bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non–small cell lung cancer: a modelling approach
Authors: Hui Wen , Song Ruomeng , Tao Hongyu , Gao Zhixiang , Zhu Min , Zhang Mingyue , Wu Huazhang , Gong Daichen , Zhang Xiyan , Cai Yuanyi 
Published: May 2023

Abstract
Background
Many studies have explored the cost-effectiveness of immunotherapy versus chemotherapy alone. However, there is paucity of evidence on direct pharmacoeconomic studies related to immunotherapy combinations. Thus, we aimed at assessing the economic outcomes of first-line immunotherapy combinations in the treatment of advanced non-small cell lung cancer (NSCLC) from the Chinese health care perspective.

Methods
The mutual hazard ratios (HRs) of ten immunotherapy combinations and one chemotherapy regimen for the overall survival (OS) and progression-free survival (PFS) were obtained from a network meta-analysis. Based on proportional hazard (PH) assumption, adjusted OS and PFS curves were established to make the effects comparable. With the parameters of cost and utility, and of scale and shape from the fit of adjusted OS and PFS curves obtained from previous studies, a partitioned survival model was designed to estimate the cost-effectiveness of immunotherapy combinations versus chemotherapy alone. Parameter uncertainty in model inputs was assessed using one-way deterministic and probabilistic sensitivity analyses.

Results
The incremental cost of camrelizumab plus chemotherapy versus chemotherapy alone was $13,180.65, the lowest among all the other immunotherapy combinations. Furthermore, sintilimab plus chemotherapy (sint-chemo) provided the highest quality-adjusted life-year (QALY) benefit versus chemotherapy alone (incremental QALYs = 0.45). Sint-chemo yielded the best incremental cost-effectiveness ratio (ICER) versus chemotherapy alone (ICER = $34,912.09/QALY), at the current price. The cost-effectiveness probabilities were 32.01% and 93.91% for pembrolizumab plus chemotherapy, and atezolizumab plus bevacizumab plus chemotherapy, respectively (if the original price of the pembrolizumab, atezolizumab, and bevacizumab were decreased by 90%).

Conclusions
Based on the fact that there is fierce competition in the PD-1/PD-L1 market, pharmaceutical enterprises should strive for greater efficacy, and optimal pricing strategy for therapies.
An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
Authors: Yamada Yosuke , Simon Ronald , Iwane Kosuke , Nakanishi Yuki , Takeuchi Yasuhide , Yoshizawa Akihiko , Takada Masahiro , Toi Masakazu , Haga Hironori , Marx Alexander , Sauter Guido 
Published: May 2023

Abstract
Background
Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ.

Methods
Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells.

Results
Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the “master regulator” of TNBCs.

Conclusions
POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs.
Ophthalmic manifestations in children with Down Syndrome in Bogotá, Colombia
Authors: Rojas‑Carabali William , Cortés-Albornoz María Camila , Flórez‑Esparza Gabriela , Cifuentes‑González Carlos , de‑la‑Torre Alejandra , Talero‑Gutiérrez Claudia 
Published: May 2023

Abstract
Background

To describe the ocular features of a cohort of children with Down Syndrome (DS) in Bogotá, Colombia.

Methods
We performed a cross-sectional study, evaluating 67 children with DS. A pediatric ophthalmologist performed a complete optometric and ophthalmological evaluation of each child, including visual acuity, ocular alignment, external eye examination, biomicroscopy, auto-refractometry, retinoscope in cycloplegia, and fundus examination. Results were reported as frequency distribution tables with percentages for categorical variables and means and standard deviation or median and interquartile ranges for continuous variables, according to their distribution. We used the Chi-square test or Fisher’s exact test for categorical variables and ANOVA or Kruskal–Wallis for continuous variables when indicated.

Results
A total of 134 eyes from 67 children were evaluated. Males represented 50.7%. The children’s age ranged from 8–16 years, with a mean of 12.3 (SD 2.30). The most frequent refractive diagnosis per eye was hyperopia (47%), followed by myopia (32.1%) and mixed astigmatism (18.7%). The most frequent ocular manifestations were oblique fissure (89.6%), followed by amblyopia (54.5%) and lens opacity (39.4%). Female sex was associated with strabismus (P = 0.009) and amblyopia (P = 0.048).

