bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain control post total knee replacement in patients given local infiltrative analgesia combined with adductor canal block compared to either modality alone: a systematic review and meta-analysis
Authors: Mott Andrew , Brady Samantha , Briggs Isabelle , Barrett Maggie , Fulbright Helen , Hamilton Thomas William , Hewitt Catherine , Palan Jeya , Pandit Hemant 
Published: November 2024

Objectives
Optimising postoperative pain following knee replacement is important for patients, healthcare professionals and healthcare funders. Adductor canal blocks (ACB) are widely used but there is uncertainty about their efficacy when combined with local infiltration analgesia (LIA) compared with either LIA or ACB alone.

Design
A systematic review and meta-analyses of randomised controlled. The primary outcome was pain over the first 72 hours. Secondary outcomes included morphine use, range of movement, distance walked, length of hospital stay, health economic outcomes and reported adverse events.

Data sources
MEDLINE, Embase, EB Health - KSR Evidence, Cochrane Central Register of Controlled Trials, CINAHL, International HTA database, ClinicalTrials.gov and the International Clinical Trials Registry Platform (WHO) were searched up to June 2023.

Eligibility criteria
Randomised controlled trials involving patients undergoing primary total knee replacement comparing LIA combined with ACB to either LIA or ACB alone.

Data extraction and synthesis
All eligible studies were data extracted independently by two reviewers. Studies were pooled for each outcome at each timepoint in a random effects meta-analysis.

Results
We identified 13 completed studies including 1154 participants. 12 studies compared LIA vs combination and 5 compared ACB vs combination. We identified that participants receiving the combination had lower pain scores at rest at 24 hours compared with LIA alone (SMD 0.42, 95% CI 0.20 to 0.64) or ACB alone (SMD 0.63, 95% CI 0.42 to 0.83). Pain on movement at 24 hours was also lower for patients with combination vs LIA alone (SMD 0.37, 95% CI 0.01 to 0.73) or ACB alone (SMD 0.81, 95% CI 0.35 to 1.26). We also identified that patients on combination used less morphine than on LIA alone (MD 1.06, 95% CI −0.09 to 2.20) or ACB alone (MD 5.94, 95% CI −2.41 to 14.29). The same was seen with range of motion at 24 hours with combination having a larger improvement than LIA alone (MD −5.19, 95% CI −5.55 to −4.83) or ACB alone (MD −3.80, 95% CI −4.37 to −3.23). These findings were consistent across all time points; however, there were no studies deemed to be at a low risk of bias.

Conclusions
Further well-designed and conducted randomised controlled trials are needed to confirm if a combination of LIA and ACB is superior to either option alone for patients undergoing primary total knee arthroplasty.

PROSPERO registration number
CRD42023436895.
Conducting observational analyses with the target trial emulation approach: a methodological systematic review
Authors: Simon-Tillaux Noémie , Martin Guillaume L , Hajage David , Scheifer Carole , Beydon Maxime , Dechartres Agnes , Tubach Florence 
Published: November 2024

Objectives
Target trial emulation is an approach that is increasingly used to improve transparency in observational studies and help mitigate biases. For studies declaring that they emulated a target trial, we aimed to evaluate the specification of the target trial, examine its consistency with the observational emulation and assess the risk of bias in the observational analysis.

Design
Methodological systematic review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Data sources
The database MEDLINE (Medical Literature Analysis and Retrieval System Online) was interrogated for all studies published from 1 January 2021 to 3 July 2022. We performed an additional manual search of 20 general medical and specialised journals that spanned the same period.

Eligibility criteria
All studies that declared emulating a hypothetical or real randomised trial were eligible.

Data extraction and synthesis
Two independent reviewers performed the whole systematic review process (screening and selection of studies, data extraction and risk of bias assessment). The main outcomes were the definition of the key protocol components of the target trial and its emulation, consistency between the target trial and its emulation and risk of bias according to the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool.

