bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.