bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eucalyptus species maintain secondary metabolite production under water stress conditions at the expense of growth
Authors: Manea Anthony , Tabassum Samiya , Leishman Michelle R. 
Published: March 2021

AbstractPlants have evolved a vast array of secondary metabolites that help defend them against natural enemy attack. The production of these secondary metabolites is influenced by environmental factors, such as temperature, rainfall (soil water availability) and atmospheric [CO2], which may be altered under climate change. This study aimed to test how two of these environmental factors, namely soil water availability and [CO2], will affect secondary metabolite and biomass production in Eucalypts. To investigate this, we measured secondary metabolite and biomass production of three Eucalypt species (Eucalyptus grandis, E. moluccana, E. saligna) grown under ambient and elevated [CO2] (400 and 600 ppm, respectively) and water‐stressed and well‐watered conditions, in a fully factorial glasshouse experiment. The secondary metabolites measured were foliar phenolic concentration as well as terpene and green leaf volatile emissions. We found that water stress did not alter secondary metabolite production. Unsurprisingly, the water‐stressed plants maximised their water uptake potential by reducing shoot biomass but maintaining root biomass. The detrimental effects of water stress on shoot biomass production were not reduced under elevated [CO2] compared to ambient [CO2], despite all species experiencing significant reductions in stomatal conductance. Further, [CO2] as a single factor did not have a significant effect on species’ net carbon gain, with an increase in green leaf volatile emissions under elevated [CO2] being mitigated by a reduction in shoot biomass production. These results suggest that reductions in carbon gains due to water stress will affect the growth of Eucalypts rather than their chemical defence capabilities.
Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort
Authors: Gheerbrant Hubert , Guillien Alicia , Vernet Raphaël , Lupinek Christian , Pison Christophe , Pin Isabelle , Demenais Florence , Nadif Rachel , Bousquet Jean , Pickl Winfried F. , Valenta Rudolf , Bouzigon Emmanuelle , Siroux Valérie 
Published: March 2021

AbstractBackgroundAllergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class‐II genomic region is a strong candidate.ObjectiveTo assess the association between HLA class‐II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules.MethodsThe analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class‐II alleles. For each sIgE sensitization and HLA class‐II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p‐values were corrected for multiple comparisons (False Discovery Rate).ResultsMost of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively).ConclusionOur results support the important role of HLA class‐II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.
Labour’s Spatial Fix: State Socialist Hungary in the 1970s
Authors: Czirfusz Márton 
Published: March 2021

AbstractLabour’s spatial fix has become a key term in labour geography scholarship in recent decades. The concept has been widely used to understand labour’s agency in its own social reproduction in different historical and geographical capitalist social formations. Departing from the position that state socialism was part of global capitalism, this paper applies the concept of labour’s spatial fix to the context of state socialist Hungary. The analysis differentiates between three dimensions of labour’s spatial fix in social reproduction: wage work (with particular attention given to female employment), income from the “second economy” and housing. The interrelatedness of these dimensions of labour’s spatial fix, as well as their different geographies, are shown in an analysis covering Hungary of the 1970s. It is argued that there is a need for more extensive research on how conditions for social reproduction are established in the concept of labour’s spatial fix.
Early delivery or expectant management for late preterm preeclampsia: A meta‐analysis of randomized controlled trials
Authors: Chatzakis Christos , Liberis Anastasios , Zavlanos Apostolos , Petousis Stamatis , Tsakmaki Evangelia , Dinas Konstantinos , Sotiriadis Alexandros 
Published: March 2021

