bluuebunny/crossref_metadata_2025_split huggingface dataset:
A patient-centered interactive voice response system for supporting self-management in kidney transplantation: design and field testing
Authors: Ganjali Raheleh , Ghorban Sabbagh Mahin , Eslami Saeid 
Published: February 2025

IntroductionSelf-management is the ability to control one's own responses to treatments, physical and psychological side effects, and lifestyle choices related to a chronic condition.PurposeTo describe the development of a standard and practical user-centered design process for an interactive voice response system (IVRS) to improve self-management in kidney transplant (KT) recipients.MethodsThe IVRS was constructed utilizing the four phases of the Center for eHealth and Wellbeing Research (CeHRes) roadmap: the contextual inquiry, the value specification, the design phase, and evaluation. First, a literature review, background analysis, and needs assessment were used to identify the needs and problems and solutions related to self-management of KT recipients. Then, with the help of a team of experts and KT recipients, a logic model was created and evaluated. The IVRS was developed through iterative design development in response to these findings. Finally, fifteen end users (KT beneficiaries and health professionals) participated in a usability field test by completing a thinking -aloud test and a questionnaire based on the System Usability Scale (SUS).ResultsThe review study indicates the necessary of self-management education and the potential outcomes and functionalities of information technology intervention. The situation analysis and needs assessment led to the final important requirements for the design of the intervention. All values were identified in three meetings with principal stakeholders, and a logic model was designed. The user test yielded an average SUS score of 81.2, and these results served as the basis for the usability requirements. Health Care Providers (HCPs) struggled with storing the profile of registered patients, setting up medication and personalizing adherence calls, and educational calls and follow-ups.ConclusionFollowing the CeHRes roadmap, an intervention based on IVRS was developed with considering the needs and preferences of KT recipients and HCPs. Designers and researchers could use the CeHRes roadmap as a reference when developing IT-based intervention systems. However, decisions must be made about the thoroughness of the execution of each phase, taking into account time constraints.
Prospective observational study to evaluate the feasibility of the mobile app for mild cognitive impairment detection and screening
Authors: Hamaguchi Reo , Hongo Seiji , Doi Naoto , Ide Hisamitsu , Saito Ryozo , Kishimoto Junji , Handa Nobuhiro , Horie Shigeo 
Published: February 2025

IntroductionThe increasing prevalence of dementia in aging populations necessitates effective and accessible cognitive screening tools. This study aimed to evaluate the feasibility and reliability of a newly developed mobile app for detecting and screening mild cognitive impairment (MCI).MethodsThe mobile app, developed by LifeQuest Co., Ltd. (Minato-ku, Tokyo), is an original tool inspired by the Japanese version of the Montreal Cognitive Assessment (MoCA-J). A prospective observational study was conducted with 20 participants, including healthy individuals, MCI patients, and those with mild to moderate-severe dementia. Participants completed both the mobile app and the MoCA-J in a randomized order within a two-week period, with a minimum one-day interval between tests.Results and conclusionThe intraclass correlation coefficient (ICC) between the mobile app and the MoCA-J was 0.956 (95% CI: 0.89-0.983), demonstrating a very high level of correlation. All participants successfully completed the mobile app assessment, highlighting its feasibility across various cognitive levels. Although minor technical issues and usability challenges were identified, the results support the mobile app as a reliable and user-friendly alternative for cognitive screening. Further studies with larger sample sizes are necessary to validate these findings and refine the app for broader clinical use.
Advancing education through e-learning innovation: the case of the Crocodile Chemistry program in higher education
Authors: Alqallaf Nawal , Almahmeed Zahra , Alsaber Ahmad , Alboloushi Bedour , Alkandari Anwaar , Alhashem Fatimah 
Published: February 2025

