bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolated optic neuritis with positive glial fibrillary acidic protein antibody
Authors: Jia Nan , Wang Jiawei , He Yuhong , Li Zhong , Lai Chuntao 
Published: April 2023

Abstract
Background and objectives
Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) has been reported as a spectrum of autoimmune, inflammatory central nervous system disorders. Linear perivascular radial gadolinium enhancement patterns on brain magnetic resonance imaging (MRI) are a hallmark of these disorders. GFAP-A is associated with cerebrospinal fluid (CSF) GFAP antibody (GFAP-Ab), while the association with serum GFAP-Ab is less clear. This study aimed to observe the clinical characteristic and MRI changes of GFAP-Ab-positive optic neuritis (ON).

Methods
We performed a retrospective, observational case study at the department of neurology, Beijing Tongren Hospital, from December 2020 to December 2021. The serum of 43 patients and CSF samples of 38 patients with ON were tested for GFAP-Ab by cell-based indirect immune-fluorescence test.

Results
Four patients (9.3%) were detected GFAP-Ab positive, and in three out of the four patients, GFAP-Abs were detected only in serum. All of them demonstrated unilateral optic neuritis. Three patients (1, 2, and 4) experienced severe visual loss (best corrected visual acuity ≤ 0.1). Two patients (2 and 4) had experienced more than one episode of ON at the time of sampling. MRI showed optic nerve hyperintensity on T2 FLAIR images in all GFAP-Ab positive patients, and orbital section involvement was the most common. During follow-up (mean 4.5 ± 1 months), only Patient 1 had a recurrent ON, and no patient developed new other neurological events or systemic symptoms.

Conclusion
GFAP-Ab is rare in patients with ON and may manifest as isolated, relapsing ON. This supports the notion that the GFAP-A spectrum should comprise isolated ON.
Two patients with ZAP-70 deficiency in China present with a different genetic, immunological, and clinical phenotype
Authors: Luo Xianze , Liu Qing , Zhou Lina , Tang Xuemei , Zhao Xiaodong , Zhang Zhiyong 
Published: April 2023

AbstractZeta(ζ)-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare autosomal recessive primary immunodeficiency disease. Little is known about this disease. In this study, we report two patients to extend the range of clinical phenotypes and immunophenotypes associated with ZAP-70 mutations. We describe the clinical, genetic, and immunological phenotypes of two patients with ZAP-70 deficiency in China, and the data are also compared with the literature. Case 1 presented with leaky severe combined immunodeficiency with low to the absence of CD8 + T cells, while case 2 suffered from a recurrent respiratory infection and had a past medical history of non-EBV-associated Hodgkin’s lymphoma. Sequencing revealed novel compound heterozygous mutations in ZAP-70 of these patients. Case 2 is the second ZAP-70 patient presenting a normal CD8 + T cell number. These two cases have been treated with hematopoietic stem cell transplantation. Selective CD8 + T cell loss is an essential feature of the immunophenotype of ZAP-70 deficiency patients, but there are exceptions. Hematopoietic stem cell transplantation can provide excellent long-term immune function and resolution of clinical problems.
From design to action: participatory approach to capacity building needs for local overdose response plans
Authors: Mallakin Maryam , Dery Christina , Woldemariam Yordanos , Hamilton Michael , Corace Kim , Pauly Bernie , Khorasheh Triti , AbuAyyash Caroline Bennett , Leece Pamela , Sellen Katherine 
Published: April 2023

Abstract
Background
In response to the rise in opioid-related deaths, communities across Ontario have developed opioid or overdose response plans to address issues at the local level. Public Health Ontario (PHO) leads the Community Opioid / Overdose Capacity Building (COM-CAP) project, which aims to reduce overdose-related harms at the community level by working with communities to identify, develop, and evaluate capacity building supports for local needs around overdose planning. The ‘From Design to Action’ co-design workshop used a participatory design approach to engage communities in identifying the requirements for capacity building support.

Methods
A participatory approach (co-design) provided opportunity for collaborative discussion around capacity building needs at the community level. The co-design workshop included three structured collaborative activities to 1) prioritize scenarios that illustrated various challenges associated with community overdose response planning, 2) prioritize the challenges within each scenario and 3) prioritize the supports to address each of these challenges. It was conducted with fifty-two participants involved in opioid/overdose-related response plans in Ontario. Participatory materials were informed by the results of a situational assessment (SA) data gathering process, including survey, interview, and focus group data. A voting system, including dot stickers and discussion notes, was applied to identify priority supports and delivery mechanisms.

Results
At the workshop, key challenges and top-priority supports were identified, for development and implementation. The prioritized challenges were organized into five categories of capacity building supports addressing: 1) stigma & equity; 2) trust-based relationships, consensus building & on-going communication; 3) knowledge development & on-going access to information and data; 4) tailored strategies and plan adaptation to changing structures and local context; and 5) structural enablers and responsive governance.