AbstractIntroductionCurrently, there is no consensus regarding the timing of delivery in women with non‐severe preeclampsia at the late preterm period. The aim of the present meta‐analysis is to compare expectant management with immediate delivery in pregnant women with preeclampsia between 34+0 and 36+6 gestational weeks, in terms of maternal and neonatal outcomes.Material and methodsA search was conducted until October 1, 2020 and eligible studies were identified in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central), the US Registry of clinical trials (www.clinicaltrials.gov), and sources of gray literature without limitations concerning the publication dates and languages. Randomized controlled trials, comparing planned delivery vs expectant management in women with preeclampsia at 34–37 weeks were included. The primary outcomes were neonatal intensive care unit (NICU) admission and progression to eclampsia. Secondary outcomes were HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, severe preeclampsia, composite adverse maternal outcome (defined by the presence of any of the potential preeclampsia‐related complications, ranging from severe hypertension to maternal death), neonatal respiratory disease, and respiratory distress syndrome. Relative risks (RRs) and mean differences with 95% CI were used for the estimation of the effect sizes; the quality of the evidence was assessed per GRADE guidelines.ResultsThe electronic search yielded 10 721 potential studies, of which six were fully reviewed and three (1773 participants) were included in the meta‐analysis. Immediate delivery increased the risk for NICU admission, (RR 1.23, 95% CI 1.05–1.45) and decreased the risk for the composite adverse maternal outcome (RR 0.86, 95% CI 0.78–0.93). There were no differences for eclampsia (RR 0.55, 95% CI 0.16–1.85), HELLP syndrome (RR 0.58, 95% CI 0.25–1.33), severe preeclampsia (RR 0.27, 95% CI 0.02–3.52), respiratory disease of neonate (RR 1.04, 95% CI 0.75–1.44), and respiratory distress syndrome (RR 2.3, 95% CI 0.73–7.25).ConclusionsImmediate delivery of women with non‐severe preeclampsia at the period of late prematurity decreases the risk of a composite adverse maternal outcome by 14%, at the cost of an increase in NICU admissions by 23%. The overall quality of the evidence for these outcomes is high, indicating a high degree of certainty for the results.
Nuclear overexpression levels of MAGE‐A3 predict poor prognosis in patients with prostate cancer
Authors: khalvandi Azadeh , Abolhasani Maryam , Madjd Zahra , Shekarabi Mehdi , Kourosh‐Arami Masoumeh , Mohsenzadegan Monireh 
Published: March 2021

Melanoma antigen gene A3 (MAGE‐A3) is one of the most immunogenic cancer testis antigens and is common in various types of cancers. In this study, for the first time, we performed immunohistochemical analysis to evaluate the expression of MAGE‐A3 in 153 prostate tissue samples including prostate cancer (PCa), benign prostatic hyperplasia (BPH), and high‐grade prostatic intraepithelial neoplasia (HPIN). Increased both nuclear and cytoplasmic expression of MAGE‐A3 was significantly found in PCa tissues compared with both HPIN and BPH tissues (nuclear expression at p = 0.011, and cytoplasmic expression at p = 0.034; for both comparisons p < 0.0001, respectively). A significant correlation was observed between higher nuclear and cytoplasmic expressions of MAGE‐A3 with Gleason score (p < 0.0001 and 0.006, respectively). Increased expression of MAGE‐A3 was associated with shorter biochemical recurrence‐free survival (BCR‐FS) and disease‐free survival (DFS) of patients (p = 0.042 and = 0.0001, respectively). In multivariate analysis, nuclear expression of MAGE‐A3 and Gleason score (≤7 vs >7) was independent predictors of the DFS (both; p = 0.019). Nuclear expression of MAGE‐A3 was also significantly related to BCR‐FS (p = 0.015). MAGE‐A3 can be considered as a predictor for poor prognosis and an option for vaccine immunotherapy in patients with PCa.
Survival outcomes of elderly patients referred to the lower gastrointestinal 2‐week wait service
Authors: Hubbard Thomas J. E. , Pringle Heather , Bethune Robert , McDermott Frank D. 
Published: March 2021

