bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAK inhibitors impair GM-CSF-mediated signaling in innate immune cells
Authors: Fujita Yuya , Matsuoka Naoki , Temmoku Jumpei , Furuya-Yashiro Makiko , Asano Tomoyuki , Sato Shuzo , Matsumoto Haruki , Watanabe Hiroshi , Kozuru Hideko , Yatsuhashi Hiroshi , Kawakami Atsushi , Migita Kiyoshi 
Published: June 2020

Abstract
Background
Innate immune cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via release of cytokines. Small-molecule inhibitors of Janus kinases (JAKi) are clinically efficacious in patients with RA. However, the isoform-specific action of each JAKi is difficult to assess, since JAKs form heterodimeric complexes with cytokine receptors. We assessed the effects of several JAKi on GM-CSF-primed human innate immune cells.

Results
Treatment with JAKi (tofacitinib, baricitinib, upadacitinib) prevented GM-CSF-induced JAK2/STAT5 phosphorylation at higher concentrations (400 nM) in THP-1 cells. Whereas compared with baricitinib or upadacitinib, the inhibitory effects of tofacitinib on the GM-CSF-induced JAK2/STAT5 phosphorylation were weak at lower concentrations (≤ 100 nM). All JAKi inhibited GM-CSF-induced IL-1β production by human neutrophils. However, the inhibitory effects of baricitinib on IL-1β production were larger compared to those of tofacitinib or upadacitinib at lower concentrations (≤ 100 nM). Similarly, all JAKi inhibited GM-CSF-induced caspase-1(p20) production by human neutrophils.

Conclusion
We conclude that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells. Although baricitinib and upadacitinib almost completely blocked GM-CSF-mediated JAK2/STAT5 signaling, the inhibitory effects of tofacitinib were weaker at lower concentrations suggesting that variation exists among these JAKi in the inhibition of JAK2 signaling pathways.
Identification of glucocorticoid receptor in Drosophila melanogaster
Authors: Bartolo Gloria , Gonzalez Leandra O. , Alameh Saleem , Valencia C. Alexander , Martchenko Shilman Mikhail 
Published: June 2020

Abstract
Background
Vertebrate glucocorticoid receptor (GR) is an evolutionary-conserved cortisol-regulated nuclear receptor that controls key metabolic and developmental pathways. Upon binding to cortisol, GR acts as an immunosuppressive transcription factor. Drosophila melanogaster, a model organism to study innate immunity, can also be immunosuppressed by glucocorticoids. However, while the genome of fruit fly harbors 18 nuclear receptor genes, the functional homolog of vertebrate GR has not been identified.

Results
In this study, we demonstrated that while D. melanogaster is susceptible to Saccharomyces cerevisiae oral infection, the oral exposure to cortisol analogs, cortisone acetate or estrogen, increases fly sensitivity to yeast challenge. To understand the mechanism of this steroid-induced immunosuppression, we identified the closest genetic GR homolog as D. melanogaster Estrogen Related Receptor (ERR) gene. We discovered that Drosophila ERR is necessary for cortisone acetate- and estrogen-mediated increase in sensitivity to fungal infection: while ERR mutant flies are as sensitive to the fungal challenge as the wildtype flies, the yeast-sensitivity of ERR mutants is not increased by these steroids. Interestingly, the fungal cortisone analog, ergosterol, did not increase the susceptibility of Drosophila to yeast infection. The immunosuppressive effect of steroids on the sensitivity of flies to fungi is evolutionary conserved in insects, as we show that estrogen significantly increases the yeast-sensitivity of Culex quinquefasciatus mosquitoes, whose genome contains a close ortholog of the fly ERR gene.

Conclusions
This study identifies a D. melanogaster gene that structurally resembles vertebrate GR and is functionally necessary for the steroid-mediated immunosuppression to fungal infections.
Metabolic changes associated with adaptive resistance to daptomycin in Streptococcus mitis-oralis
Authors: Parrett Allison , Reed Joseph M. , Gardner Stewart G. , Mishra Nagendra N. , Bayer Arnold S. , Powers Robert , Somerville Greg A. 
Published: June 2020

