bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the implementation and impact of a new model of care for integrating children and young people’s acute mental healthcare in a paediatric setting: a protocol for a realist, mixed-methods approach
Authors: Otis Michaela , Barber Susan , Green Hofer Stuart , Straus Jean , Kay Michelle , Hargreaves Dougal S , Hayhoe Benedict , Anokye Nana , Lennox Laura , Nicholls Dasha 
Published: January 2023

IntroductionThe mental health of children and young people in the UK has been declining and has continued to worsen throughout the pandemic, leading to an increase in mental health-related emergencies. In response, the Best for You programme was developed as a new service designed to integrate mental healthcare for children and young people between acute hospital and community services. The programme is comprised of four new services: a rapid assessment young people’s centre with dual-trained staff, a co-located day service offering family-based care,a digital hub, designed to integrate with the fourth element of the model, namely community support and mental health services. This evaluation protocol aims to assess the development, implementation and outcomes of the Best for You programme and develops a scalable model that could be implemented in other parts of the National Health Service (NHS).Methods and analysisThis mixed-methods realist evaluation aims to delineate the components of the system to assess their interdependent relationships within a wider context. Data collection will include interviews, participant observations, focus groups and the collection of local quantitative healthcare data. The research will be conducted across four phases. Phase 1—captures the development of the underlying programme theory. Phase 2—a process evaluation testing the programme theory. Phase 3— an outcome and economic evaluation. Phase 4—consolidation of learning from phases 1–3 to identify barriers, facilitators and wider contextual factors that have shaped implementation drawing on the Consolidated Framework for Implementation Research.Ethics and disseminationEthical approval for the evaluation was received from the NHS local ethics committee. Embedded within the evaluation is a formative review to feedback and share learning with stakeholders to scale-up the programme. Findings from this study will be disseminated in peer-reviewed journals as well as presentations to be useful to service user organisations and networks.
Venous thromboembolism risk following temporary immobilisation after injury: evaluation of the Aberdeen VTE risk tool
Authors: Almoosawy Sayed Abdulmotaleb , Ofosu-Asiedu Akosua , Hanna Julie , Conlen Ben , Elliott Hamish , Harrison Ailsa , Edmunds Christopher , Hong Tan Poh , Watson Henry G , Cooper Jamie G 
Published: January 2023

BackgroundTemporary lower limb immobilisation following injury is a risk factor for symptomatic venous thromboembolism (VTE). Pharmacological thromboprophylaxis can mitigate this risk but it is unclear which patients benefit from this intervention. The Aberdeen VTE risk tool was developed to tailor thromboprophylaxis decisions in these patients and this evaluation aimed to describe its performance in clinical practice. Secondarily, diagnostic metrics were compared with other risk assessment methods (RAMs).MethodsA prospective cohort service evaluation was conducted. Adult patients (≥16 years) managed with lower limb immobilisation for injury who were evaluated with the Aberdeen VTE risk tool prior to discharge from the ED were identified contemporaneously between February 2014 and December 2020. Electronic patient records were scrutinised up to 3 months after removal of immobilisation for the development of symptomatic VTE or sudden death due to pulmonary embolism (PE). Other RAMs, including the Thrombosis Risk Prediction for Patients with cast immobilisation (TRiP(cast)) and Plymouth scores, were assimilated retrospectively and diagnostic performance compared.ResultsOf 1763 patients (mean age 46 (SD 18) years, 51% women), 15 (0.85%, 95% CI 0.52% to 1.40%) suffered a symptomatic VTE or death due to PE. The Aberdeen VTE tool identified 1053 (59.7%) patients for thromboprophylaxis with a sensitivity of 80.0% (95% CI 54.8% to 93.0%) and specificity of 40.4% (95% CI 38.1% to 42.6%) for the primary outcome. In 1695 patients, fewer were identified as high risk by the TRiP(cast) (33.3%) and Plymouth (24.4%) scores, but with greater specificity, 67.0% and 75.6%, respectively, than dichotomous RAMs, including the Aberdeen VTE tool.ConclusionRoutine use of the Aberdeen VTE tool in our population resulted in an incidence of symptomatic VTE of less than 1%. Ordinal RAMs, such as the TRiP(cast) score, may more accurately reflect VTE risk and permit more individually tailored thromboprophylaxis decisions but prospective comparison is needed.
Matched comparison between external aortic root support and valve-sparing root replacement
Authors: Van Hoof Lucas , Lamberigts Marie , Noé Dries , El-Hamamsy Ismail , Lansac Emmanuel , Kluin Jolanda , de Kerchove Laurent , Pepper John , Treasure Tom , Meuris Bart , Rega Filip , Verbrugghe Peter 
Published: January 2023

