bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol: How can people with social care needs be supported through processes of digital care navigation to access remote primary care? A multi-site case study in UK general practice of remote care as the ‘new normal’.
Authors: Hughes Gemma , Rybczynska-Bunt Sarah , Shasha'h Sara , Greene Sarah , Shaw Sara , Greenhalgh Trisha 
Published: April 2023

Background: Care navigation refers to support for patients accessing primary care and other related services. The expansion of digitally enabled care in the UK since the coronavirus disease 2019 (COVID-19) pandemic has led to a greater need for digital care navigation: supporting people to access primary care digitally and, if necessary, to help them find alternative non-digital routes of access. Support to patients with social care needs (including but not limited to those who are homeless and insecurely housed, living in residential care and supported by domiciliary carers) increasingly involves work to navigate primary care provided remotely and accessed digitally. There is little knowledge about how this work is being done. Methods: Care Navigation involves embedded researchers identifying digital care navigation for patients accessing services in 11 GP practices recruited to a linked study of remote primary care (Remote care as the ‘new normal?’). Digital care navigation will be studied through go-along (in-person or remote) interviews with a sample of 20 people offering formal (paid or voluntary) support, 6 national and regional stakeholders who plan, commission or provide digital care navigation and a focus group with 12 social prescribers engaged in digital care navigation. A co-design workshop with people working in, or commissioning, social care settings will consider how findings can inform improved digital care navigation, for example through the development of resources or guidance for care navigators. Results (anticipated): Findings are anticipated to include evidence of how digital care navigation is practised, the work that is done to support patients in accessing remote primary care, and how this work is shaped by material resources and variations in the configuration of services and infrastructure. Conclusions: New explanations of the work needed to navigate digital care will inform policy and service developments aimed at helping patients benefit from remote primary care.
Who will save the world? –from the missing hero to the index of Captain Planet
Authors: Nagy Ádám , Fekete Mariann , Tóth Péter 
Published: April 2023

Captain Planet is a superhero, who is the main character of the animated series
having the same title. The focus is on environmental protection and diverse social
problems; the only weak point of the Captain is polluted environment which noticeably
weakens him. Each episode of the animated series deals with environmental issues like
deforestation, air or water pollution, overpopulation.
Large-scale youth research has been conducted in Hungary every four year since 2000. The
representative sample on age, gender, education, type of settlement, place of residence
(district / city) among 15-29 year olds are used to learn about the life situation of
young people, to follow their lifestyle changes and (in theory) to prepare (typically
public policy) decision-making. The most important events and specific problems of
Hungarian youngsters aged 15-29. 8000 youngsters were examined in 2020 as well,
We use the data of wave the 2020 large scale Hungarian Youth Research for mapping the
„Hungarian Captain Planet”. We found, that H. Captain Planet does not belong to
climate-fighter Generation Z, but youngsters aged 25-29 who are highly educated, who
have a stable financial situation, who are not inactive, that is they either study or
work (one third of youngsters belong to this group (32%)). It may be a commonplace,
however, it was managed to prove this commonplace scientifically.
MiR-20a promotes osteogenic differentiation in bone marrow-derived mesenchymal stem/stromal cells and bone repair of the maxillary sinus defect model in rabbits
Authors: Wang Yi-Xuan , Peng Zhu-Li , Sun Zhi-Wen , Pan Yan-Jun , Ai Hong , Mai Zhi-Hui 
Published: April 2023

