bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the feasibility of using publicly available data sources to identify healthcare data discrepancies and enhance service delivery: a retrospective cross-sectional study of four low human index scoring countries
Authors: Boisson-Walsh Alix , Lewis Jack , Neilson Matthew , Leatherman Sheila 
Published: May 2024

IntroductionQuality of care (QoC) remains a persistent challenge in countries with low Human Development Index scores (LHDIS) despite global efforts to promote universal health coverage. Addressing root causes and systematically implementing improvement interventions in LHDIS countries require a better understanding and use of QoC data. We aim to describe the data gaps and illustrate the state of quality in health services across a small set of countries. We demonstrate how we can leverage currently available, although imperfect, public data sources to compile quality metrics across multiple LHDIS countries.MethodsUsing public data sources, the Demographic Health Survey (DHS) and Service Provision Assessment (SPA), we selected relevant quality metrics and categorised them within a QoC matrix. We based the selection of metrics on the quality of care in fragile, conflict-affected and vulnerable settings framework domains and the Donabedian model. Criteria for our retrospective cross-sectional study included a LHDIS and recent availability of both DHS and SPA data for data relevance.ResultsThe approach was feasible, with relevant indicators distributed across various QoC categories. However, some cells in the indicator matrix lacked suitable indicators from SPA and DHS data. We selected the Democratic Republic of the Congo, Haiti, Afghanistan and Senegal for a snapshot of QoC in LHDIS countries. Comparisons highlighted areas of positive performance and shared challenges across these countries, with notable variability in certain categories. Senegal ranked highest overall, while Afghanistan ranked lowest across all matrix categories. Senegal had the most comprehensive data, with 94.7% of metrics available. Missing data existed for two specific metrics in all four countries, particularly within the improving clinical care domain.ConclusionThe results are a clarion call for advancing efforts to develop standardised, publicly available, routinely collected and validated data sets to measure and publicly report LHDIS countries’ state of quality to marshal global attention and action in pursuit of more significant health equity.
Impact of scaling up of kangaroo mother care on neonatal mortality among babies born with birth weight <2000 g in a district in southern India: a prospective cohort analysis
Authors: Thomas Tinku , Kar Arin , Rao Suman P N , Narayana Swaroop , Washington Maryann , Rao Shashidhar , Jayanna Krishnamurthy , Gowda Prabhu Deva , Lakkappa Mohan Harnahalli , Mony Prem 
Published: May 2024

ObjectiveTo assess the impact of scaling up of kangaroo mother care (KMC) on neonatal mortality among babies born with birth weight <2000 g across an entire district in southern India.Design, setting and participantsWithin an implementation research setting, analysis of a prospective birth cohort of babies with birth weight <2000 g born during March–December 2018 in Koppal district of Karnataka state, India, to estimate the incidence, risk and HRs of neonatal mortality associated with KMC.InterventionInitiation and maintenance of KMC.Outcome measuresNeonatal mortality.ResultsAmong 23 667 live births, 1152 (4.9%) had birth weight <2000 g; the birth weight was <1500 g in 24% and <1000 g in 4%. Among them, 213 (18%, 95% CI 16% to 21%) babies died during the neonatal period, with 56% of the mortality occurring in the first 3 days of life and risk of mortality decreasing with higher birth weight. Overall, KMC was initiated in 816 (71%) babies; KMC-initiated babies had a substantially lower risk of neonatal mortality (risk ratio 0.07 (95% CI 0.05 to 0.09)). In a subset of 705 babies ‘eligible-for-KMC’ after exclusion of deaths, referrals or ‘terminal discharges’ (leaving against medical advice) in the first 3 days of life, and whose mother was a resident of the study area, 88% (95% CI 85% to 90%) were initiated on KMC. The RR of mortality among KMC-initiated babies remained low at 0.05 (95% CI 0.03 to 0.08) after adjusting for covariates and propensity-score adjusted analysis to address selection bias. Among 874 babies with follow-up data till 29 days of life, neonatal mortality rate was 24.4% (95% CI 21.6% to 27.3%); it was 6.4% (95% CI 4.7% to 8.6%) among KMC-initiated babies and 74.8% (95% CI 67.8% to 79.1%) among non-initiated babies (n=233).ConclusionKMC implementation across a district was associated with substantial reduction in neonatal mortality. Scaling up KMC coverage across large geographies could facilitate achieving global child survival targets.
Impact of patient support programmes among patients with severe asthma treated with biological therapies: a systematic literature review and indirect treatment comparison
Authors: Rabe Adrian P J , Loke Wei J , Kielar Danuta , Morris Tamsin , Shih Vivian H , Olinger Lynda , Musat Mihaela G , Lan Zhiyi , Harricharan Sharada , Fulton Olivia , Majeed Azeem , Heaney Liam G 
Published: May 2024

