bluuebunny/crossref_metadata_2025_split huggingface dataset:
FLT3L-induced virtual memory CD8 T cells engage the immune system against tumors
Authors: Tu Hsin-Fang , Kung Yu-Jui , Lim Ling , Tao Julia , Hu Ming-Hung , Cheng Michelle , Xing Deyin , Wu T. C. , Hung Chien-Fu 
Published: January 2024

Abstract
Background
Previous research in FMS-like tyrosine kinase 3 ligands (FLT3L) has primarily focused on their potential to generate dendritic cells (DCs) from bone marrow progenitors, with a limited understanding of how these cells affect CD8 T cell function. In this study, we further investigated the in vivo role of FLT3L for the immunomodulatory capabilities of CD8 T cells.

Methods
Albumin-conjugated FLT3L (Alb-FLT3L) was generated and applied for translational medicine purposes; here it was used to treat naïve C57BL/6 and OT1 mice for CD8 T cell response analysis. Syngeneic B16ova and E.G7ova mouse models were employed for adoptive cell transfer to evaluate the effects of Alb-FLT3L preconditioning of CD8 T cells on tumor progression. To uncover the underlying mechanisms of Alb-FLT3L modulation, we conducted bulk RNA-seq analysis of the CD44high CD8 T cells. STAT1-deficient mice were used to elucidate the functional roles of Alb-FLT3L in the modulation of T cells. Finally, antibody blockade of type one interferon signaling and in vitro coculture of plasmacytoid DCs (pDCs) with naive CD8 T cells was performed to determine the role of pDCs in mediating regulation of CD44high CD8 T cells.

Results
CD44high CD8 T cells were enhanced in C57BL/6 mice administrated with Alb-FLT3L. These CD8 T cells exhibited virtual memory features and had greater proliferative and effective functions. Notably, the adoptive transfer of CD44high naïve CD8 T cells into C57BL/6 mice with B16ova tumors led to significant tumor regression. RNA-seq analysis of the CD44high naïve CD8 T cells revealed FLT3L to induce CD44high CD8 T cells in a JAK-STAT1 signaling pathway-dependent manner, as supported by results indicating a decreased ability of FLT3L to enhance CD8 T cell proliferation in STAT1-deficient mice as compared to wild-type control mice. Moreover, antibody blockade of type one interferon signaling restricted the generation of FLT3L-induced CD44high CD8 T cells, while CD44 expression was able to be induced in naïve CD8 T cells cocultured with pDCs derived from FLT3L-treated mice. This suggests the crucial role of pDCs in mediating FLT3L regulation of CD44high CD8 T cells.

Conclusions
These findings provide critical insight and support the therapeutic potential of Alb-FLT3L as an immune modulator in preconditioning of naïve CD8 T cells for cancer immunotherapy.
Circ-phkb promotes cell apoptosis and inflammation in LPS-induced alveolar macrophages via the TLR4/MyD88/NF-kB/CCL2 axis
Authors: Wei Xuxia , Yi Xiaomeng , Liu Jianrong , Sui Xin , Li Lijuan , Li Mei , Lv Haijin , Yi Huimin 
Published: January 2024

Abstract
Background
Circular RNAs (CircRNAs) have been associated with acute lung injury (ALI), but their molecular mechanisms remain unclear.

Methods
This study developed a rat model of lipopolysaccharide (LPS)-induced ALI and evaluated the modeling effect by hematoxylin and eosin staining, Masson’s trichrome staining, lung wet-to-dry weight ratio, terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA) detection of inflammatory factors (interleukin-1β, tumor necrosis factor alpha, and interleukin-6). Using lung tissues from a rat model of LPS-induced ALI, we then conducted circRNA sequencing, mRNA sequencing, and bioinformatics analysis to obtain differential circRNA and mRNA expression profiles as well as potential ceRNA networks. Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) assays to screen for circ-Phkb in ALI rat lung tissues, alveolar macrophages, and LPS-induced NR8383 cells. We conducted induction with or without LPS with circ-Phkb siRNA and overexpression lentivirus in NR8383. Cell Counting Kit-8, C5-Ethynyl-2′-deoxyuridine (Edu), TUNEL, and cytometry were used to identify proliferation and apoptosis, respectively. We detected inflammatory factors using ELISA. Finally, we used Western blot to detect the apoptosis-related proteins and TLR4/MyD88/NF-kB/CCL2 pathway activation.

