bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis
Authors: Fan Kai , Zhou Shican , Jin Ling , Tan Shiwang , Lai Ju , Zhang Zimu , Li Jingwen , Xu Xiayue , Yao Chunyan , Yan Zhiqiang , Yu Shaoqing 
Published: July 2023

Abstract
Background
Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR.

Methods
The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment.

Results
GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1.

Conclusion
Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.
Fear of falling as a mediator in the association between social frailty and health-related quality of life in community-dwelling older adults
Authors: Wu Kuan-Ying , Chen Duan-Rung , Chan Chang-Chuan , Yeh Yen-Po , Chen Hsiu-Hsi 
Published: July 2023

AbstractBackgroundSocial frailty is associated with Fear of Falling (FoF) and health-related quality of life (HrQoL). However, how social frailty simultaneously influences FoF and HrQoL remains unclear. The study aims to understand the links between social frailty, FoF, and HrQoL in older adults and the mediating role of FoF in the relations between social frailty and HrQoL.MethodsIn this cross-sectional survey, 1,933 community-dwelling older adults from Changhua County, Taiwan, were interviewed using a self-administrated questionnaire. In total, 1,251 participants with complete data were included for analysis. Data were analyzed using the SPSS PROCESS macro. A simple mediation was employed using social frailty as the independent variable, FoF as the mediator variable, and HrQoL as the outcome variable.ResultsSocial frailty was associated with HrQoL and indirectly with HrQoL through FoF, and FoF was directly associated with HrQoL. Of the 5-item social frailty index, “going out less frequently” was correlated with HrQoL and indirectly with HrQoL through FoF. Individuals who felt unhelpful toward family or friends had the worst physical HrQoL and did not talk to someone daily had the most negative influence on mental HrQoL.ConclusionsSocial frailty can directly and indirectly, through FoF decrease HrQoL. It also emphasizes the importance of social connectivity in reducing the risk of falls. This study points to the need for social connectivity and fall prevention programs as essential components of strategies to enhance the health and well-being of community-dwelling older adults.
Clinical significance of B7-H3 expression in circulating CD4+CD25high T cells, CD14+ monocytes, and plasma for the progression of HIV infection
Authors: Xu Jun-Chi , Chen Hui , Xu Ping , You Xin-Ran , Zhu Geng-chao , Gao Fei 
Published: July 2023

Abstract
Background
B7-H3 is an important immune checkpoint molecule that plays a negative role in immune regulation. This study was aimed to explore B7-H3 expression in HIV-infected patients and its clinical significance.

Methods
To explore the expression and clinical significance of B7-H3 in HIV-infected patients, we investigated the B7-H3 expression pattern and the correlation of B7-H3 expression with clinical parameters of HIV-infected patients with different levels of CD4+ T cells. To assess the role of B7-H3 in regulating the function of T cells in HIV infection, we performed a proliferation assay and T cell function test in vitro.

Results
B7-H3 expression in HIV-infected patients was significantly higher than that in healthy controls. mB7-H3 expression on CD4+CD25high T cells and CD14+ monocytes increased with disease progression. mB7-H3 expression on CD4+CD25high T cells and monocytes was negatively correlated with lymphocyte count, CD4+T cell count, and positively correlated with HIV viral load in HIV-infected patients. when the number of CD4+ T cells in HIV-infected patients was ≥ 200/µL, sB7-H3 and mB7-H3 expression levels on CD4+CD25high T cells and monocytes were negatively correlated with lymphocyte count, CD4+T cell count. sB7-H3 and mB7-H3 expression on monocytes were positively correlated with HIV viral load. B7-H3 inhibited the proliferation of lymphocytes and the secretion of IFN-γ in vitro, especially the ability of CD8+ T cells to secrete IFN-γ.

Conclusions
B7-H3 played an important negative regulatory role in anti-HIV infection immunity. It could be used as a potential biomarker for the progression of HIV infection and a novel target for the treatment of HIV infection.
Use of period analysis to provide a timely assessment of 5-year relative survival for pancreatic cancer patients from Taizhou, eastern China
Authors: Lu Ye , He Min , Lian Liyou , Lei Huijun , Cheng Yongran , Wang Liangyou , Chen Tianhui , Chen Jinfei 
Published: July 2023

