bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plant-based production and characterization of a promising Fc-fusion protein against microgravity-induced bone density loss
Authors: Xiong Yongao , Hirano Hiroto , Lane Nancy E. , Nandi Somen , McDonald Karen A. 
Published: September 2022

Microgravity-induced bone loss is a main obstacle for long term space missions as it is difficult to maintain bone mass when loading stimuli is reduced. With a typical bone mineral density loss of 1.5% per month of microgravity exposure, the chances for osteoporosis and fractures may endanger astronauts’ health. Parathyroid Hormone or PTH (1–34) is an FDA approved treatment for osteoporosis, and may reverse microgravity-induced bone loss. However, PTH proteins requires refrigeration, daily subcutaneous injection, and have a short shelf-life, limiting its use in a resource-limited environment, like space. In this study, PTH was produced in an Fc-fusion form via transient expression in plants, to improve the circulatory half-life which reduces dosing frequency and to simplify purification if needed. Plant-based expression is well-suited for space medicine application given its low resource consumption and short expression timeline. The PTH-Fc accumulation profile in plant was established with a peak expression on day 5 post infiltration of 373 ± 59 mg/kg leaf fresh weight. Once the PTH-Fc was purified, the amino acid sequence and the binding affinity to its target, PTH 1 receptor (PTH1R), was determined utilizing biolayer interferometry (BLI). The binding affinity between PTH-Fc and PTH1R was 2.30 × 10−6 M, similar to the affinity between PTH (1–34) and PTH1R (2.31 × 10−6 M). Its function was also confirmed in a cell-based receptor stimulation assay, where PTH-Fc was able to stimulate the PTH1R producing cyclic adenosine monophosphate (cAMP) with an EC50 of (8.54 ± 0.12) x 10−9 M, comparable to the EC50 from the PTH (1–34) of 1.49 × 10−8 M. These results suggest that plant recombinant PTH-Fc exhibits a similar binding affinity and potency in a PTH1R activation assay compared to PTH. Furthermore, it can be produced rapidly at high levels with minimal resources and reagents, making it ideal for production in low resource environments such as space.
Static composting of cow manure and corn stalk covered with a membrane in cold regions
Authors: Shi Fengmei , Xu Chengjiao , Liu Jie , Sun Fang , Yu Hongjiu , Wang Su , Li Pengfei , Yu Qiuyue , Li Dan , Zuo Xin , Liu Li , Pei Zhanjiang 
Published: September 2022

The disposal of livestock wastes is an urgent task in China. Compost is highly regarded for its ability to treat livestock wastes and protect arable land. In particular, some problems of livestock manure in cold regions, such as low efficiency because of low environmental temperature in winter, urgently need to be solved. In order to provide valuable composting information in the cold area at low environmental temperatures, the composting experiments were carried out with cow manure and corn stalk as substrates. The properties and bacterial community of compost samples in different stages were investigated. The electrical conductivity (EC), total nitrogen (TN), total phosphorus (TP), and organic matter (OM) of the final compost were 551 μS/cm, 1.12, 0.77, and 63.5%, respectively. No E. coli or Ascaris eggs were detected. The temperature was the key factor to affect the physical-co-chemical and biological properties. The absolutely dominant genera were Sporosarcina, Virgibacillus, Flavobacterium, and Steroidobacter in heating, high temperature, cooling, and maturing stages, respectively. Also, these bacteria could act as biological indicators during the composting process. Cryobacterium, Caldicoprobacter, Virgibacillus, and Sporosarcina were relatively novel genera in the compost piles in a cold environment. The biodegradation of exogenous substances mainly occurs in the initial and maturing stages. It is proven that composting can be carried out successfully in early spring or later autumn after a harvest.
Novel family of nitrogen-rich energetic (1,2,4-triazolyl) furoxan salts with balanced performance
Authors: Larin Alexander A. , Pivkina Alla N. , Ananyev Ivan V. , Khakimov Dmitry V. , Fershtat Leonid L. 
Published: September 2022

