bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural divergence and phylogenetic relationships of Ajania (Asteraceae) from plastomes and ETS
Authors: Yu Jingya , Han Yun , Xu Hao , Han Shuang , Li Xiaoping , Niu Yu , Chen Shilong , Zhang Faqi 
Published: October 2023

Abstract
Background
Ajania Poljakov, an Asteraceae family member, grows mostly in Asia’s arid and semi-desert areas and is a significant commercial and decorative plant. Nevertheless, the genus’ classification has been disputed, and the evolutionary connections within the genus have not been thoroughly defined. Hence, we sequenced and analyzed Ajania’s plastid genomes and combined them with ETS data to assess their phylogenetic relationships.

Results
We obtained a total of six new Ajania plastid genomes and nine ETS sequences. The whole plastome lengths of the six species sampled ranged from 151,002 bp to 151,115 bp, showing conserved structures. Combined with publicly available data from GenBank, we constructed six datasets to reconstruct the phylogenetic relationships, detecting nucleoplasmic clashes. Our results reveal the affinities of Artemisia, Chrysanthemum and Stilpnolepis to Ajania and validate the early taxonomy reclassification. Some of the plastid genes with low phylogenetic information and gene trees with topological differences may have contributed to the ambiguous phylogenetic results of Ajania. There is extensive evolutionary rate heterogeneity in plastid genes. The psbH and ycf2 genes, which are involved in photosynthesis and ATP transport, are under selective pressure. Plastomes from Ajania species diverged, and structural aspects of plastomes may indicate some of the real evolutionary connections. We suggest the ycf1 gene as a viable plastid DNA barcode because it has significant nucleotide diversity and better reflects evolutionary connections.

Conclusion
Our findings validate the early Ajania taxonomy reclassification and show evolutionary rate heterogeneity, genetic variety, and phylogenetic heterogeneity of plastid genes. This research might provide new insights into the taxonomy and evolution of Ajania, as well as provide useful information for germplasm innovation and genetic enhancement in horticultural species.
Oral midazolam vs. intranasal dexmedetomidine plus oral midazolam for sedation of pediatric outpatients: a double-blinded randomized controlled trial
Authors: Nie Juan , Chen Chanchan , Xie Jing , Ding Guicong 
Published: October 2023

Abstract
Background
Moderate to deep sedation is required for dental treatment of children with dental anxiety. Midazolam is the most commonly used sedative, whereas intranasal dexmedetomidine is increasingly used in pediatric sedation.

Objective
The aim of this trial was to compare the sedative efficacy of oral midazolam alone with that of intranasal dexmedetomidine plus oral midazolam during dental treatment of children with dental anxiety.

Design
In total, 83 children (aged 3–12 years) scheduled to undergo dental sedation were randomized to receive oral midazolam (0.5 mg/kg) and intranasal placebo, or oral midazolam (0.5 mg/kg) plus intranasal dexmedetomidine (2 µg/kg). The primary outcome was the rate of successful sedation for dental treatment. Secondary outcomes were the onset time and adverse events during and after treatment. Data analyses involved descriptive statistics and nonparametric tests.

Results
The rate of successful sedation was significantly higher in combination group (P = 0.007), although the sedation onset time was significantly longer in combination group (17.5 ± 2.4 min) than in monotherapy group (15.7 ± 1.8) (P = 0.003). No children required medical intervention or oxygen therapy for hemodynamic disturbances, and the incidences of adverse events had no significant difference between groups (P = 0.660).

Conclusion
Combined treatment with oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (2 µg/kg) is more significantly effective for managing the behavior of non-cooperative children during dental treatment, compared to oral midazolam (0.5 mg/kg) alone. (Chinese Clinical Trial Registry: ChiCTR2100042300)

Trial registration
ChiCTR2100042300, Clinical trial first registration date: 17/01/2021.
Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study
Authors: Chen Jun , Shen Jiayi , Pan Yuesong , Jing Jing , Wang Yongjun , Wei Tiemin , Lyu Lingchun 
Published: October 2023

Abstract
Background and Aims
Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden.

Methods
This study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk.

Results
A total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001) .

Conclusion
Elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.

What is already known on this topic?
Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear.

What this study adds?
Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level.

How this study might affect research, practice or policy?
Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.
Factors contributing to uncertainty in paediatric abdominal ultrasound reports in the paediatric emergency department
Authors: Hwang Soyun , Chung Hyun Jung , Park Joong Wan , Lee Eui Jun , Lee Ha Ni , Kim Jin Hee , Jue Jie Hee , Choi Young Hun , Jung Jae Yun 
Published: October 2023

Abstract
Background
Abdominal pain, which is a common cause of children presenting to the paediatric emergency department (PED), is often evaluated by ultrasonography (US). However, uncertainty in US reports may necessitate additional imaging.

