bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of 3-dimensional simulators for penile prosthesis surgery
Authors: Reisman Yacov , van Renterghem Koen , Meijer Boaz , Ricapito Anna , Fode Mikkel , Bettocchi Carlo 
Published: March 2024

Abstract

Background
The acquisition of skills in penile prosthesis surgery has many limitations mainly due to the absence of simulators and models for training. Three-dimensional (3D) printed models can be utilized for surgical simulations, as they provide an opportunity to practice before entering the operating room and provide better understanding of the surgical approach.

Aim
This study aimed to evaluate and validate a 3D model of human male genitalia for penile prosthesis surgery.

Methods
This study included 3 evaluation and validation stages. The first stage involved verification of the 3D prototype model for anatomic landmarks compared with a cadaveric pelvis. The second stage involved validation of the improved model for anatomic accuracy and teaching purposes with the Rochester evaluation score. The third stage comprised validation of the suitability of the 3D prototype model as a surgical simulator and for skill acquisition. The third stage was performed at 3 centers using a modified version of a pre-existing, validated questionnaire and correlated with the Rochester evaluation score.

Outcome
We sought to determine the suitability of 3D model for training in penile prosthesis surgery in comparison with the available cadaveric model.

Results
The evaluation revealed a high Pearson correlation coefficient (0.86) between questions of the Rochester evaluation score and modified validated questionnaire. The 3D model scored 4.33 ± 0.57 (on a Likert scale from 1 to 5) regarding replication of the relevant human anatomy for the penile prosthesis surgery procedure. The 3D model scored 4.33 ± 0.57 (on a Likert scale from 1 to 5) regarding its ability to improve technical skills, teach and practice the procedure, and assess a surgeon’s ability. Furthermore, the experts stated that compared with the cadaver, the 3D model presented greater ethical suitability, reduced costs, and easier accessibility.

Clinical implications
A validated 3D model is a suitable alternative for penile prosthesis surgery training.

Strengths and limitations
This is the first validated 3D hydrogel model for penile prosthesis surgery teaching and training that experts consider suitable for skill acquisition. Because specific validated guidelines and questionnaires for the validation and verifications of 3D simulators for penile surgery are not available, a modified questionnaire was used.

Conclusion
The current 3D model for penile prosthesis surgery shows promising results regarding anatomic properties and suitability to train surgeons to perform penile implant surgery. The possibility of having an ethical, easy-to-use model with lower costs and limited consequences for the environment is encouraging for further development of the models.
A word of caution: T-DNA-associated mutagenesis in plant reproduction research
Authors: Raabe Karel , Sun Limin , Schindfessel Cédric , Honys David , Geelen Danny 
Published: March 2024

Abstract
T-DNA transformation is prevalent in Arabidopsis research and has expanded to a broad range of crops and model plants. While major progress has been made in optimizing the Agrobacterium-mediated transformation process for various species, a variety of pitfalls associated with the T-DNA insertion may lead to the misinterpretation of T-DNA mutant analysis. Indeed, secondary mutagenesis either on the integration site or elsewhere in the genome, together with epigenetic interactions between T-DNA inserts or frequent genomic rearrangements, can be tricky to differentiate from the effect of the knockout of the gene of interest. These are mainly the case for genomic rearrangements that become balanced in filial generations without consequential phenotypical defects, which may be confusing particularly for studies that aim to investigate fertility and gametogenesis. As a cautionary note to the plant research community studying gametogenesis, we here report an overview of the consequences of T-DNA-induced secondary mutagenesis with emphasis on the genomic imbalance on gametogenesis. Additionally, we present a simple guideline to evaluate the T-DNA-mutagenized transgenic lines to decrease the risk of faulty analysis with minimal experimental effort.
An anticodon-sensing T-boxzyme generates the elongator nonproteinogenic aminoacyl-tRNA in situ of a custom-made translation system for incorporation
Authors: Lu Wei , Terasaka Naohiro , Sakaguchi Yuriko , Suzuki Takeo , Suzuki Tsutomu , Suga Hiroaki 
Published: March 2024

