bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Place-Based Primary Interventions: Levers and Tensions Related to Multilevel Governance for Community Integrated Pathways, A Multiple Case Study
Authors: Goudet Anna , Doré Chantal , Hyppolite Shelley-Rose , Lévesque Nancy , Joseph Jean-Alex , Maltais Danielle , Bourque Denis , Maillet Lara
Published: March 2024

Integrated Place-Based Primary Interventions (IPPIs) are considered an innovative response to the challenges and complex issues faced in disadvantaged areas where traditional institutional services have difficulty reaching people in vulnerable situations. IPPIs are an innovative approach to the delivery of in services, conceived as an original community-based local care and service pathways. However, these intervention practices require adaptive modes of governance. In this article, we explore how and to what extent the mode of governance of IPPIs influences the performance of community-integrated pathways. To this end, using a qualitative exploratory multiple-case study design (observation and semi-structured interviews), we describe 4 IPPIs in 3 territories in Quebec. This includes an examination of the levers of action and tensions related to their governance and the performance levels of the community-integrated pathways. We conclude that collaborative and shared multilevel governance, despite its demanding nature, appears to contribute to the longevity of the actions and benefits of IPPIs and could prevent their relevance from being questioned.
Donate to help us fight back: Political fundraising and toxic rhetoric online
Authors: Kim Seo-young Silvia , Zilinsky Jan , Brew Brian
Published: March 2024

Political candidates utilize social media to mobilize supporters, persuade voters, and raise money. However, little is known about the structure of mass electoral appeals when donors are the primary target instead of voters. Because candidates’ donors and voters can differ significantly, with donors more partisan and ideologically extreme on average, we theorize that candidates use strategic rhetoric tailored to specific audiences. To analyze how campaigns perceive and target their “financial electorate,” we leverage data from the Facebook Ad Library for 2020 U.S. congressional candidates and distinguish political ads by their persuasion targets. Using text analysis, we test the hypotheses that donor-targeting messages are more toxic, negative, and likely to reference a polarizing president than voter-targeting messages. The results support our hypotheses, and Republican candidates, on average, used more toxic language than their Democratic counterparts. As campaigns’ scramble for donations intensifies, these characteristics of fundraising appeals may further polarize the electorate.
Anti-proliferative Effects of Pinocembrin Isolated From Anomianthus dulcis on Hepatocellular Carcinoma Cells
Authors: Saengboonmee Charupong , Thithuan Kanyarat , Mahalapbutr Panupong , Taebprakhon Cheerapinya , Aman Aamir , Rungrotmongkol Thanyada , Kamkaew Anyanee , Schevenels Florian Thierry , Chompupong Tanakiat , Wongkham Sopit , Lekphrom Ratsami
Published: March 2024

Background:

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Anomianthus dulcis (Dunal) J.Sinclair (syn. Uvaria dulcis) has been used in Thai traditional medicine in various therapeutic indications. Phytochemical constituents of A. dulcis have been isolated and identified. However, their effects on liver cancer and the associated mechanisms have not been elucidated.

Methods:

Dry flowers of A. dulcis were extracted using organic solvents, and chromatographic methods were used to purify the secondary metabolites. The chemical structures of the pure compounds were elucidated by analysis of spectroscopic data. Cytotoxicity against HCC cells was examined using SRB assay, and the effects on cell proliferation were determined using flow cytometry. The mechanisms underlying HCC inhibition were examined by molecular docking and verified by Western blot analysis.

Results:

Among 3 purified flavonoids, pinocembrin, pinostrobin, and chrysin, and 1 indole alkaloid (3-farnesylindole), only pinocembrin showed inhibitory effects on the proliferation of 2 HCC cell lines, HepG2 and Li-7, whereas chrysin showed specific toxicity to HepG2. Pinocembrin was then selected for further study. Flow cytometric analyses revealed that pinocembrin arrested the HCC cell cycle at the G1 phase with a minimal effect on cell death induction. Pinocembrin exerted the suppression of STAT3, as shown by the molecular docking on STAT3 with a better binding affinity than stattic, a known STAT3 inhibitor. Pinocembrin also suppressed STAT3 phosphorylation at both Tyr705 and Ser727. Cell cycle regulatory proteins under the modulation of STAT3, namely cyclin D1, cyclin E, CDK4, and CDK6, are substantially suppressed in their expression levels.

Conclusion:

Pinocembrin extracted from A. dulcis exerted a significant growth inhibition on HCC cells via suppressing STAT3 signaling pathways and its downstream-regulated genes.
Proof of Concept: Development of a Mitral Annuloplasty Ring With Crosshatch Net
Authors: Seadler Benjamin D. , Joyce David L. , Zelten James , Sweeney Kevin , Wisgerhof Taylor , Slettehaugh Zoey , Yuan Y. William , Tefft Brandon J. , Pearson Paul J.
Published: March 2024

Objective:

Here we report our preclinical, proof-of-concept testing to assess the ability of a novel device to correct mitral regurgitation. The Milwaukee Heart device aims to enable any cardiac surgeon to perform high-quality mitral valve repair using a standard annuloplasty ring with a crosshatch of microporous, monofilament suture.

