bluuebunny/crossref_metadata_2025 huggingface dataset:
Realist Approach to Social Policies (RASP) study to reduce socioeconomic health inequalities through systems change: protocol for a research project combining mixed-methods realist research with institutional action research
Authors: Van Berkel Jantien , de Bruijn Ernst-Jan , Waardenburg Maikel , la Grouw Yvonne , van Bennekom Eline , van der Horst Hilje , Tonnon Susanne , Haggenburg- Mohammed Milou , Haveman-Nies Annemien , Madern Tamara , Knoef Marike , de Vet Emely
Published: June 2024

Introduction

Health inequalities are rooted in inequality in vital resources for health, including financial resources, a supportive informal network, a stable living situation, work or daytime activities or education and literacy. About 25% of Dutch citizens experience deprivation of such resources. Social policy consists of crucial instruments for improving resources in those groups but can also have adverse effects and lead to additional burdens. This project aims to contribute to the reduction of health inequalities through (1) a better understanding of how social policy interventions can contribute to reducing health inequality through the redistribution of burdens and resources and (2) developing anticipatory governance strategies to implement those insights, contributing to a change in social policy systems.

Methods and analysis

Two systems approaches are combined for establishing a systems change in the Netherlands. First, a realist approach enables insights into what in social policy interventions may impact health outcomes, for whom and under what circumstances. Second, an institutional approach enables scaling up these insights, by acknowledging the crucial role of institutional actors for accomplishing a systems change. Together with stakeholders, we perform a realist review of the literature and identify existing promising social policy interventions. Next, we execute mixed-methods realist evaluations of selected social policy interventions in seven municipalities, ranging from small, mid-size to large, and in both urban and rural settings. Simultaneously, through action research with (national) institutional actors, we facilitate development of anticipatory governance strategies.

Ethics and dissemination

This study is not liable to the Medical Research Involving Subjects Act (WMO). Informed consent to participate in the study is obtained from participants for the use of all forms of personally identifiable data. Dissemination will be codeveloped with target populations and includes communication materials for citizens, education materials for students, workshops, infographics and decision tools for policy-makers and publications for professionals.
Are local public expenditure reductions associated with increases in inequality in emergency hospitalisation? Time-series analysis of English local authorities from 2010 to 2017
Authors: Castro-Ávila Ana Cristina , Cookson Richard , Doran Tim , Shaw Robert , Brittain John , Sowden Sarah
Published: June 2024

Background

Reductions in local government funding implemented in 2010 due to austerity policies have been associated with worsening socioeconomic inequalities in mortality. Less is known about the relationship of these reductions with healthcare inequalities; therefore, we investigated whether areas with greater reductions in local government funding had greater increases in socioeconomic inequalities in emergency admissions.

Methods

We examined inequalities between English local authority districts (LADs) using a fixed-effects linear regression to estimate the association between LAD expenditure reductions, their level of deprivation using the Index of Multiple Deprivation (IMD) and average rates of (all and avoidable) emergency admissions for the years 2010–2017. We also examined changes in inequalities in emergency admissions using the Absolute Gradient Index (AGI), which is the modelled gap between the most and least deprived neighbourhoods in an area.

Results

LADs within the most deprived IMD quintile had larger pounds per capita expenditure reductions, higher rates of all and avoidable emergency admissions, and greater between-neighbourhood inequalities in admissions. However, expenditure reductions were only associated with increasing average rates of all and avoidable emergency admissions and inequalities between neighbourhoods in local authorities in England’s three least deprived IMD quintiles. For a LAD in the least deprived IMD quintile, a yearly reduction of £100 per capita in total expenditure was associated with a yearly increase of 47 (95% CI 22 to 73) avoidable admissions, 142 (95% CI 70 to 213) all-cause emergency admissions and a yearly increase in inequalities between neighbourhoods of 48 (95% CI 14 to 81) avoidable and 140 (95% CI 60 to 220) all-cause emergency admissions. In 2017, a LAD average population was ~170 000.

Conclusion

Austerity policies implemented in 2010 impacted less deprived local authorities, where emergency admissions and inequalities between neighbourhoods increased, while in the most deprived areas, emergency admissions were unchanged, remaining high and persistent.
Evaluation of the prehospital administration of tranexamic acid for injured patients: a state-wide observational study with sex and age-disaggregated analysis
Authors: Girardello Camille , Carron Pierre-Nicolas , Dami Fabrice , Darioli Vincent , Pasquier Mathieu , Ageron François-Xavier
Published: June 2024

Background

Tranexamic acid (TXA) decreases mortality in injured patients and should be administered as soon as possible. Despite international guidelines recommending TXA in the prehospital setting, its use remains low. The aim of this study was to assess the prehospital administration of TXA for injured patients in a Swiss region.

