bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary versus delayed ureteroscopy for ureteric stones: A systematic review and meta-analysis
Authors: Alsawi Mohammed , Nalagatla Sarika , Ahmad Nafees , Chandiramani Ashwini S , Mokool Leenesh , Nalagatla Sarath K , Somani Bhaskar , Aboumarzouk Omar M , Amer Tarik 
Published: August 2022

Background: Ureteric colic is a major clinical and economic burden on the National Health Service. There has been a recent paradigm shift to consider definitive surgery as the primary intervention at the time of initial presentation. Objective: To systematically evaluate the outcomes of primary/emergency ureteroscopy versus delayed/elective ureteroscopy. Methods: We performed a critical review of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials–CENTRAL, CINAHL, Clinicaltrials.gov, Google Scholar and individual urological journals in April 2020. A robust database search was performed using a combination of the terms ‘primary ureteroscopy’, ‘immediate ureteroscopy’, ‘delayed ureteroscopy’ and ‘emergency ureteroscopy’. Adult patients (> 16 years) with ureteric stones presenting as an emergency were included. Results: Twelve studies met the inclusion criteria, with 4 studies directly comparing primary/emergency to delayed/elective ureteroscopy for an acute presentation of ureteric colic. Across the studies, 1708 patients underwent primary/emergency ureteroscopy for ureteric calculi and 990 underwent delayed ureteroscopy. No significant differences in stone-free rates were found between both groups with primary/emergency achieving 85% and delayed/elective 91% ( p = 0.68). The majority of stones treated were located in the distal ureter in both groups. Overall, there were no differences in complications between the groups ( p = 0.42) or major complications (0.17). However, there were fewer minor complications in the primary URS group ( p = 0.02). Ureteral catheter or double-J stent insertion was used in 71% of delayed/elective ureteroscopy cases, compared to 46.8% of primary/emergency cases (p = 0.001). For patients undergoing primary/emergency ureteroscopy, 6.4% patients required auxiliary procedures. In the delayed/elective group, 7.6% required further definitive treatment (NS). Conclusion: Primary ureteroscopy is a safe and feasible procedure, when performed in suitable patients in the acute setting. It is associated with significantly lower stent usage, equivalent stone clearance, no increase in overall or major complications including sepsis, and fewer minor complications when compared to delayed/elective ureteroscopy. Prospective studies will do well to explore this area further but on current evidence, primary ureteroscopy is the safe procedure. Level of evidence: Not applicable
Design, implementation and evaluation of a postgraduate workshop on cross-border healthcare in Europe – Mixed methods research
Authors: Beuken Juliëtte A , Bouwmans Mara EJ , Dolmans Diana HJM , Hornstra Steven PA , Vogt Lina , Verstegen Daniëlle ML 
Published: August 2022

Introduction In European border regions, healthcare providers join forces to make full use of the potential of healthcare. Trainees need to be aware of the challenges and opportunities of cross-border healthcare. To increase such awareness, a workshop was designed, implemented and evaluated. The workshop was entitled ‘Creating cross-border collaborators’ and combined elements of contextual, collaborative and reflective learning. The aim of the study was to understand how this workshop enhanced trainees’ awareness of challenges and opportunities of cross-border healthcare. Methods Using a mixed-methods approach, focus-group interviews (QUAL) were held with trainees ( N = 16) and trainees ( N = 13) completed a survey (QUAN) about their workshop experiences. The workshop was held three times for three different groups of trainees. Results Quantitative analysis (of surveys) demonstrated increased self-reported awareness of cross-border healthcare. All learning principles contributed to this awareness, however reflective learning slightly less. Qualitative analysis (of focus-group interviews) unearthed the following four themes: (1) Attention to cross-border healthcare fostered awareness of its complexity; (2) real-life examples stimulated recognition of challenges and opportunities; (3) discussions in interdisciplinary and international groups helped to see different perspectives; and (4) reflection made trainees think about their own role and perspective. Quantitative and qualitative data are strongly cohered. Conclusion According to participating trainees, a workshop with elements of contextual, collaborative and reflective learning did improve trainee awareness of cross-border healthcare. This study highlights that theoretical insights into learning can and should inform the design and evaluation of workshops.
Heart Failure Caregiver Burden and Outcomes: A Systematic Review
Authors: Suksatan Wanich , Tankumpuan Thitipong , Davidson Patricia M. 
Published: August 2022

