bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown of NCAPD3 inhibits the tumorigenesis of non-small cell lung cancer by regulation of the PI3K/Akt pathway
Authors: Yang Fan , Zheng Yunfeng , Luo Qiong , Zhang Suyun , Yang Sheng , Chen Xiangqi 
Published: April 2024

Abstract
Background
Accumulating evidence indicates that aberrant non-SMC condensin II complex subunit D3 (NCAPD3) is associated with carcinogenesis of various cancers. Nevertheless, the biological role of NCAPD3 in the pathogenesis of non-small cell lung cancer (NSCLC) remains unclear.

Methods
Immunohistochemistry and Western blot were performed to assess NCAPD3 expression in NSCLC tissues and cell lines. The ability of cell proliferation, invasion, and migration was evaluated by CCK-8 assays, EdU assays, Transwell assays, and scratch wound healing assays. Flow cytometry was performed to verify the cell cycle and apoptosis. RNA-sequence and rescue experiment were performed to reveal the underlying mechanisms.

Results
The results showed that the expression of NCAPD3 was significantly elevated in NSCLC tissues. High NCAPD3 expression in NSCLC patients was substantially associated with a worse prognosis. Functionally, knockdown of NCAPD3 resulted in cell apoptosis and cell cycle arrest in NSCLC cells as well as a significant inhibition of proliferation, invasion, and migration. Furthermore, RNA-sequencing analysis suggested that NCAPD3 contributes to NSCLC carcinogenesis by regulating PI3K/Akt/FOXO4 pathway. Insulin-like growth factors-1 (IGF-1), an activator of PI3K/Akt signaling pathway, could reverse NCAPD3 silence-mediated proliferation inhibition and apoptosis in NSCLC cells.

Conclusion
NCAPD3 suppresses apoptosis and promotes cell proliferation via the PI3K/Akt/FOXO4 signaling pathway, suggesting a potential use for NCAPD3 inhibitors as NSCLC therapeutics.
Non-canonical transcriptional regulation of the poor prognostic factor UGT2B17 in chronic lymphocytic leukemic and normal B cells
Authors: Rouleau Michèle , Villeneuve Lyne , Allain Eric P. , McCabe-Leroux Jules , Tremblay Sophie , Nguyen Van Long Flora , Uchil Ashwini , Joly-Beauparlant Charles , Droit Arnaud , Guillemette Chantal 
Published: April 2024

Abstract
Background
High expression of the glycosyltransferase UGT2B17 represents an independent adverse prognostic marker in chronic lymphocytic leukemia (CLL). It also constitutes a predictive marker for therapeutic response and a drug resistance mechanism. The key determinants driving expression of the UGT2B17 gene in normal and leukemic B-cells remain undefined. The UGT2B17 transcriptome is complex and is comprised of at least 10 alternative transcripts, identified by previous RNA-sequencing of liver and intestine. We hypothesized that the transcriptional program regulating UGT2B17 in B-lymphocytes is distinct from the canonical expression previously characterized in the liver.

Results
RNA-sequencing and genomics data revealed a specific genomic landscape at the UGT2B17 locus in normal and leukemic B-cells. RNA-sequencing and quantitative PCR data indicated that the UGT2B17 enzyme is solely encoded by alternative transcripts expressed in CLL patient cells and not by the canonical transcript widely expressed in the liver and intestine. Chromatin accessible regions (ATAC-Seq) in CLL cells mapped with alternative promoters and non-coding exons, which may be derived from endogenous retrotransposon elements. By luciferase reporter assays, we identified key cis-regulatory STAT3, RELA and interferon regulatory factor (IRF) binding sequences driving the expression of UGT2B17 in lymphoblastoid and leukemic B-cells. Electrophoretic mobility shift assays and pharmacological inhibition demonstrated key roles for the CLL prosurvival transcription factors STAT3 and NF-κB in the leukemic expression of UGT2B17.