Methods:

Hemodynamic, echocardiographic, and videographic data were collected at baseline, following induction of mitral regurgitation, and after repair using porcine hearts in an ex vivo biosimulator model. A commercially available cardiac prosthesis assessment platform was then used to assess the hydrodynamic characteristics of the study device.

Results:

Porcine biosimulator pressure and flow metrics exhibited successful correction of mitral regurgitation following device implantation with similar values to baseline. Hydrodynamic results yielded pressure gradients and an effective orifice area comparable to currently approved prostheses.

Conclusions:

The study device effectively reduced mitral valve regurgitation and improved hemodynamics in our preclinical model with similar biophysical metrics to currently approved devices. Future in vivo trials are needed to evaluate the efficacy, biocompatibility, and freedom from the most likely adverse events, such as device thrombosis, embolic events, and hemolysis.
When the media goes to war: How Russian news media defend the country’s image during the conflict with Ukraine
Authors: Nguyen Nhung , Peters Pamela , Ding Hechen , Vu Hong Tien
Published: March 2024

Using the country image repair framework, this study analyzed two opinion columns in major Russian state-controlled media outlets with content related to the Russian–Ukraine conflict, Russia Today (RT) and Sputnik, from 24 February 2022 to 20 May 2022. A thematic content analysis was used to examine 60 articles by RT and 70 articles on Sputnik. Results from the analysis determined that the five strategies of country image repair, except for mortification, were used in an attempt to legitimize the conflict in Ukraine and restore the image of Russia. Theoretical and practical implications of the results are discussed in the context of a repressive news media environment.
Severe pulmonary hypertension associated with hypothyroidism and mixed aortic valve disease: A case report
Authors: Diallo Thierno Hamidou , Nana Yeboah Frederick , Djafarou Boubacar Raynatou , Faraj Raid , Boui-Issoui Keltoum , sidi Mhamed Ely Sidi , El Ghiati Hanaa , Diallo Ibrahima Dokal , Mouine Najat , Benyass Aatif
Published: March 2024

Pulmonary hypertension is a condition characterised by elevated pulmonary arterial pressures secondary to various aetiologies; the most common ones are left heart diseases. Similarly, an association between thyroid diseases and pulmonary hypertension has been reported in some cases, but the pathophysiological relationship has not been fully elucidated. Etiological investigation is an important step in the management of pulmonary hypertension and determines the appropriate treatment. In this report, we present a case of severe pulmonary hypertension in a 57-year-old woman, in which mixed aortic valve disease and hypothyroidism were involved.
A Rare Combination of Cardiac Hydatid Cyst and Pulmonary Hydatidosis in a Child
Authors: Al-Dairy Alwaleed , Shhada Eman , Aldej Nour , Kraym Islam
Published: March 2024

Hydatid disease is a common health problem in the sheep-farming countries of the Mediterranean, caused by infection with Echinococcus granulosus. The common sites are the liver and lungs. Cardiac hydatidosis is rare. Herein, we report a case of interventricular septum hydatid cyst with lung involvement in a four-year-old child. Cardiac hydatid cysts should be resected surgically even in asymptomatic patients since delayed diagnosis and treatment can lead to fatal outcomes. In spite of its rarity, the combination of cardiac and pulmonary hydatidosis can be managed with a single operation.
Vulnerability of the Agricultural Commodity Markets in Ghana to Global Oil Price Fluctuations: An Empirical Analysis
Authors: Oteng Clement , Iledare Omowumi , Sebu Joshua
Published: March 2024

Despite the advocacy for climate change goals and encouragement for renewables, crude oil continues to dominate the energy markets. Crude oil price, however, is prone to global price fluctuations. Analyses of these effects on agricultural commodity markets in Ghana is neglected which this study seeks to answer. A nonlinear approach (NARDL) is employed in evaluating the effects of global oil price fluctuation on Ghana’s agricultural commodity market vulnerability, proxied by their producer prices. Different indicators are used since crude price fluctuations might have varying impacts on macroeconomic indicators in both magnitude and signs. Quarterly time series data are sourced from different institutions including data from the Bank of Ghana, FAO, and British Petroleum Statistical Review spanning from 1980: Q1 to 2019: Q4. Empirical results indicate that crude oil price fluctuations have different signs and magnitude for agricultural food commodities prices for both short- and long-runs. The findings of the study bring to bear how the agricultural activities in Ghana respond to variability in global crude oil prices. Policies mitigating changes in prices of animal products ought to be grounded on other issues instead of changes in crude oil prices. Also, programs such as “Planting for Food and Jobs” must be implemented in effectively.

