bluuebunny/crossref_metadata_2025_split huggingface dataset:
The key role of TDP-43 in amyotrophic lateral sclerosis propagation and the disease-modifying profile of CK-1 inhibitors
Authors: Cuevas Eva P. , Martinez-Gonzalez Loreto , Gordillo Clara , Tosat Carlota , Lastra Carmen Pérez de la , Sáenz Amets , Gil Carmen , Palomo Valle , Martin-Requero Angeles , Martinez Ana 
Published: September 2023

Abstract
Background
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease without any cure nor effective treatment to reverse its progression. The main hallmark of the disease is the nuclear protein TDP-43. It suffers different post-translational modifications leading to a lack of function in the nucleus and gain of toxicity in the cytoplasm. Previous reports indicated that pathogenic TDP-43 shows prion-like propagation in several different settings. With the aim of advancing therapeutics focused on the prevention of the propagation of TDP-43 pathology, we here study the potential role of pathogenic TDP-43 in immortalized lymphocytes from sporadic ALS patients
Methods
We used lymphoblastoid cell lines from sporadic ALS patients as source of pathogenic forms of TDP-43, and healthy cells (lymphoblasts, myoblasts or human neuroblastoma SH-SY5Y or osteosarcoma U2OS cell lines) as recipient cells to first investigate the seeding and spread of the TDP-43 proteinopathy. Furthermore, we have evaluated the potential of targeting TDP-43 phosphorylation by CK-1 inhibitors in preventing the propagation of the pathology.
Results
The results herein presented indicate that pathogenic TDP-43 forms are secreted to the extracellular medium of sporadic ALS lymphoblasts and could be transported by extracellular vesicles spreading TDP-43 pathology to healthy cells. Moreover, tunnelling nanotubes (TNTs) have been also discovered in sick cells transporting TDP-43 between the cells. Interestingly, targeting TDP-43 phosphorylation by an in-house designed benzothiazole-based CK-1 inhibitor, namely IGS2.7, was enough to stop cell-to-cell transmission in addition to its known effects on restoring phosphorylation levels, mislocalization and functionality of TDP-43 protein in patients-derived cells.
Conclusions
Our data show the key role of TDP-43 in cell-to-cell disease propagation in sporadic ALS lymphoblasts model and the relevant therapeutic role of CK-1 inhibitors, specifically the small heterocyclic molecule called IGS2.7, not only in restore the functional homeostasis of TDP-43 but also in avoiding the disease transmission. These outstanding data merits the translation of this small molecule to the clinical setting where all these results may be confirmed.
Zinc oxide nanoparticles exacerbate skin epithelial cell damage by upregulating the NLRP3 inflammasome and exosome secretion in M1 macrophages after UVB irradiation-induced skin injury
Authors: W Bour-Jr , Chen Yu-Ying , Chang Hui-Hsuan , Chen Rong-Jane , Wang Ying-Jan , Lee Yu-Hsuan 
Published: September 2023

Abstract
Background:
Zinc oxide nanoparticles (ZnONPs) are common materials used in skin-related cosmetics and sunscreen products due to their whitening and strong UV light absorption properties. Although the protective effects of ZnONPs against UV light in intact skin have been well demonstrated, the effects of using ZnONPs on damaged or sunburned skin are still unclear. In this study, we aimed to reveal the detailed underlying mechanisms related to keratinocytes and macrophages exposed to UVB and ZnONPs.
Results:
We demonstrated that ZnONPs exacerbated mouse skin damage after UVB exposure, followed by increased transepidermal water loss (TEWL) levels, cell death and epithelial thickness. In addition, ZnONPs could penetrate through the damaged epithelium, gain access to the dermis cells, and lead to severe inflammation by activation of M1 macrophage. Mechanistic studies indicated that co-exposure of keratinocytes to UVB and ZnONPs lysosomal impairment and autophagy dysfunction, which increased cell exosome release.However, these exosomes could be taken up by macrophages, which accelerated M1 macrophage polarization. Furthermore, ZnONPs also induced a lasting inflammatory response in M1 macrophages and affected epithelial cell repair by regulating the autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion.
Conclusions:
Our findings propose a new concept for ZnONP-induced skin toxicity mechanismsand the safety issue of ZnONPs application on vulnerable skin. The process involved an interplay of lysosomal impairment, autophagy-mediated NLRP3 inflammasome and macrophage exosome secretion. The current finding is valuable for evaluating the effects of ZnONPs for cosmetics applications.
Key informants perspectives on creating a high impact research department in family and community medicine: a qualitative project
Authors: Gayapersad Allison , O’Brien Mary Ann , Meaney Christopher , Aditya Ishan , Baxter Julia , Selby Peter 
Published: September 2023

