bluuebunny/crossref_metadata_2025_split huggingface dataset:
On broad Kaluza-Klein gluons
Authors: Escribano Rafel , Mendizabal Mikel , Quirós Mariano , Royo Emilio 
Published: May 2021

Abstract
In theories with a warped extra dimension, composite fermions, as e.g. the right-handed top quark, can be very strongly coupled to Kaluza-Klein (KK) fields. In particular, the KK gluons in the presence of such composite fields become very broad resonances, thus remarkably modifying their experimental signatures. We have computed the pole mass and the pole width of the KK gluon, triggered by its interaction with quarks, as well as the prediction for proton-proton cross-sections using the full propagator and compared it with that obtained from the usual Breit-Wigner approximation. We compare both approaches, along with the existing experimental data from ATLAS and CMS, for the $$ t\overline{t} $$
t

t
¯

, $$ t\overline{t}W $$
t

t
¯

W
, $$ t\overline{t}Z $$
t

t
¯

Z
, $$ t\overline{t}H $$
t

t
¯

H
, and $$ tt\overline{tt} $$
tt

tt
¯

channels. We have found differences between the two approaches of up to about 100%, highlighting that the effect of broad resonances can be dramatic on present, and mainly future, experimental searches. The channel $$ tt\overline{tt} $$
tt

tt
¯

is particularly promising because the size of the cross-section signal is of the same order of magnitude as the Standard Model prediction, and future experimental analyses in this channel, especially for broad resonances, can shed light on the nature of possible physics beyond the Standard Model.
New insights into the functional role of retrotransposon dynamics in mammalian somatic cells
Authors: Mangiavacchi Arianna , Liu Peng , Della Valle Francesco , Orlando Valerio 
Published: May 2021

Abstract
Retrotransposons are genetic elements present across all eukaryotic genomes. While their role in evolution is considered as a potentially beneficial natural source of genetic variation, their activity is classically considered detrimental due to their potentially harmful effects on genome stability. However, studies are increasingly shedding light on the regulatory function and beneficial role of somatic retroelement reactivation in non-pathological contexts. Here, we review recent findings unveiling the regulatory potential of retrotransposons, including their role in noncoding RNA transcription, as modulators of mammalian transcriptional and epigenome landscapes. We also discuss technical challenges in deciphering the multifaceted activity of retrotransposable elements, highlighting an unforeseen central role of this neglected portion of the genome both in early development and in adult life.
Adiponectin receptor agonist AdipoRon ameliorates renal inflammation in diet-induced obese mice and endotoxin-treated human glomeruli ex vivo
Authors: Lindfors Sonja , Polianskyte-Prause Zydrune , Bouslama Rim , Lehtonen Eero , Mannerla Miia , Nisen Harry , Tienari Jukka , Salmenkari Hanne , Forsgård Richard , Mirtti Tuomas , Lehto Markku , Groop Per-Henrik , Lehtonen Sanna 
Published: May 2021

Abstract
Aims/hypothesis
Chronic low-grade inflammation with local upregulation of proinflammatory molecules plays a role in the progression of obesity-related renal injury. Reduced serum concentration of anti-inflammatory adiponectin may promote chronic inflammation. Here, we investigated the potential anti-inflammatory and renoprotective effects and mechanisms of action of AdipoRon, an adiponectin receptor agonist.

Methods
Wild-type DBA/2J mice were fed with high-fat diet (HFD) supplemented or not with AdipoRon to model obesity-induced metabolic endotoxaemia and chronic low-grade inflammation and we assessed changes in the glomerular morphology and expression of proinflammatory markers. We also treated human glomeruli ex vivo and human podocytes in vitro with AdipoRon and bacterial lipopolysaccharide (LPS), an endotoxin upregulated in obesity and diabetes, and analysed the secretion of inflammatory cytokines, activation of inflammatory signal transduction pathways, apoptosis and migration.

