bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury
Authors: Yuchen Cao , Hejia Zhao , Fanke Meng , Qixin Deng , Liyang Cai , Xi Guo , Yanxia Chen , Xiongyi Yang , Zhuohang Xie , Guoguo Yi , Min Fu 
Published: January 2023

BackgroundMicrovascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and macrovascular complications, referring to atherosclerosis (AS), are the main complications of diabetes. Blindness or fatal microvascular diseases are considered to be identified earlier than fatal macrovascular complications. Exploring the intrinsic relationship between microvascular and macrovascular complications and the hub of pathogenesis is of vital importance for prolonging the life span of patients with diabetes and improving the quality of life.Materials and methodsThe expression profiles of GSE28829, GSE30529, GSE146615 and GSE134998 were downloaded from the Gene Expression Omnibus database, which contained 29 atherosclerotic plaque samples, including 16 AS samples and 13 normal controls; 22 renal glomeruli and tubules samples from diabetes nephropathy including 12 DN samples and 10 normal controls; 73 lymphoblastoid cell line samples, including 52 DR samples and 21 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques including GSEA analysis, GO-KEGG functional clustering by R (version 4.0.5), PPI analysis by Cytoscape (version 3.8.2) and String database, miRNA analysis by Diana database, and hub genes analysis by Metascape database. The drug sensitivity of characteristic DEGs was analyzed.ResultA total of 3709, 4185 and 8086 DEGs were recognized in AS, DN, DR, respectively, with 1820, 1666, 888 upregulated and 1889, 2519, 7198 downregulated. GO and KEGG pathway analyses of DEGs and GSEA analysis of common differential genes demonstrated that these significant sites focused primarily on inflammation-oxidative stress and immune regulation pathways. PPI networks show the connection and regulation on top-250 significant sites of AS, DN, DR. MiRNA analysis explored the non-coding RNA upstream regulation network and significant pathway in AS, DN, DR. The joint analysis of multiple diseases shows the common influenced pathways of AS, DN, DR and explored the interaction between top-1000 DEGs at the same time.ConclusionIn the microvascular and macrovascular complications of diabetes, immune-mediated inflammatory response, chronic inflammation caused by endothelial cell activation and oxidative stress are the three links linking atherosclerosis, diabetes retinopathy and diabetes nephropathy together. Our study has clarified the intrinsic relationship and common tissue damage mechanism of microcirculation and circulatory system complications in diabetes, and explored the mechanism center of these two vascular complications. It has far-reaching clinical and social value for reducing the incidence of fatal events and early controlling the progress of disabling and fatal circulatory complications in diabetes.
Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes
Authors: Su Yu , Zhang Shuo , Wu Zezhen , Liu Weiting , Chen Jingxian , Deng Feiying , Chen Fengwu , Zhu Dan , Hou Kaijian 
Published: January 2023

AimTo evaluate the treatment effect Fand pharmacoeconomic value of Dugaglutide in women with type 2 diabetes.MethodsWomen (n=96) with type 2 diabetes recruited from June 2019 to December 2021 were randomized into two equal groups. The control group was treated with Liraglutide, and the observation group was treated with Dulaglutide, both for 24 weeks. The blood glucose levels, biochemical index, insulin resistance index (HOMA-IR), cost-effect ratio (CER), and drug safety were determined and compared between the two groups.ResultsBlood glucose levels, the biochemical index, and HOMA-IR were lower in both groups after the treatment (P &lt; 0.05), and there was no statistical difference in the blood glucose levels, biochemical index and HOMA-IR between the two groups (P &gt; 0.05). The CER levels did not differ statistically between the two groups (P &gt; 0.05). Both the cost and the incidence of drug side effects during solution injection were lower in the observation group than in the control group after 24 weeks of treatment (P &lt; 0.05).ConclusionBoth Dulaglutide and Liraglutide can reduce blood glucose levels, improve biochemical index, and HOMA-IR levels in women with type 2 diabetes. Dulaglutide is more cost-effective and safe.Clinical trial registrationhttps://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026514.
Metformin improves polycystic ovary syndrome in mice by inhibiting ovarian ferroptosis
Authors: Peng Qingjie , Chen Xiaojiang , Liang Xiaoxia , Ouyang Jiahui , Wang Qiangqiang , Ren Shuai , Xie Haibo , Wang Chunhong , Sun Yaqun , Wu Xin , Liu Hetao , Hei Changchun , Sun Miao , Chang Qing , Liu Xinrui , Li Guangyong , He Rui 
Published: January 2023