Abstract
Background
Primary care is integral to the health system and population health. Primary care research is still in development and most academic programs lack effective research investments. High impact primary care research programs are needed to advance the field to ensure a robust primary care system for the future. The project objective was to understand key informants’ views of structures, functions, and processes required to create a high impact research program in an academic primary care department.
Methods
A descriptive qualitative project with key informants from research programs in primary care. Participants included international research leaders in primary care (n = 10), department of family and community researchers (n = 37) and staff (n = 9) in an academic primary care department, other university leaders (n = 3) and members of the departmental executive leadership team (1 department; 25 members). Semi-structured interviews (n = 27), and focus groups (n = 6) were audio recorded, transcribed, and analyzed using thematic analysis. We used a socioecological framework which described macro, meso, micro levels of influence.
Results
At the micro level despite barriers with respect to funding, protected time and lack of formal mentorship, personal motivation was a key factor. At the meso level, the organizational structure that promoted collaboration and a sense of connection emerged as a key factor. Specifically research leaders identified a research faculty development pipeline based on equity, diversity, inclusion, indigeneity, and accessibility principles with thematic areas of focus as key enablers. Lastly, at the macro level, an overarching culture and policies that promoted funding and primary care research was associated with high impact programs.
Conclusion
The alignment/complementarity of micro, meso, and macro level factors influenced the creation of a high impact research department in primary care. High impact research in primary care is facilitated by the development of researchers through formalized and structured mentorship/sponsorship and a department culture that promote primary care research.
“I'm a failure again I can't do it”: Attitudes towards, and experiences of, exercise participation in adults with class III obesity
Authors: Orange Samuel , Roebuck Jessica , Marshall Phil , Madden Leigh , Vince Rebecca , Bell Beth 
Published: September 2023

AbstractBackground Exercise is first-line treatment for class III obesity. However, living within a larger body brings unique and non-trivial challenges to exercise participation, which are not well understood. This qualitative study explored the attitudes towards, and experiences of, exercise participation in adults with class III obesity. Methods We recruited 30 adults with class III obesity (mean ± SD: age: 45.0 ± 12.5 years; body mass index: 45.8 ± 8.6 kg/m2) who were participating in a 6-month home-based aerobic and resistance exercise intervention. Participants took part in semi-structured interviews after they completed the first 3-months of the intervention. Open-ended questions were used flexibly to explore their experiences of exercise participation, encompassing perceived barriers, motivations, preferences, and benefits of exercise. Interview transcripts were analysed using reflexive thematic analysis. Results Three themes were developed that encapsulate participants’ views and experiences of exercise participation: (1) a web of barriers; (2) tailored exercise facilitates positive experiences; (3) a desire to live well. People with class III obesity have a strong perception that they are unable to do exercise; a view that is attributed to a lifetime of perceived judgement by others, restrictions in mobility, pain during every day activities, and failed weight loss attempts. These complex physical and psychosocial barriers to exercise were described as contributing to exercise avoidance. High value is placed on tailored exercise that accommodates for the unique needs of moving in a larger body. A desire to live a normal life and be free to carry out basic activities of daily living underpins motivations for exercise. Conclusions Our findings suggest that multicomponent obesity interventions should move away from generic exercise prescriptions designed to maximise energy expenditure, and instead move towards addressing the unique physical and psychosocial needs of people who have class III obesity with tailored, person-centred, and weight-neutral exercise interventions.
Health service provider views on measuring patient involvement in healthcare: an interview study with researchers, clinicians, managers, and policymakers
Authors: Toft Bente Skovsby , Ellegaard Trine , Nielsen Berit Kjærside , Rossen Camilla Blach , Hørlück Jens Thusgaard , Ludvigsen Mette Spliid , Bekker Hilary Louise , Rodkjær Lotte Ørneborg 
Published: September 2023