Results
Our results revealed that both circRNA and mRNA profiles are different from those of the Sham group. We observed a significant circ-Phkb upregulation in NR8383 cells and LPS-exposed rats. Apoptosis and inflammation were greatly reduced when circ-Phkb expression was reduced in NR8383 cells, cell proliferation was increased, and circ-Phkb overexpression was decreased.

Conclusions
In terms of mechanism, circ-Phkb suppression inhibits CCL2 expression via the TLR4/MyD88/NF-kB pathway in LPS-induced alveolar macrophages.
Impaired influenza A virus replication by the host restriction factor SAMHD1 which inhibited by PA-mediated dephosphorylation of the host transcription factor IRF3
Authors: Zhao Zhilei , Han Shuyi , Zhang Qingxun , Wang Ye , Yue Kening , Abbas Salbia , He Hongxuan 
Published: January 2024

Abstract
Background
Influenza A virus (IAV) can cause severe and life-threatening illness in humans and animals. Therefore, it is important to search for host antiviral proteins and elucidate their antiviral mechanisms for the development of potential treatments. As a part of human innate immunity, host restriction factors can inhibit the replication of viruses, among which SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) can restrict the replication of viruses, such as HIV and enterovirus EV71. Viruses also developed countermeasures in the arms race with their hosts. There are few reports about whether SAMHD1 has a restriction effect on IAV.

Methods
To investigate the impact of IAV infection on SAMHD1 expression in A549 cells, we infected A549 cells with a varying multiplicity of infection (MOI) of IAV and collected cell samples at different time points for WB and RT-qPCR analysis to detect viral protein and SAMHD1 levels. The virus replication level in the cell culture supernatant was determined using TCID50 assay. Luciferase assay was used to reveal that H5N1 virus polymerase acidic protein (PA) affected the activity of the SAMHD1 promoter. To assess the antiviral capacity of SAMHD1, we generated a knockdown and overexpressed cell line for detecting H5N1 replication.

Results
In this study, we observed that SAMHD1 can restrict the intracellular replication of H5N1 and that the H5N1 viral protein PA can downregulate the expression of SAMHD1 by affecting SAMHD1 transcriptional promoter activity. We also found that SAMHD1's ability to restrict H5N1 is related to phosphorylation at 592-tyrosine.

Conclusions
In conclusion, we found that SAMHD1 may affect the replication of IAVs as a host restriction factor and be countered by PA. Furthermore, SAMHD1 may be a potential target for developing antiviral drugs.
Is blinding in studies of manual soft tissue mobilisation of the back possible? A feasibility randomised controlled trial with Swiss graduate students
Authors: Muñoz Laguna Javier , Nyantakyi Emanuela , Bhattacharyya Urmila , Blum Kathrin , Delucchi Matteo , Klingebiel Felix Karl-Ludwig , Labarile Marco , Roggo Andrea , Weber Manuel , Radtke Thomas , Puhan Milo A , Hincapié Cesar A 
Published: January 2024

AbstractStudy designSingle-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility.BackgroundTrials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment.MethodsOn 7–8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from –1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating ‘random guessing’—balanced ‘active’ and ‘control’ perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis.Results24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, −0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (−0.12 to 0.30) and −0.10 (−0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment.ConclusionsBlinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed.Trial registrationClinicalTrials.gov: NCT05822947 (retrospectively registered)
A qualitative analysis of free-text patient satisfaction responses in Care Response, a database of patient-reported outcome and experience measures
Authors: Young Kenneth J. , Young Helen C. , Field Jonathan 
Published: January 2024

Abstract
Background
Databases have become important tools in improving health care. Care Response is a database containing information on tens of thousands of chiropractic patients internationally. It has been collecting patient-reported outcomes and patient satisfaction information for more than 10 years. The purpose of this study was to contribute to the understanding of patient perceptions and priorities for chiropractic care by analysing free text entered into the patient reported experience measure (PREM) questionnaires within the Care Response system.

Methods
There were two questions of interest on the PREM for this study. One requested information about “good points” patients perceived about patients’ care experience, and the other requested information on “improvements” that could make the experience better. We conducted a word frequency analysis using a word counting macro in Microsoft Word, then used those results as a starting point for a qualitative analysis. Data were collected on 30 May 2022.

Results
The people who participated in the Care Response system often reported positive experiences with their chiropractors, including that they had reduced pain, improved function, and felt validated in their clinical condition. In addition, they appreciated having diagnostic and treatment procedures explained to them. They valued friendly, professional, and on-time service. The negative experiences were the opposite: being rushed through treatment, that the treatment was not worth the cost, or that they weren’t treated professionally, empathetically, or with respect for them as individuals. The most important themes that emerged under “good points” were satisfaction (with care), value (as a person), safety, comfort, and professionalism. Their opposites, dissatisfaction, lack of value, lack of safety, lack of comfort, and lack of professionalism emerged as the most important themes under “improvements”. We report some nuances of patient experience that have not previously been explored in the literature.

