bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond heat waves: Unlocking epigenetic heat stress memory in Arabidopsis
Authors: Nishio Haruki , Kawakatsu Taiji , Yamaguchi Nobutoshi 
Published: October 2023

Abstract
Plants remember their exposure to environmental changes and respond more effectively the next time they encounter a similar change by flexibly altering gene expression. Epigenetic mechanisms play a crucial role in establishing such memory of environmental changes and fine-tuning gene expression. With the recent advancements in biochemistry and sequencing technologies, it has become possible to characterize the dynamics of epigenetic changes on scales ranging from short term (minutes) to long term (generations). Here, our main focus is on describing the current understanding of the temporal regulation of histone modifications and chromatin changes during exposure to short-term recurring high temperatures and reevaluating them in the context of natural environments. Investigations of the dynamics of histone modifications and chromatin structural changes in Arabidopsis after repeated exposure to heat at short intervals have revealed the detailed molecular mechanisms of short-term heat stress memory, which include histone modification enzymes, chromatin remodelers, and key transcription factors. In addition, we summarize the spatial regulation of heat responses. Based on the natural temperature patterns during summer, we discuss how plants cope with recurring heat stress occurring at various time intervals by utilizing 2 distinct types of heat stress memory mechanisms. We also explore future research directions to provide a more precise understanding of the epigenetic regulation of heat stress memory.
Golgi apparatus-localized CATION CALCIUM EXCHANGER4 promotes osmotolerance of Arabidopsis
Authors: Kanamori Kazuki , Nishimura Kohji , Horie Tomoaki , Sato Masa H , Kajino Takuma , Koyama Takashi , Ariga Hirotaka , Tanaka Keisuke , Yotsui Izumi , Sakata Yoichi , Taji Teruaki 
Published: October 2023

Abstract
Calcium (Ca2+) is a major ion in living organisms, where it acts as a second messenger for various biological phenomena. The Golgi apparatus retains a higher Ca2+ concentration than the cytosol and returns cytosolic Ca2+ to basal levels after transient elevation in response to environmental stimuli such as osmotic stress. However, the Ca2+ transporters localized in the Golgi apparatus of plants have not been clarified. We previously found that a wild-type (WT) salt-tolerant Arabidopsis (Arabidopsis thaliana) accession, Bu-5, showed osmotic tolerance after salt acclimatization, whereas the Col-0 WT did not. Here, we isolated a Bu-5 background mutant gene, acquired osmotolerance-defective 6 (aod6), which reduces tolerance to osmotic, salt, and oxidative stresses, with a smaller plant size than the WT. The causal gene of the aod6 mutant encodes CATION CALCIUM EXCHANGER4 (CCX4). The aod6 mutant was more sensitive than the WT to both deficient and excessive Ca2+. In addition, aod6 accumulated higher Ca2+ than the WT in the shoots, suggesting that Ca2+ homeostasis is disturbed in aod6. CCX4 expression suppressed the Ca2+ hypersensitivity of the csg2 (calcium sensitive growth 2) yeast (Saccharomyces cerevisiae) mutant under excess CaCl2 conditions. We also found that aod6 enhanced MAP kinase 3/6 (MPK3/6)-mediated immune responses under osmotic stress. Subcellular localization analysis of mGFP-CCX4 showed GFP signals adjacent to the trans-Golgi apparatus network and co-localization with Golgi apparatus-localized markers, suggesting that CCX4 localizes in the Golgi apparatus. These results suggest that CCX4 is a Golgi apparatus-localized transporter involved in the Ca2+ response and plays important roles in osmotic tolerance, shoot Ca2+ content, and normal growth of Arabidopsis.
Detection and editing of the updated Arabidopsis plastid- and mitochondrial-encoded proteomes through PeptideAtlas
Authors: van Wijk Klaas J , Bentolila Stephane , Leppert Tami , Sun Qi , Sun Zhi , Mendoza Luis , Li Margaret , Deutsch Eric W 
Published: October 2023