Results
Among the selected sample of 100 studies, 24 (24%) did not specify the target trial. Only 40 studies (40%) provided detailed information on all components of the target trial protocol. Eligibility criteria, intervention strategies and outcomes were consistent between the target trial and its emulation in 35 studies (46% of those specifying the target trial). Overall, 28 studies (28%) exhibited serious risk of bias and 41 (41%) had misalignments in the timing of eligibility assessment, treatment assignment and the start of follow-up (time-zero). As compared with studies that did not specify the target trial, those that did specify the trial less frequently seemed to have both time-zero issues (39% vs 52%) and serious risk of bias (26% vs 33%).

Conclusions
One-quarter of studies declaring that they emulated a target trial did not specify the trial. Target trials and their emulations were particularly inconsistent for studies emulating a real randomised trial. Risk of methodological issues seemed lower in observational analyses that specified versus did not specify the target trial.
Total Water–Soluble Flavonoids From Lithocarpus litseifolius (Hance) Chun (Sweet Tea) Improve Glucose Homeostasis Through Multitarget Signalling in GDM Mice
Authors: Xu Junfei , Zhang Fenfang , Li Huanhuan , Li Pan , Zeng Junying , Wu Xianjin , Zhou Rong , Yang Chunyan , Zhang Juzuo 
Published: November 2024

Background: The oral safety of Lithocarpus litseifolius (Hance) Chun (sweet tea) that has antihyperglycemic potential has been verified. However, its specific application and action mechanism in the treatment of gestational diabetes mellitus (GDM) are still unclear.Methods: Total water–soluble flavonoids extracted from L. litseifolius (Hance) Chun (sweet tea) were applied to GDM mice. The glucose tolerance, insulin sensitivity, and histopathology of the GDM mice were evaluated through an intraperitoneal glucose tolerance test (IPGTT), an intraperitoneal insulin tolerance test (IPITT), and histochemistry. The possible mechanism was analysed through network pharmacology.Results: Compared with those in GDM model mice (MD group), blood glucose levels indicating both glucose tolerance and insulin sensitivity were improved in GDM mice treated with total water–soluble flavonoids (LLHC group) but were greater than those in normal control mice (NC group). The number of apoptotic liver cells was significantly lower in the LLHC group than in the MD group, but greater than that in the NC group. Multiple targets and signalling pathways that were acted by eight main active ingredients were involved in the process by which total water–soluble flavonoids protect against GDM. The main mechanism involved quercetin (10 targets) and luteolin (8 targets), which acted on the effector target of GAA through six main signalling pathways around the AKT1 core axis.Conclusion: Oral administration of total water–soluble flavonoids can alleviate glucose intolerance and insulin resistance via the inhibition of liver cell apoptosis. The main active ingredients act on GAA through the signalling pathways of the AKT1 core axis.
Effectiveness of Resistance Exercise for Depression, Fatigue, and Sleep Quality in Women With Fibromyalgia
Authors: Rodríguez-Domínguez Álvaro-José , Rebollo-Salas Manuel , Chillón-Martínez Raquel , Rosales-Tristancho Abel , Arana-Rodríguez Andrés , Jiménez-Rejano José-Jesús 
Published: November 2024

