bluuebunny/crossref_metadata_2025_split huggingface dataset:
Academic resilience in UK pharmacy education – a pilot study applying love and break up letters methodology
Authors: Mawdsley Andrew , Willis Sarah C. 
Published: June 2023

Abstract
Introduction
Academic resilience is seen as a positive attribute that supports academic attainment and protects against attrition and burnout. Studies have reported that UK pharmacy students have lower academic resilience and wellbeing than the general UK student population but the reasons for this have not been established. This study pilots the use of a novel methodology, love and break-up letter methodology (LBM), to explore these issues focusing on the lived experience of pharmacy students.

Method
Final year undergraduate pharmacy study were purposely recruited to the study. Employing LBM, each participant was invited to write reflective love and break-up letters to their academic resilience in higher education during a focus group. Letters and transcripts of subsequent focus group discussion on the feelings and ideas expressed in the letters were thematically analysed.

Results
Three meta-themes were identified within the data; the curriculum as gas lighting; the curriculum as abusive; and the curriculum as controlling. Students described how the curriculum diminishes academic resilience by working against their sense of agency and self-esteem. A constant threat of failure emerged as defining the student lived experience; students felt controlled by a curriculum with negative impacts on wellbeing and perseverance.

Discussion
This is the first study to use LBM to explore academic resilience in UK pharmacy students. The results provide evidence that some students view the pharmacy curriculum as a source of relentless adversity that is responsible for promoting a hidden negative connection between students and their education. Further study is required to determine if the results can be generalised across the UK pharmacy student body to explain why UK pharmacy students have lower academic resilience than other UK university students and the steps needed to improve academic resilience in UK pharmacy students.
The relationships among overcommitment, effort-reward imbalance, safety climate, emotional labour and quality of working life for hospital nurses: a structural equation modeling
Authors: Liang Hui Yu , Tseng Tzu Yi , Dai Hung Da , Chuang Jin Yun , Yu Shu 
Published: June 2023

AbstractBackgroundQuality of working life (QWL) is a highly important issue for nurses. Nurses with lower QWL tend to have lower job performance and intention to stay. The aim of this study was to apply a theoretical model to examine the structural relationships among overcommitment, effort-reward imbalance (ERI), safety climate, emotional labour and QWL for hospital nurses.MethodsA cross-sectional study design and a simple random sampling method were used to recruit 295 nurses in a teaching hospital and used a structured questionnaire was used to collect data.ResultsOverall, the nurses’ QWL was moderate. Our theoretical model showed a good model fit. Overcommintment had a significant direct positive effect on ERI (β = 0.35,p < 0.001) and indirect effects on safety climate (β= -0.149,p = 0.001), emotional labour (β = 0.105,p = 0.001) and QWL (β= -0.061,p = 0.004). Additionally, ERI not only had significant direct effects on safety climate (β= -0.42,p < 0.001), emotional labour (β = 0.30,p < 0.001) and QWL (β= -0.17,p < 0.001) but also indirectly affected QWL through safety climate (β= -0.304,p = 0.001) and emotional labour (β= -0.042,p = 0.005). Both safety climate (β = 0.72,p < 0.001) and emotional labour (β= -0.14,p = 0.003) showed significant direct effects on QWL. Our final model accounted for 72% of the variance in QWL.ConclusionOur results highlight the necessity of improving the QWL of nurses. Policymakers and hospital administrators should develop policies and strategies that encourage nurses to exhibit an appropriate level of commitment, balance effort and reward, establish a climate of safety, and reduce emotional labour to improve the QWL of hospital nurses.
Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes
Authors: Lu Feiwei , Wu Boting , Wang Yongshi 
Published: June 2023