ObjectivesDifferences in indication and technique make a randomised comparison between valve-sparing root replacement (VSRR) and personalised external aortic root support (PEARS) challenging. We performed a propensity score (PS)-matched comparison of PEARS and VSRR for syndromic root aneurysm.MethodsPatients in the PEARS 200 Database and Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (undergoing VSRR) with connective tissue disease operated electively for root aneurysm <60 mm with aortic regurgitation (AR) <1/4 were included. Using a PS analysis, 80 patients in each cohort were matched. Survival, freedom from reintervention and from AR ≥2/4 were estimated using a Kaplan-Meier analysis.ResultsMedian follow-up was 25 and 55 months for 159 PEARS and 142 VSRR patients. Seven (4.4%) patients undergoing PEARS required an intervention for coronary injury or impingement, resulting in one death (0.6%). After VSRR, there were no early deaths, 10 (7%) reinterventions for bleeding and 1 coronary intervention. Survival for matched cohorts at 5 years was similar (PEARS 98% vs VSRR 99%, p=0.99). There was no difference in freedom from valve or ascending aortic/arch reintervention between matched groups. Freedom from AR ≥2/4 at 5 years in the matched cohorts was 97% for PEARS vs 92% for VSRR (p=0.55). There were no type A dissections.ConclusionsVSRR and PEARS offer favourable mid-term survival, freedom from reintervention and preservation of valve function. Both treatments deserve their place in the surgical repertoire, depending on a patient’s disease stage. This study is limited by its retrospective nature and different follow-ups in both cohorts.
Comparative effectiveness of anesthetic technique on outcomes after lumbar spine surgery: a retrospective propensity score-matched analysis of the National Surgical Quality Improvement Program, 2009–2019
Authors: Amoroso Krizia , Okano Ichiro , Sarin Michele , Hughes Alexander P , Zelenty William D , Shue Jennifer , Sama Andrew A , Cammisa Frank P , Girardi Federico P , Soffin Ellen M 
Published: January 2023

BackgroundThe impact of anesthetic technique on spine surgery outcomes is controversial. Using a large national sample of patients, we compared outcomes after lumbar decompression under regional anesthesia (RA: spinal or epidural) or general anesthesia (GA).MethodsA retrospective population-based study of American College of Surgeons National Surgical Quality Improvement Program data (2009–2019). Patients were propensity score (PS) matched 3:1 (GA:RA) on demographic and surgical variables. The primary outcome was the association between anesthetic type and any complication (cardiac, pulmonary, renal, transfusion, stroke, infectious, deep vein thrombosis/pulmonary embolus). Secondary outcomes included the association between anesthetic type and individual complications, readmission and length of stay (LOS). Unadjusted comparisons (OR, 95% CI), logistic regression and adjusted generalized linear modeling (parameter estimate, PE, 95% CI) were performed before and after PS matching.ResultsOf 1 51 010 cases, 149 996 (99.3%) were performed under GA, and 1014 (0.67%) under RA. After matching, 3042 patients with GA were compared with 1014 patients with RA. On unadjusted analyses, RA was associated with lower odds of complications (OR 0.43, 0.3 to 0.6, p<0.001), shorter LOS (RA: 1.1±3.8 days vs GA: 1.3±3.0 days; p<0.001) and fewer blood transfusions (RA: 3/1014, 0.3% vs GA: 40/3042, 1.3%; p=0.004). In adjusted analyses, RA was associated with fewer complications (PE −0.43, –0.81 to −0.06, p=0.02) and shorter LOS (PE −0.76, –0.90 to −0.63, p<0.001). There was no significant association between anesthetic type and readmission (PE −0.34, –0.74 to 0.05, p=0.09).ConclusionsCompared with GA, RA was associated with fewer complications, less blood transfusion and shorter LOS after spine surgery. Although statistically significant, the magnitude of effects was small and requires further prospective study.
Citing retracted literature: a word of caution
Authors: De Cassai Alessandro , Volpe Francesco , Geraldini Federico , Dost Burhan , Boscolo Annalisa , Navalesi Paolo 
Published: January 2023