Purpose: Fibromyalgia is a chronic disease that mainly affects women, deteriorating the quality of life of these patients. Resistance exercise (RE) has been shown to be beneficial in this disease. The objective of this study is to evaluate the effectiveness of RE for depression, fatigue, and sleep quality in women with fibromyalgia.Design and Methods: A systematic review with meta‐analysis was conducted until September 1, 2024. Seven databases were searched as follows: PubMed, Cochrane Library, Web of Science, Scopus, Physiotherapy Evidence Database, Dialnet, and Cumulative Index to Nursing and Allied Health Literature. Randomized clinical trials were conducted in women with a diagnosis of fibromyalgia, including RE as the only intervention in any of the groups and to assess depression, fatigue, and sleep quality. For meta‐analyses, we calculated the standardized difference of means and its standard error. A random‐effects model was used. The risk of bias was assessed using the Cochrane risk‐of‐bias tool for randomized trials (RoB 2). PROSPERO Registration: CRD42021256162.Findings: Eleven trials were included in the systematic review and eight in the meta‐analysis (n = 664). RE showed statistically significant improvements in depression (SMD = −0.54; 95% CI [−0.92, −0.16], p = 0.005) and fatigue (SMD = −0.83; 95% CI [−1.41–0.25], p = 0.005). No significant differences were found in sleep quality (SMD = −0.99; 95% CI [−2.40, 0.43], p = 0.17). In general, the methodological quality of the included trials was good.Practice Implication: RE is an effective tool to improve depression and fatigue in women with fibromyalgia, achieving clinically relevant improvements of more than 50% in symptoms related to depression. RE did not show benefits for sleep quality, although this finding may be due to a lack of studies. More studies are needed to determine the effectiveness of RE on sleep quality.
Abstract A002: The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients
Authors: Woo Hyeongjung , Shin Hyun Young , Oh So Yeon , Lee Sun Min , Kim Minseok S. 
Published: November 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR002) of the Conference Program/Proceedings.
Citation Format: Hyeongjung Woo, Hyun Young Shin, So Yeon Oh, Sun Min Lee, Minseok S. Kim. The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A002.
Abstract A013: Quality control of the biobanked matched tissue: Blood samples for the development of diverse liquid based molecular assays
Authors: Gatalica Zoran , Stafford Phillip , Diehnelt Chris , Rose Inga 
Published: November 2024

Abstract
The availability of high-quality matched biological samples (tumor-blood) is the major limiting factor for research and development of novel, liquid biopsy-based assays in oncology. Frequently, ongoing specifically timed collections of blood samples are required. De-identified tissue blocks (formalin-fixed, paraffin embedded (FFPE) or flash frozen) matched with patient's blood samples collected in fixative-containing (Streck) of EDTA containing tubes, were collected at worldwide geographic locations and transferred to biobanking facility (Reference Medicine, Phoenix, AZ). Additional blood samples were collected at various times regarding the cancer surgery. Plasma and buffy coat samples were locally prepared and shipped to the biobank. A subset of blood samples without matched tissues from healthy donors were also collected. All samples were shipped under strict transport conditions. Quality control performed at the biobanking facility included pathology review and nucleic acids quality assessment. A total of over 3,000 cases were collected and provided to end-users working on various assays based on cfDNA (e.g. monitoring for minimal residual disease or multi-cancer early detection). Immuno-reactivity to various antigens in samples collected in Streck and EDTA tubes (from 50 patients) was assessed by peptide microarray binding assay. Feedback information on the quality of samples was shared in 900 cases. Approximately 4% of cases had failed internal pathology review, due to poor preservation, lack of adequate tissue composition, or low tumor volume and 11% failed internal nucleic acid quality assessment (DNA concetration and integrity). The blood collection tubes had no significant impact on serologic testing using peptide microarary assay. Customer feedback data showed that overall success rate exceeded 85%. Type of blood collection tubes (Streck vs EDTA) had no impact on serologic testing and studies looking at predicted neoantigens based on NGS data can be confirmed using peptide epitope arrays. Blood collected for NGS works without compromise on peptide arrays. Future validation of other collection tubes for blood or other types of fluids is needed to confirm their adequacy for specific assays.
Citation Format: Zoran Gatalica, Phillip Stafford, Chris Diehnelt, Inga Rose. Quality control of the biobanked matched tissue: Blood samples for the development of diverse liquid based molecular assays [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A013.
Abstract A044: Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma
Authors: Mo Wenjv , Yao Xingyun , Sun Haobo , Liang Honghao , Jin Jie , Ding Xiaowen , Gao Xiaofei 
Published: November 2024