AbstractArabidopsis (Arabidopsis thaliana) ecotype Col-0 has plastid and mitochondrial genomes encoding over 100 proteins. Public databases (e.g. Araport11) have redundancy and discrepancies in gene identifiers for these organelle-encoded proteins. RNA editing results in changes to specific amino acid residues or creation of start and stop codons for many of these proteins, but the impact of RNA editing at the protein level is largely unexplored due to the complexities of detection. Here, we assembled the nonredundant set of identifiers, their correct protein sequences, and 452 predicted nonsynonymous editing sites of which 56 are edited at lower frequency. We then determined accumulation of edited and/or unedited proteoforms by searching ∼259 million raw tandem MS spectra from ProteomeXchange, which is part of PeptideAtlas (www.peptideatlas.org/builds/arabidopsis/). We identified all mitochondrial proteins and all except 3 plastid-encoded proteins (NdhG/Ndh6, PsbM, and Rps16), but no proteins predicted from the 4 ORFs were identified. We suggest that Rps16 and 3 of the ORFs are pseudogenes. Detection frequencies for each edit site and type of edit (e.g. S to L/F) were determined at the protein level, cross-referenced against the metadata (e.g. tissue), and evaluated for technical detection challenges. We detected 167 predicted edit sites at the proteome level. Minor frequency sites were edited at low frequency at the protein level except for cytochrome C biogenesis 382 at residue 124 (Ccb382-124). Major frequency sites (&gt;50% editing of RNA) only accumulated in edited form (&gt;98% to 100% edited) at the protein level, with the exception of Rpl5-22. We conclude that RNA editing for major editing sites is required for stable protein accumulation.
DNA methylation regulates biosynthesis of tanshinones and phenolic acids during growth of Salvia miltiorrhiza
Authors: He Xinyu , Chen Yiwen , Xia Yuting , Hong Xinyu , You Huaqian , Zhang Rui , Liang Zongsuo , Cui Qi , Zhang Shuncang , Zhou Ming , Yang Dongfeng 
Published: October 2023

Abstract
DNA methylation plays a crucial role in the regulation of plant growth and the biosynthesis of secondary metabolites. Danshen (Salvia miltiorrhiza) is a valuable Chinese herbal medicine commonly used to treat cardiovascular diseases; its active ingredients are tanshinones and phenolic acids, which primarily accumulate in roots. Here, we conducted a targeted metabolic analysis of S. miltiorrhiza roots at 3 distinct growth stages: 40 d old (r40), 60 d old (r60), and 90 d old (r90). The contents of tanshinones (cryptotanshinone, tanshinone I, tanshinone IIA, and rosmariquinone) and phenolic acids (rosmarinic acid and salvianolic acid B) gradually increased during plant development. Whole-genome bisulfite sequencing and transcriptome sequencing of roots at the 3 growth stages revealed an increased level of DNA methylation in the CHH context (H represents A, T, or C) context at r90 compared with r40 and r60. Increased DNA methylation levels were associated with elevated expression of various genes linked to epigenetic regulations, including CHROMOMETHYLASE2 (SmCMT2), Decrease in DNA Methylation 1 (SmDDM1), Argonaute 4 (SmAGO4), and DOMAINS REARRANGED METHYLTRANSFERASE 1 (SmDRM1). Moreover, expression levels of many genes involved in tanshinone and salvianolic acid biosynthesis, such as copalyldiphosphate synthase 5 (SmCPS5), cytochrome P450-related enzyme (SmCYP71D464), geranylgeranyl diphosphate synthase (SmGGPPS1), geranyl diphosphate synthase (SmGPPS), hydroxyphenylpyruvate reductase (SmHPPR), and hydroxyphenylpyruvate dioxygenase (SmHPPD), were altered owing to hyper-methylation, indicating that DNA methylation plays an important role in regulating tanshinone and phenolic acid accumulation. Our data shed light on the epigenetic regulation of root growth and the biosynthesis of active ingredients in S. miltiorrhiza, providing crucial clues for further improvement of active compound production via molecular breeding in S. miltiorrhiza.
Arabidopsis reticulons inhibit ROOT HAIR DEFECTIVE3 to form a stable tubular endoplasmic reticulum network
Authors: Wang Weina , Zheng Huanquan 
Published: October 2023