Conclusion
Our cohort had a high prevalence of disregarded ophthalmological manifestations. Some of these manifestations, such as amblyopia, can be irreversible and severely affect the neurodevelopment of DS children. Therefore, ophthalmologists and optometrists should be aware of the visual and ocular affection of children with DS to assess and provide appropriate management. This awareness could improve rehabilitation outcomes for these children.
Initial postoperative plasticity as a predictor of mid-term stereoacuity outcome after surgery for intermittent exotropia
Authors: Liu Peipei , Fu Jing , Zhang Ronghan , Chu Hang 
Published: May 2023

Abstract
Background
Intermittent exotropia (IXT) would cause different degrees of damage to stereopsis. We aimed to introduce a visual perception plasticity score (VPPS) that reflects initial postoperative plasticity and evaluate its effectiveness in predicting the mid-term surgical outcome in IXT patients.

Methods
A total of 149 patients with intermittent exotropia who underwent surgery in November 2018 and October 2019 were recruited. All subjects underwent detailed ocular examinations before and after surgery. VPPS were calculated based on visual perception examination system at one week postoperatively. Demographic, angle of deviation and stereopsis were collected and analyzed with regard to the VPPSs preoperatively and at one week, one month, three months, six months postoperatively. Predictive performances of VPPS were assessed using receiver operating characteristic (ROC) curves, the area under the curve (AUC) and cut-offs were obtained.

Results
Of the 149 patients, the average deviation was 43Δ at distance and 46Δ at near. The average rate of normal stereopsis before surgery was 22.81% at distance and 29.53% at near. Higher VPPS was associated with preoperative better near stereoacuity (r = 0.362, p = 0.000), less angle of deviation at distance (r=-0.164, p = 0.046), and better near (r = 0.400, p = 0.000) and distant stereoacuity (r = 0.321, p = 0.000) during the early postoperative period (1 week). The areas under the curves suggested that VPPS could be an effective predictor of sensory outcome(AUC>0.6). Cut-off values of 50 and 80 were calculated for VPPS using ROC curve analysis.

Conclusion
Higher VPPSs were associated with a greater possibility of stereopsis improvement in patients with IXT. VPPS is a potentially promising indicator to predict the mid-term surgical outcome of intermittent exotropia.
Diffusion of a micronutrient home fortification program for infants and toddlers in a multi-ethnic population in rural western China
Authors: Ye Ruixue , Wu Yuju , Sun Chang , Wang Qingzhi , Mao Yuping , Zhou Huan , Raat Hein 
Published: May 2023

Abstract
Background
The micronutrient home fortification programs contribute to the prevention of childhood anemia. WHO suggested applying culturally appropriate strategies to implement the micronutrient home fortification programs in various communities. However, there is little knowledge on evidence-based effective diffusion strategies of the micronutrient home fortification programs in multi-ethnic populations. This study aims to examine the diffusion of a micronutrient home fortification program with micronutrient powder (MNP) in a multi-ethnic population by investigating factors associated with being an ‘early’ or a ‘later’ adopter of MNP.

Methods
We conducted a cross-sectional study in rural western China. Multistage sampling was used to select children’s caregivers in Han, Tibetan, and Yi ethnic communities (N = 570). The diffusion of innovations theory informed the data collection on caregivers’ decision process and was applied to classify participants into the MNP adopter categories of ‘leaders’, ‘followers’, ‘loungers’, and ‘laggards’. The ordered logistic regression model estimated the factors associated with the MNP adopter categories.

Results
Caregivers from the Yi ethnic subgroup were likely to adopt MNP relatively late (AOR = 1.67; 95%CI = 1.09, 2.54) compared with Han and Tibetan ethnic subgroups. Caregivers with more knowledge regarding the MNP feeding method (AOR = 0.71; 95%CI = 0.52, 0.97) and those with stronger self-efficacy in adopting MNP (AOR = 0.85; 95%CI = 0.76, 0.96) were more likely to adopt MNP earlier than others. The following messages and channels also tend to make caregivers adopt MNP earlier: hearing that ‘MNP was free’ from villagers (AOR = 0.45; 95%CI = 0.20, 0.98), and learning ‘MNP feeding method’ from township doctors (AOR = 0.16; 95%CI = 0.06, 0.48).