IntroductionEffective treatment of severe asthma requires patient adherence to inhaled and biological medications. Previous work has shown that patient support programmes (PSP) can improve adherence in patients with chronic diseases, but the impact of PSPs in patients with severe asthma treated with biologics has not been thoroughly investigated.MethodsWe conducted a systematic literature review to understand the impact of PSPs on treatment adherence, asthma control and health-related quality of life (HRQoL) in patients with severe asthma. Embase, MEDLINE and EconLit databases were searched for studies published from 2003 (the year of the first biological approval for severe asthma) to June 2023 that described PSP participation among patients with severe asthma on biological treatment. Direct pooling of outcomes was not possible due to the heterogeneity across studies, so an indirect treatment comparison (ITC) was performed to determine the effect of PSP participation on treatment discontinuation. The ITC used patient-level data from patients treated with benralizumab either enrolled in a PSP (VOICE study, Connect 360 PSP) or not enrolled in a PSP (Benralizumab Patient Access Programme study) in the UK.Findings25 records of 21 studies were selected. Six studies investigated the impact of PSPs on treatment adherence, asthma control or HRQoL. All six studies reported positive outcomes for patients enrolled in PSPs; the benefits of each PSP were closely linked to the services provided. The ITC showed that patients in the Connect 360 PSP group were less likely to discontinue treatment compared with the non-PSP group (OR 0.26, 95% CI 0.11 to 0.57, p<0.001).ConclusionsPSPs contribute to positive clinical outcomes in patients with severe asthma on biological treatment. Future analyses will benefit from thorough descriptions of PSP services, and study designs that allow direct comparisons of patient outcomes with and without a PSP.
Single and multiple breath nitrogen washout compared with the methacholine test in patients with suspected asthma and normal spirometry
Authors: Siebeneichler Aline Stalder , Schumann Desiree M , Karakioulaki Meropi , Brachsler Nora , Darie Andrei M , Grize Leticia , Heck Thiago G , Tamm Michael , Latzin Philipp , Stolz Daiana 
Published: May 2024

BackgroundMethods used to assess ventilation heterogeneity through inert gas washout have been standardised and showed high sensitivity in diagnosing many respiratory diseases. We hypothesised that nitrogen single or multiple breath washout tests, respectively nitrogen single breath washout (N2SBW) and nitrogen multiple breath washout (N2MBW), may be pathological in patients with clinical suspicion of asthma but normal spirometry. Our aim was to assess whether N2SBW and N2MBW are associated with methacholine challenge test (MCT) results in this population. We also postulated that an alteration in SIIIat N2SBW could be detected before the 20% fall of forced expiratory volume in the first second (FEV1) in MCT.Study design and methodsThis prospective, observational, single-centre study included patients with suspicion of asthma with normal spirometry. Patients completed questionnaires on symptoms and health-related quality-of-life and underwent the following lung function tests: N2SBW (SIII), N2MBW (Lung clearance index (LCI), Scond, Sacin), MCT (FEV1and sGeff) as well as N2SBW between each methacholine dose.Results182 patients were screened and 106 were included in the study, with mean age of 41.8±14 years. The majority were never-smokers (58%) and women (61%). MCT was abnormal in 48% of participants, N2SBW was pathological in 10.6% at baseline and N2MBW abnormality ranged widely (LCI 81%, Scond18%, Sacin43%). The dose response rate of the MCT showed weak to moderate correlation with the subsequent N2SBW measurements during the provocation phases (ρ 0.34–0.50) but no correlation with N2MBW.ConclusionsBoth MCT and N2washout tests are frequently pathological in patients with suspicion of asthma with normal spirometry. The weak association and lack of concordance across the tests highlight that they reflect different but not interchangeable pathological pathways of the disease.
Abstract ED07-02: Recent advances in systemic disease
Authors: Loi S. 
Published: May 2024

