bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformation to a patient-centred medical home led and delivered by an urban Aboriginal and Torres Strait Islander community, and association with engagement and quality-of-care: quantitative findings from a pilot study
Authors: Mathew Saira , Barzi Federica , Clifford-Motopi Anton , Brown Renee , Ward James , Mills Richard , Turner Lyle , White Antoinette , Eaton Martie , Butler Danielle 
Published: September 2023

Abstract
Background
The patient-centred medical home (PCMH) is a model of team-based primary care that is patient-centred, coordinated, accessible, and focused on quality and safety. In response to substantial population growth and increasing demand on existing primary care services, the Institute for Urban Indigenous Health (IUIH) developed the IUIH System of Care-2 (ISoC2), based on an international Indigenous-led PCMH. ISoC2 was piloted at an urban Aboriginal and Torres Strait Islander Community-Controlled Health Service in South-East Queensland between 2019–2020, with further adaptations made to ensure its cultural and clinical relevance to local Aboriginal and Torres Strait Islander people. Little is known on the implementation and impact of PCMH in the Australian Indigenous primary care setting. Changes in implementation process measures and outcomes relating to engagement and quality-of-care are described here.

Methods
De-identified routinely collected data extracted from electronic health records for clients regularly attending the service were examined to assess pre-post implementation changes relevant to the study. Process measures included enrolment in PCMH team-based care, and outcome measures included engagement with the health service, continuity-of-care and clinical outcomes.

Results
The number of regular clients within the health service increased from 1,186 pre implementation to 1,606 post implementation; representing a small decrease as a proportion of the services’ catchment population (38.5 to 37.6%). In clients assigned to a care team (60% by end 2020), care was more evenly distributed between providers, with an increased proportion of services provided by the Aboriginal and Torres Strait Islander Health Worker (16–17% versus 10–11%). Post-implementation, 41% of clients had continuity-of-care with their assigned care team, while total, preventive and chronic disease services were comparable pre- and post-implementation. Screening for absolute cardiovascular disease risk improved, although there were no changes in clinical outcomes.

Conclusions
The increase in the number of regular clients assigned to a team and their even distribution of care among care team members provides empirical evidence that the service is transforming to a PCMH. Despite a complex transformation process compounded by the COVID-19 pandemic, levels of service delivery and quality remained relatively stable, with some improvements in risk factor screening.
What are barriers and facilitators in sustaining lean management in healthcare? A qualitative literature review
Authors: Kunnen Y. S. , Roemeling O. P. , Smailhodzic E. 
Published: September 2023

Abstract
Background

Lean management (LM) is a continuous improvement methodology originating from manufacturing and is widely adopted in healthcare to improve processes. LM shows promising results in healthcare and research on the topic is increasing. However, it can be difficult to sustain LM over time, and an overview of facilitators or barriers that influence the sustainment of LM in a healthcare context is unavailable.

Methods

Prior to search, five inclusion and exclusion criteria were defined to establish suitability of identified articles for our research question. This study was based on 24 selected peer-reviewed studies that reported on the sustainment of LM in healthcare organisations, published in the last five years. Following the Preferred Reporting Items for Systemtic Reviews and Meta-Analyses (PRISMA) guidelines, all articles were scanned, retrieved for full-text and analysed thematically.

Results

Following thematic analysis, we identified four overarching themes: Mobilising Employees, Guiding Change Efforts, Methods, and Local Context. Key facilitators for supporting LM are fostering an improvement culture and learning culture, providing professional development opportunities, assigning more responsibilities to employees in decision making processes and appointing change agents to act as local LM leaders. Key barriers for sustaining LM include overburdening employees with responsibilities, omitting staff involvement during LM implementation, lack of patient engagement, lack of resources to engage with LM, a lack of leadership commitment and follow-up on projects, and a lack of knowledge of LM among leaders.

Conclusion
Overall, studies emphasise the importance of actively involving and engaging the workforce to embed LM into organisational culture. Reflecting on the origins of LM, healthcare organisations can find inspiration in the virtue of respecting people in their journey to sustain and cultivate an improvement culture. LM provides potential to change healthcare for the better and could help healthcare organisations to cope with increasing external pressures.
A novel natural killer-related signature to effectively predict prognosis in hepatocellular carcinoma
Authors: Xi Deyang , Wang Jialu , Yang Yinshuang , Ji Fang , Li Chunyang , Yan Xuebing 
Published: September 2023

