bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of symptoms and determinants of disease burden in dementia with Lewy bodies: DEvELOP design and baseline results
Authors: van de Beek M. , van Steenoven I. , van der Zande J. J. , Porcelijn I. , Barkhof F. , Stam C. J. , Raijmakers P. G. H. M. , Scheltens P. , Teunissen C. E. , van der Flier W. M. , Lemstra A. W. 
Published: February 2021

Abstract
Background
The DEmEntia with LEwy bOdies Project (DEvELOP) aims to phenotype patients with dementia with Lewy bodies (DLB) and study the symptoms and biomarkers over time. Here, we describe the design and baseline results of DEvELOP. We investigated the associations between core and suggestive DLB symptoms and different aspects of disease burden, i.e., instrumental activities of daily living (IADL) functioning, quality of life (QoL), and caregiver burden.

Methods
We included 100 DLB patients (69 ± 6 years, 10%F, MMSE 25 ± 3) in the prospective DEvELOP cohort. Patients underwent extensive assessment including MRI, EEG/MEG, 123FP-CIT SPECT, and CSF and blood collection, with annual follow-up. Core (hallucinations, parkinsonism, fluctuations, RBD) and suggestive (autonomous dysfunction, neuropsychiatric symptoms) symptoms were assessed using standardized questionnaires. We used multivariate regression analyses, adjusted for age, sex, and MMSE, to evaluate how symptoms related to the Functional Activities Questionnaire, QoL-AD questionnaire, and Zarit Caregiver Burden Interview.

Results
In our cohort, RBD was the most frequently reported core feature (75%), while visual hallucinations were least frequently reported (39%) and caused minimal distress. Suggestive clinical features were commonly present, of which orthostatic hypotension was most frequently reported (64%). Ninety-five percent of patients showed EEG/MEG abnormalities, 88% of 123FP-CIT SPECT scans were abnormal, and 53% had a CSF Alzheimer’s disease profile. Presence of fluctuations, lower MMSE, parkinsonism, and apathy were associated with higher IADL dependency. Depression, constipation, and lower IADL were associated with lower QoL-AD. Apathy and higher IADL dependency predisposed for higher caregiver burden.

Conclusion
Baseline data of our prospective DLB cohort show clinically relevant associations between symptomatology and disease burden. Cognitive and motor symptoms are related to IADL functioning, while negative neuropsychiatric symptoms and functional dependency are important determinants of QoL and caregiver burden. Follow-up is currently ongoing to address specific gaps in DLB research.
Human umbilical cord-derived mesenchymal stem/stromal cells: a promising candidate for the development of advanced therapy medicinal products
Authors: Mebarki Miryam , Abadie Camille , Larghero Jérôme , Cras Audrey 
Published: February 2021

AbstractUmbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) emerge as a perspective for therapeutic use in immune and inflammatory diseases. Indeed, immunomodulatory and anti-inflammatory properties, associated to fewer ethical, availability, and safety issues, position UC-MSCs as a promising active substance to develop medicinal products. Since 2007, UC-MSC-based products are classified as advanced therapy medicinal products (ATMP) according to the European Regulation 1394/2007/EC. This new regulatory status required a total adaptation of stakeholders wishing to develop UC-MSC-based ATMPs. Cell production in tissue and cell banks has been replaced by the manufacturing of a medicine, in authorized establishments, according to the good manufacturing practices (GMP) specific to ATMPs. After a brief description of UC-MSCs, we described in this review their recent use in a large panel of immune and inflammatory pathologies, including early and late phase clinical trials. Despite the use of the same product, we noticed an important heterogeneity in terms of indication, posology and study design. Then, we discussed regulatory and manufacturing challenges for stakeholders, especially in terms of process harmonization and cells characterization. Our aim was to point that despite MSCs use for several decades, the development of an UC-MSC-based ATMP remains at this day a real challenge for both academic institutions and pharmaceutical companies.
“Top-down bottom-up” estimation of per capita cost of new-born care interventions in four regions of Ghana: beyond implementation to scalability and sustainability
Authors: Alhassan Robert Kaba , Nketiah-Amponsah Edward , Twum-Danso Nana A. Y. , Bawa John , Kwarah Williams , Ucer Sebnem , Ibn Abass Abdul Fatawu 
Published: February 2021

Abstract
Background
Limited financial, human and material health resources coupled with increasing demand for new-born care services require efficiency in health systems to maximize the available sources for improved health outcomes. Making Every Baby Count Initiative (MEBCI) implemented by local and international partners in 2013 in Ghana aimed at attaining neonatal mortality of 21 per 1000 livebirths by 2018 in four administrative regions in Ghana. MEBCI interventions benefited 4027 health providers, out of which 3453 (86%) were clinical healthcare staff.