Abstract
The endoplasmic reticulum (ER) is a network of interconnected tubules and sheets stretching throughout the cytoplasm of plant cells. In Arabidopsis (Arabidopsis thaliana), ROOT HAIR DEFECTIVE3 (RHD3) mediates ER tubule fusion, while reticulon proteins induce ER membrane curvature to produce ER tubules. However, it is unclear if and how RHD3–reticulon interplay during the formation of the interconnected tubular ER network. We discovered that RHD3 physically interacts with Arabidopsis reticulon proteins, including reticulon-like protein subfamily B3 (RTNLB3), on ER tubules and at 3-way junctions of the ER. The RTNLB3 protein is widely expressed in Arabidopsis seedlings and localizes to ER tubules. Although the growth of knockout rtnlb3 mutant plants was relatively normal, root hairs of rtnlb3 were shorter than those of wild type. The ER in mature mutant cells was also more sheeted than that in wild type. rhd3 is known to have short roots and root hairs and less branched ER tubules in cells. Interestingly, rtnlb3 genetically antagonizes rhd3 in plant root development and in ER interconnectivity. We show that reticulons including RTNLB3 inhibit the ER fusion activity of RHD3, partly by interfering with RHD3 dimerization. We conclude that reticulon proteins negatively regulate RHD3 to balance its ER fusion activity for the formation of a stable tubular ER network in plant cell growth.
Scaling behavior for electric vehicle chargers and road map to addressing the infrastructure gap
Authors: Wadell Alexius , Guttenberg Matthew , Kempes Christopher P , Viswanathan Venkatasubramanian 
Published: October 2023

Abstract
Enabling widespread electric vehicle (EV) adoption requires a substantial build-out of charging infrastructure in the coming decade. We formulate the charging infrastructure needs as a scaling analysis problem and use it to estimate the EV infrastructure needs of the USA at a county-level resolution. We find that gasoline and EV charging stations scale sub-linearly with their respective vehicle registrations, recovering the sub-linear scaling typical of infrastructure. Surprisingly, we find that EV charging stations scale super-linearly with population size within counties, deviating from the sub-linear scaling of gasoline stations. We discuss how this demonstrates the infancy of both EVs and EV infrastructure while providing a framework for estimating future EV infrastructure demands. By considering the power delivery of existing gasoline stations, and appropriate EV efficiencies, we estimate the EV infrastructure gap at the county level, providing a road map for future EV infrastructure expansion.
The ATTRACT study: screening for the early identification of axial psoriatic arthritis in a cohort of Italian psoriatic patients
Authors: Luchetti Gentiloni Michele Maria , Paci Valentino , Cimaroli Ilaria , Agostinelli Alice , Giannoni Melania , Campanati Anna , Diotallevi Federico , Carotti Marina , Sessa Francesco , Sordillo Raffaella , Macchini Cristina , Fiorini Federico , Massaccesi Leonardo , Ciferri Monia , Gigli Marco , Marconi Valentina , Perini Lucia , Marani Andrea , Giovagnoni Andrea , Polonara Gabriele , Offidani Anna Maria , Benfaremo Devis , Proft Fabian , Poddubnyy Denis , Moroncini Gianluca 
Published: October 2023

Abstract

Objective
There is growing interest in the early identification of patients with axial PsA (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients.

Methods
The dermatologist-centred screening (DCS) questionnaire was administrated by dermatologists to consecutive patients fulfilling the inclusion criteria [(i) age ≥18 years and (ii) clinical diagnosis of psoriasis made by a dermatologist] to identify patients eligible (affirmative answers 1–3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic and imaging data were collected from all referred patients.

Results
Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months and 140 (53%) reporting back pain onset before the age of 45 years. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients. Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with psoriasis without PsA.

