bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the prognostic significance of PKCε variants in cervical cancer
Authors: Zafar Sameen , Khan Khushbukhat , Badshah Yasmin , Shahid Kanza , Trembley Janeen H. , Hafeez Amna , Ashraf Naeem Mahmood , Arslan Hamid , Shabbir Maria , Afsar Tayyaba , Almajwal Ali , Razak Suhail 
Published: September 2023

Abstract
Background
Protein Kinase C-epsilon (PKCε) is a member of the novel subfamily of PKCs (nPKCs) that plays a role in cancer development. Studies have revealed that its elevated expression levels are associated with cervical cancer. Previously, we identified pathogenic variations in its different domains through various bioinformatics tools and molecular dynamic simulation. In the present study, the aim was to find the association of its variants rs1553369874 and rs1345511001 with cervical cancer and to determine the influence of these variants on the protein-protein interactions of PKCε, which can lead towards cancer development and poor survival rates.

Methods
The association of the variants with cervical cancer and its clinicopathological features was determined through genotyping analysis. Odds ratio and relative risk along with Fisher exact test were calculated to evaluate variants significance and disease risk. Protein-protein docking was performed and docked complexes were subjected to molecular dynamics simulation to gauge the variants impact on PKCε’s molecular interactions.

Results
This study revealed that genetic variants rs1553369874 and rs1345511001 were associated with cervical cancer. Smad3 interacts with PKCε and this interaction promotes cervical cancer angiogenesis; therefore, Smad3 was selected for protein-protein docking. The analysis revealed PKCε variants promoted aberrant interactions with Smad3 that might lead to the activation of oncogenic pathways. The data obtained from this study suggested the prognostic significance of PRKCE gene variants rs1553369874 and rs1345511001.

Conclusion
Through further in vitro and in vivo validation, these variants can be used at the clinical level as novel prognostic markers and therapeutic targets against cervical cancer.
Cost-effectiveness analysis of pembrolizumab in combination with chemotherapy compared with chemotherapy alone as first-line treatment for patients with advanced biliary tract cancer in China
Authors: Zheng Zhiwei , Fang Ling , Cai Hongfu 
Published: September 2023

Abstract
Objective
The objective of this study is to evaluate the cost-effectiveness of adding pembrolizumab to the standard first-line therapy of advanced biliary tract cancer (BTC) with gemcitabine and cisplatin from the perspective of the Chinese healthcare system.

Methods
The partitioned survival model developed from clinical data obtained in The KEYNOTE-966 trial served as the basis for a simulation in the TreeAge Pro 2011 software. The objective of the research was to estimate the 10-year life expectancy and total healthcare costs of patients with BTC, utilizing primary outcomes that evaluated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). To establish the willingness-to-pay (WTP) threshold, the 2022 Chinese per capita gross domestic product (GDP) of $37304.346/QALY was adopted. Furthermore, sensitivity analysis was conducted to ascertain the study’s results under varying levels of uncertainty.

Results
Compared to chemotherapy alone, the addition of pembrolizumab to chemotherapy has been shown to yield an incremental gain of 0.184 quality-adjusted life years (QALY) at an additional cost of $103940.706. This translates into an incremental cost-effectiveness ratio (ICER) of $564895.141/QALY, which exceeds the willingness-to-pay (WTP) threshold in China. One-way sensitivity analyses performed on the model recognize the utility of PD, subsequent cost, and the cost of Pembrolizumab 100 mg had a major influence on the outcomes. However, no parameter elicited an ICER lower than the willingness-to-pay (WTP) threshold.