IntroductionE-learning innovations have transformed higher education, particularly in STEM fields like chemistry. Traditional laboratory instruction faces limitations such as high costs, safety concerns, and accessibility issues. Virtual laboratories provide scalable alternatives to enhance student engagement and comprehension. This study evaluates the effectiveness of the Crocodile Chemistry program in improving students’ understanding of chemical concepts, academic performance, and motivation at the Public Authority for Applied Education and Training (PAAET).MethodsA quasi-experimental design compared an experimental group (n = 102) using Crocodile Chemistry with a control group (n = 103) following traditional laboratory instruction. Pre-test and post-test assessments were conducted using the Alternative Chemical Concepts Test. Paired t-tests measured performance changes, and correlation analysis assessed learning consistency. The Partial Credit Model (PCM) evaluated test reliability and instructional effectiveness.ResultsPaired t-tests revealed significant performance improvements for the experimental group (p &lt; 0.05), whereas the control group showed minimal changes. PCM analysis demonstrated higher reliability for the experimental group (0.774) compared to the control (0.403), indicating better differentiation of student abilities. Correlation analysis showed a strong relationship between pre- and post-test scores (r = −0.795, p &lt; 0.001), confirming the program’s role in enhancing learning outcomes.DiscussionThe findings highlight the potential of virtual laboratories to modernize chemistry education by improving comprehension, engagement, and academic performance. This study supports the integration of digital tools in higher education to enhance learning outcomes and student motivation.
Contribution of cuproptosis and immune-related genes to idiopathic pulmonary fibrosis disease
Authors: Jin Chengji , Li Jia , Li Qiaoyu , Zhang Lipeng , Zheng Shaomao , Feng Qiong , Li Yongjie , Zheng Yu , Nie Qiuli , Liang Jin , Wang Jing 
Published: February 2025

BackgroundIdiopathic pulmonary fibrosis (IPF) is a degenerative respiratory condition characterized by significant mortality rates and a scarcity of available treatment alternatives. Cuproptosis, a novel form of copper-induced cell death, has garnered attention for its potential implications. The study aimed to explore the diagnostic value of cuproptosis-related hub genes in patients with IPF. Additionally, multiple bioinformatics analyses were employed to identify immune-related biomarkers associated with the diagnosis of IPF, offering valuable insights for future treatment strategies.MethodsFour microarray datasets were selected from the Gene Expression Omnibus (GEO) collection for screening. Differentially expressed genes (DEGs) associated with IPF were analyzed. Additionally, weighted gene coexpression network analysis (WGCNA) was employed to identify the DEGs most associated with IPF. Ultimately, we analyzed five cuproptosis-related hub genes and assessed their diagnostic value for IPF in both the training and validation sets. Additionally, four immune-related hub genes were screened using a protein–protein interaction (PPI) network and evaluated through the receiver operating characteristic (ROC) curve. Lastly, single-cell RNA-seq was employed to further investigate differential gene distribution.ResultsWe identified a total of 92 DEGs. Bioinformatics analysis highlighted five cuproptosis-related genes as candidate biomarkers, including three upregulated genes (CFH, STEAP1, and HDC) and two downregulated genes (NUDT16 and FMO5). The diagnostic accuracy of these five genes in the cohort was confirmed to be reliable. Additionally, we identified four immune-related hub genes that demonstrated strong diagnostic performance for IPF, with CXCL12 showing an AUROC of 0.90. We also examined the relationship between these four genes and immune cells. CXCL12 was significantly negatively associated with neutrophils, while CXCR2 was associated exclusively with neutrophils, consistent with our single-cell sequencing results. CTSG showed a primarily positive association with follicular helper T, and SPP1 was most strongly associated with macrophages. Finally, our single-cell sequencing data revealed that in patients with IPF, CXCL12 was highly expressed in the endothelial cell subset (ECs), while SPP1 exhibited high expression in multiple cellular populations. The expression of the CTSG showed statistically significant differences in monocyte macrophages.ConclusionThe research methodically depicted the intricate interplay among five cuproptosis-related genes, four immune-related hub genes, and IPF, offering new ideas for diagnosing and treating patients with IPF.
Multi-omics analysis reveals the sensitivity of immunotherapy for unresectable non-small cell lung cancer
Authors: Wu Rui , Wei Kunchen , Huang Xingshuai , Zhou Yinge , Feng Xiao , Dong Xin , Tang Hao 
Published: February 2025