AbstractAimThe benefit to elderly patients (≥80 years old) of referral to the resource‐intensive lower gastrointestinal 2‐week wait (LGI‐2WW) pathway is unknown. The aim of this study was to investigate the survival outcome of elderly patients referred to a LGI‐2WW service.MethodThis study comprised a retrospective analysis of a prospectively gathered database of patients referred to a single‐centre LGI‐2WW service and conformed to STROBE guidelines. The primary outcome was all‐cause mortality. Statistical analysis was performed with the chi‐square test and Kaplan–Meier survival curves compared with the generalized log‐rank test.ResultsA total of 10 155 patients referred to the LGI‐2WW service between 1 January 2015 and 31 December 2018 were analysed; median follow‐up was 37.0 months (range 0–66 months). Six hundred and ninety one cancers were diagnosed (6.8% detection rate); 551 (80%) of these were lower GI cancers (LGICas) [517 (75%) colorectal; 34 (5%) anal]. Forty per cent of LGICas were diagnosed via the LGI‐2WW service. Patients aged ≥80 years with LGICa were more likely to be treated with palliative intent [age <80 years, 92/360 (26%) vs. age ≥80 years, 105/191 (55%); p < 0.001]. LGICa patients aged <85 years had a survival difference between those treated with curative intent (LGICa‐Cur) or palliative intent (LGICa‐Pal) (median survival for patients aged 80–84 years: LGICa‐Cur 57 months vs. LGICa‐Pal 15 months; p < 0.001). Patients aged ≥85 years did not have any survival difference by treatment intent (median survival for patients aged 85–89 years: LGICa‐Cur 31 months vs. LGICa‐Pal 16 months; p = 0.062; median survival for patients aged ≥90 years: LGICa‐Cur 14 months vs. LGICa‐Pal 16 months; p = 0.703).ConclusionPatients with LGICa aged ≥85 years have similar survival whether treated with curative or palliative intent. This can inform management discussions with patients and LGI‐2WW referral pathway prioritization approaches.
Influence of 4‐week or 12‐week glucocorticoid treatment on metabolic changes in patients with active moderate‐to‐severe thyroid‐associated ophthalmopathy
Authors: Chen Xiaoman , Abudukerimu Buatikamu , Li Qin , Li Qing , Qiao Jie , Lin Dongping , Sui Chunhua , Ye Lin , Zhai Hualing , Jiang Boren , Wang Ningjian , Jiang Mengda , Tao Xiaofeng , Shao Ziyang , Zhu Chenfang , Ma Yubo , Xiong Ping , Sun Jing , Zhou Huifang , Han Bing , Lu Yingli 
Published: March 2021

AbstractThyroid‐associated ophthalmopathy (TAO) is a serious, progressive, vision‐threatening and difficult‐to‐treat organ‐specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High‐dose intravenous glucocorticoid (IVGC) therapy is considered a first‐line treatment for active moderate‐to‐severe TAO, but there is still insufficient evidence regarding the treatment duration. Long‐term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty‐eight patients with active moderate‐to‐severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12‐week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p < 0.001), and low‐density lipoprotein (p < 0.001) after therapy. The patients in both groups had reduced bone metabolism markers after therapy. Thyroid peroxidase antibody and thyrotropin receptor antibody levels decreased after treatment in both groups (p < 0.001). A significant decrease in thyroglobulin antibody levels was found in the 4‐week group (p = 0.006). The change in the ADC was higher in the 4‐week group than in the 12‐week group (p = 0.014). However, there were no significant differences in CAS values between the two groups. Therefore, 4‐week IVGC therapy was recommended for patients with TAO with glucose and lipid disorders.
Exploratory window‐of‐opportunity trial to investigate the tumor pharmacokinetics/pharmacodynamics of the IAP antagonist Debio 1143 in patients with head and neck cancer
Authors: Gomez‐Roca Carlos , Even Caroline , Le Tourneau Christophe , Basté Neus , Delord Jean‐Pierre , Sarini Jerome , Vergez Sebastien , Temam Stephane , Hoffmann Caroline , Rochaix Philippe , Borcoman Edith , Gavillet Bruno , Rouits Elisabeth , Ménétrey Annick , Brichory Franck , Purcea Daniela , Vuagniaux Gregoire , Zanna Claudio 
Published: March 2021