Introduction:This study aimed to determine whether miR-20 promoted osteogenic differentiation in bone marrow-derived mesenchymal stem/stromal cells (BMSCs) and accelerated bone formation in the maxillary sinus bone defect model in rabbits.Methods:BMSCs were transfected with miR-20a or anti-miR-20a for 12 h, followed by detection of RUNX2, Sp7 mRNA, bone morphogenetic protein 2 (BMP2), and RUNX2 protein expression. Alkaline phosphatase (ALP) activity and Alizarin Red S staining were used to detect calcified nodule deposition. In the rabbit maxillary sinus bone defect model, miR-20a loaded with AAV and BMP2 protein were mixed with Bio-Oss bone powder for filling the bone defect. At 4 weeks and 8 weeks, bone density was detected by cone beam computed tomography (CBCT), and new bone, osteoblasts, and collagen type 1 were evaluated by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining.Results:Overexpression of miR-20a enhanced the mRNA and protein levels of BMP2, RUNX2, and SP7, the activity of ALP, and the levels of matrix mineralization, whereas the levels and activity of the aforementioned factors were decreased by anti-miR-20a treatment of BMSCs. Furthermore, miR-20a significantly increased the bone density, the number of osteoblasts, and the secretion of collagen type 1 in bone defects compared with Bio-Oss bone powder in the rabbit maxillary sinus bone defect model.Conclusion:Overall, miR-20a can induce osteogenic differentiation in BMSCs and accelerate bone formation of maxillary sinus defects in rabbits.
Blood pressure dynamics during home blood pressure monitoring with a digital blood pressure coach—a prospective analysis of individual user data
Authors: Beger Christian , Rüegger Dominik , Lenz Anna , Wagner Steffen , Haller Herrmann , Schmidt-Ott Kai Martin , Volland Dirk , Limbourg Florian P. 
Published: April 2023

IntroductionSelf-monitoring of blood pressure at home is a better predictor of prognosis and recommended in hypertension guidelines. However, the influence of baseline blood pressure category and measurement schedule on BP values during a period of home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application.MethodsWe analysed temporal BP changes and performed BP classification tracking in users with self-reported hypertension performing HBPM with a digital and interactive blood pressure coach.ResultsOf 3175 users who enrolled in HBPM, 74.1% completed the first measurement period. Overall, mean systolic BP dropped significantly after the first day, but stratification by BP category demonstrated that initial category influenced BP course. BP classification tracking revealed that time to reach final BP category was dependent on baseline category, with users in categories high normal and grade 1 hypertension requiring more days to decrease BP class volatility and to reach their definitive BP class. This was driven by an intense switching between directly neighbouring categories until the middle phase of the HBPM period, while more distant class switching occurred less often and only early on. Overall, &gt;90% of users maintained their category by day 5. Omitting the first day from analysis lead to therapeutically relevant reclassification in 3.8% of users. Users who completed at least two HBPM periods (n = 864) showed a mean SBP/DBP decrease of 2.6/1.6 mmHg, which improved hypertension control from 55.6% to 68.1%.ConclusionThe optimal length of HBPM period depends on BP category. HBPM with a digital coach is associated with a reduction in average BP and improvement in BP control.
Anti-amphiphysin encephalitis: Expanding the clinical spectrum
Authors: Sun Yueqian , Qin Xiaoxiao , Huang Danxia , Zhou Ziqi , Zhang Yudi , Wang Qun 
Published: April 2023

ObjectiveAn analysis of the clinical features of autoimmune encephalitis accompanied by anti-amphiphysin antibodies.MethodsThe data of encephalitis patients with anti-amphiphysin antibodies were retrospectively evaluated, including demographics, neurological and laboratory findings, imaging, treatment, and prognostic predictions.ResultsTen patients aged between 29 and 78 years (median age 52 years) were included. The male: female ratio was 4:6. Limbic encephalitis was found in nine patients while epileptic seizures were present in seven patients. All patients showed anti-amphiphysin antibody positivity in sera while one ninth was positive for CSF antibody. The EEG findings were abnormal, including reductions in background activity, and the presence of diffuse slow waves, sharp waves, and spikes and waves. Five patients showed signs of increased T2 signals in the medial temporal lobe on MRI while PET showed either hyper- or hypo-metabolic changes in several brain regions, including the temporal lobe, hippocampus, basal ganglia, frontal and parietal cortices. Nine of ten patients were treated with immunotherapy, with improvements of varying degrees. There was a significant reduction in seizure frequency, and all patients were seizure-free at last follow-up.ConclusionAutoimmune encephalitis with anti-amphiphysin antibodies has a variety of clinical manifestations. The most common symptom is limbic encephalitis. Although relief from seizures can be achieved relatively easily, many patients suffer psychiatric, cognitive, and sleep sequelae. The disease was found to be associated with a lower incidence of cancer than has been previously reported for paraneoplastic neurologic syndromes.
Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19
Authors: Lee Chan Mi , Kim Minji , Kang Chang Kyung , Choe Pyoeng Gyun , Kim Nam Joong , Bang Hyeeun , Cho Taeeun , Shin Hyun Mu , Kim Hang-Rae , Park Wan Beom , Oh Myoung-don 
Published: April 2023

