bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of the novel immune risk scoring system related to CD8+ T cells in uterine corpus endometrial carcinoma
Authors: Zhang Ganghua , Yin Zhijing , Fang Jianing , Wu Anshan , Chen Guanjun , Cao Ke 
Published: June 2023

Abstract
Background
Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all potential beneficiaries of immunotherapy. Consequently, it is necessary to construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy.

Methods
CIBERSORT combined with weighted gene co-expression network analysis (WGCNA), non-negative matrix factorization (NMF), and random forest algorithms to screen the module associated with CD8+ T cells, and key genes related to prognosis were selected out by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to develop the novel immune risk score (NIRS). Kaplan–Meier (K-M) analysis was used to compare the difference of survival between high- and low- NIRS groups. We also explored the correlations between NIRS, immune infiltration and immunotherapy, and three external validation sets were used to verify the predictive performance of NIRS. Furthermore, clinical subgroup analysis, mutation analysis, differential expression of immune checkpoints, and drug sensitivity analysis were performed to generate individualized treatments for patients with different risk scores. Finally, gene set variation analysis (GSVA) was conducted to explore the biological functions of NIRS, and qRT-PCR was applied to verify the differential expressions of three trait genes at cellular and tissue levels.

Results
Among the modules clustered by WGCNA, the magenta module was most positively associated with CD8+ T cells. Three genes (CTSW, CD3D and CD48) were selected to construct NIRS after multiple screening procedures. NIRS was confirmed as an independent prognostic factor of UCEC, and patients with high NIRS had significantly worse prognosis compared to those with low NIRS. The high NIRS group showed lower levels of infiltrated immune cells, gene mutations, and expression of multiple immune checkpoints, indicating reduced sensitivity to immunotherapy. Three module genes were identified as protective factors positively correlated with the level of CD8+ T cells.

Conclusions
In this study, we constructed NIRS as a novel predictive signature of UCEC. NIRS not only differentiates patients with distinct prognoses and immune responsiveness, but also guides their therapeutic regimens.
Performance of a novel melting curve-based qPCR assay for malaria parasites in routine clinical practice in non-endemic setting
Authors: van Bergen Kim J. M. , Stuitje Antoine R. , Akkers Robert C. , Vermeer Henricus J. , Castel Rob , Mank Theo G. 
Published: June 2023

Abstract
Background
High-quality malaria diagnosis is essential for effective treatment and clinical disease management. Microscopy and rapid diagnostic tests are the conventional methods performed as first-line malaria diagnostics in non-endemic countries. However, these methods lack the characteristic to detect very low parasitaemia, and accurate identification of the Plasmodium species can be difficult. This study evaluated the performance of the MC004 melting curve-based qPCR for the diagnosis of malaria in routine clinical practice in non-endemic setting.

Methods and results
Whole blood samples were collected from 304 patients with clinical suspicion of malaria and analysed by both the MC004 assay and conventional diagnostics. Two discrepancies were found between the MC004 assay and microscopy. Repeated microscopic analysis confirmed the qPCR results. Comparison of the parasitaemia of nineteen Plasmodium falciparum samples determined by both microscopy and qPCR showed the potential of the MC004 assay to estimate the parasite load of P. falciparum. Eight Plasmodium infected patients were followed after anti-malarial treatment by the MC004 assay and microscopy. The MC004 assay still detected Plasmodium DNA although no parasites were seen with microscopy in post-treatment samples. The rapid decline in Plasmodium DNA showed the potential for therapy-monitoring.

Conclusion
Implementation of the MC004 assay in non-endemic clinical setting improved the diagnosis of malaria. The MC004 assay demonstrated superior Plasmodium species identification, the ability to indicate the Plasmodium parasite load, and can potentially detect submicroscopic Plasmodium infections.
Associations between food groups and liver cancer: a systematic review and meta-analysis of observational studies
Authors: Liu Ke , Chen Weiwei , Zhou Yi , Xu Liuhong , Sun Xiaohui , Mao Yingying , Ye Ding 
Published: June 2023

Abstract
Context
Diet is emerging as a modifiable component of lifestyle for influencing the incidence of liver cancer.

Objective
To investigate and quantify the potential relationship between food groups and liver cancer.

Data sources
PubMed and Web of Science were searched for eligible observational studies until 31st March, 2023.

Data extraction
The meta-analysis was conducted by pooling relative risk (RR), odds ratio (OR) or hazards ratio (HR) with 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by subgroup analysis. Sensitivity analysis and publication bias test were also carried out.

