bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidisciplinary meeting review in nonsmall cell lung cancer: a systematic review and meta-analysis
Authors: Stirling Rob G. , Harrison Amelia , Huang Joanna , Lee Vera , Taverner John , Barnes Hayley 
Published: May 2024

Background:Lung cancer diagnosis, staging and treatment may be enhanced by multidisciplinary participation and presentation in multidisciplinary meetings (MDM). We performed a systematic review and meta-analysis to explore literature evidence of clinical impacts of MDM exposure.Methods:A study protocol was registered (PROSPERO identifier CRD42021258069). Randomised controlled trials and observational cohort studies including adults with nonsmall cell lung cancer and who underwent MDM review, compared to no MDM, were included. MEDLINE, CENTRAL, Embase andClinicalTrials.govwere searched on 31 May 2021. Studies were screened and extracted by two reviewers. Outcomes included time to diagnosis and treatment, histological confirmation, receipt of treatments, clinical trial participation, survival and quality of life. Risk of bias was assessed using the ROBINS-I (Risk of Bias in Non-randomised Studies – of Interventions) tool.Results:2947 citations were identified, and 20 studies were included. MDM presentation significantly increased histological confirmation of diagnosis (OR 3.01, 95% CI 2.30–3.95; p<0.00001) and availability of clinical staging (OR 2.55, 95% CI 1.43–4.56; p=0.002). MDM presentation significantly increased likelihood of receipt of surgery (OR 2.01, 95% CI 1.29–3.12; p=0.002) and reduced the likelihood of receiving no active treatment (OR 0.32, 95% CI 0.21–0.50; p=0.01). MDM presentation was protective of both 1-year survival (OR 3.23, 95% CI 2.85–3.68; p<0.00001) and overall survival (hazard ratio 0.63, 95% CI 0.55–0.72; p<0.00001).Discussion:MDM presentation was associated with increased likelihood of histological confirmation of diagnosis, documentation of clinical staging and receipt of surgery. Overall and 1-year survival was better in those presented to an MDM, although there was some clinical heterogeneity in participants and interventions delivered. Further research is required to determine the optimal method of MDM presentation, and address barriers to presentation.
African ancestry-derived APOL1 risk genotypes show proximal epigenetic associations
Authors: Breeze Charles E. , Lin Bridget M. , Winkler Cheryl A. , Franceschini Nora 
Published: May 2024

AbstractApolipoprotein L1 (APOL1) coding variants, termed G1 and G2, are established genetic risk factors for a growing spectrum of diseases, including kidney disease, in individuals of African ancestry. Evidence suggests that the risk variants, which show a recessive mode of inheritance, lead to toxic gain-of-function changes of the APOL1 protein. Disease occurrence and presentation vary, likely due to modifiers or second hits. To understand the role of the epigenetic landscape in relation to APOL1 risk variants, we performed methylation quantitative trait locus (meQTL) analysis to identify differentially methylated CpGs influenced by APOL1 risk variants in 611 African American individuals. We identified five CpGs that were significantly associated with APOL1 risk alleles in discovery and replication studies, and one CpG-APOL1 association was independent of other genomic variants. Our study highlights proximal DNA methylation alterations that may help explain the variable disease risk and clinical manifestation of APOL1 variants.
Healthcare utilization patterns of individuals with depression after national policy to increase the mental health workforce in primary care: a data linkage study
Authors: Dros Jesper T. , van Dijk Christel E. , Böcker Koen B.E. , Bruins Slot Lotte C.J.A.F , Verheij Robert A. , Meijboom Bert R. , Dik Jan-Willem , Bos Isabelle 
Published: May 2024

Abstract
Background
The deployment of the mental health nurse, an additional healthcare provider for individuals in need of mental healthcare in Dutch general practices, was expected to substitute treatments from general practitioners and providers in basic and specialized mental healthcare (psychologists, psychotherapists, psychiatrists, etc.). The goal of this study was to investigate the extent to which the degree of mental health nurse deployment in general practices is associated with healthcare utilization patterns of individuals with depression.

Methods
We combined national health insurers’ claims data with electronic health records from general practices. Healthcare utilization patterns of individuals with depression between 2014 and 2019 (N = 31,873) were analysed. The changes in the proportion of individuals treated after depression onset were assessed in association with the degree of mental health nurse deployment in general practices.

Results
The proportion of individuals with depression treated by the GP, in basic and specialized mental healthcare was lower in individuals in practices with high mental health nurse deployment. While the association between mental health nurse deployment and consultation in basic mental healthcare was smaller for individuals who depleted their deductibles, the association was still significant. Treatment volume of general practitioners was also lower in practices with higher levels of mental health nurse deployment.