JEL Classification: Q02; C32; E31; H23
Married Women Decision-Making Autonomy on Contraceptive Use in East Africa: A Multilevel Analysis of Recent Demographic and Health Survey
Authors: Asmamaw Desale Bihonegn , Shewarega Ever Siyoum , Fentie Elsa Awoke , Negash Wubshet Debebe , Fetene Samrawit Mihret , Teklu Rediet Eristu , Alemu Tewodros Getaneh , Eshetu Habitu Birhan , Belay Daniel Gashaneh , Aragaw Fantu Mamo
Published: March 2024

The utilization of contraceptives depends on women’s autonomy in making decisions. Limited and inconclusive information is available on women’s decision-making autonomy to use contraceptives in East Africa. Therefore, the main objective of this study was to assess married women’s decision-making autonomy on contraceptive use and associated factors in East African countries. The most recent Demographic and Health Surveys were used for this study. The study included a total weighted sample of 41,893 married reproductive-age women. A multilevel mixed-effect binary logistic regression model was fitted. The prevalence of married women’s decision-making autonomy on contraceptive use was 18.91% (95% CI: 18.54, 19.29). Respondents who are employed (AOR = 1.24; 95% CI: 1.03, 1.44), having more than two alive children (AOR = 1.38; 95% CI: 1.13, 1.67), and visited a health facility in the last 12 months (AOR = 1.22; 95% CI: 1.05, 1.45), urban residency (AOR = 1.39; 95% CI: 1.27, 1.50), lower middle-income level 1.37 (AOR = 1.37; 95% CI: 1.17, 1.60), and community media exposure to family planning message (AOR = 1.25; 95% CI: 1.04, 1.45) were significantly associated with women’s decision making autonomy on contraceptive use. Despite the fact that every woman has the right to participate in her own healthcare decisions, less than one-fifth of married women in East Africa have contraceptive decision-making autonomy. Hence, Women’s decision-making autonomy on contraceptives should be promoted through mass media as an essential part of sexual and reproductive rights, with particular attention paid to rural women, women with no children, and women living in low-income households.
Biomarker Testing and Role of Tyrosine Kinase Inhibitors and Immunotherapy for Esophageal Squamous Cell Carcinoma
Authors: Mahmud Muftah , Munjal Ananya , Savani Malvi , Win Hninyee , Rozell Umbreen , Arshad Junaid
Published: March 2024

Esophageal squamous cell carcinoma (ESCC) constitutes an aggressive subset of esophageal cancers that portends a poor prognosis. Management of ESCC has been historically challenging due to the limited effective therapeutic options. Broadening our understanding of the molecular landscape and identifying reliable biomarkers are essential in early detection, monitoring disease response and advancing treatment strategies. Recently, immunotherapy and tyrosine kinase inhibitors have changed the treatment algorithm of ESCC. In this review, we explore the molecular landscape and biomarkers that can aid in the management of ESCC and discuss the role of immunotherapy and tyrosine kinase inhibitors in the treatment of ESCC.
An Examination of Inter-State Variation in Utilization of Healthcare Services, Associated Financial Burden and Inequality: Evidence from Nationally Representative Survey in India
Authors: Aashima  , Sharma Rajesh
Published: March 2024

This study examines the health care utilization pattern, associated financial catastrophes, and inequality across Indian states to understand the subnational variations and aid the policy makers in this regard. Data from recent National Sample Survey (2017–2018), titled, “Household Social Consumption: Health,” covering 113,823 households, was employed in the study. Descriptive statistics, Erreygers concentration index (CI), and recentered influence function decomposition were applied in the study. We found that, in India, 7 percent of households experienced catastrophic health expenditure (CHE) and 1.9 percent of households were pushed below poverty line due to out-of-pocket expenditure on hospitalization. Notably, outpatient care was more burdensome (CHE: 12.1%; impoverishment: 4%). Substantial interstate variations were observed, with high financial burden in poorer states. Utilization of health care services from private health care providers was pro-rich (hospitalization CI 0.31; outpatient CI 0.10), while the occurrence of CHE incidence was pro-poor (hospitalization CI −0.10; outpatient CI −0.14). Education level, economic status, health insurance, and area of residence contributed significantly to inequalities in utilization of health care services from private providers and financial burden. The high financial burden of seeking health care necessitates the need to increase public health spending and strengthen public health infrastructure. Also, concerted efforts directed towards increasing awareness about health insurance and introducing comprehensive health insurance products (covering both inpatient and outpatient services) are imperative to augment financial risk protection in India.
Adoptive transfer of donor B lymphocytes: a phase 1/2a study for patients after allogeneic stem cell transplantation
Authors: Winkler Julia , Tittlbach Hannes , Schneider Andrea , Vasova Ingrid , Strobel Julian , Herold Susanne , Maas Stefanie , Spriewald Bernd M. , Repp Roland , Kordelas Lambros , Mach Michael , Wolff Daniel , Edinger Matthias , Mackensen Andreas , Winkler Thomas H.
Published: March 2024

Immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is slow and patients carry a high and prolonged risk of opportunistic infections. We hypothesized that the adoptive transfer of donor B cells can foster after HSCT immuno-reconstitution. Here, we report, to our knowledge, the results of a first-in-human phase 1/2a study aimed to evaluate the feasibility and safety of adoptively transferred donor B cells and to test their activity upon recall vaccination. Good manufactoring practice (GMP) B-cell products were generated from donor apheresis products using 2-step magnetic cell separation. Fifteen patients who had undergone allo-HSCT were enrolled and treated after taper of immunosuppression (median, day +148; range, 130-160). Patients received 4 different doses of B cells (0.5 × 106 to 4.0 × 106 B cells per kg body weight). To test the activity of infused donor memory B cells in vivo, patients were vaccinated with a pentavalent vaccine 7 days after B-cell transfer. We observed the mobilization of plasmablasts and an increase in serum titers against vaccine antigens, with a stronger response in patients receiving higher B-cell numbers. Analysis of immunoglobulin VH-sequences by next-generation sequencing revealed that plasmablasts responding to vaccination originated from memory B-cell clones from the donor. Donor B-cell transfer was safe, as no Epstein-Barr virus (EBV) reactivation was observed, and only low-grade graft-versus-host disease (GVHD) occurred in 4 out of 15 patients. This pilot trial may pave the way for further studies exploring the adoptive transfer of memory B cells to reduce the frequency of infections after allo-HSCT. This trial was registered at ClinicalTrial.gov as #NCT02007811.
Towards Sustainable Grinding of Difficult-to-Cut Alloys—A Holistic Review and Trends
Authors: Qian Ning , Chen Jiajia , Khan Aqib Mashood , Zhao Biao , Chen Yurong , Ding Wenfeng , Fu Yucan , Xu Jiuhua
Published: March 2024

Grinding, a critical precision machining process for difficult-to-cut alloys, has undergone continual technological advancements to improve machining efficiency. However, the sustainability of this process is gaining heightened attention due to significant challenges associated with the substantial specific grinding energy and the extensive heat generated when working with difficult-to-cut alloys, renowned for their exceptional physical and mechanical properties. In response to these challenges, the widespread application of massive coolant in manufacturing industries to dissipate grinding heat has led to complex post-cleaning and disposal processes. This, in turn, has resulted in issues such as large energy consumption, a considerable carbon footprint, and concerns related to worker health and safety, which have become the main factors that restrict the development of grinding technology. This paper provides a holistic review of sustainability in grinding difficult-to-cut alloys, encompassing current trends and future directions. The examination extends to developing grinding technologies explicitly tailored for these alloys, comprehensively evaluating their sustainability performance. Additionally, the exploration delves into innovative sustainable technologies, such as heat pipe/oscillating heat pipe grinding wheels, minimum quantity lubrication, cryogenic cooling, and others. These groundbreaking technologies aim to reduce dependence on hazardous coolants, minimizing energy and resource consumption and carbon emissions associated with coolant-related or subsequent disposal processes. The essence of these technologies lies in their potential to revolutionize traditional grinding practices, presenting environmentally friendly alternatives. Finally, future development trends and research directions are put forward to pursue the current limitation of sustainable grinding for difficult-to-cut alloys. This paper can guide future research and development efforts toward more environmentally friendly grinding operations by understanding the current state of sustainable grinding and identifying emerging trends.
Serum soluble alpha-klotho klotho and cognitive functioning in older adults aged 60 and 79: an analysis of cross-sectional data of the National Health and Nutrition Examination Survey 2011 to 2014
Authors: Ge Song , Dong Fanghong , Tian Chong , Yang Chih-Hsiang , Liu Minhui , Wei Jingkai
Published: March 2024

Objectives

Klotho, consisting of membrane klotho and soluble alpha-klotho, is found to be associated with better cognitive outcomes in small samples of the aged population. We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults.

Method

A total of 2,173 U.S. older adults aged 60–79 years in the National Health and Nutrition Examination Survey from 2011 to 2014 were included in this cross-sectional analysis. Serum soluble alpha-klotho was measured in the laboratory and analyzed with an ELISA kit. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest (CERAD-WL) immediate and delayed memory, the Animal fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on sample means and standard deviations. Multivariable linear regression models were applied to examine the association of quartiles and continuous value of serum soluble alpha-klotho with test-specific and global cognition z-scores. Subgroup analysis was conducted by sex. The following covariates were included in the analysis- age, sex, race/ethnicity, education, depressive symptoms, smoking status, body mass index (BMI), physical activity, stroke, prevalent coronary heart disease, total cholesterol, and systolic blood pressure. All the information was self-reported or obtained from health exams.

