bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the impact of an AI-enabled conversational agent mobile app on users’ mental health and wellbeing with a self-reported maternal event: a mixed method real-world data mHealth study
Authors: Inkster Becky , Kadaba Madhura , Subramanian Vinod 
Published: June 2023

BackgroundMaternal mental health care is variable and with limited accessibility. Artificial intelligence (AI) conversational agents (CAs) could potentially play an important role in supporting maternal mental health and wellbeing. Our study examined data from real-world users who self-reported a maternal event while engaging with a digital mental health and wellbeing AI-enabled CA app (Wysa) for emotional support. The study evaluated app effectiveness by comparing changes in self-reported depressive symptoms between a higher engaged group of users and a lower engaged group of users and derived qualitative insights into the behaviors exhibited among higher engaged maternal event users based on their conversations with the AI CA.MethodsReal-world anonymised data from users who reported going through a maternal event during their conversation with the app was analyzed. For the first objective, users who completed two PHQ-9 self-reported assessments (n = 51) were grouped as either higher engaged users (n = 28) or lower engaged users (n = 23) based on their number of active session-days with the CA between two screenings. A non-parametric Mann–Whitney test (M–W) and non-parametric Common Language effect size was used to evaluate group differences in self-reported depressive symptoms. For the second objective, a Braun and Clarke thematic analysis was used to identify engagement behavior with the CA for the top quartile of higher engaged users (n = 10 of 51). Feedback on the app and demographic information was also explored.ResultsResults revealed a significant reduction in self-reported depressive symptoms among the higher engaged user group compared to lower engaged user group (M–W p = .004) with a high effect size (CL = 0.736). Furthermore, the top themes that emerged from the qualitative analysis revealed users expressed concerns, hopes, need for support, reframing their thoughts and expressing their victories and gratitude.ConclusionThese findings provide preliminary evidence of the effectiveness and engagement and comfort of using this AI-based emotionally intelligent mobile app to support mental health and wellbeing across a range of maternal events and experiences.
Influences of resolvin D1 and D2 on the risk of type 2 diabetes mellitus: a Chinese community-based cohort study
Authors: Sun Qian , Wang Junrong , Jing Yang , Liu Jingchao , Jin Jianrong , Wang Sudan , Zhang Jin , Liu Kaili , Chen Xiaofang , Zhou Hui , Dong Chen 
Published: June 2023

BackgroundAlthough cellular and animal studies have reported that resolvin D1 (RvD1) and resolvin D2 (RvD2) are mechanisms involved in the development of type 2 diabetes mellitus (T2DM), the impact of RvD1 and RvD2 on the risk of T2DM at a population level remains unclear.MethodsWe included 2755 non-diabetic adults from a community-based cohort in China and followed them for seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of RvD1 and RvD2 with T2DM probability. Time-dependent receiver operator characteristics (ROC) curve was used to evaluate the predictive performance of RvD1 and RvD2 for the risk of T2DM based on the Chinese CDC T2DM prediction model (CDRS).ResultsA total of 172 incident T2DM cases were identified. Multivariate-adjusted HRs (95% CI) for T2DM across quartiles of RvD1 levels (Q1, Q2, Q3 and Q4) were 1.00, 1.64 (1.03-2.63), 1.80 (1.13-2.86) and 1.61 (1.01-2.57), respectively. Additionally, body mass index (BMI) showed a significant effect modification in the association of RvD1 with incident T2DM (Pinteraction = 0.026). After multivariate adjustment, the HR (95% CI) for T2DM in the fourth compared with the first quartile of RvD2 was 1.94 (95% CI: 1.24-3.03). Time-dependent ROC analysis showed that the area under time-dependent ROC curves of the “CDRS+RvD1+RvD2” model for the 3-, 5- and 7-year risk of T2DM were 0.842, 0.835 and 0.828, respectively.ConclusionsHigher RvD1 and RvD2 levels are associated with a higher risk of T2DM at the population level.
A hepatitis B virus-derived peptide combined with HBsAg exerts an anti-HBV effect in an HBV transgenic mouse model as a therapeutic vaccine
Authors: Choi Yu-Min , Kim Dong Hyun , Jang Junghwa , Kim Bum-Joon 
Published: June 2023

