bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics ofSalvia miltiorrhizamethylome and the regulatory mechanism of DNA methylation in tanshinone biosynthesis
Authors: Li Jiang , Li Caili , Deng Yuxing , Wei Hairong , Lu Shanfa 
Published: May 2023

AbstractSalvia miltiorrhiza is a model medicinal plant with significant economic and medicinal value. Its roots produce a group of diterpenoid lipophilic bioactive components, termed tanshinones. Biosynthesis and regulation of tanshinones has attracted widespread interest. However, the methylome of S. miltiorrhiza has not been analysed and the regulatory mechanism of DNA methylation in tanshinone production is largely unknown. Here we report single-base resolution DNA methylomes from roots and leaves. Comparative analysis revealed differential methylation patterns for CG, CHG, and CHH contexts and the association between DNA methylation and the expression of genes and small RNAs. Lowly methylated genes always had higher expression levels and 24-nucleotide sRNAs could be key players in the RdDM pathway in S. miltiorrhiza. DNA methylation variation analysis showed that CHH methylation contributed mostly to the difference. Go enrichment analysis showed that diterpenoid biosynthetic process was significantly enriched for genes with downstream overlapping with hypoCHHDMR in July_root when comparing with those in March_root. Tanshinone biosynthesis-related enzyme genes, such as DXS2, CMK, IDI1, HMGR2, DXR, MDS, CYP76AH1, 2OGD25, and CYP71D373, were less CHH methylated in gene promoters or downstream regions in roots collected in July than those collected in March. Consistently, gene expression was up-regulated in S. miltiorrhiza roots collected in July compared with March and the treatment of DNA methylation inhibitor 5-azacytidine significantly promoted tanshinone production. It suggests that DNA methylation plays a significant regulatory role in tanshinone biosynthesis in S. miltiorrhiza through changing the levels of CHH methylation in promoters or downstreams of key enzyme genes.
FvWRKY50 is an important gene that regulates both vegetative growth and reproductive growth in strawberry
Authors: Chen Yating , Liu Liping , Feng Qianqian , Liu Chuang , Bao Yujuan , Zhang Nan , Sun Ronghui , Yin Zhaonan , Zhong Chuanfei , Wang Yuanhua , Li Qian , Li Bingbing 
Published: May 2023

Abstract
The WRKY transcription factors play important roles in plant growth and resistance, but only a few members have been identified in strawberry. Here we identified a WRKY transcription factor, FvWRKY50, in diploid strawberry which played essential roles in strawberry vegetative growth, and reproductive growth. Knocking out FvWRKY50 by genome editing accelerated flowering time and leaf senescence but delayed anthocyanin accumulation in fruit. Further analysis showed that FvWRKY50 acted as a transcriptional repressor to negatively regulate the expression of flowering- and leaf senescence-related genes, including FvFT2, FvCO, FvFT3, and FvSAUR36. Notably, FvWRKY50 directly upregulated the expression of FvCHI and FvDFR by binding their promoter under normal conditions, but at low temperature FvWRKY50 was phosphorylated by FvMAPK3 and then induced protein degradation by ubiquitination, delaying anthocyanin accumulation. In addition, the homozygous mutant of FvWRKY50 was smaller while the biallelic mutant showed normal size. These new findings provide important clues for us to further reveal the regulatory mechanisms of strawberry growth and fruit ripening
The Conditional Association Between Populism, Ideological Extremity, and Affective Polarization
Authors: Stefanelli Alberto 
Published: May 2023