Objective
Determine the per capita cost of the MEBCI interventions towards enhancing new-born care best practices through capacity trainings for frontline clinical and non-clinical staff.

Methods
Parameters for determining per capita cost of the new-born care interventions were estimated using expenditure on trainings, supervisions, monitoring and evaluation, advocacy, administrative/services and medical logistics. Data collection started in October 2017 and ended in September 2018. Data sources for the per capita cost estimations were invoices, expense reports and ledger books at the national, regional and district levels of the health system.

Results
Total of 4027 healthcare providers benefited from the MEBCI training activities comprising of 3453 clinical staff and 574 non-clinical personnel. Cumulative cost of implementing the MEBCI interventions did not necessarily match the cost per capita in staff capacity building; average cost per capita for all staff (clinical and non-clinical staff) was approximately US$ 982 compared to a per capita cost of US$ 799 for training only core clinical staff. Average cost per capita for all regions was approximately US$ 965 for all staff compared to US$ 777 per capita cost for only clinical staff. Per capita cost of training was relatively lower in regions with more staff than regions with lower numbers, perhaps due to economies of scale.

Conclusion
The MEBCI intervention had a wide coverage in terms of training for frontline healthcare providers albeit the associated cost may be potentially unsustainable for Ghana’s health system. Emerging digital training platforms could be leveraged to reduce per capita cost of training. Large-scale on-site batch-training approach could also be replaced with facility-based workshops using training of trainers (TOTs) approach to promote efficiency.
Dapagliflozin attenuates hypoxia/reoxygenation-caused cardiac dysfunction and oxidative damage through modulation of AMPK
Authors: Tsai Kun-Ling , Hsieh Pei-Ling , Chou Wan-Ching , Cheng Hui-Ching , Huang Yu-Ting , Chan Shih-Hung 
Published: February 2021

Abstract
Background
Emerging evidence demonstrated dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, prevented various cardiovascular events. However, the detailed mechanisms underlying its cardioprotective properties remained largely unknown.

Results
In the present study, we sought to investigate the effects of DAPA on the cardiac ischemia/reperfusion (I/R) injury. Results from in vitro experiments showed that DAPA induced the phosphorylation of AMPK, resulting in the downregulation of PKC in the cardiac myoblast H9c2 cells following hypoxia/reoxygenation (H/R) condition. We demonstrated that DAPA treatment diminished the H/R-elicited oxidative stress via the AMPK/ PKC/ NADPH oxidase pathway. In addition, DAPA prevented the H/R-induced abnormality of PGC-1α expression, mitochondrial membrane potential, and mitochondrial DNA copy number through AMPK/ PKC/ NADPH oxidase signaling. Besides, DAPA reversed the H/R-induced apoptosis. Furthermore, we demonstrated that DAPA improved the I/R-induced cardiac dysfunction by echocardiography and abrogated the I/R-elicited apoptosis in the myocardium of rats. Also, the administration of DAPA mitigated the production of myocardial infarction markers.

Conclusions
In conclusion, our data suggested that DAPA treatment holds the potential to ameliorate the I/R-elicited oxidative stress and the following cardiac apoptosis via modulation of AMPK, which attenuates the cardiac dysfunction caused by I/R injury.
On the fractional p-Laplacian problems
Authors: Choi Q-Heung , Jung Tacksun 
Published: February 2021

AbstractThis paper deals with nonlocal fractionalp-Laplacian problems with difference. We get a theorem which shows existence of a sequence of weak solutions for a family of nonlocal fractionalp-Laplacian problems with difference. We first show that there exists a sequence of weak solutions for these problems on the finite-dimensional subspace. We next show that there exists a limit sequence of a sequence of weak solutions for finite-dimensional problems, and this limit sequence is a sequence of the solutions of our problems. We get this result by the estimate of the energy functional and the compactness property of continuous embedding inclusions between some special spaces.
Cluster randomised controlled feasibility study of HENRY: a community-based intervention aimed at reducing obesity rates in preschool children
Authors: Bryant Maria , Collinson Michelle , Burton Wendy , Stamp Elizabeth , Schofield Holly , Copsey Bethan , Hartley Suzanne , Webb Edward , Farrin Amanda J. 
Published: February 2021