Background and objectivePCOS is a common metabolic disorder in women of reproductive age, which pathogenesis is very complex. The role of ferroptosis in PCOS is a novel finding, and the mechanistic studies are not clear. Metformin is a commonly used drug of PCOS but few studies on whether metformin can improve the follicle development and ovarian function in PCOS. We aims to use PCOS mouse model to study the effect of metformin on PCOS based on the ovarian function and explored the regulation of metformin in PCOS mice by intervening in ferroptosis pathway.Materials and methodsC57 BL/6J female mice aged 4-5 weeks were purchased and gavaged with letrozole (1 mg/kg/day) combined with high-fat diet for 21days to establish PCOS model, and control group was set up. After modeling, the mice were divided into PCOS model group and metformin treatment group (Met) (n=6).The Met group were gavaged metformin (200 mg/kg/day) for 28 days. The body weight, estrous cycle, glucose tolerance test (OGTT)and insulin resistance test (ITT) were monitored. Then, The mice were euthanized to collect serum and ovaries. Elisa was used to detect changes in related serum hormones (E2, LH, FSH, TP). Ovaries used for molecular biology experiments to detect changes in GPX4, SIRT3, AMPK/p-AMPK, and mTOR/p-mTOR by Western blot and qPCR.ResultsCompared with the model group mice, body weight was significantly reduced, and their estrous cycle was restored in Met group. The results of OGTT and ITT showed an improvment of glucose tolerance and insulin resistance. Morphological results showed that after metformin treatment, polycystic lesions in ovaries were reduced, the ovarian function was restored, and the expressions of SIRT3 and GPX4 were elevated. WB results demonstrated that the expressions of p-mTOR and p-AMPK in ovaries were significantly reduced in Model group, but reversed in MET group.ConclusionOur study confirmed metformin could not only improve body weight and metabolism disorders, but also improve ovarian dysfunction in PCOS mice.In addition, we explored metformin could regulate ferroptosis to improve PCOS via the SIRT3/AMPK/mTOR pathway. Our study complements the mechanisms by which metformin improves PCOS.
Performance of a dual-hormone closed-loop system versus insulin-only closed-loop system in adolescents with type 1 diabetes. A single-blind, randomized, controlled, crossover trial
Authors: Lindkvist Emilie Bundgaard , Laugesen Christian , Reenberg Asbjørn Thode , Ritschel Tobias Kasper Skov , Svensson Jannet , Jørgensen John Bagterp , Nørgaard Kirsten , Ranjan Ajenthen G. 
Published: January 2023