Conclusions
UGT2B17 expression in B-CLL is driven by key regulators of CLL progression. Our data suggest that a NF-κB/STAT3/IRF/UGT2B17 axis may represent a novel B-cell pathway promoting disease progression and drug resistance.
Long-term follow-up demonstrates change in conformation shape of the focal choroidal excavation lesions
Authors: Sulavikova Zuzana , Sustykevicova Zuzana , Kacerik Marek , Kozak Igor 
Published: April 2024

Abstract
Purpose
This study aims to present long-term observation of 5 eyes with focal choroidal excavation (FCE), focusing on morphological changes in conformity of the lesion.

Methods
A retrospective case series was conducted, including 5 eyes of 5 patients with FCE. The study utilized multimodal imaging including color fundus photography, optical coherence tomography (OCT), enhanced depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), red free imaging, and OCT angiography.

Results
The mean age at diagnosis was 51 ± 10.65 years, with a mean follow-up period 37 ± 13.59 months. All cases were unilateral, with 1 presenting FCE as an isolated lesion, and one patient exhibiting 2 FCEs in one eye. The mean choroidal thickness measured by EDI-OCT was 268.2 ± 63.39 μm in the affected eye. One patient displayed choroidal thickening and pachyvessels. Of the 5 eyes, one had conforming and 4 non-conforming FCE. We observed a conversion in conformity in all patients, with 4 cases transitioning from non-conforming FCE to conforming type (3 spontaneously, 1 treatment-induced). In conforming FCE, a hyporeflective space appeared twice between neuroretina and retinal pigment epithelium with spontaneous regression.

Conclusion
We observed change in shape from the conforming to non-conforming FCE and vice versa in all patients. We consider this small change in the hyporeflective space as non-pathologic and clinically insignificant.
Recurrent myocardial injury in a de novo SON mutation ZTTK syndrome patient: a case report
Authors: Na Jia , Cui Lang , Zhen Zhen , Chen Xi , Li Qirui , Gao Lu , Yuan Yue 
Published: April 2024

Abstract
Background
Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case.

Case presentation
A 7-year-old girl was admitted to the Cardiology Department of Beijing Children’s Hospital in November 2019 due to myocardial injury following respiratory infection. She displayed elevated myocardial enzymes and severe T-wave changes on electrocardiogram. Over the past three years, she had experienced myocardial injury on three occasions. Additionally, she exhibited intellectual disability, congenital amblyopia, and dysmorphic facial features. Genetic analysis revealed a de novo heterozygous mutation c.3852_3856delGGTAT in the SON gene, which was confirmed by Sanger sequencing of her parents. She received anti-infection treatment and was administered metoprolol orally. Her condition was stable at the time of discharge. Over a 42-month follow-up period at the outpatient clinic, she complained intermittent fatigue and palpitation.

Conclusions
The identified SON mutation, which plays a crucial role in heart development and mitochondrial function, may be associated with an increased susceptibility to myocardial injury or cardiomyopathy. This case report contributes novel insights into this rare condition and suggests the expansion of the ZTTK syndrome phenotype.
Association of childhood trauma, social support, cognition, and suicidality in females with bipolar disorder
Authors: Yang Min , Li Jiaxin , Fu Yaqian , Wang Guotao , Liu Minghui , Chen Jindong , Liu Jieyu 
Published: April 2024

Abstract
Background
Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD.

Methods
This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales.

Results
Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016).

Conclusions
This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk.
Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia
Authors: He Jingqi , Li Jinguang , Wei Yisen , He Zhangyin , Liu Junyu , Yuan Ning , Zhou Risheng , He Xingtao , Ren Honghong , Gu Lin , Liao Yanhui , Chen Xiaogang , Tang Jinsong 
Published: April 2024

Abstract
Background
Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels.

Methods
Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB).

Result
The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction.

Conclusion
Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.
Social support predicted subsequent subjective well-being during the COVID-19 pandemic: a prospective study
Authors: Mao Yanhui , Chen Junpeng , Liu Xinqi , Dang Junhua , Schiöth Helgi B. 
Published: April 2024

Abstract
Background
Subjective well-being (SWB) is associated with social support in cross-sectional studies. However, it remains unclear whether and how social support predicts SWB longitudinally, especially during the COVID-19 contingency.

Methods
By adopting a prospective design, the current work addressed this research question in a sample of 594 participants from the U.K. The data were collected via the online platform, Prolific, at two time points (June, 2020 and August, 2021) with a 14-month interval. Descriptive analysis and a moderated mediation model were conducted to test the proposed hypotheses.