AbstractAssessing long-term tumor survival rates is crucial for evaluating the effectiveness of tumor treatment and burden. However, timely assessment of long-term survival in patients with pancreatic cancer is lagging in China. In this study, we applied period analysis to estimate the long-term survival of pancreatic cancer patients using data from four population-based cancer registries in Taizhou city, eastern China. A total of 1121 patients diagnosed with pancreatic cancer between 2004 and 2018 were included. We assessed the 5-year relative survival (RS) using period analysis and further stratified by sex, age at diagnosis, and region. The 5-year RS during 2014–2018 overall reached 18.9% (14.7% for men and 23.3% for women, respectively). A decrease of the 5-year RS from 30.3% to 11.2% was observed in four diagnostic age gradients (< 55, 55–64, 65–74, and > 74 years age groups). The 5-year RS was higher in urban (24.2%) than in rural (17.4%) areas. Moreover, the 5-year RS of pancreatic cancer patients showed an overall increasing trend for the three periods (2004–2008, 2009–2013, and 2014–2018). Our study, using period analysis for the first time in China, provides the latest estimates of the survival of patients with pancreatic cancer, which provides essential evidence for the prevention and intervention of pancreatic cancer. The results also indicate the importance of further applications of the period analysis for more up-to-date and accurate survival estimates.
The association between physical activity and subjective well-being among adolescents in southwest China by parental absence: a moderated mediation model
Authors: Zhang Ming , Xu Xiaohe , Jiang Jianjun , Ji Yuanyi , Yang Ruixi , Liu Qijiao , Li Shiying , Li Yuchen , Liu Qiaolan 
Published: July 2023

Abstract
Objectives
Built on the Positive Youth Development (PYD) framework, this study examined how physical activity affected the subjective well-being of adolescents in the multi-ethnic area of southwest China. The mediating role of school connectedness as an external development asset and the moderating role of resilience as an internal development asset were specified and tested within the framework of sport-based PYD.

Methods
A cross-sectional survey of 3143 adolescents (47.2% boys with mean age = 12.88 and SD = 1.68) was conducted in 2020. A structural equation model (SEM) was developed to estimate the direct effect of physical activity, the mediating effect of school connectedness, and the moderating effect of resilience on adolescents’ subjective well-being. Multi-group comparison was made to investigate differences and similarities across three parental absence subgroups: (1) both parents present, (2) one parent absent, and (3) both parents absent.

Results
As surmised, physical activity, school connectedness, and resilience all positively and significantly affected adolescents’ subjective well-being. SEM analyses revealed that school connectedness mediated the effect of physical activity on subjective well-being. Moreover, resilience moderated both the direct and indirect effects of physical activity (through school connectedness) on subjective well-being. Finally, the multi-group comparison revealed a moderating effect of parental absence on the moderated mediation model.

Limitations
This study is a cross-sectional survey, so inference of causal associations among the study variables is impossible.

Conclusions
Healthy lifestyle behaviors, school-supportive settings, and positive individual development assets can enhance the subjective well-being of adolescents in southwest China, especially those whose parents were absent. Physical activity interventions informed by the PYD framework should be incorporated into public health programs designed to foster the physical and mental health of left-behind adolescents in southwest China.
Ventilator management and risk of air leak syndrome in patients with SARS-CoV-2 pneumonia: a single-center, retrospective, observational study
Authors: Miyake Nodoka , Igarashi Yutaka , Nakae Ryuta , Mizobuchi Taiki , Masuno Tomohiko , Yokobori Shoji 
Published: July 2023

Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia is reportedly associated with air leak syndrome (ALS), including mediastinal emphysema and pneumothorax, and has a high mortality rate. In this study, we compared values obtained every minute from ventilators to clarify the relationship between ventilator management and risk of developing ALS.

Methods
This single-center, retrospective, observational study was conducted at a tertiary care hospital in Tokyo, Japan, over a 21-month period. Information on patient background, ventilator data, and outcomes was collected from adult patients with SARS-CoV-2 pneumonia on ventilator management. Patients who developed ALS within 30 days of ventilator management initiation (ALS group) were compared with those who did not (non-ALS group).

Results
Of the 105 patients, 14 (13%) developed ALS. The median positive-end expiratory pressure (PEEP) difference was 0.20 cmH2O (95% confidence interval [CI], 0.20–0.20) and it was higher in the ALS group than in the non-ALS group (9.6 [7.8–20.2] vs. 9.3 [7.3–10.2], respectively). For peak pressure, the median difference was -0.30 cmH2O (95% CI, -0.30 – -0.20) (20.4 [17.0–24.4] in the ALS group vs. 20.9 [16.7–24.6] in the non-ALS group). The mean pressure difference of 0.0 cmH2O (95% CI, 0.0–0.0) (12.7 [10.9–14.6] vs. 13.0 [10.3–15.0], respectively) was also higher in the non-ALS group than in the ALS group. The difference in single ventilation volume per ideal body weight was 0.71 mL/kg (95% CI, 0.70–0.72) (8.17 [6.79–9.54] vs. 7.43 [6.03–8.81], respectively), and the difference in dynamic lung compliance was 8.27 mL/cmH2O (95% CI, 12.76–21.95) (43.8 [28.2–68.8] vs. 35.7 [26.5–41.5], respectively); both were higher in the ALS group than in the non-ALS group.