Conclusion
Using a participatory approach, the workshop provided an opportunity for sharing, generating, and mobilizing knowledge to address research-practice gaps at the community level for opioid response planning. The application of health design methods such as the ‘From Design to Action’ co-design workshop supports teams to gain a deeper understanding of needs for capacity building as well as illustrating the application of participatory approaches in identifying capacity building needs for complex public health issues such as the overdose crisis.
Development and assessment of a curriculum model for virtual simulation in nursing: curriculum development and pilot-evaluation
Authors: Shin Hyunsook , Rim Dahae 
Published: April 2023

Abstract
Background
To introduce virtual simulation as a strategy of nursing education and provide valid educational content, the best curriculum model of virtual simulation needs to be developed.

Methods
Curriculum development process and pilot evaluation was used. The curriculum content and structure was developed by analyzing literature including previous studies and major nursing classification systems, and key words derived from focus group interviews of 14 nurses and 20 faculty members with expertise in simulation education. 35 nursing students participated in the evaluation of the developed virtual simulation curriculum.

Results
The curriculum developed for virtual simulation in nursing education contained three domains of content areas: (1) enhancing clinical decision-making, (2) experiencing low-exposed situations, and (3) building professional resilience. In addition, seven subdomains of content areas and 35 representative topics in the virtual simulation curriculum were derived. Scenarios of nine representative topics were created, translated into 3D modeling and pilot-evaluated.

Conclusions
Considering that nursing education is encountering new demands and challenges from students and the changing society, the newly suggested curriculum for virtual nursing simulation can help nurse educators to plan better educational opportunities for students.
Pregnant women’s use and attitude toward Mobile phone features for self-management
Authors: Nabovati Ehsan , Farzandipour Mehrdad , Vahedpoor Zahra , Akbari Hossein , Anvari Shima , Sharif Reihane , Fatehi Farhad 
Published: April 2023

Abstract
Background
This study aimed to examine the current use of mobile phones by pregnant women and their attitudes towards the use of a variety of prenatal care services through mHealth.

Methods
This descriptive cross-sectional study was conducted in Iran in 2021. The study population included 168 pregnant women who referred to specialist obstetrics and gynecology clinic. The data collection tool was a questionnaire that included the demographics of the participants, their current mobile phone usage, and their attitudes toward mobile phone use for prenatal care services. The data were analyzed in SPSS with descriptive and analytical statistics.

Results
The majority of participants (84.2%) had a smartphone and access to mobile internet. More than half of the respondents (58.9%) used their mobile phone for (only) phone calls, and 36.7% occasionally used mobile internet to access prenatal care services. To get information about the pregnancy and to communicate with other pregnant women, the participants mainly used social media, and to get reminders, they preferred phone calls.

Conclusions
In this study, pregnant women have a positive attitude towards using mobile phones for obtaining health services and prefer social media to seek prenatal care services. There seems to be a need for pregnant women to have high levels of digital health literacy and be advised by healthcare providers on using this technology to access prenatal care services.
The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study
Authors: Emery Paul , Tanaka Yoshiya , Bykerk Vivian P. , Bingham Clifton O. , Huizinga Thomas W. J. , Citera Gustavo , Huang Kuan-Hsiang Gary , Wu Chun , Connolly Sean E. , Elbez Yedid , Wong Robert , Lozenski Karissa , Fleischmann Roy 
Published: April 2023

Abstract
Background
AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy.

Methods
During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 [CRP]) < 2.6, were assessed. For patients achieving early sustained SDAI remission at weeks 24/40/52, flow between disease activity categories and individual trajectories was evaluated; flow was also evaluated for later remitters (weeks 40/52 but not week 24).

Results
Among patients treated with abatacept + methotrexate (n/N = 451/752) at IP week 24, 22% achieved SDAI remission, 17% achieved Boolean remission, and 42% achieved DAS28 (CRP) < 2.6; of these, 56%, 58%, and 74%, respectively, sustained a response throughout IP weeks 40/52. Among patients with a sustained response at IP weeks 24/40/52, 82% (14/17) on weekly abatacept + methotrexate, 81% (13/16) on abatacept monotherapy, 63% (12/19) who de-escalated/withdrew abatacept, and 65% (11/17) on abatacept placebo + methotrexate were in SDAI remission at end of the DE period; rates were higher than for later remitters in all arms except abatacept placebo + methotrexate.

Conclusions
A high proportion of individual patients achieving clinical endpoints at IP week 24 with abatacept + methotrexate sustained their responses through week 52. Of patients achieving early and sustained SDAI remission through 52 weeks, numerically more maintained remission during the DE period if weekly abatacept treatment continued.