IntroductionInappropriate citation of retracted literature is a common problem in the general medical literature. In 2020, more than 2300 articles were retracted, a dramatic increase from 38 in 2000. By exploring a contemporary series of retractions by one research group, we aimed to evaluate if citations of retracted articles is occurring in the area of regional anesthesiology.MethodsUsing the Scopus database, we examined the full text of all the articles citing research articles coauthored by an anesthesiologist who had multiple articles retracted in 2022. After excluding the research articles citing non-retracted articles authored by the above mentioned anesthesiologist, we included in our analysis all the articles containing a retracted citation and published after the retraction notice.ResultsThe search was performed on October 30, 2022, retrieving a total of 121 articles citing the researcher’s work. Among the retrieved articles, 53 correctly cited non-retracted research and 37 were published before the retraction notice. Among the 31 remaining articles, 42 retracted research papers were cited. Twenty-five of the retracted articles were cited in the Discussion section of the manuscripts, 15 in the Introduction section, 1 in the Methods section (description of a technique), and one was cited in a review. No manuscript used the flawed data to calculate the sample size.DiscussionIn this contemporary example from the regional anesthesia literature, we identified that citation of retracted work remains a common phenomenon.
Effectiveness and cost-effectiveness of palliative care in natural experiments: a systematic review
Authors: Jiang Jingjing , Kim Narae , Garrido Melissa M , Jacobson Mireille , Mockler David , May Peter 
Published: January 2023

ContextInvestigators in palliative care rely heavily on routinely collected data, which carry risk of unobserved confounding and selection bias. ‘Natural experiments’ offer opportunities to generate credible causal treatment effect estimates from observational data.ObjectivesWe aimed first to review studies that employed ‘natural experiments’ to evaluate palliative care, and second to consider implications for expanding use of these methods.MethodsWe searched systematically seven databases to identify studies using ‘natural experiments’ to evaluate palliative care’s effect on outcomes and costs. We searched three grey literature repositories, and hand-searched journals and prior systematic reviews. We assessed reporting using the Strengthening the Reporting of Observational Studies in Epidemiology checklist and a bespoke methodological quality tool, using two reviewers at each stage. We combined results in a narrative synthesis.ResultsWe included 17 studies, which evaluated a wide range of interventions and populations. Seven studies employed a difference-in-differences design; five each used instrumental variables and interrupted time series analysis. Outcomes of interest related mostly to healthcare use. Reporting quality was variable. Most studies reported lower costs and improved outcomes associated with palliative care, but a third of utilisation and place of death evaluations found no effect.ConclusionAmong the large number of observational studies in palliative care, a small minority have employed causal mechanisms. High-volume routine data collection, the expansion of palliative care services worldwide and recent methodological advances offer potential for increased use of ‘natural experiments’. Such studies would improve the quality of the evidence base.
Searches for QCD instantons with forward proton tagging
Authors: Tasevsky Marek , Khoze Valery , Milne Daniel , Ryskin Michail 
Published: January 2023

AbstractWe study the possibility to observe heavy ($$M_{\textrm{inst}}> 60$$

M
inst

>
60

GeV) QCD instantons at the LHC in events with one or two tagged leading protons including fast simulation of detector and pile-up effects. We show that the expected instanton signal in a single-tagged configuration is strongly affected by central detector and pile-up effects. For double-tagged approach, where larger integrated luminosities and hence larger pile-up contaminations need to be considered, the combinatorial background overwhelms the expected signal. We suggest that additional time information about tracks at central and forward rapidities would be crucial for potential improvements.
Massive particle pair production and oscillation in Friedman Universe: its effect on inflation
Authors: Xue She-Sheng 
Published: January 2023

AbstractWe study the classical Friedman equations for the time-varying cosmological term $$\tilde{\Lambda }$$

Λ
~

and Hubble function H, together with quantised field equations for the production of massive $$M\gg H$$