IntroductionFor complete or functional cure of hepatitis B virus (HBV) infection, application of immunotherapy is now being attempted. Recently, we reported that a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, exerts a strong anticancer effect in tumor-implanted mice through inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner, suggesting its potential as a vaccine adjuvant.MethodsIn this study, we explored the potential of Poly6 in combination with HBsAg as a therapeutic vaccine against hepatitis B virus infection. We investigated the immunotherapeutic potential of Poly6 combined with HBsAg vaccination against hepatitis B virus infection in C57BL/6 mice or an HBV transgenic mouse model.ResultsIn C57BL/6 mice, Poly6 enhanced DC maturation and DC migration capacity in an IFN-I-dependent manner. Moreover, the addition of Poly6 to alum in combination with HBsAg also led to enhanced HBsAg-specific cell-mediated immune (CMI) responses, suggesting its potential as an adjuvant of HBsAg-based vaccines. In HBV transgenic mice, vaccination with Poly6 combined with HBsAg exerted a strong anti-HBV effect via induction of HBV-specific humoral and cell-mediated immune responses. In addition, it also induced HBV-specific effector memory T cells (TEM).DiscussionOur data indicated that vaccination with Poly6 in combination with HBsAg exerts an anti-HBV effect in HBV transgenic mice, which is mainly mediated by HBV-specific CMI and humoral immune responses via IFN-I-dependent DC activation, suggesting the feasibility of Poly6 as an adjuvant for an HBV therapeutic vaccine.
The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age
Authors: Orillard E. , Spehner L. , Mansi L. , Bouard A. , Falcoz A. , Lepiller Q. , Renaude E. , Pallandre JR. , Vienot A. , Kroemer M. , Borg C. 
Published: June 2023

PurposeCancer patients are at risk of severe COVID-19 infection, and vaccination is recommended. Nevertheless, we observe a failure of COVID-19 vaccines in this vulnerable population. We hypothesize that senescent peripheral T-cells alter COVID-19 vaccine-induced immunity.MethodsWe performed a monocentric prospective study and enrolled cancer patients and healthy donors before the COVID-19 vaccination. The primary objective was to assess the association of peripheral senescent T-cells (CD28-CD57+KLRG1+) with COVID-19 vaccine-induced immunity.ResultsEighty cancer patients have been included, with serological and specific T-cell responses evaluated before and at 3 months post-vaccination. Age ≥ 70 years was the principal clinical factor negatively influencing the serological (p=0.035) and specific SARS-CoV-2 T-cell responses (p=0.047). The presence of senescent T-cells was correlated to lower serological (p=0.049) and specific T-cell responses (p=0.009). Our results sustained the definition of a specific cut-off for senescence immune phenotype (SIP) (≥ 5% of CD4 and ≥ 39.5% of CD8 T-cells), which was correlated to a lower serological response induced by COVID-19 vaccination for CD4 and CD8 SIPhigh (p=0.039 and p=0.049 respectively). While CD4 SIP level had no impact on COVID-19 vaccine efficacy in elderly patients, our results unraveled a possible predictive role for CD4 SIPhigh T-cell levels in younger cancer patients.ConclusionsElderly cancer patients have a poor serological response to vaccination; specific strategies are needed in this population. Also, the presence of a CD4 SIPhigh affects the serological response in younger patients and seems to be a potential biomarker of no vaccinal response.
Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma
Authors: Esposito Ilaria , Kontra Ioanna , Giacomassi Chiara , Manou-Stathopoulou Sotiria , Brown James , Stratton Richard , Verykokou Galateia , Buccafusca Roberto , Stevens Michael , Nissim Ahuva , Lewis Myles J. , Pfeffer Paul E. 
Published: June 2023

