bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tendency of dynamic vasoactive and inotropic medications data as a robust predictor of mortality in patients with septic shock: An analysis of the MIMIC-IV database
Authors: Ning Yi-Le , Sun Ce , Xu Xiang-Hui , Li Li , Ke Yan-Ji , Mai Ye , Lin Xin-Feng , Yang Zhong-Qi , Xian Shao-Xiang , Chen Wei-Tao 
Published: March 2023

BackgroundSeptic shock patients fundamentally require delicate vasoactive and inotropic agent administration, which could be quantitatively and objectively evaluated by the vasoactive–inotropic score (VIS); however, whether the dynamic trends of high-time-resolution VIS alter the clinical outcomes remains unclear. Thus, this study proposes the term VIS Reduction Rate (VRR) to generalise the tendency of dynamic VIS, to explore the association of VRR and mortality for patients with septic shock.MethodsWe applied dynamic and static VIS data to predict ICU mortality by two models: the long short-term memory (LSTM) deep learning model, and the extreme gradient boosting (XGBoost), respectively. The specific target cohort was extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database by the sophisticated structured query language (SQL). Enrolled patients were divided into four groups by VRR value: ≥50%, 0 ~ 50%, −50% ~ 0, and &lt; −50%. Statistical approaches included pairwise propensity score matching (PSM), Cox proportional hazards regression, and two doubly robust estimation models to ensure the robustness of the results. The primary and secondary outcomes were ICU mortality and in-hospital mortality, respectively.ResultsVRR simplifies the dosing trends of vasoactive and inotropic agents represented by dynamic VIS data while requiring fewer data. In total, 8,887 septic shock patients were included. Compared with the VRR ≥50% group, the 0 ~ 50%, −50% ~ 0, and &lt; −50% groups had significantly higher ICU mortality [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.17–1.50, p &lt; 0.001; HR 1.79, 95% CI 1.44–2.22, p &lt; 0.001; HR 2.07, 95% CI 1.61–2.66, p &lt; 0.001, respectively] and in-hospital mortality [HR 1.43, 95% CI 1.28–1.60, p &lt; 0.001; HR 1.75, 95% CI 1.45–2.11, p &lt; 0.001; HR 2.00, 95% CI 1.61–2.49, p &lt; 0.001, respectively]. Similar findings were observed in two doubly robust estimation models.ConclusionThe trends of dynamic VIS in ICU might help intensivists to stratify the prognosis of adult patients with septic shock. A lower decline of VIS was remarkably associated with higher ICU and in-hospital mortality among septic shock patients receiving vasoactive–inotropic therapy for more than 24 h.
Causes of academic dropout in higher education in Andalusia and proposals for its prevention at university: A systematic review
Authors: de la Cruz-Campos Juan-Carlos , Victoria-Maldonado Juan-José , Martínez-Domingo José-Antonio , Campos-Soto María-Natalia 
Published: March 2023

IntroductionOne of the main problems facing the university system is the high student dropout rate due to a number of variables, accentuated by the COVID-19 pandemic. This is a problem not only in Spanish universities but is prevalent worldwide. It is therefore important to understand and analyze the underlying reasons for dropout so that it can be addressed and mechanisms implemented to limit dropout in higher education to the greatest extent possible.MethodA systematic review was carried out summarizing the results of studies and reports on university dropout in Spain and specifically in the universities of the Autonomous Community of Andalusia. The review was conducted in accordance with the PRISMA statement by searching the scientific databases Scopus and Web of Science, limiting the search to articles published between 2010 and 2022.ResultsThe main publications in both Spain and the Autonomous Community of Andalusia were identified. The review included the main causes of university dropout indicated in each of the selected studies and the proposals to reduce it, including educational policies, the rise of distance education, academic failure in basic educational stages, and social, personal, psychological, and economic variables.ConclusionThere is a lack of research on university dropout, with only 25% of Spanish universities having carried out research on this subject in the last 12 years. The studies analyzed conclude that the most frequent causes of university dropout are associated with low academic performance, poor social support in the new academic environment, low socio-economic status, pessimism, and lack of motivation, together with other less significant factors such as poor relationships with teachers, lack of vocation, work incompatibility, and previous academic performance. Further research on the causes of university dropout and its prevention is needed both before university entrance, by providing meaningful information to secondary school students, and during the university stay, through institutional and teaching policies that improve family support and social roots, produce positive academic experiences, favor associationism, and encourage activities that improve planning and time management, together with cognitive learning strategies, motivational strategies and the use of advanced learning materials [such as Information and Communication Technology (ICT) tools].
Different cell compositions and a novel somatic KCNJ5 variant found in a patient with bilateral adrenocortical adenomas secreting aldosterone and cortisol
Authors: Zhao Liling , Wan Jinjing , Wang Yujun , Yang Wenjun , Liang Qi , Wang Jinrong , Jin Ping 
Published: March 2023

