchical Class-Aware Domain Adaptive Network (HCA-DAN), which includes a new 3D neural network that efficiently bridges an Anisotropic neural network and a Transformer (AsTr) for extracting multi-scale context features from the CT images with anisotropic resolution, and a hierarchical class-aware domain alignment (HCADA) module for adaptively aligning multi-scale context features across two domains by integrating a class attention map with class-specific information. We evaluate the proposed method on an in-house CT image dataset collected from four medical centers and validate its segmentation performance in both in-center and cross-center test scenarios.

Results
Our baseline segmentation network (i.e., AsTr) achieves best results compared to other 3D segmentation models, with a mean dice similarity coefficient (DSC) of 59.26%, 55.97%, 48.83% and 67.28% in four in-center test tasks, and with a DSC of 56.42%, 55.94%, 46.54% and 60.62% in four cross-center test tasks. In addition, the proposed cross-center segmentation network (i.e., HCA-DAN) obtains excellent results compared to other unsupervised domain adaptation methods, with a DSC of 58.36%, 56.72%, 49.25%, and 62.20% in four cross-center test tasks.

Conclusions
Comprehensive experimental results demonstrate that the proposed method outperforms compared methods on this multi-center database and is promising for routine clinical workflows.