bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomolecular condensates in plant RNA silencing: insights into formation, function, and stress responses
Authors: Li Qi , Liu Yang , Zhang Xiaoming 
Published: September 2023

Abstract
Biomolecular condensates are dynamic structures formed through diverse mechanisms, including liquid-liquid phase separation. These condensates have emerged as crucial regulators of cellular processes in eukaryotic cells, enabling the compartmentalization of specific biological reactions while allowing for dynamic exchange of molecules with the surrounding environment. RNA silencing, a conserved gene regulatory mechanism mediated by small RNAs (sRNAs), plays pivotal roles in various biological processes. Multiple types of biomolecular condensate, including dicing bodies, processing bodies, small interfering RNA bodies, and Cajal bodies, have been identified as key players in RNA silencing pathways. These biomolecular condensates provide spatial compartmentation for the biogenesis, loading, action, and turnover of small RNAs. Moreover, they actively respond to stresses, such as viral infections, and modulate RNA silencing activities during stress responses. This review summarizes recent advances in understanding of dicing bodies and other biomolecular condensates involved in RNA silencing. We explore their formation, roles in RNA silencing, and contributions to antiviral resistance responses. This comprehensive overview provides insights into the functional significance of biomolecular condensates in RNA silencing and expands our understanding of their roles in gene expression and stress responses in plants.
Deciphering the structure, function, and mechanism of lysine acetyltransferase cGNAT2 in cyanobacteria
Authors: Jia Kun , Yang Mingkun , Liu Xin , Zhang Qi , Cao Gaoxiang , Ge Feng , Zhao Jindong 
Published: September 2023

Abstract
Lysine acetylation is a conserved regulatory posttranslational protein modification that is performed by lysine acetyltransferases (KATs). By catalyzing the transfer of acetyl groups to substrate proteins, KATs play critical regulatory roles in all domains of life; however, no KATs have yet been identified in cyanobacteria. Here, we tested all predicted KATs in the cyanobacterium Synechococcus sp. PCC 7002 (Syn7002) and demonstrated that A1596, which we named cyanobacterial Gcn5-related N-acetyltransferase (cGNAT2), can catalyze lysine acetylation in vivo and in vitro. Eight amino acid residues were identified as the key residues in the putative active site of cGNAT2, as indicated by structural simulation and site-directed mutagenesis. The loss of cGNAT2 altered both growth and photosynthetic electron transport in Syn7002. In addition, quantitative analysis of the lysine acetylome identified 548 endogenous substrates of cGNAT2 in Syn7002. We further demonstrated that cGNAT2 can acetylate NAD(P)H dehydrogenase J (NdhJ) in vivo and in vitro, with the inability to acetylate K89 residues, thus decreasing NdhJ activity and affecting both growth and electron transport in Syn7002. In summary, this study identified a KAT in cyanobacteria and revealed that cGNAT2 regulates growth and photosynthesis in Syn7002 through an acetylation-mediated mechanism.
Mitochondrial VOLTAGE-DEPENDENT ANION CHANNEL 3 regulates stomatal closure by abscisic acid signaling
Authors: Qin Haixia , Yang Wenqi , Liu Zile , Ouyang Yi , Wang Xiao , Duan Haiyang , Zhao Bing , Wang Shujie , Zhang Junli , Chang Yuankai , Jiang Kun , Yu Ke , Zhang Xuebin 
Published: September 2023