Conclusion
The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA.
Multilevel innovation policy mix: impact of regional, national, and European R&D grants
Authors: Acebo Enrique , Miguel-Dávila José-Ángel 
Published: October 2023

Abstract
Research and Development (R&D) grants are one of the most commonly employed programmes by regional, national, and European governments to promote innovation at the firm level. This study contributes to the existing literature on innovation policy mix by investigating whether combinations of the three funding sources can yield positive effects on various measurements of innovation outcomes. Using a panel of 10,045 Spanish firms from 2004 to 2016 and a flexible conditional difference-in-differences approach, our findings reveal that R&D grants funded by European sources exert the most substantial positive impact on firms’ product and process innovations. Conversely, national funding demonstrates this impact on new-to-market innovations and patent applications. Notably, the positive effect on innovation outcomes is evident only when considering the combination of all three distinct funding schemes and the amalgamation of regional and national R&D grants. These results reject the possibility of substitutive effects among different funding schemes, particularly between regional and national institutions.
River Drainage Reorganization and Reticulate Evolution in the Two-Lined Salamander (Eurycea bislineata) Species Complex
Authors: Pierson Todd W , Kozak Kenneth H , Glenn Travis C , Fitzpatrick Benjamin M 
Published: October 2023

Abstract
The origin and eventual loss of biogeographic barriers can create alternating periods of allopatry and secondary contact, facilitating gene flow among distinct metapopulations and generating reticulate evolutionary histories that are not adequately described by a bifurcating evolutionary tree. One such example may exist in the two-lined salamander (Eurycea bislineata) species complex, where discordance among morphological and molecular datasets has created a “vexing taxonomic challenge.” Previous phylogeographic analyses of mitochondrial DNA (mtDNA) suggested that the reorganization of Miocene paleodrainages drove vicariance and dispersal, but the inherent limitations of a single-locus dataset precluded the evaluation of subsequent gene flow. Here, we generate triple-enzyme restriction site-associated DNA sequencing (3RAD) data for &gt; 100 individuals representing all major mtDNA lineages and use a suite of complementary methods to demonstrate that discordance among earlier datasets is best explained by a reticulate evolutionary history influenced by river drainage reorganization. Systematics of such groups should acknowledge these complex histories and relationships that are not strictly hierarchical. [Amphibian; hybridization; introgression; Plethodontidae; stream capture.]
Sex-Based Differences in Inflammatory Bowel Disease Surgical Outcomes
Authors: Sundel Margaret H. , Newland John J. , Blackburn Kyle W. , Vesselinov Roumen M. , Eisenstein Samuel , Bafford Andrea C. ,   On Behalf of the NSQIP IBD Collaborative
Published: October 2023

BACKGROUND:
Although there are discrepancies in the development and progression of inflammatory bowel disease based on biologic sex, little is known about differences in postoperative outcomes between men and women undergoing surgery for this condition.

OBJECTIVE:
Our objective was to compare rates of anastomotic leaks, wound complications, and serious adverse events between men and women undergoing surgery for inflammatory bowel disease.

DESIGN:
This was a retrospective cohort study.

SETTINGS:
Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program Inflammatory Bowel Disease Collaborative database, which includes 15 high-volume inflammatory bowel disease surgery centers.

PATIENTS:
All adult patients undergoing surgery for inflammatory bowel disease were included. Subjects with missing data for exposure or outcome variables were excluded.

MAIN OUTCOME MEASURES:
Rates of anastomotic leaks, wound complications, and serious adverse events were compared between women and men.

RESULTS:
A total of 3143 patients were included. There was a significant association between sex and body mass index, inflammatory bowel disease type, and preoperative medication use. Women had decreased odds of serious adverse events compared to men (OR=0.73, 95% CI: 0.55-0.96), but there was no significant association between sex and anastomotic leaks or wound complications. Inflammatory bowel disease type was found to be an effect measure modifier of the relationship between sex and serious adverse events. Among ulcerative colitis patients, women had a 54% decrease in the odds of serious adverse events compared to men, while there was no significant difference between women and men with Crohn’s disease.

LIMITATIONS:
This study was limited by capturing only 30 days of postoperative outcomes.

CONCLUSIONS:
Women undergoing surgery for ulcerative colitis had decreased odds of serious adverse events compared to men. Understanding sex-based differences in outcomes allows clinicians to make patient-centered decisions regarding surgical planning and perioperative management for inflammatory bowel disease patients..
A Strategy for Rescuing a Child From Clonazepam Poisoning: A Case Study
Authors: Zhao Xuemei , Zhang Rui , Li Wenjing 
Published: October 2023

Background:
This report describes the successful rescue of a 12-year-old girl who ingested large quantities of clonazepam tablets.