AbstractBackgroundAn association has been indicated between atopic dermatitis (AD), a prevalent chronic inflammatory skin disease, and diabetes mellitus. However, the exact causal relationship between AD and both type 1 diabetes (T1D) and type 2 diabetes (T2D) remains controversial. This study aimed to explore the causal association between AD and diabetes by Mendelian Randomization (MR) approaches.MethodsPublic genetic summary data for AD was obtained from EAGLE study. Single nucleotide polymorphisms of diabetes were retrieved from four genome-wide association studies that had been performed in European populations. Inverse variance weighted (IVW) in MR analysis was used as the primary means of causality estimation. Several complementary analyses and sensitivity analyses were performed to calculate MR estimates and to enhance the causal inference, respectively. The R package ‘TwoSampleMR’ was used for analysis.ResultsGenetically predicted AD led to a higher risk of T1D (OR, 1.19; 95% CI, 1.05, 1.34;P = 0.006) and T2D (OR, 1.07; 95% CI, 1.02, 1.11;P = 0.003) based on random-effect IVW method. The complementary analyses provided similar positive results. Cochran’s Q test and I2statistics indicated moderate heterogeneity between AD and both T1D and T2D. No significant horizontal pleiotropy was detected by MR-Egger Intercept p except summary data from FinnGen consortium.ConclusionGenetically predicted AD is a risk factor for both T1D and T2D. These findings imply potential shared pathological mechanisms between AD and diabetes, thus suggesting the significance of early clinical diagnosis and prevention of AD in reducing the incidence of diabetes.
Mitochondrial DNA induces nucleus pulposus cell pyroptosis via the TLR9-NF-κB-NLRP3 axis
Authors: Lu Peng , Zheng Huayong , Meng Hao , Liu Chuan , Duan Lianhong , Zhang Jianzheng , Zhang Zhicheng , Gao Jie , Zhang Yang , Sun Tiansheng 
Published: June 2023

Abstract
Background
Nucleus pulposus cell (NPC) death and progressive reduction play important roles in intervertebral disc degeneration (IVDD). As part of a damage-associated molecular pattern, mitochondrial DNA (mtDNA) can be recognized by TLR9 and triggers the expression of NF-κB and NLRP3 inflammasomes, inducing pyroptosis and inflammatory response. However, whether mtDNA induces NPC pyroptosis via the TLR9-NF-κB-NLRP3 axis and promotes IVDD remains uncertain.

Methods
We constructed an in vitro NPC oxidative stress injury model to clarify the mechanism of mtDNA release, TLR9-NF-κB signaling pathway activation, and NPC injury. We further verified the mechanism of action underlying the inhibition of mtDNA release or TLR9 activation in NPC injury in vitro. We then constructed a rat punctured IVDD model to understand the mechanism inhibiting mtDNA release and TLR9 activation in IVDD.

Results
We used human NP specimen assays to show that the expression levels of TLR9, NF-κB, and NLRP3 inflammasomes correlated with the degree of IVDD. We demonstrated that mtDNA mediated TLR9-NF-κB-NLRP3 axis activation in oxidative stress-induced human NPC pyroptosis in vitro. Oxidative stress can damage the mitochondria of NPCs, causing the opening of the mitochondrial permeability transition pores (mPTP) and leading to the release of mtDNA into the cytosol. Furthermore, inhibition of mPTP opening or TLR9 activation blocked TLR9-NF-κB-NLRP3 axis activation and thereby mediated NPC pyroptosis and IVDD.

Conclusion
mtDNA plays a key role in mediating NPC pyroptosis and IVDD via the TLR9-NF-κB-NLRP3 axis. Our findings provide new potential targets for IVDD.
Encouraging visual outcomes in children with idiopathic and JIA associated uveitis: a population-based study
Authors: Siiskonen Mira , Hirn Iida , Pesälä Roosa , Ohtonen Pasi , Hautala Nina 
Published: June 2023

Abstract
Background
Pediatric uveitis is typically asymptomatic and may become chronic affecting ocular structures and vision. We evaluated visual outcomes, clinical features, medication, and uveitis activity in children with either idiopathic uveitis (idio-U) or juvenile idiopathic arthritis associated uveitis (JIA-U).