Methods

We conducted a retrospective observational study in Switzerland between 2018 and 2021. Inclusion criteria were injured patients ≥18 years for whom an ambulance or helicopter was dispatched. The exclusion criterion was minor injury defined by a National Advisory Committee for Aeronautics score <3. The primary outcome was the proportion of patients treated with TXA according to guidelines. The European guidelines were represented by the risk of death from bleeding (calculated retrospectively using the Bleeding Audit for Trauma and Triage (BATT) score). Factors impacting the likelihood of receiving TXA were assessed by multivariate analysis.

Results

Of 13 944 patients included in the study, 2401 (17.2%) were considered at risk of death from bleeding. Among these, 257 (11%) received prehospital TXA. This represented 38% of those meeting US guidelines. For European guidelines, the treatment rate increased with the risk of death from bleeding: 6% (95% CI 4.4% to 7.0%) for low risk (BATT score 3–4); 13% (95% CI 11.1% to 15.9%) for intermediate risk (BATT score 5–7); and 21% (95% CI 17.6% to 25.6%) for high risk (BATT score ≥8) (p<0.01). Women and the elderly were treated less often than men and younger patients, irrespective of the risk of death from bleeding and the mechanism of injury.

Conclusion

The proportion of injured patients receiving TXA in the prehospital setting of the State of Vaud in Switzerland was low, with even lower rates for women and older patients. The reasons for this undertreatment are probably multifactorial and would require specific studies to clarify and correct them.
Initiation of mechanical thrombectomy in an insular setting with helicopter transfer: a 2-year experience from the first, complete, tertiary stroke center in the Caribbean
Authors: Bourgeois-Beauvais Quentin , Sellin Doriane , Arnaud Isaure , Tuttle Celia , Landais Anne , Lannuzel Annie , Signate Aissatou , Berge Jerome , Iosif Christina
Published: June 2024

Background

This is the first cohort study of patients treated with mechanical thrombectomy (MT) for acute ischemic stroke in the French West Indies, with a mothership center and helicopter transfer.

Objective

To describe the population and to evaluate imaging, clinical, and time metric outcomes, in order to assess the feasibility and adjust the territorial organization.

Methods

In this observational study, we retrospectively analyzed our prospectively collected data of a population of consecutive patients treated with MT for anterior and posterior circulation large vessel occlusions. Primary outcome was 3-month functional independence (modified Rankin Scale score ≤2). Secondary outcomes included aerial and terrestrial times of arrival, in-hospital delays, demographics, imaging and clinical data at onset, discharge, and at 3 months. We compared the results of the mothership and drip-and-ship paradigms.

Results

Between January 2020 and December 2021, 223 patients were included (74% mothership, 26% drip-and-ship). Mean National Institutes of Health Stroke Scale (NIHSS) score of the population was 16 before MT, with significant reduction (NIHSS score 6) at discharge (9 mothership, 12 drip-and-ship, P=0.025). There was significant difference in onset-to-operation room times among the two centers (335 min mothership, 500 min drip-and-ship, P=0.004). Successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b–3) was 80.3%. Functional independence at 3 months was 35%, symptomatic intracranial hemorrhage was 11%, and the complication rate was 9.4%, all without statistically significant difference between the two groups.

Conclusion

The population has distinct risk factors. MT with helicopter transfer is feasible in the French West Indies. Reduction of prehospital and in-hospital times is mandatory; evaluation of the territorial strategy is underway, to avoid over-selection of transferred patients.
Rectus sheath block added to parasternal block may improve postoperative pain control and respiratory performance after cardiac surgery: a superiority single-blinded randomized controlled clinical trial
Authors: Strumia Alessandro , Pascarella Giuseppe , Sarubbi Domenico , Di Pumpo Annalaura , Costa Fabio , Conti Maria Cristina , Rizzo Stefano , Stifano Mariapia , Mortini Lara , Cassibba Alessandra , Schiavoni Lorenzo , Mattei Alessia , Ruggiero Alessandro , Agrò Felice E , Carassiti Massimiliano , Cataldo Rita
Published: June 2024

Background

The population undergoing cardiac surgery confronts challenges from uncontrolled post-sternotomy pain, with possible adverse effects on outcome. While the parasternal block can improve analgesia, its coverage may be insufficient to cover epigastric area. In this non-blinded randomized controlled study, we evaluated the analgesic and respiratory effect of adding a rectus sheath block to a parasternal block.

Methods

58 patients undergoing cardiac surgery via median sternotomy were randomly assigned to receive parasternal block with rectus sheath block (experimental) or parasternal block with epigastric exit sites of chest drains receiving surgical infiltration of local anesthetic (control). The primary outcome of this study was pain at rest at extubation. We also assessed pain scores at rest and during respiratory exercises, opiate consumption and respiratory performance during the first 24 hours after extubation.

Results

The median (IQR) maximum pain scores (on a 0–10 Numeric Rate Scale (NRS)) at extubation were 4 (4, 4) in the rectus sheath group and 5 (4, 5) in the control group (difference 1, p value=0.03). Rectus sheath block reduced opioid utilization by 2 mg over 24 hours (IC 95% 0.0 to 2.0; p<0.01), reduced NRS scores at other time points, and improved respiratory performance at 6, 12, and 24 hours after extubation.