Nitrogen-rich energetic materials comprised of a combination of several heterocyclic subunits retain their leading position in the field of materials science. In this regard, a preparation of novel high-energy materials with balanced set of physicochemical properties is highly desired. Herein, we report the synthesis of a new series of energetic salts incorporating a (1,2,4-triazolyl) furoxan core and complete evaluation of their energetic properties. All target energetic materials were well characterized with IR and multinuclear NMR spectroscopy and elemental analysis, while compound 6 was further characterized by single-crystal X-ray diffraction study. Prepared nitrogen-rich salts have high thermal stability (up to 232°C), good experimental densities (up to 1.80 g cm−3) and high positive enthalpies of formation (344–1,095 kJ mol−1). As a result, synthesized energetic salts have good detonation performance (D = 7.0–8.4 km s−1; p = 22–32 GPa), while their sensitivities to impact and friction are quite low.
Case report: Cytokine therapy and an intracoronary autologous bone marrow-derived cell infusion with Impella support in a patient with dilated cardiomyopathy and a severely reduced ejection fraction
Authors: Hall Russell Charles , Ramaseshan Rohini , Reid Alice , Jones Daniel A. , Mathur Anthony 
Published: September 2022

IntroductionThis is the first reported case of a patient with dilated cardiomyopathy (DCM) and severely impaired left ventricular function to receive a combined treatment of granulocyte colony-stimulating factor therapy and an intracoronary delivery of autologous bone marrow-derived mononuclear cells with percutaneous circulatory assistance (the Impella CP device; Abiomed, Danvers, MA).Main symptoms and outcomeThree months post-treatment, the gentleman in his early 70s demonstrated an improvement in left ventricular ejection fraction (13–17%) and a reduction in New York Heart Association class from III to class I. There was also an improvement in his 6-minute walk test (147–357 meters), N-terminal pro-brain natriuretic peptide level (14,099–7,129 ng/l) and quality of life scores. There were no safety concerns during the treatment or follow-up.ConclusionThis case report suggests combined cell and cytokine therapy with adjunctive circulatory support could be a safe and promising treatment for patients with DCM and severely reduced ejection fraction.
Prevalence of genetically defined familial hypercholesterolemia and the impact on acute myocardial infarction in Taiwanese population: A hospital-based study
Authors: Chen Yen-Ju , Chen I-Chieh , Chen Yi-Ming , Hsiao Tzu-Hung , Wei Chia-Yi , Chuang Han-Ni , Lin Wei-Wen , Lin Ching-Heng 
Published: September 2022

BackgroundFamilial hypercholesterolemia (FH) is a common genetic disorder with markedly increased risk of coronary artery diseases (CAD), especially acute myocardial infarction (AMI). However, genetic tests for FH are not always necessary in the current diagnostic criteria of FH, which might lead to underestimation of the prevalence of FH and a lack of awareness of FH-associated CAD and AMI. We aimed to explore the prevalence of genetically defined FH in the hospital-based population and to determine the impact of FH risk variants on CAD and AMI.MethodsThe study participants were recruited between June 24, 2019 and May 12, 2021, at a medical center in Taiwan, in cooperation with the Taiwan Precision Medicine Initiative (TPMI) project. The prevalence of FH was calculated and the effects of FH pathogenic variants on CAD and AMI were analyzed by logistic regression models and shown as ORs and 95% CI.ResultsThe prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan. Highest LDL and total cholesterol levels were observed in patients with LDLR rs28942084 (LDL 219.4±55.2; total cholesterol 295.8±55.4). There was an approximately 4-fold increased risk of hyperlipidemia in subjects with the LDLR rs769446356 polymorphism (OR, 4.42; 95% CI, 1.92-10.19) and AMI in individuals with the LDLR rs730882109 polymorphism (OR, 3.79; 95% CI, 2.26-6.35), and a 2-fold increased risk of CAD in those with the LDLR rs749038326 polymorphism (OR, 2.14; 95% CI, 1.31-3.50), compared with the groups without pathogenic variants of FH.ConclusionsThe prevalence of genetically defined FH was 1.13% in the hospital-based population in Taiwan, which was higher than the rate observed in individuals with clinically defined FH. The risk of CAD and AMI was increased to varying degrees in subjects with different FH risk alleles. Close monitoring and risk stratification strategy are essential in high-risk patients with FH risk alleles to facilitate early detection and treatments.
Expanding the theory for reducing the CO2 disaster—Hypotheses from partial least-squares regression and machine learning
Authors: Xu Bai-Zhou , Li Xiao-Liang , Wang Wen-Feng , Chen Xi 
Published: September 2022