BackgroundTo construct a prediction model consisting of metabolites and proteins in peripheral blood plasma to predict whether patients with unresectable stage III and IV non-small cell lung cancer can benefit from immunotherapy before it is administered.MethodsPeripheral blood plasma was collected from unresectable stage III and IV non-small cell lung cancer patients who were negative for driver mutations before receiving immunotherapy. Then we classified samples according to the follow-up results after two courses of immunotherapy and non-targeted metabolomics and proteomics analyses were performed to select different metabolites and proteins. Finally, potential biomarkers were picked out by applying machine learning methods including random forest and stepwise regression and prediction models were constructed by logistic regression.ResultsThe presence of metabolites and proteins in peripheral blood plasma was causally associated with both non-small cell lung cancer and PD-L1/PD-1 expression levels. A total of 2 differential metabolites including 5-sulfooxymethylfurfural and Anthranilic acid and 2 differential proteins including Immunoglobulin heavy variable 1-45 and Microfibril-associated glycoprotein 4 were selected as reliable biomarkers. The area under the curve (AUC) of the prediction model built on clinical risks was merely 0.659. The AUC of metabolomics prediction model was 0.977 and the AUC of proteomics was 0.875 while the AUC of the integrative-omics prediction model was 0.955.ConclusionsMetabolic and protein biomarkers in peripheral blood both have high efficacy and reliability in the prediction of immunotherapy sensitivity in unresectable stage III and IV non-small cell lung cancer, but validation in larger population-based cohorts is still needed.
Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers
Authors: Garrido Ameth N. , Machhar Rohan , Cruz-Correa Omar F. , Ganatra Darshini , Crome Sarah Q. , Wither Joan , Jurisica Igor , Gladman Dafna D. 
Published: February 2025

ObjectiveTo identify biomarkers that distinguish psoriatic arthritis (PsA) from cutaneous psoriasis without arthritis (PsC) and healthy controls (HC) using single cell RNA sequencing (scRNA-seq).MethodPeripheral blood mononuclear cell samples from three patients with PsA fulfilling CASPAR criteria, three patients with PsC and two HC were profiled using scRNA-seq. Differentially expressed genes (DEGs) identified through scRNA-seq were validated on classical monocytes, and CD4+ and CD8+ T cell subsets derived from an independent cohort of patients using the NanoString nCounter® platform. Protein expression was measured in CD4+ and CD8+ T cells by immunoblotting.ResultsA total of 18 immune cell population clusters were identified. Across 18 cell clusters, we identified 234 DEGs. NFKBIA and TNFAIP3 were overexpressed in PsA vs HC and PsC patients. Immunoblotting of the proteins encoded in these genes (IκBα and A20, respectively) showed higher levels in PsA CD4+ T cells compared to HC. Conversely, lower levels were observed in PsA CD8+ T cell lysates compared to HC for both proteins.ConclusionThese results suggest that translation of TNFAIP3 and NFKBIA may be inhibited in PsA CD8+ T cells. This study provides insight into the cellular heterogeneity of PsA, showing that non-cell type specific expression of genes associated with the disease can be dysregulated through different mechanisms in distinct cell types.
Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis
Authors: Mao Jia-yu , Xie Ya-wen , Lei Xian-li , Zhang Jia-hui , Cheng Wei , Cui Na 
Published: February 2025

BackgroundNeutrophil acts as a double-edged sword in the immune system. We hypothesized that an elevated neutrophil granule protein level is associated with sepsis-associated lymphopenia (SAL).MethodsWe enrolled 61 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between May 2022 and October 2023 in this study. Clinical and immunological parameters were recorded. Levels of neutrophil granule proteins, including myeloperoxidase (MPO) and neutrophil elastase (NE), and pyroptosis factors were examined.ResultsLevels of neutrophil granule proteins (MPO, 82.9 vs. 175.3, p &lt; 0 &lt;.0001; NE, 56.3 vs. 144.2, p &lt; 0.0001) were significantly higher in patients with sepsis with lymphopenia. Neutrophil granule protein levels were independently associated with SAL risk (MPO: OR = 1.0841, 95% CI, 1.0020–1.1730; NE: OR = 1.0540, 95% CI, 1.0040–1.1065). The area under the curve of MPO levels predicting SAL occurrence was 0.939 (95% CI, 0.846–0.984), and that of NE was 0.950 (95% CI, 0.862–0.989). Furthermore, neutrophil granule proteins were significantly correlated with CD4+ T cell and its pyroptosis [MPO and CD4+ T cells (r = −0.4039, p &lt; 0.0001), CD4+NLRP3 (r = 0.4868, p &lt; 0.0001), NE and CD4+ T cells (r = −0.5140, p &lt; 0.0001), and CD4+NLRP3 (r = 0.6513, p &lt; 0.0001)].ConclusionIncreased levels of neutrophil granule proteins were significantly associated with SAL incidence, and a significant relationship between neutrophil granule proteins and the pyroptosis pathway of CD4+ T cells was revealed.Clinical trial registrationchictr.org.cn identifier ChiCTR-ROC-17010750.
Adjuvanted subunit intranasal vaccine reduces SARS-CoV-2 onward transmission in hamsters
Authors: Sui Yongjun , Kar Swagata , Chawla Bhavna , Hoang Tanya , Yu YuanKai , Wallace Shannon M. , Andersen Hanne , Berzofsky Jay A. 
Published: February 2025

