bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between Wnt/β-catenin signaling pathway and EMT pathway mediates the mechanism of sunitinib resistance in renal cell carcinoma
Authors: Cai Fangzhen , Li Jianwei , Zhang Yanmei , Huang Sihuai , Liu Wenbin , Zhuo Weifeng , Qiu Chengzhi 
Published: February 2024

Abstract
Background
Targeted drugs are the main methods of RCC treatment. However, drug resistance is common in RCC patients, in-depth study of the drug-resistant mechanism is essential.

Methods
We constructed sunitinib resistant and Twist overexpressed A498 cells, and studied its mechanisms in vitro and in vivo.

Results
In cell research, we found that either sunitinib resistance or Twist overexpression can activate Wnt/β-catenin and EMT signaling pathway, and the sunitinib resistance may work through β-catenin/TWIST/TCF4 trimer. In zebrafish research, we confirmed the similarity of Twist overexpression and sunitinib resistance, and the promoting effect of Twist overexpression on drug resistance.

Conclusions
Sunitinib resistance and Twist overexpression can activate Wnt/β-catenin signaling pathway and EMT to promote the growth and metastasis of RCC cells.
‘Fear, uncertain, tired…...’ psychological distress among pulmonary hypertension patients: a qualitative interview study
Authors: Zhang Juxia , Zhang Yiyin , Yin Yuhuan , Feng Yuping , Zhang Rong , Meng Hongyan , Wang Jing 
Published: February 2024

Abstract
Background
Patient-centered health care for patients with pulmonary hypertension (PH) is important and requires an understanding of patient experiences. However, there is a lack of approaches to examine what's the effects and how the disease impact patients’ psychological well-beings.

Methods
We conducted qualitative interviews with PH patient representatives to understand patient psychological experiences and inform patient-centered research and care. Participants were chosen from a tertiary hospital located in northwest China. 20 patients with PH who be treated at the hospital (13 participants were women, aged 18-74 years) were strategically selected and individually interviewed. We used qualitative analysis to identify themes relating to existential psychological distress that would clarify the nature of such concerns.

Results
We found that patients experience tremendous psychological distress throughout the treatment process. Four categories that describe patients' psychological experiences emerged: burden of PH treatment, fear and uncertainty about the disease, frustration in social and family role, and lack of recognition of the condition.

Conclusions
Existential concerns are salient in PH and involve the experience of loss and disruptions to the sense of self and relationships. Healthcare practitioners must work more in collaboration to detect patients' need for support and to develop the patient's own skills to manage daily life. The PH teams should tailor interventions to provide emotional, informational and instrumental support and guidance to patients.
Associations between ADHD and risk of six psychiatric disorders: a Mendelian randomization study
Authors: Guo Yanwei , Li Junyao , Hu Renqin , Luo Huirong , Zhang Zheng , Tan Jinglan , Luo Qinghua 
Published: February 2024

Abstract
Background
Observational studies and diagnostic criteria have indicated that Attention Deficit Hyperactivity Disorder (ADHD) frequently comorbid with various psychiatric disorders. Therefore, we conducted a Mendelian randomization (MR) study to explore this potential genetic association between ADHD and six psychiatric disorders.

Methods
Using a two-sample Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of ADHD and six psychiatric disorders, with the inverse variance weighted (IVW) method as the primary approach.

Results
The study revealed a positive and causal association between ADHD and the risk of ASD, with an odds ratio (OR) of 2.328 (95%CI: 1.241–4.368) in the IVW MR analysis. Additionally, ADHD showed a positive causal effect on an increased risk of schizophrenia, with an OR of 1.867 (95%CI: 1.260–2.767) in the IVW MR analysis. However, no causal effect of Tic disorder, Mental retardation, Mood disorders and Anxiety disorder with ADHD was found in the analysis mentioned above.