M
≫
H

particles, namely, the $$\tilde{\Lambda }$$

Λ
~

CDM scenario of dark energy and matter interactions. Classical slow components $${\mathcal O}(H^{-1})$$

O
(

H

-
1

)

are separated from quantum fast components $${\mathcal O}(M^{-1})$$

O
(

M

-
1

)

. The former obeys the Friedman equations, and the latter obeys a set of nonlinear differential equations. Numerically solving equations for quantum fast components, we find the production and oscillation of massive particle-antiparticle pairs in microscopic time scale $${\mathcal O}(M^{-1})$$

O
(

M

-
1

)

. Their density and pressure averages over microscopic time do not vanish. It implies the formation of a massive pair plasma state in macroscopic time scale $${\mathcal O}(H^{-1})$$

O
(

H

-
1

)

, whose effective density and pressure contribute to the Friedman equations. Considering the inflation driven by the time-varying cosmological term and slowed down by the massive pair plasma state, we obtain the relation of spectral index and tensor-to-scalar ratio in agreement with recent observations. We discuss the singularity-free pre-inflation, the CMB large-scale anomaly, and dark-matter density perturbations imprinting on power spectra.
Alternative to Buy-and-Hold: Predicting Indices Direction and Improving Returns Using a Novel Hybrid LSTM Model
Authors: Beniwal Mohit , Singh Archana , Kumar Nand 
Published: January 2023

Predicting stock direction is challenging as stock price time series are extremely noisy. Moreover, the widely accepted efficient market hypothesis states that it is impossible to consistently generate excess returns than the market over a long-term horizon. Hence, the best approach for investors is thought to be the passive buy-and-hold strategy in indices. However, some researchers suggest that the market does have a predictable component. This paper’s objective is to provide investors with an alternative predictive system that generates an excess return over the classical buy-and-hold strategy and reduces risk. The authors propose an alternative investing model, Average True Range (ATR) and Momentum-based Long Short-Term Memory online (a-m-LSTM-o), that innovatively uses the technical indicators with Long Short-Term Memory (LSTM). Further, this study experiments with multiple other LSTM investing models using daily indices data of the world’s top five economies. Based on the prediction, the proposed model’s return is 172%, which is significantly higher than the buy-and-hold return of 139%, and it also has a lower drawdown of −49% compared to −51% for the buy-and-hold strategy. Hence, the authors suggest that the proposed model may be a good alternative to the passive approach of the investors.
Active Remodeling of Capillary Endothelium via Cancer Cell–Derived MMP9 Promotes Metastatic Brain Colonization
Authors: Karreman Matthia A. , Bauer Alexander T. , Solecki Gergely , Berghoff Anna S. , Mayer Chanté D. , Frey Katharina , Hebach Nils , Feinauer Manuel J. , Schieber Nicole L. , Tehranian Cedric , Mercier Luc , Singhal Mahak , Venkataramani Varun , Schubert Marc C. , Hinze Daniel , Hölzel Michael , Helfrich Iris , Schadendorf Dirk , Schneider Stefan W. , Westphal Dana , Augustin Hellmut G. , Goetz Jacky G. , Schwab Yannick , Wick Wolfgang , Winkler Frank 
Published: January 2023

AbstractCrossing the blood–brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the underlying cellular and molecular processes cannot be adequately investigated using in vitro models and endpoint in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization. Successful extravasation of arrested cancer cells occurred when adjacent capillary endothelial cells (EC) entered into a distinct remodeling process. After extravasation, capillary loops were formed, which was characteristic of aggressive metastatic growth. Upon cancer cell arrest in brain microcapillaries, matrix-metalloprotease 9 (MMP9) was expressed. Inhibition of MMP2/9 and genetic perturbation of MMP9 in cancer cells, but not the host, reduced EC projections, extravasation, and brain metastasis outgrowth. These findings establish an active role of ECs in the process of cancer cell extravasation, facilitated by cross-talk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.Significance:Tracking single extravasating cancer cells using multimodal correlative microscopy uncovers a brain seeding mechanism involving endothelial remodeling driven by cancer cell–derived MMP9, which might enable the development of approaches to prevent brain metastasis.See related commentary by McCarty, p. 1167
Event-Free Survival as a Surrogate for Overall Survival in Gastric and Gastroesophageal Junction Adenocarcinoma: A Meta-analysis in the Neoadjuvant ± Adjuvant Setting
Authors: Wainberg Zev A. , Xie Jipan , Valderrama Adriana , Yin Lei , Zhang Shujing , Shih Chie-Schin , Bhagia Pooja , Gu Qianqian , Shitara Kohei , Janjigian Yelena Y. , Tabernero Josep 
Published: January 2023