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.
Integrated bioinformatics and machine-learning screening for immune-related genes in diagnosing non-alcoholic fatty liver disease with ischemic stroke and RRS1 pan-cancer analysis
Authors: Bao Huayan , Li Jianwen , Zhang Boyang , Huang Ju , Su Danke , Liu Lidong 
Published: April 2023

BackgroundThe occurrence of ischemic stroke (IS) is associated with nonalcoholic fatty liver disease (NAFLD). The cancer burden of NAFLD complicated by IS also warrants attention. This study aimed to identify candidate immune biomarkers linked to NAFLD and IS and analyze their association with cancer.MethodsTwo of each of the NAFLD and IS datasets were downloaded, differentially expressed genes (DEGs) were identified, and module genes were screened via weighted gene coexpression network analysis (WGCNA). Subsequently, utilizing machine learning (least absolute shrinkage and selection operator regression, random forest and support vector machine-recursive feature elimination) and immune cell infiltration analysis, immune-related candidate biomarkers for NAFLD with IS were determined. Simultaneously, a nomogram was established, the diagnostic efficacy was assessed, and the role of candidate biomarkers in cancer was ascertained through pan-cancer analyses.ResultsIn this study, 117 and 98 DEGs were identified from the combined NAFLD and IS datasets, respectively, and 279 genes were obtained from the most significant modules of NAFLD. NAFLD module genes and IS DEGs were intersected to obtain nine genes, which were enriched in the inflammatory response and immune regulation. After overlapping the results of the three machine learning algorithms, six candidate genes were obtained, based on which a nomogram was constructed. The calibration curve demonstrated good accuracy, and the candidate genes had high diagnostic values. The genes were found to be related to the immune dysregulation of stroke, and RRS1 was strongly associated with the prognosis, immune cell infiltration, microsatellite instability (MSI), and tumor mutation burden (TMB).ConclusionSix common candidate immune-related genes (PTGS2, FCGR1A, MMP9, VNN3, S100A12, and RRS1) of NAFLD and IS were identified, and a nomogram for diagnosing NAFLD with IS was established. RRS1 may serve as a candidate gene for predicting the prognosis of patients with cancer who have NAFLD complicated by IS, which could aid in their diagnosis and treatment.
Chronic alcohol administration alters metabolomic profile of murine bone marrow
Authors: Pontes Pereira Tássia Tatiane , Fideles Duarte-Andrade Filipe , Gardone Vitório Jéssica , do Espírito Santo Pereira Taiane , Braga Martins Flavia Rayssa , Marques Souza Jéssica Amanda , Malacco Nathália Luisa , Mathias Melo Eliza , Costa Picossi Carolina Raíssa , Pinto Ernani , Santiago Gomez Ricardo , Martins Teixeira Mauro , Nori de Macedo Adriana , André Baptista Canuto Gisele , Soriani Frederico Marianetti 
Published: April 2023