The rapid increase in atmospheric CO2 concentration has caused a climate disaster (CO2 disaster). This study expands the theory for reducing this disaster by analyzing the possibility of reinforcing soil CO2 uptake (Fx) in arid regions using partial least-squares regression (PLSR) and machine learning models such as artificial neural networks. The results of this study demonstrated that groundwater level is a leading contributor to the regulation of the dynamics of the main drivers of Fx–air temperature at 10 cm above the soil surface, the soil volumetric water content at 0–5 cm (R2=0.76, RMSE=0.435), and soil pH (R2=0.978, RMSE=0.028) in arid regions. Fx can be reinforced through groundwater source management which influences the groundwater level (R2=0.692, RMSE=0.03). This study also presents and discusses some basic hypotheses and evidence for quantitively reinforcing Fx.
First-Order Stratigraphic Boundaries of the Late Cretaceous–Paleogene Retroarc Foreland Basin in Colombia
Authors: Carvajal-Torres Juan , Catuneanu Octavian , Mora Andres , Caballero Victor , Reyes Martin 
Published: September 2022

The present-day Magdalena Valley, Eastern Cordillera, and Llanos Basin were part of a regional multiphase basin that started as an extensional basin in the Jurassic. Then, it was transformed into a retroarc foreland basin in the Late Cretaceous and subsequently separated into a hinterland and a foreland basin during the late Eocene. We incorporated new data from the Llanos Basin and Eastern Cordillera and chronostratigraphically correlated it with the adjacent basins. Their correlation contributed to establishing the stratigraphic boundaries formed during the first-order changes that marked the beginning and the end of the lifespan of the retroarc foreland basin. In the initial stage, the lateral extent along the dip of the significant depocenter that extended from the Magdalena Valley to the westernmost Llanos Basin was approximately 300–470 km. At the same time, the western flank of the Eastern Cordillera and most of the Llanos Basin were uplifting. The contact between the retrograding marine facies of the Upper Lidita, Buscavidas, Umir, Guadalupe, and Palmichal units marks a late Campanian maximum regressive surface formed during the initial exhumation of the orogen, the Central Cordillera. Therefore, it represents a first-order stratigraphic surface. This surface does not extend across the whole basin. In the uplifting areas, subaerial unconformities truncate the middle Campanian rocks. Their combination represents the lower first-order boundary of the sequence, and their diachroneity is the product of the northward migration of the orogen. The Teruel, Hoyon, Bogota, Cacho, Socha, Barco, and Cuervos formations are truncated by a regional subaerial unconformity. It was formed during orogenic unloading that marks the termination of the foreland basin in the Eocene. As it marks another first-order change, it is the upper boundary of the first-order sequence.
First observation of paired microseismic signals during solution salt mining
Authors: Qian Jiawei , Wang Kangdong , Zhang Haijiang , Tan Yuyang , Xu Chuanjian , Wang Qingsong , Xiong Qiangqing , Malinowski Michal 
Published: September 2022

To monitor the status of cavern roof instability induced by solution salt mining, we deployed a surface microseismic monitoring system for Dongxing salt mine, Dingyuan county, China. The microseismic monitoring system consists of 11 three-component geophones installed in shallow holes of 5 m deep. From 7-month continuous monitoring data, we have detected a novel type of signal that consists of two events. The first event has a long duration (&gt;15 s) and generally has higher frequencies at the beginning. The 2nd event has a shorter duration of ∼3 s with lower frequencies. The two events are separated by ∼30–90 s in time. From May 2017 to November 2017, there are a total of 88 distinct paired signals with two events in sequence. We propose the first event corresponds to a series of fracturing processes on the cavern roof, and microseismic signals associated with different fractures are mixed and overlapped to produce a mixed signal with a longer duration. Due to a series of fracturing processes, some zones of cavern roof become instable and some rock debris may fall from the roof and collide on the cavern floor. This collision can produce a short duration signal, which corresponds to the 2nd event of the paired signal. The further analysis of polarities of the first arrivals for the 2nd event further proves its collision origin. The time interval between two events is related to the time for the falling rock debris through the brine, which is controlled by the cavern height and various physical properties of the rock debris and brine. Through the detailed analysis of paired signals, we can have a better understanding of the cavity development status for solution salt mining.
Booster dose of COVID-19 mRNA vaccine does not increase risks of myocarditis and pericarditis compared with primary vaccination: New insights from the vaccine adverse event reporting system
Authors: Chen Congqin , Fu Fang , Ding Lingqing , Fang Jie , Xiao Jie 
Published: September 2022