Conclusion

The addition of a rectus sheath block with a parasternal block improves analgesia for cardiac surgery requiring chest drains emerging in the epigastric area.

Trial registration number

NCT05764616.
Radiofrequency ablation versus intra-articular mesenchymal stem cell injection for knee osteoarthritis: a systematic review and network meta-analysis
Authors: Park Sukhee , Park Soyoon , Jang Jae Ni , Choi Young-Soon , Kim Dong Seong , Sohn Jeong Eun , Park Ji-Hoon
Published: June 2024

Background

Knee osteoarthritis (OA) is a prevalent degenerative disease and causes disability, pain and imposes a substantial burden on patients. Conventional treatments for knee OA show limited effectiveness. Consequently, innovative treatments, such as radiofrequency ablation (RFA) and intra-articular mesenchymal stem cells (IA MSC), have gained attention for addressing these limitations.

Objective

We compared the efficacy of RFA and IA MSC for knee OA through a network meta-analysis (NMA).

Evidence review

A literature search was conducted using PubMed, MEDLINE, Embase, Cochrane Library, Web of Science and handsearching. Randomized controlled trials (RCTs) comparing RFA or IA MSC to conventional treatments for knee OA were included. The primary outcomes comprised the pain score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The clinical outcomes were compared using a frequentist approach, and the treatments were ranked using the surface under the cumulative ranking curve (SUCRA) values.

Findings

We included 34 RCTs (n=2371). Our NMA revealed that RFA and IA MSC were significantly more effective than conventional treatments in managing pain at both 3 and 6 months with moderate certainty. Specifically, RFA demonstrated the highest SUCRA values, indicating its superior efficacy. For WOMAC scores, both RFA and MSC showed significant improvements at 3 months, with RFA maintaining its lead at 6 months, although MSC did not display significant superiority at this stage.

Conclusions

This analysis suggests that RFA and MSC are resilient treatment options in knee OA. Despite some study heterogeneity, these treatments consistently outperformed conventional treatments, particularly in the short to mid-term, although with varying levels of certainty in their efficacy.

PROSPERO registration number

CRD42023492299.
Upper Triassic igneous rocks of the southern Kenai Peninsula, Alaska—prelude to Early Jurassic subduction along the Western Wrangellia composite terrane margin
Authors: Hudson Travis L. , Wilson Frederic H. , O'Sullivan Paul
Published: June 2024

New U–Pb zircon geochronology identifies a latest Triassic (ca 214–201 Ma) igneous suite of tuff, hypabyssal dikes, and a pluton on the southern Kenai Peninsula, Alaska. The igneous suite was emplaced within Upper Triassic sedimentary rocks along the southern margin of Western Wrangellia, the western-most fragment of the Wrangellia composite terrane. The igneous rocks range from mafic (50.6% SiO2) to felsic (78.3% SiO2), characteristically have less than 1.55% K2O, and generally have low trace element abundances. The tonalitic and trondhjemitic magmas were largely sourced in mafic-rich lower crust and incompletely assimilated quartz and other mineral xenocrysts are common. Fractionation involving plagioclase and amphibole is indicated for some magmas and composite intrusions and igneous xenoliths indicate magma mixing was possible. Paleozoic and Precambrian inherited zircons and initial 87Sr/86Sr (0.704103–0.705609) and 143Nd/144Nd (0.512396–0.512777) ratios indicate that the Western Wrangellia crustal sources are heterogeneous and contain sialic components. The latest Triassic magmatism reflects processes that preceded Early Jurassic subduction along the Wrangellia composite terrane and Pacific Ocean plate boundary. These processes involved heating and melting of mantle lithosphere and lower crust as mantle instabilities accompanied the breaking of the plate boundary linkages. The Late Triassic transition to subduction along the Wrangellia composite terrane margin coincided with the transition to subduction cessation in the Late Triassic arcs of the western Intermontane terranes of Canada. The shift to subduction along the outboard Wrangellia composite terrane margin marks the beginning of the Pacific Ocean–Cordillera plate interactions that came to dominate the tectonic evolution of the northern Cordillera from the Early Jurassic to today.
An Introduction to the Compute Express Link (CXL) Interconnect
Authors: Das Sharma Debendra , Blankenship Robert , Berger Daniel
Published: June 2024

The Compute Express Link (CXL) is an open industry-standard interconnect between processors and devices such as accelerators, memory buffers, smart network interfaces, persistent memory, and solid-state drives. CXL offers coherency and memory semantics with bandwidth that scales with PCIe bandwidth while achieving significantly lower latency than PCIe. All major CPU vendors, device vendors, and datacenter operators have adopted CXL as a common standard. This enables an inter-operable ecosystem that supports key computing use cases including highly efficient accelerators, server memory bandwidth and capacity expansion, multi-server resource pooling and sharing, and efficient peer-to-peer communication. This survey provides an introduction to CXL covering the standards CXL 1.0, CXL 2.0, and CXL 3.0. We further survey CXL implementations, discuss CXL's impact on the datacenter landscape, and future directions.
The Short‐Term and One‐Year Clinical Outcomes in Patients with Optical Coherence Tomography‐Guided Magmaris Implantation: A Real‐World Clinical Practice
Authors: Chuang Ming-Ju , Huang Wei-Chieh , Chen Ying-Ying , Lu Tse-Min
Published: June 2024