Abstract
In Arabidopsis (Arabidopsis thaliana), stomatal closure mediated by abscisic acid (ABA) is redundantly controlled by ABA receptor family proteins (PYRABACTIN RESISTANCE 1 [PYR1]/PYR1-LIKE [PYLs]) and subclass III SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2 (SnRK2s). Among these proteins, the roles of PYR1, PYL2, and SnRK2.6 are more dominant. A recent discovery showed that ABA-induced accumulation of reactive oxygen species (ROS) in mitochondria promotes stomatal closure. By analyzing stomatal movements in an array of single and higher order mutants, we revealed that the mitochondrial protein VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3) jointly regulates ABA-mediated stomatal closure with a specialized set of PYLs and SnRK2s by affecting cellular and mitochondrial ROS accumulation. VDAC3 interacted with 9 PYLs and all 3 subclass III SnRK2s. Single mutation in VDAC3, PYLs (except PYR1 and PYL2), or SnRK2.2/2.3 had little effect on ABA-mediated stomatal closure. However, knocking out PYR1, PYL1/2/4/8, or SnRK2.2/2.3 in vdac3 mutants resulted in significantly delayed or attenuated ABA-mediated stomatal closure, despite the presence of other PYLs or SnRK2s conferring redundant functions. We found that cellular and mitochondrial accumulation of ROS induced by ABA was altered in vdac3pyl1 mutants. Moreover, H2O2 treatment restored ABA-induced stomatal closure in mutants with decreased stomatal sensitivity to ABA. Our work reveals that VDAC3 ensures redundant control of ABA-mediated stomatal closure by canonical ABA signaling components.
Spontaneous coronary artery dissection: an overview
Authors: Kaddoura Rasha , Cader Fathima Aaysha , Ahmed Ashraf , Alasnag Mirvat 
Published: September 2023

AbstractThe prevalence of spontaneous coronary artery dissection (SCAD) has increased over the last decades in young adults presenting with acute coronary syndrome. Although the diagnostic tools, including intracoronary imaging, have permitted a more accurate diagnosis of SCAD, the prognosis and overall outcomes remain dismal. Furthermore, the disproportionate sex distribution affecting more women and the underdiagnosis in many parts of the world render this pathology a persistent clinical challenge, particularly since the management remains largely supportive with a limited and controversial role for percutaneous or surgical interventions. The purpose of this review is to summarize the available literature on SCAD and to provide insights into the gaps in knowledge and areas requiring further investigation.
Adalimumab serum levels and anti-drug antibodies: associations to treatment response and drug survival in inflammatory joint diseases
Authors: Jyssum Ingrid , Gehin Johanna E , Sexton Joseph , Kristianslund Eirik Klami , Hu Yi , Warren David John , Kvien Tore K , Haavardsholm Espen A , Syversen Silje Watterdal , Bolstad Nils , Goll Guro Løvik 
Published: September 2023

Abstract

Objectives
To explore associations between serum adalimumab level, treatment response and drug survival in order to identify optimal drug levels for therapeutic drug monitoring of adalimumab. Also, to assess the occurrence and risk factors of anti-drug antibody (ADAb) formation.

Methods
Non-trough adalimumab and ADAb levels were measured by automated fluorescence assays in serum collected after 3 months of adalimumab treatment in patients with RA, PsA or axial SpA (axSpA) included in the observational NOR-DMARD study. Treatment response was evaluated after 3 months and drug survival was evaluated during long-term follow-up.

Results
In 340 patients (97 RA, 69 PsA, 174 axSpA), the median adalimumab level was 7.3 mg/l (interquartile range 4.0–10.3). A total of 33 (10%) patients developed ADAbs. Findings were comparable across diagnoses. In RA and PsA, adalimumab levels ≥6.0 mg/l were associated with treatment response [odds ratio (OR) 2.2 (95% CI 1.0, 4.4)] and improved drug survival [hazard ratio 0.49 (95% CI 0.27, 0.80)]. In axSpA, a therapeutic level could not be identified, but higher adalimumab levels were associated with response. Factors associated with ADAb formation were previous bDMARD use, no methotrexate comedication and the use of adalimumab originator compared with GP2017.

