bluuebunny/crossref_metadata_2025_split huggingface dataset:
Best practice for the selection, design and implementation of UK Kidney Association guidelines: a modified Delphi consensus approach
Authors: Burton James O , Chilcot Joseph , Fielding Katie , Frankel Andrew H , Lakhani Niraj , Nye Pam , Parker Kathrine , Priestman William , Willingham Fiona 
Published: June 2024

BackgroundDespite research into how to effectively implement evidence-based recommendations into clinical practice, a lack of standardisation in the commissioning and development of clinical practice guidelines can lead to inconsistencies and gaps in implementation. This research aimed to ascertain how topics in kidney care worthy of guideline development within the UK should be chosen, prioritised, designed and implemented.MethodsFollowing a modified Delphi methodology, a multi-disciplinary panel of experts in kidney healthcare from across the UK developed 35 statements on the issues surrounding the selection, development and implementation of nephrology guidelines. Consensus with these statements was determined by agreement using an online survey; the consensus threshold was defined as 75% agreement.Results419 responses were received. Of the 364 healthcare practitioners (HCPs), the majority had over 20 years of experience in their role (n=123) and most respondents were nephrologists (n=95). Of the 55 non-clinical respondents, the majority were people with kidney disease (n=41) and the rest were their carers or family. Participants were from across England, Northern Ireland, Scotland and Wales. Consensus between HCPs was achieved in 32/35 statements, with 28 statements reaching ≥90% agreement. Consensus between patients and patient representatives was achieved across all 20 statements, with 13/20 reaching ≥90% agreement.ConclusionsThe current results have provided the basis for six recommendations to improve the selection, design and implementation of guidelines. Actioning these recommendations will help improve the accessibility of, and engagement with, clinical guidelines, contributing to the continuing development of best practice in UK kidney care.
National trend in the prevalence and mortality of COPD in South Korea from 2008 to 2017
Authors: Kim Sun-Hyung , Park Jong Eun , Yang Bumhee , Kim So Young , Kim Yeon Yong , Park Jong Hyock 
Published: June 2024

BackgroundExisting studies on chronic obstructive pulmonary disease (COPD) in Korea lack full population coverage, relying on small sample sizes. Therefore, this study aims to investigate the prevalence and mortality of COPD in the entire Korean population.MethodsThis serial cross-sectional study used national databases, linking the National Health Information Database (2008–2017) with Causes of Death Statistics. Identification of individuals with COPD used diagnostic codes (International Classification of Diseases-10: J41–J44) or a history of COPD-related hospitalisation, focusing on adults aged 40 and above. Prevalence and mortality rates, calculated for 2008–2017, encompassed both crude and age-standardised and sex-standardised measures. A multivariate Poisson regression model estimated the association between COPD and all-cause and cause-specific mortality, presenting incidence rate ratios (IRRs) and 95% CIs, using data from the year 2017.ResultsAge-adjusted COPD prevalence exhibited a notable increase from 2008 (7.9%) to 2017 (16.7%) in both sexes. The prevalences of diabetes mellitus, hypertension, dyslipidaemia, ischaemic heart disease, cancer, osteoporosis and tuberculosis were higher in the COPD group than in the group without COPD (p for all <0.001). The incidence of stroke and myocardial infarction (p for all <0.001) and overall mortality were higher in the COPD group (adjusted IRR 1.23, 95% CI 1.22 to 1.24, p<0.001). In particular, incidence rate and risk of mortality due to lung cancer were higher than that of those without COPD compared with other cancer types (adjusted IRR 2.51, 95% CI 2.42 to 2.60, p<0.001). It was significantly higher the incidence rate and risk of mortality among group with COPD than those without COPD in lower respiratory disease (adjusted IRR 16.62, 95% CI 15.07 to 18.33, p<0.001), asthma (adjusted IRR 6.41, 95% CI 5.47 to 7.51, p<0.001) and bronchiectasis (adjusted IRR 11.77, 95% CI 7.59 to 18.26, p<0.001), respectively.DiscussionOur study showed that the prevalence of COPD is gradually increasing from 9.2% in 2009 to 16.7% in 2018. Furthermore, in overall (all-cause) mortality, it was significantly higher in group with COPD than in group without COPD. The mortality rate of group with COPD was much higher than the overall mortality rate but is gradually decreasing.
Clinical outcomes with thin versus thick strut polymer-free biolimus-coated stents at 3 years
Authors: Eberli Franz R , Oldroyd Keith G , Urban Philip , Krucoff Mitchell W , Morice Marie-Claude , Tanguay Jean-François , Leon Martin B , Brunel Philippe , Maillard Luc , Lipiecki Janus , Cook Stéphane , Berland Jacques , Hovasse Thomas , Carrié Didier , Schütte Diana , Sadozai Slama Sara , Garot Philippe 
Published: June 2024