AbstractPurpose:This study assessed the trial-level association between event-free survival (EFS) and overall survival (OS) in gastric or gastroesophageal junction (GEJ) adenocarcinoma in the neoadjuvant ± adjuvant settings.Experimental Design:A systematic literature review was conducted to identify randomized controlled trials (RCT) that evaluated neoadjuvant therapies with or without adjuvant therapies for gastric or GEJ adenocarcinoma. A meta-analysis was performed using weighted linear regressions of the treatment effect of OS on the treatment effect of EFS. The coefficient of determination (R²) and associated 95% confidence interval (CI) were used to evaluate the association between treatment effects of EFS and OS. The threshold used for defining good trial-level surrogacy was a correlation coefficient (R) of 0.8 or R² of 0.65, based on prior literature. Sensitivity analyses were performed to assess the robustness of the association with divergent study designs, including study population, inclusion of adjuvant therapy, and definitions of EFS and OS.Results:The main analysis included 16 comparisons from 15 RCTs. The log(HR) of EFS was a significant predictor of log(HR) of OS, with an estimated coefficient of 0.72 (P &lt; 0.001) and R² = 0.75 (95% CI, 0.49–0.95), indicating that EFS was a good surrogate outcome for OS. The results of the sensitivity analyses were consistent with the primary results, with R² ranging from 0.76 to 0.89.Conclusions:This study suggests that EFS is a good surrogate for OS in gastric or GEJ adenocarcinoma in the neoadjuvant ± adjuvant setting.
Abstract IA015: The tick-tock of epigenetic clocks in patients with cancer
Authors: Burd Christin E. 
Published: January 2023

Abstract
There is a growing need to understand how aging influences cancer outcomes in older adults. Prior work shows that older adults with cancer would elect to forgo life-prolonging therapies that would lead to cognitive or physical disability. Here, we hypothesized that aging biomarkers would define individuals at risk for impairment and identify therapeutic regimens associated with accelerated aging. We first tested whether published epigenetic clocks would maintain validity in isolated CD3+ T cells. Potential advantages of using this approach in cancer patients include reduced sample complexity, the ability to survey aging in the context of clonal B cell expansions, and the critical importance of this cell population in cancer control. The Hannum, Horvath, GrimAge, PhenoAge, and PACE clocks increased with chronologic age in CD3+ T cells from 185 healthy donors. However, accelerated epigenetic age varied in PBMCs and CD3+ T cells isolated from the same blood sample. Next, we conducted a longitudinal analysis of adults ≥60 years of age newly diagnosed with non-small cell lung cancer (n=41) or hematologic malignancy (n=94). Standard clinical tools were used to assess fitness (ECOG performance, IADLs, SPPB), comorbidities, cognition (BOMC), and potential for therapeutic toxicity (CARG chemo-toxicity calculator). Relationships between these metrics and baseline CD3+ T cell epigenetic age were investigated. These analyses revealed a direct correlation between epigenetic age and increasing ECOG performance score. Cancer therapies, including high-dose chemotherapy, immunotherapies, and hypomethylating agents, significantly impacted patient epigenetic age. No relationship between outcome and baseline epigenetic age was observed in either population. These data support the use of the Hannum, Horvath, GrimAge, PhenoAge, and PACE clocks to measure aging in CD3+ T cells, though differences in PBMC and CD3+ T cell measurements suggest that the rate of epigenetic aging may differ in each sample type. The inability of epigenetic clocks to consistently measure physical function and cognition or predict patient outcomes implies that new clocks may be required to circumvent the heterogeneity of disease, therapies, and comorbidities in older adults with cancer.
Citation Format: Christin E. Burd. The tick-tock of epigenetic clocks in patients with cancer [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr IA015.