Abstract

Background Strategies aimed at promoting patient involvement vary in purpose across different healthcare settings and are assessed using a wide range of outcomes. However, there is no consensus on the most appropriate measurement tools or ways to evaluate patient involvement initiatives.
This qualitative study aimed to explore the perspectives of stakeholders from micro, meso, and macro levels within the Danish healthcare system on patient involvement and its measurement.
MethodsThis descriptive, explorative study employed semi-structured interviews with open-ended questions to elicit participants’ views and experiences of patient involvement and measurement tools. A purposeful sample of participants was identified, to include decision makers, researchers, and health professionals (n=20) with experiences of patient involvement in healthcare at micro, meso, and macro levels across Danish organizations. Data underwent reflexive thematic analysis.
Results Three main themes were identified: 1) Determining the purpose of patient involvement and measurement alignment; 2) Reflecting on the qualities, fit, and usefulness of measures; 3) Recognizing conflicting stakeholder paradigms. Despite the interest in and positive attitudes toward patient involvement, views on the meaning and value of evaluating involvement and innovating varied; in part, this was attributable to challenges in selecting criteria, methods, and measures for evaluation.
Conclusion The findings indicate the need to integrate the perspectives of all key stakeholders in designing the evaluation of patient involvement initiatives. The application of a multiple stakeholder approach and co-production of a multidimensional evaluation may provide some common ground for selecting evaluation criteria and measurement tools in the healthcare setting.
Trial registration Danish Data Protection Agency (1-16-02-400-21) 15 October 2021.
International Journal of Information Security: A Bibliometric Study, 2007-2023
Authors: Dwivedi Rahul 
Published: September 2023

Abstract
This study employs various bibliometric analysis techniques to examine the intellectual structure of the International Journal of Information Security from 2007 to 2023. The aim is to identify the most cited journals, underlying research themes within the article corpus, and gradual changes in the research themes over time. “Lecture Notes on Computer Science” is the most referenced knowledge source. In addition, articles on the theme of encryption techniques received the highest average citations, followed by key management and authentication protocols. Moreover, machine learning, blockchain, and the Internet of Things are emerging topics of interest among published authors in the International Journal of Information Security. Qualitative and quantitative comparisons between open-access and regular articles suggested a few notable differences in author keywords but no differences in the number of citations received. Furthermore, regression analysis found a negative correlation between citation counts with the length of the article abstract and article title and a positive correlation with page count, being published in a special issue, and if at least the affiliation of one of the authors is different from others. Finally, we also identified prominent authors, articles, institutions, and countries published in this journal.
Are Deaf College Students More Sensitive to Unfair Information？
Authors: Du Xue , Gong Yuqi , Chen Xiaoyi , Jiang Jun 
Published: September 2023

Abstract
To investigate whether fairness decision among deaf college students is the sameto the normal hearing college students, we recorded event-related potentials (ERPs) to examine how the brain affected when the deaf college students perform the ultimatum gaming task.
For the behavioral outcomes, a main effect of proposal type was found for both deaf and normal hearing college students, the more unfair of the offer, the lower of acceptance rate have, which indicated that the deaf college students have the same unfairness aversion and fair decision-making as normal hearing college students at the behavioral level.
The ERPs results revealed there was a significant interaction between group and proposal type at the early stage (N1). Interestingly, only in the deaf college group, the mean wave amplitude of N1 induced by moderately and very unfair offers were significantly greater than that of fair offers. In addition, we found that the deaf college students had smaller amplitudes on P2 and P3 than normal hearing college students, which showed the deaf college students are more strongly motivated to be fair. Based on these, we should provide more fairness information and attention to the mental health of the deaf people.
Akkermansia muciniphila may mediate the association between prenatal metal mixture exposure and childhood depressive symptoms
Authors: Nagdeo Kiran , Midya Vishal , Lane Jamil M. , Torres-Olascoaga Libni A. , Martínez Gabriela Gil , Horton Megan K. , Gennings Chris , Téllez-Rojo Martha Maria , Wright Robert O. , Arora Manish , Eggers Shoshannah 
Published: September 2023