Conclusions
There was no association between higher ventilator pressures and the development of ALS. The ALS group had higher dynamic lung compliance and tidal volumes than the non-ALS group, which may indicate a pulmonary contribution to ALS. Ventilator management that limits tidal volume may prevent ALS development.
Associations of health literacy, personality traits, and pro-individualism with the willingness to complete advance directives in Taiwan
Authors: Chen Duan-Rung , Weng Hui-Ching 
Published: July 2023

Abstract
Background
Studies indicated that patients with advance directives (ADs) have a generally better quality of life near death. Yet, the concept of ADs is relatively new in East Asian countries. This study examined the associations between health literacy, pro-individualism in end-of-life (EOL) decisions (i.e., EOL pro-individualism), and master-persistence personality traits with the willingness to complete ADs.

Methods
The data is from a representative data of 1478 respondents from the 2022 Taiwan Social Change Survey. Generalized structural equation modeling (GSEM) was used to conduct path analysis.

Results
Nearly half of the respondents (48.7%) were willing to complete ADs. Health literacy has direct and indirect effects through EOL pro-individualism values on the willingness to complete ADs. Noncognitive factors such as mastery-persistence personality traits and EOL pro-individualism values enhanced the willingness to complete ADs.

Conclusion
A personalized communication strategy, mindful of personality dimensions and cultural values, can address individual fears and concerns, promoting the benefits of advance care planning (ACP). These influences can provide a roadmap for healthcare providers to customize their approach to ACP discussions, improving patient engagement in AD completion.
The dual role dilemma of liver transplantation health care professionals
Authors: Binder Annette , Fenchel Julia , Lang Immanuel , Batra Anil 
Published: July 2023

Abstract
Background
Similar to many other countries, in Germany patients with alcohol-related liver disease are obliged to prove their abstinence before being accepted on a waitlist for liver transplantation. Health care professionals (HCPs) must both treat patients and ensure that patients have proven their abstinence. The aim of this exploratory study was to develop a deeper understanding of how HCPs deal with this dual role.

Methods
The study used semi-structured interviews as the source of data. 11 healthcare professionals from ten of the 22 German transplant centers were interviewed. After transcription, a qualitative content analysis was performed.

Results
We found that these HCPs faced an ethical dilemma, as they must balance the roles of being both a treatment provider (the therapist role) and an assessor (the monitoring role). To solve this dilemma, the strategy seems to be a tendency for the HCPs to take on one dominant role amongst these two roles. HCPs who prefer to take on the therapist role seem to feel burdened by the 6-month abstinence rule and the obligation to monitor their patients. HCPs who prefer to take on the monitoring role tend to have negative assumptions about the patients. HCPs also reported the impression that patients perceive HCPs as more involved in monitoring and less open to the therapeutic role. From this it can be deduced that current regulations and structures lead both to stress for HCPs and to suboptimal therapy for those affected.

Conclusions
The results showed that current transplantation guidelines can have a negative impact on both patient care and the burdens on the HCPs. From our point of view, there are various changes that could be made to the current clinical practice that would help solve this dilemma. For instance, integrating other assessment criteria that are more closely adapted to the health status trajectory and psychosocial background of the individual patient would be both possible and would lead to improvements in practice.
Institutional review boards in Saudi Arabia: the first survey-based report on their functions and operations
Authors: AlFattani Areej , AlBedah Norah , AlShahrani Asma , Alkawi Ammar , AlMeharish Amani , Altwaijri Yasmin , Omar Abeer , AlKawi M. Zuheir , Khogeer Asim 
Published: July 2023

Abstract
Background
Institutional review boards (IRBs) are formally designated to review, approve, and monitor biomedical research. They are responsible for ensuring that researchers comply with the ethical guidelines concerning human research participants. Given that IRBs might face different obstacles that cause delays in their processes or conflicts with investigators, this study aims to report the functions, roles, resources, and review process of IRBs in Saudi Arabia.

Method
This was a cross-sectional self-reported survey conducted from March 2021 to March 2022. The survey was sent to 53 IRB chairpersons and the administration directors (or secretary) across the country through email after receiving verbal consent. The validated survey consisted of eight aspects: (a) organizational aspects, (b) membership and educational training, (c) submission arrangements and materials, (d) minutes, (e) review procedures, (f) communicating a decision, (g) continuing review, and (h) research ethics committee (REC) resources. A total of 200 points indicated optimal IRB functions.