Methods
A longitudinal, population-based cohort study of children with uveitis in 2008–2017. The data included parameters for age, gender, age at diagnosis, laterality, chronicity, anatomical distribution, etiology, systemic association, uveitis activity, medication, and visual outcomes.

Results
A total of 119 patients aged < 16 years with uveitis were included. Uveitis was idio-U in 23% and associated with JIA in 77% of cases. 37% of the patients in the idio-U group and 65% in the JIA-U were girls (p = 0.014). The mean age at first uveitis was 10.0 (SD 3.4) years in idio-U and 5.5 (SD 3.3) years in JIA-U (p < 0.001). Anterior location of uveitis was noted in 74% in idio-U and 99% in JIA-U (p < 0.001). Mostly, uveitis was chronic (59% in idio-U and 75% in JIA-U) and bilateral (56% in idio-U and 64% in JIA-U). Topical corticosteroids were initially used by 89% and 100%, systemic corticosteroids by 30% and 27% in some extent during the follow-up, disease-modifying antirheumatic drugs (DMARDs) by 33% and 85% (p < 0.001) of the patients in idio-U and JIA-U, respectively. Biologic disease-modifying antirheumatic drugs (bDMARDs) were more common in JIA-U (55% vs. 15% in idio-U, respectively, p < 0.001). Most patients had normal visual acuity (Snellen > 0.8, [6/7.5]) in the affected eye and bilaterally in 85% idio-U and 70% JIA-U. Only 5 patients (4%) had visual impairment in one, but none in both eyes. Uveitis activity by SUN classification was 0 + in 81% and 72%, 0.5 + in 19% and 25%, and 1 + in 0% and 3% in the idio-U and JIA-U, respectively.

Conclusions
Children with uveitis have good visual acuity and a low rate for visual impairment. In addition, modern treatment with DMARDs and bDMARDs seems to save vision.
Immune profile of primary and recurrent epithelial ovarian cancer cases indicates immune suppression, a major cause of progression and relapse of ovarian cancer
Authors: Kumar Pavan , Ranmale Samruddhi , Mehta Sanket , Tongaonkar Hemant , Patel Vainav , Singh Amit Kumar , Mania-Pramanik Jayanti 
Published: June 2023

Abstract
Background
Ovarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes. Procartaplex, and ELISA were used to measure soluble ligands and cytokines of HGSOC patients.

Results
Among the enrolled 51 EOC patients, 33 were primary high grade serous epithelial ovarian cancer (pEOC) and 18 were recurrent epithelial ovarian cancer (rEOC) patients. Blood samples from 46 age matched healthy controls (HC) were used for comparative analysis. Results revealed, frequency of circulatory CD56Bright NK, CD56Dim NK, NKT-like, and T cells was reduced with activating receptors while alterations in immune subsets with inhibitory receptors were observed in both groups. Study also highlights differential immune profile of primary and recurrent ovarian cancer patients. We have found increased soluble MICA which might have acted as “decoy” molecule and could be a reason of decrease in NKG2D positive subsets in both groups of patients. Furthermore, elevated level of serum cytokines IL-2, IL-5, IL-6, IL-10, and TNF-α in ovarian cancer patients, might be associated with ovarian cancer progression. Profiling of tumor infiltrated immune cells revealed the reduced level of DNAM-1 positive NK and T cells in both groups than their circulatory counterpart, which might have led to decrease in NK cell’s ability of synapse formation.

Conclusions
The study brings out differential receptor expression profile on CD56BrightNK, CD56DimNK, NKT-like, and T cells, cytokines levels and soluble ligands which may be exploited to develop alternate therapeutic approaches for HGSOC patients. Further, few differences in the circulatory immune profiles between pEOC and rEOC cases, indicates the immune signature of pEOC undergoes some changes in circulation that might facilitated the disease relapse. They also maintains some common immune signatures such as reduced expression of NKG2D, high level of MICA as well as IL-6, IL10 and TNF-α, which indicates irreversible immune suppression of ovarian cancer patients. It is also emphasized that a restoration of cytokines level, NKG2D and DNAM-1on tumor infiltrated immune cells may be targeted to develop specific therapeutic approaches for high-grade serous epithelial ovarian cancer.
Assignment of the somatic A/B compartments to chromatin domains in giant transcriptionally active lampbrush chromosomes
Authors: Krasikova Alla , Kulikova Tatiana , Rodriguez Ramos Juan Sebastian , Maslova Antonina 
Published: June 2023