Abstract
In recent years there has been an increasing interest in whether populism is related to opinion extremity. Yet, research on the topic offers little direct evidence on whether and under which conditions populist ideas at the individual level are related to policy extremity and inter-party dislike. This article aims to fill this gap by focusing on the reasons populist individuals hold more or less extreme opinions. Using data from the 2016 American National Electoral Study, I find that populist attitudes are a strong correlate of both ideological extremity and affective polarization, yet this association is conditional on respondent’s party affiliation. Populism is related to higher levels of ideological extremity among Democrats and stronger negative leader evaluations among Republicans. This finding indicates that the relationship between populism and citizens’ political judgements varies depending on the ability of populist leaders to make certain dimensions of the competition salient (i.e., ideological or affective) and exploit pre-existing ideological and partisan rivalries (i.e., party identity).
Genomic Analyses of Longitudinal Mycobacterium abscessus Isolates in a Multicenter Cohort Reveal Parallel Signatures of In-Host Adaptation
Authors: Choi JooHee , Keen Eric C , Wallace Meghan A , Fishbein Skye , Prusa Jerome , Zimbric Madsen , Mejia-Chew Carlos R , Mehta Shail B , Bailey Thomas C , Caverly Lindsay J , Burnham Carey-Ann D , Dantas Gautam 
Published: May 2023

Abstract

Background
Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasingly frequent cause of opportunistic infections. Mycobacterium abscessus complex (MABC) is one of the major NTM lung pathogens that disproportionately colonize and infect the lungs of individuals with cystic fibrosis (CF). MABC infection can persist for years, and antimicrobial treatment is frequently ineffective.

Methods
We sequenced the genomes of 175 isolates longitudinally collected from 30 patients with MABC lung infection. We contextualized our cohort amidst the broader MABC phylogeny and investigated genes undergoing parallel adaptation across patients. Finally, we tested the phenotypic consequences of parallel mutations by conducting antimicrobial resistance and mercury-resistance assays.

Results
We identified highly related isolate pairs across hospital centers with low likelihood of transmission. We further annotated nonrandom parallel mutations in 22 genes and demonstrated altered macrolide susceptibility co-occurring with a nonsynonymous whiB1 mutation. Finally, we highlighted a 23-kb mercury-resistance plasmid whose loss during chronic infection conferred phenotypic susceptibility to organic and nonorganic mercury compounds.

Conclusions
We characterized parallel genomic processes through which MABC is adapting to promote survival within the host. The within-lineage polymorphisms we observed have phenotypic effects, potentially benefiting fitness in the host at the putative detriment of environmental survival.
Serial Casting as an Effective Method for Burn Scar Contracture Rehabilitation: A Case Series
Authors: Schetzsle Stephanie , Lin Weber Wei Chiang , Purushothaman Prabhu , Ding Jie , Kwan Peter , Tredget Edward E 
Published: May 2023

Abstract
Guidelines and protocols for orthoses in burn scar contracture rehabilitation are limited. The current study aims to determine the optimal frequency of casting, potentially facilitating the development of a serial casting protocol. Previous literature supporting casting has low generalizability due to methodology limitations. Seven patients with burn scar contracted joints, who did not respond to traditional therapy, were recruited in this study. Patients were serially casted once, three times, or five times a week. Joint range of motion was maximized with stretching and exercise techniques before every new cast application. Across all patients, active range of motion increased from 65.8 ± 27.8° to 108.1 ± 23.3° with casting; or from 57.8 ± 16.2% to 96.7 ± 2.9% of normal. Similarly, scars improved from 9.5 ± 1.5 to 4.9 ± 1.4 on the Modified Vancouver Scar Scale score. This therapeutic effect was achieved within an average of 8.5 ± 3.7 d and 4.0 ± 2.2 new cast applications. Given the study findings, the procedures outlined could be used to develop a standardized serial casting protocol for burn scar contracture rehabilitation.
The bacterial effector SidN/Lpg1083 promotes cell death by targeting Lamin-B2
Authors: Gao Jiajia , Xu Wenwen , Tang Feng , Xu Minrui , Zhou Qin , Yang Xingyuan , Zhang Nannan , Ma Jinming , Yang Qi , Chen Xiaofang , Qin Ximing , Ge Honghua 
Published: May 2023