AbstractBackgroundViridans group streptococci of theStreptococcus mitis-oralissubgroup are important endovascular pathogens. They can rapidly develop high-level and durable non-susceptibility to daptomycin both in vitro and in vivo upon exposure to daptomycin. Two consistent genetic adaptations associated with this phenotype (i.e., mutations incdsAandpgsA) lead to the depletion of the phospholipids, phosphatidylglycerol and cardiolipin, from the bacterial membrane. Such alterations in phospholipid biosynthesis will modify carbon flow and change the bacterial metabolic status. To determine the metabolic differences between daptomycin-susceptible and non-susceptible bacteria, the physiology and metabolomes ofS. mitis-oralisstrains 351 (daptomycin-susceptible) and 351-D10 (daptomycin non-susceptible) were analyzed.S. mitis-oralisstrain 351-D10 was made daptomycin non-susceptible through serial passage in the presence of daptomycin.ResultsDaptomycin non-susceptibleS. mitis-oralishad significant alterations in glucose catabolism and a re-balancing of the redox status through amino acid biosynthesis relative to daptomycin susceptibleS. mitis-oralis. These changes were accompanied by a reduced capacity to generate biomass, creating a fitness cost in exchange for daptomycin non-susceptibility.ConclusionsS. mitis-oralismetabolism is altered in daptomycin non-susceptible bacteria relative to the daptomycin susceptible parent strain. As demonstrated inStaphylococcus aureus, inhibiting the metabolic changes that facilitate the transition from a daptomycin susceptible state to a non-susceptible one, inhibits daptomycin non-susceptibility. By preventing these metabolic adaptations inS. mitis-oralis, it should be possible to deter the formation of daptomycin non-susceptibility.
Biocontrol of tomato bacterial wilt by the new strain Bacillus velezensis FJAT-46737 and its lipopeptides
Authors: Chen Meichun , Wang Jieping , Liu Bo , Zhu Yujing , Xiao Rongfeng , Yang Wenjing , Ge Cibin , Chen Zheng 
Published: June 2020

AbstractBackgroundThere is an urgent need to discover biocontrol agents to control bacterial wilt. This study reports on a new lipopeptide-producing biocontrol strain FJAT-46737 and explores its lipopeptidic compounds, and this study investigates the antagonistic effects of these compounds.ResultsBased on a whole genome sequence analysis, the new strain FJAT-46737 was identified asBacillus velezensis, and seven gene clusters responsible for the synthesis of bioactive secondary metabolites in FJAT-46737 were predicted. The antimicrobial results demonstrated that FJAT-46737 exhibited broad-spectrum antimicrobial activities in vitro against three bacteria and three fungi. Pot experiments showed that the control efficiencies for tomato bacterial wilt of the whole cultures, the 2-fold diluted supernatants and the crude lipopeptide of FJAT-46737 were 66.2%, 82.0%, and 96.2%, respectively. The above results suggested that one of the antagonistic mechanisms of FJAT-46737 was the secretion of lipopeptides consisting of iturins, fengycins and surfactins. The crude lipopeptides had significant antagonistic activities against several pathogens (includingRalstonia solanacearum,Escherichia coliandFusarium oxysporum) and fengycins were the major antibacterial components of the lipopeptides againstR. solanacearumin vitro. Furthermore, the rich organic nitrogen sources (especially yeast extracts) in the media promoted the production of fengycin and surfactin by FJAT-46737. The secretion of these two lipopeptides was related to temperature fluctuations, with the fengycin content decreasing by 96.6% and the surfactins content increasing by 59.9% from 20 °C to 40 °C. The optimal temperature for lipopeptide production by FJAT-46737 varied between 20 °C and 25 °C.ConclusionsTheB. velezensisstrain FJAT-46737 and its secreted lipopeptides could be used as new sources of potential biocontrol agents against several plant pathogens, and especially the bacterial wilt pathogenR. solanacearum.
Sensitive marker for evaluation of hypertensive heart disease: extracellular volume and myocardial strain
Authors: Niu Junqiao , Zeng Mu , Wang Yan , Liu Jun , Li Hui , Wang Shanshan , Zhou Xiaoyue , Wang Jia , Li Yanyu , Hou Feng , Zhu Junwen 
Published: June 2020

Abstract
Background
Evaluation of tissue fibrosis and myocardial hypertrophy in left ventricular (LV) remodeling is the basis of post-treatment evaluation of hypertensive heart disease (HHD). Extracellular volume (ECV) and myocardial strain parameters can indirectly reflect the changes of both. Our objective was to analyze the characteristics of ECV and strain parameters in LV myocardium of HHD with varying degrees of systolic dysfunction, and to explore the changes of both after treatment for hypertension.