Introduction/Objective: This review aimed to summarize articles describing caregiver burden and the relationship between health outcomes as well as describing interventions focusing on this population. Methods: The review used the PRISMA statement and Whittemore and Knafl guidelines. The search engines Scopus, PubMed, Ovid (PsycINFO), and CINAHL were searched for articles published in English. Results: This review included 30 studies that met the criteria. Physical, psychological, and social factors were associated with HF caregiver burden. HF caregiver interventions included health education, post-discharge home visits, phone calls, counseling, and support groups that demonstrated some potential to reduce the caregivers’ burden. Discussion: Healthcare provider team should screen for caregiver burden and promote healthy behaviors, and strategies to improve quality of life. Further studies should include caregivers as care team members and embed social networking in the interventions for reducing HF caregiver burden. The caregivers’ burden could influence the poor outcomes of care, including physical, psychological, societal, and functional dimensions. Future interventions should develop to alleviate HF caregiver burden.
Reconstruction of Two Wall Orbital Fractures: Experience With the 3D Titan Implant and Intraoperative Computed Tomography
Authors: Holan Cole A. , Yan Derek J. , Hancock Ellen , Harshbarger Raymond 
Published: August 2022

Background: Orbital fractures are common in maxillofacial trauma and have varying anatomical deficits depending on the mechanism of injury. Orbital floor fractures are most common, but many patients suffer from two wall-floor and medial wall defects. Precise reconstruction and positioning of the orbital implant post traumatic injury can be technically challenging, especially in two wall fractures. We present our experience using the 3D Titan implant on a series of 7 patients with combined medial wall and orbital floor fractures. Methods: A retrospective chart review was performed of patients with combined medial wall and orbital floor fractures treated with 3D Titan between February 2016 and June 2020. The inclusion criteria were unilateral combined medial and orbital floor fractures due to traumatic etiologies, no previous history of orbital trauma, age older than 18 years, a contralateral healthy orbit, and a clinical follow-up of at least 1 month. Variables and outcomes included patient age, gender, mechanism of injury, visual defects, post-op infections, enophthalmos, proptosis, and diplopia. An O-arm intraoperative CT scanner was used to verify the implant position. Results: Ten patients presented with combined medial wall and orbital floor fractures, 3 were lost to follow-up. There were 6 men and 1 woman, and their ages ranged from 24 to 57 (mean age 38). Follow-up time ranged from 4 to 52 weeks, and a mean of 20 weeks. None of the patients experienced intraoperative complications such as hemorrhage, soft tissue incarceration, or acute optic neuropathy. No patients had postoperative infection or any change in visual acuity. All patients had satisfactory implant positioning as verified by intraoperative CT. Conclusions: The prefabricated design of the 3D Titan along with use of intraoperative CT guidance allows for efficient and precise reconstruction of combined medial wall and orbital floor fractures.
A novel role of FoxO3a in the migration and invasion of trophoblast cells: from metabolic remodeling to transcriptional reprogramming
Authors: Chen Hao , Wang Shi-Han , Chen Chang , Yu Xin-Yang , Zhu Jia-Nan , Mansell Toby , Novakovic Boris , Saffery Richard , Baker Philip N. , Han Ting-Li , Zhang Hua 
Published: August 2022

Abstract
Background
The forkhead box O3a protein (FoxO3a) has been reported to be involved in the migration and invasion of trophoblast, but its underlying mechanisms unknown. In this study, we aim to explore the transcriptional and metabolic regulations of FoxO3a on the migration and invasion of early placental development.

Methods
Lentiviral vectors were used to knock down the expression of FoxO3a of the HTR8/SVneo cells. Western blot, matrigel invasion assay, wound healing assay, seahorse, gas-chromatography-mass spectrometry (GC–MS) based metabolomics, fluxomics, and RNA-seq transcriptomics were performed.