Conclusion
Our MR analysis provides robust evidence of the causal role of ADHD in increasing the risk of ASD and schizophrenia. However, ADHD is not associated with the risk of Tic Disorder, Mental Retardation, Mood Disorders and Anxiety Disorder. This suggests the need for increased attention to the co-occurrence of ADHD-ASD or ADHD-schizophrenia and the implementation of timely intervention and treatment.
Monthly engagement with EIP keyworkers was associated with a five-fold increase in the odds of engagement with psychosocial interventions
Authors: Darker C. D. , Nicolson G. , Reddon H. , O’Connor K. , Jennings R. , O’Connell N. 
Published: February 2024

Abstract
Background
Early intervention in psychosis (EIP) supports people who are experiencing their first episode of psychosis (FEP). A new Model of Care (MoC) for EIP services was launched in Ireland in 2019. Three EIP demonstration sites were chosen to test this MoC through a ‘hub and spoke’ approach. These services were a new way of organising care for people experiencing FEP, based upon a recovery model of care, and which sought to standardise care, improve access by clinically led multidisciplinary teams. This included newly created EIP keyworker roles whereby keyworkers assumed responsibilities regarding assessment, comprehensive individual care planning and coordination of care.

Methods
A mixed methods design utilising the UK Medical Research Council’s process evaluation framework. Purposive sampling techniques were utilised. Descriptive analyses and logistic regression were performed to examine how increased keyworker engagement influenced the use of other psychosocial interventions within the EIP demonstration sites. Thematic analyses was used for qualitative data.

Results
There was a strong positive relationship between keyworker contacts and psychosocial interventions offered. Specifically, the odds of achieving at least monthly engagement with cognitive behavioural therapy for psychosis (CBTp; (5.76 (2.43–13.64), p < 0.001), and behavioural family therapy (BFT; (5.52(1.63–18.69, p < 0.006)) increased by fivefold with each additional monthly keyworker contact. For individual placement support (IPS) each additional monthly keyworker contact was associated with a three-fold increase in the odds of achieving monthly attendance with IPS (3.73 (1.64–8.48), p < 0.002). Qualitative results found that the EIP keyworker role as viewed by both service users and staff as a valuable nodal point, with a particular emphasis on care coordination and effective communication.

Conclusions
This study advances the understanding of keyworker effects through qualitative evidence of keyworkers functioning as a “linchpin” to the service, while the positive response association between keyworker contacts and engagement with other services provides quantitative support for keyworkers reducing the organisational or structural barriers to service access. Given the importance of these positions, health systems should ensure that EIP programmes identify qualified and experienced staff to fill these roles, as well as allocate the appropriate funding and protected time to support keyworker engagement and impact.
Pornography, sexual orientation and ambivalent sexism in young adults in Spain
Authors: Sanz-Barbero Belén , Estévez-García J. Francisco , Madrona-Bonastre Raquel , Vicens Gemma Renart , Serra Laura , Vives-Cases Carmen 
Published: February 2024

Background
On line platforms offer access to an almost unlimited variety of pornographic material that shows high levels of sexism. Despite this fact, there are still few studies that assess the effect of pornography on sexism in young adults The aim of this study is to analyze the association of pornography consumption and sexual orientation with benevolent sexism (BS) and hostile sexism (HS) in young men and women.

Methods
We surveyed 2,346 people aged 18–35 years old. Multiple regression models were carried out for BS and HS. The independent variables: current pornography consumption and sexual orientation. Covariates: socio-demographic variables -age, sex, level of education and place of birth-.

Results
A) HS: Men who consumed pornography had higher median values of HS than those who did not [β(95%CI):2.39(0.67;4.10)]. Homosexual/ bisexual men displayed lower values of HS than heterosexual men [β(95%CI):-2.98(-4.52;-1.45)]. The increase in HS levels associated with pornography consumption was notably greater in homosexual and bisexual women relative to heterosexual women, where that pattern was not observed [β(95%CI for interaction): 2.27(0.11; 4.43)]. B) BS: Mean values of BS were observed to be lower for both women [β(95%CI):-2.16(-2.99;-1.32)] and men [β(95%CI):-4.30(-5.75;-2.86)] who consumed pornography compared to those who did not. Homosexual/bisexual men recorded mean values of BS lower than heterosexual men [β(95%CI):-3.10(-4.21;-1.99)].