Objective
In this study, we evaluated factors contributing to uncertainty in paediatric abdominal US reports in the PED.

Materials and methods
This retrospective cohort study included children younger than 18 years of age who underwent abdominal US in the PED of the study hospital between January 2017 and December 2019. After exclusion, the researchers manually reviewed and classified all US reports as ‘certain’ or ‘uncertain’. Univariate and multivariate logistic regression analyses were performed to identify the factors contributing to uncertain reports.

Results
In total, 1006 patients were included in the final analysis., 796 patients were tagged as having certain reports, and 210 as having uncertain reports. Children with uncertain reports had a significantly higher rate of undergoing an additional computed tomography (CT) scan (31.0% vs. 2.5%, p < 0.001) and a longer PED median length of stay (321.0 (Interquartile range (IQR); 211.3-441.5) minutes vs. 284.5 (IQR; 191.8-439.5) minutes, p = 0.042). After logistic regression, US performed by a radiology resident (odds ratio, 5.01; 95% confidence interval, 3.63–7.15) was the most significant factor contributing to uncertainty in paediatric abdominal US reports followed by obesity and age.

Conclusion
Several factors contribute to uncertainty in paediatric abdominal US reports. Uncertain radiological reports increase the likelihood of additional CT scans. Measures to improve the clarity of radiological reports must be considered to improve the quality of care for children visiting the PED.
Clinical systematic reviews – a brief overview
Authors: Iddagoda Mayura Thilanka , Flicker Leon 
Published: October 2023

Abstract
Objective
Systematic reviews answer research questions through a defined methodology. It is a complex task and multiple articles need to be referred to acquire wide range of required knowledge to conduct a systematic review. The aim of this article is to bring the process into a single paper.

Method
The statistical concepts and sequence of steps to conduct a systematic review or a meta-analysis are examined by authors.

Results
The process of conducting a clinical systematic review is described in seven manageable steps in this article. Each step is explained with examples to understand the method evidently.

Conclusion
A complex process of conducting a systematic review is presented simply in a single article.
Dedicated neuroimaging analysis in children with primary headaches: prevalence of lesions and a comparison between patients with and without migraines
Authors: Jeon Cha Woong , Lim Gye Yeon , Moon Ja Un 
Published: October 2023

Abstract
Background
This study evaluated the prevalence and types of intracranial lesions through dedicated imaging analysis of primary headaches in children and compared them between patients with and without migraine.

Methods
This study included 190 children diagnosed with primary headache who underwent neuroimaging, including brain computed tomography (CT), CT angiography (CTA), and brain magnetic resonance imaging (MRI). All patients with primary headaches was divided into two groups, namely, the migraine and non-migraine groups, on the basis of data from electronic medical records. Clinical characteristics and imaging findings were evaluated and compared between the two groups.

Results
Patients with migraine were old and had a longer period from symptom onset to diagnosis. CT was normal in 71 of 95 patients, whereas 7 of 29 patients who underwent CTA had vascular lesions; the migraine group (n = 6/20, [30%]) had higher incidence of vascular lesions than the non-migraine group (n = 1/9, [11.1%]); however, there was no statistically significant difference (p = 0.382). Furthermore, 57.5% (61/106) of children showed normal brain MRI. The most common brain MRI finding was dilated perivascular space (n = 18, [16.8%]). Most perivascular spaces were located in the basal ganglia (n = 72, [75.8%]) and were in linear patterns (n = 58, [63.0%]). There was no statistically significant difference between the two groups.

Conclusion
A low prevalence of significant abnormalities was found in children with primary headaches. Dilated perivascular space was the most common finding in both groups on MRI. CTA showed more vascular lesions in the migraine group than in the non-migraine group. Therefore, further evaluations are needed to reveal the relationship between vascular lesions or dilated perivascular space and pediatric primary headaches.
Integrated bioinformatic analysis reveals NOS2 as a novel ferroptosis-related biomarker for pre-eclampsia
Authors: Cai Shuangming , Huang Shan , Zhang Wenni , Xiao Huanshun , Yu Danfeng , Zhong Xuan , Tao Pei , Luo Yiping 
Published: October 2023