Abstract
Background
Community-based obesity prevention interventions are often commissioned despite the limited evidence base. HENRY (Health, Exercise, Nutrition for the Really Young) is a programme delivered to parents of preschool children across the UK. Early evidence suggests that it may be effective, but a robust evaluation has not been conducted. We initiated a systematic evaluation of HENRY by studying the feasibility of conducting a multi-centre definitive trial to evaluate its effectiveness and cost-effectiveness to prevent obesity. Objectives were to assess the feasibility of recruiting local authorities, centres and parents; test processes and time required to train and certify intervention staff; explore HENRY commissioning processes; identify potential sources (and associated impact) of contamination; and consider the feasibility of trial procedures.

Methods
We conducted a multi-centre, open labelled, two group, prospective, cluster randomised, controlled, feasibility study, with embedded process evaluation and pre-defined criteria for progression to definitive trial. We sought to recruit 120 parents from 12 children’s centres, across two UK local authority (government) areas. Within each local authority, we planned to randomise three centres to HENRY and three to ‘standard care’ control. Our plan was to collect data in family homes at baseline and 12 months, including parent and child height and weight, and parent-reported questionnaires on self-efficacy, feeding, eating habits, quality of life and resource use. Contamination, implementation and study acceptability were explored using parent interviews.

Results
We recruited two local authorities and 12 children’s centres within eight months. One hundred and seventeen parents were recruited (average 3.9 parents per programme) and follow-up data were collected from 85% of participants. Process data from 20 parents and 24 members of staff indicate that both would benefit from more detail about their involvement as participants, but that methods were acceptable. Contamination was likely, though the impact of this on behaviour was unclear.

Conclusion
Our findings indicate that a cluster RCT of HENRY to assess its effect on childhood obesity prevention is feasible. This study has allowed us to design a pragmatic definitive trial with minimal bias, taking account of lessons learnt from conducting evaluation research in public health settings.

Trial registration
ClinicalTrials.gov Identifier NCT03333733 registered 6th November 2017.
British and Japanese international retirement migration and creative responses to health and care challenges: a bricolage perspective
Authors: Hall Kelly , Ono Mayumi , Kohno Ayako 
Published: February 2021

AbstractMost research on international retirement migration has focused on the Western context and the motivations and lifestyle choices of migrants when they are healthy. This paper instead explores how British retirees in Spain and Japanese retirees in Malaysia respond to declining health and increasing care needs through bricolage as they begin to ‘age in place’. The paper combines qualitative interviews, focus groups and observations collected by the authors from 215 British and Japanese international retirement migrants. We focus on two key types of bricolage behaviour: ‘within-system bricolage’ undertaken by migrants to help them access and navigate existing health and care systems; and ‘added-to-system bricolage’ that is enacted to fill gaps in health and care provision. Our analysis suggests that IRMs engage in ‘transnational care bricolage’ by combining multiple economic, social and legal resources across local and transnational spaces to address their health and care needs.
Community-driven citizen science approach to explore cardiovascular disease risk perception, and develop prevention advocacy strategies in sub-Saharan Africa: a programme protocol
Authors: Okop Kufre Joseph , Murphy Kathy , Lambert Estelle Victoria , Kedir Kiya , Getachew Hailemichael , Howe Rawleigh , Niyibizi Jean Berchmans , Ntawuyirushintege Selemani , Bavuma Charlotte , Rulisa Stephen , Kasenda Stephen , Chipeta Effie , Bunn Christopher , Crampin Amelia C. , Chapotera Gertrude , King Abby C. , Banchoff Ann , Winter Sandra J. , Levitt Naomi S. 
Published: February 2021