Methods
A total of 62 HHD patients were divided into 3 groups according to ejection fraction (EF < 30, 30%≦EF < 50%, EF≧50%). Twenty-one of these patients underwent cardiac magnetic resonance (CMR) reexamination more than six months after receiving antihypertensive medication. The initial T1 time and post-enhancement T1 time of each segment were measured, and the ECV was calculated. Radial strain (RS), circumferential strain (CS) and longitudinal strain (LS) of LV were measured by cvi42 software, and the differences in CMR parameters between different groups and before and after treatment were compared.

Results
①The mean, basal and middle ECV value of HHD groups with different EF were all higher than that of the control group (P < 0.05), but the difference between HHD groups was not statistically significant. ②With the decrease of EF, the absolute value of both the global or local strain decreased. Strain is related to LVMI and ECV. ③In general, ECV, global RS (GRS) and global CS (GCS) improved after treatment, but the improvement of LS impairment in HHD patients is difficult.

Conclusions
ECV and myocardial strain parameters are more sensitive to myocardial abnormalities, and ECV, GRS and GCS are more sensitive to treatment. However it is difficult to improve longitudinal strain impairment in HHD patients. ECV and myocardial strain parameters can be used as good makers for long-term monitoring of the efficacy of HHD patients.
Adherence to statins and its impact on clinical outcomes: a retrospective population-based study in China
Authors: Zhao Boya , He Xiaoning , Wu Jing , Yan Shu 
Published: June 2020

Abstract
Background
While the benefit of adherence to statins on clinical outcomes has been proved, this benefit may be heterogeneous among patients who initiated statins for primary or secondary prevention purpose. This study aimed to investigate the impact of statin adherence on clinical outcomes among patients who initiated statins for primary and secondary prevention in China.

Methods
Adult patients in Tianjin Urban Employee Basic Medical Insurance database who initiated ≥2 prescriptions of statins from 2012 through 2013 were included and grouped into primary and secondary prevention subgroups according to their cardiovascular diseases (CVD) history during the prior 12-month baseline period. Proportion of days covered (PDC) was used to measure statin adherence in the initial 12-month follow-up. Clinical outcomes were measured by the incidence of major adverse cardiovascular events (MACE) during the 13th–24th months follow-up, and were compared between the patients with PDC ≥ 0.5 and patients with PDC < 0.5 using Cox regression models in primary and secondary prevention subgroups. Sensitivity analyses were conducted in propensity score matched groups.

Results
99,655 patients were finally included. The mean (SD) PDC was 0.19 (0.15) in primary prevention subgroup (N = 34,372), with 5.4% patients had PDC ≥ 0.5. The patients with PDC ≥ 0.5 had a 37% reduced risk of MACE compared with patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 1.1% vs. 1.4%; all-adjusted HR = 0.63; 95% CI, 0.41–0.98). While, no significant difference was observed in the secondary prevention subgroup (N = 65,283) between patients with PDC ≥ 0.5 and patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 4.6% vs. 2.8%; all-adjusted HR = 1.08, 95% CI, 0.92–1.28). These findings were confirmed by the sensitivity analyses in propensity score matched groups.

Conclusions
Statin adherence was very poor in China, and statin adherence is associated with decreased risk of MACE in patients for primary prevention, while further exploration is needed for secondary prevention.
Comparison of the effect of membrane sizes and fibre arrangements of two membrane oxygenators on the inflammatory response, oxygenation and decarboxylation in a rat model of extracorporeal membrane oxygenation
Authors: Edinger Fabian , Schneck Emmanuel , Schulte Charlotte , Gehron Johannes , Mueller Sabrina , Sander Michael , Koch Christian 
Published: June 2020

Abstract
Background
Extracorporeal membrane oxygenation (ECMO) has gained widespread acceptance for the treatment of critically ill patients suffering from cardiac and/or respiratory failure. Various animal models have been developed to investigate the adverse effects induced by ECMO. Different membrane oxygenators have been used with varying priming volumes and membrane surfaces (Micro-1, small animal membrane oxygenator (SAMO)).