Abstract
Background: Alongside traditional imaging, current development in non-invasive breast carcinoma (BC) diagnosis, such as cell-free DNA-based technologies, have demonstrated promising potential in BC diagnosis. However, achieving early detection remains a challenge. Micronuclei (MN) are extranuclear bodies containing damaged chromosome segments indicative of genomic instability. Elevated levels of MN-containing erythrocytes have been studied in genotoxicity testing and cancer diagnosis. Here, we sequenced the isolated and purified micronuclei DNA (MN-DNA) from erythrocytes in 2ml peripheral blood using a method we previously developed (WO2021/228246 A1) and identified a series of distinct features in read counts that enabled to detect early-stage BC patients. Methods: We collected a clinical study cohort of 172 BC patients and 216 non-BC controls from 1-2ml peripheral blood. MN-DNA was isolated from erythrocytes and performed whole-genome sequencing. We selected distinctive tumor-associated MN-DNA features identified by genome-wide analysis to differentiate between controls and BC for KEGG pathway enrichment and constructed a classification model based on these features. Results: Genome-wide analysis of MN-DNA revealed significant regions between controls and BC patients. Based on covered genes, we observed significant enrichment in the estrogen signaling pathway. Utilizing these distinct MN- DNA features, we constructed a classification model that achieved an AUC of 96%, with a 95% specificity and 88% sensitivity in the test cohort. The model identified early BC (stage 0-I) and advanced BC (stage II-IV) with sensitivities of 100% or 84%, respectively. Conclusions: Our findings highlight that MN-DNA, a form of cytoplasmic DNA, provides a valuable tool for the accurate detection of BC, particularly in its early stages. The MN-DNA pattern is linked to the estrogen signaling pathway, offering novel insights and mechanisms that differ from current diagnostic approaches. Research sponsor: Timing Biotech. Early Detection of Primary Cancer and Relapse
Citation Format: Wenjv Mo, Xingyun Yao, Haobo Sun, Honghao Liang, Jie Jin, Xiaowen Ding, Xiaofei Gao. Utilizing breast cancer-specific micronuclei DNA features from erythrocytes for early detection of breast carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A044.
Abstract A061: A cost-effective two-step approach for multi-cancer early detection in general population
Authors: Mao Mao , Geng shuai peng  , Li shi yong  , Wei Wu , Yin Chang Yin 
Published: November 2024

Abstract
In population-wide cancer screening, three key issues need to be focused on: number of cancer cases identified, the issue of false positives, and cost. A high false positive rate can result in a significant waste of healthcare resources. Large-scale screening inevitably leads to significant financial burdens on the healthcare system which is a key factor constraining nationwide screening. OncoSeek is a multi-cancer early detection (MCED) test using a panel of seven plasma protein tumor markers (PTMs) and artificial intelligence (AI). SeekInCare is a MCED test that integrates the seven PTMs and four cancer genomic features (aneuploidy, fragment size, end motifs, and oncogenic viruses) from cell-free DNA (cfDNA) by shallow whole-genome sequencing (sWGS). In a two-step approach, the initial screening is conducted using OncoSeek and SeekInCare is then used as the secondary test for those individuals who tested positive by OncoSeek. In a case-control study (n = 1197) including both OncoSeek and SeekInCare testing results, OncoSeek showed 49.9% sensitivity at 91.0% specificity, while SeekInCare demonstrated 60.0% sensitivity at 98.3% specificity. In the two-step process, specificity significantly increased from 91.0% to 99.3%, while sensitivity decreased from 49.9% to 39.9%. We modeled a screening in five million adults aged ≥ 50 years with a cancer incidence rate of 1.9%. The simulated real-world sensitivities of OncoSeek and two-step were adjusted downward proportionally to 28.0% and 22.4% based on the sensitivity differences observed between GRAIL’s CCGA study (case-control, 51.5%) and PATHFINDER study (prospective, 28.9%). While at 91.0% specificity OncoSeek had 441,450 cases of false positives, using the two-step approach significantly reduced false positives to 34,335 (0.7%). Although Galleri ($949 per test) identified more cancer cases than the two-step MCED, with 27,455 and 21,280 cases respectively, its total cost for the former reached $4,745 million. As the positive predictive value (PPV) of two-step (38.3%) was the same as Galleri (38.3%), it reduced cost 6.6-fold, amounting to a total cost of $713.6 million and a cost of $143 per individual screened. The cost of per cancer case detected using Galleri is $172,828 compared to $33,534 using the two-step MCED, which represents a 5.2-fold difference. In conclusion, the two-step approach not only significantly reduces false positives, but also cuts the screening cost down substantially, making it a cost-effective strategy for population-wide cancer screening.
Citation Format: Mao Mao, Geng shuai peng, Li shi yong, Wu Wei, Chang Yin Yin. A cost-effective two-step approach for multi-cancer early detection in general population [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A061.
Abstract A062: Insightful analysis: Harnessing aqueous humor ctDNA for retinoblastoma stratification
Authors: Montigel Sophia H , Ryl Tatsiana , Volz Stefanie , Afanasyeva Elena , Wedig Tatjana , Schwarz Nathalie , Pfister Stefan M , Pajtler Kristian W , Ketteler Petra , Maaß Kendra K 
Published: November 2024