Results
Baseline social support was a significant predictor of subjective well-being (SWB) 14 months later, even after controlling for baseline SWB and other covariates such as personality traits. Additionally, affect balance (i.e., the affective component of SWB) fully mediated the link between baseline social support and subsequent life satisfaction (i.e., the cognitive component of SWB). Moreover, household income moderated this relationship, indicating a stronger mediation for individuals with lower monthly household income.

Conclusion
The present work sheds light on the underlying mechanism and boundary condition of the association between social support and different components of SWB during the COVID-19 pandemic.
The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks
Authors: Wang Hsin-Yi , Tsai Shih-Chuan , Lin Yi-Ching , Hou Jing-Uei , Chao Chih-Hao 
Published: April 2024

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure.MethodsData from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated.ResultsThe antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264–0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant.DiscussionThis study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.
Neq2X7: a multi-purpose and open-source fusion DNA polymerase for advanced DNA engineering and diagnostics PCR
Authors: Hernández-Rollán Cristina , Ehrmann Anja K. , Vlassis Arsenios , Kandasamy Vijayalakshmi , Nørholm Morten H. H. 
Published: April 2024

AbstractThermostable DNA polymerases, such as Taq isolated from the thermophilic bacterium Thermus aquaticus, enable one-pot exponential DNA amplification known as polymerase chain reaction (PCR). However, properties other than thermostability - such as fidelity, processivity, and compatibility with modified nucleotides - are important in contemporary molecular biology applications. Here, we describe the engineering and characterization of a fusion between a DNA polymerase identified in the marine archaea Nanoarchaeum equitans and a DNA binding domain from the thermophile Sulfolobus solfataricus. The fusion creates a highly active enzyme, Neq2X7, capable of amplifying long and GC-rich DNA, unaffected by replacing dTTP with dUTP in PCR, and tolerant to various known PCR inhibitors. This makes it an attractive DNA polymerase for use, e.g., with uracil excision (USER) DNA assembly and for contamination-free diagnostics. Using a magnification via nucleotide imbalance fidelity assay, Neq2X7 was estimated to have an error rate lower than 2 ∙ 10−5 bp−1 and an approximately 100x lower fidelity than the parental variant Neq2X, indicating a trade-off between fidelity and processivity – an observation that may be of importance for similarly engineered DNA polymerases. Neq2X7 is easy to produce for routine application in any molecular biology laboratory, and the expression plasmid is made freely available.
Effect of evidence-based nursing practices training programme on the competency of nurses caring for mechanically ventilated patients: a randomised controlled trial
Authors: Elhabashy Sameh , Moriyama Michiko , Mahmoud Eman Ibrahim El-Desoki , Eysa Basem 
Published: April 2024

Abstract
Background
Evidence-Based Practice (EBP) has been recognised worldwide as a standardised approach for enhancing the quality of healthcare and patient outcomes. Nurses play a significant role in integrating EBP, especially in Intensive Care Unit (ICU). Consequently, this study aims to examine the effect of an adapted evidence-based nursing practices training programme on the competency level of nurses caring for mechanically ventilated patients.

Methods
A prospective open-label parallel 1:1 randomised controlled trial was conducted on 80 nurses caring for ICU patients at the National Hepatology and Tropical Medicine Research Institute, Egypt. The trial was carried out between November 2022 and February 2023 under the registration number NCT05721664. The enrolled nurses were randomly divided into intervention and control groups. The intervention group received the evidence-based nursing practice training programme (EBNPTP) in accordance with the Johns Hopkins EBP conceptional model, whereas the control group received traditional in-service education. Four assessments (one pre- and three post-assessments) were conducted to evaluate nurses’ competency level over time using the adapted evidence-based nursing competency assessment checklist. The primary endpoint was an increase the competency levels among nurses caring for mechanically ventilated patients.

Results
The current study results revealed statistically significant differences between intervention and control groups in relation to their level of competency across the three post-assessments, with (p <.001). The study also demonstrated that the nurses’ competency level continued to decline significantly over time, with (p <.001). Additionally, a significant correlation was found between the nurses’ pre-assessment and educational level, acting as independent variables (predictors), and the third endpoint assessment (p <.01), indicated by multiple linear regression.