Conclusions
Respondents seemed to value effective care provided in a safe, professional, friendly, and aesthetically pleasing environment. Chiropractors should note these priorities and engage with patients according to them. Education institutions should consider how good practice in these areas might be incorporated into curricula.
Allogenic hematopoietic stem cell transplantation outcomes of patients aged ≥ 55 years with acute myeloid leukemia or myelodysplastic syndromes in China: a retrospective study
Authors: Gao Lu , Yang Li , Zhou Shiyuan , Zhu Wenjuan , Han Yue , Chen Suning , Xue Shengli , Wang Ying , Qiu Huiying , Wu Depei , Wu Xiaojin 
Published: January 2024

Abstract
Background
Elderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe.

Methods
Our retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests.

Results
The median age of the cohort was 57 years (range: 55–75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P < 0.001, HR = 0.596), higher incidence of relapses (HR = 2.300, P = 0.013), and inferior relapse-free survival (RFS) (HR = 1.740, HR = 0.016) regardless of donor type. When it came to graft-versus-host-disease-free, relapse-free survival (GRFS), MUDs turned out to be superior to HIDs (HR = 0.472, P = 0.026) according to the multivariable analysis. In contrast, we found MSDs had an inferior GRFS to HIDs in parallel (HR = 1.621, P = 0.043).

Conclusion
The choice of donor type did not significantly affect the outcomes of allo-HSCT. However, when considering the quality of post-transplant life, MUDs or HIDs from younger donors may be the optimal choice for elderly patients.
Differences in quality of life and fitness level among men and women in the adulthood: a cross-sectional analysis
Authors: Alvarez-Bueno Celia , del Saz-Lara Alicia , Cavero-Redondo Ivan , Rodriguez-Gutierrez Eva , Gonzalez-Molinero Marta , Bizzozero-Peroni Bruno , Pascual-Morena Carlos , Lucas-Torres Maribel Luceron 
Published: January 2024

Abstract
Background
This study aimed to examine the associations between physical fitness components and health-related quality of life (HRQoL) among adults stratified by sex and age. In addition, we aimed to examine whether these associations change based on socioeconomic, clinical, and biochemical characteristics.

Methods
A total of 297 participants aged 47.41 (standard deviation: 9.08) years from the “Validity of a Model of Accelerated Vascular Aging as a Cardiovascular Risk Index in Healthy Adults: the EVasCu cross-sectional study” were included in this analysis. HRQoL, physical fitness, socioeconomic status (SES), waist circumference, and blood pressure were measured. Additionally, blood samples were extracted to determine cholesterol, triglyceride, and glycated hemoglobin A1c (HbA1c) levels. Analyses of covariance (ANCOVAs) were estimated to test mean differences in physical and mental health-related health measures (HRQoL) between fitness categories (fixed factors) by sex and age categories.

Results
The physical HRQoL was related to the levels of fitness parameters among women, independent of age, while for men, it was related to better levels of general fitness and cardiorespiratory fitness among men aged < 50 and men aged ≥ 50, respectively. In contrast, mental HRQoL was related to cardiorespiratory fitness only among women aged < 50 years; speed/agility and flexibility among men aged < 50 years; and general fitness, strength, and flexibility among men aged ≥ 50 years. These data did not change when SES, clinical variables, or biochemical determinations were included in the analyses, neither for the physical nor for the mental HRQoL.

Conclusion
Gender and age are important factors to be considered when analysing health indicators and influences in the population. In addition, SES, clinical characteristics, and biochemical parameters do not seem to influence the relationship between HRQoL and fitness.
Mean compression ratio of a self-expandable valve is associated with the need for pacemaker implantation after transcatheter aortic valve replacement
Authors: Qi Yiming , Ding Yuefan , Pan Wenzhi , Zhang Xiaochun , Lin Xiaolei , Chen Shasha , Zhang Lei , Zhou Daxin , Ge Junbo 
Published: January 2024

Abstract
Background
The risk and timing of permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR) is still hard to predict. We aimed to analyze the relationship between the compression ratio of a self-expandable valve (SEV) and the need for PPMI after TAVR.