BackgroundThe chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase (MPO) in ANCA-positive EGPA (eosinophilic granulomatosis with polyangiitis). Previous research has shown that oxidative post-translational modification (oxPTM) of proteins is an important mechanism by which autoantibody responses may escape immune tolerance. Autoantibodies to oxPTM autoantigens in SEA have not previously been studied.MethodsPatients with EGPA and SEA were recruited as well as healthy control participants. Autoantigen agnostic approach: Participant serum was incubated with slides of unstimulated and PMA-stimulated neutrophils and eosinophils, and autoantibodies to granulocytes were identified by immunofluorescence with anti-human IgG FITC antibody. Target autoantigen approach: Candidate proteins were identified from previous literature and FANTOM5 gene set analysis for eosinophil expressed proteins. Serum IgG autoantibodies to these proteins, in native and oxPTM form, were detected by indirect ELISA.ResultsImmunofluorescence studies showed that serum from patients with known ANCA stained for IgG against neutrophils as expected. In addition, serum from 9 of 17 tested SEA patients stained for IgG to PMA-stimulated neutrophils undergoing NETosis. Immunofluorescent staining of eosinophil slides was evident with serum from all participants (healthy and with eosinophilic disease) with diffuse cytoplasmic staining except for one SEA individual in whom subtle nuclear staining was evident. FANTOM5 gene set analysis identified TREM1 (triggering receptor expressed on myeloid cells 1) and IL-1 receptor 2 (IL1R2) as eosinophil-specific targets to test for autoantibody responses in addition to MPO, eosinophil peroxidase (EPX), and Collagen-V identified from previous literature. Indirect ELISAs found high concentrations of serum autoantibodies to Collagen-V, MPO, and TREM1 in a higher proportion of SEA patients than healthy controls. High concentrations of serum autoantibodies to EPX were evident in serum from both healthy and SEA participants. The proportion of patients with positive autoantibody ELISAs was not increased when examining oxPTM compared to native proteins.DiscussionAlthough none of the target proteins studied showed high sensitivity for SEA, the high proportion of patients positive for at least one serum autoantibody shows the potential of more research on autoantibody serology to improve diagnostic testing for severe asthma.Clinical trial registrationClinicalTrials.gov, identifier, NCT04671446.
A synthetic glycodendropeptide induces methylation changes on regulatory T cells linked to tolerant responses in anaphylactic-mice
Authors: Núñez Rafael , Rodríguez María J. , Lebrón-Martín Clara , Martín-Astorga María del Carmen , Ramos-Soriano Javier , Rojo Javier , Torres María J. , Cañas José A. , Mayorga Cristobalina 
Published: June 2023

IntroductionLipid transfer proteins (LTPs) are allergens found in a wide range of plant-foods. Specifically, Pru p 3, the major allergen of peach, is commonly responsible for severe allergic reactions. The need for new alternatives to conventional food allergy treatments, like restrictive diets, suggests allergen immunotherapy as a promising option. It has been demonstrated that sublingual immunotherapy (SLIT) with synthetic glycodendropeptides, such as D1ManPrup3, containing mannose and Pru p 3 peptides induced tolerance in mice and that the persistence of this effect depends on treatment dose (2nM or 5nM). Moreover, it produces changes associated with differential gene expression and methylation profile of dendritic cells, as well as phenotypical changes in regulatory T cells (Treg). However, there are no works addressing the study of epigenetic changes in terms of methylation in the cell subsets that sustain tolerant responses, Treg. Therefore, in this work, DNA methylation changes in splenic-Treg from Pru p 3 anaphylactic mice were evaluated.MethodsIt was performed by whole genome bisulphite sequencing comparing SLIT-D1ManPrup3 treated mice: tolerant (2nM D1ManPrup3), desensitized (5nM D1ManPrup3), and sensitized but not treated (antigen-only), with anaphylactic mice.ResultsMost of the methylation changes were found in the gene promoters from both SLIT-treated groups, desensitized (1,580) and tolerant (1,576), followed by the antigen-only (1,151) group. Although tolerant and desensitized mice showed a similar number of methylation changes, only 445 genes were shared in both. Remarkably, interesting methylation changes were observed on the promoter regions of critical transcription factors for Treg function like Stat4, Stat5a, Stat5b, Foxp3, and Gata3. In fact, Foxp3 was observed exclusively as hypomethylated in tolerant group, whereas Gata3 was only hypomethylated in the desensitized mice.DiscussionIn conclusion, diverse D1ManPrup3 doses induce different responses (tolerance or desensitization) in mice, which are reflected by differential methylation changes in Tregs.
Exploration of the impact of multimode thermal therapy versus radiofrequency ablation on CD8+ T effector cells of liver malignancies based on single cell transcriptomics
Authors: Wang Ying , Wang Guang-Zhi , Chen Chao , Huang Hao-Zhe , Wang Yao-Hui , He Xin-Hong , Xu Lisa X. , Xu Li-Chao , Li Wen-Tao 
Published: June 2023

IntroductionMultimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies.MethodsIn this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment. ResultsThere was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8+ effector T (CD8+ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway. ConclusionThis study confirmed that MTT could more effectively activate peripheral CD8+ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.
Dectin-1 signaling coordinates innate and adaptive immunity for potent host defense against viral infection
Authors: Kim Hyeong Won , Ko Mi-Kyeong , Park So Hui , Hwang Seong Yun , Kim Dong Hyeon , Park Sun Young , Ko Young-Joon , Kim Su-Mi , Park Jong-Hyeon , Lee Min Ja 
Published: June 2023