Conclusion
The EBP training programme demonstrated a significant increase in the nurses’ level of competency compared with traditional in-service education. This suggests that by training the nurses in various settings with the essential skills and knowledge for EBP, their competency level can be enhanced, leading to the delivery of effective care and improving patient outcomes. However, the long-term sustainability of the EBP adoptions was insufficient; further studies are needed to investigate the factors that affect the durability of EBP adoption.

Trial registration
The study was registered with Clinical Trials.gov (Registration # NCT05721664) on 10/02/2023.
“To do or not to do”, male nurses’ experiences of providing intimate care to female patients in China, a constructivist grounded theory study
Authors: Lyu Xiao-Chen , Sun Xiang-Yun , Lee Li-Hung , Yang Cheng-I 
Published: April 2024

Abstract
Background
Some studies suggest that female patients have more concerns about receiving intimate care from male than female nurses. Thus, providing intimate care to female patients is a challenging experience for male nurses. The purpose of this study was to explore Chinese male nurses’ experiences and process of providing intimate clinical care to female patients.

Methods
A constructivist grounded theory approach was used to develop a theoretical understanding of male nurses’ experiences. This study included participants from 3 hospitals in different locations in China. Twenty-five male nurses were recruited using purposive and theoretical sampling. Semi-structured interviews were conducted. Data analysis was completed using initial coding, focused coding, theoretical coding and memo writing to produce core concepts and categories, and theory development.

Results
Chinese male nurses’ experiences of providing intimate care to female patients can be constructed as a three-stage process: (1) anticipation of the level of embarrassment, (2) deciding on the process: do it or not do it and (3) protecting both parties and dealing with embarrassment. Additionally, seven themes and associated categories were identified to represent the important factors in the process of male nurses providing intimate care to female patients in China.

Conclusions
Chinese traditional culture may affect the embarrassment in Chinese male nurses providing intimate care to female patients. The embarrassing situation can be divided into three different stages, and male nurses have different main concerns in each stage. Hospital nursing administrators should consider the experiences and needs of male nurses in providing intimate care and provide them with psychological support, education and training.
Building resilience: analysis of health care leaders’ perspectives on the Covid-19 response in Region Stockholm
Authors: Savage Carl , Tragl Leonard , Castillo Moa Malmqvist , Azizi Louisa , Hasson Henna , Sundberg Carl Johan , Mazzocato Pamela 
Published: April 2024

Abstract
Background
The Covid-19 pandemic has tested health care organizations worldwide. Responses have demonstrated great variation and Sweden has been an outlier in terms of both strategy and how it was enacted, making it an interesting case for further study. The aim of this study was to explore how health care leaders experienced the challenges and responses that emerged during the initial wave of the Covid-19 pandemic, and to analyze these experiences through an organizational resilience lens.

Methods
A qualitative interview study with 12 senior staff members who worked directly with or supervised pandemic efforts. Transcripts were analyzed using traditional content analysis and the codes directed to the Integrated Resilience Attributes Framework to understand what contributed to or hindered organizational resilience, i.e. how organizations achieve their goals by utilizing existing resources during crises.

Results/Findings
Organizational resilience was found at the micro (situated) and meso (structural) system levels as individuals and organizations dealt with acute shortages and were forced to rapidly adapt through individual sacrifices, resource management, process management, and communications and relational capacity. Poor systemic resilience related to misaligned responses and a lack of learning from previous experiences, negatively impacted the anticipatory phase and placed greater pressure on individuals and organizations to respond. Conventional crisis leadership could hamper innovation, further cement chronic challenges, and generate a moral tension between centralized directives and clinical microsystem experiences.

Conclusions
The pandemic tested the resilience of the health care system, placing undue pressure on micro and meso systems responses. With improved learning capabilities, some of this pressure may be mitigated as it could raise the anticipatory resilience potential, i.e. with better health systems learning, we may need fewer heroes. How crisis leadership could better align decision-making with frontline needs and temper short-term acute needs with a longer-term infinite mindset is worth further study.