Aims. We aimed to evaluate the acute performance and short‐ and long‐term outcomes of optical coherence tomography (OCT)‐guided Magmaris deployment. Methods. This was a retrospective study of 28 consecutive patients (23 men, mean age: 59.8 years) with 28 Magmaris implantations in de novo coronary lesions. OCT was performed at the baseline and after the final postdilatation. The choice of stent and postdilatation balloon size was based on OCT measurements. The following indices were determined using OCT: prestenting minimum lumen diameter and area, poststenting minimum lumen diameter and area, acute lumen area gain, residual area stenosis, eccentricity and symmetry indices, incomplete strut apposition, strut fracture, tissue prolapse, and edge dissection. Results. Before the stenting, OCT analysis revealed a minimal lumen area of 1.55 ± 0.59 mm2, a minimal lumen diameter of 1.19 ± 0.38 mm, a minimal scaffold area of 6.78 ± 1.58 mm2, and a minimal scaffold diameter of 2.88 ± 0.50 mm2. The prolapse area was 1.2 ± 1.5 mm2. The mean percentage of RAS was 13.3 ± 7.1% and 6 (21.4%) patients had scaffold RAS more than 20%. Only one proximal edge intimal dissection was noted. The mean eccentricity index was 0.86 ± 0.04 and symmetry index 0.33 ± 0.08. ISA analysis showed that the percentage of malapposed struts was 1.5%. There were no short‐term cardiovascular events, and only 2 incidents of target lesion failure (TLF) occurred 13 months later. Conclusion. The Magmaris has excellent acute mechanical performance and no short‐term cardiovascular events occurred. There were only 2 TLFs that occurred 13 months later. It is suitable and feasible to treat vessels using the Magmaris.
Figure S5 from Fc-Silent Anti-TIGIT Antibodies Potentiate Antitumor Immunity without Depleting Regulatory T Cells
Authors: Piovesan Dana , de Groot Amber E. , Cho Soonweng , Anderson Amy E. , Ray Rebecca D. , Patnaik Amita , Foster Paul G. , Mitchell Casey G. , Lopez Espinoza Alejandra Y. , Zhu Wandi S. , Stagnaro Carlo E. , Singh Hema , Zhao Xiaoning , Seitz Lisa , Walker Nigel P. , Walters Matthew J. , Sivick Kelsey E.
Published: June 2024

Figure S5
Figure S3 from Fc-Silent Anti-TIGIT Antibodies Potentiate Antitumor Immunity without Depleting Regulatory T Cells
Authors: Piovesan Dana , de Groot Amber E. , Cho Soonweng , Anderson Amy E. , Ray Rebecca D. , Patnaik Amita , Foster Paul G. , Mitchell Casey G. , Lopez Espinoza Alejandra Y. , Zhu Wandi S. , Stagnaro Carlo E. , Singh Hema , Zhao Xiaoning , Seitz Lisa , Walker Nigel P. , Walters Matthew J. , Sivick Kelsey E.
Published: June 2024

Figure S3
Figure S10 from Fc-Silent Anti-TIGIT Antibodies Potentiate Antitumor Immunity without Depleting Regulatory T Cells
Authors: Piovesan Dana , de Groot Amber E. , Cho Soonweng , Anderson Amy E. , Ray Rebecca D. , Patnaik Amita , Foster Paul G. , Mitchell Casey G. , Lopez Espinoza Alejandra Y. , Zhu Wandi S. , Stagnaro Carlo E. , Singh Hema , Zhao Xiaoning , Seitz Lisa , Walker Nigel P. , Walters Matthew J. , Sivick Kelsey E.
Published: June 2024

Figure S10
Supplementary Tables from Integration of Pan-Cancer Cell Line and Single-Cell Transcriptomic Profiles Enables Inference of Therapeutic Vulnerabilities in Heterogeneous Tumors
Authors: Zhang Weijie , Maeser Danielle , Lee Adam , Huang Yingbo , Gruener Robert F. , Abdelbar Israa G. , Jena Sampreeti , Patel Anand G. , Huang R. Stephanie
Published: June 2024

Supplementary Tables
Supplementary Information 1 from Integration of Pan-Cancer Cell Line and Single-Cell Transcriptomic Profiles Enables Inference of Therapeutic Vulnerabilities in Heterogeneous Tumors
Authors: Zhang Weijie , Maeser Danielle , Lee Adam , Huang Yingbo , Gruener Robert F. , Abdelbar Israa G. , Jena Sampreeti , Patel Anand G. , Huang R. Stephanie
Published: June 2024