Results
We found that FoxO3a depletion restrained the migration and invasion of HTR8/SVneo cells. Metabolomics, fluxomics, and seahorse demonstrated that FoxO3a knockdown resulted in a switch from aerobic to anaerobic respiration and increased utilization of aromatic amino acids and long-chain fatty acids from extracellular nutrients. Furthermore, our RNA-seq also demonstrated that the expression of COX-2 and MMP9 decreased after FoxO3a knockdown, and these two genes were closely associated with the migration/invasion progress of trophoblast cells.

Conclusions
Our results suggested novel biological roles of FoxO3a in early placental development. FoxO3a exerts an essential effect on trophoblast migration and invasion owing to the regulations of COX2, MMP9, aromatic amino acids, energy metabolism, and oxidative stress.
Measuring interictal burden among people affected by migraine: a descriptive survey study
Authors: Hubig Lena T. , Smith Timothy , Williams Emma , Powell Lauren , Johnston Karissa , Harris Linda , L’Italien Gilbert , Coric Vladimir , Lloyd Andrew J. , Lo Siu Hing 
Published: August 2022

Abstract
Background
Previous research has extensively documented the impact of migraine episodes (‘ictal’) on patients’ health-related quality of life. Few studies have looked at the impact of migraine on migraine-free days (‘interictal’). This study was designed to describe interictal burden of migraine in a mixed group of people affected by migraine and to explore patient characteristics associated with interictal burden.

Methods
People with migraine in the United States (US) and Germany were recruited for a cross-sectional online survey, including a subgroup treated with calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb). The survey included the Migraine Interictal Burden Scale (MIBS-4), Headache Impact Test (HIT-6), and items measuring patient demographics, clinical and treatment background. Data were analyzed using descriptive statistics and linear regression.

Results
Five hundred six people with migraine completed the survey (US: n = 257; Germany: n = 249), of whom 195 had taken a CGRP mAb for three or more months. Participants had a mean of 8.5 (SD = 6.4) Monthly Migraine Days (MMD) and 10.4 (SD = 7.1) Monthly Headache Days (MHD). The mean MIBS-4 score was 6.3 (SD = 3.4), with 67% reporting severe interictal burden (MIBS-4: ≥5). The mean HIT-6 score was 65.3 (SD = 6.0), with 86% reporting severe migraine impact (HIT-6: ≥60). MIBS-4 was correlated with the HIT-6 (r = 0.37), MMD and MHD (both r = 0.27). The HIT-6, MMD, MHD, CGRP mAb treatment, and depression all had an independent positive association with the MIBS-4.

Conclusion
Two-thirds of the study sample reported substantial interictal burden. Whilst interictal burden was associated with migraine frequency and impact of migraine attacks, study results also show it represented a distinct aspect of the overall disease burden. Study findings further indicate unique associations between interictal burden and depression. A unique positive association between interictal burden and CGRP mAb treatment suggests a remaining unmet need among people affected by migraine treated with CGRP mAb.
Taxonomy, comparative genomics of Mullein (Verbascum, Scrophulariaceae), with implications for the evolution of Verbascum and Lamiales
Authors: Dong Xiang , Mkala Elijah Mbandi , Mutinda Elizabeth Syowai , Yang Jia-Xin , Wanga Vincent Okelo , Oulo Millicent Akinyi , Onjolo Victor Omondi , Hu Guang-Wan , Wang Qing-Feng 
Published: August 2022

Abstract
Background
The genus Verbascum L. (Scrophulariaceae) is distributed in Africa, Europe, and parts of Asia, with the Mediterranean having the most species variety. Several researchers have already worked on the phylogenetic and taxonomic analysis of Verbascum by using ITS data and chloroplast genome fragments and have produced different conclusions. The taxonomy and phylogenetic relationships of this genus are unclear.