Conclusions
Based on the perspective of the Chinese healthcare system, the utilization of pembrolizumab in combination with chemotherapy as an first-line treatment option for BTC does not appear to be a cost-effective approach compared to chemotherapy as a standalone therapy.
Clinical trials in cancer screening, prevention and early diagnosis (SPED): a systematic mapping review
Authors: O’Dowd Emma L. , Merriel Samuel W. D. , Cheng Vinton W. T. , Khan Sam , Howells Lynne M. , Gopal Dipesh P. , Roundhill Elizabeth A. , Brennan Paul M. , Crosbie Philip A. J. , Neal Richard D. , Brown Karen , Crosbie Emma J. , Baldwin David R. 
Published: September 2023

Abstract
Background
Global annual cancer incidence is forecast to rise to 27.5 M by 2040, a 62% increase from 2018. For most cancers, prevention and early detection are the most effective ways of reducing mortality. This study maps trials in cancer screening, prevention, and early diagnosis (SPED) to identify areas of unmet need and highlight research priorities.

Methods
A systematic mapping review was conducted to evaluate all clinical trials focused on cancer SPED, irrespective of tumour type. The National Cancer Research Institute (NCRI) portfolio, EMBASE, PubMed and Medline were searched for relevant papers published between 01/01/2007 and 01/04/2020. References were exported into Covidence software and double-screened. Data were extracted and mapped according to tumour site, geographical location, and intervention type.

Results
One hundred seventeen thousand seven hundred one abstracts were screened, 5157 full texts reviewed, and 2888 studies included. 1184 (52%) trials focussed on screening, 554 (24%) prevention, 442 (20%) early diagnosis, and 85 (4%) a combination. Colorectal, breast, and cervical cancer comprised 61% of all studies compared with 6.4% in lung and 1.8% in liver cancer. The latter two are responsible for 26.3% of global cancer deaths compared with 19.3% for the former three. Number of studies varied markedly according to geographical location; 88% were based in North America, Europe, or Asia.

Conclusions
This study shows clear disparities in the volume of research conducted across different tumour types and according to geographical location. These findings will help drive future research effort so that resources can be directed towards major challenges in cancer SPED.
circFNDC3B promotes esophageal squamous cell carcinoma progression by targeting MYO5A via miR-370-3p/miR-136-5p
Authors: Song Dan , Ye Ziqi , Chen Fangyu , Zhan Liangliang , Sun Xinchen 
Published: September 2023

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor worldwide. Circular RNA (circRNA) is of great value in tumorigenesis progression. However, the mechanism of circFNDC3B in ESCC remains to be clarified.

Methods
Firstly, the circular characteristics of circFNDC3B were evaluated by Actinomycin D and RNase R measurements. The functions of circFNDC3B in ESCC cells were examined by CCK-8, EdU and flow cytometry. Subsequently, the molecular mechanism of circFNDC3B was explained using luciferase reporter gene detection. Finally, we constructed xenograft model to prove the role of circFNDC3B in vivo.

Results
Our study revealed that circFNDC3B was more stable than its linear RNA and prominently upregulated in ESCC. Functional findings suggested that silencing of circFNDC3B reduced the proliferation and enhanced apoptosis of ESCC cells in vitro. Meanwhile, knockdown of circFNDC3B attenuated tumor progression in vivo. Next, miR-370-3p/miR-136-5p was discovered to bind circFNDC3B. miR-370-3p/miR-136-5p reversed the promotive effect on cell proliferation and the inhibitory effect on cell apoptosis of circFNDC3B. MYO5A was a downstream target of miR-370-3p/miR-136-5p. CircFNDC3B served as a sponge for miR-370-3p/miR-136-5p and alleviated the prohibitory effect of miR-370-3p/miR-136-5p on MYO5A, which accelerated ESCC progression.

Conclusion
circFNDC3B positively adjusted the MYO5A expression via spongy miR-370-3p/miR-136-5p, hence achieving the cancer-promoting effect on ESCC. circFNDC3B was a prospective diagnosis marker for ESCC.
Clinical characteristics of infants hospitalized with early congenital syphilitic nephropathy: a single-center retrospective cross-sectional study in China
Authors: Wang Caiying , Lun Wenhui , Pang Lin 
Published: September 2023

Abstract
Background
Early studies claimed that early congenital syphilitic (CS) nephropathy was rare, and systematic studies about this disease are absent, which may lead to poor awareness of early CS nephropathy in clinicians and result in misdiagnosis and poor patient prognosis. The present study systematically and comprehensively analyzes the clinical characteristics of infants with early CS nephropathy hospitalized in Beijing Ditan Hospital, an infectious disease hospital in China in order to improve the understanding and management of this disorder.