Conclusions
Pornography consumption is related to sexism and differs according to sex and sexual orientation. As sexism is the substratum of inequality between men and women, it is urgent to launch affective-sexual education programs for young people that take into account the determinants of sexism.
Comparison of performances of SIREN or MFSRS in stroke risk prediction in an African environment
Authors: Onwuakagba Ifeoma Uchenna , Okoye Emmanuel Chiebuka , Kanu Favour Chidera , Kalu Chukwuemeka Michael , Akosile Christopher Olusanjo 
Published: February 2024

Abstract
Background
The Modified Framingham Stroke Risk Score (MFSRS) is a widely utilized stroke risk assessment algorithm usually applied in international comparison. The Stroke Investigative Research and Educational Network (SIREN) is the only known African-specific stroke risk assessment algorithm.

Aims and objectives
To compare stroke risk estimates from the SIREN and the MFSRS in an African community.

Methods
This was a population-based cross-sectional survey involving consecutively recruited 310 consenting adult residents (mean age = 37.21 ± 15.84 years) of a Nigerian community. Risk factors of stroke were assessed among the participants and were utilized in calculating stroke risk estimates on the MFSRS and the SIREN. The obtained data were analyzed using descriptive statistics and the Spearman-rank order correlation test at an alpha level of 0.05.

Results
The percentage stroke risk scores estimated by the SIREN and the MFSRS were 34.5% and 6.79% respectively. The most prevalent risk factors among the participants were hypertriglyceridemia (100.0%), raised waist-hip ratio (50.6%), hypercholesterolemia (45.5), physical inactivity (43.2%), psychological stress (41.3%), and hypertension (37.7%). Only two (hypertriglyceridemia and high blood pressure) out of the six factors considered in the MFSRS were rated among the first 10 most impactful risks by the SIREN. There was a weak correlation between the total scores on the MFSRS and the SIREN (rho = 0.39; p < 0.01) suggesting that the two ratings were discordant.

Conclusion
There were disagreements between the risk estimates on the SIREN and MFSRS with SIREN having a higher estimate that corresponded with the literature; this may be suggesting a poorer estimation of stroke risks by the MFSRS in an African environment. There is a need for large African-based quality control studies to determine and address these lapses.
Success rates of single-thread and double-thread orthodontic miniscrews in the maxillary arch
Authors: Merati Mohsen , Ghaffari Hassanali , Javid Fatemeh , Ahrari Farzaneh 
Published: February 2024

Abstract
Aim
There is limited research on the clinical performance of double-thread orthodontic miniscrews. This study aimed to compare the stability of double-thread and single-thread orthodontic miniscrews and identify the potential associations between patient-related and location-related factors with miniscrew stability.

Methods
This retrospective cohort study involved 90 orthodontic miniscrews (45 single-thread, 45 double-thread) with identical dimensions (8 mm length, 1.6 mm diameter). The screws were inserted in various locations within the upper jaw of 83 patients (54 females, 29 males; mean age = 15.1 ± 2.4 years). Failure was defined as excessive mobility or loss of miniscrew after placement. The data recorded were patient age, gender, insertion site, side of insertion (buccal or lingual), duration of force application, and failure occurrence.

Results
The overall success rate within the sample was 92.2%. Double-thread miniscrews exhibited a significantly higher success rate than single-thread miniscrews (P = 0.049), with 97.8% and 86.7% success rates, respectively. Gender, age, insertion location, and side of insertion did not show significant associations with failure (P > 0.05). Log-rank analysis revealed a significant difference between the two groups (P = 0.046), indicating a higher probability of survival for the double-thread design.

Conclusions
The overall success rate of orthodontic miniscrews was high in the present sample. Double-thread miniscrews placed in various locations within the maxillary arch demonstrated superior stability and survival rates compared to their single-thread counterparts. Therefore, double-thread miniscrews may be preferred when bone quality is inadequate, such as in young patients.
Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis
Authors: Alayyash Afnan , Alam Mohammad Khursheed , Rashid Mohammed Enamur , Mathew Asok , Di Blasio Marco , Ronsivalle Vincenzo , Cicciù Marco , Minervini Giuseppe 
Published: February 2024

Abstract
Background
The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive.