Conclusion
Higher adalimumab levels were associated with a better response and improved drug survival for all diagnoses, with a suggested lower threshold of 6.0 mg/l for RA/PsA. This finding, the large variability in drug levels among patients receiving standard adalimumab dose and the high proportion of patients developing ADAbs encourages further investigations into the potential role of therapeutic drug monitoring of adalimumab.
Acquired factor XIII deficiency
Authors: Duranteau Olivier , Tatar Guney , Demulder Anne , Tuna Turgay 
Published: September 2023

Acquired factor XIII (FXIII) deficiency is a very rare haemostatic defect that can be either immune (rare development of an autoantibody targeting FXIII epitopes) or nonimmune (diminished synthesis or increased consumption of the same factor). The aim of this study is to review the symptomatology, the diagnostic method used, but above all to determine the most frequently used and potentially most effective treatment for acquired FXIII deficiency.
PubMed, Medline, embase/Ovid databases were queried from 1 January 2012 to 3 April 2022. Data extraction was performed using the keywords ‘Acquired FXIII deficiency.’
The systematic search identified 474 records. After screening titles and abstracts, only 36 articles met the eligibility criteria.
The mean age of all patients was 57.6 [range, 1–84] years. The male to female ratio was 35 : 25.
The majority of cases described were due an autoimmune reaction with antibody production (24 manuscripts), only six manuscripts described consumption. The most prevalent symptoms were local haematoma (31).
Six cases died, two from haemorrhagic shock, two from haemorrhagic stroke, one from respiratory distress, and 1 from septic shock.
Given the patient outcomes, this review confirms that the most appropriate treatment consists of one of the following elements or a combination of several of these elements: FXIII concentrate, corticosteroids, cyclophosphamide, rituximab for autoimmune cases, and FXIII concentrate supplementation only in case of consumption.
The clinical and financial burden of nonhepatocellular carcinoma focal lesions detected during the surveillance of patients with cirrhosis
Authors: Nahon Pierre , Layese Richard , Ganne-Carrié Nathalie , Moins Cécile , N’Kontchou Gisèle , Chaffaut Cendrine , Ronot Maxime , Audureau Etienne , Durand-Zaleski Isabelle , Natella Pierre-André ,   for the ANRS CO12 CirVir and CIRRAL groups
Published: September 2023

Background and Aims:
HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance.

Approach and Results:
We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087€ for non-HCC HFL and €1572 for HCC.

Conclusions:
Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies.
Impact on Emergency Department Interventions After Implementing a Guideline Based on the Pediatric Emergency Care Applied Research Network Prediction Rule for Identifying Low-Risk Febrile Infants 29 to 60 Days Old
Authors: Mukherjee Gargi , Orenstein Evan , Jain Shabnam , Hames Nicole 
Published: September 2023

Background
The Pediatric Emergency Care Applied Research Network (PECARN) prediction rule identifies febrile infants at low risk for serious bacterial infection (SBI). However, its impact on avoidable interventions in the emergency department remains unknown.

Objective
To study the impact on lumbar puncture (LP) performance, empiric antibiotic use, and admissions after implementing a febrile infant clinical practice guideline for infants aged 29 to 60 days based on the PECARN prediction rule in the pediatric emergency department.

Methods
This single center preintervention to postintervention study included infants 29 to 60 days old who presented with a chief complaint of fever from November 2018 to November 2021 and were assessed for SBI via blood culture and either urinalysis or urine culture. A new clinical practice guideline based on the PECARN prediction rule was implemented on December 2019. Lumbar puncture attempts, antibiotic administration, and admissions were compared preimplementation and postimplementation and in subgroups of low- and high-risk patients.

Results
Of 1597 (PRE: 785, POST: 812) infants presenting with fever, 1032 (PRE: 500, POST: 532) met inclusion criteria. Adoption of guideline recommendations (measured as procalcitonin order rate) was 89.7% in eligible infants postimplementation. Overall, there was a significant decrease in LPs (PRE: 30.6%, POST: 22.6%, P < 0.05) and no significant change in antibiotics or admissions. Among low-risk infants, there was a significant reduction in LPs (PRE: 17.2%, POST: 4.4%, P < 0.05) and antibiotics (PRE: 14.5%, POST: 4.1%; P < 0.05). There was no change in missed SBI (PRE: 3, POST: 2, P = 0.65). No cases of missed meningitis preimplementation or postimplementation were observed.

