bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond Blood and Legal Ties The Impact of Dominant Conservative Socializing Agents on Attitudes toward Adoption by Same-Sex Couples
Authors: Grigoropoulos Iraklis 
Published: October 2022

Even though public opinion may be more supportive of sexual minorities and marriage equality there may be less support for same-sex adoption rights and same-sex parenthood. This study examines if individual-level differences in religiosity and political positioning have significant discriminative power by examining a model in which religious opposition to equal adoption rights is motivated, at least in part, by conservative political ideology and opposition to adoption in general. A cross-sectional study was conducted between May 2 and July 2, 2022, via an online survey. One hundred ninety-six respondents aged between 18 and 56 years old (_M_= 24.93; _SD_= 0.50) participated in the study. A bivariate correlation was generated to explore the associations between variables of interest. Next, hypotheses were examined by performing a bootstrapping analysis for parallel multiple mediation models (Hayes, 2013; Model 4). Both political positioning and attitudes toward adoption partially mediated the relationship between religiosity and attitudes toward adoption by same-sex couples. This study’s results demonstrate that exposure to less permissive and more traditional socializing agents can significantly influence individuals' attitudes toward same-sex adoption.
Herramientas digitales interactivas para fortalecer la enseñanza de la comprensión lectora
Authors: Tacuri Jara Freddy Patricio , Toledo Moncayo Cecilia 
Published: October 2022

Las herramientas digitales en la actualidad han ido tomando fuerza en las actividades que realizan los docentes en sus clases, sin embargo hay muchos de los docentes que todavía no tienen total conocimiento del uso adecuado para ciertas áreas específicas de enseñanza, por esta razón la investigación se trata de Analizar y Facilitar a los docentes herramientas digitales interactivas que permita mejorar la comprensión lectora, para la obtención de la cantidad de docentes que no conocen y no han utilizado se utilizó una metodología de la investigación que permite recopilar datos de una población pequeña de docentes con un método cuantitativo y no experimental y además con un instrumento en este caso un cuestionario elaborado con la escala de Likert mediante el cual ayudo a obtener los datos necesarios para así de esta manera determinar la propuesta, en este caso la información que fue tabulada mediante una tabla de frecuencia se obtuvo que el 83,3 del total de la población casi nunca aplicado herramientas como Quizizz, Genially para evaluar a estudiantes, y que el 94,4 del total de la población casi nunca ha usado herramientas digitales para la comprensión lectora. Dados estos datos estadísticos se presentó una propuesta al docente que consiste en algunas herramientas digitales que puede utilizar en sus clases entre las cuales son: Genially, Quizizz, mésela, nearpod y padlet y de esta manera se cumple con los objetivos planteados desde un inicio de la investigación.
Real-world national trends and socio-economic factors preference of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in China
Authors: Li Cao , Guo Shanshan , Huo Jiping , Gao Yiming , Yan Yilong , Zhao Zhigang 
Published: October 2022

BackgroundsRobust evidence have demonstrated the beneficial effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in T2D patients with cardiovascular diseases and chronic kidney disease. Multiple studies analyzed patterns and predictors of SGLT2i and GLP-1RA in the US, Europe and worldwide. However, there is no study about the utilization of these two classes of drugs in real-world in China.MethodA total of 181743 prescriptions of SGLT2i and 59720 GLP-1RA were retrospectively pooled from Hospital Prescription Analysis Cooperation Project from 2018 to 2021. The social-economic characteristics of patients and prescribers, including age, gender, residency, hospital level, insurance type, department visited, and payment amount, were collected and analyzed to study trends and risk factors associated with preference among two antidiabetics.ResultsAnnual number of prescriptions of SGLT2i significantly increased to approximately 140 folds, while GLP-1RA increased to about 6.5 folds. After adjustment for socio-economic information, several patients or physician characteristics were positively associated with the preference of GLP-1RA, including female gender (OR 1.581, 95% CI 1.528-1.635), residents in second-tier cities (OR 1.194, 95% CI 1.148-1.142), visiting primary or secondary hospital level (OR 2.387, 95% CI 2.268-2.512); while other factors were associated with the preference of SGLT2i, including older adults (OR 0.713, 95% CI 0.688-0.739), uncovered by insurance (OR 0.310, 95% CI 0.293-0.329), visiting other departments compared with endocrinology. In addition, the share of SGLT2i and GLP-1RA was low but in an increasing tendency.ConclusionsSGLT2i and GLP-1RA prescription significantly increased from 2018 to 2021. The socio-economic risk factors in choosing SGLT2i or GLP-1RA highlight an effort required to reduce disparities and improve health outcomes.
Design optimization of district heating systems: A review
Authors: Sporleder Maximilian , Rath Michael , Ragwitz Mario 
Published: October 2022