Abstract
Background: Prenatal metal exposure may be associated with childhood depressive symptoms. Emerging research suggests links between gut microbiome (GM) disruptions and depressive disorders. Akkermansia muciniphila, a GM bacteria, has been studied for its potential antidepressant effects. However, its role in mediating the association between prenatal metal exposures and depressive symptoms in later childhood is not known. We aim to estimate the associations between prenatal mixed metal exposures, A. mucinipnila presence in the gut microbiome at 9-11 years old, and concurrent depressive symptoms.
Methods: We leverage existing data from a subset of 112 participants in the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort. Metal concentrations (Pb, As, Cd, Cr, Zn, Se, Sb, Cu, Cs, Co, Mn) were measured in 2nd and 3rd trimester maternal whole blood. Stool samples were collected at 9–11 years of age and underwent metagenomic sequencing to assess the GM. The presence of A. muciniphila was detected using GM data. Children’s Depression Inventory (CDI) was administered at 9-11 years. We used weighted quantile sum (WQS) regression to separately estimate associations between prenatal metal mixture exposure at 2nd and 3rd trimesters and CDI. We used a nonparametric bootstrap approach to estimate the proportion of these associations mediated by A. muciniphila.
Results: A. muciniphila was detected in 24% of participants. The presence of A. muciniphila was associated with a significantly decreased log-transformed, t-score normalized CDI score (log tCDI) (ß=-0.13, 95%CI=[-0.21,-0.04]), suggesting a protective effect. Second and 3rd-trimester metal mixtures were associated with increased log tCDI (ß=0.06 per increase in quartile, 95%CI=[0.01,0.10] and ß=0.03 per increase in quartile, 95%CI=[-0.02,0.09], respectively). A quartile increase in these metal mixtures trended towards decreased odds of A. muciniphila (OR=0.54, 95%CI=[0.23,1.24] and OR=0.58, 95%CI=[0.23,1.49] at 2nd and 3rd trimesters respectively). The presence of A. muciniphila may mediate the association between the 2nd-trimester metal mixture and log tCDI by 34%.
Conclusion: We found suggestive evidence that A. muciniphila may attenuate the association between prenatal metal exposures and childhood depressive symptoms. A. muciniphila supplementation may be a promising intervention strategy to mitigate metal-associated depressive symptoms. Additional studies are needed to confirm these findings.
Association of ITGA2 Dual Site Variants with Recurrent Ischemic Events in Patients Undergoing Stenting for Symptomatic Intracranial Atherosclerotic StenosisAuthor list
Authors: Dong Yiwen , Ye Jiadan , Cheng Sheng , Yang Hongge , Li Ze , Di Xuan , Lou Xin , Li Xingang , Ma Ning 
Published: September 2023

Abstract
Objective
We aimed to investigate the relationship between gene polymorphisms and the occurrence of adverse clinical events following dual antiplatelet therapy in Patients with Symptomatic Intracranial Atherosclerotic Stenosis.
Methods
A total of 195 patients were enrolled, categorized into 32 cases (those with clinical adverse events) and 163 controls (without events). Genotyping of 20 SNPs from 17 genes was executed. Statistical analyses (Fisher’s exact test, logistic regression) were applied to determine associations.
Results
The ITGA2 rs1126643 (C807T) and rs1062535 (G873A) polymorphisms were significantly correlated with adverse clinical events. Specifically, the mutant frequency of allele C (ITGA2 rs1126643) and allele G (ITGA2 rs1062535) was significantly higher in cases compared to controls (OR = 2.97, 95%CI = 1.702–5.172, P = 0.0001; OR = 3.27, 95%CI = 1.762–6.066, P = 0.0002, respectively). Other genotypes showed no significant differences between the groups.
Conclusion
The ITGA2 C807T and G873A polymorphisms may elevate the risk of vascular events in Chinese patients. Detecting these polymorphisms may be valuable in identifying patients at risk of recurrent ischemic events.
xCT as a potential marker for neuroendocrine cells in high-risk prostate cancer and the relation to AL122023.1-miR-26a/30d/30e axis
Authors: Wilhelm Elena D. , Wiesehöfer Marc , Dankert Jaroslaw Thomas , Wach Sven , Wagner Mathias , Spahn Martin , de Julio Marianna Kruithof , Wennemuth Gunther 
Published: September 2023