BackgroundDespite the likely association between coronavirus 2019 (COVID-19) mRNA vaccines and cases of myocarditis/pericarditis, the benefit–risk assessment by the Centers for Disease Control (CDC) still showed a favorable balance for the primary series of COVID-19 mRNA vaccinations. Since August 2021, a full-scale booster vaccination in certain recipients has been recommended. Great concerns about whether the COVID-19 mRNA booster vaccination could increase the risks of myocarditis/pericarditis have been raised since then. The present study aimed to compare the incidence rates and risks of myocarditis/pericarditis between booster and primary vaccination programs.MethodsThe CDC COVID Data Tracker and the Vaccines Adverse Event Reporting System (VAERS) were queried between December 11, 2020 and March 15, 2022. Incidence rates were calculated by cases of myocarditis/pericarditis divided by the number of vaccinated people or the total doses of COVID-19 mRNA vaccines. Disproportionality patterns for myocarditis/pericarditis of different COVID-19 mRNA vaccinations were accessed based on the reporting odds and proportional reporting ratios (ROR and PRR, respectively).ResultsA total of 2,588 reports of myocarditis/pericarditis were identified after administration of primary-series COVID-19 mRNA vaccination and 269 after the booster dose program during the study period. The incidence of myocarditis/pericarditis following booster COVID-19 mRNA vaccination was lower than that of primary series. The results showed significantly high reporting of myocarditis/pericarditis following the administration of primary COVID-19 mRNA vaccination, whereas the disproportional level was lower in the booster-dose vaccination.ConclusionThis study found that the booster dose of COVID-19 mRNA vaccination when compared with primary series course did not lead to an increase in the risks of myocarditis/pericarditis.
Circulating immune-complexes of IgG/IgM bound to B2-glycoprotein-I associated with complement consumption and thrombocytopenia in antiphospholipid syndrome
Authors: Naranjo Laura , Stojanovich Ljudmila , Djokovic Aleksandra , Andreoli Laura , Tincani Angela , Maślińska Maria , Sciascia Savino , Infantino Maria , Garcinuño Sara , Kostyra-Grabczak Kinga , Manfredi Mariangela , Regola Francesca , Stanisavljevic Natasa , Milanovic Milomir , Saponjski Jovica , Roccatello Dario , Cecchi Irene , Radin Massimo , Benucci Maurizio , Pleguezuelo Daniel , Serrano Manuel , Shoenfeld Yehuda , Serrano Antonio 
Published: September 2022

BackgroundAntiphospholipid syndrome (APS) is a multisystemic autoimmune disorder characterized by thrombotic events and/or gestational morbidity in patients with antiphospholipid antibodies (aPL). In a previous single center study, APS-related clinical manifestations that were not included in the classification criteria (livedo reticularis, thrombocytopenia, leukopenia) were associated with the presence of circulating immune-complexes (CIC) formed by beta-2-glycoprotein-I (B2GP1) and anti-B2GP1 antibodies (B2-CIC). We have performed a multicenter study on APS features associated with the presence of B2-CIC.MethodsA multicenter, cross-sectional and observational study was conducted on 303 patients recruited from six European hospitals who fulfilled APS classification criteria: 165 patients had primary APS and 138 APS associated with other systemic autoimmune diseases (mainly systemic lupus erythematosus, N=112). Prevalence of B2-CIC (IgG/IgM isotypes) and its association with clinical manifestations and biomarkers related to the disease activity were evaluated.ResultsB2-CIC prevalence in APS patients was 39.3%. B2-CIC-positive patients with thrombotic APS presented a higher incidence of thrombocytopenia (OR: 2.32, p=0.007), heart valve thickening and dysfunction (OR: 9.06, p=0.015) and triple aPL positivity (OR: 1.83, p=0.027), as well as lower levels of C3, C4 and platelets (p-values: &lt;0.001, &lt;0.001 and 0.001) compared to B2-CIC-negative patients. B2-CIC of IgM isotype were significantly more prevalent in gestational than thrombotic APS.ConclusionsPatients with thrombotic events and positive for B2-CIC had lower platelet count and complement levels than those who were negative, suggesting a greater degree of platelet activation.
Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers
Authors: Liu Xiaoyu , Xu Xu , Wu Zhuozhuo , Shan Qungang , Wang Ziyin , Wu Zhiyuan , Ding Xiaoyi , Huang Wei , Wang Zhongmin 
Published: September 2022