Abstract
In the hypothetical RNA world, ribozymes could have acted as modern aminoacyl-tRNA synthetases (ARSs) to charge tRNAs, thus giving rise to the peptide synthesis along with the evolution of a primitive translation apparatus. We previously reported a T-boxzyme, Tx2.1, which selectively charges initiator tRNA with N-biotinyl-phenylalanine (BioPhe) in situ in a Flexible In-vitro Translation (FIT) system to produce BioPhe-initiating peptides. Here, we performed in vitro selection of elongation-capable T-boxzymes (elT-boxzymes), using para-azido-l-phenylalanine (PheAZ) as an acyl-donor. We implemented a new strategy to enrich elT-boxzyme-tRNA conjugates that self-aminoacylated on the 3′-terminus selectively. One of them, elT32, can charge PheAZ onto tRNA in trans in response to its cognate anticodon. Further evolution of elT32 resulted in elT49, with enhanced aminoacylation activity. We have demonstrated the translation of a PheAZ-containing peptide in an elT-boxzyme-integrated FIT system, revealing that elT-boxzymes are able to generate the PheAZ-tRNA in response to the cognate anticodon in situ of a custom-made translation system. This study, together with Tx2.1, illustrates a scenario where a series of ribozymes could have overseen aminoacylation and co-evolved with a primitive RNA-based translation system.
Structural basis of how MGME1 processes DNA 5′ ends to maintain mitochondrial genome integrity
Authors: Mao Eric Y C , Yen Han-Yi , Wu Chyuan-Chuan 
Published: March 2024

Abstract
Mitochondrial genome maintenance exonuclease 1 (MGME1) helps to ensure mitochondrial DNA (mtDNA) integrity by serving as an ancillary 5′-exonuclease for DNA polymerase γ. Curiously, MGME1 exhibits unique bidirectionality in vitro, being capable of degrading DNA from either the 5′ or 3′ end. The structural basis of this bidirectionally and, particularly, how it processes DNA from the 5′ end to assist in mtDNA maintenance remain unclear. Here, we present a crystal structure of human MGME1 in complex with a 5′-overhang DNA, revealing that MGME1 functions as a rigid DNA clamp equipped with a single-strand (ss)-selective arch, allowing it to slide on single-stranded DNA in either the 5′-to-3′ or 3′-to-5′ direction. Using a nuclease activity assay, we have dissected the structural basis of MGME1-derived DNA cleavage patterns in which the arch serves as a ruler to determine the cleavage site. We also reveal that MGME1 displays partial DNA-unwinding ability that helps it to better resolve 5′-DNA flaps, providing insights into MGME1-mediated 5′-end processing of nascent mtDNA. Our study builds on previously solved MGME1–DNA complex structures, finally providing the comprehensive functional mechanism of this bidirectional, ss-specific exonuclease.
Uncovering the GacS-mediated role in evolutionary progression through trajectory reconstruction in Pseudomonas aeruginosa
Authors: Jiang Bo , Qiu Huifang , Lu Chenghui , Lu Mingqi , Li Yuanhao , Dai Weijun 
Published: March 2024

Abstract
The genetic diversities of subpopulations drive the evolution of pathogens and affect their ability to infect hosts and cause diseases. However, most studies to date have focused on the identification and characterization of adaptive mutations in single colonies, which do not accurately reflect the phenotypes of an entire population. Here, to identify the composition of variant subpopulations within a pathogen population, we developed a streamlined approach that combines high-throughput sequencing of the entire population cells with genotyping of single colonies. Using this method, we reconstructed a detailed quorum-sensing (QS) evolutionary trajectory in Pseudomonas aeruginosa. Our results revealed a new adaptive mutation in the gacS gene, which codes for a histidine kinase sensor of a two-component system (TCS), during QS evolution. This mutation reduced QS activity, allowing the variant to sweep throughout the whole population, while still being vulnerable to invasion by the emerging QS master regulator LasR-null mutants. By tracking the evolutionary trajectory, we found that mutations in gacS facilitated QS-rewiring in the LasR-null mutant. This rapid QS revertant caused by inactive GacS was found to be associated with the promotion of ribosome biogenesis and accompanied by a trade-off of reduced bacterial virulence on host cells. In conclusion, our findings highlight the crucial role of the global regulator GacS in modulating the progression of QS evolution and the virulence of the pathogen population.
Ketogenic diet combined with intermittent fasting: an option for type 2 diabetes remission?
Authors: Zhou Xiao-Ying , Guo Kai-Heng , Huang Shao-Feng , Liu Rui-Ke , Zeng Chun-Ping 
Published: March 2024