Abstract
Background
The three-dimensional configuration of the eukaryotic genome is an emerging area of research. Chromosome conformation capture outlined genome segregation into large scale A and B compartments corresponding mainly to transcriptionally active and repressive chromatin. It remains unknown how the compartmentalization of the genome changes in growing oocytes of animals with hypertranscriptional type of oogenesis. Such oocytes are characterized by highly elongated chromosomes, called lampbrush chromosomes, which acquire a typical chromomere-loop appearance, representing one of the classical model systems for exploring the structural and functional organization of chromatin domains.

Results
Here, we compared the distribution of A/B compartments in chicken somatic cells with chromatin domains in lampbrush chromosomes. We found that in lampbrush chromosomes, the extended chromatin domains, restricted by compartment boundaries in somatic cells, disintegrate into individual chromomeres. Next, we performed FISH-mapping of the genomic loci, which belong to A or B chromatin compartments as well as to A/B compartment transition regions in embryonic fibroblasts on isolated lampbrush chromosomes. We found, that in chicken lampbrush chromosomes, clusters of dense compact chromomeres bearing short lateral loops and enriched with repressive epigenetic modifications generally correspond to constitutive B compartments in somatic cells. A compartments align with lampbrush chromosome segments with smaller, less compact chromomeres, longer lateral loops, and a higher transcriptional status. Clusters of small loose chromomeres with relatively long lateral loops show no obvious correspondence with either A or B compartment identity. Some genes belonging to facultative B (sub-) compartments can be tissue-specifically transcribed during oogenesis, forming distinct lateral loops.

Conclusions
Here, we established a correspondence between the A/B compartments in somatic interphase nucleus and chromatin segments in giant lampbrush chromosomes from diplotene stage oocytes. The chromomere-loop structure of the genomic regions corresponding to interphase A and B compartments reveals the difference in how they are organized at the level of chromatin domains. The results obtained also suggest that gene-poor regions tend to be packed into chromomeres.
B cell subsets in adult-onset Still’s disease: potential candidates for disease pathogenesis and immunophenotyping
Authors: Fang Xiangyu , Ye Hua , Xie Yang , Wei Chaonan , Liu Shuyan , Yao Haihong , Li Zhanguo , Jia Yuan , Hu Fanlei 
Published: June 2023

Abstract
Background
Adult-onset Still’s disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD.

Methods
B cell subsets in the peripheral blood of AOSD patients and healthy controls (HCs) were detected by flow cytometry. Firstly, the frequencies of B cell subsets were compared. Then, the correlation analysis was performed to explore the correlation between B cell subsets and clinical manifestations in AOSD. Finally, unbiased hierarchical clustering was performed to divide AOSD patients into three groups with different B cell subset features, and the clinical characteristics of the three groups were compared.

Results
The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as naïve B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24hiCD27+ B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. In addition, the altered B cell subsets in AOSD correlated with the clinical and immunological features, such as immune cells, coagulation features, and liver enzymes. Intriguingly, AOSD patients could be divided into three groups with distinct B cell immunophenotyping: group 1 (naïve B cells-dominant), group 2 (CD27+ memory B cells-dominant), and group 3 (precursors of autoantibody-producing plasma cells-dominant). Moreover, these three group patients demonstrated differential manifestations, including immune cells, liver or myocardial enzymes, coagulation features, and systemic score.