Methods
Data of the children with early CS from July 1, 2008, to December 31, 2021, were collected from the electronic medical record system of the hospital. Each patient’s demographic characteristics, clinical history, mother’s history of syphilitic infection, and laboratory values were extracted. The patients were enrolled to either the nephropathy group or the non-nephropathy group depending on diagnosis. Descriptive statistics was used to report basic demographics, clinical and laboratory test values, and variables were compared between the two groups by nonparametric tests, t test or χ2 tests.

Results
Of the 122 children with early CS enrolled, 24(19.7%) were diagnosed with early CS nephropathy. All of the children with CS nephropathy were young infants < 6 months old. A majority of them showed typical congenital syphilitic skin lesions, but a quarter of them did not have skin lesions. Compared with non-nephropathic children with early CS, those with nephropathy had higher frequency of hepatosplenomegaly, fever, edema, gastrointestinal (GI) symptoms, and anemia, as well as decreased C3 levels. Urinalysis results showed hematuria in all patients with early CS nephropathy, with proteinuria and renal function impairment in 91.7% and 12.5% of the patients, respectively. Nephritic-type nephrotic syndrome and glomerulonephritis were diagnosed in 45.8% and 54.2% of these patients, respectively. All infants with CS nephropathy were cured or improved after appropriate treatments.

Conclusion
Infants with early CS nephropathy often presented with nephritic-type nephrotic syndrome or glomerulonephritis, and the typical skin lesions, fever, hepatosplenomegaly, and edema, etc., were its common clinical presentations, and these characteristics could help with the diagnosis. But for infants with nephropathy who did not have typical clinical presentations, CS should also be screened as an important etiology to avoid misdiagnosis.
Towards an integrative hope-dysfunctional beliefs perspective to personal recovery in schizophrenia: a path analysis
Authors: Wong Daniel Fu Keung , Cheung Yves Cho Ho , Zhuang Xiaoyu , Ng Yat-nan Petrus , Oades Lindsey G. , Ye Shengquan Sam 
Published: September 2023

Abstract
Background
Evidence shows that negative symptoms of schizophrenia and underlying dysfunctional cognition are related to persistently low functioning and quality of life. However, despite the abundance of existing recovery programs for people with schizophrenia, few have examined whether and how the widely-adopted hope-motivation recovery pathway and the deficit-oriented cognitive pathway might converge to influence functioning and quality of life.

Methods
A cross-sectional, quantative survey recruited a convenient sample of adult outpatients with DSM-5 schizophrenia spectrum disorders and low social functioning (n = 124). Self-reported measurements included personal recovery (30-item Mental Health Recovery Measure), social functioning (8-item Social Functioning Questionnaire), hope (12-item Hope Scale), quality of life (28-item World Health Organization Quality of Life Scale-Abbreviated Version-Hong Kong), defeatist beliefs (15-item extracted from Dysfunctional Attitude Scale), and asocial beliefs (15-item extracted from Revised Social Anhedonia Scale). Correlation analysis and structural equation modelling was applied to investigate how the two pathways intertwined to predict social functioning and quality of life.

Results
Asocial beliefs and hope separately mediated two partial mediation pathways from defeatist beliefs to recovery outcomes (social functioning and personal recovery). Meanwhile, defeatist beliefs, social functioning, and personal recovery further predicted quality of life.