Conclusion
Individuals receiving care at a general practice with a higher degree of mental health nurse deployment have lower odds of being treated by mental healthcare providers in other healthcare settings. More research is needed to evaluate to what extent substitution of care from specialized mental healthcare towards general practices might be associated with waiting times for specialized mental healthcare.
Greatly isolated heterogeneous circulating tumor cells using hybrid engineered cell membrane-camouflaged magnetic nanoparticles
Authors: Jiang Xinbang , Zhang Xiangyun , Guo Chen , Liu Zhuang , Guo Xiaofang , Tian Ziying , Wang Zimeng , Yang Jingxuan , Huang Xinglu , Ou Lailiang 
Published: May 2024

Abstract
Background
Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation.

Methods
To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis.

Conclusions
This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.

Graphical abstract
FGF21 attenuates neuroinflammation following subarachnoid hemorrhage through promoting mitophagy and inhibiting the cGAS-STING pathway
Authors: Ma Yue , Liu Zhiqin , Deng Lele , Du Jingjing , Fan Zenghui , Ma Tian , Xiong Jing , Xiuyun Xue , Gu Naibing , Di Zhengli , Zhang Yu 
Published: May 2024

Abstract
Background
Subarachnoid hemorrhage (SAH) represents a form of cerebrovascular event characterized by a notable mortality and morbidity rate. Fibroblast growth factor 21 (FGF21), a versatile hormone predominantly synthesized by the hepatic tissue, has emerged as a promising neuroprotective agent. Nevertheless, the precise impacts and underlying mechanisms of FGF21 in the context of SAH remain enigmatic.

Methods
To elucidate the role of FGF21 in inhibiting the microglial cGAS-STING pathway and providing protection against SAH-induced cerebral injury, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, RNA sequencing, and behavioral assays, were employed.

Results
Administration of recombinant fibroblast growth factor 21 (rFGF21) effectively mitigated neural apoptosis, improved cerebral edema, and attenuated neurological impairments post-SAH. Transcriptomic analysis revealed that SAH triggered the upregulation of numerous genes linked to innate immunity, particularly those involved in the type I interferon (IFN-I) pathway and microglial function, which were notably suppressed upon adjunctive rFGF21 treatment. Mechanistically, rFGF21 intervention facilitated mitophagy in an AMP-activated protein kinase (AMPK)-dependent manner, thereby preventing mitochondrial DNA (mtDNA) release into the cytoplasm and dampening the activation of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Conditional knockout of STING in microglia markedly ameliorated the inflammatory response and mitigated secondary brain injuries post-SAH.

Conclusion
Our results present the initial evidence that FGF21 confers a protective effect against neuroinflammation-associated brain damage subsequent to SAH. Mechanistically, we have elucidated a novel pathway by which FGF21 exerts this neuroprotection through inhibition of the cGAS-STING signaling cascade.
Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale
Authors: Tran Nhi T. , Penny Tayla R. , Chan Kyra YY. , Tang Tanya , Papagianis Paris C. , Sepehrizadeh Tara , Nekkanti Lakshmi , Zahra Valerie A. , Pham Yen , Yawno Tamara , Nitsos Ilias , Kelly Sharmony B. , Thiel Alison M. , de Veer Michael , Alahmari Dhafer M. , Fahey Michael C. , Jenkin Graham , Miller Suzanne L. , Galinsky Robert , Polglase Graeme R. , McDonald Courtney A. 
Published: May 2024

Abstract
Background
Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury.

Methods
Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively.

Results
In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls.

Conclusions
UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.
The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis
Authors: Zhuang Weisheng , Li Tianshu , Li Yuefang , Zhang Ying , Gao Jiahuan , Wang Xu , Ding Qixin , Li Wanyue 
Published: May 2024

Abstract
Objective
To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections.

Methods
One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients’ conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up.

Results
Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups.

Conclusions
The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.
Treatment characteristics of patients with hereditary transthyretin amyloidosis: a cohort study
Authors: Qarni Taha N. , Jones Felipe J. S. , Drachman Brian , Khella Sami , Pieretti Janice , Bustamante Nicolas Sarmiento , Karam Chafic 
Published: May 2024

Abstract
Background
There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy.

Objectives
To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy.

Methods
We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality.

Results
One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (p=0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8, p=0.21).