Trial registration
NCT02504268 (ClinicalTrials.gov), registered July 21, 2015.
Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease
Authors: Ali Muhammad , Archer Derek B. , Gorijala Priyanka , Western Daniel , Timsina Jigyasha , Fernández Maria V. , Wang Ting-Chen , Satizabal Claudia L. , Yang Qiong , Beiser Alexa S. , Wang Ruiqi , Chen Gengsheng , Gordon Brian , Benzinger Tammie L. S. , Xiong Chengjie , Morris John C. , Bateman Randall J. , Karch Celeste M. , McDade Eric , Goate Alison , Seshadri Sudha , Mayeux Richard P. , Sperling Reisa A. , Buckley Rachel F. , Johnson Keith A. , Won Hong-Hee , Jung Sang-Hyuk , Kim Hang-Rai , Seo Sang Won , Kim Hee Jin , Mormino Elizabeth , Laws Simon M. , Fan Kang-Hsien , Kamboh M. Ilyas , Vemuri Prashanthi , Ramanan Vijay K. , Yang Hyun-Sik , Wenzel Allen , Rajula Hema Sekhar Reddy , Mishra Aniket , Dufouil Carole , Debette Stephanie , Lopez Oscar L. , DeKosky Steven T. , Tao Feifei , Nagle Michael W. ,   Knight Alzheimer Disease Research Center (Knight ADRC),   the Dominantly Inherited Alzheimer Network (DIAN),   Alzheimer’s Disease Neuroimaging Initiative (ADNI),   ADNI-DOD, A4 Study Team,   the Australian Imaging Biomarkers, Lifestyle (AIBL) Study, Hohman Timothy J. , Sung Yun Ju , Dumitrescu Logan , Cruchaga Carlos 
Published: April 2023

AbstractAmyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer’s disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; β = 0.35, SE = 0.01, P = 6.2 × 10–311, MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4. APOE ɛ4 and ε2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; β = 0.07, SE = 0.01, P = 9.2 × 10–09, MAF = 0.32), CR1 (rs6656401/chr1q.32.2; β = 0.1, SE = 0.02, P = 2.4 × 10–10, MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; β = 0.16, SE = 0.03, P = 1.1 × 10–09, MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, β = 0.79, SE = 0.14, P = 1.4 × 10–08, MAF = 0.006, sex-interaction P = 9.8 × 10–07) and chr11p.15.2 (rs192346166, β = 0.94, SE = 0.17, P = 3.7 × 10–08, MAF = 0.004, sex-interaction P = 1.3 × 10–03). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.
Metabolic mechanism of astaxanthin biosynthesis in Xanthophyllomyces dendrorhous in response to sodium citrate treatment
Authors: Pan Xueshan , Li Tonggang , Wang Baobei , Qi Shuhua , Yang Dandan , Huang Zheng , Gao Renfei , Li Jingyan , Ling Xueping , Lu Yinghua 
Published: April 2023

AbstractAstaxanthin is an important ketocarotenoid widely used in industries. However, its application is limited because of its low yield. Sodium citrate (Na-citrate), one of the major carbon sources for microorganisms, can promote cell growth and product accumulation. The basidiomycetous red yeast Xanthophyllomyces dendrorhous was thus used to study the effect of Na-citrate on cell growth and astaxanthin synthesis. The highest biomass and astaxanthin yield (6.0 g/L and 22.5 mg/L) were obtained in shake-flask when 3 g/L Na-citrate was added at 24 h and were 1.8 and 2.0 times higher than those of the control group, respectively. Furthermore, metabolomics and real-time reverse transcription PCR (qRT-PCR) analysis were conducted to study the metabolic pathways of X. dendrorhous in response to Na-citrate. The qRT-PCR assay revealed that Na-citrate facilitated glucose consumption, promoted the metabolic flux from glycolysis, and regulated the tricarboxylic acid (TCA) cycle, providing more energy and substrates for the synthesis of astaxanthin. The gene analysis revealed that adding Na-citrate significantly upregulated the expression of six key genes (ICL, HMGS, crtE, crtYB, crtI, and crtS) involved in pathways related to astaxanthin biosynthesis. These results suggest that exogenous Na-citrate treatment is a potentially valuable strategy to stimulate astaxanthin production in X. dendrorhous.
Regeneration of the heart: from molecular mechanisms to clinical therapeutics
Authors: Guo Qian-Yun , Yang Jia-Qi , Feng Xun-Xun , Zhou Yu-Jie 
Published: April 2023