Conclusions
This is one of the very few studies that provides empirical evidence of a deficit-strength linkage in the recovery from schizophrenia. Remediation of dysfunctional beliefs and the injection of hope and successful experiences should be undertaken concurrently in recovery as they are associated with differential effects on enhancing social functioning and personal recovery, which then converge and contribute to a better quality of life.
Transdiagnostic considerations of the relationship between reward sensitivity and psychopathological symptoms - a cross-lagged panel analysis
Authors: Potsch L. , Rief W. 
Published: September 2023

Abstract
Background
Reward sensitivity constitutes a potential key mechanism regarding the etiology and maintenance of mental disorders, especially depression. However, due to a lack of longitudinal studies, the temporal dynamics are not clear yet. Although some evidence indicates that reward processing could be a transdiagnostic mechanism of disorders, these observations could be also a product of comorbidity with depression. This study aimed at investigating the temporal dynamics of reward sensitivity and the course of psychopathological symptoms in a longitudinal investigation, while taking a possible mediating role of depression into account.

Methods
We conducted a three-wave longitudinal online survey with a 4-week interval. A total of N = 453 participants filled out all three questionnaires. Reward sensitivity was assessed with the Positive Valence System Scale-21 (PVSS-21), depression with the Patient Health Questionnaire (PHQ-9), eating disorder symptoms with the Eating Disorder Examination-Questionnaire-8 (EDE-Q-8), social anxiety with the Mini-social phobia inventory (Mini-SPIN) and alcohol consumption with the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Cross-lagged panels and mediation analyses were calculated using path analyses.

Results
Depressive and eating disorder symptoms predicted reward insensitivity at later points in time. Effects were larger from T2 to T3. A bidirectional relationship concerning social anxiety was found. Higher alcohol consumption predicted higher reward sensitivity. Depression at T2 fully mediated the association between psychopathological symptoms at T1 and reward sensitivity at T3 for social anxiety and eating disorder symptoms.

Conclusions
Our findings imply that reduced reward sensitivity seems to be a consequence rather than an antecedent of psychopathological symptoms. Comorbid depression plays a crucial role in other mental disorders regarding observed hyposensitivity towards rewards. Therefore, our results do not support a transdiagnostic notion of reward sensitivity, but they indicate a potential role of reward sensitivity for symptom persistence.

Trial registration
The study was preregistered at the Open Science Framework (OSF) (https://archive.org/details/osf-registrations-6n3s8-v1; registration DOI https://doi.org/10.17605/OSF.IO/6N3S8).
The effect of web-based educational interventions on mental health literacy, stigma and help-seeking intentions/attitudes in young people: systematic review and meta-analysis
Authors: Nazari Abouzar , Garmaroudi Gholamreza , Foroushani Abbas Rahimi , Hosseinnia Maede 
Published: September 2023

Abstract
Objectives
This study aims to provide a systematic review and meta-analysis of the literature on The Effect of Web-Based Educational Interventions on Mental Health Literacy, Stigma and Help-seeking intentions/attitudes in young people.

Methods
Articles in English published between April 1975 and February 2023 were retrieved from seven databases, leading to a total of 2023 articles identified.

Results
20 studies were included after applying exclusion criteria, 10 of which were eligible for meta-analysis. Results showed that web-based educational interventions had a significant positive effect on mental health literacy knowledge (SMD = 0.70, 95% CI = [0.16, 1.25]), but not on stigma (SMD = -0.20, 95% CI = [-0.48, 0.08]) or help-seeking intentions/attitudes (SMD = 0.48, 95% CI = [-0.50, 1.46]).