BackgroundFor high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the safety and efficacy of a stainless steel polymer-free biolimus-coated stent (SS-BCS) with 30 days of dual antiplatelet treatment (DAPT). The LEADERS FREE III (LF III) trial investigated clinical outcomes after PCI with the next-generation cobalt-chromium thin-strut polymer-free biolimus-coated stent (CoCr-BCS) in HBR patients.AimsTo report the final 3-year results of the LF III trial and compare them to LF II.MethodsLF III was a prospective, multicentre, open-label single-arm study to evaluate the safety and efficacy of the CoCr-BCS stent. The primary safety endpoint was the composite of cardiac death (CD), myocardial infarction(MI) or definite/probable stent thrombosis (ST). The primary efficacy endpoint was clinically driven target lesion revascularisation (cd-TLR). We performed a propensity-matched comparison to the 3-year outcomes of LF II.ResultsAfter 3 years, CD/MI/ST had occurred in 57 patients (15%, 95% CI 11.8% to 19%) and cd-TLR in 23 (6.2%, 95% CI 4.1% to 9.2%) patients. In a propensity-matched comparison of patients treated with the CoCr-BCS versus the SS-BCS, there were similar rates of CD (6.6% vs 7.8%, p=0.50), MI (7.1% vs 8.3%, p=0.47) and definite/probable ST (1.1% vs 2%, HR 0.56, 95% CI 0.16 to 1.93, p=0.35). The rates of cd-TLR were 5.3% with CoCr-BCS versus 9.8% with SS-BCS (HR 0.54, 95% CI 0.31 to 0.96, p=0.03).ConclusionLF III confirms the long-term safety and efficacy of the CoCr-BCS in HBR patients treated with 1 month of DAPT.Trial registration numberNCT02843633,NCT03118895.
Abstract PO-002: Intrinsically disordered regions -induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers
Authors: Zhang Xinyan , Xiao Qian , Zeng Longhui , Hashmi Fawzaan , Su Xiaolei 
Published: June 2024

Abstract
Chimeric antigen receptor (CAR)-T cell-based therapies demonstrate remarkable efficacy for the treatment of otherwise intractable cancers, particularly B-cell malignancies. However, CAR-T cells respond to only a subset of cancers and are limited by low signaling efficiency: a few hundred or thousand antigen molecules are required to activate a CAR T cell whereas a single peptide-loaded MHC molecule is sufficient to trigger the activation of a normal T cell. This low antigen sensitivity not only limits the current CAR-T therapy to high antigen-expressing cancers, but also results in high frequencies of relapse, during which high antigen-expressing cancers downregulate their antigen levels to escape CAR-T’s attacking. To improve the antigen sensitivity of CAR-T cells, we engineered CARs targeting CD19 by including intrinsically disordered regions (IDRs) that promote signaling condensation. The “IDR CARs” triggered enhanced membrane-proximal signaling in the CAR-T synapse, which led to an increased release of cytotoxic factors, a higher killing activity towards low antigen-expressing cancer cells in vitro, and an improved anti-tumor efficacy in vivo. No elevated tonic signaling was observed in IDR CAR-Ts. Together, we demonstrated IDRs as a new tool set to enhance CAR-T cytotoxicity and to broaden CAR-T’s application to low antigen-expressing cancers.
Citation Format: Xinyan Zhang, Qian Xiao, Longhui Zeng, Fawzaan Hashmi, Xiaolei Su. Intrinsically disordered regions -induced CAR condensation improves the cytotoxicity of CAR-Ts against low-antigen cancers [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-002.
Abstract PO-006: ABBV-319: A CD19–targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies
Authors: Chang Chewei (Anderson) 
Published: June 2024