District heating systems offer the possibility of lowering emissions and support the goal of reaching a carbon-neutral energy system by integrating renewable heat sources. Therefore, this work provided a systematic literature review to identify potential research gaps and show the literature distribution over the relevant topics. The focus is on the design optimization with (non-)linear programming of district heating systems in the context of decarbonization. Furthermore, crucial energy balance equations were extracted from the literature for a potential optimization problem. The systematic literature review limited its search to two databases, 10 years timespan, a quality measure, and uses keywords regarding topic and method. Categories were derived based on the subject and literature to cluster the found publications and identify potential research gaps. The results showed potential research gaps in the depiction of different stakeholder decisions, reduction of computational efforts, and their resulting uncertainties. Additionally, they identified gaps in the integration of low-grade heat sources, thermal storage facilities, and energy converters, especially geothermal energy, large-scale heat pumps, and seasonal storages.
Monitoring dryland trees with remote sensing. Part B: Combining tree cover and plant architecture data to assess degradation and recovery of Argania spinosa woodlands of South Morocco
Authors: Kirchhoff Mario , Marzolff Irene , Stephan Robin , Seeger Manuel , Aït Hssaine Ali , Ries Johannes B. 
Published: October 2022

The argan woodlands of South Morocco represent an open-canopy dryland forest with traditional silvopastoral usage that includes browsing by goats, sheep and camels, oil production as well as agricultural use. In the past, these forests have undergone extensive clearing, but are now protected by the state. However, the remaining argan woodlands are still under pressure from intensive grazing and illegal firewood collection. Although the argan-forest area seems to be overall decreasing due to large forest clearings for intensive agriculture, little quantitative data is available on the dynamics and overall state of the remaining argan forest. To determine how the argan woodlands in the High Atlas and the Anti-Atlas had changed in tree-crown cover from 1972 to 2018 we used historical black and white HEXAGON satellite images as well as recent WorldView satellite images (see Part A of our study). Because tree shadows can oftentimes not be separated from the tree crown on panchromatic satellite images, individual trees were mapped in three size categories to determine if trees were unchanged, had decreased/increased in crown size or had disappeared or newly grown. The current state of the argan trees was evaluated by mapping tree architectures in the field. Tree-cover changes varied highly between the test sites. Trees that remained unchanged between 1972 and 2018 were in the majority, while tree mortality and tree establishment were nearly even. Small unchanged trees made up 48.4% of all remaining trees, of these 51% showed degraded tree architectures. 40% of small (re-) grown trees were so overbrowsed that they only appeared as bushes, while medium (3–7 m crown diameter) and large trees (&gt;7 m) showed less degraded trees regardless if they had changed or not. Approaches like grazing exclusion or cereal cultivation lead to a positive influence on tree architecture and less tree-cover decrease. Although the woodland was found to be mostly unchanged 1972–2018, the analysis of tree architecture reveals that a lot of (mostly small) trees remained stable but in a degraded state. This stability might be the result of the small trees’ high degradation status and shows the heavy pressure on the argan forest.
A multiphase contrast-enhanced CT radiomics model for prediction of human epidermal growth factor receptor 2 status in advanced gastric cancer
Authors: Ma Tingting , Cui Jingli , Wang Lingwei , Li Hui , Ye Zhaoxiang , Gao Xujie 
Published: October 2022

Background: Accurate evaluation of human epidermal growth factor receptor 2 (HER2) status is of great importance for appropriate management of advanced gastric cancer (AGC) patients. This study aims to develop and validate a CT-based radiomics model for prediction of HER2 overexpression in AGC.Materials and Methods: Seven hundred and forty-five consecutive AGC patients (median age, 59 years; interquartile range, 52–66 years; 515 male and 230 female) were enrolled and separated into training set (n = 521) and testing set (n = 224) in this retrospective study. Radiomics features were extracted from three phases images of contrast-enhanced CT scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator method. Univariable and multivariable logistical regression analysis were used to establish predictive model with independent risk factors of HER2 overexpression. The predictive performance of radiomics model was assessed in the training and testing sets.Results: The positive rate of HER2 was 15.9% and 13.8% in the training set and testing set, respectively. The positive rate of HER2 in intestinal-type GC was significantly higher than that in diffuse-type GC. The radiomics signature comprised eight robust features demonstrated good discrimination ability for HER2 overexpression in the training set (AUC = 0.84) and the testing set (AUC = 0.78). A radiomics-based model that incorporated radiomics signature and pathological type showed good discrimination and calibration in the training (AUC = 0.85) and testing (AUC = 0.84) sets.Conclusion: The proposed radiomics model showed favorable accuracy for prediction of HER2 overexpression in AGC.
A randomized, double-blind, placebo-controlled, dose-escalating phase I trial to evaluate safety and immunogenicity of a plant-produced, bivalent, recombinant norovirus-like particle vaccine
Authors: Leroux-Roels Isabel , Maes Cathy , Joye Jasper , Jacobs Bart , Jarczowski Franziska , Diessner André , Janssens Yorick , Waerlop Gwenn , Tamminen Kirsi , Heinimäki Suvi , Blazevic Vesna , Leroux-Roels Geert , Klimyuk Victor , Adachi Hiroshi , Hiruta Kazuyuki , Thieme Frank 
Published: October 2022

