bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphodiesterases 2, 3 and 4 can decrease cardiac effects of H2-histamine-receptor activation in isolated atria of transgenic mice
Authors: Neumann Joachim , Voss Rafaela , Laufs Ulrich , Werner Christian , Gergs Ulrich 
Published: February 2021

AbstractHistamine exerts cAMP-dependent positive inotropic effects (PIE) and positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic mice which overexpress the human H2-receptor in the heart (=H2-TG). To determine whether these effects are antagonized by phosphodiesterases (PDEs), contractile studies were done in isolated left and right atrial preparations of H2-TG. The contractile effects of histamine were tested in the additional presence of the PDE-inhibitorserythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA, 1 μM, PDE2-inhibitor) or cilostamide (1 μM, PDE3-inhibitor), rolipram (10 μM, a PDE4-inhibitor), and their combinations. Cilostamide (1 μM) and EHNA (1 μM), rolipram (1 μM), and EHNA (1 μM) and the combination of rolipram (0.1 μM) and cilostamide (1 μM) each increased the potency of histamine to elevate the force of contraction (FOC) in H2-TG. Cilostamide (1 μM) and rolipram (10 μM) alone increased and EHNA (1 μM) decreased alone, and their combination increased the potency of histamine to increase the FOC in H2-TG indicating that PDE3 and PDE4 regulate the inotropic effects of histamine in H2-TG. The PDE inhibitors (EHNA, cilostamide, rolipram) alone did not alter the potency of histamine to increase the heart beat in H2-TG whereas a combination of rolipram, cilostamide, and EHNA, or of rolipram and EHNA increased the potency of histamine to act on the beating rate. In summary, the data suggest that the PCE of histamine in H2-TG atrium involves PDE 2 and 4 activities, whereas the PIE of histamine are diminished by activity of PDE 3 and 4.
Can Left Atrioventricular Valve Reduction Index (LAVRI) Predict the Surgical Strategy for Repair of Atrioventricular Septal Defect?
Authors: Schleiger Anastasia , Kramer Peter , Schafstedde Marie , Yigitbasi Mustafa , Danne Friederike , Murin Peter , Cho Mi-Young , Photiadis Joachim , Berger Felix , Ovroutski Stanislav 
Published: February 2021

AbstractDespite improved survival, surgical treatment of atrioventricular septal defect (AVSD) remains challenging. The optimal technique for primary left atrioventricular valve (LAVV) repair and prediction of suitability for biventricular approach in unbalanced AVSD are still controversial. We evaluated the ability of our recently developed echocardiographic left atrioventricular valve reduction index (LAVRI) in predicting LAVV reoperation rate and surgical strategy for unbalanced AVSD. Retrospective echocardiographic analysis was available in 352 of 790 patients with AVSD treated in our institution and included modified atrioventricular valve index (mAVVI), ventricular cavity ratio (VCR), and right ventricle/left ventricle (RV/LV) inflow angle. LAVRI estimates LAVV area after complete cleft closure and was analyzed with regard to surgical strategy in primary LAVV repair and unbalanced AVSD. Of the entire cohort, 284/352 (80.68%) patients underwent biventricular repair and 68/352 (19.31%) patients underwent univentricular palliation. LAVV reoperation was performed in 25/284 (8.80%) patients after surgical correction of AVSD. LAVRI was significantly lower in patients requiring LAVV reoperation (1.92 cm2/m2 [IQR 1.31] vs. 2.89 cm2/m2 [IQR 1.37], p = 0.002) and significantly differed between patients receiving complete and no/partial cleft closure (2.89 cm2/m2 [IQR 1.35] vs. 2.07 cm2/m2 [IQR 1.69]; p = 0.002). Of 82 patients diagnosed with unbalanced AVSD, 14 were suitable for biventricular repair (17.07%). mAVVI, LAVRI, VCR, and RV/LV inflow angle accurately distinguished between balanced and unbalanced AVSD and predicted surgical strategy (all p < 0.001). LAVRI may predict surgical strategy in primary LAVV repair, LAVV reoperation risk, and suitability for biventricular approach in unbalanced AVSD anatomy.
Host defence peptides identified in human apolipoprotein B as promising antifungal agents
Authors: Dell’Olmo Eliana , Gaglione Rosa , Cesaro Angela , Cafaro Valeria , Teertstra Wieke R. , de Cock Hans , Notomista Eugenio , Haagsman Henk P. , Veldhuizen Edwin J. A. , Arciello Angela 
Published: February 2021