Results
In HFD-fed mice, AdipoRon attenuated renal inflammation, as demonstrated by reduced expression of glomerular activated NF-κB p65 subunit (NF-κB-p65) (70%, p < 0.001), TNFα (48%, p < 0.01), IL-1β (51%, p < 0.001) and TGFβ (46%, p < 0.001), renal IL-6 and IL-4 (21% and 20%, p < 0.05), and lowered glomerular F4/80-positive macrophage infiltration (31%, p < 0.001). In addition, AdipoRon ameliorated HFD-induced glomerular hypertrophy (12%, p < 0.001), fibronectin accumulation (50%, p < 0.01) and podocyte loss (12%, p < 0.001), and reduced podocyte foot process effacement (15%, p < 0.001) and thickening of the glomerular basement membrane (18%, p < 0.001). In cultured podocytes, AdipoRon attenuated the LPS-induced activation of the central inflammatory signalling pathways NF-κB-p65, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38-MAPK) (30%, 36% and 22%, respectively, p < 0.001), reduced the secretion of TNFα (32%, p < 0.01), and protected against podocyte apoptosis and migration. In human glomeruli ex vivo, AdipoRon reduced the LPS-induced secretion of inflammatory cytokines IL-1β, IL-18, IL-6 and IL-10.

Conclusions/interpretation
AdipoRon attenuated the renal expression of proinflammatory cytokines in HFD-fed mice and LPS-stimulated human glomeruli, which apparently contributed to the amelioration of glomerular inflammation and injury. Mechanistically, based on assays on cultured podocytes, AdipoRon reduced LPS-induced activation of the NF-κB-p65, JNK and p38-MAPK pathways, thereby impelling the decrease in apoptosis, migration and secretion of TNFα. We conclude that the activation of the adiponectin receptor by AdipoRon is a potent strategy to attenuate endotoxaemia-associated renal inflammation.

Graphical abstract
The effect of age, sex and a firm-textured surface on postural control
Authors: Palazzo Francesco , Nardi Alessandra , Lamouchideli Niloofar , Caronti Alfio , Alashram Anas , Padua Elvira , Annino Giuseppe 
Published: May 2021

AbstractIn previous studies, the influence of plantar sensation has been examined using various textured surfaces with different stiffness materials to assess static balance. This study investigated the effects of a Firm Textured Surface (FTS) along with age and sex-related influences on postural control under different visual conditions. Forty subjects (20 elderly, 10 males, mean age 68.30, 10 females, mean age 68.00, and 20 young people, 10 males, mean age 25.45, 10 females, mean age 27.30) participated in this study maintained a quiet standing on FTS, foam and firm surfaces with eyes open and closed. The center of pressure displacement (CoPDISP), CoP velocity (CoPVEL), and sway velocity of the CoP in anteroposterior (AP) and mediolateral (ML) direction (VA/P and VM/L) were measured. FTS was associated with lower postural sway measures in both the groups with eyes open and closed. However, the foam surface showed the worst results in all postural parameters under all experimental conditions. Separate four-way ANOVAs were applied to each dependent variable. The main effects of surface (p < 0.0001), vision (p < 0.0001) and age (p < 0.0001 for CoPDISP, CoPVEL and VA/P; p = 0.0003 for VM/L) were significant in each of the four fitted models. Sex was never significant, either as a main effect or an interaction with other experimental factors. Eyes open were able to reduce the negative effects of the foam surfaces but without vision the proprioceptive sensory system cues of the body state become more important for maintaining balance. A good stimulation with rigid texture should be considered as relief to reduce the physiological-related decline of afferent information with age.
An ADH toolbox for raspberry ketone production from natural resources via a biocatalytic cascade
Authors: Becker Aileen , Böttcher Dominique , Katzer Werner , Siems Karsten , Müller-Kuhrt Lutz , Bornscheuer Uwe T. 
Published: May 2021

Abstract
Raspberry ketone is a widely used flavor compound in food and cosmetic industry. Several processes for its biocatalytic production have already been described, but either with the use of genetically modified organisms (GMOs) or incomplete conversion of the variety of precursors that are available in nature. Such natural precursors are rhododendrol glycosides with different proportions of (R)- and (S)-rhododendrol depending on the origin. After hydrolysis of these rhododendrol glycosides, the formed rhododendrol enantiomers have to be oxidized to obtain the final product raspberry ketone. To be able to achieve a high conversion with different starting material, we assembled an alcohol dehydrogenase toolbox that can be accessed depending on the optical purity of the intermediate rhododendrol. This is demonstrated by converting racemic rhododendrol using a combination of (R)- and (S)-selective alcohol dehydrogenases together with a universal cofactor recycling system. Furthermore, we conducted a biocatalytic cascade reaction starting from naturally derived rhododendrol glycosides by the use of a glucosidase and an alcohol dehydrogenase to produce raspberry ketone in high yield.