Methods
A comprehensive literature search was conducted to identify relevant studies published up to the study’s cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI).

Results
The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies’ findings. Further research is needed to clarify these associations.

Conclusion
The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition’s origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.
E-portfolio as an effective tool for improvement of practitioner nurses’ clinical competence
Authors: Najaffard Nastaran , Mohammadi Aeen , Mojtahedzadeh Rita , Zarei Afagh 
Published: February 2024

Abstract
Background
Clinical competence is essential for providing effective patient care. Clinical Governance (CG) is a framework for learning and assessing clinical competence. A portfolio is a work-placed-based tool for monitoring and reflecting on clinical practice. This study aimed to investigate the effect of using an e-portfolio on the practitioner nurses’ competence improvement through the CG framework.

Methods
This was a quasi-experimental study with 30 nurses in each intervention and control group. After taking the pretests of knowledge and performance, the participants attended the in-person classes and received the educational materials around CG standards for four weeks. In addition, nurses in the intervention group received the links to their e-portfolios individually and filled them out. They reflected on their clinical practice and received feedback. Finally, nurses in both groups were taken the post-tests.

Results
Comparing the pre-and post-test scores in each group indicated a significant increase in knowledge and performance scores. The post-test scores for knowledge and performance were significantly higher in the intervention group than in the control one, except for the initial patient assessment.

Conclusion
This study showed that the e-portfolio is an effective tool for the improvement of the nurses’ awareness and performance in CG standards. Since the CG standards are closely related to clinical competencies, it is concluded that using portfolios effectively improves clinical competence in practitioner nurses.
An LQT2-related mutation in the voltage-sensing domain is involved in switching the gating polarity of hERG
Authors: Liu Zhipei , Wang Feng , Yuan Hui , Tian Fuyun , Yang Chuanyan , Hu Fei , Liu Yiyao , Tang Meiqin , Ping Meixuan , Kang Chunlan , Luo Ting , Yang Guimei , Hu Mei , Gao Zhaobing , Li Ping 
Published: February 2024

Abstract
Background
Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the “opposite” voltage-sensing properties of hERG and HCN remains unknown.

Results
We found the voltage-sensing domain (VSD) involves in modulating the gating polarity of hERG. We identified that a long-QT syndrome type 2-related mutation within the VSD, K525N, mediated an inwardly rectifying non-deactivating current, perturbing the channel closure, but sparing the open state and inactivated state. K525N rescued the current of a non-functional mutation in the pore helix region (F627Y) of hERG. K525N&F627Y switched hERG into a hyperpolarization-activated channel. The reactivated inward current induced by hyperpolarization mediated by K525N&F627Y can be inhibited by E-4031 and dofetilide quite well. Moreover, we report an extracellular interaction between the S1 helix and the S5-P region is crucial for modulating the gating polarity. The alanine substitution of several residues in this region (F431A, C566A, I607A, and Y611A) impaired the inward current of K525N&F627Y.

Conclusions
Our data provide evidence that a potential cooperation mechanism in the extracellular vestibule of the VSD and the PD would determine the gating polarity in hERG.
Th1 cells contribute to retinal ganglion cell loss in glaucoma in a VCAM-1-dependent manner
Authors: He Chong , Peng Kun , Zhu Xiong , Wang Zuo , Xiu Wenbo , Zhang Gao , Chen Yang , Sun Chaonan , Xiao Xiao , Liu Donghua , Li An , Gao Yanping , Wang Jinxia , Shuai Ping , Chen Yilian , Yu Ling , Lu Fang 
Published: February 2024

AbstractGlaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.
Graphical Abstract
The role of NLRP3 inflammasome in aging and age-related diseases
Authors: Liang Ruikai , Qi Xinrui , Cai Qi , Niu Liyan , Huang Xi , Zhang Deju , Ling Jitao , Wu Yuting , Chen Yixuan , Yang Pingping , Liu Jianping , Zhang Jing , Yu Peng 
Published: February 2024

AbstractThe gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.