Abstract
Therapeutic options to treat invasive fungal infections are still limited. This makes the development of novel antifungal agents highly desirable. Naturally occurring antifungal peptides represent valid candidates, since they are not harmful for human cells and are endowed with a wide range of activities and their mechanism of action is different from that of conventional antifungal drugs. Here, we characterized for the first time the antifungal properties of novel peptides identified in human apolipoprotein B. ApoB-derived peptides, here named r(P)ApoBLPro, r(P)ApoBLAla and r(P)ApoBSPro, were found to have significant fungicidal activity towards Candida albicans (C. albicans) cells. Peptides were also found to be able to slow down metabolic activity of Aspergillus niger (A. niger) spores. In addition, experiments were carried out to clarify the mechanism of fungicidal activity of ApoB-derived peptides. Peptides immediately interacted with C. albicans cell surfaces, as indicated by fluorescence live cell imaging analyses, and induced severe membrane damage, as indicated by propidium iodide uptake induced upon treatment of C. albicans cells with ApoB-derived peptides. ApoB-derived peptides were also tested on A. niger swollen spores, initial hyphae and branched mycelium. The effects of peptides were found to be more severe on swollen spores and initial hyphae compared to mycelium. Fluorescence live cell imaging analyses confirmed peptide internalization into swollen spores with a consequent accumulation into hyphae. Altogether, these findings open interesting perspectives to the application of ApoB-derived peptides as effective antifungal agents.

Key points

Human cryptides identified in ApoB are effective antifungal agents.

ApoB-derived cryptides exert fungicidal effects towards C. albicans cells.

ApoB-derived cryptides affect different stages of growth of A. niger.

Graphical abstract
PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung
Authors: Goldmann Torsten , Marwitz Sebastian , Nitschkowski Dörte , Krupar Rosemarie , Backman Max , Elfving Hedvig , Thurfjell Viktoria , Lindberg Amanda , Brunnström Hans , La Fleur Linnea , Mezheyeuski Artur , Mattsson Johanna Sofia Margareta , Botling Johan , Micke Patrick , Strell Carina 
Published: February 2021

AbstractGene amplification is considered to be one responsible cause for upregulation of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) and to represent a specific molecular subgroup possibly associated with immunotherapy response. Our aim was to analyze the frequency of PD-L1 amplification, its relation to PD-L1 mRNA and protein expression, and to characterize the immune microenvironment of amplified cases. The study was based on two independent NSCLC cohorts, including 354 and 349 cases, respectively. Tissue microarrays were used to evaluate PD-L1 amplification by FISH and PD-L1 protein by immunohistochemistry. Immune infiltrates were characterized immunohistochemically by a panel of immune markers (CD3, CD4, CD8, PD-1, Foxp3, CD20, CD138, CD168, CD45RO, NKp46). Mutational status was determined by targeted sequencing. RNAseq data was available for 197 patients. PD-L1 amplification was detected in 4.5% of all evaluable cases. PD-L1 amplification correlated only weakly with mRNA and protein expression. About 37% of amplified cases were negative for PD-L1 protein. PD-L1 amplification did not show any association with the mutational status. In squamous cell cancer, PD-L1 amplified cases were enriched among patients with high tumoral immune cell infiltration and showed gene expression profiles related to immune exhaustion. In conclusion, PD-L1 amplification correlates with PD-L1 expression in squamous cell cancer and was associated with an immune cell rich tumor phenotype. The correlative findings help to understand the role of PD-L1 amplification as an important immune escape mechanism in NSCLC and suggest the need to further evaluate PD-L1 amplification as predictive biomarker for checkpoint inhibitor therapy.
Regulatory T cells promote glioma cell stemness through TGF-β–NF-κB–IL6–STAT3 signaling
Authors: Liu Shasha , Zhang Chaoqi , Wang Boqiao , Zhang Huanyu , Qin Guohui , Li Congcong , Cao Ling , Gao Qun , Ping Yu , Zhang Kai , Lian Jingyao , Zhao Qitai , Wang Dan , Zhang Zhen , Zhao Xuan , Yang Li , Huang Lan , Yang Bo , Zhang Yi 
Published: February 2021

AbstractGlioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and tumor microenvironment. Here, we found that intense infiltration of regulatory T cells (Tregs) facilitated the qualities of GSCs through TGF-β secretion that helped coordinately tumor growth. Mechanistic investigations indicated that TGF-β acted on cancer cells to induce the core cancer stem cell-related genes CD133, SOX2, NESTIN, MUSASHI1 and ALDH1A expression and spheres formation via NF-κB–IL6–STAT3 signaling pathway, resulting in the increased cancer stemness and tumorigenic potential. Furthermore, Tregs promoted glioma tumor growth, and this effect could be abrogated with blockade of IL6 receptor by tocilizumab which also demonstrated certain level of therapeutic efficacy in xenograft model. Additionally, expression levels of CD133, IL6 and TGF-β were found to serve as prognosis markers of glioma patients. Collectively, our findings reveal a new immune-associated mechanism underlying Tregs-induced GSCs. Moreover, efforts to target this network may be an effective strategy for treating glioma.
Konstruktion, Intuition: algorithmisch
Authors: Nake Frieder 
Published: February 2021

ZusammenfassungKonstruktion ist der starke Pfeiler aller Ingenieursarbeit, so auch der Arbeit des Programmierens. Konstruktives Handeln zieht jedoch explizit auch in Textgestaltung und Bildende Kunst des 20. Jahrhunderts ein. Intuition ist das Finden ohne Suchen, das künstlerisches Schaffen oft auszuzeichnen scheint. Sie steht aber gewiss auch bei manchem Programmiertrick Pate. Mit dem für informatisches Tun zentralen algorithmischen Denken werfen wir einen Blick zurück auf den Beginn ästhetischer Experimente mit Rechenmaschinen Ende der 1950er und Anfang der 1960er Jahre.
On L-Close Sperner Systems
Authors: Nagy Dániel T. , Patkós Balázs 
Published: February 2021

AbstractFor a set L of positive integers, a set system $${\mathcal F}\subseteq 2^{[n]}$$

F
⊆

2

[
n
]

is said to be L-close Sperner, if for any pair F, G of distinct sets in $${\mathcal F}$$
F
the skew distance $$sd(F,G)=\min \{|F\setminus G|,|G\setminus F|\}$$

s
d
(
F
,
G
)
=
min
{
|
F
\
G
|
,
|
G
\
F
|
}

belongs to L. We reprove an extremal result of Boros, Gurvich, and Milanič on the maximum size of L-close Sperner set systems for $$L=\{1\}$$

L
=
{
1
}

, generalize it to $$|L|=1$$

|
L
|
=
1

, and obtain slightly weaker bounds for arbitrary L. We also consider the problem when L might include 0 and reprove a theorem of Frankl, Füredi, and Pach on the size of largest set systems with all skew distances belonging to $$L=\{0,1\}$$

L
=
{
0
,
1
}

.
Effect of high intake of cod or salmon on serum total neopterin concentration: a randomised clinical trial
Authors: Helland Anita , Bratlie Marianne , Hagen Ingrid V. , Midttun Øivind , Sveier Harald , Mellgren Gunnar , Ueland Per Magne , Gudbrandsen Oddrun A. 
Published: February 2021

Abstract
Purpose
Primarily, to investigate the effect of high intake of cod (lean fish) or salmon (fatty fish) on serum concentration of total neopterin, a marker of cellular immune activation that is associated with cardiovascular disease. Second, to investigate effects of high cod/salmon intake on antioxidant vitamins and elements essential for activity of antioxidant enzymes.

Methods
In this randomised clinical trial, 63 participants with overweight/obesity consumed 750 g/week of either Atlantic cod (N = 22) or Atlantic salmon (N = 22) or were instructed to continue their normal eating habits but avoid fish intake (Control group, N = 19) for 8 weeks. Food intake was recorded, and fasting serum were collected at baseline and endpoint.

Results
Serum total neopterin concentration was reduced in the Cod group (median change − 2.65 (25th, 75th percentiles − 3.68, − 0.45) nmol/l, P = 0.018) but not in the Salmon group (median change 0.00 (25th, 75th percentiles − 4.15, 3.05) nmol/l, P = 0.59) when compared with the Control group after 8 weeks. The estimated daily intake of selenium, iron, magnesium and zinc were similar between all groups. Increased serum concentration of selenium was observed only after cod intake when compared to the Control group (P = 0.017). Changes in serum concentrations of copper, iron, magnesium, all-trans retinol, α-tocopherol and γ-tocopherol were similar between the groups.

Conclusion
A high intake of cod, but not of salmon, lowered serum total neopterin concentration when compared to the Control group.