Key points
• LB-ADH, LK-ADH and LS-ADH oxidize (R)-rhododendrol
• RR-ADH and ADH1E oxidize (S)-rhododendrol
• Raspberry ketone production via glucosidase and alcohol dehydrogenases from a toolbox

Graphical abstract
Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients
Authors: Ma Jing , Ai Xiaofei , Wang Jinhuan , Xing Limin , Tian Chen , Yang Hongliang , Yu Yong , Zhao Haifeng , Wang Xiaofang , Zhao Zhigang , Wang Yafei , Cao Zeng 
Published: May 2021

AbstractChromosomal abnormalities play an important role in classification and prognostication of myelodysplastic syndrome (MDS) patients. However, more than 50% of low-risk MDS patients harbor a normal karyotype. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MDS patients. To characterize the subset of MDS with normal karyotype or failed chromosome banding analysis, we analyzed 144 patient samples with normal karyotype or undetectable through regular chromosome banding analysis, which were subjected to parallel comparison via fluorescence in situ hybridization (FISH) and MLPA. MLPA identifies copy number changes in 16.7% of 144 MDS patients, and we observed a significant difference in overall survival (OS) (median OS: undefined vs 27 months, p=0.0071) in patients with normal karyotype proved by MLPA versus aberrant karyotype cohort as determined by MLPA. Interestingly, patients with undetectable karyotype via regular chromosome banding indicated inferior outcome. Collectively, MDS patients with normal or undetectable karyotype via chromosome banding analysis can be further clarified by MLPA, providing more prognostic information that benefit for individualized therapy.
Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer
Authors: Rönnau C. G. H. , Fussek S. , Smit F. P. , Aalders T. W. , van Hooij O. , Pinto P. M. C. , Burchardt M. , Schalken J. A. , Verhaegh G. W. 
Published: May 2021

Abstract
Purpose
Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role.

Methods
In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion.

Results
In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (− 4.5-fold; p = 0.0009), miR-92b (− 3.1 fold; p < 0.0001) were downregulated and miR-3195 (5.6-fold; p < 0.0001), miR-3687 (8.7-fold; p = 0.0006) and miR-4417 (5.0-fold; p = 0.0005) were most upregulated. While KLK3, miR-21 and miR-141 expression levels in androgen-treated VCaP and LNCaP cells were increased, the expression levels of miR-3687 and miR-4417 were reduced. None of the miRNAs were androgen-regulated in the AR-negative PC3 cell line. Overexpression of miR-3687 reduced cell migration and cell invasion, whilst miR-3195 enhanced cell migration.

Conclusion
We have identified several novel deregulated miRNAs in CRPC tissue, including two microRNAs that are potentially involved in tumor invasion. Our data support the hypothesized involvement of miRNAs in PCa tumorigenesis and progression to CRPC. The applicability of these miRNAs as novel biomarkers for CRPC remains to be further investigated.
The value of serum amylase and drain fluid amylase to predict postoperative pancreatic fistula after pancreatoduodenectomy: a retrospective cohort study
Authors: van Dongen Jelle C. , Merkens Steven , Aziz M. Hossein , Groot Koerkamp Bas , van Eijck Casper H. J. 
Published: May 2021

Abstract
Purpose
Serum and drain amylase have been identified as important predictors of postoperative pancreatic fistula (POPF) and might be useful to guide postoperative drain management after pancreatoduodenectomy. We aimed to determine and compare the value of serum amylase and drain fluid amylase to predict postoperative pancreatic fistula after pancreatoduodenectomy.

Methods
This retrospective cohort study included patients after pancreatoduodenectomy from 2012 to 2019. The primary endpoint of our study was grade B/C POPF. Serum amylase on postoperative day 1 (SA-1) and drain fluid amylase on postoperative day 2 (DFA-2) were analyzed.

Results
A total of 92 of 437 patients (21.1%) developed a grade B/C POPF. SA-1 was higher in patients who developed a grade B/C POPF (336 U/L vs. 97 U/L, p<0.001). Similarly, DFA-2 was higher in patients who developed a grade B/C POPF (1764 U/L vs. 78 U/L, p<0.001). SA-1 and DFA-2 had similar predictive accuracy (AUC: 0.82 vs. 0.85, respectively, p=0.329). Patients with SA-1<100 U/L (n=178) had a risk of 2.2% of developing grade B/C POPF, compared to 38.2% in patients with SA-1 >100 U/L (n=207). Patients with DFA-2<100 U/L (n=141) had a risk of 0% of developing grade B/C POPF, compared to 36.2% in patients with DFA-2>100 U/L (n=196). SA-1 and DFA-2 were strongly associated at a cut-off of 100 U/L (p<0.001, 89% concordance rate).