Abstract
Glucocorticoids such as prednisone (P) and dexamethasone (D) are key components in standard-of-care immuno-chemotherapy regimens (e.g., R-CHOP, EPOCH-R, Hyper-CVAD) for the treatment of B-cell malignancy. However, prolonged systemic glucocorticoid treatment is associated with several adverse events that often result in dose reduction and reduced therapeutic efficacy. ABBV-319 is a CD19-targeting antibody-drug conjugate (ADC) with a glucocorticoid receptor modulator (GRM) payload engineered to reduce glucocorticoid-associated toxicities while possessing three distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) CD19 receptor-mediated delivery of potent glucocorticoid receptor modulator (GRM) payload to induce apoptosis, (2) inhibition of B-cell receptor (BCR) stimulated CD19 signaling, and (3) enhanced Fc-mediated effector function via afucosylation of the antibody backbone. ABBV-319 elicited potent GRM-driven anti-tumor activity against multiple malignant B-cell lines in vitro as well as in cell line-derived xenografts (CDXs) and patient-derived xenografts (PDXs) in vivo. Remarkably, a single-dose of ABBV-319 induced sustained tumor regression and enhanced anti-tumor activity compared to repeat dosing of systemic prednisolone at the maximum tolerated dose (MTD) in mice. The unconjugated CD19 monoclonal antibody (mAb) also displayed anti-proliferative activity on a subset of B-cell lymphoma cell lines through the inhibition of PI3K signaling. Moreover, afucosylation of the CD19 mAb enhanced Fc-mediated antibody-dependent cellular cytotoxicity (ADCC), and this activity was maintained after conjugation with GRM payload. Notably, ABBV-319 displayed superior efficacy compared to afucosylated CD19 mAb in human CD34+ PBMC-engrafted NSG-tg(Hu-IL15) transgenic mice, demonstrating enhanced anti-tumor activity in vivo when multiple MOAs are enabled concurrently. ABBV-319 also showed potent anti-tumor activity across multiple B-cell lymphoma models, including non-germinal center B-cell (GCB) DLBCL and relapsed lymphoma treated with R-CHOP treatment. Collectively, these data support the ongoing evaluation of ABBV-319 for the treatment of B-cell malignancy in Phase I clinical trial (NCT05512390).
Disclosures: All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.
Citation Format: Chewei (Anderson) Chang. ABBV-319: A CD19–targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-006.
Abstract PO-030: Single cell spatial analysis of large B cell lymphoma identifies biomarkers correlated with genetic subtypes and clincal outcomes
Authors: Xu Alexander , Lownik Joseph , Villamejor Anton , Mahov Simeon , Li Ying , Xu-Monette Yidan , Young Ken , Merchant Akil 
Published: June 2024