Conclusions
Disparities in adopting MNP existing among different ethnic groups require more effective diffusion strategies in disadvantaged minority ethnic groups. Enhancing self-efficacy in adopting MNP and knowledge on feeding method of MNP have the potential to make caregivers adopt MNP earlier. Peer networks and township doctors can be effective agencies to facilitate the diffusion and adoption of MNP.
Barriers to oral care: a cross-sectional analysis of the Canadian longitudinal study on aging (CLSA)
Authors: De Rubeis Vanessa , Jiang Ying , de Groh Margaret , Dufour Lisette , Bronsard Annie , Morrison Howard , Bassim Carol W. 
Published: May 2023

Abstract
Background
Oral health plays a role in overall health, indicating the need to identify barriers to accessing oral care. The objective of this study was to identify barriers to accessing oral health care and examine the association between socioeconomic, psychosocial, and physical measures with access to oral health care among older Canadians.

Methods
A cross-sectional study was conducted using data from the Canadian Longitudinal Study on Aging (CLSA) follow-up 1 survey to analyze dental insurance and last oral health care visit. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between socioeconomic, psychosocial, and physical measures with access to oral care, measured by dental insurance and last oral health visit.

Results
Among the 44,011 adults included in the study, 40% reported not having dental insurance while 15% had not visited an oral health professional in the previous 12 months. Several factors were identified as barriers to accessing oral health care including, no dental insurance, low household income, rural residence, and having no natural teeth. People with an annual income of <$50,000 were four times more likely to not have dental insurance (adjusted OR: 4.09; 95% CI: 3.80–4.39) and three times more likely to report not visiting an oral health professional in the previous 12 months (adjusted OR: 3.07; 95% CI: 2.74–3.44) compared to those with annual income greater than $100,000.

Conclusions
Identifying barriers to oral health care is important when developing public health strategies to improve access, however, further research is needed to identify the mechanisms as to why these barriers exist.
Effects of blue-light LED toothbrush on reducing dental plaque and gingival inflammation in orthodontic patients with fixed appliances: a crossover randomized controlled trial
Authors: Manphibool Chavirakarn , Matangkasombut Oranart , Chantarangsu Soranun , Chantarawaratit Pintu-on 
Published: May 2023

Abstract
Background
Patients with fixed orthodontic appliances have higher plaque accumulation and gingival inflammation. Our aim was to compare the effectiveness of a light emitting diode (LED) toothbrush with a manual toothbrush in reducing dental plaque and gingival inflammation in orthodontic patients with fixed appliances, and to investigate the effect of the LED toothbrush on Streptococcus mutans (S. mutans) biofilm in vitro.

Methods
Twenty-four orthodontic patients were recruited and randomly assigned into 2 groups: (1) started with manual and (2) started with LED toothbrushes. After a 28-day usage and 28-day wash-out period, the patients switched to the other intervention. The plaque and gingival indices were determined at baseline and 28 days after each intervention. The patients’ compliance and satisfaction scores were collected using questionnaires. For the in vitro experiments, S. mutans biofilm was divided into 5 groups (n = 6) with 15-, 30-, 60-, or 120-sec LED exposure, and without LED exposure as a control group.

Results
There was no significant difference in the gingival index between the manual and LED toothbrush groups. The manual toothbrush was significantly more effective in reducing the plaque index in the proximal area on the bracket side (P = 0.031). However, no significant difference was found between the two groups in other areas around the brackets or on the non-bracket side. After LED exposure in vitro, the percentages of bacterial viability after LED exposure for 15–120 s were significantly lower compared with the control (P = 0.006).

Conclusion
Clinically, the LED toothbrush was not more effective in reducing dental plaque or gingival inflammation than the manual toothbrush in orthodontic patients with fixed appliances. However, the blue light from the LED toothbrush significantly reduced the number of S. mutans in biofilm when it was exposed to the light for at least 15 s in vitro.

Clinical Trial Registration
Thai Clinical Trials Registry (TCTR20210510004). Registered 10/05/2021.
Impact of the number of cycles of platinum-based chemotherapy for early stage ovarian clear cell carcinoma on survival: a retrospective study
Authors: Gao Yang 
Published: May 2023

Abstract
Background
Ovarian clear cell carcinoma (OCCC) is a unique subtype of ovarian epithelial ovarian cancer. The number of chemotherapy cycles for early-stage patients is still debated. This study aimed to evaluate whether at least 4 cycles of adjuvant platinum-based chemotherapy have better prognostic value than 1–3 cycles in early-stage OCCC.

Methods
We retrospectively retrieved data from 102 patients with stage I-IIA OCCC between 2008 and 2017. All patients underwent complete surgical staging followed by adjuvant platinum-based chemotherapy. Kaplan-Meier curves and Multivariate Cox analysis were performed to estimate 5-year overall survival (OS) and progression-free (PFS) according to the number of chemotherapy cycles.