Abstract
With increasing attention to diabetes remission, various special dietary patterns have been found to be effective in achieving diabetes remission. The effect of a single dietary pattern on lowering blood glucose is clear, but studies on the synergistic effects of different dietary patterns are limited. This article describes the types of intermittent fasting and ketogenic diets, potential mechanisms, contraindications of combination diets, recommendations for combination diets, and their health outcomes. This paper aims to illustrate the evidence for intermittent fasting combined with a ketogenic diet on outcomes of diabetes remission and effect on blood glucose control. Knowledge of these findings can help doctors and patients determine dietary patterns for achieving diabetes remission and understanding their application.
Salvage Surgery for Initially Unresectable HCC With PVTT Converted by Locoregional Treatment Plus Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody
Authors: Wang Lei , Feng Jin-Kai , Lu Chong-De , Wu Jia-Yi , Zhou Bin , Wang Kang , Wei Xu-Biao , Liang Chao , Zhou Hong-Kun , Shi Jie , Guo Wei-Xing , Lau Wan Yee , Yan Mao-Lin , Cheng Shu-Qun 
Published: March 2024

Abstract

Background
This study aimed to compare the survival outcomes of patients with initially unresectable hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) who underwent or did not undergo salvage surgery followed by a triple combination conversion treatment consisted of locoregional treatment (LRT), tyrosine kinase inhibitors (TKIs), and anti-PD-1 antibodies.

Methods
The data from 93 consecutive patients with initially unresectable HCC and PVTT across 4 medical centers were retrospectively reviewed. They were converted successfully by the triple combination treatment and underwent or did not undergo salvage resection. The baseline characteristics, conversion schemes, conversion treatment-related adverse events (CTRAEs), overall survival (OS), and progression-free survival (PFS) of the salvage surgery and non-surgery groups were compared. Multivariate Cox regression analysis was performed to identify independent risk factors for OS and PFS. Additionally, subgroup survival analysis was conducted by stratification of degree of tumor response and type of PVTT.

Results
Of the 93 patients, 44 underwent salvage surgery, and 49 did not undergo salvage surgery. The OS and PFS of the salvage surgery and non-surgery groups were not significantly different (P = .370 and .334, respectively). The incidence and severity of CTRAEs of the 2 groups were also comparable. Subgroup analyses revealed that for patients with complete response (CR) or types III-IV PVTT, there was a trend toward better survival in patients who did not undergo salvage surgery. Multivariate analysis showed that baseline α-fetoprotein and best tumor response per mRECIST criteria were independent prognostic factors for OS and PFS.

Conclusions
For patients with initially unresectable HCC and PVTT who were successfully converted by the triple combination therapy, salvage liver resection may not be necessary, especially for the patients with CR or types III-IV PVTT.
Regulatory loops between rice transcription factors OsNAC25 and OsNAC20/26 balance starch synthesis
Authors: Wang Juan , Zhang Haiqin , Wang Yuanjiang , Meng Shanshan , Liu Qing , Li Qian , Zhao Zhiwen , Liu Qiaoquan , Wei Cunxu 
Published: March 2024