Conclusion
Postoperative serum and drain amylase values below 100 U/L both effectively rule out POPF after pancreatoduodenectomy. The advantage of serum amylase measurement is that it can be used in patients who are managed without surgical drains.
A mesh-independent framework for crack tracking in elastodamaging materials through the regularized extended finite element method
Authors: Benvenuti Elena , Orlando Nicola 
Published: May 2021

AbstractWe propose a formulation for tracking general crack paths in elastodamaging materials without mesh adaptivity and broadening of the damage band. The idea is to treat in a unified way both the damaging process and the development of displacement discontinuities by means of the regularized finite element method. With respect to previous authors’ contributions, a novel damage evolution law and an original crack tracking framework are proposed. We face the issue of mesh objectivity through several two-dimensional tests, obtaining smooth crack paths and reliable structural results.
Palliative care for children and young people with stage 5 chronic kidney disease
Authors: Craig Finella , Henderson Ellen M. , Patel Bhumik , Murtagh Fliss E. M. , Bluebond-Langner Myra 
Published: May 2021

AbstractDeath from stage 5 chronic kidney disease (CKD 5) in childhood or adolescence is rare, but something that all paediatric renal physicians and most paediatricians will encounter. In this paper, we present the literature on three key areas of palliative care practice essential to good clinical management: shared decision-making, advance care planning, and symptom management, with particular reference to CKD 5 where kidney transplant is not an option and where a decision has been made to withdraw or withhold dialysis. Some areas of care, particularly with regard to symptom management, have not been well-studied in children and young people (CYP) with CKD 5 and recommendations with regard to drug choice and dose modification are based on adult literature, known pharmacokinetics, and clinical experience.
Pegfilgrastim for primary prophylaxis of febrile neutropenia in multiple myeloma
Authors: Cerchione Claudio , Nappi Davide , Martinelli Giovanni 
Published: May 2021

AbstractMultiple myeloma (MM) survival rates have been substantially increased thanks to novel agents that have improved survival outcomes and shown better tolerability than treatments of earlier years. These new agents include immunomodulating imide drugs (IMiD) thalidomide and lenalidomide, the proteasome inhibitor bortezomib (PI), recently followed by new generation IMID pomalidomide, monoclonal antibodies daratumumab and elotuzumab, and next generation PI carfilzomib and ixazomib. However, even in this more promising scenario, febrile neutropenia remains a severe side effect of antineoplastic therapies and can lead to a delay and/or dose reduction in subsequent cycles. Supportive care has thus become key in helping patients to obtain the maximum benefit from novel agents. Filgrastim is a human recombinant subcutaneous preparation of G-CSF, largely adopted in hematological supportive care as “on demand” (or secondary) prophylaxis to recovery from neutropenia and its infectious consequences during anti-myeloma treatment. On the contrary, pegfilgrastim is a pegylated long-acting recombinant form of granulocyte colony-stimulating factor (G-CSF) that, given its extended half-life, can be particularly useful when adopted as “primary prophylaxis,” therefore before the onset of neutropenia, along chemotherapy treatment in multiple myeloma patients. There is no direct comparison between the two G-CSF delivery modalities. In this review, we compare data on the two administrations’ modality, highlighting the efficacy of the secondary prophylaxis over multiple myeloma treatment. Advantage of pegfilgrastim could be as follows: the fixed administration rather than multiple injections, reduction in neutropenia and febrile neutropenia rates, and, finally, a cost-effectiveness advantage.
Hydrogen electrosorption properties of electrodeposited Pd-Ir alloys
Authors: Hubkowska K. , Pająk M. , Czerwiński A. 
Published: May 2021