Results

Serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (beta [β] =-0.13, 95% confidence interval [CI]: -0.25, -0.01). For subgroup analysis, serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (β=-0.16, 95% CI: -0.32, -0.003) and global cognition (β=-0.14, 95% CI: -0.28, -0.01) among female participants. No association was found between continuous serum soluble alpha-klotho and cognitive functioning among the participants.

Conclusions

Lower serum soluble alpha-klotho quartile was associated with poorer cognitive functioning among older women. Future studies are expected to examine the longitudinal association between klotho levels and cognitive outcomes.
Decreasing incidence of hospital diagnosed CKD/CKDu in North Central Province of Sri Lanka: is it related to provision of drinking water reverse osmosis plants?
Authors: Ranasinghe Asanga Venura , Somatunga Lakshmi C. , Kumara Gardiye Weligamage Gamini Priyantha , Karunarathna Ranamuka Henayage , De Silva Ambepitiyawaduge Pubudu , Gunawardena Jayaprakara Mudiyanselage Chathurik , Kumari Sembu Kuttige Champika Ruwan , Sarjana Mohamed Shali Fathima , De Silva Mannikawadumesthri Vipula Chandu
Published: March 2024

Background

We assessed the possible impact of provision of reverse osmosis (RO) water on the incidence of hospital diagnosed CKD/CKDu in North Central Province (NCP) of Sri Lanka.

Methods

An ecological study was conducted on data from 2010–2020 on the incidence of hospital diagnosed CKD/CKDu, CKD/CKDu screening and provision of drinking water RO plants in NCP. Analysis was conducted using descriptive statistics, ANOVA and chi-square test.

Results

The annual incidence of hospital diagnosed CKD/CKDu (per 100 000 population) in 2010–2013, 2014–2016 and 2017–2020 periods in Anuradhapura district were 129.07, 331.06 and 185.57 (p = 0.002) while in Polonnaruwa district these were 149.29, 326.12 and 296.73 (p = 0.04) respectively. In NCP provision of RO plants commenced after 2011 and the decline in the incidence of hospital diagnosed CKD/CKDu was seen in 25 of the 29 Divisional Secretary Divisions when more than 20% of the families received access to drinking RO water projects.

Conclusions

The annual incidence of hospital diagnosed CKD/CKDu increased in NCP from 2010 to 2016 and continuously decreased thereafter. Continuous declining of CKD/CKDu incidence was seen after more than 20% of the families received access to drinking water RO plants.
Neuropilin-1 and placental growth factor as prognostic factors in metastatic breast cancer
Authors: Mäenpää Niina , Tiainen Leena , Hämäläinen Mari , Luukkaala Tiina , Tanner Minna , Lahdenperä Outi , Vihinen Pia , Karihtala Peeter , Kellokumpu-Lehtinen Pirkko-Liisa , Moilanen Eeva , Jukkola Arja
Published: March 2024

Background

Angiogenesis is crucial for tumor development, progression, and metastasizing. The most important regulator of angiogenesis is the vascular endothelial growth factor (VEGF) family, which is involved in multiple pathways in tumor microenvironment. The objective of this study was to investigate the prognostic value of the VEGF family in patients treated for metastatic breast cancer. The emphasis was on neuropilin-1 (NRP-1) and placental growth factor (PlGF).

Materials and methods

An analysis of eight members of the VEGF family was performed using baseline plasma samples of 65 patients treated for metastatic HER2 negative breast cancer in a phase II first-line bevacizumab plus chemotherapy trial. The patients were divided into two groups, high or low, according to the median for each VEGF family member. Progression-free survival (PFS) and overall survival (OS) were determined for each VEGF family member.

Results

The patients with low plasma levels of NRP-1 and PlGF had a longer OS than those with high plasma levels [multivariable adjusted hazard ratios (HRs) 2.54 (95% confidence interval (CI) 1.11–5.82, p = 0.02) and 3.11 (95% CI 1.30–7.47, p = 0.01), respectively]. The patients with low levels of both NRP-1 and PlGF had a remarkably long OS with HR of 6.24, (95% CI 1.97–19.76, p = 0.002). In addition, high baseline NRP-1 level was associated with a significantly shorter PFS [multivariable adjusted HR 2.90 (95% CI 1.02–8.28, p = 0.04)] than that in the low-level group, and a high baseline vascular endothelial growth factor receptor-2 level was associated with a longer PFS [multivariable adjusted HR 0.43 (95% CI 0.19–0.98, p = 0.04)].

Conclusion

Especially NRP-1 and PlGF have prognostic potential in metastatic breast cancer patients treated with a bevacizumab-taxane combination. Patients with low plasma levels of NRP-1 or PlGF have longer OS than patients with high levels. Patients with both low NRP-1 and PlGF levels appear to have excellent long-term survival.