Methods
Sixteen male Lewis rats (350–400 g) were randomly assigned to receive ECMO with Micro-1 or SAMO (n = 8, respectively). Venoarterial ECMO was established after cannulation of the femoral artery and the jugular vein. The cardiac output was measured using a left-ventricular conductance catheter. The oxygen fraction of the ECMO was set to 1.0, 0.75, 0.5 and 0.21 after a stabilisation period of 15 min. Further, arterial blood gas analyses were performed at baseline, and during the first hour every 15 min after commencing the ECMO, and subsequently every 30 min. Dilutional anaemia was calculated using haemoglobin concentration at baseline, and 15 min after the start of ECMO therapy. Moreover, inflammation was determined by measuring tumour necrosis factor alpha, interleukin-6 and -10 at baseline and every 30 min.

Results
Animals of the Micro-1 group showed a significantly lower dilutional anaemia (ΔHaemoglobin t0 – t0.25: SAMO 6.3 [5.6–7.5] g/dl vs. Micro-1 5.6 [4.6–5.8] g/dl; p = 0.028). Further, significantly higher oxygen partial pressure was measured in the SAMO group, at an oxygen fraction of 0.75, 0.5 and 0.21 (380 [356–388] vs. 314 [263–352] mmHg, p = 0.002; 267 [249–273] mmHg vs. 197 [140–222] mmHg, p = 0.002; 87 [82–106] mmHg vs. 76 [60–79] mmHg, p = 0.021, respectively). However, no differences were found regarding the oxygen fraction of 1.0, in terms of carbon-dioxide partial pressure and cardiac output. Moreover, in the Micro-1 group tumour necrosis factor alpha was increased after 60 min and interleukin-6 after 120 min.

Conclusion
While the dilutional anaemia was increased after commencing the ECMO, the oxygenation was augmented in the SAMO group. The inflammatory response was elevated in the Micro-1 group.
A novel framework for classification of selection processes in epidemiological research
Authors: Björk Jonas , Nilsson Anton , Bonander Carl , Strömberg Ulf 
Published: June 2020

Abstract
Background
Selection and selection bias are terms that lack consistent definitions and have varying meaning and usage across disciplines. There is also confusion in current definitions between underlying mechanisms that lead to selection and their consequences. Consequences of selection on study validity must be judged on a case-by-case basis depending on research question, study design and analytical decisions. The overall aim of the study was to develop a simple but general framework for classifying various types of selection processes of relevance for epidemiological research.

Methods
Several original articles from the epidemiological literature and from related areas of observational research were reviewed in search of examples of selection processes, used terminology and description of the underlying mechanisms.

Results
We classified the identified selection processes in three dimensions: i) selection level (selection at the population level vs. study-specific selection), ii) type of mechanism (selection in exposure vs. selection in population composition), iii) timing of the selection (at exposure entry, during exposure/follow-up or post-outcome).

Conclusions
Increased understanding of when, how, and why selection occur is an important step towards improved validity of epidemiological research.
Older adults’ preferences for, adherence to and experiences of two self-management falls prevention home exercise programmes: a comparison between a digital programme and a paper booklet
Authors: Mansson Linda , Lundin-Olsson Lillemor , Skelton Dawn A. , Janols Rebecka , Lindgren Helena , Rosendahl Erik , Sandlund Marlene 
Published: June 2020

Abstract
Background
Fall prevention exercise programmes are known to be effective, but access to these programmes is not always possible. The use of eHealth solutions might be a way forward to increase access and reach a wider population. In this feasibility study the aim was to explore the choice of programme, adherence, and self-reported experiences comparing two exercise programmes – a digital programme and a paper booklet.

Methods
A participant preference trial of two self-managed fall prevention exercise interventions. Community-dwelling adults aged 70 years and older exercised independently for four months after one introduction meeting. Baseline information was collected at study start, including a short introduction of the exercise programme, a short physical assessment, and completion of questionnaires. During the four months intervention period, participants self-reported their performed exercises in an exercise diary. At a final meeting, questionnaires about their experiences, and post-assessments, were completed. For adherence analyses data from diaries were used and four subgroups for different levels of participation were compared. Exercise maintenance was followed up with a survey 12 months after study start.