Conclusions
After implementation of a guideline based on the PECARN prediction rule, we observed a reduction of LPs and antibiotics in low-risk infants. Overall, a decrease in LPs was observed, whereas antibiotic use and admissions remained unchanged.
Color-Contrast Technique Using Fluorescein and Blue Marker to Maximize Visualization during Lymphaticovenous Anastomosis
Authors: Alshomer Feras , Cho Jeongmok , Pak Changsik John , Suh Hyunsuk Peter , Hong Joon Pio 
Published: September 2023

Summary:
Lymphatic vessel wall and lumen visualization during anastomosis is challenging. Different techniques with variable efficacy have been described. Double-opposing color contrast is created using 10% fluorescein sodium, which stains lymphatic fluid yellow, causing a clear contrast to the blue marker–painted lymphatic wall, improving intralumen visualization during the anastomosis process. In this retrospective study, the authors evaluated the success rate of performing anastomosis between the side of the lymphatic vessel and the end of the vein (S-to-E LVA) in 281 patients. The LVA assessment showed mean lymphatic diameter of 0.44 ± 0.09 mm and mean vein diameter of 0.57 ± 0.14 mm with S-to-E success rate of 100% confirmed by postanastomosis indocyanine green lymphography. No adverse events were encountered. Fluorescein sodium was not used in 2 patients because of positive skin allergy test results. This method has the advantages of not needing an additional device, allowing clear visualization, and not staining the surrounding structures. This approach using opposing color contrast between fluorescent yellow and blue marker improved vessel edge identification, which translated into higher visualization and patency with 100% success rate in S-to-E LVA performance.
Rigid versus Nonrigid Fixation for Bilateral Mandibular Angle Fractures: A Retrospective Multicenter Review
Authors: Young Thomas K. , Tuckett Joel , Johnson Nigel R. , Breik Omar 
Published: September 2023

Background:
Fractures involving the bilateral mandibular angle are an uncommon occurrence with limited evidence to inform the ideal fixation requirements for adequate treatment. The aim of this study was to evaluate the outcomes of managing bilateral mandibular angle fractures and determine whether rigid fixation on 1 side improves outcomes compared with bilateral nonrigid fixation.

Methods:
Patients with isolated bilateral mandibular angle fractures treated surgically at the Royal Brisbane and Women’s Hospital, Princess Alexandra Hospital, Gold Coast University Hospital, and Townsville University Hospital between January 1, 2010, and December 31, 2022, were identified retrospectively. Data collected included patient demographics, mechanism of injury, fixation scheme, postoperative occlusion, and the occurrence of postoperative complications and subsequent management.

Results:
Eighty-four patients met the inclusion criteria. Fifty-two patients had nonrigid fixation applied to both fractures, and 32 had rigid fixation placed on at least 1 side. All cases proceeded to union. There was no statistically significant difference between the groups for occlusal outcomes, wound dehiscence, infection, or plate or screw loosening.

Conclusion:
The authors’ results suggest that bilateral nonrigid fixation can be used to treat bilateral mandibular angle fractures in the appropriate clinical context.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
All Stressors Are Not Equal: The Salience of Racial Discrimination and Appraisal for Blood Pressure in African American Women
Authors: Reeves Alexis , Michaels Eli K. , Thomas Marilyn D. , Okoye Uche , Price Melisa M. , Hasson Rebecca E. , Chae David H. , Allen Amani M. 
Published: September 2023

ABSTRACT

Objective
Psychosocial stress is a major predictor of chronic disease among African American (AA) women. Stress is a process involving exposure, appraisal of threat, coping, and psychobiologic adaptation. However, many studies focus on the frequency of stress events and/or coping; few explicitly study stress events and their appraisals; and AA women experience high levels of racial discrimination, a well-known form of social identity threat (i.e., negative experiences due to judgment based on identity). Stressors related to social identity threat may be differentially appraised and associated with divergent physiologic outcomes. This study examined the differences in the frequency and stressfulness associated with general stressors and racial discrimination in relation to blood pressure (BP) among AA women.

Methods
Multivariable regression was used on cross-sectional data from 208 middle-aged AA women residing in the San Francisco Bay Area.