Trial registration

ClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008.
The impact of a regionally based translational cancer research collaborative in Australia using the FAIT methodology
Authors: Paul Christine L. , Verrills Nicole M. , Ackland Stephen , Scott Rodney , Goode Susan , Thomas Ann , Lukeman Sarah , Nielsen Sarah , Weidenhofer Judith , Lynam James , Fradgley Elizabeth A. , Martin Jarad , Greer Peter , Smith Stephen , Griffin Cassandra , Avery-Kiejda Kelly A. , Zdenkowski Nick , Searles Andrew , Ramanathan Shanthi
Published: March 2024

Background

Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type.

Method

The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches.

Results

In addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world’s first real-time patient treatment verification system (Watchdog); (vi) inventing the effective ‘EAT’ psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research.

Conclusion

Using FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.
Exploring cross-boundary collaboration for youth mental health in Sweden – a qualitative study using the integrative framework for collaborative governance
Authors: Richter Sundberg Linda , Gotfredsen Anne , Christianson Monica , Wiklund Maria , Hurtig Anna-Karin , Goicolea Isabel
Published: March 2024

Background

Youth mental health is a major health concern in almost every country. Mental health accounts for about 13% of the global burden of disease in the 10-to-19-year age group. Still there are significant gaps between the mental health needs of young people and the quality and accessibility of available services. Collaboration between health and social service actors is a recognized way of reducing gaps in quality and access. Yet there is little scientific evidence on how these collaborations are applied, or on the challenges of cross-boundary collaboration in the youth mental health space. This study aims to explore how collaboration is understood and practiced by professionals working in the Swedish youth mental health system.

Methods

We conducted 42 interviews (November 2020 to March 2022) with health and social care professionals and managers in the youth mental health system in Sweden. Interviews explored participants’ experience and understanding of the purpose, realization, and challenges of collaboration. Data were analysed under an emergent study design using reflexive thematic analysis.

Results

The analysis produced three themes. The first shows that collaboration is considered as essential and important, and that it serves diverse purposes and holds multiple meanings in relation to professionals’ roles and responsibilities. The second addresses the different layers of collaboration, in relation to activities, relationships, and target levels, and the third captures the challenges and criticisms in collaborating across the youth mental health landscape, but also in growing possibilities for future development.

Conclusion

We conclude that collaboration serves multiple purposes and takes many shapes in the Swedish youth mental health system. Despite the many challenges, participants saw potential in further building collaboration. Interestingly our participants also raised concerns about too much collaboration. There was scepticism about collaboration directing attention away from young people to the professionals, thereby risking the trust and confidentiality of their young clients. Collaboration is not a panacea and will not compensate for an under-resourced youth mental health system.
Gap analysis of diabetes-related foot disease management systems in Pacific Islands Countries and Territories
Authors: Hon Kay Y. , McMillan Neil , Fitridge Robert A.
Published: March 2024

Background

Pacific Island Countries and Territories (PICTs) are known to have high prevalence of Diabetes Mellitus and high incidence of diabetes-related foot disease. Diabetes-related foot disease can lead to lower limb amputation and is associated with poor outcomes, with increased morbidity and mortality. The purpose of this study was to gain a better understanding of diabetes-related foot disease management in selected countries in PICTs and to identify potential barriers in management of diabetes-related foot disease management in the region.

Methods

A cross-sectional survey was sent to eleven hospitals across six selected PICTs. The survey instrument was designed to provide an overview of diabetes-related foot disease (number of admissions, and number of lower limb amputations over 12 months) and to identify clinical services available within each institution. Two open-ended questions (free text responses) were included in the instrument to explore initiatives that have helped to improve management and treatment of diabetes-related foot diseases, as well as obstacles that clinicians have encountered in management of diabetes-related foot disease. The survey was conducted over 6 weeks.

Results

Seven hospitals across four countries provided responses. Number of admissions and amputations related to diabetes-related foot disease were only reported as an estimate by clinicians. Diabetes-related foot disease was managed primarily by general medicine physician, general surgeon and/or orthopaedic surgeon in the hospitals surveyed, as there were no subspecialty services in the region. Only one hospital had access to outpatient podiatry. Common themes identified around barriers faced in management of diabetes-related foot disease by clinicians were broadly centred around resource availability, awareness and education, and professional development.