Abstract
Purpose
Prostate cancer is the second most common type of cancer in male worldwide. Stromal-epithelial interaction is thought to have a major impact on cancer development and progression. Interaction via soluble factors previously revealed a reduction in the expression of xCT and AL122023.1 in prostate carcinoma cells LNCaP after seven days of co-culture with stromal primary p21 cells. Furthermore, xCT is known to be a putative target for miR-26a, miR-30d and miR-30e which in turn potentially interact with the lncRNA AL122023.1.
Methods
We validated the repression of xCT and AL122023.1 at RNA level by quantitative real-time PCR and at protein level by Western Blotting. The lncRNA-miRNA-interaction was analyzed by luciferase reporter assays whereas the localization and distribution of xCT in prostate tissue of different developmental stages was evaluated by immunostaining.
Results
The interaction between AL122023.1 and miR-26a/-30d/-30e was verified and further investigated at protein level regarding xCT. An indirect inhibitory effect of AL122023.1 on the xCT expression could be shown, but miR-26a/-30d/-30e caused no inhibition. Moreover, immunostaining displayed a precise xCT expression in neuroendocrine cells ranging from fetal, healthy juvenile and adult prostate tissue to benign prostatic hyperplasia and finally advanced prostate cancer.
Conclusion
This study explores the relevance and function of xCT and AL122023.1 in the prostate and exposes xCT as a potential marker or therapeutic target in high-risk prostate cancer.
GOIZ ZAINDU trial: a FINGER-like multidomain lifestyle intervention feasibility study to prevent dementia in Southern Europe.
Authors: Tainta Mikel , Ecay-Torres Mirian , de Arriba Maria , Barandiaran Myriam , Otaegui-Arrazola Ane , Iriondo Ane , Garcia-Sebastian Maite , Estanga Ainara , Saldias Jon , Clerigue Montserrat , Gabilondo Alazne , Ros Naia , Mugica Justo , Barandiaran Aitziber , Mangialasche Francesca , Kivipelto Miia , Arrospide Arantzazu , Mar Javier , Martinez-Lage Pablo 
Published: September 2023

Abstract
Background:
GOIZ ZAINDU ("caring early" in Basque) is a pilot study to adapt the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) methodology to the Basque population and evaluate feasibility and adherence to a FINGER-like multidomain intervention program. Additional aims included the assessment of efficacy on cognition and collecting data to design a large efficacy trial.
Method:
GOIZ ZAINDU is a one-year, randomized, controlled trial of a multidomain intervention in persons aged 60+ years, with Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score ≥ 6, no dementia, and below-than-expected performance in at least one of three cognitive screening tests. Randomization to a Multidomain intervention (MD-Int) or Regular Health Advice (RHA) was stratified by sex, age (>/≤ 75), and cognitive status (Mild Cognitive Impairment (MCI)/normal cognition). MD-Int included cardiovascular risk factors control, nutritional counseling, physical activity, and cognitive training. The primary outcome was retention rate and adherence to the intervention program. Exploratory cognitive outcomes included Neuropsychological Test Battery z-scores change. Analyses were carried out by intention to treat.
Results:
One hundred twenty-five participants were recruited (mean age: 75.64 (±6.46); 58% women). MD-Int (n=61) and RHA (n=64) groups were balanced in demographics and cognition. 52 (85%) participants from RHA and 56 (88%) from the MD-Int group completed the study. More than 70% of participants presented good overall adherence to intervention activities. The risk of cognitive decline was higher in the RHA group compared with MD-Int regarding executive function (p=.019) and processing speed scores (p=.026).
Conclusions:
The GOIZ-ZAINDU study has proved that the FINGER methodology is adaptable and feasible in a different socio-cultural environment. Exploratory efficacy results show a lower risk of decline in executive function and processing speed. These results support the design of a large-scale efficacy trial.