Data analysis
Through stepwise screening, a total of 27 studies were included. The pooled estimates of liver cancer for whole grains and legumes intake were 0.66 (95% CI: 0.54–0.82; I2 = 25.3%) and 0.86 (95% CI: 0.75–0.99; I2 = 14.3%), respectively. However, there were null associations of nuts, poultry, egg and sweetened beverages consumption with liver cancer and the association between refined grains and liver cancer was inconclusive. In dose-response meta-analysis, the pooled estimates of liver cancer were 0.77 (95% CI: 0.65–0.91) for every 50 g/day increment in whole grains intake. Non-linear dose-response relationship (P = 0.031) was observed in the association between the intake of legumes and liver cancer, and the protective effect occurred with the dose ranging from 8 g/day to 40 g/day.

Conclusions
This meta-analysis shows that whole grains and legumes were inversely associated with liver cancer, whereas intake of nuts, poultry, egg and sweetened beverages may not be associated with liver cancer. Further quantitative research needs to be undertaken within a range of populations to investigate the relationship between food groups and liver cancer.

Systematic review registration
PROSPERO registration no. CRD42021246142
The biological function of tumor-derived extracellular vesicles on metabolism
Authors: Fu Xiaoyu , Song Junlong , Yan Wei , Downs Bradley M. , Wang Weixing , Li Juanjuan 
Published: June 2023

AbstractMultiple studies have shown that extracellular vesicles (EVs) play a key role in the process of information transfer and material transport between cells. EVs are classified into different types according to their sizes, which includes the class of exosomes. In comparison to normal EVs, tumor-derived EVs (TDEs) have both altered components and quantities of contents. TDEs have been shown to help facilitate an environment conducive to the occurrence and development of tumor by regulation of glucose, lipids and amino acids. Furthermore, TDEs can also affect the host metabolism and immune system. EVs have been shown to have multiple clinically useful properties, including the use of TDEs as biomarkers for the early diagnosis of diseases and using the transport properties of exosomes for drug delivery. Targeting the key bioactive cargoes of exosomes could be applied to provide new strategies for the treatment of tumors. In this review, we summarize the finding of studies focused on measuring the effects of TDE on tumor-related microenvironment and systemic metabolism.
Islets in the body are never flat: transitioning from two-dimensional (2D) monolayer culture to three-dimensional (3D) spheroid for better efficiency in the generation of functional hPSC-derived pancreatic β cells in vitro
Authors: Diane Abdoulaye , Mohammed Layla Ibrahim , Al-Siddiqi Heba H. 
Published: June 2023

AbstractDiabetes mellitus (DM), currently affecting more than 537 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from a defect in insulin secretion, action, or both due to the loss or dysfunction of pancreatic β cells. Since cadaveric islet transplantation using Edmonton protocol has served as an effective intervention to restore normoglycaemia in T1D patients for months, stem cell-derived β cells have been explored for cell replacement therapy for diabetes. Thus, great effort has been concentrated by scientists on developing in vitro differentiation protocols to realize the therapeutic potential of hPSC-derived β cells. However, most of the 2D traditional monolayer culture could mainly generate insulin-producing β cells with immature phenotype. In the body, pancreatic islets are 3D cell arrangements with complex cell–cell and cell–ECM interactions. Therefore, it is important to consider the spatial organization of the cell in the culture environment. More recently, 3D cell culture platforms have emerged as powerful tools with huge translational potential, particularly for stem cell research. 3D protocols provide a better model to recapitulate not only the in vivo morphology, but also the cell connectivity, polarity, and gene expression mimicking more physiologically the in vivo cell niche. Therefore, the 3D culture constitutes a more relevant model that may help to fill the gap between in vitro and in vivo models. Interestingly, most of the 2D planar methodologies that successfully generated functional hPSC-derived β cells have switched to a 3D arrangement of cells from pancreatic progenitor stage either as suspension clusters or as aggregates, suggesting the effect of 3D on β cell functionality. In this review we highlight the role of dimensionality (2D vs 3D) on the differentiation efficiency for generation of hPSC-derived insulin-producing β cells in vitro. Consequently, how transitioning from 2D monolayer culture to 3D spheroid would provide a better model for an efficient generation of fully functional hPSC-derived β cells mimicking in vivo islet niche for diabetes therapy or drug screening.
Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
Authors: Fellows Christopher J. , Simone-Finstrom Michael , Anderson Troy D. , Swale Daniel R. 
Published: June 2023