Conclusion

Despite the high prevalence of diabetes-related foot disease within PICTs, there appears to be a lack of functional multi-disciplinary foot services (MDFs). To improve the outcomes for diabetes-related foot disease patients in the region, there is a need to establish functional MDFs and engage international stakeholders to provide ongoing supports in the form of education, mentoring, as well as physical resources.
Equity in family planning policies and programs in Uganda: conceptualization, dimensions and implementation constraints
Authors: Namuhani Noel , Wanyenze Rhoda K. , Kiwanuka Suzanne N. , Matovu Joseph K. B. , Makumbi Fredrick E.
Published: March 2024

Background

Equity is at the core and a fundamental principle of achieving the family planning (FP) 2030 Agenda. However, the conceptualization, definition, and measurement of equity remain inconsistent and unclear in many FP programs and policies. This paper aims to document the conceptualization, dimensions and implementation constraints of equity in FP policies and programs in Uganda.

Methods

A review of Ugandan literature and key informant interviews with 25 key stakeholders on equity in FP was undertaken between April and July 2020. We searched Google, Google Scholar and PubMed for published and grey literature from Uganda on equity in FP. A total of 112 documents were identified, 25 met the inclusion criteria and were reviewed. Data from the selected documents were extracted into a Google master matrix in MS Excel. Data analysis was done across the thematic areas by collating similar information. Data were analyzed using thematic content analysis approach.

Results

A limited number of documents had an explicit definition of equity, which varied across documents and stakeholders. The definitions revolved around universal access to FP information and services. There was a limited focus on equity in FP programs in Uganda. The dimensions most commonly used to assess equity were either geographical location, or socio-demographics, or wealth quintile. Almost all the key informants noted that equity is a very important element, which needs to be part of FP programming. However, implementation constraints (e.g. lack of quality comprehensive FP services, duplicated FP programs and a generic design of FP programs with limited targeting of the underserved populations) continue to hinder effective implementation of equitable FP programs in Uganda. Clients’ constraints (e.g. limited contraceptive information) and policy constraints (inadequate focus on equity in policy documents) also remain key challenges.

Conclusions

There is lack of a common understanding and definition of equity in FP programs in Uganda. There is need to build consensus on the definitions and measurements of equity with a multidimensional lens to inform clear policy and programming focus on equity in FP programs and outcomes. To improve equitable access to and use of FP services, attention must be paid to addressing implementation, client and policy constraints.
The construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments
Authors: Chen Tao , Deng Jieyi , Zhang Yongli , Liu Bingfeng , Liu Ruxin , Zhu Yiqiang , Zhou Mo , Lin Yingtong , Xia Baijin , Lin Keming , Ma Xiancai , Zhang Hui
Published: March 2024

Background

Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank.

Methods

Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells. For this purpose, we initially screened healthy donors and cultured their T cells to obtain a higher proportion of stem cell-like memory T (TSCM) cells, which exhibit robust self-renewal capacity, sustainability and cytotoxicity. To reduce the alloreactivity, the T cells were further edited by double knockout of the T cell receptor (TCR) and class I human leukocyte antigen (HLA-I) genes utilizing the CRISPR/Cas9 system. The well-growing and genetically stable universal cells carrying the CAR-moiety were then stored as a stable and unified cell bank. Subsequently, the SDcatcher/GVoptiTag system, which generate an isopeptide bond, was used to covalently connect the purified scFvs of antibody targeting different antigens to the recovered CAR-T cells.

Results

The resulting CAR-T cells can perform different functions by specifically targeting various cells, such as the eradication of human immunodeficiency virus type 1 (HIV-1)-latenly-infected cells or elimination of T lymphoma cells, with similar efficiency as the traditional CAR-T cells did.

Conclusion

Taken together, our strategy allows the production of CAR-T cells more modularization, and makes the quality control and pharmaceutic manufacture of CAR-T cells more feasible.
Metastatic melanoma to small bowel: metastasectomy is supported in the era of immunotherapy and checkpoint inhibitors
Authors: Wong Paul , Wisneski Andrew D. , Tsai Katy K. , Chang Tammy T. , Hirose Kenzo , Nakakura Eric K. , Daud Adil I. , Maker Ajay V. , Corvera Carlos U.
Published: March 2024

Background

Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy.

Case Presentation

We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free.

Conclusions

This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.
Plasma oligomer beta-amyloid is associated with disease severity and cerebral amyloid deposition in Alzheimer’s disease spectrum
Authors: Wang Sheng-Min , Kang Dong Woo , Um Yoo Hyun , Kim Sunghwan , Lee Chang Uk , Scheltens Philip , Lim Hyun Kook
Published: March 2024

Background

Multimer detection system-oligomeric amyloid-β (MDS-OAβ) is a measure of plasma OAβ, which is associated with Alzheimer’s disease (AD) pathology. However, the relationship between MDS-OAβ and disease severity of AD is not clear. We aimed to investigate MDS-OAβ levels in different stages of AD and analyze the association between MDS-OAβ and cerebral Aβ deposition, cognitive function, and cortical thickness in subjects within the AD continuum.