Results
Twenty-six IRBs across Saudi Arabia responded to the survey. Overall, the IRBs in this study scored a total of 150/200 of the points on the self-assessment tool. Relatively newer IRBs (established less than ten years ago) conducted meetings at least once in a month, had annual funding, had more balanced gender representation, tended to score higher than older IRBs. The organizational aspect score was the lowest among all items in the survey (14.3 score difference, p-value < 0.01). The average turnaround time for expedited research from proposal submission to final decision was 7 days, while it was 20.5 days for the full committee review.

Conclusion
Saudi IRBs performed generally well. However, there is room for focused improvement with respect to extra resources and organizational issues that require closer evaluation and guidance from the regulatory bodies.
Liver in infections: a single-cell and spatial transcriptomics perspective
Authors: Zou Ju , Li Jie , Zhong Xiao , Tang Daolin , Fan Xuegong , Chen Ruochan 
Published: July 2023

AbstractThe liver is an immune organ that plays a vital role in the detection, capture, and clearance of pathogens and foreign antigens that invade the human body. During acute and chronic infections, the liver transforms from a tolerant to an active immune state. The defence mechanism of the liver mainly depends on a complicated network of intrahepatic and translocated immune cells and non-immune cells. Therefore, a comprehensive liver cell atlas in both healthy and diseased states is needed for new therapeutic target development and disease intervention improvement. With the development of high-throughput single-cell technology, we can now decipher heterogeneity, differentiation, and intercellular communication at the single-cell level in sophisticated organs and complicated diseases. In this concise review, we aimed to summarise the advancement of emerging high-throughput single-cell technologies and re-define our understanding of liver function towards infections, including hepatitis B virus, hepatitis C virus, Plasmodium, schistosomiasis, endotoxemia, and corona virus disease 2019 (COVID-19). We also unravel previously unknown pathogenic pathways and disease mechanisms for the development of new therapeutic targets. As high-throughput single-cell technologies mature, their integration into spatial transcriptomics, multiomics, and clinical data analysis will aid in patient stratification and in developing effective treatment plans for patients with or without liver injury due to infectious diseases.
Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes
Authors: Shumba Patience , Sura Thomas , Moll Kirsten , Chakrakodi Bhavya , Tölken Lea A. , Hoßmann Jörn , Hoff Katharina J. , Hyldegaard Ole , Nekludov Michael , Svensson Mattias , Arnell Per , Skrede Steinar ,   INFECT Study Group, Hedetoft Morten , Bruun Trond , Oppegaard Oddvar , Nedrebø Torbjørn , Rath Eivind , Madsen Martin Bruun , Norrby-Teglund Anna , Siemens Nikolai 
Published: July 2023

Abstract
Background
Streptococcus pyogenes (group A streptococci; GAS) is the main causative pathogen of monomicrobial necrotizing soft tissue infections (NSTIs). To resist immuno-clearance, GAS adapt their genetic information and/or phenotype to the surrounding environment. Hyper-virulent streptococcal pyrogenic exotoxin B (SpeB) negative variants caused by covRS mutations are enriched during infection. A key driving force for this process is the bacterial Sda1 DNase.

Methods
Bacterial infiltration, immune cell influx, tissue necrosis and inflammation in patient´s biopsies were determined using immunohistochemistry. SpeB secretion and activity by GAS post infections or challenges with reactive agents were determined via Western blot or casein agar and proteolytic activity assays, respectively. Proteome of GAS single colonies and neutrophil secretome were profiled, using mass spectrometry.

Results
Here, we identify another strategy resulting in SpeB-negative variants, namely reversible abrogation of SpeB secretion triggered by neutrophil effector molecules. Analysis of NSTI patient tissue biopsies revealed that tissue inflammation, neutrophil influx, and degranulation positively correlate with increasing frequency of SpeB-negative GAS clones. Using single colony proteomics, we show that GAS isolated directly from tissue express but do not secrete SpeB. Once the tissue pressure is lifted, GAS regain SpeB secreting function. Neutrophils were identified as the main immune cells responsible for the observed phenotype. Subsequent analyses identified hydrogen peroxide and hypochlorous acid as reactive agents driving this phenotypic GAS adaptation to the tissue environment. SpeB-negative GAS show improved survival within neutrophils and induce increased degranulation.

Conclusions
Our findings provide new information about GAS fitness and heterogeneity in the soft tissue milieu and provide new potential targets for therapeutic intervention in NSTIs.