Abstract
To facilitate survival, replication, and dissemination, the intracellular pathogen Legionella pneumophila relies on its unique type IVB secretion system (T4SS) to deliver over 330 effectors to hijack host cell pathways in a spatiotemporal manner. The effectors and their host targets are largely unexplored due to their low sequence identity to the known proteins and functional redundancy. The T4SS effector SidN (Lpg1083) is secreted into host cells during the late infection period. However, to the best of our knowledge, the molecular characterization of SidN has not been studied. Herein, we identified SidN as a nuclear envelope-localized effector. Its structure adopts a novel fold, and the N-terminal domain is crucial for its specific subcellular localization. Furthermore, we found that SidN is transported by eukaryotic karyopherin Importin-13 into the nucleus, where it attaches to the N-terminal region of Lamin-B2 to interfere with the integrity of the nuclear envelope, causing nuclear membrane disruption and eventually cell death. Our work provides new insights into the structure and function of an L. pneumophila effector protein, and suggests a potential strategy utilized by the pathogen to promote host cell death and then escape from the host for secondary infection.
Consensus report of the 2021 National Cancer Institute neuroendocrine tumor clinical trials planning meeting
Authors: Singh Simron , Hope Thomas A , Bergsland Emily B , Bodei Lisa , Bushnell David L , Chan Jennifer A , Chasen Beth R , Chauhan Aman , Das Satya , Dasari Arvind , Del Rivero Jaydira , El-Haddad Ghassan , Goodman Karyn A , Halperin Daniel M , Lewis Mark A , Lindwasser O Wolf , Myrehaug Sten , Raj Nitya P , Reidy-Lagunes Diane L , Soares Heloisa P , Strosberg Jonathan R , Kohn Elise C , Kunz Pamela L ,   NET CTPM participants, Bergsland Emily , Beveridge Tom , Bodei Lisa , Borek Anita , Brockman Michelle , Bushnell David , Capala Jacek , Chan Jennifer , Chasen Beth , Chauhan Aman , Das Satya (Nanu) , Arvind Dasari N , Davies-Venn Cynthia , Del Rivero Jaydira , Demaria Sandra , Donoghue Martha , Eads Jennifer , El-Haddad Ghassan , Fielman Natalie , Fishbein Lauren , Gericke Germo , Goodman Karyn , Halperin Daniel , Hendifar Andrew , Hicks Rodney , Hobbs Robert , Hobday Timothy , Hope Thomas , Iyer Renuka , Jaffe Deborah , Kennedy Andrew , Kohn Elise , Kulke Matthew , Kunos Charles , Kunz Pamela L , Lewis Mark , Lin Frank , Lindwasser Wolf , Mailman Josh , McDonald Michael , McEwan Sandy , Myrehaug Sten , Nakasato Antonio , Nothwehr Steve , Ou Fang-Shu , Padda Sukhmani , Pavel Marianne , Pilowa Anthony , Raj Nitya , Ramnaraign Brian , Reidy-Lagunes Diane , Rubinstein Larry , Saletan Stephen , Shah Manisha , Singh Simron , Soares Heloisa , Soulen Michael , Strosberg Jonathan , Untch Brian , Wahba Mona , Wong Rebecca , Yao James 
Published: May 2023

Abstract
Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT.
A Method for Epicuticular Wax and Contaminant Removal from Herbarium Specimens for Scanning Electron Microscopy
Authors: Dai Guang-Yi , Qin Qiao-Mei , Deng Ru-Fang , Hu Xiao-Ying 
Published: May 2023

Abstract
We describe a method for cleaning leaf epicuticular wax and contaminants from herbarium specimens in preparation for scanning electron microscopy. Specimens are rinsed in chloroform, heated at 50°C for 8 hrs, ultrasonicated in 70% ethanol, and subjected to critical-point drying. This method helps preserve and reveal the surface details of specimens that are heavily covered with epicuticular wax and contaminants, making many morphologically and functionally important details readily visible. We tested our method by using it to clean herbarium specimens and comparing the results with those obtained using three other chemicals: acetone, xylene, and 1:1 acetone:xylene, confirming that chloroform treatment was the most effective.
Assessing Common Content and Responsiveness of the QoR-15 and the SF-8 in the Context of Recovery from Regional Anesthesia for Joint Replacement
Authors: Aloziem Okechukwu U , Williams Brian A , Mikolic Joseph M , Boudreaux-Kelly Monique Y , Faruque Saurab , Piva Sara R , Ibinson James W , Switzer Galen E 
Published: May 2023

