bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘It depends’: what 86 systematic reviews tell us about what strategies to use to support the use of research in clinical practice
Authors: Boaz Annette , Baeza Juan , Fraser Alec , Persson Erik 
Published: February 2024

Abstract
Background
The gap between research findings and clinical practice is well documented and a range of strategies have been developed to support the implementation of research into clinical practice. The objective of this study was to update and extend two previous reviews of systematic reviews of strategies designed to implement research evidence into clinical practice.

Methods
We developed a comprehensive systematic literature search strategy based on the terms used in the previous reviews to identify studies that looked explicitly at interventions designed to turn research evidence into practice. The search was performed in June 2022 in four electronic databases: Medline, Embase, Cochrane and Epistemonikos. We searched from January 2010 up to June 2022 and applied no language restrictions. Two independent reviewers appraised the quality of included studies using a quality assessment checklist. To reduce the risk of bias, papers were excluded following discussion between all members of the team. Data were synthesised using descriptive and narrative techniques to identify themes and patterns linked to intervention strategies, targeted behaviours, study settings and study outcomes.

Results
We identified 32 reviews conducted between 2010 and 2022. The reviews are mainly of multi-faceted interventions (n = 20) although there are reviews focusing on single strategies (ICT, educational, reminders, local opinion leaders, audit and feedback, social media and toolkits). The majority of reviews report strategies achieving small impacts (normally on processes of care). There is much less evidence that these strategies have shifted patient outcomes. Furthermore, a lot of nuance lies behind these headline findings, and this is increasingly commented upon in the reviews themselves.

Discussion
Combined with the two previous reviews, 86 systematic reviews of strategies to increase the implementation of research into clinical practice have been identified. We need to shift the emphasis away from isolating individual and multi-faceted interventions to better understanding and building more situated, relational and organisational capability to support the use of research in clinical practice. This will involve drawing on a wider range of research perspectives (including social science) in primary studies and diversifying the types of synthesis undertaken to include approaches such as realist synthesis which facilitate exploration of the context in which strategies are employed.
Successful tricuspid valve repair and right atrial mass excision for calcified thrombus causing severe tricuspid regurgitation and near-occlusion of inferior vena cava
Authors: Pennacchio Caroline , Rosinski Brad , Grimm Richard , Unai Shinya 
Published: February 2024

Abstract
Background
Calcified right atrial thrombus is rare and commonly occurs secondary to atrial fibrillation and long-term central venous catheterization which present risk for embolization. Treatment typically involves anticoagulation and antiplatelet therapy but rarely surgical excision can be performed, especially in patients with venous obstruction or concomitant valvular dysfunction.

Case presentation
We present the case of a 69 year old symptomatic female with a history of atrial fibrillation and long-term venous catheterization found to have a large calcified right atrial thrombus causing inferior vena cava obstruction and severe tricuspid regurgitation. Patient underwent full median sternotomy with ascending arterial cannulation with superior vena cava and femoral venous cannulation. Intraoperatively, extensive right atrial calcified thrombus was found extending into the inferior vena cava and involving the septal portion of the tricuspid valve annulus causing regurgitation. The calcified thrombus was removed which resolved the inferior vena cava obstruction and the tricuspid valve was repaired by transecting septal leaflet chordae, commissuroplasty, and ring annuloplasty. Postoperative course was uncomplicated and pathology confirmed a calcified right atrial thrombus. At 6 month follow up, the patient was asymptomatic with echocardiogram showing no inferior vena cava stenosis and trivial tricuspid regurgitation.

Conclusions
Surgical excision of calcified right atrial thrombus is rare and is often indicated for symptomatic patients with extensive involvement causing venous inflow obstruction or valvular dysfunction. Sufficient preoperative imaging and a multi-disciplinary approach are essential for accurate diagnosis to guide targeted treatment. When the tricuspid valve is involved, repair is preferred over replacement in this patient population given their propensity for calcification and thrombus formation which may result in an increased risk of early bioprosthetic valve degeneration or mechanical valve thrombosis.
The anatomy of safe surgical teams: an interview-based qualitative study among members of surgical teams at tertiary referral hospitals in Norway
Authors: Vikan Magnhild , Deilkås Ellen CT. , Valeberg Berit T. , Bjørnnes Ann K. , Husby Vigdis S. , Haugen Arvid S. , Danielsen Stein O. 
Published: February 2024

Abstract
Background
In spite of the global implementation of surgical safety checklists to improve patient safety, patients undergoing surgical procedures remain vulnerable to a high risk of potentially preventable complications and adverse outcomes. The present study was designed to explore the surgical teams’ perceptions of patient safety culture, capture their perceptions of the risk for adverse events, and identify themes of interest for quality improvement within the surgical department.