Methods:
The patient was promptly treated with flumazenil and hemoperfusion to alleviate the symptoms of central depression. Therapeutic drug monitoring was used to evaluate detoxification efficacy. The authors analyzed the rescue protocol for clonazepam poisoning based on the pathophysiology, clinical manifestations, and pharmacokinetics of clonazepam overdose.

Results:
The patient responded well to the treatment and was discharged from the hospital without adverse events.

Conclusions:
This case study demonstrated the effectiveness and safety of combining flumazenil with hemoperfusion as a treatment for clonazepam poisoning. This study aimed to provide insights into more effective methods for treating clonazepam overdose and contribute to the ongoing issue of managing this condition.
Implementation of an Evidence-Based Medicine Curriculum for Postgraduate Emergency Medicine Physician Assistant and Nurse Practitioner Fellows
Authors: Kerstan Karissa , Elli Megan , Belcher Anne E. , Beuning Alex 
Published: October 2023

Introduction
Within physician assistant (PA) education, the inclusion of evidence-based medicine (EBM) is mandatory. Despite existing literature on EBM training methodologies for PA students and emergency medicine (EM) physician residents, there exists a dearth of published data concerning EBM instruction within postgraduate PA EM programs. A pilot study is described providing an overview of implementation of an EBM curriculum in a single-institution postgraduate physician assistant and nurse practitioner emergency medicine fellowship.

Methods
Quantitative data using pre-curriculum and post-curriculum surveys were collected. The curriculum included statistical concept screencasts, required attendance at a journal club with assigned topics for discussion, and used a critical appraisal tool designed to help fellows better analyze and understand the articles being reviewed. Upon graduation, fellows participated in structured interviews to collect qualitative data about the curriculum and application of learned concepts to the clinical setting.

Results
There was a statistically significant improvement in fellows' reported confidence in discussing the medical literature with practicing providers (P = .02). However, there was no difference in prescores and postscores on EBM knowledge questions or on fellows' feelings of importance of EBM to clinical practice. Qualitative data revealed several themes, including helpfulness of tools provided in the curriculum, appreciation of curricular changes made secondary to fellow suggestions, and reports of improvement in reviewing medical literature and comfort in participation in local journal clubs upon graduation from the fellowship program.

Discussion
Limitations, including small sample size and validity concerns, are discussed. Positive changes were made to the curriculum based on qualitative data collected. The authors advocate for subsequent investigations into this subject within a multi-institutional and multispecialty context, thereby enhancing the breadth of the findings. Nevertheless, this study furnishes the initial accessible substantiation of the viability of introducing an EBM curriculum within this specific demographic.
Fetal Anomaly: Family Experiences and Preferences for Care
Authors: Theroux Rosemary , Violette Cathy 
Published: October 2023

Background:
The prenatal diagnosis of a fetal anomaly is unexpected, creating a family crisis. Expectant parents are at an increased risk for perinatal depression and traumatic stress. Prior reviews examined parents' experiences when terminating but not continuing the pregnancy. This review synthesized qualitative research to describe the experiences, emotional responses, and needs of families continuing their pregnancy.

Methods:
An integrative review was performed using the Whitemore and Knafl methodology and PRISMA guidelines. A systematic review of peer-reviewed articles published between 2000 and 2200 on the experiences of fetal anomaly was performed using 5 databases. Eligible articles included qualitative studies describing families' experiences with a fetal anomaly diagnosis who elected to continue their pregnancy. Methodological quality was evaluated using the Critical Skills Appraisal Program checklist.

Results:
Of the 678 article results, 16 met inclusion criteria. There were 298 participants from 5 countries. The major overarching theme of Response to the Diagnosis of Fetal Anomaly was identified. The major categories were emotional response, coping strategies, influences, health care experiences, and family needs. Uncertainty and grief were the most common emotions.

Discussion:
Parents choosing to continue pregnancy benefit from compassionate, sensitive care, and accurate, concise information, provided in tailored instruction using multiple styles.