Results
AA women reported less frequency of racial discrimination compared with general stressors, but were more likely to appraise racial discrimination events as stressful. Racial discrimination stressfulness was more strongly associated with systolic BP (SBP) than the number of racial discrimination events. There was a U-shaped association between racial discrimination stress and SBP, with those reporting “none” and “high/very high” distress having the highest SBP (b = 12.2 [2.7 to 21.8] and b = 15.7 [1.5–29.8], respectively, versus moderate stress). Conversely, those reporting “very low” general stressfulness had the lowest SBP (b = −7.9 [−15.8 to −0.1], versus moderate stress). Diastolic BP followed a similar pattern, although results were nonsignificant.

Conclusions
This study highlights the importance of stress appraisal measures and adds to the body of evidence documenting racial discrimination as a salient psychosocial stressor for AA women.
A new direction for cytomegalovirus prophylaxis among transplant recipients: Benefits and nonviral outcomes of letermovir use as primary CMV prophylaxis
Authors: Moore W. Justin , Boutin Catherine-Audrey , Tanna Sajal 
Published: September 2023

Purpose of review
Letermovir has changed the game of primary prophylaxis against cytomegalovirus (CMV) for hematopoietic stem cell transplant (HSCT) and more recently, solid organ transplant recipients. This is largely due to letermovir's similar efficacy in protecting against CMV reactivation and disease, along with its superior safety profile, notably reduced myelotoxicity, and lack of renal dose adjustment compared to standard agents like valganciclovir. This review will describe the potential benefits and clinical considerations of letermovir as prophylaxis among transplant recipients, with a focus on recent evidence describing nonviral outcomes of CMV.

Recent findings
Recent evidence has demonstrated improved safety (e.g., less myelosuppression) and tolerability with no difference in rates of CMV infection or disease in kidney transplant recipients given letermovir compared to valganciclovir. Real-world studies and meta-analyses in HSCT populations have explored various nonviral outcomes with letermovir use. Letermovir prophylaxis was associated with reduced mortality, lower rates of graft versus host disease, delayed CMV immune reconstitution, improved tolerability with extended durations, and decreased healthcare utilization.

Summary
Letermovir is an effective antiviral agent for CMV prevention and has demonstrated enhanced safety, which may allow for extended durations of primary prophylaxis among transplant recipients along with other improved clinical outcomes by mitigating the indirect effects of CMV.
Integrative analysis of multi-omics and machine learning highlighted an m6A-related mRNA signature as a robust AAA progression predictor
Authors: He Yuchen , Xing Jia , Wang Shiyue , Jiang Han , Lun Yu , Han Yanshuo , Erhart Philipp , Böckler Dittmar , Xin Shijie , Zhang Jian 
Published: September 2023

AbstractObjectiveAbdominal aortic aneurysm (AAA) is a life-threatening disease in vascular surgery with significant morbidity and mortality rates upon rupture. Despite surgical interventions, effective targeted drugs for non-surgical candidates are lacking. M6A methylation, a dynamic RNA modification, has been implicated in various diseases, but its role in AAA remains poorly understood. In this study, we aimed to explore the participation of M6A in the progression of AAA progression through multi-omics and machine learning.Approach and Resultswe conducted methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) to profile the m6A methylome in AAA tissues, identifying differentially methylated genes (DMGs). Integrating multi-omics data from RNA-sequencing (RNA-seq) in GEO databases, we developed a machine learning-based AAA m6A-related mRNA signature (AMRMS) to predict AAA dilation risk. The AMRMS demonstrated robust predictive performance in distinguishing AAA patients with large AAA and small AAA. Notably, the AMRMS highlighted FKBP11 as a key gene with a significant impact on the predicted model. Subsequent single-cell RNA sequencing (ScRNA-seq) revealed the pivotal role of FKBP11-positive plasma cells in AAA progression.ConclusionsOur study provides novel insights into the regulatory role of m6A modification in AAA pathogenesis, and further develop a promising AMRMS for risk evaluation in AAA patients. Furthermore, the identification of FKBP11 positive plasma cells as significant contributors to AAA progression opens new avenues for targeted therapeutic interventions.