Methods
This qualitative study had an explorative design with an abductive approach. Individual semi-structured in-depth interviews were conducted between 10/01/23 and 11/05/23. The participants were members of surgical teams (n = 17), general and orthopedic surgeons (n = 5), anesthesiologists (n = 4), nurse anesthetists (n = 4) and operating room nurses (n = 4). Middle managers recruited purposively from general and orthopedic surgical teams in two tertiary hospitals in Norway, aiming for a maximum variation due to gender, age, and years within the specialty. The data material was analyzed following Braun and Clarke’s method for reflexive thematic analysis to generate patterns of meaning and develop themes and subthemes.

Results
The analysis process resulted in three themes describing the participants’ perceptions of patient safety culture in the surgical context: (1) individual accountability as a safety net, (2) psychological safety as a catalyst for well-being and safe performance in the operating room, and (3) the importance of proactive structures and participation in organizational learning.

Conclusions
This study provided an empirical insight into the culture of patient safety in the surgical context. The study highlighted the importance of supporting the individuals’ competence, building psychological safety in the surgical team, and creating structures and culture promoting a learning organization. Quality improvement projects, including interventions based on these results, may increase patient safety culture and reduce the frequency of adverse events in the surgical context.
Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade
Authors: Zhang Baoyuan , Li Ning , Gao Jiaming , Zhao Yuxi , Jiang Jun , Xie Shuang , Zhang Cuiping , Zhang Qingyu , Liu Leo , Wang Zaiqi , Ji Dongmei , Wu Lingying , Ren Ruibao 
Published: February 2024

Abstract
Backgrounds
Immune checkpoint blockade (ICB) is widely considered to exert long-term treatment benefits by activating antitumor immunity. However, many cancer patients show poor clinical responses to ICB due in part to the lack of an immunogenic niche. Focal adhesion kinase (FAK) is frequently amplified and acts as an immune modulator across cancer types. However, evidence illustrates that targeting FAK is most effective in combination therapy rather than in monotherapy.

Methods
Here, we used drug screening, in vitro and in vivo assays to filter out that doxorubicin and its liposomal form pegylated liposome doxorubicin (PLD) showed synergistic anti-tumor effects in combination with FAK inhibitor IN10018. We hypothesized that anti-tumor immunity and immunogenic cell death (ICD) may be involved in the treatment outcomes through the data analysis of our clinical trial testing the combination of IN10018 and PLD. We then performed cell-based assays and animal studies to detect whether FAK inhibition by IN10018 can boost the ICD of PLD/doxorubicin and further established syngeneic models to test the antitumor effect of triplet combination of PLD, IN10018, and ICB.

Results
We demonstrated that the combination of FAK inhibitor IN10018, and PLD/doxorubicin exerted effective antitumor activity. Notably, the doublet combination regimen exhibited response latency and long-lasting treatment effects clinically, outcomes frequently observed in immunotherapy. Our preclinical study confirmed that the 2-drug combination can maximize the ICD of cancer cells. This approach primed the tumor microenvironment, supplementing it with sufficient tumor-infiltrating lymphocytes (TILs) to activate antitumor immunity. Finally, different animal studies confirmed that the antitumor effects of ICB can be significantly enhanced by this doublet regimen.

Conclusions
We confirmed that targeting FAK by IN10018 can enhance the ICD of PLD/doxorubicin, further benefiting the anti-tumor effect of ICB. The animal tests of the triplet regimen warrant further discovery in the real world.
High levels of fatty acid-binding protein 5 excessively enhances fatty acid synthesis and proliferation of granulosa cells in polycystic ovary syndrome
Authors: Liu Jingyu , Li Jie , Wu Xin , Zhang Mei , Yan Guijun , Sun Haixiang , Li Dong 
Published: February 2024

Abstract
Background
Polycystic ovary syndrome (PCOS) is one of the most complex endocrine disorders in women of reproductive age. Abnormal proliferation of granulosa cells (GCs) is an important cause of PCOS. This study aimed to explore the role of fatty acid-binding protein 5 (FABP5) in granulosa cell (GC) proliferation in polycystic ovary syndrome (PCOS) patients.

Methods
The FABP5 gene, which is related to lipid metabolism, was identified through data analysis of the gene expression profiles of GSE138518 from the Gene Expression Omnibus (GEO) database. The expression levels of FABP5 were measured by quantitative real-time PCR (qRT‒PCR) and western blotting. Cell proliferation was evaluated with a cell counting kit-8 (CCK-8) assay. Western blotting was used to assess the expression of the proliferation marker PCNA, and immunofluorescence microscopy was used to detect Ki67 expression. Moreover, lipid droplet formation was detected with Nile red staining, and qRT‒PCR was used to analyze fatty acid storage-related gene expression.