ObjectiveTo assess the efficacy and safety of a dual-hormone (DH [insulin and glucagon]) closed-loop system compared to a single-hormone (SH [insulin only]) closed-loop system in adolescents with type 1 diabetes.MethodsThis was a 26-hour, two-period, randomized, crossover, inpatient study involving 11 adolescents with type 1 diabetes (nine males [82%], mean ± SD age 14.8 ± 1.4 years, diabetes duration 5.7 ± 2.3 years). Except for the treatment configuration of the DiaCon Artificial Pancreas: DH or SH, experimental visits were identical consisting of: an overnight stay (10:00 pm until 7:30 am), several meals/snacks, and a 45-minute bout of moderate intensity continuous exercise. The primary endpoint was percentage of time spent with sensor glucose values below range (TBR [&lt;3.9 mmol/L]) during closed-loop control over the 26-h period (5:00 pm, day 1 to 7:00 pm, day 2).ResultsOverall, there were no differences between DH and SH for the following glycemic outcomes (median [IQR]): TBR 1.6 [0.0, 2.4] vs. 1.28 [0.16, 3.19]%, p=1.00; time in range (TIR [3.9-10.0 mmol/L]) 68.4 [48.7, 76.8] vs. 75.7 [69.8, 87.1]%, p=0.08; and time above range (TAR [&gt;10.0 mmol/L]) 28.1 [18.1, 49.8] vs. 23.3 [12.3, 27.2]%, p=0.10. Mean ( ± SD) glucose was higher during DH than SH (8.7 ( ± 3.2) vs. 8.1 ( ± 3.0) mmol/L, p&lt;0.001) but coefficient of variation was similar (34.8 ( ± 6.8) vs. 37.3 ( ± 8.6)%, p=0.20). The average amount of rescue carbohydrates was similar between DH and SH (6.8 ( ± 12.3) vs. 9.5 ( ± 15.4) grams/participant/visit, p=0.78). Overnight, TIR was higher, TAR was lower during the SH visit compared to DH. During and after exercise (4:30 pm until 7 pm) the SH configuration produced higher TIR, but similar TAR and TBR compared to the DH configuration.ConclusionsDH and SH performed similarly in adolescents with type 1 diabetes during a 26-hour inpatient monitoring period involving several metabolic challenges including feeding and exercise. However, during the night and around exercise, the SH configuration outperformed DH.
Muscle regeneration in gilthead sea bream: Implications of endocrine and local regulatory factors and the crosstalk with bone
Authors: Otero-Tarrazón Aitor , Perelló-Amorós Miquel , Jorge-Pedraza Violeta , Moshayedi Fatemeh , Sánchez-Moya Albert , García-Pérez Isabel , Fernández-Borràs Jaume , García de la serrana Daniel , Navarro Isabel , Blasco Josefina , Capilla Encarnación , Gutierrez Joaquin 
Published: January 2023

Fish muscle regeneration is still a poorly known process. In the present study, an injury was done into the left anterior epaxial skeletal muscle of seventy 15 g gilthead sea bream (Sparus aurata) juveniles to evaluate at days 0, 1, 2, 4, 8, 16 and 30 post-wound, the expression of several muscle genes. Moreover, transcripts’ expression in the bone (uninjured tissue) was also analyzed. Histology of the muscle showed the presence of dead tissue the first day after injury and how the damaged fibers were removed and replaced by new muscle fibers by day 16 that kept growing up to day 30. Gene expression results showed in muscle an early upregulation of igf-2 and a downregulation of ghr-1 and igf-1. Proteolytic systems expression increased with capn2 and ctsl peaking at 1 and 2 days post-injury, respectively and mafbx at day 8. A pattern of expression that fitted well with active myogenesis progression 16 days after the injury was then observed, with the recovery of igf-1, pax7, cmet, and cav1 expression; and later on, that of cav3 as well. Furthermore, the first days post-injury, the cytokines il-6 and il-15 were also upregulated confirming the tissue inflammation, while tnfα was only upregulated at days 16 and 30 to induce satellite cells recruitment; overall suggesting a possible role for these molecules as myokines. The results of the bone transcripts showed an upregulation first, of bmp2 and ctsk at days 1 and 2, respectively; then, ogn1 and ocn peaked at day 4 in parallel to mstn2 downregulation, and runx2 and ogn2 increased after 8 days of muscle injury, suggesting a possible tissue crosstalk during the regenerative process. Overall, the present model allows studying the sequential involvement of different regulatory molecules during muscle regeneration, as well as the potential relationship between muscle and other tissues such as bone to control musculoskeletal development and growth, pointing out an interesting new line of research in this group of vertebrates.
Simultaneous treatment of phosphorus and fluoride wastewater using acid-modified iron-loaded electrode capacitive deionization: Preparation and performance
Authors: Dai Zhijian , Qin Tian , Bai Chengke , Wu Zhibin , Gao Ya , Qin Pufeng 
Published: January 2023