AbstractThe study of the hydrogen sorption process in metals/alloys of different forms is crucial for developing the fields of catalysis and energy storage. The objective of this research was to examine basic hydrogen electrosorption properties of Pd-Ir alloy thin films obtained through electrodeposition. Pd-Ir alloys, containing more than 87% at. Pd, were successfully potentiostatically electrodeposited from aqueous baths containing PdCl2 and IrCl3. X-ray diffractometry confirmed the Pd-Ir alloy formation and homogeneity of the deposits. The hydrogen electrochemical absorption was carried out with the use of cyclic voltammetry and chronoamperometry. The values of H/(Pd+Ir) for Pd-Ir alloys containing less than 3% at. Ir are similar, comparable to Pd. The further increase of Ir content results in the abrupt drop of hydrogen absorbing capacity. The linear decrease of the potential of α→β phase transition versus Pd content is observed, confirming classification of the Pd-Ir alloys to the group of the contracted alloys.
Graphical abstract
MMP-3 plays a major role in calcium pantothenate-promoted wound healing after fractional ablative laser treatment
Authors: Huth Sebastian , Huth Laura , Marquardt Yvonne , Cheremkhina Maria , Heise Ruth , Baron Jens Malte 
Published: May 2021

AbstractAblative fractional laser treatment leads to a loss of matrix metalloproteinase-3 (MMP-3) expression; therefore, in the present in vitro study, we addressed the role of MMP-3 and its regulation by calcium pantothenate in wound healing processes at the molecular level. Utilizing confocal laser microscopy, we investigated MMP-3 protein expression in fractional ablative CO2 laser-irradiated skin models. In addition, we established full-thickness 3D skin models using fibroblasts and keratinocytes with a MMP-3 knockdown that were irradiated with a fractional ablative Er:YAG laser to set superficial injuries with standardized dimensions and minimal thermal damage to the surrounding tissue. We revealed an upregulation of MMP-3 protein expression in laser-irradiated skin models receiving aftercare treatment with calcium pantothenate. Skin models with MMP-3 knockdown exhibited a slower wound closure after laser treatment compared to controls. Gene expression profiling detected an MMP-3 knockdown-dependent upregulation of cytokines and chemokines (e.g. IL-36B, CXCL17, IL-37, CXCL5), antimicrobial peptides (e.g., S100A7, S100A12), epidermal crosslinking enzymes (TGM5), and differentiation markers (e.g., LOR, KRT1, FLG2). We also detected a downregulation of cathepsin V and MMP-10, both of which play a prominent role in wound healing processes. After fractional ablative laser injury, an aftercare treatment with calcium pantothenate accelerated wound closure in MMP-3 expressing models faster than in MMP-3 knockdown models. Our data substantiate a major role of MMP-3 in wound healing processes after ablative laser treatments. For the first time, we could show that calcium pantothenate exerts its wound healing-promoting effects at least partly via MMP-3.
Implantation depth and its influence on complications after TAVI with self-expanding valves
Authors: Breitbart Philipp , Minners Jan , Hein Manuel , Schröfel Holger , Neumann Franz-Josef , Ruile Philipp 
Published: May 2021

AbstractPrior studies in patients with transcatheter aortic valve implantation (TAVI) demonstrated an influence of transcatheter heart valve (THV) position on the occurrence of new conductions disturbances (CD) and paravalvular leakage (PVL) post TAVI in balloon-expandable valves (BEV). Purpose of this study was to investigate the THV implantation depth and its influence on the occurrence of CD and PVL in self-expanding valves (SEV). We performed fusion imaging of pre- and post-procedural computed tomography angiography in 104 TAVI-patients (all with Evolut R) to receive a 3-D reconstruction of the THV within the native annulus region. The THV length below the native annulus was measured for assessment of implantation depth. Electrocardiograms pre-discharge were assessed for conduction disturbances (CD), PVL was determined in transthoracic echocardiography. The mean implantation depth of the THV in the whole cohort was 4.3 ± 3.0 mm. Using the best cut-off of ≥ 4 mm in receiver operating characteristic curve analysis (sensitivity 83.3%, specificity 60.0%) patients with lower THV position developed more new CD after TAVI (68.2 vs. 23.7%, P < 0.001). A deep THV position was identified as the only predictor for new CD after TAVI (odds ratio [CI] 1.312[1.119–1.539], P = 0.001). The implantation depth showed no influence on the grade of PVL (r = 0.052, P = 0.598). In patients with TAVI using the Evolut R SEV, a lower THV positioning (≥ 4 mm length below annulus) was a predictor for new conduction disturbances. In contrast, implantation depth was not associated with the extent of PVL.
Graphic abstract

Prostheses positions of self-expanding valves and their influence on the occurrence of new conduction disturbances and the grade of paravalvular leakage after TAVI.