ABSTRACT

Purpose
There is no consensus regarding how best to measure postoperative quality of recovery after anesthesia/surgery (e.g., using 24-hour survey instruments) in veterans or active military. Our goals were to (1) describe health-related quality-of-life (HRQoL) and recovery across time in veterans, (2) examine the commonality between the quality of recovery (QoR-15) and short-form (SF) surveys (including the SF-8, 24-hour version), and (3) examine the responsiveness of these surveys.

Materials and Methods
This study was approved by the Institutional Review Boards from the University of Pittsburgh, the VA Pittsburgh, and the Human Research Protection Office of the Department of Defense. Secondary analyses of data were executed based on a randomized trial dataset of knee/hip arthroplasty patients, the study having recruited 135 total veterans. QoR-15 and HRQoL SF surveys were completed and self-reported before surgery (pre-op), on postoperative day 2 (PO-D2), and 6 weeks postoperatively. Descriptive statistics were used to examine scores across time. Common content was examined using Pearson’s r. Responsiveness was examined using distribution-based methods.

Results
Average veteran age was 67 year, 89% were male, 88% white, and average body mass index was 33 kg∙m−2. QoR-15 scores declined from pre-op to PO-D2 but were higher than pre-op at 6 weeks. SF physical component summary (PCS) scores were low both pre-op and PO-D2, but were elevated over baseline at 6 weeks. SF mental component summary (MCS) scores declined from baseline to PO-D2 but were higher than pre-op at 6 weeks. Associations of the QoR-15 total score and PCS/MCS were medium/large and statistically significant at P ≤ .01. Both instruments were responsive to changes.

Conclusion
QoR-15 and SF-8 have high content commonality and performed similarly in veterans across time. SF-8 has added benefits of (1) brevity, (2) assessment of physical and mental health components, and (3) being normed to the general population. The SF-8, if used without the QoR-15 in tandem in future study of anesthesia-related outcomes, would need to be supplemented by separate questions addressing postoperative nausea/vomiting (a frequent outcome after anesthesia that is relevant to same-day and next-day mobilization after elective joint replacement surgery).
DIANA-miRPath v4.0: expanding target-based miRNA functional analysis in cell-type and tissue contexts
Authors: Tastsoglou Spyros , Skoufos Giorgos , Miliotis Marios , Karagkouni Dimitra , Koutsoukos Ioannis , Karavangeli Anna , Kardaras Filippos S , Hatzigeorgiou Artemis G 
Published: May 2023

Abstract
DIANA-miRPath is an online miRNA analysis platform harnessing predicted or experimentally supported miRNA interactions towards the exploration of combined miRNA effects. In its latest version (v4.0, http://www.microrna.gr/miRPathv4), DIANA-miRPath breaks new ground by introducing the capacity to tailor its target-based miRNA functional analysis engine to specific biological and/or experimental contexts. Via a redesigned modular interface with rich interaction, annotation and parameterization options, users can now perform enrichment analysis on Gene Ontology (GO) terms, KEGG and REACTOME pathways, sets from Molecular Signatures Database (MSigDB) and PFAM. Included miRNA interaction sets are derived from state-of-the-art resources of experimentally supported (DIANA-TarBase v8.0, miRTarBase and microCLIP cell-type-specific interactions) or from in silico miRNA–target interactions (updated DIANA-microT-CDS and TargetScan predictions). Bulk and single-cell expression datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression project (GTEx) and adult/fetal single-cell atlases are integrated and can be used to assess the expression of enriched term components across a wide range of states. A discrete module enabling enrichment analyses using CRISPR knock-out screen datasets enables the detection of selected miRNAs with potentially crucial roles within conditions under study. Notably, the option to upload custom interaction, term, expression and screen sets further expands the versatility of miRPath webserver.
Efficient gene activation in plants by the MoonTag programmable transcriptional activator
Authors: Casas-Mollano J Armando , Zinselmeier Matthew H , Sychla Adam , Smanski Michael J 
Published: May 2023