AbstractInhibitor of apoptosis proteins (IAPs) regulate apoptosis and modulate NF‐κB signaling thereby driving expression of genes involved in immune/inflammatory responses. The orally available IAP antagonist Debio 1143 has potential to enhance tumor response to chemoradiotherapy and/or immunotherapy. Patients with pre‐operative squamous cell carcinomas of the head and neck (SCCHN) received: Debio 1143 monotherapy (200 mg/day [D]1–15 +/‐ 2); Debio 1143 (200 mg/day D1–15 +/‐ 2) plus cisplatin (40 mg/m2 D 1 and 8); cisplatin alone (40 mg/m2 D 1 and 8; EudraCT: 2014‐004655‐31). Pharmacokinetic/pharmacodynamic effects were assessed in plasma and resected tumors. Primary end point; effect of Debio 1143 on cellular IAP‐1 (cIAP‐1). Levels of cIAP‐1/‐2, X‐linked inhibitor of apoptosis protein (XIAP), tumor infiltrating lymphocytes (TILs), including CD8+ T cells, programmed cell death protein 1 (PD‐1), PD‐ligand 1 (PD‐L1), and gene expression were also analyzed. Twenty‐three of 26 patients completed treatment. In the Debio 1143 monotherapy cohort (n = 13), mean tumor concentrations of Debio 1143 were 18‐fold (maximum 55.2‐fold) greater than in plasma, exceeding the half‐maximal inhibitory concentration for cIAPs and XIAP by 100 to 1000‐fold, with significant engagement/degradation of cIAP‐1 (p < 0.05). Overall, levels of CD8+ TILs, PD‐1, and PD‐L1 positive immune cells increased significantly (p < 0.05) following Debio 1143 treatment. Changes were observed in the expression of genes related to NF‐κB signaling. Treatments were well‐tolerated. Debio 1143 penetrated SCCHN tumors, engaged cIAP‐1, and induced immune inflammatory changes in the tumor microenvironment. Based on the mode of action demonstrated here and in previous studies, these data support future combinations of Debio 1143 with immune‐checkpoint agents.
A pharmacokinetic simulation study to assess the performance of a sparse blood sampling approach to quantify early drug exposure
Authors: Sathe Abhishek G. , Brundage Richard C. , Ivaturi Vijay , Cloyd James C. , Chamberlain James M. , Elm Jordan J. , Silbergleit Robert , Kapur Jaideep , Coles Lisa D. 
Published: March 2021

AbstractEstimating early exposure of drugs used for the treatment of emergent conditions is challenging because blood sampling to measure concentrations is difficult. The objective of this work was to evaluate predictive performance of two early concentrations and prior pharmacokinetic (PK) information for estimating early exposure. The performance of a modeling approach was compared with a noncompartmental analysis (NCA). A simulation study was performed using literature‐based models for phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA). These models were used to simulate rich concentration‐time profiles from 0 to 2 h. Profiles without residual unexplained variability (RUV) were used to obtain the true partial area under the curve (pAUC) until 2 h after the start of drug infusion. From the profiles with the RUV, two concentrations per patient were randomly selected. These concentrations were analyzed under a population model to obtain individual population PK (PopPK) pAUCs. The NCA pAUCs were calculated using a linear trapezoidal rule. Percent prediction errors (PPEs) for the PopPK pAUCs and NCA pAUCs were calculated. A PPE within ±20% of the true value was considered a success and the number of successes was obtained for 100 simulated datasets. For PHT, LEV, and VPA, respectively, the median value of the success statistics obtained using the PopPK approach of 81%, 92%, and 88% were significantly higher than the 72%, 80%, and 67% using the NCA approach (p < 0.05; Mann–Whitney U test). This study provides a means by which early exposure can be estimated with good precision from two concentrations and a PopPK approach. It can be applied to other settings in which early exposures are of interest.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of HBM9161, a novel FcRn inhibitor, in a phase I study for healthy Chinese volunteers
Authors: Yap Desmond Y. H. , Hai Jojo , Lee Paul C. H. , Zhou Xueying , Lee Michael , Zhang Yu , Wang Meng , Chen Xiaoxiang 
Published: March 2021