IntroductionPeople with hazardous alcohol use are more susceptible to viral, bacterial, and fungal infections due to the effect of alcohol on immune system cell function. Metabolized ethanol reduces NAD+ to NADH, affecting critical metabolic pathways. Here, our aim was to investigate whether alcohol is metabolized by bone marrow cells and if it impacts the metabolic pathways of leukocyte progenitor cells. This is said to lead to a qualitative and quantitative alteration of key metabolites which may be related to the immune response.MethodsWe addressed this aim by using C57BL/6 mice under chronic ethanol administration and evaluating the metabolomic profile of bone marrow total cells by gas chromatography–coupled mass spectrometry (GC–MS).ResultsWe identified 19 metabolites. Our data demonstrated that chronic ethanol administration alters the metabolomic profile in the bone marrow, resulting in a statistically diminished abundance of five metabolites in ethanol-treated animals: uracil, succinate, proline, nicotinamide, and tyrosine.DiscussionOur results demonstrate for the first time in the literature the effects of alcohol consumption on the metabolome content of hematopoietic tissue and open a wide range of further studies to investigate mechanisms by which alcohol compromises the cellular function of the immune system.
Rapid and sustained T cell-based immunotherapy against invasive fungal disease via a combined two step procedure
Authors: Tischer-Zimmermann Sabine , Salzer Elisabeth , Bitencourt Tamires , Frank Nelli , Hoffmann-Freimüller Christine , Stemberger Julia , Maecker-Kolhoff Britta , Blasczyk Rainer , Witt Volker , Fritsch Gerhard , Paster Wolfgang , Lion Thomas , Eiz-Vesper Britta , Geyeregger René 
Published: April 2023

IntroductionAspergillus fumigatus (Asp) infections constitute a major cause of morbidity and mortality in patients following allogeneic hematopoietic stem cell transplantation (HSCT). In the context of insufficient host immunity, antifungal drugs show only limited efficacy. Faster and increased T-cell reconstitution correlated with a favorable outcome and a cell-based therapy approach strongly indicated successful clearance of fungal infections. Nevertheless, complex and cost- or time-intensive protocols hampered their implementation into clinical application.MethodsTo facilitate the clinical-scale manufacturing process of Aspergillus fumigatus-specific T cells (ATCs) and to enable immediate (within 24 hours) and sustained (12 days later) treatment of patients with invasive aspergillosis (IA), we adapted and combined two complementary good manufacturing practice (GMP)-compliant approaches, i) the direct magnetic enrichment of Interferon-gamma (IFN-γ) secreting ATCs using the small-scale Cytokine Secretion Assay (CSA) and ii) a short-term in vitro T-cell culture expansion (STE), respectively. We further compared stimulation with two standardized and commercially available products: Asp-lysate and a pool of overlapping peptides derived from different Asp-proteins (PepMix).ResultsFor the fast CSA-based approach we detected IFN-γ+ ATCs after Asp-lysate- as well as PepMix-stimulation but with a significantly higher enrichment efficiency for stimulation with the Asp-lysate when compared to the PepMix. In contrast, the STE approach resulted in comparably high ATC expansion rates by using Asp-lysate or PepMix. Independent of the stimulus, predominantly CD4+ helper T cells with a central-memory phenotype were expanded while CD8+ T cells mainly showed an effector-memory phenotype. ATCs were highly functional and cytotoxic as determined by secretion of granzyme-B and IFN-γ.DiscussionFor patients with IA, the immediate adoptive transfer of IFN-γ+ ATCs followed by the administration of short-term in vitro expanded ATCs from the same donor, might be a promising therapeutic option to improve the clinical outcome.
Association of clinical prediction scores with hospital mortality in an adult medical and surgical intensive care unit in Kenya
Authors: Brotherton B. Jason , Joshi Mugdha , Otieno George , Wandia Sarah , Gitura Hannah , Mueller Ariel , Nguyen Tony , Letchford Steve , Riviello Elisabeth D. , Karanja Evelyn , Rudd Kristina E. 
Published: April 2023