Methods

In this cross-sectional study, we analyzed a total 126 participants who underwent plasma MDS-OAβ, structural magnetic resonance image of brain, and neurocognitive measures using Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease, and cerebral Aβ deposition or amyloid positron emission tomography (A-PET) assessed by [18F] flutemetamol PET. Subjects were divided into 4 groups: N = 39 for normal control (NC), N = 31 for A-PET-negative mild cognitive impairment (MCI) patients, N = 30 for A-PET-positive MCI patients, and N = 22 for AD dementia patients. The severity of cerebral Aβ deposition was expressed as standard uptake value ratio (SUVR).

Results

Compared to the NC (0.803 ± 0.27), MDS-OAβ level was higher in the A-PET-negative MCI group (0.946 ± 0.137) and highest in the A-PET-positive MCI group (1.07 ± 0.17). MDS-OAβ level in the AD dementia group was higher than in the NC, but it fell to that of the A-PET-negative MCI group level (0.958 ± 0.103). There were negative associations between MDS-OAβ and cognitive function and both global and regional cerebral Aβ deposition (SUVR). Cortical thickness of the left fusiform gyrus showed a negative association with MDS-OAβ when we excluded the AD dementia group.

Conclusions

These findings suggest that MDS-OAβ is not only associated with neurocognitive staging, but also with cerebral Aβ burden in patients along the AD continuum.
Left atrial myxoma with cardiogenic shock following a myocardial infarction: a case report
Authors: Lancaster Ian , Hrobowski-Blackman Tara , Patel Deep , Chatoor Lubna , Simon Joshini , Willinger Andrew
Published: March 2024

Background

Myxomas are the most common primary cardiac tumor and typically originate in the left atrium. Atrial myxomas may present following complications of obstruction and emboli. If an atrial myxoma goes untreated, complications such as congestive heart failure, embolic stroke, and sudden death can occur.

Case presentation

A 58-year-old Caucasian male presented following a cardiac arrest. He was taken emergently to the cardiac catheterization lab and received two drug eluting stents. Following the procedure, he was found to have a left atrial mass that was intermittently obstructing the mitral valve on echocardiography. After leaving the cardiac catheterization lab, he was hypotensive and placed on multiple intravenous medications for hemodynamic support as well as an Impella device. Following medical optimization, he underwent one vessel coronary artery bypass graft as well as surgical excision of the left atrial mass, which pathology had shown to be an atrial myxoma.

Conclusion

This patient’s case of cardiogenic shock following revascularization was complicated by the identification of an atrial myxoma, which, when large enough, can obstruct blood flow through the mitral valve leading to acute mitral dynamic stenosis. This condition results in circulatory collapse due to obstruction of the left ventricle in diastole as the myxoma occludes the mitral valve.
Volatile organic compounds emitted by Megaplatypus mutatus associated fungi: chemical identification and temperature-modulated responses by the ambrosial beetle
Authors: Ceriani-Nakamurakare Esteban D. , Slodowicz Mariel , Carmarán Cecilia , Gonzalez-Audino Paola
Published: March 2024

Background

In ambrosia and bark beetles–fungi interaction, volatile organic compounds (VOCs) play a central role in mediating various aspects of community dynamics of beetles and/or fungi. These functions include facilitating beetle habitat location, mate identification, and fungal partner differentiation. However, the understanding on this context remains limited, especially in the globally distributed subfamily Platypodinae, which comprises predominantly ambrosia beetles. There is a lack of chemical data on ambrosia fungi from native South American species. This study addresses this gap by characterizing VOCs from twelve fungal species associated with Megaplatypusmutatus and assessing species-specific behavioral responses during dispersal.

Methods

Fungal VOCs were collected by gas chromatography–mass spectrometry combined with solid-phase microextraction and Y-olfactometry assays of males and females were performed at dispersal stage. Statistical analyses involved: non-metric multidimensional scaling multivariate plot and PERMANOVA test, a cluster analysis through unweighted pair group method with Jaccard index, and finally, a chi-square goodness-of-fit test for beetle behavioral assays.

Results

We identified 72 VOCs from the fungal species isolated from M.mutatus galleries, exocuticle, and gut. The olfactory behavior of M.mutatus demonstrated its capacity to discriminate between volatile profiles, showing a preference for either the fungus or the control source. Our results also enhance the understanding in a chemotaxonomic context and in the behavioral responses of M.mutatus revealing the beetle's remarkable low temperature tolerance and its capability to maintain mobility and orientation toward volatile sources even after zero-degree Celsius exposure.

Conclusion

This study presents a comprehensive insight into fungal VOC profiles, emphasizing the sources of isolation within pest associated fungi, as well as its symbiotic species from the Raffaelea genus. In conclusion, our findings suggest that Megaplatypusmutatus exhibits a general aversion to its fungal VOCs symbiont. However, a notable exception arises when the beetles are pre-exposed for 48 h to freezing conditions, highlighting the beetles' ability to withstand freezing conditions as adults and to exhibit altered responses to their fungal associates under these circumstances.