BackgroundThe main objective of this study was to analyze the effects of KRAS/TP53 mutation status and tumor sideness on the immune microenvironment of colorectal cancer using integrated scRNA-seq data.MethodsA total of 78 scRNA-seq datasets, comprising 42 treatment-naive colorectal tumors, 13 tumor adjacent tissues and 23 normal mucosa tissues were included. Standardized Seurat procedures were applied to identify cellular components with canonical cell marks. The batch-effect was assessed and corrected using harmony algorithm. The scMetabolism algorithm was used for single-cell metabolic analysis. The results and clinical significance were further validated using immunofluorescent-staining and TCGA-COAD datasets. Immune-infiltration scores of bulk-RNA-seq data were estimated using ssGSEA. The presto-wilcoxauc algorithm was used to identify differentially enriched genes or pathways across different subgroups. Two-sided p-value less than 0.05 was considered statistically significant.ResultsWe refined the landscape of functional immune cell subtypes, especially T cells and myeloid cells, across normal mucosa, tumor adjacent and tumor tissue. The existence and function of two states of exhausted CD8+ T (Tex) subtypes in colorectal cancer, and FOLR2+ LYVE1+ macrophages indicating unfavorable prognosis in colorectal cancer were identified and validated. The diverse tumor mutation status reshaped the immune cell function and immune checkpoint ligands/receptors (ICLs/ICRs) expression pattern. Importantly, the KRAS/TP53 dual mutations significantly reduced the major energy metabolic functions in immune cells, and promoted the cell-to-cell communications towards immunosuppression in colorectal cancers. The results revealed LAG3, CD24-SIGLEC10 and HBEGF-CD9 pathways as potential therapeutic targets for dual mutant colorectal cancers.ConclusionsWe revealed that the immune microenvironment underwent a gradual remodeling with an enrichment of immunosuppressive myeloid cells from normal mucosa to tumor regions in colorectal cancers. Moreover, we revealed the metabolic heterogeneity of tumor-infiltrating immune cells and suggested that the KRAS/TP53 dual mutation may impair antitumor immunity by reducing T and myeloid cell energy metabolism and reshaping cellular interactions toward immunosuppression.
CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis
Authors: Liu Ting , Liu Yu , Liu Chen-xi , Jiang Yong-mei 
Published: September 2022

CXCL13 is a chemokine that is widely involved in the pathogenesis of autoimmune diseases, tumors and inflammatory diseases. In this study, we investigate the role of CXCL13 in the pathogenesis of inflammatory bowel disease using both clinical specimens and animal models. We found that the serum CXCL13 concentration in IBD patients was significantly higher than that in healthy controls, and correlated with that of CRP, neutrophils counts and hemoglobin. The increase of CXCL13 in IBD patients might be related to the significant decrease of circulating CD4+CXCR5+ T cells, the increase of CD19+CD5+ B cells and the enhancement of humoral immunity. In mice colitis model, we also found elevated levels of CXCL13 in colon tissue. Cxcl13-/- knockout mice exhibited a mild, self-limiting form of disease. Additionally, CXCL13 deficiency restricted CD4+CXCR5+ T cells migration in mesenteric lymph nodes, resulting locally regulatory B cells increased in colon. In conclusion, our findings raise the possibility that CXCL13 plays a critical role in the pathogenesis of IBD. We believe that our findings will contribute to the understanding of the etiology, and that antagonizing or inhibiting CXCL13 may work as a potential adjunctive therapy strategy for patients with IBD.