AbstractHeart injury such as myocardial infarction leads to cardiomyocyte loss, fibrotic tissue deposition, and scar formation. These changes reduce cardiac contractility, resulting in heart failure, which causes a huge public health burden. Military personnel, compared with civilians, is exposed to more stress, a risk factor for heart diseases, making cardiovascular health management and treatment innovation an important topic for military medicine. So far, medical intervention can slow down cardiovascular disease progression, but not yet induce heart regeneration. In the past decades, studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury. Insights have emerged from studies in animal models and early clinical trials. Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease. In this review, we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.
The gut microbiome of solitary bees is mainly affected by pathogen assemblage and partially by land use
Authors: Fernandez De Landa Gregorio , Alberoni Daniele , Baffoni Loredana , Fernandez De Landa Mateo , Revainera Pablo Damian , Porrini Leonardo Pablo , Brasesco Constanza , Quintana Silvina , Zumpano Francisco , Eguaras Martìn Javier , Maggi Matias Daniel , Di Gioia Diana 
Published: April 2023

AbstractPollinators, including solitary bees, are drastically declining worldwide. Among the factors contributing to this decline, bee pathogens and different land uses are of relevance. The link between the gut microbiome composition and host health has been recently studied for social pollinators (e.g. honeybees), whereas the information related to solitary bees is sparse. This work aimed at the characterization of the gut microbiome of the solitary bees Xylocopa augusti, Eucera fervens and Lasioglossum and attempted to correlate the gut microbial composition with the presence and load of different pathogens and land uses. Solitary bees were sampled in different sites (i.e. a farm, a natural reserve, and an urban plant nursery) showing different land uses. DNA was extracted from the gut, 16S rRNA gene amplified and sequenced. Eight pathogens, known for spillover from managed bees to wild ones, were quantified with qPCR. The results showed that the core microbiome profile of the three solitary bees significantly varied in the different species. Pseudomonas was found as the major core taxa in all solitary bees analyzed, whereas Lactobacillus, Spiroplasma and Sodalis were the second most abundant taxa in X. augusti, E. fervens and Lasioglossum, respectively. The main pathogens detected with qPCR were Nosema ceranae, Nosema bombi and Crithidia bombi, although differently abundant in the different bee species and sampling sites. Most microbial taxa did not show any correlation with the land use, apart from Snodgrassella and Nocardioides, showing higher abundances on less anthropized sites. Conversely, the pathogens species and load strongly affected the gut microbial composition, with Bifidobacterium, Apibacter, Serratia, Snodgrassella and Sodalis abundance that positively or negatively correlated with the detected pathogens load. Therefore, pathogens presence and load appear to be the main factor shaping the gut microbiome of solitary bees in Argentina.
Advanced pathophysiology mimicking lung models for accelerated drug discovery
Authors: Phan Thanh Huyen , Shi Huaikai , Denes Christopher E. , Cole Alexander J. , Wang Yiwei , Cheng Yuen Yee , Hesselson Daniel , Roelofs Susan H. , Neely Graham Gregory , Jang Jun-Hyeog , Chrzanowski Wojciech 
Published: April 2023

Abstract

Background

Respiratory diseases are the 2
nd
leading cause of death globally. The current treatments for chronic lung diseases are only supportive. Very few new classes of therapeutics have been introduced for lung diseases in the last 40 years, due to the lack of reliable lung models that enable rapid, cost-effective, and high-throughput testing. To accelerate the development of new therapeutics for lung diseases, we established two classes of lung-mimicking models: (i) healthy, and (ii) diseased lungs – COPD.

Methods
To establish models that mimic the lung complexity to different extents, we used five design components: (i) cell type, (ii) membrane structure/constitution, (iii) environmental conditions, (iv) cellular arrangement, (v) substrate, matrix structure and composition. To determine whether the lung models are reproducible and reliable, we developed a quality control (QC) strategy, which integrated the real-time and end-point quantitative and qualitative measurements of cellular barrier function, permeability, tight junctions, tissue structure, tissue composition, and cytokine secretion.

Results
The healthy model is characterised by (i) continuous tight junctions, (ii) physiological cellular barrier function, (iii) a full thickness epithelium composed of multiple cell layers, and (iv) the presence of ciliated cells and goblet cells. Meanwhile, the disease model emulates human COPD disease: (i) dysfunctional cellular barrier function, (ii) depletion of ciliated cells, and (ii) overproduction of goblet cells. The models developed here have multiple competitive advantages when compared with existing in vitro lung models: (i) the macroscale enables multimodal and correlative characterisation of the same model system, (ii) the use of cells derived from patients that enables the creation of individual models for each patient for personalised medicine, (iii) the use of an extracellular matrix proteins interface, which promotes physiological cell adhesion and differentiation, (iv) media microcirculation that mimics the dynamic conditions in human lungs.

Conclusion
Our model can be utilised to test safety, efficacy, and superiority of new therapeutics as well as to test toxicity and injury induced by inhaled pollution or pathogens. It is envisaged that these models can also be used to test the protective function of new therapeutics for high-risk patients or workers exposed to occupational hazards.

Graphical Abstract