IntroductionMost COVID-19 vaccine trials have focused on recipient protection, not protection of their contacts, a critical need. As a subunit intranasal COVID-19 vaccine reduced nasopharyngeal virus more than did an intramuscular (IM) vaccine, we hypothesized that this vaccine might reduce onward transmission to others.MethodsWe vaccinated hamsters with either the IM-administrated licensed mRNA vaccine twice or one dose of mRNA IM followed by adjuvanted subunit intranasal vaccine. 24 hours after SARS-CoV-2 challenge, these animals were housed with naïve recipients in a contactless chamber that allows airborne transmission.ResultsOnward airborne transmission was profoundly blocked: the donor and recipients of the intranasal vaccine-boosted group had lower oral and lung viral loads (VL), which correlated with mucosal ACE2 inhibition activity. Notably, in this head-to-head comparison of COVID-19 booster vaccines on SARS-CoV-2 onward transmission, we found that statistically significant viral reduction in the lung tissues and oral swabs was observed only in the intranasal S1 nanoparticle vaccine-boosted group, but not in the systemic mRNA vaccine-boosted group, suggesting the superior protection of this intranasal vaccine, which could act as an attractive vaccine booster candidate to complement the current licensed systemic vaccines.DiscussionOverall, our study strongly supports the use of the intranasal vaccine as a boost to protect not only the vaccinated person, but also people exposed to the vaccinated person, a key public health goal.
Bradykinin B1 receptor signaling triggers complement activation on endothelial cells
Authors: Lopatko Fagerström Ingrid , Gerogianni Alexandra , Wendler Markus , Arvidsson Ida , Tontanahal Ashmita , Kristoffersson Ann-Charlotte , Qadri Fatimunnisa , Bader Michael , Karpman Diana 
Published: February 2025

IntroductionThe complement and kallikrein-kinin systems (KKS) are both activated during vascular inflammation, and there are many known interactions between the two systems. This study investigated if KKS activation induced complement activation on endothelial cells, and if activation was dependent on bradykinin B1 receptor (B1R) signaling.MethodsKKS was activated in normal human serum by kaolin or activated factor XII (FXIIa). ADP-preactivated primary glomerular endothelial cells (PGECs) were incubated with serum, with or without kaolin or FXIIa, and with or without the B1R antagonist (R715) or the inositol triphosphate receptor (IP3R) inhibitor 2-aminoethoxydiphenyl borate (2-APB). Complement factors C3a, factor Ba and C5b-9 were evaluated by ELISA or immunoblotting. B1/B2 receptor double knock-out and wild-type mice were injected with lipopolysaccharide from E. coli B5:O55, to induce KKS activation.ResultsSupernatants from PGECs incubated with serum exposed to kaolin or FXIIa exhibited higher levels of Ba and C5b-9, which were significantly reduced in the presence of the B1R antagonist. Complement activation induced by FXIIa was also reduced in the presence of the IP3R inhibitor. Likewise, cell lysates showed higher levels of C3a and C5b-9 in the presence of kaolin and FXIIa, and complement activation was significantly reduced in the presence of the B1R antagonist. B1/B2 receptor double knock-out mice exhibited less C3 and C5b-9 deposition in glomeruli compared to wild-type mice.ConclusionThis study demonstrates that KKS activation contributes to complement activation on the endothelium by B1R signaling. Blocking the B1R may have a role in reducing complement deposition and its effects on the endothelium.
Acupuncture for somatosensory deficits after stroke: a systematic review and meta-analysis
Authors: Ren Shumeng , Chen Yuhang , Liu Yu , Lv Qiuyi , Peng Jing , Song Lei , Zou Yihuai , Zhang Hua , Chen Xing 
Published: February 2025