Results
We found that FABP5 was upregulated in ovarian GCs obtained from PCOS patients and PCOS mice. FABP5 knockdown suppressed lipid droplet formation and proliferation in a human granulosa-like tumor cell line (KGN), whereas FABP5 overexpression significantly enhanced lipid droplet formation and KGN cell proliferation. Moreover, we determined that FABP5 knockdown inhibited PI3K-AKT signaling by suppressing AKT phosphorylation and that FABP5 overexpression activated PI3K-AKT signaling by facilitating AKT phosphorylation. Finally, we used the PI3K-AKT signaling pathway inhibitor LY294002 and found that the facilitation of KGN cell proliferation and lipid droplet formation induced by FABP5 overexpression was inhibited. In contrast, the PI3K-AKT signaling pathway agonist SC79 significantly rescued the suppression of KGN cell proliferation and lipid droplet formation caused by FABP5 knockdown.

Conclusions
FABP5 promotes active fatty acid synthesis and excessive proliferation of GCs by activating PI3K-AKT signaling, suggesting that abnormally high expression of FABP5 in GCs may be a novel biomarker or a research target for PCOS treatment.
Profiles of subgingival microbiomes and gingival crevicular metabolic signatures in patients with amnestic mild cognitive impairment and Alzheimer’s disease
Authors: Qiu Che , Zhou Wei , Shen Hui , Wang Jintao , Tang Ran , Wang Tao , Xie Xinyi , Hong Bo , Ren Rujing , Wang Gang , Song Zhongchen 
Published: February 2024

Abstract
Background
The relationship between periodontitis and Alzheimer’s disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival crevicular fluid (GCF) metabolic signatures in AD patients have rarely been characterized; thus, little evidence exists to support the oral-brain axis hypothesis. Therefore, our study aimed to characterize both the microbial community of subgingival plaque and the metabolomic profiles of GCF in patients with AD and amnestic mild cognitive impairment (aMCI) for the first time.

Methods
This was a cross-sectional study. Clinical examinations were performed on all participants. The microbial community of subgingival plaque and the metabolomic profiles of GCF were characterized using the 16S ribosomal RNA (rRNA) gene high-throughput sequencing and liquid chromatography linked to tandem mass spectrometry (LC–MS/MS) analysis, respectively.

Results
Thirty-two patients with AD, 32 patients with aMCI, and 32 cognitively normal people were enrolled. The severity of periodontitis was significantly increased in AD patients compared with aMCI patients and cognitively normal people. The 16S rRNA gene sequencing results showed that the relative abundances of 16 species in subgingival plaque were significantly correlated with cognitive function, and LC–MS/MS analysis identified a total of 165 differentially abundant metabolites in GCF. Moreover, multiomics Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) analysis revealed that 19 differentially abundant metabolites were significantly correlated with Veillonella parvula, Dialister pneumosintes, Leptotrichia buccalis, Pseudoleptotrichia goodfellowii, and Actinomyces massiliensis, in which galactinol, sn-glycerol 3-phosphoethanolamine, D-mannitol, 1 h-indole-1-pentanoic acid, 3-(1-naphthalenylcarbonyl)- and L-iditol yielded satisfactory accuracy for the predictive diagnosis of AD progression.

Conclusions
This is the first combined subgingival microbiome and GCF metabolome study in patients with AD and aMCI, which revealed that periodontal microbial dysbiosis and metabolic disorders may be involved in the etiology and progression of AD, and the differential abundance of the microbiota and metabolites may be useful as potential markers for AD in the future.
Polyhydramnios associated with rare genetic syndromes: two case reports
Authors: Lim C. W. C. , Lustestica I. E. , Poon W. B. , Tan W. C. 
Published: February 2024

Abstract
Background
We present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to highlight these rare genetic conditions when obstetricians consider differential diagnoses of polyhydramnios in the third trimester.

Case presentation
Patient 1 is a 34-year-old Asian woman who was diagnosed with polyhydramnios at 28 weeks’ gestation. First trimester testing, fetal anomaly scan, and intrauterine infection screen were normal. Subsequent antenatal ultrasound scans revealed macroglossia, raising the suspicion for Beckwith–Wiedemann syndrome. Chromosomal microarray analysis revealed a female profile with no pathological copy number variants. The patient underwent amnioreduction twice in the pregnancy. The patient presented in preterm labor at 34 weeks’ gestation but elected for an emergency caesarean section. Postnatally, the baby was noted to have a bell-shaped thorax, coat hanger ribs, hypotonia, abdominal distension, and facial dysmorphisms suggestive of Kagami–Ogata syndrome. Patient 2 is a 30-year-old Asian woman who was diagnosed with polyhydramnios at 30 weeks’ gestation. She had a high-risk first trimester screen but declined invasive testing; non-invasive prenatal testing was low risk. Ultrasound examination revealed a macrosomic fetus with grade 1 echogenic bowels but no other abnormalities. Intrauterine infection screen was negative, and there was no sonographic evidence of fetal anemia. She had spontaneous rupture of membranes at 37 + 3 weeks but subsequently delivered by caesarean section in view of pathological cardiotocography. The baby was noted to have inspiratory stridor, hypotonia, low-set ears, and bilateral toe polysyndactyly. Further genetic testing revealed a female profile with a pathogenic variant of the GLI3 gene, confirming a diagnosis of Greig cephalopolysyndactyly syndrome.