Abstract
Recent advances in the treatment of HER2 positive breast cancer have focussed on the antibody drug conjugate Trastuzumab Deruxetecan, which is now approved for 2nd line use and beyond. Results show remarkable efficacy in this context, with durable progression free and increased overall survival. Deciphering mechanisms of resistance to T-DXD and ways to overcome this is currently of high clinical interest. In this talk we shall discuss what we know about resistance mechanisms to TDXD
Citation Format: S. Loi. Recent advances in systemic disease [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED07-02.
Abstract ED11-02: Surgical controversies in IBC
Authors: Lucci A. 
Published: May 2024

Abstract
In an era of treatment de-escalation, there remain questions regarding the optimal surgical management for patients with inflammatory breast cancer (IBC). For years, the standard surgical approach for patients with IBC has been modified radical mastectomy (MRM) (including complete axillary node dissection as a component of MRM) with delayed breast reconstruction. In the recent past, some authors have proposed the use of breast conserving surgery, sentinel lymph node mapping, skin-sparing mastectomy, and even immediate reconstruction as possibly appropriate procedures for the treatment of patients with IBC. In this educational session, we plan to review the available data to try and reach a conclusion on what surgical procedures appear to provide the best outcomes for patients with IBC.
Citation Format: A. Lucci. Surgical controversies in IBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED11-02.
Abstract PO1-04-05: Effectiveness and safety of inetetamab + pyrotinib + vinorelbine in ≥second-line treatment of HER2-positive metastatic breast cancer
Authors: Wu Fan , Chen Mulan , Huang Weiwei , Wang Lili , Li Nani , Wu Xiufeng , Chen Xinhua , Hong Yi , Lin Lin , Chen Kan , liu Jian 
Published: May 2024

Abstract
Background: In real-world settings, Patients with HER2-positive metastatic breast cancer (MBC) who cannot receive antibody-drug conjugates (ADCs) as standard second-line therapy due to cost–benefit ratios and who have no preferred options as ≥third-line regimen by NCCN guidelines, require new regimens to meet their clinical needs. This study aims to explore the effectiveness and safety of inetetamab + pyrotinib + vinorelbine for ≥second-line treatment of HER2-positive MBC. Methods: Patients with HER2-positive MBC who received ≥second-line treatment at our hospital from June 2020 to December 2022 were enrolled. Progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR) and adverse reactions were assessed. Patients received inetetamab + pyrotinib + vinorelbine until disease progression or unacceptable toxicity were evaluated every two cycles according to the RECIST 1.1 criteria. Results: 89 patients were included based on the inclusion and exclusion criteria. Among them, 45 patients received second-line treatment who couldn't use T-DM1 or T-DXd, and 44 patients received ≥third-line treatment. The median PFS of the second-line treatment subgroup was 17months, the ORR and CBR were 60.0% and 86.7%, respectively, which were significantly higher than those in the ≥third-line treatment subgroup and numerically superior to T-DM1 as a second-line treatment option. Additionally, the ORR and CBR of patients with baseline brain metastasis who did not receive radiotherapy were 27.3% and 72.7%, respectively. The most common adverse events observed were leukopenia (37.1%), neutropenia (42.7%), anemia (34.8%) and diarrhea (67.4%). The incidence of grade 3-4 leukopenia, neutropenia, anemia and diarrhea were 11.2%, 15.7%, 55.6% and 27.0%, respectively. A total of 8 patients (8.9%) discontinued medication due to adverse reactions. Conclusions: Inetetamab + pyrotinib + vinorelbine demonstrates good efficacy and controllable toxicity as a second-line treatment for HER2-positive MBC. This therapeutic regimen provides a viable alternative option for patients who are unable to receive ADCs as the second-line treatment.
Citation Format: Fan Wu, Mulan Chen, Weiwei Huang, Lili Wang, Nani Li, Xiufeng Wu, Xinhua Chen, Yi Hong, Lin Lin, Kan Chen, Jian liu. Effectiveness and safety of inetetamab + pyrotinib + vinorelbine in ≥second-line treatment of HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-05.
Abstract PO1-08-02: Population-based screening of Uruguayan Ashkenazi Jews for recurrent BRCA1 and BRCA2 pathogenic sequence variants
Authors: Castillo Cecilia , Camejo Natalia , Artagaveytia Nora , Brignoni Lucia , Laitman Yael , Cayota Alfonso , Krygier Gabriel , Delgado Lucia , Friedman Eitan 
Published: May 2024