IntroductionThis study aimed to explore the possible pathogenesis of a rare case of co-existing Cushing’s syndrome (CS) and primary aldosteronism (PA) caused by bilateral adrenocortical adenomas secreting aldosterone and cortisol, respectively.MethodsA 41-year-old Chinese woman with severe hypertension and hypokalemia for 5 and 2 years, respectively, was referred to our hospital. She had a Cushingoid appearance. Preoperative endocrinological examinations revealed autonomous cortisol and aldosterone secretion. Computed tomography revealed bilateral adrenal adenomas. Subsequently, adrenal vein sampling and sequential left and right partial adrenalectomy indicated the presence of a left aldosterone-producing tumor and a right cortisol-producing tumor. Pathological examination included immunohistochemical analysis of the resected specimens. Secretions of aldosterone and cortisol were observed both in vivo and in vitro. Further, whole-exome sequencing was performed for DNA that was extracted from peripheral blood leukocytes and bilateral adrenal adenomas in order to determine whether the patient had relevant variants associated with PA and CS.ResultsImmunohistochemical staining revealed that the left adenoma primarily comprised clear cells expressing CYP11B2, whereas the right adenoma comprised both eosinophilic compact and clear cells expressing CYP11B1. The mRNA levels of steroidogenic enzymes (including CYP11B1 and CYP17A1) were high in the right adenoma, whereas CYP11B2 was highly expressed in the left adenoma. A novel somatic heterozygous missense variant—KCNJ5 c.503T &gt; G (p.L168R)—was detected in the left adrenal adenoma, but no other causative variants associated with PA and CS were detected in the peripheral blood or right adrenocortical adenoma. In the primary cell culture of the resected hyperplastic adrenal adenomas, verapamil and nifedipine, which are two calcium channel blockers, markedly inhibited the secretion of both aldosterone and cortisol.ConclusionWe present an extremely rare case of bilateral adrenocortical adenomas with distinct secretion of aldosterone and cortisol. The heterogeneity of the tumor cell compositions of aldosterone- and cortisol-producing adenoma (A/CPA) and somatic mutation of KCNJ5 may have led to different hormone secretions in the bilateral adrenal adenomas.
Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism
Authors: Lu Shuai , Chen Xi , Gong Maoqi , Chen Shuo , Zhang Jianyu , Zhang Xigong , Wu Chengai , Cui Aimin , Jiang Xieyuan 
Published: March 2023

ObjectiveTo explore the difference in parathyroid tissue-derived cells between male and female PHPT patients.MethodsResected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells.ResultsNo substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes.ConclusionThese findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis.
Influence of forest infrastructure on the responses of ecosystem services to climate extremes in the Midwest and Northeast United States from 1980 to 2019
Authors: Kicklighter David W. , Lin Tzu-Shun , Zhang Jiaqi , Chen Mengye , Vörösmarty Charles J. , Jain Atul K. , Melillo Jerry M. 
Published: March 2023

Forests provide several critical ecosystem services that help to support human society. Alteration of forest infrastructure by changes in land use, atmospheric chemistry, and climate change influence the ability of forests to provide these ecosystem services and their sensitivity to existing and future extreme climate events. Here, we explore how the evolving forest infrastructure of the Midwest and Northeast United States influences carbon sequestration, biomass increment (i.e., change in vegetation carbon), biomass burning associated with fuelwood and slash removal, the creation of wood products, and runoff between 1980 and 2019 within the context of changing environmental conditions and extreme climate events using a coupled modeling and assessment framework. For the 40-year study period, the region’s forests functioned as a net atmospheric carbon sink of 687 Tg C with similar amounts of carbon sequestered in the Midwest and the Northeast. Most of the carbon has been sequestered in vegetation (+771 Tg C) with more carbon stored in Midwestern trees than in Northeastern trees to provide a larger resource for potential wood products in the future. Runoff from forests has also provided 4,651 billion m3of water for potential use by humans during the study period with the Northeastern forests providing about 2.4 times more water than the Midwestern forests. Our analyses indicate that climate variability, as particularly influenced by heat waves, has the dominant effect on the ability of forest ecosystems to sequester atmospheric CO2to mitigate climate change, create new wood biomass for future fuel and wood products, and provide runoff for potential human use. Forest carbon sequestration and biomass increment appear to be more sensitive to heat waves in the Midwest than the Northeast while forest runoff appears to be more sensitive in the Northeast than the Midwest. Land-use change, driven by expanding suburban areas and cropland abandonment, has enhanced the detrimental heat-wave effects in Midwestern forests over time, but moderated these effects in Northeastern forests. When developing climate stabilization, energy production and water security policies, it will be important to consider how evolving forest infrastructure modifies ecosystem services and their responses to extreme climate events over time.
The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study
Authors: Kootbodien Tahira , London Leslie , Martin Lorna J. , Defo Joel , Ramesar Raj 
Published: March 2023