Here, capacitive deionization technology (CDI) using modified activated carbon fiber felt (ACF) electrodes was proposed to provide a new strategy for the challenge of simultaneous phosphorus and fluoride wastewater treatment. The acid-modified iron-loaded ACF (A@Fe-ACF) was obtained by modifying ACF through a two-step impregnation method. After the modification, the oxygen-containing functional groups on ACF increased and provided more adsorption sites. The electron transfer efficiency on the A@Fe-ACF was increased by introducing Fe and synergistically promoted the adsorption of phosphorus and fluorine. Results showed that the removal efficiencies of total phosphorus (TP) and total fluorine (TF) in wastewater reached 89.4% and 85% under optimal conditions (voltage intensity 1.5 V, pH 7, plate spacing 1 cm), while the adsorption mechanism of phosphorus and fluorine was dominated by chemical adsorption. Meanwhile, A@Fe-ACF electrode has good recyclability and stability after five cycles.
Mapping of nighttime light trends and refugee population changes in Ukraine during the Russian–Ukrainian War
Authors: Huang Chaoqing , Hong Song , Niu Xiaoxiao , Wu Qian , Zhong Yanmei , Yang Huan , Zhang Haoran 
Published: January 2023

The nighttime lights accurately and coherently depict how humans live. This study uses nighttime light measurements to quantify changes in nighttime lighting and refugee population in Ukraine before and after the war. We combined the Theil–Sen estimator with the M-K test to explore the trends of nighttime light. In addition, we constructed a linear model using nighttime light data and a portion of the UNHCR refugee data. Our results reveal that 1 week after the start of the Russo-Ukrainian War, the nighttime light area and the average nighttime light DN value in Ukraine exhibited a steep decline of about 50 percent. Our findings showed taht refugee population changes calculated through models and nighttime light data were mostly consistent with UNHCR data. We thought that the nighttime light data might be used directly to dynamically estimate changes in the refugee movement throughout the war. Nighttime light changes has significant implications for international humanitarian assistance and post-war reconstruction.
Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation
Authors: Pepple Ashley L. , Guy Joey L. , McGinnis Reliza , Felsted Amy E. , Song Brian , Hubbard Ryan , Worlikar Tejaswi , Garavaglia Hannah , Dib Joe , Chao Hannah , Boyle Nicoleen , Olszewski Michal , Xu Zhen , Ganguly Anutosh , Cho Clifford S. 
Published: January 2023

IntroductionHistotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects.MethodsTo measure the spatiotemporal kinetics of local andabscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and contralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.ResultsUnilateral histotripsy triggered abscopal tumor growth inhibition. Within the ablation zone, early high mobility group box protein 1 (HMGB1) release and necroptosis were accompanied by immunogenic cell death transcriptional responses in tumor cells and innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Delayed CD8+ T cell intratumoral infiltration was spatiotemporally aligned with cancer cell features of ferroptosis; this effect was enhanced by CTLA-4 blockade and recapitulated in vitro when tumor-draining lymph node CD8+ T cells were co-cultured with tumor cells. Inoculation with cell-free tumor fractions generated by histotripsy but not radiation or freeze/thaw conferred partial protection from tumor challenge.DiscussionWe propose that histotripsy may evoke local necroptotic immunogenic cell death, priming systemic adaptive immune responses and abscopal ferroptotic cancer cell death.
Persistent T cell-mediated immune responses against Omicron variants after the third COVID-19 mRNA vaccine dose
Authors: Belik Milja , Liedes Oona , Vara Saimi , Haveri Anu , Pöysti Sakari , Kolehmainen Pekka , Maljanen Sari , Huttunen Moona , Reinholm Arttu , Lundberg Rickard , Skön Marika , Österlund Pamela , Melin Merit , Hänninen Arno , Hurme Antti , Ivaska Lauri , Tähtinen Paula A. , Lempainen Johanna , Kakkola Laura , Jalkanen Pinja , Julkunen Ilkka 
Published: January 2023