AbstractBackgroundPre-eclampsia (PE) is a common condition in pregnancy; however, methods for early diagnosis and effective treatment options are lacking. Ferroptosis is a newly identified iron-dependent cell death pathway. The aim of this study was to investigate the role of ferroptosis-related genes in PE, the underlying mechanism, and their potential diagnostic value using a bioinformatics approach.MethodsWe downloaded the GSE48424 and GSE98224 datasets from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PE and healthy pregnancy samples were identified in the GSE48424 dataset and subjected to weighted gene co-expression network analysis; the most relevant modules were intersected with known ferroptosis-related genes to distinctly identify the role of ferroptosis in PE. We further searched transcription factors and microRNAs that are predicted to regulate these ferroptosis-related genes, and patients in the GSE48424 dataset were divided into two groups according to high or low expression of the key ferroptosis-related genes associated with PE. To obtain robust key ferroptosis-related genes in PE, we validated their expression levels in the external dataset GSE98224. Finally, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was utilized to access the expression of these genes in the PE and normal blood samples.ResultsSix ferroptosis-related genes involved in PE were obtained by overlapping 3661 genes most associated with PE, 565 DEGs between PE and normal samples, and 259 known ferroptosis-related genes. Among these genes, patients with PE displaying lower expression levels ofNOS2and higher expression levels ofPTGS2had a higher ferroptosis potential index. The expression pattern ofNOS2was consistent in the GSE48424 and GSE98224 datasets. RT-qPCR data confirmed thatNOS2expression was more significantly elevated in patients with PE than in those with a normal pregnancy.ConclusionsOur study explored the diagnostic value of ferroptosis-related genes in PE, and identifiedNOS2as the key gene linking ferroptosis and PE, suggesting a new candidate biomarker for early PE diagnosis.
Incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted antibody-drug conjugates: a systematic review and meta-analysis of randomized controlled trials
Authors: Fu Zhiwen , Gao Chen , Xie Jiyi , Zhang Cong , Li Shijun , Gu Ming , Shi Chen 
Published: October 2023

Abstract
Objective
Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been associated with several fatal adverse events, such as pneumonia, interstitial lung disease, and infection. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted ADCs.

Methods
We performed a systematic search in Embase, PubMed, Web of Science, and Scopus databases from inception to February 1, 2022, and the last search was updated to July 1, 2023. The eligible studies for inclusion in our analysis were limited to RCTs of HER2-targeted ADCs that were approved by the US Food and Drug Administration and examined on cancer patients with available data on fatal adverse events. The protocol for this study was registered in PROSPERO (No. CRD42022331627).

Results
Fifteen studies (13 RCTs) involving 7,277 patients were finally included for meta-analysis. Of these patients, 4,246 received HER2-targeted ADCs and 3,481 received the control treatment. The data were combined using Bayesian hierarchical modeling, which allowed for the estimation of the mean incidence of fatal adverse events to be 0.78% (95% CrI: 0.28-1.37%, τ = 0.006) for the patients treated with HER2-targeted ADCs. The relative risk was 0.80 (95% CrI, 0.5–1.26, τ = 0.17) compared to control patients. Among 43 reported deaths caused by HER2-targeted ADCs, the most common fatal adverse event was respiratory toxicity, including pneumonia, pneumonitis, and interstitial lung disease. On subgroup analysis, no difference in the risk of fatal adverse events was found between different HER2-targeted ADCs or cancer types.

Conclusion
Our findings suggest that the risk of fatal adverse events with HER2-targeted ADCs may be lower compared to standard control therapies in cancer patients, and there is no significant difference in risk observed between different HER2-targeted ADCs or cancer types. However, the most common fatal adverse event was respiratory toxicity, suggesting that cancer patients who use the above drugs should strengthen respiratory system monitoring and take preventive measures in some severe cases.
A case of mitomycin C toxicity after XEN gel stent implantation with the XEN air technique in a glaucoma patient
Authors: Baeg Joon Young , Choi Han Sol , Lee Si Hyung 
Published: October 2023

Abstract
Background
To discuss the first case of mitomycin C (MMC) toxicity after XEN® gel stent implantation in a glaucoma patient, conducted using the XEN “air” technique with an ophthalmic viscosurgical device (OVD).

Case presentation
A 44-year-old Asian male presented with increased intraocular pressure (IOP; 52 mmHg) accompanied by keratic precipitates and an edematous cornea. He was diagnosed with uveitic glaucoma in the left eye, and the IOP was controlled with a topical anti-glaucoma agent. However, glaucoma progression was revealed by Humphrey visual field (HVF) and optical coherence tomography (OCT) examinations. The patient underwent uneventful XEN gel stent implantation using the XEN air technique and an MMC (0.02%, 0.1 mL) injection, with subconjunctival air and OVD injection provided prior to XEN implantation in the left eye. The patient exhibited a decreased IOP (11 mmHg), elevated bleb, and extensive subconjunctival hemorrhage on postoperative day 1. On postoperative day 18, diffuse conjunctival injection and a large avascular bleb was noticed around the XEN gel stent. The patient complained of severe eye pain and discomfort, suggestive of MMC toxicity, and the IOP was 12 mmHg. The patient was treated with a topical steroid and antibiotics tapered over a 6-month period. Finally, the toxicity was successfully controlled, with the IOP stabilizing at around 15 mmHg.