Supplementary Information 1
Supplementary Data 5 from Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
Authors: Öfverholm Ingegerd , Wallander Karin , Haglund Cecilia , Chellappa Venkatesh , Wejde Johan , Gellerbring Anna , Wirta Valtteri , Renevey Annick , Caceres Eva , Tsagkozis Panagiotis , Mayrhofer Markus , Papakonstantinou Andri , Linder-Stragliotto Christina , Bränström Robert , Larsson Olle , Lindberg Johan , Lin Yingbo , Haglund de Flon Felix
Published: June 2024

Table S5
Supplementary Data 3 from Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
Authors: Öfverholm Ingegerd , Wallander Karin , Haglund Cecilia , Chellappa Venkatesh , Wejde Johan , Gellerbring Anna , Wirta Valtteri , Renevey Annick , Caceres Eva , Tsagkozis Panagiotis , Mayrhofer Markus , Papakonstantinou Andri , Linder-Stragliotto Christina , Bränström Robert , Larsson Olle , Lindberg Johan , Lin Yingbo , Haglund de Flon Felix
Published: June 2024

Table S3
Supplementary Figure 1 from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

Supplementary Figure 1. Study design.
Supplementary Data 1 from Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer
Authors: Harrold Emily , Keane Fergus , Walch Henry , Chou Joanne F. , Sinopoli Jenna , Palladino Silvia , Al-Rawi Duaa H. , Chadalavada Kalyani , Manca Paolo , Chalasani Sree , Yang Jessica , Cercek Andrea , Shia Jinru , Capanu Marinela , Bakhoum Samuel F. , Schultz Nikolaus , Chatila Walid K. , Yaeger Rona
Published: June 2024

Supplementary tables and figures
Data from Mutation Patterns Predict Drug Sensitivity in Acute Myeloid Leukemia
Authors: Qin Guangrong , Dai Jin , Chien Sylvia , Martins Timothy J. , Loera Brenda , Nguyen Quy H. , Oakes Melanie L. , Tercan Bahar , Aguilar Boris , Hagen Lauren , McCune Jeannine , Gelinas Richard , Monnat Raymond J. , Shmulevich Ilya , Becker Pamela S.
Published: June 2024

AbstractPurpose:
The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community.
Experimental Design:
We performed targeted sequencing, high-throughput drug screening, and single-cell genomic profiling on leukemia cell samples derived from patients with AML. Statistical approaches and machine learning models were applied to identify signatures for drug response prediction. We also integrated large public datasets to understand the co-occurring mutation patterns and further investigated the mutation profiles in the single cells. The features revealed in the co-occurring or mutual exclusivity pattern were further subjected to machine learning models.
Results:
We detected genetic signatures associated with sensitivity or resistance to specific agents, and identified five co-occurring mutation groups. The application of single-cell genomic sequencing unveiled the co-occurrence of variants at the individual cell level, highlighting the presence of distinct subclones within patients with AML. Using the mutation pattern for drug response prediction demonstrates high accuracy in predicting sensitivity to some drug classes, such as MEK inhibitors for RAS-mutated leukemia.
Conclusions:
Our study highlights the importance of considering the gene mutation patterns for the prediction of drug response in AML. It provides a framework for categorizing patients with AML by mutations that enable drug sensitivity prediction.
Data from Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
Authors: Öfverholm Ingegerd , Wallander Karin , Haglund Cecilia , Chellappa Venkatesh , Wejde Johan , Gellerbring Anna , Wirta Valtteri , Renevey Annick , Caceres Eva , Tsagkozis Panagiotis , Mayrhofer Markus , Papakonstantinou Andri , Linder-Stragliotto Christina , Bränström Robert , Larsson Olle , Lindberg Johan , Lin Yingbo , Haglund de Flon Felix
Published: June 2024

AbstractPurpose:
Tumor classification is a key component in personalized cancer care. For soft-tissue and bone tumors, this classification is currently based primarily on morphology assessment and IHC staining. However, these standard-of-care methods can pose challenges for pathologists. We therefore assessed how whole-genome and whole-transcriptome sequencing (WGTS) impacted tumor classification and clinical management when interpreted together with histomorphology.
Experimental Design:
We prospectively evaluated WGTS in routine diagnostics of 200 soft-tissue and bone tumors suspicious for malignancy, including DNA and RNA isolation from the tumor, and DNA isolation from a peripheral blood sample or any non-tumor tissue.
Results:
On the basis of specific genomic alterations or absence of presumed findings, WGTS resulted in reclassification of 7% (13/197) of the histopathologic diagnoses. Four cases were downgraded from low-grade sarcomas to benign lesions, and two cases were reclassified as metastatic malignant melanomas. Fusion genes associated with specific tumor entities were found in 30 samples. For malignant soft-tissue and bone tumors, we identified treatment relevant variants in 15% of cases. Germline pathogenic variants associated with a hereditary cancer syndrome were found in 22 participants (11%).
Conclusions:
WGTS provides an important dimension of data that aids in the classification of soft-tissue and bone tumors, correcting a significant fraction of clinical diagnoses, and identifies molecular targets relevant for precision medicine. However, genetic findings need to be evaluated in their morphopathologic context, just as germline findings need to be evaluated in the context of patient phenotype and family history.
LI-RADS Category Can Be a Post-Surgical Prognostic Factor for Intrahepatic Cholangiocarcinoma in Patients with Liver Cirrhosis or Chronic Hepatitis B
Authors: Park Sungeun , Koo Boyeon , Jeong Boryeong , Choi Sang Hyun , Lee Jeong Min
Published: June 2024