AbstractBlockade of the binding between neonatal Fc receptor and IgG‐Fc reduces circulating IgG, and thus emerges as a potential therapy for IgG‐mediated autoimmune conditions. This was a double blind, randomized, single ascending dose study to evaluate the safety, pharmacokinetics, and pharmacodynamics of HBM9161 (a fully humanized Fc receptor monoclonal antibody) in healthy Chinese volunteers. Subjects were randomized to receive a single s.c. dose of HBM9161 or placebo in a 3:1 ratio in 3 dosing cohorts (340 mg, 510 mg, or 680 mg, respectively), and then followed up for 85 days. Study end points included incidence of adverse event (AE), serum drug concentration, IgG and its subclasses, and anti‐drug antibodies (ADAs). Twenty‐four subjects were randomized. Dose‐dependent reduction of total IgG occurred rapidly from baseline to reach nadir at day 11, then recovered steadily from day 11 to day 85. The mean maximum percentage reductions from baseline total IgG were 21.0 ± 9.3%, 39.8 ± 5.13%, and 41.2 ± 10.4% for subjects receiving HBM9161 340 mg, 510 mg, and 680 mg, respectively. The exposure of HBM9161 (areas under the curve [AUCs] and peak plasma concentration [Cmax]) increased in a more than dose‐proportional manner at the dose examined. All reported AEs were mild in severity. The most reported AEs in the HBM9161 groups were influenza‐like illness and rash. Two subjects developed ADA during the study period. A single s.c. dose of HBM9161 results in sustained and dose‐dependent IgG reduction, and was well‐tolerated at a dose up to 680 mg in Chinese subjects. The data warrant further investigation of its effects in IgG‐mediated autoimmune disorders.
Identification of Corynespora cassiicola causing leaf spot on Syringa species
Authors: Wang Shuhe , Liu Huidi 
Published: March 2021

ABSTRACTLilacs (Syringa spp.), a genus of trees and shrubs in the Oleaceae, are known for their beautiful, fragrant flowers and are widely cultivated as ornamentals. In September 2017, a new leaf spot disease was observed on S. oblata in the Sui and Tang Ruins Dynasties Botanical Garden in Luoyang, Henan Province, China. Leaf symptoms appeared as small brown lesions at earlier stages, which with age turned into suborbicular brown, faintly zonate and depressed. Fully mature lesions were mostly irregular to circular, concentric rings with taupe and dark brown bands. A total of 12 monoconidial isolates were obtained from S. oblata showing leaf symptoms. Colonies were grey to light brown and darker underneath on potato dextrose agar. Based upon morphological characteristics and multilocus phylogenetic analyses using ITS, TEF1 and RPB2 loci, isolates were identified as Corynespora cassiicola. Pathogenicity tests on leaves produced symptoms matching those described above and the fungus was re‐isolated, confirming Koch's postulates. This study represents the first report of C. cassiicola on lilacs in China.
Fecal microbiota transplantation ameliorates gut microbiota imbalance and intestinal barrier damage in rats with stress‐induced depressive‐like behavior
Authors: Rao Jingjing , Xie Ruining , Lin Li , Jiang Jian , Du Lei , Zeng Xindie , Li Gongying , Wang Chunmei , Qiao Yi 
Published: March 2021

AbstractThe gut–microbiota–brain axis is the most important complex and bidirectional pathway between the gastrointestinal tract and the central nervous system. This study investigated the potential of microbe‐induced gut‐to‐brain signaling to modulate the effect of stress on depressive‐like behavior, intestinal barrier, and neuroinflammation. Result showed that fecal microbiota transplantation increased the consumption of sucrose solutions and decreased the immobility time in forced swimming test. This treatment also increased Firmicutes and decreased Bacteroidetes and Desulfobacterota at phylum levels; reduced the loss of villi and epithelial cells; suppressed the inflammatory cell infiltration in the ileum; increased the expression of ZO‐1, occludin; protected the mucosal layer function; and suppressed the high levels of inflammasomes (NLRP3, ASC, caspase‐1, and IL‐1β) in rat brain. In summary, fecal microbiota transplantation improves the depressive‐like behavior, alters the gut microbiota imbalance, and alleviates the intestinal tract inflammation, intestinal mucosa disruption, and neuroinflammation in rats induced by chronic unpredictable mild stress.