Conclusions
B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis. These findings would inspire B cell-based diagnosis and targeted therapies for this refractory disease.
CITED1 as a marker of favourable outcome in anti-endocrine treated, estrogen-receptor positive, lymph-node negative breast cancer
Authors: Dahlgren Malin , Lettiero Barbara , Dalal Hina , Mårtensson Kira , Gaber Alexander , Nodin Björn , Gruvberger-Saal Sofia K. , Saal Lao H. , Howlin Jillian 
Published: June 2023

Abstract
Objective
To investigate CITED1 as a potential biomarker of anti-endocrine response and breast cancer recurrence, given its previously determined role in mediating estrogen-dependant transcription. The study is a continuation of earlier work establishing the role of CITED1 in mammary gland development.

Results
CITED1 mRNA is associated with estrogen-receptor positivity and selectively expressed in the GOBO dataset of cell lines and tumours representing the luminal-molecular subtype. In patients treated with tamoxifen, higher CITED1 correlated with better outcome, suggesting a role in anti-estrogen response. The effect was particularly evident in the subset of estrogen-receptor positive, lymph-node negative (ER+/LN−) patients although noticeable divergence of the groups was apparent only after five years. Tissue microarray (TMA) analysis further validated the association of CITED1 protein, by immunohistochemistry, with favourable outcome in ER+, tamoxifen-treated patients. Although we also found a favourable response to anti-endocrine treatment in a larger TCGA dataset, the tamoxifen-specific effect was not replicated. Finally, MCF7 cells overexpressing CITED1 showed selective amplification of AREG but not TGFα suggesting that maintenance of specific ERα-CITED1 mediated transcription is important for the long-term response to anti-endocrine therapy. These findings together confirm the proposed mechanism of action of CITED1 and support its potential use as a prognostic biomarker.
H2 generated by fermentation in the human gut microbiome influences metabolism and competitive fitness of gut butyrate producers
Authors: Campbell Austin , Gdanetz Kristi , Schmidt Alexander W. , Schmidt Thomas M. 
Published: June 2023

Abstract
Background
Hydrogen gas (H2) is a common product of carbohydrate fermentation in the human gut microbiome and its accumulation can modulate fermentation. Concentrations of colonic H2 vary between individuals, raising the possibility that H2 concentration may be an important factor differentiating individual microbiomes and their metabolites. Butyrate-producing bacteria (butyrogens) in the human gut usually produce some combination of butyrate, lactate, formate, acetate, and H2 in branched fermentation pathways to manage reducing power generated during the oxidation of glucose to acetate and carbon dioxide. We predicted that a high concentration of intestinal H2 would favor the production of butyrate, lactate, and formate by the butyrogens at the expense of acetate, H2, and CO2. Regulation of butyrate production in the human gut is of particular interest due to its role as a mediator of colonic health through anti-inflammatory and anti-carcinogenic properties.

Results
For butyrogens that contained a hydrogenase, growth under a high H2 atmosphere or in the presence of the hydrogenase inhibitor CO stimulated production of organic fermentation products that accommodate reducing power generated during glycolysis, specifically butyrate, lactate, and formate. Also as expected, production of fermentation products in cultures of Faecalibacterium prausnitzii strain A2-165, which does not contain a hydrogenase, was unaffected by H2 or CO. In a synthetic gut microbial community, addition of the H2-consuming human gut methanogen Methanobrevibacter smithii decreased butyrate production alongside H2 concentration. Consistent with this observation, M. smithii metabolic activity in a large human cohort was associated with decreased fecal butyrate, but only during consumption of a resistant starch dietary supplement, suggesting the effect may be most prominent when H2 production in the gut is especially high. Addition of M. smithii to the synthetic communities also facilitated the growth of E. rectale, resulting in decreased relative competitive fitness of F. prausnitzii.

Conclusions
H2 is a regulator of fermentation in the human gut microbiome. In particular, high H2 concentration stimulates production of the anti-inflammatory metabolite butyrate. By consuming H2, gut methanogenesis can decrease butyrate production. These shifts in butyrate production may also impact the competitive fitness of butyrate producers in the gut microbiome.