Abstract
Retinoblastoma (RB) the most common intraocular malignancy in children poses a significant challenge as traditional tissue biopsies are not feasible. Due to its critical location within the eye and the high risk of tumor seeding, clinicians are limited in performing molecular analysis-based risk stratification prior to enucleation. In this study, we explored the potential of aqueous humor (AH) as a source for minimally invasive liquid biopsies, aiming to establish a molecular profiling methodology for circulating tumor DNA (ctDNA) for risk stratification. We analyzed AH samples and corresponding tumor tissues from 19 enucleated eyes of patients diagnosed with RB. The extracted ctDNA from AH underwent low-coverage whole-genome sequencing (lcWGS) and methylation profiling. These data were then compared with the genomic and methylation landscapes of the matched tumor DNA. Additionally, we assessed the ability of AH- derived ctDNA to predict retinoblastoma methylation cluster. Our findings demonstrate a high concordance between ctDNA from AH and the primary tumor DNA in both methylation patterns and genomic alterations detected by lcWGS allowing the correct prediction of the retinoblastoma molecular group. The shared aberrations underscore the potential of AH as a reliable surrogate for tumor tissue in retinoblastoma. Additionally, the methylation profiles revealed consistent epigenetic modifications, further supporting the accuracy of AH-derived ctDNA in reflecting the tumor’s molecular characteristics. This study highlights the feasibility and effectiveness of using AH for molecular ctDNA genetic analysis in retinoblastoma. The overall high concordance between ctDNA profiles with primary tumor DNA and the ability to accurately predict RB methylation classes, highlights the superiority of the liquid biopsy approach overcoming the limitations of traditional biopsies and transforming the potential for early molecular analysis and risk stratification. This revolutionary technique could redefine pre-enucleation diagnostics, offering unprecedented insights and paving the way for tailored, precision medicine in retinoblastoma care.
Citation Format: Sophia H Montigel, Tatsiana Ryl, Stefanie Volz, Elena Afanasyeva, Tatjana Wedig, Nathalie Schwarz, Stefan M Pfister, Kristian W Pajtler, Petra Ketteler, Kendra K Maaß. Insightful analysis: Harnessing aqueous humor ctDNA for retinoblastoma stratification [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A062.
Abstract A063: Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers
Authors: Mudgal Poorva , Bandoski Cheryl , Opheim Zachary , Mehnert Martin , Anschau Valesca , Isaac Issa , Ezrin Alan , Hembrough Todd 
Published: November 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR013) of the Conference Program/Proceedings.
Citation Format: Poorva Mudgal, Cheryl Bandoski, Zachary Opheim, Martin Mehnert, Valesca Anschau, Issa Isaac, Alan Ezrin, Todd Hembrough. Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A063.