Introduction: The Liver Imaging Reporting and Data System (LI-RADS) categorization has been proposed as a potential prognostic indicator for primary liver neoplasms in patients with liver cirrhosis or chronic hepatitis B. This multicenter study aimed to determine whether LI-RADS categorization can offer additional post-surgical prognostic value for intrahepatic cholangiocarcinoma (ICCA) when used in conjunction with the American Joint Committee on Cancer (AJCC) guidelines. Methods: Patients with high risk for hepatocellular carcinoma, surgically confirmed ICCAs, and available preoperative MRI were enrolled. LI-RADS categorization of ICCAs was performed using MRI features, and multivariate analyses were conducted incorporating LI-RADS category, AJCC staging, and clinicopathologic factors to evaluate their predictive value for postoperative recurrence-free survival (RFS) and overall survival (OS). In patients with early recurrence (<2 years), the percentages of AJCC stage I and LR-M or LR tumor-in-vein (TIV) were calculated, respectively. Results: Among the 166 ICCAs analyzed, 13.3% (22/166) were classified as LR-4/5, 77.7% (129/166) as LR-M, and 9.0% (15/166) as LR TIV. Classifications according to the 8th AJCC guidelines for patients with available post-surgical pathologic data and follow-up imaging were 40.6% (63/155) stage I tumors, 23.9% (37/155) stage II, and 35.5% (55/155) stage III. Multivariate analysis revealed that LI-RADS category (LR-M or LR-TIV) was a significant factor for predicting both RFS (hazard ratio [HR] = 2.86, p = 0.02) and OS (HR = 3.18, p = 0.03). Additionally, AJCC staging (II or III) was a significant factor for RFS (HR = 3.90, p < 0.001) and OS (HR = 3.29, p < 0.001), male sex was a significant factor for RFS (HR = 1.89, p = 0.006) and OS (HR = 2.23, p = 0.002), and positive resection margin was a significant factor for OS (HR = 1.91, p = 0.03). Among the 80 patients with early recurrence, 97.5% displayed LR-M or LR-TIV features, while 11.3% were AJCC stage I patients. Conclusion: The MRI-based preoperative LI-RADS categorization of ICCA provides additional post-surgical prognostic value beyond the AJCC guidelines, with significant implications for both RFS and OS.
Migraine Risk in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Nationwide Cohort Study in South Korea
Authors: Chung Yeon Hak , Han Kyung-Do , Jung Jin Hyung , Kwon Soonwook , Cho Eun Bin , Park Junhee , Shin Dong Wook , Min Ju-Hong
Published: June 2024

Introduction: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. Methods: This study analyzed claims data from 1,492 patients with MS and 1,551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. Results: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15−1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95% CI: 0.87−1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction = 0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. Conclusion: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.
Live, Love, and Suffer: The Lived Experiences of Trans Women Parents with Children in Cebu
Authors: Bacus Hans , Herames Christine Silvery , Solibaga Sean Joseph , Villamor Roque Luis Manuel , Cimafranca John Stephen , Talens Diana Marie , Maghanoy Sarah Jean , Gagani Flordeliza
Published: June 2024

Parenthood entails daunting responsibilities, even more so if parents are of a different gender spectrum such as trans women. Against a rigid heteronormative society, this phenomenological study explored the challenges and the struggles, as well as the coping mechanisms, of the trans-women parents in Metro Cebu, Philippines. Through Husserlian’s descriptive phenomenology, five participants were chosen through snowball sampling to share their experiences through in-depth interviews in 2023. Utilizing Colaizzi’s method of data analysis, the study revealed seven (7) recurring themes: (1) Financial Instability; (2) Societal Acceptance; (3) Shifting Family Dynamics; (4) Lack of Legal Government Protection; (5) Employment Possibilities; (6) Perseverance; and (7) Communication. These findings provided insights into the lives of trans-women parents in the Philippines and offered recommendations for policies that could help address the issues faced by this sub-group of parents. Moreover, this study served as a contribution to the literature on non-heteronormative families through the lived experiences of trans-women parents in a heteronormative society like the Philippines.
Social, Economic, and Technological Barriers of the Music Industry in Cebu Province Through the Lens of Management Functions
Authors: Almaden Antoniette M. , Ocampo Alex P. , Delantar Alexander Franco A.
Published: June 2024