Conclusion
This study reviewed and analyzed the effect of web-based educational interventions on mental health literacy, stigma, and help-seeking intentions/attitudes among young people. The results showed that web-based educational interventions improved mental health literacy knowledge, but not stigma or help-seeking outcomes. The study suggested several recommendations to enhance the effectiveness of web-based educational interventions on stigma and help-seeking outcomes, such as using more rigorous designs and methods, more comprehensive and multifaceted interventions, more tailored and targeted interventions, and more collaborative and participatory approaches. The study concluded that web-based educational interventions may have a greater impact on reducing stigma and promoting help-seeking among young people, which may ultimately lead to better mental health outcomes and well-being for this population.
Mixed methods feasibility and usability testing of a childhood obesity risk estimation tool
Authors: Grove Grace , Ziauddeen Nida , Roderick Paul , Vassilev Ivaylo , Appleton Jane V. , Smith Dianna , Alwan Nisreen A. 
Published: September 2023

Abstract
Background
A Childhood Obesity Risk Estimation tool (SLOPE CORE) has been developed based on prediction models using routinely available maternity and early childhood data to estimate risk of childhood obesity at 4–5 years. This study aims to test the feasibility, acceptability and usability of SLOPE CORE within an enhanced health visiting (EHV) service in the UK, as one context in which this tool could be utilised.

Methods
A mixed methods approach was used to assess feasibility of implementing SLOPE CORE. Health Visitors (HVs) were trained to use the tool, and in the processes for recruiting parents into the study. HVs were recruited using purposive sampling and parents by convenience sampling. HVs and parents were invited to take part in interviews or focus groups to explore their experiences of the tool. HVs were asked to complete a system usability scale (SUS) questionnaire.

Results
Five HVs and seven parents took part in the study. HVs found SLOPE CORE easy to use with a mean SUS of 84.4, (n = 4, range 70–97.5) indicating excellent usability. Five HVs and three parents took part in qualitative work. The tool was acceptable and useful for both parents and HVs. Parents expressed a desire to know their child’s risk of future obesity, provided this was accompanied by additional information, or support to modify risk. HVs appreciated the health promotion opportunity that the tool presented and felt that it facilitated difficult conversations around weight, by providing ‘clinical evidence’ for risk, and placing the focus of the conversation onto the tool result, rather than their professional judgement. The main potential barriers to use of the tool included the need for internet access, and concerns around time needed to have a sensitive discussion around a conceptually difficult topic (risk).

Conclusions
SLOPE CORE could potentially be useful in clinical practice. It may support targeting limited resources towards families most at risk of childhood obesity. Further research is needed to explore how the tool might be efficiently incorporated into practice, and to evaluate the impact of the tool, and any subsequent interventions, on preventing childhood obesity.
The systematic development of guidance for parents on talking to children of primary school age about weight
Authors: Gillison Fiona B. , Grey Elisabeth B. , Baber Fran , Chater Angel , Atkinson Lou , Gahagan Alison 
Published: September 2023

AbstractBackgroundThe prevalence of overweight and obesity in children is increasing, alongside increases in rates of children’s anxiety and worry about their weight. In many countries children’s weight is measured, and parents are made aware if a child has been classified as having overweight or obesity. However, many parents are concerned that raising their child’s awareness of their weight, and talking to children about their weight could harm their wellbeing. The aim of this project was to develop guidance for parents on constructive ways to talk to children of primary school age about weight when they need to.MethodsThe project followed a mixed-methods design: Phase 1 involved the collation of evidence including (a) two previously published systematic literature reviews to identify the associations between parent–child weight talk, and broader health discussions, and children’s wellbeing, (b) interviews with children, and (c) development and refinement of narrative messaging (previously published). In Phase 2 we developed a conceptual model and mapped primary findings to techniques and content within a draft guidance document for parents on talking to children about weight. Phase 3 involved a modified Delphi process with 29 stakeholders to refine and agree a final version.ResultsAn acceptable draft guidance was agreed following two stages of feedback from Delphi participants. Key areas for debate and adaptation included: encouraging discussion about health and growth with lesser focus on weight; finding ways to reduce stigma and perceptions of blame; emphasising a whole-family approach; inclusive representation of diversity among children and families.ConclusionsConsensus on the content of guidance for parents on talking to children about weight was achieved through a process of evidence review and stakeholder and expert engagement. The next steps are to measure the impact of the resource on improving the experience of parents and children in communicating about weight.