ImportanceMortality prediction among critically ill patients in resource limited settings is difficult. Identifying the best mortality prediction tool is important for counseling patients and families, benchmarking quality improvement efforts, and defining severity of illness for clinical research studies.ObjectiveCompare predictive capacity of the Modified Early Warning Score (MEWS), Universal Vital Assessment (UVA), Tropical Intensive Care Score (TropICS), Rwanda Mortality Probability Model (R-MPM), and quick Sequential Organ Failure Assessment (qSOFA) for hospital mortality among adults admitted to a medical-surgical intensive care unit (ICU) in rural Kenya. We performed a pre-planned subgroup analysis among ICU patients with suspected infection.Design, setting, and participantsProspective single-center cohort study at a tertiary care, academic hospital in Kenya. All adults 18 years and older admitted to the ICU January 2018–June 2019 were included.Main outcomes and measuresThe primary outcome was association of clinical prediction tool score with hospital mortality, as defined by area under the receiver operating characteristic curve (AUROC). Demographic, physiologic, laboratory, therapeutic, and mortality data were collected. 338 patients were included, none were excluded. Median age was 42 years (IQR 33–62) and 61% (n = 207) were male. Fifty-nine percent (n = 199) required mechanical ventilation and 35% (n = 118) received vasopressors upon ICU admission. Overall hospital mortality was 31% (n = 104). 323 patients had all component variables recorded for R-MPM, 261 for MEWS, and 253 for UVA. The AUROC was highest for MEWS (0.76), followed by R-MPM (0.75), qSOFA (0.70), and UVA (0.69) (p &lt; 0.001). Predictive capacity was similar among patients with suspected infection.Conclusion and relevanceAll tools had acceptable predictive capacity for hospital mortality, with variable observed availability of the component data. R-MPM and MEWS had high rates of variable availability as well as good AUROC, suggesting these tools may prove useful in low resource ICUs.
L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults
Authors: Isotalus Hanna K. , Carr Will J. , Blackman Jonathan , Averill George G. , Radtke Oliver , Selwood James , Williams Rachel , Ford Elizabeth , McCullagh Liz , McErlane James , O’Donnell Cian , Durant Claire , Bartsch Ullrich , Jones Matt W. , Muñoz-Neira Carlos , Wearn Alfie R. , Grogan John P. , Coulthard Elizabeth J. 
Published: April 2023

IntroductionMillions of people worldwide take medications such as L-DOPA that increase dopamine to treat Parkinson’s disease. Yet, we do not fully understand how L-DOPA affects sleep and memory. Our earlier research in Parkinson’s disease revealed that the timing of L-DOPA relative to sleep affects dopamine’s impact on long-term memory. Dopamine projections between the midbrain and hippocampus potentially support memory processes during slow wave sleep. In this study, we aimed to test the hypothesis that L-DOPA enhances memory consolidation by modulating NREM sleep.MethodsWe conducted a double-blind, randomised, placebo-controlled crossover trial with healthy older adults (65–79 years, n = 35). Participants first learned a word list and were then administered long-acting L-DOPA (or placebo) before a full night of sleep. Before sleeping, a proportion of the words were re-exposed using a recognition test to strengthen memory. L-DOPA was active during sleep and the practice-recognition test, but not during initial learning.ResultsThe single dose of L-DOPA increased total slow-wave sleep duration by approximately 11% compared to placebo, while also increasing spindle amplitudes around slow oscillation peaks and around 1–4 Hz NREM spectral power. However, behaviourally, L-DOPA worsened memory of words presented only once compared to re-exposed words. The coupling of spindles to slow oscillation peaks correlated with these differential effects on weaker and stronger memories. To gauge whether L-DOPA affects encoding or retrieval of information in addition to consolidation, we conducted a second experiment targeting L-DOPA only to initial encoding or retrieval and found no behavioural effects.DiscussionOur results demonstrate that L-DOPA augments slow wave sleep in elderly, perhaps tuning coordinated network activity and impacting the selection of information for long-term storage. The pharmaceutical modification of slow-wave sleep and long-term memory may have clinical implications.Clinical trial registrationEudract number: 2015-002027-26; https://doi.org/10.1186/ISRCTN90897064, ISRCTN90897064.