Conclusion
These cases illustrate the importance of considering rare genetic causes of polyhydramnios in the differential diagnosis, particularly when fetal anomalies are not apparent at the 20-week structural scan. We would like to raise awareness for these rare conditions, as a high index of suspicion enables appropriate counseling, prenatal testing, and timely referral to pediatricians and geneticists. Early identification and diagnosis allow planning of perinatal care and birth in a tertiary center managed by a multidisciplinary team.
Willingness to pay for an mRNA-based anti-cancer treatment: results from a contingent valuation study in Israel
Authors: Ben-Aharon Omer , Sergienko Ruslan , Iskrov Georgi , Greenberg Dan 
Published: February 2024

Abstract
Background
mRNA technology is currently being investigated for a range of oncology indications. We assessed the willingness to pay (WTP) of the general population in Israel for a hypothetical novel mRNA-based treatment for oncology indications.

Methods
We used a contingent valuation methodology to elicit WTP using a web-based questionnaire. A sample of adult participants were presented with a hypothetical scenario in which an mRNA-based intervention increased the likelihood of a cure for various cancer types from 20% to 40% (half of the sample), or 60% (the other half of the sample).

Results
531 respondents completed the questionnaire. The mean, median and mode WTP for the proposed hypothetical treatment in both scenarios were ILS65,000 (± ILS114,000), ILS20,000 and ILS50,000, respectively (1USD = 3.4ILS). The WTP was skewed towards zero, and 9.6% of the respondents were not willing to pay any amount. WTP higher amounts was significantly associated with higher income (p < 0.01), self-reported good health (p < 0.05), supplementary health insurance (p < 0.05), Jews compared to other populations (p < 0.01), interest in technology (p < 0.001) and a tendency to adopt medical innovations (p < 0.001). No statistical difference between the 40% vs. the 60% potential cure scenarios was found. Logistic and OLS regressions indicated that age, religion, income, and interest in adopting medical innovations were the best predictors of respondents' WTP.

Conclusion
Despite the scientific breakthroughs in oncology treatment over the last few decades, many types of cancer are still incurable. Given the expected development of innovative mRNA-based treatments for cancer, these results should inform policymakers, the pharmaceutical industry and other stakeholders on the future coverage and reimbursement of these technologies incorporating patients’ and societal views. To date, WTP considerations have not been given much weight in prioritization of drug reimbursement processes, neither in Israel nor in other countries. As a pioneer in adoption of the mRNA technology, Israel can also lead the incorporation of WTP considerations in this field.
Sustainability reporting in focus: analysing Spanish transposition of the Non-Financial Reporting European Directive in the agri-food sector
Authors: Anguiano-Santos Carlos , Rodríguez-Entrena Macario 
Published: February 2024

AbstractIn recent decades, the business world has undergone a paradigm shift, prioritizing social and environmental considerations over the exclusive pursuit of economic profits. Corporate social responsibility has become an essential practice, and Sustainability reports (SRs) play a crucial role in facilitating the disclosure of these practices. In the European Union (EU), Directive 2014/95/EU (Non-Financial Reporting Directive—NFRD) was enacted to compel companies to disclose information on matters addressing social, environmental, ethical, and corporate governance aspects. Spain transposed this directive through Law 11/2018, considered one of the strictest in the EU. This study aims to explore and analyse its impact on the agri-food sector. For this purpose, the SRs of 16 agri-food companies that used the Global reporting initiative standard before and after the enforcement of Law 11/2018 were evaluated applying content analysis along with repeated measures ANOVA. The results show a low level of disclosure for both periods and that Law 11/2018 does not succeed in improving the level of disclosure. This suggests that legislators should develop regulations that ensure the usefulness of the disclosed information and that companies should be more involved in the preparation of SRs.
Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins
Authors: Chen Tian-Qi , Huang Heng-Jing , Zhu Shun-Xin , Chen Xiao-Tong , Pu Ke-Jia , Wang Dan , An Yan , Lian Jun-Yi , Sun Yu-Meng , Chen Yue-Qin , Wang Wen-Tao 
Published: February 2024

Abstract
Background
Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements.

Methods
qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux.

Results
The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation.

Conclusions
The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.