Noroviruses (NoV) are the leading cause of epidemic acute gastroenteritis in humans worldwide and a safe and effective vaccine is needed. Here, a phase I, double-blind, placebo-controlled clinical trial was performed in 60 healthy adults, 18 to 40 years old. Safety (primary objective) and immunogenicity (secondary and exploratory objectives) of a bivalent (GI.4 and GII.4), plant-produced, virus-like particle (VLP), NoV vaccine candidate formulation were investigated at two dose levels (50 µg + 50 µg and 150 µg + 150 µg) without adjuvant. Overall, 13 subjects (65.0%) in the 50 µg group, 16 subjects (80.0%) in the 150 µg group, and 14 subjects (70.0%) in the placebo group reported at least 1 solicited local or general symptom during the 7-day post-vaccination periods following each dose. Severe solicited adverse events (AEs) were rare (2 events in the 50 µg group). A total of 8 subjects (40.0%) in each group reported at least one unsolicited AE during the 28-day post-vaccination periods. Immunogenicity was assessed on days 1, 8, 29, 57, 183 and 365. All subjects were pre-exposed to norovirus as indicated by baseline levels of the different immunological parameters examined. Vaccine-specific humoral and cellular immune responses increased after the first dose but did not rise further after the second vaccination. Increased GI.4- and GII.4-specific IgG titers persisted until day 365. The vaccine elicited cross-reactive IgG antibodies against non-vaccine NoV VLPs, which was more pronounced for NoV strains of the same genotype as the GII.4 vaccine strain than for non-vaccine genotypes. Significant blocking anti-GI.4 and anti-GII.4 VLP titers were triggered in both dose groups. Lymphoproliferation assays revealed strong cell-mediated immune responses that persisted until day 365. In conclusion, both dose levels were safe and well-tolerated, and no higher incidence of AEs was observed in the higher dose group. The data show that a single dose of the vaccine formulated at 50 µg of each VLP is sufficient to reach a peak immune response after 8 to 28 days. The results of this Phase I study warrant further evaluation of the non-adjuvanted vaccine candidate.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/record/NCT05508178, identifier (NCT05508178).
A necroptosis related prognostic model of pancreatic cancer based on single cell sequencing analysis and transcriptome analysis
Authors: Chen Liang , Zhang Xueming , Zhang Qixiang , Zhang Tao , Xie Jiaheng , Wei Wei , Wang Ying , Yu Hongzhu , Zhou Hongkun 
Published: October 2022

BackgroundAs a tumor type with high mortality and poor therapeutic effect, the pathogenesis of pancreatic cancer is still unclear. It is necessary to explore the significance of necroptosis in pancreatic cancer.MethodsPancreatic cancer transcriptome data were obtained from the TCGA database, ICGC database, and GSE85916 in the GEO database. The TCGA cohort was set as a training cohort, while the ICGC and GSE85916 cohort were set as the validation cohorts. Single-cell sequencing data of pancreatic cancer were obtained from GSE154778 in the GEO database. The genes most associated with necroptosis were identified by weighted co-expression network analysis and single-cell sequencing analysis. COX regression and Lasso regression were performed for these genes, and the prognostic model was established. By calculating risk scores, pancreatic cancer patients could be divided into NCPTS_high and NCPTS_low groups, and survival analysis, immune infiltration analysis, and mutation analysis between groups were performed. Cell experiments including gene knockdown, CCK-8 assay, clone formation assay, transwell assay and wound healing assay were conducted to explore the role of the key gene EPS8 in pancreatic cancer. PCR assays on clinical samples were further used to verify EPS8 expression.ResultsWe constructed the necroptosis-related signature in pancreatic cancer using single-cell sequencing analysis and transcriptome analysis. The calculation formula of risk score was as follows: NCPTS = POLR3GL * (-0.404) + COL17A1 * (0.092) + DDIT4 * (0.007) + PDE4C * (0.057) + CLDN1 * 0.075 + HMGA2 * 0.056 + CENPF * 0.198 +EPS8 * 0.219. Through this signature, pancreatic cancer patients with different cohorts can be divided into NCPTS_high and NCPTS_low group, and the NCPTS_high group has a significantly poorer prognosis. Moreover, there were significant differences in immune infiltration level and mutation level between the two groups. Cell assays showed that in CAPAN-1 and PANC-1 cell lines, EPS8 knockdown significantly reduced the viability, clonogenesis, migration and invasion of pancreatic cancer cells. Clinical PCR assay of EPS8 expression showed that EPS8 expression was significantly up-regulated in pancreatic cancer (*P&lt;0.05).ConclusionOur study can provide a reference for the diagnosis, treatment and prognosis assessment of pancreatic cancer.
GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC
Authors: Xie Huaying , Yan Tingting , Lu Xinxin , Du Yueyao , Xu Shuguang , Kong Yu , Yu Liangjie , Sun Jian , Zhou Liheng , Ma Jun 
Published: October 2022

BackgroundTNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC.MethodsWe analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis.ResultsIn the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC.ConclusionsThese results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC.
Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma
Authors: Zhao Fangchao  , Wang Zengying , Li Zhirong , Liu Shiquan , Li Shujun 
Published: October 2022

Lactic acid, once considered as an endpoint or a waste metabolite of glycolysis, has emerged as a major regulator of cancer development, maintenance, and progression. However, studies about lactic acid metabolism-related genes (LRGs) in lung adenocarcinoma (LUAD) remain unclear. Two distinct molecular subtypes were identified on basis of 24 LRGs and found the significant enrichment of subtype A in metabolism-related pathways and had better overall survival (OS). Subsequently, a prognostic signature based on 5 OS-related LRGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. Then, a highly accurate nomogram was cosntructed to improve the clinical application of the LRG_score. By further analyzing the LRG_score, higher immune score and lower stromal score were found in the low LRG_score group, which presented a better prognosis. Patients with low LRG_score also exhibited lower somatic mutation rate, tumor mutation burden (TMB), and cancer stem cell (CSC) index. Three more independent cohorts (GSE126044: anti-PD-1, GSE135222: anti-PD-1, and IMvigor210: anti-PD-L1) were analyzed, and the results showed that patients in the low LRG_score category were more responsive to anti-PD-1/PD-L1 medication and had longer survival times. It was also determined that gefitinib, etoposide, erlotinib, and gemcitabine were more sensitive to the low LRG_score group. Finally, we validated the stability and reliability of LRG_score in cell lines, clinical tissue samples and HPA databases. Overall, the LRG_score may improve prognostic information and provide directions for current research on drug treatment strategies for LUAD patients.
IL-17 and IL-22 are pivotal cytokines to delay wound healing of S. aureus and P. aeruginosa infected skin
Authors: Lecron Jean-Claude , Charreau Sandrine , Jégou Jean-François , Salhi Nadjet , Petit-Paris Isabelle , Guignouard Emmanuel , Burucoa Christophe , Favot-Laforge Laure , Bodet Charles , Barra Anne , Huguier Vincent , Mcheik Jiad , Dumoutier Laure , Garnier Julien , Bernard François-Xavier , Ryffel Bernhard , Morel Franck 
Published: October 2022

IntroductionAlthough the presence of pathogens in skin wounds is known to delay the wound healing process, the mechanisms underlying this delay remain poorly understood. In the present study, we have investigated the regulatory role of proinflammatory cytokines on the healing kinetics of infected wounds.MethodsWe have developed a mouse model of cutaneous wound healing, with or without wound inoculation with Staphylococcus aureus and Pseudomonas aeruginosa, two major pathogens involved in cutaneous wound bacterial infections.ResultsAseptic excision in C57BL/6 mouse skin induced early expression of IL-1β, TNFα and Oncostatin M (OSM), without detectable expression of IL-22 and IL-17A/F. S. aureus and P. aeruginosa wound inoculation not only increased the expression of IL-1β and OSM, but also induced a strong cutaneous expression of IL-22, IL-17A and IL-17F, along with an increased number of infiltrating IL-17A and/or IL-22-producing γδ T cells. The same cytokine expression pattern was observed in infected human skin wounds. When compared to uninfected wounds, mouse skin infection delayed the wound healing process. Injection of IL-1α, TNFα, OSM, IL-22 and IL-17 together in the wound edges induced delayed wound healing similar to that induced by the bacterial infection. Wound healing experiments in infected Rag2KO mice (deficient in lymphocytes) showed a wound healing kinetic similar to uninfected Rag2KO mice or WT mice. Rag2KO infected-skin lesions expressed lower levels of IL-17 and IL-22 than WT, suggesting that the expression of these cytokines is mainly dependent on γδ T cells in this model. Wound healing was not delayed in infected IL-17R/IL-22KO, comparable to uninfected control mice. Injection of recombinant IL-22 and IL-17 in infected wound edges of Rag2KO mice re-establish the delayed kinetic of wound healing, as in infected WT mice.ConclusionThese results demonstrate the synergistic and specific effects of IL-22 and IL-17 induced by bacterial infection delay the wound healing process, regardless of the presence of bacteria per se. Therefore, these cytokines play an unexpected role in delayed skin wound healing.