AbstractBackgroundIn sub-Saharan Africa (SSA), which experiences a disproportionately high cardiovascular disease (CVD) burden, population-based screening and prevention measures are hampered by low levels of knowledge about CVD and associated risk factors, and inaccurate perceptions of severity of risk.MethodsThis protocol describes the planned processes for implementing community-driven participatory research, using a citizen science method to explore CVD risk perceptions and to develop community-specific advocacy and prevention strategies in the rural and urban SSA settings. Multi-disciplinary research teams in four selected African countries will engage with and train community members living in rural and urban communities as citizen scientists to facilitate conceptualization, co-designing of research, data gathering, and co-creation of knowledge that can lead to a shared agenda to support collaborative participation in community-engaged science. The emphasis is on robust community engagement, using mobile technology to support data gathering, participatory learning, and co-creation of knowledge and disease prevention advocacy.DiscussionContextual processes applied and lessons learned in specific settings will support redefining or disassembling boundaries in participatory science to foster effective implementation of sustainable prevention intervention programmes in Low- and Middle-income countries.
Design of PSMA ligands with modifications at the inhibitor part: an approach to reduce the salivary gland uptake of radiolabeled PSMA inhibitors?
Authors: Felber Veronika Barbara , Valentin Manuel Amando , Wester Hans-Jürgen 
Published: February 2021

Abstract
Aim
To investigate whether modifications of prostate-specific membrane antigen (PSMA)-targeted radiolabeled urea-based inhibitors could reduce salivary gland uptake and thus improve tumor-to-salivary gland ratios, several analogs of a high affinity PSMA ligand were synthesized and evaluated in in vitro and in vivo studies.

Methods
Binding motifs were synthesized ‘on-resin’ or, when not practicable, in solution. Peptide chain elongations were performed according to optimized standard protocols via solid-phase peptide synthesis. In vitro experiments were performed using PSMA+ LNCaP cells. In vivo studies as well as μSPECT/CT scans were conducted with male LNCaP tumor xenograft-bearing CB17-SCID mice.

Results
PSMA ligands with A) modifications within the central Zn2+-binding unit, B) proinhibitor motifs and C) substituents & bioisosteres of the P1′-γ-carboxylic acid were synthesized and evaluated. Modifications within the central Zn2+-binding unit of PSMA-10 (Glu-urea-Glu) provided three compounds. Thereof, only natLu-carbamate I (natLu-3) exhibited high affinity (IC50 = 7.1 ± 0.7 nM), but low tumor uptake (5.31 ± 0.94% ID/g, 1 h p.i. and 1.20 ± 0.55% ID/g, 24 h p.i.). All proinhibitor motif-based ligands (three in total) exhibited low binding affinities (> 1 μM), no notable internalization and very low tumor uptake (< 0.50% ID/g). In addition, four compounds with P1′-ɣ-carboxylate substituents were developed and evaluated. Thereof, only tetrazole derivative natLu-11 revealed high affinity (IC50 = 16.4 ± 3.8 nM), but also this inhibitor showed low tumor uptake (3.40 ± 0.63% ID/g, 1 h p.i. and 0.68 ± 0.16% ID/g, 24 h p.i.). Salivary gland uptake in mice remained at an equally low level for all compounds (between 0.02 ± 0.00% ID/g and 0.09 ± 0.03% ID/g), wherefore apparent tumor-to-submandibular gland and tumor-to-parotid gland ratios for the modified peptides were distinctly lower (factor 8–45) than for [177Lu]Lu-PSMA-10 at 24 h p.i.

Conclusions
The investigated compounds could not compete with the in vivo characteristics of the EuE-based PSMA inhibitor [177Lu]Lu-PSMA-10. Although two derivatives (3 and 11) were found to exhibit high affinities towards LNCaP cells, tumor uptake at 24 h p.i. was considerably low, while uptake in salivary glands remained unaffected. Optimization of the established animal model should be envisaged to enable a clear identification of PSMA-targeting radioligands with improved tumor-to-salivary gland ratios in future studies.
What are the key themes associated with the positive learning experience in MOOCs? An empirical investigation of learners’ ratings and reviews
Authors: Deng Ruiqi , Benckendorff Pierre 
Published: February 2021