Conclusions
While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy.
Veno-venous extracorporeal membrane oxygenation (VV ECMO) cannula malposition identified with point-of-care ultrasound
Authors: Becker Taylor , Struble Roger D. , Rappaport Charles 
Published: May 2024

Abstract
Background
Point-of-care ultrasound (POCUS) has become a mainstay in the evaluation of critically ill patients in the intensive care unit (ICU). ECMO patients are susceptible to complications during prolonged ICU stay, including cannula malposition, which has deleterious consequences. Although the literature surrounding utility of ultrasound on ECMO patients is expansive, direct comparison between radiographic imaging versus ultrasound for identification of cannula malposition is lacking.

Case presentation
The authors identified four patients with cannula malposition discovered through POCUS that was missed on routine radiographic imaging. Identification and correction of malposition changed their ECMO course.

Conclusion
This case series is the first in literature demonstrating that ultrasound may be superior to radiographic images for ECMO cannula malposition. Further investigation into this subject is warranted.
The quality of COVID-19 systematic reviews during the coronavirus 2019 pandemic: an exploratory comparison
Authors: McDermott Kevin T. , Perry Mark , Linden Willemijn , Croft Rachel , Wolff Robert , Kleijnen Jos 
Published: May 2024

Abstract
Background
The unprecedented volume and speed at which COVID-19-related systematic reviews (SRs) may have been produced has raised questions regarding the quality of this evidence. It is feasible that pandemic-related factors may have led to an impairment in quality (reduced internal validity, increased risk of bias [RoB]). This may have serious implications for decision-making related to public health and individual healthcare.

Objective
The primary objective was to compare the quality of SRs published during the pandemic that were related to COVID-19 with SRs published during the pandemic that were unrelated to COVID-19 (all of which were fully appraised in the KSR Evidence database of SRs in healthcare). Our secondary objective was to compare the quality of SRs published during the pandemic (regardless of research topic), with SRs published pre-pandemic.

Methods
We compared all SRs related to COVID-19 to all SRs unrelated to COVID-19 that (i) were published during the pandemic (between 1st March 2020 and September 14, 2022), (ii) were included in KSR Evidence, and (iii) had been appraised using the ROBIS tool. We then compared all SRs published during the pandemic (regardless of research topic) with a pre-pandemic sample of SRs.

Results
For SRs published during the pandemic, we found there was no statistically significant difference in quality between those SRs tagged as being related to COVID-19 and those that were not [relative risk (RR) of low RoB for COVID-19 versus COVID-19-unrelated reviews: 0.94; 95% confidence interval (CI): 0.66 to 1.34]. Generally, COVID-19 SRs and COVID-19-unrelated SRs were both of low quality with only 10% of COVID-19 reviews and 11% of COVID-19-unrelated reviews rated as low RoB. However, SRs (regardless of topic) published during the pandemic were of lower quality than those published pre-pandemic (RR for low RoB for ‘during pandemic’ versus ‘pre-pandemic’: 0.30; 95% CI: 0.26 to 0.34) with 11% of pandemic and 36% of pre-pandemic SRs rated as low RoB.

Conclusion
These results suggest COVID-19 and COVID-19-unrelated SRs published during the pandemic are equally of low quality. SRs published during the pandemic were generally lower quality compared with SRs published pre-pandemic irrespective of COVID-19 focus. Moreover, SR quality in general is seriously lacking, and considerable efforts need to be made to substantially improve the quality and rigour of the SR process.
Sequential inertial linear ADMM algorithm for nonconvex and nonsmooth multiblock problems with nonseparable structure
Authors: Xue Zhonghui , Yang Kaiyuan , Ma Qianfeng , Dang Yazheng 
Published: May 2024

AbstractThe alternating direction method of multipliers (ADMM) has been widely used to solve linear constrained problems in signal processing, matrix decomposition, machine learning, and many other fields. This paper introduces two linearized ADMM algorithms, namely sequential partial linear inertial ADMM (SPLI-ADMM) and sequential complete linear inertial ADMM (SCLI-ADMM), which integrate linearized ADMM approach with inertial technique in the full nonconvex framework with nonseparable structure. Iterative schemes are formulated using either partial or full linearization while also incorporating the sequential gradient of the composite term in each subproblem’s update. This adaptation ensures that each iteration utilizes the latest information to improve the efficiency of the algorithms. Under some mild conditions, we prove that the sequences generated by two proposed algorithms converge to the critical points of the problem with the help of KŁ property. Finally, some numerical results are reported to show the effectiveness of the proposed algorithms.