Results
Among stage I-IIA disease, twenty (19.6%) patients received 1–3 cycles, and eighty-two (80.4%) patients received at least 4 cycles of adjuvant chemotherapy. Univariate analysis revealed that the patients in 1-3cycles group had not significantly improved 5-year OS and PFS than those in the ≥ 4 cycles group (5-year OS: hazard ratio [HR] 1.21; 95% confidence interval [CI] 0.25– 5.78, p = 0.1), and 5-year PFS: HR 0.79; 95% CI 0.26– 2.34, p = 0.1). In the multivariate analysis, there was no impact of 1–3 versus ≥ 4 cycles of chemotherapy on 5-year OS (HR 1.21, 95% CI 0.25–3.89, p = 0.8) or 5-year PFS (HR 0.94, 95% CI 0.32–2.71, p = 0.9). The potential independent risk factors associated with 5-year OS and PFS included the surgery approach and FIGO stage.

Conclusion
The number of cycles of platinum-based chemotherapy could not be associated with a survival benefit for patients with early-stage OCCC.
FAIRness through automation: development of an automated medical data integration infrastructure for FAIR health data in a maximum care university hospital
Authors: Parciak Marcel , Suhr Markus , Schmidt Christian , Bönisch Caroline , Löhnhardt Benjamin , Kesztyüs Dorothea , Kesztyüs Tibor 
Published: May 2023

Abstract
Background
Secondary use of routine medical data is key to large-scale clinical and health services research. In a maximum care hospital, the volume of data generated exceeds the limits of big data on a daily basis. This so-called “real world data” are essential to complement knowledge and results from clinical trials. Furthermore, big data may help in establishing precision medicine. However, manual data extraction and annotation workflows to transfer routine data into research data would be complex and inefficient. Generally, best practices for managing research data focus on data output rather than the entire data journey from primary sources to analysis. To eventually make routinely collected data usable and available for research, many hurdles have to be overcome. In this work, we present the implementation of an automated framework for timely processing of clinical care data including free texts and genetic data (non-structured data) and centralized storage as Findable, Accessible, Interoperable, Reusable (FAIR) research data in a maximum care university hospital.

Methods
We identify data processing workflows necessary to operate a medical research data service unit in a maximum care hospital. We decompose structurally equal tasks into elementary sub-processes and propose a framework for general data processing. We base our processes on open-source software-components and, where necessary, custom-built generic tools.

Results
We demonstrate the application of our proposed framework in practice by describing its use in our Medical Data Integration Center (MeDIC). Our microservices-based and fully open-source data processing automation framework incorporates a complete recording of data management and manipulation activities. The prototype implementation also includes a metadata schema for data provenance and a process validation concept. All requirements of a MeDIC are orchestrated within the proposed framework: Data input from many heterogeneous sources, pseudonymization and harmonization, integration in a data warehouse and finally possibilities for extraction or aggregation of data for research purposes according to data protection requirements.

Conclusion
Though the framework is not a panacea for bringing routine-based research data into compliance with FAIR principles, it provides a much-needed possibility to process data in a fully automated, traceable, and reproducible manner.
The sexuality experience of stoma patients: a meta-ethnography of qualitative research
Authors: Lin Siting , Yin Guo , Chen Linghui 
Published: May 2023

Abstract
Background
As the quality of life of stoma patients has become a research hotspot, sexual health as an integral part of patients’ lives has received more and more attention. However, there is a lack of comprehensive reviews on the sexual experiences of patients with stomas. This study aims to synthesize the qualitative literature on the subjective experience of stoma patients’ sexual life, to identify their sexual needs, and to provide evidence for the content and methods of sexual health interventions for healthcare professionals.

Methods
PubMed, Embase, Web of Science, CINAHL, and Scopus were searched for qualitative studies on the sexual experience of stoma patients (from the inception to January 2023). Titles, abstracts, and full texts were reviewed by two researchers. We used the Critical Appraisal Program (CASP) checklist to assess the quality of included articles.

Results
A total of 1388 articles were retrieved, and eight studies were included. Data was extracted, including three main themes: 1) sexual problems due to changes in physical function and psychological disorders; 2) the relationship with spouse changes; 3) the cognition of sexual life and the need for sexual knowledge.

Conclusion
Healthcare professionals should pay attention to the sexual life status and sexual health needs of stoma patients and their partners, and give professional guidance and support in treatment and nursing to improve the quality of sexual life of stoma patients.