Abstract
Single cell and multiplex imaging modalities have opened new insights into the organization and architecture of the immune microenvironment of cancer. Our group was one of the first to demonstrate these methods in the analysis of Hodgkin [1,2] and non-Hodgkin lymphoma [3]. Most recently, we demonstrated that spatial biomarkers outperform gene-expression biomarkers in predicting relapse after autologous transplant [4]. Here we present previously unpublished data demonstrating single cell multiplexed spatial analysis, using the imaging mass cytometry platform, in a cohort of 426 patients with large cell lymphoma. Gene expression and mutational analysis are available for a majority of cases allowing us to correlate spatial signature with genetic classes such as LymphGen [5], and deconvolution methods such as EcoTyper [6]. Using this cohort, we identify spatial biomarkers that improve prediction of clinical outcomes beyond cell of origin or genetic subgroup and identify novel targets for clinical development. Finally, we will present our approaches to move our discovery level spatial profiling into clinical diagnostic space through application of automated multiplex immunofluorescence imaging and a machine learning based image analysis pipeline. [1] Aoki T, et al. Single-Cell Transcriptome Analysis Reveals Disease-Defining T-cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma. Cancer Discov. 2020 doi: 10.1158/2159-8290.CD-19-0680. [2] Xu, A. et al. Single cell spatial analysis and biomarker discovery in Hodgkin lymphoma. Biorxiv, 2023. https://doi.org/10.1101/2023.05.24.542195. [3] Colombo AR, et al. Single-cell spatial analysis of tumor immune architecture in diffuse large B-cell lymphoma. Blood Adv. 2022 doi: 10.1182/bloodadvances.2022007493. [4] Aoki T, et al. Spatially Resolved Tumor Microenvironment Predicts Treatment Outcomes in Relapsed/Refractory Hodgkin Lymphoma. J Clin Oncol. 2024 doi: 10.1200/JCO.23.01115. [5] Wright GW, et al. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 doi: 10.1016/j.ccell.2020.03.015. [6] Steen CB, et al. The landscape of tumor cell states and ecosystems in diffuse large B cell lymphoma. Cancer Cell. 2021 doi: 10.1016/j.ccell.2021.08.011.
Citation Format: Alexander Xu, Joseph Lownik, Anton Villamejor, Simeon Mahov, Ying Li, Yidan Xu-Monette, Ken Young, Akil Merchant. Single cell spatial analysis of large B cell lymphoma identifies biomarkers correlated with genetic subtypes and clincal outcomes [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PO-030.
Abstract PR03: Immunosurveillance of precancerous germinal center B cells
Authors: Zhang Lingling , Atkins Oscar , Hung Miu Shing , Reinhardt Hans Christian , Parente Calado Dinis Pedro 
Published: June 2024

Abstract
Most Non-Hodgkin Lymphomas (NHLs) originate from germinal center (GC) or post-GCB cells. While the immune system actively targets precancerous cells in epithelial-derived cancers, it is uncertain if the same applies to precancerous GCB cells. Knowledge on Follicular Lymphoma (FL), the most common low-grade NHL derived from GCB cells, prompted us to develop novel mouse models to mimic the precancerous state. In FL, BCL2 translocation and CREBBP loss-of-function (LoF) mutations are characteristic of a precancerous state. These mutations can be detected years before FL diagnosis, hinting at potential immune involvement in preventing FL. Our research affirms the effectiveness of the mouse models in replicating the FL precancerous state. Mice with BCL2 overexpression (OE) alone or together with CREBBP LoF showed increased GCB cell expansion, up to 6-fold compared to control. This expansion involved reduced GCB cell death rather than increased proliferation, consistent with FL slow-growing nature. Mice harboring mutant GCB cells also exhibited a significant increase in memory B cells, up to 20-fold when compared to control. As the GC reaction progressed, the impact of CREBBP LoF emerged, profoundly altering GCB cell phenotypes, and triggering a remarkable surge in cell expansion, escalating up to 80-fold compared to mice with BCL2 OE alone or control. However, this hyperplasia was swiftly followed by a decline, indicative of immunosurveillance targeting precancerous GCB cells. Prior to the reduction of GCB cells with BCL2 OE and CREBBP LoF, we observed a notable expansion of PD1+ CD8+ T cells expressing granzyme A and perforin. These activated CD8+ T cells also expressed CXCR5, facilitating their infiltrating into the B cell follicle to specifically eliminate GCB cells with BCL2 OE and CREBBP LoF. Preemptive depletion of CD8+ T cell effectively prevented the loss of precancerous GCB cells. The examination of the GC reaction over time provided new perspectives into the immunosurveillance of precancerous GCB cells and FL development. The data supports the concept that precancerous GCB cells must overcome robust anti-tumor immunity for Lymphoma to ensue. This knowledge offers potential explanation for the infrequent and extended duration of the transition from precancerous GCB cells to full-blown FL. These models provide a foundation to explore mechanisms underlying immune evasion by precancerous GCB cells.
Citation Format: Lingling Zhang, Oscar Atkins, Miu Shing Hung, Hans Christian Reinhardt, Dinis Pedro Parente Calado. Immunosurveillance of precancerous germinal center B cells [abstract]. In: Proceedings of the Fourth AACR International Meeting on Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2024 Jun 19-22; Philadelphia, PA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(3_Suppl):Abstract nr PR03.
OUTCOME COMPARISON OF LASER-ASSISTED IN SITU KERATOMILEUSIS IN VARIOUS DEGREE OF MYOPIA
Authors: Rahmani Syifa , Musa Ine Renata 
Published: June 2024