Background: Suicidal behaviour (SB) refers to behaviours, ranging from non-fatal suicidal behaviour, such as suicidal ideation and attempt, to completed suicide. Despite recent advancements in genomic technology and statistical methods, it is unclear to what extent the spectrum of suicidal behaviour is explained by shared genetic aetiology.Methods: We identified nine genome-wide association statistics of suicidal behaviour (sample sizes, n, ranging from 62,648 to 125,844), ten psychiatric traits [n up to 386,533] and collectively, nine summary datasets of anthropometric, behavioural and socioeconomic-related traits [n ranging from 58,610 to 941,280]. We calculated the genetic correlation among these traits and modelled this using genomic structural equation modelling, identified shared biological processes and pathways between suicidal behaviour and psychiatric disorders and evaluated potential causal associations using Mendelian randomisation.Results: Among populations of European ancestry, we observed strong positive genetic correlations between suicide ideation, attempt and self-harm (rg range, 0.71–1.09) and moderate to strong genetic correlations between suicidal behaviour traits and a range of psychiatric disorders, most notably, major depression disorder (rg = 0.86, p = 1.62 × 10−36). Multivariate analysis revealed a common factor structure for suicidal behaviour traits, major depression, attention deficit hyperactivity disorder (ADHD) and alcohol use disorder. The derived common factor explained 38.7% of the shared variance across the traits. We identified 2,951 genes and 98 sub-network hub genes associated with the common factor, including pathways associated with developmental biology, signal transduction and RNA degradation. We found suggestive evidence for the protective effects of higher household income level on suicide attempt [OR = 0.55 (0.44–0.70), p = 1.29 × 10−5] and while further investigation is needed, a nominal significant effect of smoking on suicide attempt [OR = 1.24 (1.04–1.44), p = 0.026].Conclusion: Our findings provide evidence of shared aetiology between suicidal behaviour and psychiatric disorders and indicate potential common molecular mechanisms contributing to the overlapping pathophysiology. These findings provide a better understanding of the complex genetic architecture of suicidal behaviour and have implications for the prevention and treatment of suicidal behaviour.
Tumor-associated macrophages respond to chemotherapy by detrimental transcriptional reprogramming and suppressing stabilin-1 mediated clearance of EGF
Authors: Larionova Irina , Kiselev Artem , Kazakova Elena , Liu Tengfei , Patysheva Marina , Iamshchikov Pavel , Liu Quan , Mossel Dieuwertje M. , Riabov Vladimir , Rakina Militsa , Sergushichev Alexey , Bezgodova Natalia , Vtorushin Sergei , Litviakov Nikolai , Denisov Evgeny , Koshkin Philipp , Pyankov Denis , Tsyganov Matvei , Ibragimova Marina , Cherdyntseva Nadezhda , Kzhyshkowska Julia 
Published: March 2023

IntroductionTumor resistance to chemotherapy and metastatic relapse account for more than 90% of cancer specific mortality. Tumor-associated macrophages (TAMs) can process chemotherapeutic agents and impair their action. Little is known about the direct effects of chemotherapy on TAMs.MethodsThe effect of chemotherapeutic platinum agent cisplatin was assessed in the model system of human ex vivo TAMs. Whole-transcriptome sequencing for paired TAMs stimulated and not stimulated by cisplatin was analysed by NGS. Endocytic uptake of EGF was quantified by flow cytometry. Confocal microscopy was used to visualize stabilin-1-mediated internalization and endocytic trafficking of EGF in CHO cells expressing ectopically recombinant stabilin-1 and in stabilin-1+ TAMs. In cohort of patients with breast cancer, the effect of platinum therapy on the transcriptome of TAMs was validated, and differential expression of regulators of endocytosis was identified.ResultsHere we show that chemotherapeutic agent cisplatin can initiate detrimental transcriptional and functional programs in TAMs, without significant impairment of their viability. We focused on the clearance function of TAMs that controls composition of tumor microenvironment. For the first time we demonstrated that TAMs’ scavenger receptor stabilin-1 is responsible for the clearance of epidermal growth factor (EGF), a potent stimulator of tumor growth. Cisplatin suppressed both overall and EGF-specific endocytosis in TAMs by bidirectional mode: suppression of positive regulators and stimulation of negative regulators of endocytosis, with strongest effect on synaptotagmin-11 (SYT11), confirmed in patients with breast cancer.ConclusionOur data demonstrate that synergistic action of cytostatic agents and innovative immunomodulators is required to overcome cancer therapy resistance.
The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer
Authors: Zhao Zihan , Liu Siyang , Sun Rui , Zhu Wenjie , Zhang Yulin , Liu Tianyao , Li Tianhang , Jiang Ning , Guo Hongqian , Yang Rong 
Published: March 2023

IntroductionBladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of ICIs is limited by low response rate. Oxaliplatin (OXP), a second line chemotherapy drug for BLCA, may reshape the tumor immune microenvironment (TIME) via recruiting immune cells. Here, we conducted the study of oxaliplatin combined with anti-PD-1 inhibitor in BLCA mice models.MethodsThe 6-8 weeks old female C57BL/6J mice were used to establish subcutaneous model of bladder tumor. After tumors developed, mice were given tail vein injections of PBS or oxaliplatin (2.5 mg/kg) and/or anti-PD-1 antibody (10 mg/kg). Tumor tissue samples and peripheral blood mononuclear cell (PBMC) were collected to systemically evaluate the efficiency and safety of combination OXP and anti-PD-1 inhibitor. The change of immune cells populations and the corresponding phenotypic diversity in TIME and PBMC were analysed by flow cytometry.ResultsTumor growth experiments clarified that the combination therapy was more efficient than medication alone. Flow cytometry analysis of tumor samples showed significant differences between untreated and treated mice. Oxaliplatin influences the TIME by increasing immune cells infiltration, including CD3+ T cells, CD4+ T cells, CD8+ T cells, dendritic cells (DC cells) and natural killer cells (NK cells). As for infiltrating cells, oxaliplatin upregulated the expression of CD134 and downregulated TIM-3 of CD4+ T cells, downregulated the PD-L1 expression of DC cells, which contributed to improve the anti-tumor effect and the treatment response of ICIs. Additionally, the evaluation of PBMC found that there were no significant changes in immune cell subsets and phenotypes, which validated the safety of the combination therapy. These results show the therapeutic potential for the combination of OXP and anti-PD-1 inhibitor in BLCA.ConclusionOXP could increase the infiltration of immune cells in TIME to promote the anti-tumor activity of anti-PD-1 inhibitor. The present research provided an appropriate rationale of combination chemotherapy and immunotherapy therapy for BLCA.
Identification of cuproptosis hub genes contributing to the immune microenvironment in ulcerative colitis using bioinformatic analysis and experimental verification
Authors: Yang Cejun , Wang Wendi , Li Sang , Qiao Zhengkang , Ma Xiaoqian , Yang Min , Zhang Juan , Cao Lu , Yao Shanhu , Yang Zhe , Wang Wei 
Published: March 2023

InstructionUlcerative colitis (UC) can cause a variety of immune-mediated intestinal dysfunctions and is a significant model of inflammatory bowel disease (IBD). Colorectal cancer (CRC) mostly occurs in patients with ulcerative colitis. Cuproptosis is a type of procedural death that is associated with different types of diseases to various degrees.MethodsWe used a combination of bioinformatic prediction and experimental verification to study the correlation between copper poisoning and UC. We used the Gene Expression Omnibus database to obtain disease gene expression data and then identified relevant genes involved in various expression levels in normal and UC samples. The Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed to cluster the genes that are highly responsible and find the central interaction in gene crosstalk. Notably, DLD, DLAT, and PDHA1 were present in high-scoring PPI networks. In addition, hub gene expression information in UC tissues was integrated to estimate the relationship between UC copper poisoning and the immune environment.ResultsIn our study, the expression of DLD, DLAT, and PDHA1 in UC tissues was lower than that in normal tissues. The key genes associated with cuproptosis have therapeutic effects on immune infiltration. We verified the expression of DLD, DLAT, and PDHA1 using real-time quantitative polymerase chain reaction in mouse models of UC induced by DSS.DiscussionNotably, this study clearly indicates that bioinformatic analysis performed to verify the experimental methods provides evidence that cuproptosis is associated with UC. This finding suggests that immune cell infiltration in UC patients is associated with cuproptosis. The key genes associated with cuproptosis can be helpful for discovering the molecular mechanism of UC, thus facilitating the improvement of UC treatment and preventing the associated CRC.