Abstract
Background
Hepatocellular carcinoma (HCC) is a prevalent tumor that poses a significant threat to human health, with 80% of cases being primary HCC. At present, Early diagnosis and predict prognosis of HCC is challenging and the it is characterized by a high degree of invasiveness, both of which negatively impact patient prognosis. Natural killer cells (NK) play an important role in the development, diagnosis and prognosis of malignant tumors. The potential of NK cell-related genes for evaluating the prognosis of patients with hepatocellular carcinoma remains unexplored. This study aims to address this gap by investigating the association between NK cell-related genes and the prognosis of HCC patients, with the goal of developing a reliable model that can provide novel insights into evaluating the immunotherapy response and prognosis of these patients. This work has the potential to significantly advance our understanding of the complex interplay between immune cells and tumors, and may ultimately lead to improved clinical outcomes for HCC patients.

Methods
For this study, we employed transcriptome expression data from the hepatocellular carcinoma cancer genome map (TCGA-LIHC) to develop a model consisting of NK cell-related genes. To construct the NK cell-related signature (NKRLSig), we utilized a combination of univariate COX regression, Area Under Curve (AUC) LASSO COX regression, and multivariate COX regression. To validate the model, we conducted external validation using the GSE14520 cohort.

Results
We developed a prognostic model based on 5-NKRLSig (IL18RAP, CHP1, VAMP2, PIC3R1, PRKCD), which divided patients into high- and low-risk groups based on their risk score. The high-risk group was associated with a poor prognosis, and the risk score had good predictive ability across all clinical subgroups. The risk score and stage were found to be independent prognostic indicators for HCC patients when clinical factors were taken into account. We further created a nomogram incorporating the 5-NKRLSig and clinicopathological characteristics, which revealed that patients in the low-risk group had a better prognosis. Moreover, our analysis of immunotherapy and chemotherapy response indicated that patients in the low-risk group were more responsive to immunotherapy.

Conclusion
The model that we developed not only sheds light on the regulatory mechanism of NK cell-related genes in HCC, but also has the potential to advance our understanding of immunotherapy for HCC. With its strong predictive capacity, our model may prove useful in evaluating the prognosis of patients and guiding clinical decision-making for HCC patients.
RTS,S/AS01E vaccine defaults in Ghana: a qualitative exploration of the perspectives of defaulters and frontline health service providers
Authors: Okyere Joshua , Bediako Vincent Bio , Ackah Josephine Akua , Acheampong Emmanuella , Owusu Bernard Afriyie , Agbemavi Wonder , Nwameme Adanna Uloaku , Kamau Edward Mberu , Asampong Emmanuel 
Published: September 2023

Abstract
Background
While Ghana has a good track record in the Expanded Programme on Immunization, there are substantial challenges with regards to subsequent vaccinations, particularly after the first year of life of the child. Given that the last dose of the RTS, S/AS01E vaccine against malaria is administered at 24 months, there is a high likelihood of default. Hence, it is imperative to understand the dynamics and reasons for the defaults to enable the development of effective implementation strategies. This study explored why caregivers default on the RTS, S/AS01E vaccine from the perspective of health service providers and caregivers.

Methods
This study employed an exploratory, descriptive approach. Using a purposive sampling technique, caregivers who defaulted and health service providers directly involved in the planning and delivery of the RTS, S/AS01E vaccine at the district level were recruited. A total of five health service providers and 30 mothers (six per FGD) participated in this study. Data analysis was done using NVivo-12 following Collaizi’s thematic framework for qualitative analysis. The study relies on the Standards for Reporting Qualitative Research.

Results
Reasons for defaulting included the overlap of timing of the last dose and the child starting school, disrespectful attitudes of some health service providers, concerns about adverse side effects and discomforts, travel out of the implementing district, the perception that the vaccines are too many, and lack of support from partners.

Conclusion
To reduce the occurrence of defaulting on the RTS, S/AS01E vaccine programme, stakeholders must reconsider the timing of the last dose of the vaccine. The schedule of the RTS, S/AS01E vaccine should be aligned with the established EPI schedule of Ghana. This will significantly limit the potential of defaults, particularly for the last dose. Also, the findings from this study underscore a need to encourage male partner involvement in the RTS, S/AS01E vaccine programme. Health promotion programmes could be implemented to raise caregivers’ awareness of potential adverse reactions and discomforts—this is necessary to prepare the caregiver for the vaccine process psychologically.
Barriers to accessing malaria treatment amongst school-age children in rural Malawi
Authors: Mhango Patani , Malata Monica Patricia , Chipeta Effie , Sixpence Alick , Taylor Terrie E. , Wilson Mark L. , Cohee Lauren M. , Mangani Charles , Mathanga Don P. 
Published: September 2023

Abstract
Background
Over the last two decades, many countries have moved from malaria control toward malaria elimination. However, some sub-Saharan African countries, like Malawi, have recently seen a reversal in malaria control progress with reported increases in confirmed malaria cases. This may be the result of inadequate access to effective malaria control interventions by key population groups that perpetuate transmission. This study aimed to assess the barriers to accessing malaria treatment among school-aged children (SAC) in Malawi.