AbstractDeclines in managed honey bee populations are multifactorial but closely associated with reduced virus immunocompetence and thus, mechanisms to enhance immune function are likely to reduce viral infection rates and increase colony viability. However, gaps in knowledge regarding physiological mechanisms or ‘druggable’ target sites to enhance bee immunocompetence has prevented therapeutics development to reduce virus infection. Our data bridge this knowledge gap by identifying ATP-sensitive inward rectifier potassium (KATP) channels as a pharmacologically tractable target for reducing virus-mediated mortality and viral replication in bees, as well as increasing an aspect of colony-level immunity. Bees infected with Israeli acute paralysis virus and provided KATP channel activators had similar mortality rates as uninfected bees. Furthermore, we show that generation of reactive oxygen species (ROS) and regulation of ROS concentrations through pharmacological activation of KATP channels can stimulate antiviral responses, highlighting a functional framework for physiological regulation of the bee immune system. Next, we tested the influence of pharmacological activation of KATP channels on infection of 6 viruses at the colony level in the field. Data strongly support that KATP channels are a field-relevant target site as colonies treated with pinacidil, a KATP channel activator, had reduced titers of seven bee-relevant viruses by up to 75-fold and reduced them to levels comparable to non-inoculated colonies. Together, these data indicate a functional linkage between KATP channels, ROS, and antiviral defense mechanisms in bees and define a toxicologically relevant pathway that can be used for novel therapeutics development to enhance bee health and colony sustainability in the field.
Perilipin5 protects against non-alcoholic steatohepatitis by increasing 11-Dodecenoic acid and inhibiting the occurrence of ferroptosis
Authors: Xu Xinming , Qiu Jin , Li Xiaoya , Chen Juntong , Li Yue , Huang Xinmei , Zang Shufei , Ma Xinran , Liu Jun 
Published: June 2023

Abstract
Background
Non-alcoholic steatohepatitis (NASH) is a major contributor to liver cirrhosis and hepatocellular carcinoma. There remains no effective pharmacological therapy. The hepatic lipid metabolism and fatty acid β-oxidation are regulated by Perilipin5 (Plin5). However, it is yet unknown how Plin5 affects NASH and the molecular process.

Methods
High-fat, high-cholesterol and high-fructose (HFHC) diets were used to mimic the progression of NASH in wild type (WT) mice and Plin5 knockout (Plin5 KO) mice. The degree of ferroptosis was measured by detecting the expression of key genes of ferroptosis and the level of lipid peroxide. The degree of NASH was judged by observing the morphology of the liver, detecting the expression of inflammation and fibrosis related genes of liver damage. Plin5 was overexpressed in the liver of mice by tail vein injection of adenovirus, and the process of NASH was simulated by methionine choline deficiency (MCD) diet. The occurrence of ferroptosis and NASH was detected by the same detection method. Targeted lipidomics sequencing was used to detect the difference in free fatty acid expression in the WT Plin5 KO group. Finally, it was verified in cell experiments to further study the effect of free fatty acids on ferroptosis of hepatocytes.

Results
In various NASH models, hepatic Plin5 was dramatically reduced. Plin5 knockout (KO) worsened NASH-associated characteristics in mice given a high-fat/high-cholesterol (HFHC) diet, such as lipid accumulation, inflammation and hepatic fibrosis. It has been shown that ferroptosis is involved in NASH progression. We revealed that Plin5 KO in mice aggravated the degree of ferroptosis in NASH models. Conversely, overexpression of Plin5 significantly alleviated ferroptosis and further ameliorated progression of MCD-induced NASH. Analysis of livers obtained from HFHC diet-fed mice by targeted lipidomics revealed that 11-Dodecenoic acid was significantly decreased in Plin5 KO mice. Addition of 11-Dodecenoia acid to Plin5 knockdown hepatocytes effectively prevented ferroptosis.

Conclusion
Our study demonstrates that Plin5 protects against NASH progression by increasing 11-Dodecenoic acid level and further inhibiting ferroptosis, suggesting that Plin5 has therapeutic potential as a target for the management of NASH.
Patient with composite haemangioendothelioma containing angiosarcoma-like areas in the setting of congenital lymphoedema mimicking Stewart-Treves syndrome: a case report
Authors: Balko Jan , Ozaniak Andrej , Krskova Lenka , Strizova Zuzana , Lischke Robert , Zamecnik Josef 
Published: June 2023