Results
The complete plastomes (cp) lengths for V. chaixii, V. songaricum, V. phoeniceum, V. blattaria, V. sinaiticum, V. thapsus, and V. brevipedicellatum ranged from 153,014 to 153,481 bp. The cp coded 114 unique genes comprising of 80 protein-coding genes, four ribosomal RNA (rRNA), and 30 tRNA genes. We detected variations in the repeat structures, gene expansion on the inverted repeat, and single copy (IR/SC) boundary regions. The substitution rate analysis indicated that some genes were under purifying selection pressure. Phylogenetic analysis supported the sister relationship of (Lentibulariaceae + Acanthaceae + Bignoniaceae + Verbenaceae + Pedaliaceae) and (Lamiaceae + Phyrymaceae + Orobanchaceae + Paulowniaceae + Mazaceae) in Lamiales. Within Scrophulariaceae, Verbascum was sister to Scrophularia, while Buddleja formed a monophyletic clade from (Scrophularia + Verbascum) with high bootstrap support values. The relationship of the nine species within Verbascum was highly supported.

Conclusion
Based on the phylogenetic results, we proposed to reinstate the species status of V. brevipedicellatum (Engl.) Hub.-Mor. Additionally, three genera (Mazus, Lancea, and Dodartia) placed in the Phyrymaceae family formed a separate clade within Lamiaceae. The classification of the three genera was supported by previous studies. Thus, the current study also suggests the circumscription of these genera as documented previously to be reinstated. The divergence time of Lamiales was approximated to be 86.28 million years ago (Ma) (95% highest posterior density (HPD), 85.12–89.91 Ma). The complete plastomes sequence data of the Verbascum species will be important for understanding the Verbascum phylogenetic relationships and evolution in order Lamiales.
Evolutionary analysis and functional characterization of BZR1 gene family in celery revealed their conserved roles in brassinosteroid signaling
Authors: Zuo Chunliu , Zhang Lan , Yan Xinyue , Guo Xinyue , Zhang Qing , Li Songyang , Li Yanling , Xu Wen , Song Xiaoming , Wang Jinpeng , Yuan Min 
Published: August 2022

Abstract
Background
Brassinosteroids (BRs) are a group of essential steroid hormones involved in diverse developmental and physiological processes in plants. The Brassinazole-resistant 1 (BZR1) transcription factors are key components of BR signaling and integrate a wide range of internal and environmental signals to coordinate plant development, growth, and resistance to abiotic and biotic stresses. Although the BZR1 family has been fully studied in Arabidopsis, celery BZR1 family genes remain largely unknown.

Results
Nine BZR1 genes were identified in the celery genome, and categorized into four classes based on phylogenetic and gene structure analyses. All the BZR1 proteins shared a typical bHLH (basic helix-loop-helix) domain that is highly conserved across the whole family in Arabidopsis, grape, lettuce, ginseng, and three Apiaceae species. Both duplications and losses of the BZR1 gene family were detected during the shaping of the celery genome. Whole-genome duplication (WGD) or segmental duplication contributed 55.56% of the BZR1 genes expansion, and the γ as well as celery-ω polyploidization events made a considerable contribution to the production of the BZR1 paralogs in celery. Four AgBZR1 members (AgBZR1.1, AgBZR1.3, AgBZR1.5, and AgBZR1.9), which were localized both in the nucleus and cytoplasm, exhibit transcription activation activity in yeast. AgBZR1.5 overexpression transgenic plants in Arabidopsis showed curled leaves with bent, long petioles and constitutive BR-responsive phenotypes. Furthermore, the AgBZR1 genes possessed divergent expression patterns with some overlaps in roots, petioles, and leaves, suggesting an extensive involvement of AgBZR1s in the developmental processes in celery with both functional redundancy and divergence.

Conclusions
Our results not only demonstrated that AgBZR1 played a conserved role in BR signaling but also suggested that AgBZR1 might be extensively involved in plant developmental processes in celery. The findings lay the foundation for further study on the molecular mechanism of the AgBZR1s in regulating the agronomic traits and environmental adaptation of celery, and provide insights for future BR-related genetic breeding of celery and other Apiaceae crops.
The patient education strategy “learning and coping” improves adherence to cardiac rehabilitation in primary healthcare settings: a pragmatic cluster-controlled trial
Authors: Pedersen Charlotte Gjørup , Nielsen Claus Vinther , Lynggaard Vibeke , Zwisler Ann Dorthe , Maribo Thomas 
Published: August 2022