Methods
A qualitative study was conducted between September and October 2020, where data were gathered in rural Malawi using free-listing interviews, key-informant interviews, semi-structured interviews and focus group discussions. Purposively sampled participants included SAC, parents of SAC, health workers and key stakeholders at community and district levels. Interviews were digitally recorded and transcribed verbatim. Data were organized using NVivo 12 software and analysed using the thematic method.

Results
The study recruited 252 participants, with 156 being SAC, equally divided between boys and girls. Health system barriers to malaria treatment included long waiting hours and queues at clinics, frequent stock-outs of medical supplies, and travel time to the facility. Provider barriers included negative attitude and limited service hours. Individual and cultural barriers included fear of malaria tests and beliefs associating witchcraft as the best treatment for malaria. In addition, COVID-19-related barriers included the inability to follow preventive measures, a shift in focus from malaria to COVID-19, and fear of contracting COVID-19 and/or being tested for COVID-19 at the facility.

Conclusions
This study shows most of the barriers to accessing malaria treatment among SAC are similar to those experienced by other population groups. Furthermore, COVID-19 adversely affected SAC’s access to treatment. Interventions that support SAC access to prompt diagnosis and treatment are urgently needed to improve the effective control of malaria.
Clinically conserved genomic subtypes of gastric adenocarcinoma
Authors: Jeong Yun Seong , Eun Young-Gyu , Lee Sung Hwan , Kang Sang-Hee , Yim Sun Young , Kim Eui Hyun , Noh Joo Kyung , Sohn Bo Hwa , Woo Seon Rang , Kong Moonkyoo , Nam Deok Hwa , Jang Hee-Jin , Lee Hyun-Sung , Song Shumei , Oh Sang Cheul , Lee Jeeyun , Ajani Jaffer A. , Lee Ju-Seog 
Published: September 2023

AbstractGastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions.
Non-spatial and spatial heterogeneity revealed a suppressive immune feature of Siglec-15 in lung adenocarcinomas
Authors: Li Baihui , Guo Yan , Yi Yeran , Huang Ziqi , Ren Yulin , Wang Hao , Yang Lili 
Published: September 2023

Abstract
Background
Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has emerged as a novel immunotherapy candidate, which deserves a comprehensive investigation in lung adenocarcinoma (LUAD).

Methods
Multiplex fluorescence‐based immunohistochemistry was conducted to assess Siglec-15 expression and tumor-infiltrating immune cells in LUAD from Tianjin cohort, with validation cohorts Xinchao 04 and 07.

Results
This study revealed that Siglec-15 was positively correlated with CD8+ T cells and tumor-associated macrophages (TAMs) infiltration, but CD8+ T cells were mostly infiltrated in the stroma area, not in the tumor area. Spatially, fewer CD8+ T cells surrounded Siglec-15+ tumor cells in PD-L1− cells, and more TAMs surrounded Siglec-15+ tumor cells in PD-L1−/+ cells. Siglec-15+ TAMs infiltrated with more CD8+ T cells, and were closer to CD8+ T cells than Siglec-15− TAMs and Siglec-15+ tumor cells. Siglec-15+ TAMs infiltrated with more Tregs and were closer to Tregs than Siglec-15+ tumor cells. Siglec-15+ tumor cells or TAMs reversed CD8+ T cells prognosis value, and enhanced the prognosis value of Tregs and TAMs. The immunotyping based on Siglec-15 and CD8A / CD8+ T cells revealed that patients with high CD8A and Siglec-15 expression exhibited immune activation. Patients with low CD8A expression / CD8+ T cells infiltration and Siglec-15 overexpression were related to the activation of immunosuppressive signature and metabolism-related pathway, and infiltrated with more TAMs.