AbstractBackgroundComposite haemangioendothelioma is a rare vascular neoplasm with indolent to intermediate malignant potential. Diagnosis of this disease relays on histopathological identification of at least two different morphologically distinctive vascular components in proper clinical settings. Exceedingly rare cases of this neoplasm can exhibit areas resembling high-grade angiosarcoma, which does not change the biological behaviour. Such lesions tend to occur in the setting of chronic lymphoedema and thus, can mimic Stewart-Treves syndrome, which has a much worse clinical outcome and prognosis.Case presentationWe present a case of 49 years old male suffering from chronic lymphoedema of the left lower extremity who had developed a composite haemangioendothelioma with high grade angiosarcoma-like areas mimicking the Stewart-Treves syndrome. Given the multifocality of the disease, the only potentially curable surgical treatment would be hemipelvectomy, which was refused by the patient. The patient has been followed-up, with no signs of local progression of the remaining disease, nor a distant spread outside the involved extremity for two years.ConclusionsComposite haemangioendothelioma represents a rare malignant vascular tumour, with significantly more favourable biological behaviour than angiosarcoma, even in cases where angiosarcoma-like areas are present. For that reason, composite haemangioendothelioma can be easily misdiagnosed as true angiosarcoma. The rarity of this disease unfortunately hampers the development of clinical practice guidelines and the implementation of treatment recommendations. Most of the patients with localized tumour are treated by wide surgical resection, without neo- or adjuvant radiotherapy or chemotherapy. However, in the case of this diagnosis, the watch-and-wait approach is better than mutilating procedure, highlighting the necessity of establishing of the correct diagnosis.
Patients’ perspectives on the use of artificial intelligence in dentistry: a regional survey
Authors: Ayad Nasim , Schwendicke Falk , Krois Joachim , van den Bosch Stefanie , Bergé Stefaan , Bohner Lauren , Hanisch Marcel , Vinayahalingam Shankeeth 
Published: June 2023

AbstractThe use of artificial intelligence (AI) in dentistry is rapidly evolving and could play a major role in a variety of dental fields. This study assessed patients’ perceptions and expectations regarding AI use in dentistry. An 18-item questionnaire survey focused on demographics, expectancy, accountability, trust, interaction, advantages and disadvantages was responded to by 330 patients; 265 completed questionnaires were included in this study. Frequencies and differences between age groups were analysed using a two-sided chi-squared or Fisher’s exact tests with Monte Carlo approximation. Patients’ perceived top three disadvantages of AI use in dentistry were (1) the impact on workforce needs (37.7%), (2) new challenges on doctor–patient relationships (36.2%) and (3) increased dental care costs (31.7%). Major expected advantages were improved diagnostic confidence (60.8%), time reduction (48.3%) and more personalised and evidencebased disease management (43.0%). Most patients expected AI to be part of the dental workflow in 1–5 (42.3%) or 5–10 (46.8%) years. Older patients (> 35 years) expected higher AI performance standards than younger patients (18–35 years) (p < 0.05). Overall, patients showed a positive attitude towards AI in dentistry. Understanding patients’ perceptions may allow professionals to shape AI-driven dentistry in the future.
Determinants of early initiation of breastfeeding in The Gambia: a population-based study using the 2019–2020 demographic and health survey data
Authors: Darboe Muhammed L , Jeyakumar Angeline , Mansour Salma M. A. , Valawalkar Shahanara 
Published: June 2023

Abstract
Background
Early initiation of breastfeeding within the first hour of life prevents neonatal and infant mortality. Sustainable Development Goals (SDGs) Target 3.2 aims to reduce neonatal mortality and under 5 mortality globally. The decline in the early initiation of breastfeeding in The Gambia coincides with deviations from the SDGs, due to poor indicators of child survival. Our work studied the determinants of early initiation of breastfeeding in The Gambia.

Methods
We used the 2019–2020 Gambia Demographic Health Survey (GDHS) conducted across all regions of the country. Since our population of interest was children born two years preceding the study, we only included children less than 24 months of age, living with an eligible respondent. Thus, a weighted sample of 5691 mother-child pairs was applied in the analysis. We reported summary statistics of individuals’ sociodemographic, obstetrics and antenatal, household, and community-level factors. A logistic regression model was used to determine associations between early initiation of breastfeeding and covariates.

Results
The prevalence of early initiation of breastfeeding was 64.3% (n = 3659). Mothers who had secondary education or higher educational level had higher odds of early initiation of breastfeeding (AOR 1.22; 95% CI 1.07, 1.40). Regions with rural population notably Lower and Central and Upper River Region had lower odds of early initiation of breastfeeding [Mansakonko (AOR 0.37; 95% CI 0.26, 0.15), Kerewan (AOR 0.26; 95% CI 0.19, 0.36), Kuntaur (AOR 0.39; 95% CI 0.28, 0.54), Janjanbureh (AOR 0.48; 95% CI 0.35, 0.66) and Basse (AOR 0.64; 95%CI 0.49, 0.85)]. Also, women in the high quintile of the wealth index were more likely to initiate breastfeeding early (AOR 1.29; 95% CI 1.06, 1.57). Four or more antenatal care visits did not increase early initiation of breastfeeding.

Conclusions
The results of the analyses demand affirmative action to improve maternal education, reduce poverty and inequality and empower rural communities in The Gambia. The IYCF component in antenatal care needs to be strengthened. Programs and policies on IYCF must resonate to address determinants of timely breastfeeding initiation to chart progress towards the SDG.