Abstract
In Ashkenazi Jews (AJ) three recurring pathogenic sequence variants (PSVs) are detected in ~2.5% of the general population in the BRCA1 (c.68_69del = 185delAG, c.5266dup = 5382insC), and BRCA2 (c.5946del = 6174delT). Population-based screening for these PSVs in AJ women is part of the health basket in Israel. To assess the feasibility and outcome of BRCA genotyping in the Jewish population of Uruguay, AJ in the greater Montevideo area were recruited using ethically approved protocol and without pretest counseling were genotyped for the three predominant AJ PSVs in the BRCA genes. Independently confirmed PSV carriers were counseled, and genetic testing was offered to additional family members. Overall, 327 participants were enrolled: 312 (95%) female, 261 (80%) had all four grandparents AJ, and 14 (4%) women were breast cancer survivors with a mean age ± standard deviation (SD) 50 ± 11.5 years. The BRCA1 c.68_69del PSV was detected in three cancer free participants (0.92%, CI 95% 0.31-2.6), all with a suggestive family history. No carriers of the other two recurrent PSVs were detected. Online oncogenetic counseling was provided for all carriers. In conclusion, the rate of the BRCA1 c.68_69del PSV was similar with the rate in other AJ communities. AJ population BRCA genotyping screens in Uruguay seem feasible and should be promoted.
Pedigrees of the carrier cases (a-c)
Citation Format: Cecilia Castillo, Natalia Camejo, Nora Artagaveytia, Lucia Brignoni, Yael Laitman, Alfonso Cayota, Gabriel Krygier, Lucia Delgado, Eitan Friedman. Population-based screening of Uruguayan Ashkenazi Jews for recurrent BRCA1 and BRCA2 pathogenic sequence variants [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-02.
Abstract PO1-13-11: ZNF689 promotes homologous recombination via NBS1 ubiquitination and its loss confers sensitivity to PARP inhibition in triple-negative breast cancer
Authors: Ge Li-Ping , Wang Zi-Yu , Jin Xi , Jiang Yi-Zhou , Shao Zhi-Ming 
Published: May 2024