Conclusions
We revealed the distinct characteristics between Siglec-15+ tumor cells and TAMs in relation to CD8+ T cells, and a unique relationship between Siglec-15 and immunosuppressive TIME in LUAD, which may provide potential value for anti-Siglec-15 therapy.
Off‐loading and compression therapy strategies to treat diabetic foot ulcers complicated by lower limb oedema: a scoping review
Authors: Tansley Justine , Collings Richard , Williams Jennifer , Paton Joanne 
Published: September 2023

AbstractBackgroundLower limb oedema is a common co‐morbidity in those with diabetes and foot ulceration and is linked with increased amputation risk. There is no current guidance for the treatment of concurrent diabetic foot ulcers and lower limb oedema, leading to uncertainty around the safety and efficacy of combination approaches incorporating offloading and compression therapies.To determine indications and contraindications for such strategies and identify any other supplementary treatment approaches, a scoping review was undertaken to map the evidence relating to off‐loading and compression therapy strategies to treat both diabetic foot ulcers and lower limb oedema in combination.MethodsFollowing the Joanna Briggs Institute (JBI) and PRISMA – Scoping Review (ScR) guidance, this review included published and unpublished literature from inception to April 2022. Literature was sourced using electronic databases including Cochrane Library, PubMed, CINAHL, AMED; websites; professional journals and reference lists of included literature. Eligible literature discussed the management of both diabetic foot ulceration and lower limb oedema and included at least one of the treatment strategies of interest. Data extraction involved recording any suggested off‐loading, compression therapy or supplementary treatment strategies and any suggested indications, contraindications and cautions for their use.ResultsFive hundred twenty‐two publications were found relating to the management of diabetic foot ulcers with an off‐loading strategy or the management of lower limb oedema with compression therapy. 51 publications were eligible for inclusion in the review. The majority of the excluded publications did not discuss the situation where diabetic foot ulceration and lower limb oedema present concurrently.ConclusionsMost literature, focused on oedema management with compression therapy to conclude that compression therapy should be avoided in the presence of severe peripheral arterial disease. Less literature was found regarding off‐loading strategies, but it was recommended that knee‐high devices should be used with caution when off‐loading diabetic foot ulcers in those with lower limb oedema. Treatment options to manage both conditions concurrently was identified as a research gap. Integrated working between specialist healthcare teams, was the supplementary strategy most frequently recommended. In the absence of a definitive treatment solution, clinicians are encouraged to use clinical reasoning along with support from specialist peers to establish the best, individualised treatment approach for their patients.Trial registrationOpen Science Framework (osf.io/crb78).
Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis
Authors: Fan Zhenziang , Kernan Kate F. , Qin Yidi , Canna Scott , Berg Robert A. , Wessel David , Pollack Murray M. , Meert Kathleen , Hall Mark , Newth Christopher , Lin John C. , Doctor Allan , Shanley Tom , Cornell Tim , Harrison Rick E. , Zuppa Athena F. , Sward Katherine , Dean J. Michael , Park H. J. , Carcillo Joseph A. 
Published: September 2023

Abstract
Background
One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network’s objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis.

Methods
We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis without hyperferritinemia. Causal inference analysis of these 41 variables, MAS, and mortality was performed.

Results
Mortality was increased in children with hyperferritinemic sepsis (27/117, 23% vs 16/280, 5.7%; Odds Ratio = 4.85, 95% CI [2.55–9.60]; z = 4.728; P-value < 0.0001). Hyperferritinemic sepsis had higher C-reactive protein, sCD163, IL-22, IL-18, IL-18 binding protein, MIG/CXCL9, IL-1β, IL-6, IL-8, IL-10, IL-17a, IFN-γ, IP10/CXCL10, MCP-1/CCL2, MIP-1α, MIP-1β, TNF, MCP-3, IL-2RA (sCD25), IL-16, M-CSF, and SCF levels; lower ADAMTS13 activity, sFasL, whole blood ex vivo TNF response to endotoxin, and TRAIL levels; more Adenovirus, BK virus, and multiple virus DNAemias; and more MAS (P-value < 0.05). Among these variables, only MCP-1/CCL2 (the monocyte chemoattractant protein), MAS, and ferritin levels were directly causally associated with mortality. MCP-1/CCL2 and hyperferritinemia showed direct causal association with depressed ex vivo whole blood TNF response to endotoxin. MCP-1/CCL2 was a mediator of MAS. MCP-1/CCL2 and MAS were mediators of hyperferritinemia.

Conclusions
These findings establish hyperferritinemic sepsis as a high-risk condition characterized by increased cytokinemia, viral DNAemia, thrombotic microangiopathy, immune depression, macrophage activation syndrome, and death. The causal analysis provides rationale for designing anti-inflammatory trials that reduce macrophage activation to improve survival and enhance infection clearance in pediatric hyperferritinemic sepsis.