Abstract
Several starch synthesis regulators have been identified, but these regulators are situated in the terminus of the regulatory network. Their upstream regulators and the complex regulatory network formed between these regulators remain largely unknown. A previous study demonstrated that NAM, ATAF, and CUC (NAC) transcription factors, OsNAC20 and OsNAC26 (OsNAC20/26), redundantly and positively regulate the accumulation of storage material in rice (Oryza sativa) endosperm. In this study, we detected OsNAC25 as an upstream regulator and interacting protein of OsNAC20/26. Both OsNAC25 mutation and OE resulted in a chalky seed phenotype, decreased starch content, and reduced expression of starch synthesis–related genes, but the mechanisms were different. In the osnac25 mutant, decreased expression of OsNAC20/26 resulted in reduced starch synthesis; however, in OsNAC25-overexpressing plants, the OsNAC25–OsNAC20/26 complex inhibited OsNAC20/26 binding to the promoter of starch synthesis–related genes. In addition, OsNAC20/26 positively regulated OsNAC25. Therefore, the mutual regulation between OsNAC25 and OsNAC20/26 forms a positive regulatory loop to stimulate the expression of starch synthesis–related genes and meet the great demand for starch accumulation in the grain filling stage. Simultaneously, a negative regulatory loop forms among the 3 proteins to avoid the excessive expression of starch synthesis–related genes. Collectively, our findings demonstrate that both promotion and inhibition mechanisms between OsNAC25 and OsNAC20/26 are essential for maintaining stable expression of starch synthesis–related genes and normal starch accumulation.
Chromosome ends initiate homologous chromosome pairing during rice meiosis
Authors: You Hanli , Tang Ding , Liu Huixin , Zhou Yue , Li Yafei , Shen Yi , Gong Zhiyun , Yu Hengxiu , Gu Minghong , Jiang Jiming , Zhang Tao , Cheng Zhukuan 
Published: March 2024

Abstract
During meiotic prophase I, chromosomes undergo large-scale dynamics to allow homologous chromosome pairing, prior to which chromosome ends attach to the inner nuclear envelope and form a chromosomal bouquet. Chromosome pairing is crucial for homologous recombination and accurate chromosome segregation during meiosis. However, the specific mechanism by which homologous chromosomes recognize each other is poorly understood. Here, we investigated the process of homologous chromosome pairing during early prophase I of meiosis in rice (Oryza sativa) using pooled oligo probes specific to an entire chromosome or chromosome arm. We revealed that chromosome pairing begins from both ends and extends toward the center from early zygotene through late zygotene. Genetic analysis of both trisomy and autotetraploidy also showed that pairing initiation is induced by both ends of a chromosome. However, healed ends that lack the original terminal regions on telocentric and acrocentric chromosomes cannot initiate homologous chromosome pairing, even though they may still enter the telomere clustering region at the bouquet stage. Furthermore, a chromosome that lacks the distal parts on both sides loses the ability to pair with other intact chromosomes. Thus, the native ends of chromosomes play a crucial role in initiating homologous chromosome pairing during meiosis and likely have a substantial impact on genome differentiation.
Subtilisin-like proteases from Fusarium graminearum induce plant cell death and contribute to virulence
Authors: Xiong Jiang , Luo Mingyu , Chen Yunshen , Hu Qianyong , Fang Ying , Sun Tongjun , Hu Guanjing , Zhang Cui-Jun 
Published: March 2024

Abstract
Fusarium head blight (FHB), caused by Fusarium graminearum, causes huge annual economic losses in cereal production. To successfully colonize host plants, pathogens secrete hundreds of effectors that interfere with plant immunity and facilitate infection. However, the roles of most secreted effectors of F. graminearum in pathogenesis remain unclear. We analyzed the secreted proteins of F. graminearum and identified 255 candidate effector proteins by liquid chromatography-mass spectrometry (LC-MS). Five subtilisin-like family proteases (FgSLPs) were identified that can induce cell death in Nicotiana benthamiana leaves. Further experiments showed that these FgSLPs induced cell death in cotton (Gossypium barbadense) and Arabidopsis (Arabidopsis thaliana). A signal peptide and light were not essential for the cell death-inducing activity of FgSLPs. The I9 inhibitor domain and the entire C-terminus of FgSLPs were indispensable for their self-processing and cell death-inducing activity. FgSLP-induced cell death occurred independent of the plant signal transduction components BRI-ASSOCIATED KINASE 1 (BAK1), SUPPRESSOR OF BIR1 1 (SOBIR1), ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), and PHYTOALEXIN DEFICIENT 4 (PAD4). Reduced virulence was observed when FgSLP1 and FgSLP2 were simultaneously knocked out. This study reveals a class of secreted toxic proteins essential for F. graminearum virulence.
CARM1 drives triple-negative breast cancer progression by coordinating with HIF1A
Authors: Feng Dandan , Gao Jie , Liu Ruiqiong , Liu Wei , Gao Tianyang , Yang Yunkai , Zhang Die , Yang Tianshu , Yin Xin , Yu Hefen , Huang Wei , Wang Yan 
Published: March 2024