Abstract
CRISPR/Cas-based transcriptional activators have been developed to induce gene expression in eukaryotic and prokaryotic organisms. The main advantages of CRISPR/Cas-based systems is that they can achieve high levels of transcriptional activation and are very easy to program via pairing between the guide RNA and the DNA target strand. SunTag is a second-generation system that activates transcription by recruiting multiple copies of an activation domain (AD) to its target promoters. SunTag is a strong activator; however, in some species it is difficult to stably express. To overcome this problem, we designed MoonTag, a new activator that works on the same basic principle as SunTag, but whose components are better tolerated when stably expressed in transgenic plants. We demonstrate that MoonTag is capable of inducing high levels of transcription in all plants tested. In Setaria, MoonTag is capable of inducing high levels of transcription of reporter genes as well as of endogenous genes. More important, MoonTag components are expressed in transgenic plants to high levels without any deleterious effects. MoonTag is also able to efficiently activate genes in eudicotyledonous species such as Arabidopsis and tomato. Finally, we show that MoonTag activation is functional across a range of temperatures, which is promising for potential field applications.
Constitutional Review in the European Legal Space: A Political Science Perspective
Authors: Landfried Christine 
Published: May 2023

Abstract
In this contribution, I present the hypothesis that constitutional review in both the democratic nation-state and the European legal space allows for a method of reflecting on social problems that differs from the mode of politics and, precisely because of the difference between judicial and political decision-making, increases the capacity for legitimate and effective governance. There are six conditions for such a positive potential of constitutional review for democracies. First, citizens must trust constitutional courts and law should be rooted in socially accepted values. Second, democratic, transparent, and diversity-oriented procedures for the selection and election of constitutional court judges are necessary for legitimate constitutional review. Third, constitutional review requires independent courts and a specific way of judicial decision-making that differs from politics. Fourth, a division of labour between constitutional courts and parliaments, linked to the functions of both institutions, ensures the effective protection of the constitution. Fifth, complying with the principle of subsidiarity is crucial because supranational and international courts have insufficient knowledge of national law and, vice versa, national constitutional courts have insufficient knowledge of European law. And finally, the sixth condition is to develop a European understanding of the legal norms of the European Union and the Council of Europe while respecting cultural, legal, and political differences between nation-states. After describing these normative conditions, I will empirically examine whether and to what extent these conditions for the legitimacy and problem-solving capacity of constitutional review are actually met in the European legal space.
New treatment for osteoarthritis: Gene therapy
Authors: Li Xinyu , Shen Leyao , Deng Zhenghan , Huang Zeyu 
Published: May 2023

Abstract
Osteoarthritis is a complex degenerative disease that affects the entire joint tissue. Currently, non-surgical treatments for osteoarthritis focus on relieving pain. While end-stage osteoarthritis can be treated with arthroplasty, the health and financial costs associated with surgery have forced the search for alternative non-surgical treatments to delay the progression of osteoarthritis and promote cartilage repair. Unlike traditional treatment, the gene therapy approach allows for long-lasting expression of therapeutic proteins at specific sites. In this review, we summarize the history of gene therapy in osteoarthritis, outlining the common expression vectors (non-viral, viral), the genes delivered (transcription factors, growth factors, inflammation-associated cytokines, non-coding RNAs) and the mode of gene delivery (direct delivery, indirect delivery). We highlight the application and development prospects of the gene editing technology CRISPR/Cas9 in osteoarthritis. Finally, we identify the current problems and possible solutions in the clinical translation of gene therapy for osteoarthritis.