Introduction: The femtosecond Laser-Assisted in Situ Keratomileusis (fs-LASIK) procedure is commonly used for myopia correction because of good efficacy, safety, and predictability. The aim of this study was to compare the outcome of the fs-LASIK procedure among myopia groups in Cicendo Eye Hospital from January to December 2021.
Methods: This retrospective study included 212 patients (399 eyes) and the data were obtained from medical records from January 2021 to December 2021 using ICD-10 coding for LASIK (S0800), consisting of fs-LASIK procedures. The outcome variables were safety index, and efficacy index.
Results: The median of safety index was not statistically significant different between groups, 1,00(0,50-1,67) in low myopia, 1,00(0,20-1,43) in moderate myopia, and 1,00(0,30-3,33) in high myopia. The median of efficacy index was statistically significant different between groups, 1,00(0,40-1,67) in low myopia, 1,00(0,20-1,43) in moderate myopia, and 1,00(0,30-3,33) in high myopia. The proportion of eye with UCVA > 6/12 on the first month after the procedure was higher in the mild myopia group (223;99,2%) than in moderate myopia (87;98,8%) and high myopia (77;88,5%) with p=0,0001. The proportion of eye with BCVA > 6/12 on the first month after the procedure was also higher in the mild myopia group (224;100%) than in moderate myopia (87;98,8%) and high myopia (82;94,3%) with p=0,0001.
Conclusion: There was no statistically significant difference of the safety index between groups. The efficacy index was statistically significant different between groups.
From wings to whiskers to stem cells: why every model matters in fragile X syndrome research
Authors: Sandoval Soraya O. , Méndez-Albelo Natasha M. , Xu Zhiyan , Zhao Xinyu 
Published: June 2024

AbstractFragile X syndrome (FXS) is caused by epigenetic silencing of the X-linked fragile X messenger ribonucleoprotein 1 (FMR1) gene located on chromosome Xq27.3, which leads to the loss of its protein product, fragile X messenger ribonucleoprotein (FMRP). It is the most prevalent inherited form of intellectual disability and the highest single genetic cause of autism. Since the discovery of the genetic basis of FXS, extensive studies using animal models and human pluripotent stem cells have unveiled the functions of FMRP and mechanisms underlying FXS. However, clinical trials have not yielded successful treatment. Here we review what we have learned from commonly used models for FXS, potential limitations of these models, and recommendations for future steps.
Restricted antennal movement impacts the tandem running dynamics in a ponerine ant
Authors: Mukhopadhyay Snigdha , Halder Subhashis , Halder Eshika , Annagiri Sumana 
Published: June 2024

Abstract
Background
Tandem running is a recruitment method found in some species of ants where one ant follows another ant to reach a destination having maintained a physical contact with its antennae, throughout the journey. It is considered that the exchange of information regarding the destination among the nestmates happened during the process of tandem running. We examined the impact of restricting antennal movement on tandem running by using Diacamma indicum, a tandem-running ponerine ant by following 480 tandem runs across 9 treatment colonies and comparing it with 10 control relocating colonies.

Result
Though all the 19 colonies relocated successfully, treatment colonies took significantly longer time to do so. Restricted antennal movement did not influence the ability to become tandem leaders, initiate tandem runs or the work organization significantly. However, antennae-restricted ants performed fewer tandem runs and took significantly longer time. Followers with single or both antennae-restriction performed significantly higher number of interruptions and the alignment between the leader and follower was impacted as antenna-restricted followers subtended a greater angle and walked more to the side of the leader as compared to the control followers.

Conclusion
This study showed unhindered movement of the followers’ antennae is important for tandem-running ants. In the next step, to gain a comprehensive understanding of this recruitment method, it is essential to individually delineate different sensory modalities.