Abstract
Coactivator-associated arginine methyltransferase 1 (CARM1) promotes the development and metastasis of estrogen receptor alpha (ERα)-positive breast cancer. The function of CARM1 in triple-negative breast cancer (TNBC) is still unclear and requires further exploration. Here, we report that CARM1 promotes proliferation, epithelial–mesenchymal transition, and stemness in TNBC. CARM1 is upregulated in multiple cancers and its expression correlates with breast cancer progression. Genome-wide analysis of CARM1 showed that CARM1 is recruited by hypoxia-inducible factor-1 subunit alpha (HIF1A) and occupy the promoters of CDK4, Cyclin D1, β-Catenin, HIF1A, MALAT1, and SIX1 critically involved in cell cycle, HIF-1 signaling pathway, Wnt signaling pathway, VEGF signaling pathway, thereby modulating the proliferation and invasion of TNBC cells. We demonstrated that CARM1 is physically associated with and directly interacts with HIF1A. Moreover, we found that ellagic acid, an inhibitor of CARM1, can suppress the proliferation and invasion of TNBC by directly inhibiting CDK4 expression. Our research has determined the molecular basis of CARM1 carcinogenesis in TNBC and its effective natural inhibitor, which may provide new ideas and drugs for cancer therapy.
Maximizing Adherence and Minimizing Time to Antibiotics: A Multi-Disciplinary Institutional Trauma Bay Protocol for Single Antibiotic Prophylaxis in Open Fractures
Authors: Heiman Erick , Delaune Joss , Hong Ian S. , Lamb Matthew , Fisher Marissa , Molino Bruno , Moreau Sandy , Devivo Maria , Liporace Frank A. , Yoon Richard S. , Jankowski Jaclyn M. 
Published: March 2024

Objectives:
To determine if a multi-disciplinary institutional protocol can optimize the time to antibiotic (Abx) administration for open fractures (openFx) and improve compliance with the administration of Abx prophylaxis during trauma activation.

Methods:
Design: Retrospective pre-post study design.

Setting:
Single Level II Trauma Center.

Patient Selection Criteria:
All patients that triggered a trauma activation with suspected openFx and were treated according to the institutional single antibiotic regimen were eligible for inclusion. Patients were excluded if fractures did not involve the appendicular skeleton. Patients treated prior to implementation of a standardized institutional protocol where premixed IV bags of antibiotics were stocked in automated dispensing systems within ED trauma bays (Jan 2021-Oct 2022) were defined as the “pre” group, and those treated following implementation the “post” group.
Outcome Measures and Comparisons: The primary outcome was time from trauma bay arrival to antibiotic aministration, measured in minutes, with comparisons made between pre- and post-protocol implementation. Secondary outcomes for comparison included rates (%) of time to Abx < 60 minutes, allergic reactions, acute kidney injury, ototoxicity, surgical site infection, multi-drug resistant organisms identified in blood or biopsy cultures in cases requiring reoperation, and Clostridium difficile infection in the gastrointestinal system, confirmed by stool test results, within 30 days.

Results:
Twenty-four patients (mean age 39.5±16.3) met the criteria after protocol implementation compared to 72 patients (mean age 34.3±14.8) prior to implementation. Implementation of the institutional protocol resulted in a significant reduction in the time to Abx administration for openFx from 87.9±104.6min to 22.2±12.8min in the post-protocol group (p<0.001). Additionally, only 53% in the pre-protocol group received Abx within 60 minutes compared to 97% in post-protocol group (p<0.001). Post-hoc power analysis revealed that the study was powered at 92% (effect size=0.72) to detect a significant difference between the pre- and post-protocol groups.

Conclusion:
This study provides evidence that a multi-disciplinary institutional protocol for the administration of Abx prophylaxis can be an effective strategy for optimizing the time to Abx administration in cases of suspected openFx. This protocol may be implemented in other trauma centers to optimize time to Abx administration for openFx.

Level of evidence:
III, Retrospective pre-post study.