BackgroundMost commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety.ObjectivesTo address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection.MethodsWe demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan.Resultsβ-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host’s innate and adaptive immunity.ConclusionOur study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine’s safety and efficacy, it represents a breakthrough among next-generation FMD vaccines.
The evaluation of JAK inhibitors on effect and safety in alopecia areata: a systematic review and meta-analysis of 2018 patients
Authors: Mao Mei-qi , Ding Yu-xin , Jing Jing , Tang Zhen-wei , Miao Yu-jie , Yang Xiao-shuang , Chen Yu-hong , Chen Sheng-zhao , Wu Xian-jie , Lu Zhong-fa 
Published: June 2023

BackgroundJAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking.ObjectiveEvaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis.MethodsEligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata.Results6 randomized controlled trials with 1455 patients exhibited SALT50 (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT90 (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT5 was 0.71(95% CI, 0.65-0.78), SALT50 was 0.54(95% CI 0.46-0.63), SALT90 was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions.LimitationsFew randomized controlled trials met the inclusion criteria and insufficiency of eligible data.ConclusionJAK inhibitors are effective in alopecia areata, although associated with an increased risk.
Recognition and location of marine animal sounds using two-stream ConvNet with attention
Authors: Hu Shaoxiang , Hou Rong , Liao Zhiwu , Chen Peng 
Published: June 2023

There are abundant resources and many endangered marine animals in the ocean. Using sound to effectively identify and locate them, and estimate their distribution area, has a very important role in the study of the complex diversity of marine animals (Hanny et al., 2013). We design a Two-Stream ConvNet with Attention (TSCA) model, which is a two-stream model combined with attention, in which one branch processes the temporal signal and the other branch processes the frequency domain signal; It makes good use of the characteristics of high time resolution of time domain signal and high recognition rate of frequency domain signal features of sound, and it realizes rapid localization and recognition of sound of marine species. The basic network architecture of the model is YOLO (You Only Look Once) (Joseph et al., 2016). A new loss function focal loss is constructed to strengthen the impact on the tail class of the sample, overcome the problem of data imbalance and avoid over fitting. At the same time, the attention module is constructed to focus on more detailed sound features, so as to improve the noise resistance of the model and achieve high-precision marine species identification and location. In The Watkins Marine Mammal Sound Database, the recognition rate of the algorithm reached 92.04% and the positioning accuracy reached 78.4%.The experimental results show that the algorithm has good robustness, high recognition accuracy and positioning accuracy.
Sex distinctive patterns in the association between serum bicarbonate and uric acid levels among healthy adults. Qatar biobank data
Authors: Ibrahim Wisam Nabeel , Shi Zumin , Abdallah Atiyeh M. , Abu-Madi Marawan Abdelhamid 
Published: June 2023

BackgroundUric acid is the final product of purine metabolism and is a potent plasma antioxidant but with pro-inflammatory effects. At high levels, it may increase the risk of developing multiple chronic diseases, such as gout, atherosclerosis, hypertension, and renal diseases. The aim of this study was to assess the sex-specific association between serum bicarbonate and uric acid levels among healthy adults.MethodologyThis retrospective cross-sectional study included 2,989 healthy Qatari adults (36.4 ± 11.1  years) from the Qatar Biobank database. Serum uric acid and bicarbonate levels were estimated alongside other serological markers. Participants free from chronic diseases were divided into four quartiles based on serum bicarbonate levels. The sex-specific relationship between serum bicarbonate and uric acid levels was assessed through univariate and multivariate analyses.ResultsIn men, low serum uric acid levels were significantly associated with higher quartiles of serum bicarbonate levels after adjusting for age. The association remained significant after further adjustment for BMI, smoking, and renal function. The subgroup analysis using the restricted cubic spline method confirmed a significant dose–response association between the variation coefficients of uric acid by serum bicarbonate level in men with adjustments for age, BMI, smoking, and renal function. In women, no significant association was found between quartiles of serum bicarbonate and uric acid levels following the same adjustments. However, using the restricted cubic spline method, a significant bidirectional relation was demonstrated between serum bicarbonate and the variation coefficients of uric acid that were positive for serum bicarbonate levels below 25 mEq/L and negative at higher levels.ConclusionSerum bicarbonate levels are linearly associated with reduced serum uric acid levels among healthy adult men, which may be a potential protective factor against hyperuricemia-related complications. Further research is needed to determine the underlying mechanisms.