IntroductionThe prime-boost COVID-19 mRNA vaccination strategy has proven to be effective against severe COVID-19 disease and death. However, concerns have been raised due to decreasing neutralizing antibody levels after COVID-19 vaccination and due to the emergence of new immuno-evasive SARS-CoV-2 variants that may require additional booster vaccinations.MethodsIn this study, we analyzed the humoral and cell-mediated immune responses against the Omicron BA.1 and BA.2 subvariants in Finnish healthcare workers (HCWs) vaccinated with three doses of COVID-19 mRNA vaccines. We used enzyme immunoassay and microneutralization test to analyze the levels of SARS-CoV-2 specific IgG antibodies in the sera of the vaccinees and the in vitro neutralization capacity of the sera. Activation induced marker assay together with flow cytometry and extracellular cytokine analysis was used to determine responses in SARS-CoV-2 spike protein stimulated PBMCs.ResultsHere we show that within the HCWs, the third mRNA vaccine dose recalls both humoral and T cell-mediated immune responses and induces high levels of neutralizing antibodies against Omicron BA.1 and BA.2 variants. Three weeks after the third vaccine dose, SARS-CoV-2 wild type spike protein-specific CD4+ and CD8+ T cells are observed in 82% and 71% of HCWs, respectively, and the T cells cross-recognize both Omicron BA.1 and BA.2 spike peptides. Although the levels of neutralizing antibodies against Omicron BA.1 and BA.2 decline 2.5 to 3.8-fold three months after the third dose, memory CD4+ T cell responses are maintained for at least eight months post the second dose and three months post the third vaccine dose.DiscussionWe show that after the administration of the third mRNA vaccine dose the levels of both humoral and cell-mediated immune responses are effectively activated, and the levels of the spike-specific antibodies are further elevated compared to the levels after the second vaccine dose. Even though at three months after the third vaccine dose antibody levels in sera decrease at a similar rate as after the second vaccine dose, the levels of spike-specific CD4+ and CD8+ T cells remain relatively stable. Additionally, the T cells retain efficiency in cross-recognizing spike protein peptide pools derived from Omicron BA.1 and BA.2 subvariants. Altogether our results suggest durable cellmediated immunity and protection against SARS-CoV-2.
Validation of a deep neural network-based algorithm supporting clinical management of adnexal mass
Authors: Reilly Gerard P. , Dunton Charles J. , Bullock Rowan G. , Ure Daniel R. , Fritsche Herbert , Ghosh Srinka , Pappas Todd C. , Phan Ryan T. 
Published: January 2023

BackgroundConservative management of adnexal mass is warranted when there is imaging-based and clinical evidence of benign characteristics. Malignancy risk is, however, a concern due to the mortality rate of ovarian cancer. Malignancy occurs in 10–15% of adnexal masses that go to surgery, whereas the rate of malignancy is much lower in masses clinically characterized as benign or indeterminate. Additional diagnostic tests could assist conservative management of these patients. Here we report the clinical validation of OvaWatch, a multivariate index assay, with real-world evidence of performance that supports conservative management of adnexal masses.MethodsOvaWatch utilizes a previously characterized neural network-based algorithm combining serum biomarkers and clinical covariates and was used to examine malignancy risk in prospective and retrospective samples of patients with an adnexal mass. Retrospective data sets were assembled from previous studies using patients who had adnexal mass and were scheduled for surgery. The prospective study was a multi-center trial of women with adnexal mass as identified on clinical examination and indeterminate or asymptomatic by imaging. The performance to detect ovarian malignancy was evaluated at a previously validated score threshold.ResultsIn retrospective, low prevalence (N = 1,453, 1.5% malignancy rate) data from patients that received an independent physician assessment of benign, OvaWatch has a sensitivity of 81.8% [95% confidence interval (CI) 65.1–92.7] for identifying a histologically confirmed malignancy, and a negative predictive value (NPV) of 99.7%. OvaWatch identified 18/22 malignancies missed by physician assessment. A prospective data set had 501 patients where 106 patients with adnexal mass went for surgery. The prevalence was 2% (10 malignancies). The sensitivity of OvaWatch for malignancy was 40% (95% CI: 16.8–68.7%), and the specificity was 87% (95% CI: 83.7–89.7) when patients were included in the analysis who did not go to surgery and were evaluated as benign. The NPV remained 98.6% (95% CI: 97.0–99.4%). An independent analysis set with a high prevalence (45.8%) the NPV value was 87.8% (95% CI: 95% CI: 75.8–94.3%).ConclusionOvaWatch demonstrated high NPV across diverse data sets and promises utility as an effective diagnostic test supporting management of suspected benign or indeterminate mass to safely decrease or delay unnecessary surgeries.