This research aimed to investigate the multifaceted challenges faced by music core groups in Cebu Province, analyzing social, economic, and technological barriers. Its primary goal was to propose an innovative management framework for ensuring sustainable growth in the music industry. Utilizing qualitative multiple-case study, this study delved into the complex landscape shaped by challenges for music creators, artists, and organizations. It involved a comprehensive management framework encompassing planning, organizing, leading, and controlling. The study identified themes including navigating professional dynamics, social equity and empowerment dynamics, obstacles in creative pursuits, financial sustainability, economic instability, challenges in technology utilization, and industry adaptation. Various coping mechanisms such as faith, self-care, and community involvement were observed. While the study provided valuable insights, the limited representation of diverse industry positions highlights the need for further research to fully grasp the complexities and challenges of the music industry. The Amplify Cebu Music Management Framework, incorporating TechHarmony Integration, aimed to seamlessly integrate technology into the industry. Tailored interventions addressed leadership development, promotion strategies, artist well-being, creative hubs, education, and government support. The study's insights transcend the local context, offering globally applicable frameworks for fostering inclusive and effective industry development, thereby enhancing social equity and empowerment dynamics. This research presents a comprehensive roadmap for overcoming barriers and enhancing resilience, contributing to a vibrant and sustainable music industry in Cebu while aligning local scenes with global audiences.
Saúde e bem-estar em ambientes de trabalho para gerações emergentes no pós pandemia
Authors: Bussi Luize Cristina Andreazza , Almeida Maristela Moraes de
Published: June 2024

Las nuevas concepciones que separan el significado de la salud de la mera ausencia de enfermedad, junto con la responsabilidad del ciudadano en el cumplimiento de la Agenda de Desarrollo Sostenible para el año 2030, son los principios rectores de este artículo. Los arquitectos, esforzándose por diseñar espacios que fomenten una sensación de bienestar, al enfrentarse a situaciones excepcionales como la pandemia de COVID-19, necesitan ampliar su repertorio y comprender a los individuos para quienes están diseñando y las características del entorno futuro. Se entiende que los periodos de excepción han acelerado cambios en la forma en que se abordan los diseños. El enfoque interdisciplinario, que aporta conocimientos de otras áreas o especialidades, se percibe como un recurso potencial para abordar desafíos y condiciones y alcanzar soluciones adecuadas. Este artículo se deriva de una disertación de maestría y tiene como objetivo comprender y redactar pautas consideradas relevantes para el desarrollo de entornos laborales destinados a las generaciones emergentes. Emplea un enfoque metodológico cualitativo basado en revisión narrativa de literatura, razonamiento hipotético-deductivo y dialéctico. Como resultado se obtienen pautas de diseño dentro del contexto y específicas de lo propuesto. Este artículo aborda tendencias en el diseño de ambientes construidos, que surgen de la interpolación entre perspectivas antropocéntricas y biocéntricas.
Uma roteirização midiática para a pandemia de Covid-19 no Brasil
Authors: Ribeiro Patricia Ferreira Neves , Gomes Luciana da Silva
Published: June 2024

Faced with the pandemic crisis caused by the spread of a new type of coronavirus, an undeniable representative of an imminent danger to public health, there has been a huge mobilization of the media towards disseminating information about this health crisis of global proportions. Within this context, this article aims to identify how and which socio-discursive imaginaries are activated to guide the construction of narrative scripts about the disease throughout 2021 on the covers of O Globo, a news outlet with huge diffusion in the State of Rio de Janeiro. For this mapping, this research aims to focus, from a microtextual perspective, on linguistic-discursive resources that emerge from this text, as well as dealing, in a macrotextual dimension, with the mode of narrative organization. To this end, the study is based on the theoretical-methodological framework of the Semiolinguistic Theory of Discourse Analysis (Charaudeau, 2012).
Tema e Significação na constituição do signo ideológico “cura” em narrativas autobiográficas de terapeutas em práticas integrativas e complementares em saúde
Authors: Vieira Daniele Vasconcelos Fernandes , Alves Benedito Francisco , Alencar Claudiana Nogueira de
Published: June 2024

The objective of this study is to analyze the theme and the meaning in the constitution of the ideological sign “cure” as enunciated by a participant of the “Updating Course in Hand Therapy: Focus on Practices and Narratives in Massage Therapy and Shantala”. The subject participating in this study is a popular educator and therapist in health, who bases their practice on the precepts of Freire's pedagogy for the promotion of health care. The corpus of this study consists of several autobiographical narratives collected throughout the training. For analysis, the concept of meaning and theme (Volóchinov, 2017) was used, drawing from discussions about discursive genre in Bakhtin (2006), ideological sign (Volóchinov, opus cit), and the notion of Popular Education (Freire, 1970; 1992). The analysis revealed that, in the context of the enunciative construction, the sign "cure" for the educator only acquires meaning if it is associated with connection and well-being if the touch opens the heart to the flow of the unconditional and makes the being vibrate.
Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and Eicosapentaenoic Acid (RESPECT-EPA)
Authors: Miyauchi Katsumi , Iwata Hiroshi , Nishizaki Yuji , Inoue Teruo , Hirayama Atsushi , Kimura Kazuo , Ozaki Yukio , Murohara Toyoaki , Ueshima Kenji , Kuwabara Yoshihiro , Tanaka-Mizuno Sachiko , Yanagisawa Naotake , Sato Tosiya , Daida Hiroyuki ,   RESPECT-EPA Investigators
Published: June 2024

BACKGROUND:

Low plasma levels of eicosapentaenoic acid (EPA) are associated with cardiovascular events. This trial aimed to assess the clinical benefits of icosapent ethyl in patients with coronary artery disease, a low EPA/arachidonic acid (AA) ratio, and statin treatment.