AbstractPast MOOC research has tended to focus on learning outcomes valued in traditional higher education settings, such as achievement and retention. This study recognises that student ratings are an important alternative outcome measure in MOOCs. This paper adopted a semiautomatic text mining approach to collect and analyse 8475 ratings and reviews submitted for 1794 MOOCs. The analysis revealed six important themes that contributed to positive ratings: ‘learning’, ‘understanding’, ‘interesting’, ‘videos’, ‘recommend’, and ‘questions’. The paper then investigated the characteristics of each identified theme based on the proximity of themes, distribution of concepts within themes, and important connections. Based on research findings, the paper presents the following propositions to assist educators and providers to enhance the learning experience in MOOCs: (1) provide realistic learning contexts and instructional conditions in MOOCs to facilitate the acquisition of knowledge that transfers more readily to real-world practices; (2) carefully design the instructional conditions so that some mental challenge and stimulation is required for learners to achieve a full understanding of the content, rather than making MOOCs too simple or effortless to complete; (3) design the course content, materials, and communications to generate interest; (4) allocate sufficient resources to create high-quality video lectures; (5) employ video lectures to elicit positive emotions from MOOC learners and simplify complex, difficult concepts; and (6) incorporate discussion boards in MOOCs and invest in human and digital resources to address learners’ queries.
Differential expression of viral pathogen-associated molecular pattern receptors mRNA in Egyptian chronic hepatitis C virus patients
Authors: Suef Reda A. , Mohamed Ezz Elden M. , Mansour Mohamed T. M. , Weigand Kilian , Farag Mohamed M. S. 
Published: February 2021

Abstract
Background
One possible mechanism utilized by hepatitis C virus (HCV) to escape from the host’s innate immune surveillance is modification of its pathogen-associated molecular patterns (PAMPs) by altering or hiding its RNA which interfering with toll-like receptors (TLRs) signaling and ultimately hindering the production of proinflammatory cytokines, chemokines, and interferons (IFNs). This study aimed to examine the expression levels of TLR3, TLR7, and IFN-α to investigate the correlated expression pattern among them in chronic HCV patients. Patients included in this study were categorized into two different groups, non-treated chronic HCV patients and treated chronic HCV patients, in addition to healthy volunteers as a control group. The blood samples were assessed for HCVAb, HCVRNA, HCV genotypes, and different biochemical analyses. The mRNA levels of TLR3, TLR7, and IFN-α in peripheral blood of chronic HCV patients were quantitatively measured in comparison to healthy controls.

Results
The expression levels of TLR3, TLR7, and IFN-α were significantly downregulated in non-treated chronic HCV patients compared to both treated HCV patients and control subjects. On the other hand, treated HCV patients showed non-significant downregulation of the same three sensing receptors (TLR3, TLR7, and IFN-α) compared to control group. Obviously, the expression levels of IFN-α were positively correlated with the levels of both TLR3 and TLR7.

Conclusion
The exhausted innate immunity against HCV may correlate to HCV downregulation of TLR3 and TLR7 expression on innate immune cells with a subsequent decrease in INF-α production and the possibility of targeting these receptors to enhance the immune response and clear the infection needs further studies.
Urinary epidermal growth factor as a marker for lupus nephritis: clinical, laboratory, and histopathological study
Authors: Hefny Hesham M. , Abualfadl Esam M. , Youssef Emad A. M. , Ismail Mohamed Ali , Soliman Tamer M. , Ahmed Ahmed Roshdi Hamed , Abozaid Hanan S. M. 
Published: February 2021

Abstract
Background
Lupus nephritis can be seen in up to 60% of all SLE patients with 10–15% of nephritis patients progressing to end-stage renal disease; late diagnosis of lupus nephritis is correlated with a higher frequency of renal insufficiency. The study aim is determination of the value of urinary human epidermal growth factor (urinary EGF) as an early biomarker of lupus nephritis in SLE patients and its relevance to disease activity and renal histopathology.

Results
The study included 58 SLE patients and 30 healthy controls; a significant difference was noticed between SLE and controls in urinary protein, creatinine, protein/creatinine ratio, and urinary EGF. The mean level of urinary EGF was less in classes IV and V renal nephritis than in classes I, II, and III.
There is a significant difference in urinary EGF (33±29, 27±16, P = 0.04) between class II and class III lupus nephritis, with no significant differences in urinary protein, creatinine, protein/creatinine ratio, and SLEDAI. On the other hand, the comparison between classes II and IV showed significant difference not only in urinary EGF (33±29, 11.7±4.9 m, P=0.003), but also in SLEDAI (37.4±8, 70.5±27, P= 0.007), and protein/creatinine ratio (0.98±0.62, 3±1.8, P=0.006).

Conclusion
This study raises the attention to test the sensitivity of urinary EGF in detecting the early and the subsequent changes in renal pathology of SLE patients as an easy, non-invasive, accurate, cheap marker that could help in following up the nephritis progression and adjusting the plan of treatment; also, it can be used to guide the time of biopsy or as an alternative in cases where renal biopsy is contraindicated.