Abstract
Background
Adherence and completion of programmes in educational and physical exercise sessions is essential in cardiac rehabilitation (CR) to obtain the known benefits on morbidity, mortality, risk factors, lifestyle, and quality of life. The patient education strategy “Learning and Coping” (LC) has been reported to positively impact adherence and completion in a hospital setting. It is unknown if LC has impact on adherence in primary healthcare settings, and whether LC improves self-management. The aim of this pragmatic primary healthcare-based study was to examine whether patients attending CR based on LC had a better adherence to patient education and physical exercise, higher program completion rate, and better self-management compared to patients attending CR based on a consultation program Empowerment, Motivation and Medical Adherence (EMMA).

Method
A pragmatic cluster-controlled trial of two types of patient education LC and EMMA including ten primary healthcare settings and 514 patients (LC, n = 266; EMMA, n = 248) diagnosed with ischaemic heart disease discharged from hospital and referred to CR between August 1, 2018 and July 31, 2019. Adherence was defined as participation in ≥ 75% of provided sessions. Completion was defined as patients attended the final interview at the end of the 12-weeks programme. Patient Activation Measure (PAM) was used to obtain information on a person's knowledge, skills and confidence for self-management. PAM questionnaire was completed at baseline and 12-weeks follow-up. Multiple and Linear regression analyses adjusted for potential confounder variables and cluster effect were performed.

Result
Patients who followed CR based on LC had a higher adherence rate to educational and physical exercise sessions compared to patients who followed CR based on EMMA (p < 0.01). High-level of completion was found at the end of CR with no statistically significant between clusters (78.9% vs. 78.2%, p > 0.05). At 12-weeks, there was no statistical differences in PAM-score between clusters (p > 0.05).

Conclusion
This study indicates that the LC positively impacts adherence in CR compared to EMMA. We found non-significant difference in completing CR and in patient self-management between the two types of patient education. Future studies are needed to investigate if the higher adherence rate achieved by LC in primary healthcare settings translates into better health outcomes.
Oxygen debt repayment in the early phase of veno-arterial extracorporeal membrane oxygenation: a cluster analysis
Authors: Kurniawati E. R. , Teerenstra S. , Vranken N. P. A. , Sharma A. S. , Maessen J. G. , Weerwind P. W. 
Published: August 2022

Abstract
Introduction
Early oxygen debt repayment is predictive of successful weaning from veno-arterial extracorporeal membrane oxygenation (V-A ECMO). However, studies are limited by the patient cohort’s heterogeneity. This study aimed to understand the early state of oxygen debt repayment and its association with end-organ failure and 30-day survival using cluster analysis.

Methods
A retrospective, single-center study was conducted on 153V-A ECMO patients. Patients were clustered using a two-step cluster analysis based on oxygen debt and its repayment during the first 24 h of ECMO. Primary outcomes were end-organ failure and 30-day survival.

Results
The overall mortality was 69.3%. For cluster analysis, 137 patients were included, due to an incomplete data set. The mortality rate in this subset was 67.9%. Three clusters were generated, representing increasing levels of total oxygen debt from cluster 1 to cluster 3. Thirty-day survival between clusters was significantly different (cluster 1: 46.9%, cluster 2: 23.4%, and cluster 3: 4.8%, p = 0.001). Patients in cluster 3 showed less decrement in liver enzymes, creatinine, and urea blood levels. There were significant differences in the baseline oxygen debt and the need for continuous veno-venous hemofiltration (CVVH) between survivors and non-survivors (p < 0.05). Forty-seven patients (34.3%) migrated between clusters within the first 24 h of support. Among these patients, 43.4% required CVVH. Notably, patients requiring CVVH and who migrated to a cluster with a higher oxygen debt repayment showed better survival rates compared to those who migrated to a cluster with a lower oxygen debt repayment.

Conclusions
Oxygen debt repayment during the first 24 h of V-A ECMO shows to correspond with survival, where the baseline oxygen debt value and the necessity for continuous kidney replacement therapy appear to be influential.