METHODS:

In this prospective, multicenter, randomized, open-label, blinded end-point study, patients with stable coronary artery disease and a low EPA/AA ratio (<0.4) were randomized to EPA (1800 of icosapent ethyl administered daily) or control group. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina pectoris, and coronary revascularization. The secondary composite end points of coronary events included sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina requiring emergency hospitalization and coronary revascularization, or coronary revascularization.

RESULTS:

Overall, 3884 patients were enrolled at 95 sites in Japan. Among them, 2506 patients had a low EPA/AA ratio, and 1249 and 1257 patients were randomized to the EPA and control group, respectively. The median EPA/AA ratio was 0.243 (interquartile range, 0.180–0.314) and 0.235 (interquartile range, 0.163–0.310) in the EPA and control group, respectively. Over a median period of 5 years, the primary end point occurred in 112 of 1225 patients (9.1%) and 155 of 1235 patients (12.6%) in the EPA and control group, respectively (hazard ratio, 0.79 [95% CI, 0.62–1.00];
P
=0.055). Meanwhile, the secondary composite end point of coronary events in the EPA group was significantly lower (81/1225 [6.6%] versus 120/1235 [9.7%] patients; hazard ratio, 0.73 [95% CI, 0.55–0.97]). Adverse events did not differ between the groups, but the rate of new-onset atrial fibrillation was significantly higher in the EPA group (3.1% versus 1.6%;
P
=0.017).

CONCLUSIONS:

Icosapent ethyl treatment resulted in a numerically lower risk of cardiovascular events that did not reach statistical significance in patients with chronic coronary artery disease, a low EPA/AA ratio, and statin treatment.

REGISTRATION:

URL:
https://www.umin.ac.jp/ctr/
; Unique identifier: UMIN000012069.
Prognostic Significance of Proteomics‐Discovered Circulating Inflammatory Biomarkers in Patients With Pulmonary Arterial Hypertension
Authors: Yokokawa Tetsuro , Boucherat Olivier , Martineau Sandra , Lemay Sarah‐Eve , Breuils‐Bonnet Sandra , Krishna Vinod , Kalyana‐Sundaram Shanker , Jeyaseelan Jey , Potus François , Bonnet Sébastien , Provencher Steeve
Published: June 2024

Background

Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation‐related circulating proteins that add incremental value to current risk stratification models for long‐term survival in patients with PAH.

Methods and Results

Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C‐statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin‐like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long‐Term PAH Disease Management) 2.0 risk scores, and the refined 4‐strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline‐injected and pulmonary artery banding‐subjected rats).

Conclusions

In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.
CYP2C19
Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention
Authors: Tunehag Kayla R. , Thomas Cameron D. , Franchi Francesco , Rossi Joseph S. , Keeley Ellen C. , Anderson R. David , Beitelshees Amber L. , Duarte Julio D. , Gong Yan , Kerensky Richard A. , McDonough Caitrin W. , Nguyen Anh B. , Ortega‐Paz Luis , Venkatesh Sanjay , Wang Yehua , Johnson Julie A. , Winterstein Almut G. , Stouffer George A. , Angiolillo Dominick J. , Cavallari Larisa H. , Lee Craig R.
Published: June 2024

Background

Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of
CYP2C19
genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.

Methods and Results

Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical
CYP2C19
genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of
P
<0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel‐treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person‐years; adjusted hazard ratio, 2.00 [95% CI, 1.20–3.33],
P
=0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.

Conclusions

Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real‐world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype‐guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
Child Rights and Realities
Authors: Bendo Daniella
Published: June 2024

This paper explores how children’s rights are operationalised in practice, specifically by Canadian child and youth advocate offices (all 12 offices across Canada), international children’s commissioners’ offices (in Northern Ireland, Australia, New Zealand, Belgium, Norway and Denmark), and their institutional structures. A total of 24 participants took part in the study, including 12 current child and youth advocates from the Canadian Council of Child and Youth Advocates (cccya), two former advocates from the cccya, three additional staff members of the cccya (collectively, representing all 12 jurisdictions across Canada), one children’s commissioner and six designates on behalf of various international children’s commissioners. This paper shifts the research focus of children’s rights and childhood studies from the narrow confines of the individual child to a focus on the broader relational and interdependent aspects inherent within institutions that protect and promote children’s rights.