Clinical trial registration
This trial was registered at clinicaltrials.gov as NCT02350595
Neighbourhood deprivation and obesity among 5656 pre-school children—findings from mandatory school enrollment examinations
Authors: Nguyen Thuy Ha , Götz Simon , Kreffter Katharina , Lisak-Wahl Stefanie , Dragano Nico , Weyers Simone 
Published: February 2021

AbstractThe risk of child obesity is strongly related to socioeconomic factors such as individual socioeconomic position (SEP) and neighbourhood deprivation. The present study analyses whether the relationship between neighbourhood deprivation and child obesity differs by child’s individual SEP. Data from 5656 children (5–7 years) from the mandatory school enrollment examinations of the pre-school cohorts 2017/2018 in Düsseldorf were analysed. Obesity was determined by the age- and gender-specific body mass index (BMI); neighbourhood deprivation by using the socio-spatial degree of deprivation of the children’s residential addresses; and individual SEP by the level of parental education. Using Poisson regression, we estimated prevalence ratios (PR with 95% confidence interval (CI)) of child obesity by neighbourhood deprivation and parental education. Interactions between neighbourhood deprivation and parental education were tested. The prevalence of child obesity increases with the degree of neighbourhood deprivation. Compared to children living in low deprivation neighbourhoods, the proportion of obese children was twice as high in high deprivation neighbourhoods (PR=2.02; CI=1.46–2.78). Likewise, children from families with medium and low education have twice the risk for obesity compared to children with high parental education (PR=2.05; CI=1.46–2.78). The relationship between neighbourhood deprivation and child obesity was significantly moderated by parental education; it was stronger for higher parental education than for medium and low parental education (p<.001).Conclusion: Our findings suggest that children from deprived neighbourhoods and families with lower education have a higher risk for child obesity. The identification of particularly deprived neighbourhoods with structural interventions in combination with the strengthening of parental health literacy seems reasonable.

What is Known:• Studies show that children from disadvantaged neighbourhoods are more frequently obese.

What is New:• The relationship between neighbourhood deprivation and child obesity is significantly moderated by parental education. It is stronger for children with higher parental education than for children with medium and low parental education.
Total flavonoids of Radix Tetrastigma suppress inflammation-related hepatocellular carcinoma cell metastasis
Authors: Liu Zhendong , Ding Fangmi , Shen Xingyong 
Published: February 2021

AbstractThis study aimed to investigate the effects of the total flavonoids of Radix Tetrastigma (RTF) on inflammation-related hepatocellular carcinoma (HCC) development. Extracted RTF was diluted to different concentrations for subsequent experiments. HCC cells were cotreated with lipopolysaccharide (LPS) and RTF to investigate the effects of RTF on LPS-stimulated HCC cells. A CCK-8 kit was used to measure cell proliferation. Apoptosis was detected with a flow cytometer. Cell migration and invasion were quantified by wound healing and Transwell assays, respectively. The expression of TLR4 and COX-2 and activation of the NF-κB pathway were determined by Western blotting. Treatment with LPS significantly enhanced cell proliferation and decreased the apoptosis rate, while cell migration and invasion were notably upregulated. RTF suppressed the proliferation and invasion induced by LPS stimulation and promoted HCC cell apoptosis. The protein levels of Bax and cleaved caspase-3 were decreased and that of Bcl-2 was increased by LPS in HCC cells, which could be rescued by RTF. RTF significantly inhibited the LPS-induced expression of the proinflammatory mediators IL-6 and IL-8 in HCC cells. Mechanistically, with RTF treatment, the upregulated expression of TLR4 and COX-2 induced by LPS was obviously downregulated. Furthermore, the phosphorylation of NF-κB/p65 was significantly decreased in LPS-stimulated cells after supplementation with RTF. Our study suggests that RTF exerts a significant inhibitory effect on the LPS-induced enhancement of the malignant behaviors of HCC cells via inactivation of TLR4/NF-κB signaling. RTF may be a promising chemotherapeutic agent to limit HCC development and inflammation-mediated metastasis.
Differential assessment of fluid compartments by bioimpedance in pediatric patients with kidney diseases
Authors: Frey Sandra M. , Vogt Bruno , Simonetti Giacomo D. , Büscher Rainer , Habbig Sandra , Schaefer Franz 
Published: February 2021

Abstract
Background
The kidney is central for maintaining water balance. As a corollary, patients with impaired kidney function are prone to pathological fluid volumes. Total body water (TBW) is distributed between the extracellular (ECW) and intracellular fluid compartments (ICW). In clinical practice, the judgment of hydration status does not allow to distinguish between ECW and ICW. Here, we evaluate the hydration status in children with chronic kidney disease by analyzing TBW, ECW, and ICW.

Methods
Hydration was quantified using whole-body bioimpedance spectroscopy (BCM) in 128 outpatients (1–25 years, 52 girls). Forty-two were transplanted (TPL), 43 suffered from chronic kidney disease without kidney replacement therapy (CKD), 21 were on peritoneal dialysis (PD), and 22 on hemodialysis (HD). HD patients were investigated before, after, and sequentially during dialysis.