Abstract
Background: Triple-negative breast cancer (TNBC) poses significant clinical challenges due to the lack of targeted therapies and poor prognosis. Homologous recombination (HR) deficiency is a defining characteristic of TNBC and renders tumors susceptible to Poly (ADP-ribose) polymerase (PARP) inhibitors. However, not all TNBC patients respond to PARP inhibitors, highlighting the need to identify novel biomarkers to predict therapeutic response and improve treatment strategies. Methods: In this study, we investigated the role of zinc finger protein 689 (ZNF689) in DNA damage response (DDR) and its impact on PARP inhibitor sensitivity in TNBC. Using a comprehensive set of molecular and cellular techniques, including immunoprecipitation, in vitro and in vivo ubiquitination assays, protein expression analysis, and functional assays using TNBC cell lines, patient-derived organoids (PDOs), patient-derived xenograft (PDX) models, and cell line xenograft models, we elucidated the mechanistic role of ZNF689 in HR and PARP inhibitor response. Results: Our findings revealed ZNF689 as a novel player in DDR. ZNF689 is activated by ATM-mediated phosphorylation and recruited to DNA damage sites in an ATM-dependent manner. At the DNA double-strand break sites, ZNF689 collaborates directly with NBS1 to facilitate K63-linked ubiquitination of NBS1 via the E3 ligase SKP2. Furthermore, ZNF689-mediated NBS1 ubiquitination stabilizes the MRE11-RAD50-NBS1 (MRN) complex and feedbacks activation of ATM, therefore accelerating HR repair. Loss of ZNF689 results in HR deficiency, leading to increased sensitivity of TNBC cells to PARP inhibitors in both in vitro and in vivo models. Additionally, the combination of PARP inhibitors and paclitaxel demonstrated potential for improved efficacy in treating ZNF689-deficient TNBC. In our clinical analysis, we observed a positive correlation between ZNF689 expression and the levels of NBS1 and phosphorylated ATM in TNBC patient samples. Importantly, low ZNF689 expression was associated with a favorable response to PARP inhibitors in TNBC patients. Conclusions: Our study highlights the significant role of ZNF689 in HR and its impact on the response to PARP inhibitors in TNBC. These findings suggest ZNF689 as a promising therapeutic target for enhancing the effectiveness of PARP inhibitors in TNBC patients.
Working Modle
Citation Format: Li-Ping Ge, Zi-Yu Wang, Xi Jin, Yi-Zhou Jiang, Zhi-Ming Shao. ZNF689 promotes homologous recombination via NBS1 ubiquitination and its loss confers sensitivity to PARP inhibition in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-11.
Abstract PO1-13-12: Mechanistic Analysis and Potential Therapeutic Implications in Breast Cancer with Fibrotic Focus
Authors: Fang Canbin , Tsang Julia Y. S. , Tse Gary M.K. 
Published: May 2024

Abstract
A fibrotic focus (FF) is a scar-like region that forms in the center of carcinoma due to excessive tumor stroma formation. In our earlier studies, we found FF as an independent poor prognostic factor for breast cancers. However, the underlying mechanisms of how the presence of FF contributed to a poor prognosis are still unknown. To improve our understanding of FF in breast cancer, we have investigated genes associated with FF and their impacts on breast cancer prognosis. Analysis of data from The Cancer Genome Atlas Program (TCGA) indicated that Bone Morphogenetic Protein 8A (BMP8A) was significantly upregulated in breast cancers with FF. To further validate this finding, immunohistochemistry (IHC) on BMP8A was performed on a local cohort of breast cancers (N= 900). Of these samples, 147 (16.3%) were found to be BMP8A positive, and there was a significant association between the presence of FF and high expression of BMP8A (p-value=0.026). We also found that high expression of BMP8A was positively correlated with apocrine phenotype, necrosis, increased Ki67 expression, and triple-negative breast cancer subtype; and most of these are poor prognostic factors for breast cancer. Kaplan-Meier survival estimate analysis revealed that high expression of BMP8A was significantly associated with poor overall survival (p-value=0.035). Gene ontology (GO) analysis showed that "Extracellular matrix organization" was the prominent biological process associated with BMP8A. KEGG pathway analysis suggested that BMP8A was significantly related to "Protein digestion and absorption", "ECM-receptor interaction", and "Focal adhesion" pathways, further validating its correlation with stromal FF. In cellular studies using MCF7 and MDA-MB-231 cell lines, overexpression of BMP8A was found to enhance breast cancer cell proliferation, invasion, and migration. Similar tumor-promoting phenotypes were exhibited when stimulating the cell lines with recombinant human BMP8A. In conclusion, our findings suggested that BMP8A was associated with FF in breast cancer, contributing at least partly to the aggressive features of these cancers. Our findings also provided new insights into the precision treatment and diagnosis of breast cancer. Further exploration of BMP8A as a therapeutic target and prognostic factor may contribute to improved management of breast cancer patients.
Citation Format: Canbin Fang, Julia Y. S. Tsang, Gary M.K. Tse. Mechanistic Analysis and Potential Therapeutic Implications in Breast Cancer with Fibrotic Focus [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-12.