Results
Sixty-seven participants, with mean age 77 ± 4 years were included, 72% were women. Forty-three percent chose the digital programme. Attrition rate was 17% in the digital programme group and 37% in the paper booklet group (p = .078). In both groups 50–59% reported exercise at least 75% of the intervention period. The only significant difference for adherence was in the subgroup that completed ≥75% of exercise duration, the digital programme users exercised more minutes per week (p = .001). Participants in both groups were content with their programme but digital programme users reported a significantly higher (p = .026) degree of being content, and feeling supported by the programme (p = .044). At 12 months follow-up 67% of participants using the digital programme continued to exercise regularly compared with 35% for the paper booklet (p = .036).

Conclusions
Exercise interventions based on either a digital programme or a paper booklet can be used as a self-managed, independent fall prevention programme. There is a similar adherence in both programmes during a 4-month intervention, but the digital programme seems to facilitate long-term maintenance in regular exercise.

Trial registration
ClinTrial: NCT02916849.
The influence of exposure to Toxoplasma Gondii on host lipid metabolism
Authors: Xu Fei , Lu Xiwan , Cheng Ruitang , Zhu Yuwei , Miao Sunhan , Huang Qinyi , Xu Yongliang , Qiu Liying , Zhou Yonghua 
Published: June 2020

Abstract
Background
Mounting evidence suggested a complex correlation between host lipid metabolism and Toxoplasma gondii (T. gondii) infection. However, the inherent association between T. gondii infection and host lipid state remains elusive either in mice or in human hosts.

Methods
Through a study in a sample of 1045 healthy participants from eastern China, we determined the association of T. gondii infection and host lipid levels using serological methods. We then examined the host lipid levels in C57BL/6 J mice at both acute and chronic T. gondii infection stages (for a period up to 36 weeks post infection).

Results
In our case-control study, T. gondii seropositive individuals had higher low-density lipoproteins (LDL) (P = 0.0043) and total cholesterol (TC) (P = 0.0134) levels compared to seronegative individuals. Furthermore, individuals with LDL (OR = 3.25; 95% CI:1.60–6.61) and TC (OR = 2.10; 95% CI:1.22–3.63) levels above the upper limit of normal range had higher odds ratio to be T. gondii IgG positive. Consistently, in vivo data revealed that a significantly increased LDL level was first observed at early acute stage but plateaued to later time (chronic infection with T. gondii).

Conclusions
In both healthy population and T. gondii-infected mice, seropositive individuals had higher LDL level. Individuals with positive T. gondii IgG had more odds of being with LDL and TC abnormality. Latent T. gondii infection is common worldwide, potential medical interventions to host lipid metabolism may be a breakthrough point to the prevention and control of this parasite infection.
Application of 1H-MRS in end-stage renal disease with depression
Authors: Wang Jiachen , Zhou Tong , Liu Jihua , Shangguan Jingjun , Liu Xuejun , Li Zhiming , Zhou Xiaoming , Ren Yande , Wang Chengjian 
Published: June 2020

Abstract
Background
To investigate the metabolite changes in the frontal lobe of the end-stage renal disease (ESRD) patients with depression using proton magnetic resonance spectroscopy (1H-MRS).

Methods
All subjects were divided into three groups: ESRD patients with depression (30 cases), ESRD patients without depression (27 cases) and 32 normal subjects. ESRD with depression patients were further divided into two groups according to the severity of depression: 14 cases of ESRD with severe depression group (Hamilton Depression Rating Scale (HAMD) score ≥ 35) and 16 cases of ESRD with mild to moderate depression group (20 ≤ HAMD score<35). 1H-MRS was used in brain regions of all subjects to measure N-acetylaspartate/creatine (NAA/Cr), choline-containing compounds/creatine (Cho/Cr) and myo-inositol/creatine (MI/Cr) ratios of the frontal lobe. Correlations between the metabolite ratio and HAMD score as well as clinical finding were confirmed, respectively.

Results
ESRD patients with depression showed lower NAA/Cr ratio and higher Cho/Cr ratio compared with ESRD patients without depression and normal subjects. NAA/Cr ratio was negatively correlated with the HAMD score. Cho/Cr ratio was positively correlated with the HAMD score. There were positive correlations between NAA/Cr ratio and blood urea notrogen (BUN) as well as creatinine (CRE) concentration, respectively. There was a negative correlation between Cho/Cr ratio and sodium concentration. The Cho/Cr ratio was positively correlated with the potassium concentration.

Conclusions
MR spectroscopy identified some metabolite changes in ESRD patients with depression.