Results
The ECW and ICW values obtained by BCM were of the same magnitude as those from the literature using isotope dilution. When compared with a healthy control group, TBW was increased in 9 TPL, 9 CKD, 1 PD, and 11 HD patients before but in none after dialysis. The decline of overhydration during dialysis (p < 0.001, n = 22) correlated with the change in body weight (R2 = 0.62). The kinetics of fluid compartment changes assessed twice in six HD patients revealed a reproducible linear decay of the ECW/ICW ratio due to an increase of ICW and a decrease of ECW.

Conclusion
BCM quantifies TBW and acute changes of ECW and ICW in children with chronic kidney failure. The clinical utility of measuring TBW, ECW, and ICW should be defined in the future.
The Dirichlet problem for the Jacobian equation in critical and supercritical Sobolev spaces
Authors: Guerra André , Koch Lukas , Lindberg Sauli 
Published: February 2021

AbstractWe study existence and regularity of solutions to the Dirichlet problem for the prescribed Jacobian equation,$$\det D u =f$$detDu=f, wherefis integrable and bounded away from zero. In particular, we take$$f\in L^p$$f∈Lp, where$$p>1$$p>1, or in$$L\log L$$LlogL. We prove that for a Baire-genericfin either space there are no solutions with the expected regularity.
Assessment of crop risk due to climate change in Sao Tome and Principe
Authors: Costa Resende Ferreira Nicole , Martins Minella , da Silva Tavares Priscila , Chan Chou Sin , Monteiro Armando , Gomes Ludmila , Santana Adérito 
Published: February 2021

AbstractSao Tome and Principe is a small insular country in the west coast of Central Africa. The small dimensions of the islands and the limited natural resources put these islands under highly vulnerable to climate change. To assess the possible future impacts and risks on their agricultural activities, the high-resolution 4-km downscaled climate change projections using Eta regional climate model are used. A crop risk index (CRI) is proposed to assess the risk of climate change on cocoa (Theobroma cacaoL.), pepper (Piper nigrumL. andPiper guinesseL.), taro (Colocasia esculenta(L.) Schott), and maize (Zea maysL.). The index takes into account the vulnerability to climate conditions and the crop yield in the future, and it is classified intovery-high,high,moderate,low, andvery-low. The climate change projections indicate increase in the risk of taro crop, partly due to thermal stress and partly due to the susceptibility to the leaf blight crop disease in taro. The risk of production of the pepper crop is very-high, mainly due to water stress. In mountain regions, the greater risk is due to the thermal stress caused by low temperatures. The cocoa crop is at risk due to water stress, mainly in the northwestern part of the Sao Tome Island, where major local production occurs. The projection indicates increase of the area with very-high risk to maize crops due to the increase of thermal stress and susceptibility to rust. In addition, in parts of the coastal regions, the risk changed from very-low to high risk, due to the low productivity potential. In general, the risks of the four major crops of Sao Tome and Principe increase in the future climate conditions.
Training Image Free High-Order Stochastic Simulation Based on Aggregated Kernel Statistics
Authors: Yao Lingqing , Dimitrakopoulos Roussos , Gamache Michel 
Published: February 2021

AbstractA training image free, high-order sequential simulation method is proposed herein, which is based on the efficient inference of high-order spatial statistics from the available sample data. A statistical learning framework in kernel space is adopted to develop the proposed simulation method. Specifically, a new concept of aggregated kernel statistics is proposed to enable sparse data learning. The conditioning data in the proposed high-order sequential simulation method appear as data events corresponding to the attribute values associated with the so-called spatial templates of various geometric configurations. The replicates of the data events act as the training data in the learning framework for inference of the conditional probability distribution and generation of simulated values. These replicates are mapped into spatial Legendre moment kernel spaces, and the kernel statistics are computed thereafter, encapsulating the high-order spatial statistics from the available data. To utilize the incomplete information from the replicates, which partially match the spatial template of a given data event, the aggregated kernel statistics combine the ensemble of the elements in different kernel subspaces for statistical inference, embedding the high-order spatial statistics of the replicates associated with various spatial templates into the same kernel subspace. The aggregated kernel statistics are incorporated into a learning algorithm to obtain the target probability distribution in the underlying random field, while preserving in the simulations the high-order spatial statistics from the available data. The proposed method is tested using a synthetic dataset, showing the reproduction of the high-order spatial statistics of the sample data. The comparison with the corresponding high-order simulation method using TIs emphasizes the generalization capacity of the proposed method for sparse data learning.