ObjectiveThis meta-analysis aimed to evaluate the randomized controlled trials (RCTs) of acupuncture for somatosensory deficits after stroke to provide the current best evidence for clinical practice.MethodsA systematic search was performed for eligible articles on the acupuncture for somatosensory deficits after stroke based on 14 databases. Two reviewers independently screened the RCTs, extracted data, and evaluated the methodological quality. A meta-analysis of RCTs was conducted using STATA 11.0 software.ResultsA total of 57 RCTs were included. Meta-analysis results showed that compared with the control group, the acupuncture group had a higher effective rate [risk ratio (RR) = 1.21, 95% CI (1.17, 1.24), I2 = 10.6%, P &lt; 0.001] and a better sensory disturbance score [mean difference (MD) = 5.37, 95%CI (3.81, 6.92), I2 = 93.9%, P &lt; 0.001]. The Visual Analog Scale in the acupuncture group was lower [MD = −1.44, 95%CI (−1.81, −1.07), I2 = 94.5%, P &lt; 0.001]. The acupuncture also showed an improvement in the ability of daily living [MD = 12.19, 95% CI (8.50, 15.87), I2 = 97.2%, P &lt; 0.001] and the symptoms of neurological deficit [Standardized Mean Difference (SMD) = −1.53, 95%CI (−2.04, −1.03), I2 = 89.7%, P &lt; 0.001].ConclusionsThe current best evidence shows that acupuncture has advantages in raising the effective rate, alleviating sensory disturbance, relieving pain, enhancing the ability of daily living, and improving the symptoms of neurological deficits for somatosensory deficits after stroke compared with the control group. And the adverse reactions in acupuncture group were acceptable. However, further well-designed high-quality and multicenter international studies are needed to verify the effectiveness and safety of acupuncture for somatosensory deficits after stroke.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020186040.
Severe soft tissue injuries in multiple trauma patients—a challenge we can meet? A matched-pair analysis from the TraumaRegister DGU®
Authors: Kirsten Nora , Franke Georg Maximilian , Lefering Rolf , Klüter Tim , Weuster Matthias , Müller Michael , Lippross Sebastian , Seekamp Andreas ,   TraumaRegister DGU®, Fitschen-Oestern Stefanie 
Published: February 2025

IntroductionDespite tremendous clinical efforts over the past few decades, the treatment of severely injured patients remains still challenging. Concomitant soft tissue injuries represent a particular challenge, as they can lead to complications at any time of trauma care, hold a high risk of infection and often require multiple surgical interventions and interdisciplinary collaboration.MethodsThis retrospective, multicentric study used the TraumaRegister DGU® to examine the effect of open fractures and severe soft tissue injuries on outcome of multiple trauma patients. Primary admitted multiple trauma patients at the age of 16 to 70 years, treated from 2010 to 2021, were included. A Matched pair analysis was performed for better comparability of trauma patients with and without open fractures and/or severe soft tissue injuries.ResultsAfter applying the matching criteria, 5,795 pairs were created and analyzed. The group with sustained soft tissue injuries/open fractures was found to have a higher ISS ([mean ± SD] 22.1 ± 10.4 vs. 20.6 ± 10.2, p &lt; 0.001). Endotracheal tube insertion (27.7% vs. 30.4%, p = 0.003), catecholamine administration (6.0% vs. 8.4%, p &lt; 0.001) and cardio-pulmonary resuscitation (1.6% vs. 2.1%, p = 0.027) were more frequent in the group with sustained soft tissue injury. Both groups were equally frequent admitted to the intensive care unit (ICU) and length of stay (LOS) at the ICU (median (quartiles) 3 (1–9) versus 3 (1–9)) did not differ significantly. However, total LOS at the hospital was longer for the group with sustained soft tissue injury (median (quartiles) 18 (11–29) versus 17 (10–27)). Sepsis occurred more often in patients with soft tissue injury (4.3% vs. 5.2%, p = 0.034). There was no significant difference in prevalence of multi organ failure, 24 h-mortality (2.1% vs. 2.5%, p = 0.151) and overall-mortality (3.6% vs. 3.9%, p = 0.329) between both groups.ConclusionDue to database analysis and revision of guidelines, the treatment of severely injured patients has steadily improved in recent years. Patients with severe soft tissue injuries/open fractures required more medical interventions and length of stay at the hospital was longer. In this study, we were able to show that although concomitant severe soft tissue injuries required more ICU interventions and led to a longer length of stay, 24-h and all-cause mortality were not significantly increased.