Methods
A total of 106 patients who were implanted with the VitaFlow transcatheter aortic valve system and for whom complete imaging information was available were included in this retrospective cohort study. Eight lines perpendicular to the long axis of the SEV were drawn (the top and bottom of the SEV and the intersection of each row of wires) for measurement purposes. The compression ratio was calculated as 1 − (in vivo meridian/in vitro meridian) and compared between patients undergoing and those not undergoing PPMI after adjusting for implantation depth. Multivariable logistic regression and Cox proportional hazards models were used to assess factors associated with the risk and timing of the need for PPMI.

Results
Fifteen (14.2%) patients underwent PPMI after TAVR. Patients with a higher mean compression ratio (20%, odds ratio [OR] = 214.82; p < 0.001) and prior right bundle branch block (OR = 51.77; p = 0.015) had a higher risk of the need for PPMI after TAVR. These two factors were also associated with the timing of PPMI, according to the Cox proportional hazards model.

Conclusions
The compression ratio of the SEV was positively associated with the risk of PPMI after TAVR, and the association was most significant in the annular and supravalvular planes. The compression ratio may also affect the time to PPMI.
Comment on: Proposal for a new diagnostic classification of photodistributed Stevens–Johnson syndrome and toxic epidermal necrolysis
Authors: Thwala Bukiwe N. , Teixeira Nadine , Zitha Eddy , Mpungose Aneliswa , Isaacs Thuraya , Peter Jonathan G. , Lehloenya Rannakoe J. 
Published: January 2024

AbstractStevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap (SJS/TEN), collectively referred to SJS/TEN, form a spectrum of severe life-threatening adverse drug reactions whose pathomechanism is not fully understood. The article "Photodistributed Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Proposal for a New Diagnostic Classification" by McKinley et. al., discusses a distinct distribution of epidermal necrosis in SJS/TEN, attributable to preceding exposure to ultraviolet radiation (UVR), and relative sparing of photo-protected areas. After reviewing numerous cases within the Immune-mediated Adverse drug Reactions in African HIV endemic setting Register and Biorepository (IMARI-SA) at the University of Cape Town with a similar clinical pattern as those published by McKinley et. al., we propose that the relative sparing of some areas giving an impression of photo-distribution is due to localised increase in skin pressure that reduces the blood supply in that area below a critical threshold. A dip in blood supply below this critical threshold quantitively limited T lymphocytes and cytokines that drive SJS/TEN to reach and damage the skin.
Differentially expressed long non-coding RNAs and mRNAs of cadmium exposure on learning disability of offspring rats
Authors: Liu Hui , Wan Xichen , Yao Liyun , Zhao Qihan , Yang Yong , Liu Hongtao , Shang Jun , Zeng Fanfan , Wang Xin , Huang Shaoxin 
Published: January 2024

Abstract
Background
Cadmium (Cd) exposure has been found to have detrimental effects on the development of the central nervous system and cognitive ability in children. However, there is ongoing debate regarding the impact of maternal Cd exposure on the cognitive ability of offspring. In this study, we aimed to investigate the mechanisms underlying the influence of maternal Cd exposure on the cognitive ability of offspring rats.

Methods
Here, we constructed a model of cadmium poisoning in first-generation rats through gavage. The cognitive and memory abilities of its offspring were evaluated by water maze experiment. Then, we used the gene chip to find out the key genes, and we performed qRT-PCR detection of these genes. Subsequently, enrichment analysis was employed to identify pathways. Finally, we constructed a co-expression network consisting of LncRNAs and mRNAs to elucidate the biological functions and regulatory mechanisms of LncRNAs.

Results
The results of the water maze trial demonstrated that the offspring of rats exposed to cadmium in the first generation had reduced cognitive and memory abilities. Through an analysis of gene expression in the hippocampus of the cadmium-treated rats' offspring and the control group, we identified a correlation between the islet secretion pathway and the cognitive impairment observed in the offspring. Utilizing various algorithms, we identified Cpa1 and Prss1 as potential key genes associated with the cognitive impairment caused by cadmium. The results of qRT-PCR demonstrated a decrease in the expression levels of these genes in the hippocampus of the cadmium-treated rats’ offspring. In addition, in the co-expression network, we observed that Cpa1 was co-expressed with 11 LncRNAs, while Prss1 was associated with 4 unexplored LncRNAs. Furthermore, we conducted an analysis to examine the relationship between Cpa1, Prss1-related transcription factors, and LncRNAs.

Conclusion
Overall, this study provides novel insights into the molecular effects of first generation Cd exposure on the cognitive ability of offspring. The target genes and signaling pathways investigated in this study could serve as potential targets for improving neurodevelopment and cognitive ability in children.