Conclusions
Although significantly greater lowering of the IOP can be expected with the use of subconjunctival OVD injection and MMC during XEN gel stent implantation, a cautious approach and a longer monitoring period are required.
Attention-deficit hyperactivity disorder in children is related to maternal screen time during early childhood in Taiwan: a national prospective cohort study
Authors: Shih Ping , Chiang Tung-liang , Lin Ping-I , Lin Ming-Yu , Guo Yue Leon 
Published: October 2023

Abstract
Background
It is unclear to familial screen time in early childhood is associated with the subsequent diagnosis of attention-deficit and hyperactivity disorder (ADHD). Our study is to evaluate the association between screen time during early childhood in families and the incidence of ADHD.

Methods
We conducted a population-based birth cohort study by using the Taiwan Birth Cohort Study, which recruited 24 200 mother–child pairs when children were 6 months old. Screen time exposure for children and parents were collected at the age of 18 and 36 months. Whether the child has ever been diagnosed with ADHD was determined at a follow-up interview at age 8. Factors including socioeconomic factors and screen time were analyzed using logistic regression to determine their association with the rate of ADHD.

Results
A total of 16 651 term singletons were included in the final analysis. Of them, 382 (2.3%) were diagnosed as having ADHD before the age of 8 years. No significant relationship between children’s or fathers’ screen time and ADHD was noted. When compared to children whose mothers spent less time on screens, those whose mothers spent more than 3 h a day on screens when the child was 3 years old exhibited a higher incidence of ADHD (adjusted OR [aOR]: 1.31, 95% CI: 1.03–1.66).

Conclusion
Higher maternal screen time when the child was 3 years old was associated with an increased incidence of ADHD in this population-based study. However, children’s screen time did not find related to ADHD. We found that it was the mother’s screen time, who typically serves as the primary caregiver in our study participants, not the child’s, that mattered. In addition to superficial screen use time, future research is needed to replicate the findings and clarify mechanisms underlying this association.
A naturalistic study comparing the efficacy of unilateral and bilateral sequential theta burst stimulation in treating major depression – the U-B-D study protocol
Authors: Watson Molly , Chaves Arthur R. , Gebara Abir , Desforges Manon , Broomfield Antoinette , Landry Noémie , Lemoyne Alexandra , Shim Stacey , Drodge Jessica , Cuda Jennifer , Kiaee Nasim , Nasr Youssef , Carleton Christophe , Daskalakis Zafiris J. , Taylor Reggie , Tuominen Lauri , Brender Ram , Antochi Ruxandra , McMurray Lisa , Tremblay Sara 
Published: October 2023

Abstract
Background
Major depressive disorder (MDD) is a prevalent mental health condition affecting millions worldwide, leading to disability and reduced quality of life. MDD poses a global health priority due to its early onset and association with other disabling conditions. Available treatments for MDD exhibit varying effectiveness, and a substantial portion of individuals remain resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS), applied to the left and/or right dorsolateral prefrontal cortex (DLPFC), is an alternative treatment strategy for those experiencing treatment-resistant MDD. The objective of this study is to investigate whether this newer form of rTMS, namely theta burst stimulation (TBS), when performed unilaterally or bilaterally, is efficacious in treatment-resistant MDD.

Methods
In this naturalistic, randomized double-blinded non-inferiority trial, participants with a major depressive episode will be randomized to receive either unilateral (i.e., continuous TBS [cTBS] to the right and sham TBS to the left DLPFC) or bilateral sequential TBS (i.e., cTBS to the right and intermittent TBS [iTBS] to the left DLPFC) delivered 5 days a week for 4–6 weeks. Responders will move onto a 6-month flexible maintenance phase where TBS treatment will be delivered at a decreasing frequency depending on degree of symptom mitigation. Several clinical assessments and neuroimaging and neurophysiological biomarkers will be collected to investigate treatment response and potential associated biomarkers. A non-inferiority analysis will investigate whether bilateral sequential TBS is non-inferior to unilateral TBS and regression analyses will investigate biomarkers of treatment response. We expect to recruit a maximal of 256 participants. This trial is approved by the Research Ethics Board of The Royal's Institute of Mental Health Research (REB# 2,019,071) and will follow the Declaration of Helsinki. Findings will be published in peer-reviewed journals.

Discussion
Comprehensive assessment of symptoms and neurophysiological biomarkers will contribute to understanding the differential efficacy of the tested treatment protocols, identifying biomarkers for treatment response, and shedding light into underlying mechanisms of TBS. Our findings will inform future clinical trials and aid in personalizing treatment selection and scheduling for individuals with MDD.

Trial registration
The trial is registered on https://clinicaltrials.gov/ct2/home (#NCT04142996).