bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validating biomarkers and models for epigenetic inference of alcohol consumption from blood
Authors: Maas Silvana C. E. , Vidaki Athina , Teumer Alexander , Costeira Ricardo , Wilson Rory , van Dongen Jenny , Beekman Marian , Völker Uwe , Grabe Hans J. , Kunze Sonja , Ladwig Karl-Heinz , van Meurs Joyce B. J. , Uitterlinden André G. , Voortman Trudy , Boomsma Dorret I. , Slagboom P. Eline , van Heemst Diana , van der Kallen Carla J. H. , van den Berg Leonard H. , Waldenberger Melanie , Völzke Henry , Peters Annette , Bell Jordana T. , Ikram M. Arfan , Ghanbari Mohsen , Kayser Manfred 
Published: October 2021

Abstract
Background
Information on long-term alcohol consumption is relevant for medical and public health research, disease therapy, and other areas. Recently, DNA methylation-based inference of alcohol consumption from blood was reported with high accuracy, but these results were based on employing the same dataset for model training and testing, which can lead to accuracy overestimation. Moreover, only subsets of alcohol consumption categories were used, which makes it impossible to extrapolate such models to the general population. By using data from eight population-based European cohorts (N = 4677), we internally and externally validated the previously reported biomarkers and models for epigenetic inference of alcohol consumption from blood and developed new models comprising all data from all categories.

Results
By employing data from six European cohorts (N = 2883), we empirically tested the reproducibility of the previously suggested biomarkers and prediction models via ten-fold internal cross-validation. In contrast to previous findings, all seven models based on 144-CpGs yielded lower mean AUCs compared to the models with less CpGs. For instance, the 144-CpG heavy versus non-drinkers model gave an AUC of 0.78 ± 0.06, while the 5 and 23 CpG models achieved 0.83 ± 0.05, respectively. The transportability of the models was empirically tested via external validation in three independent European cohorts (N = 1794), revealing high AUC variance between datasets within models. For instance, the 144-CpG heavy versus non-drinkers model yielded AUCs ranging from 0.60 to 0.84 between datasets. The newly developed models that considered data from all categories showed low AUCs but gave low AUC variation in the external validation. For instance, the 144-CpG heavy and at-risk versus light and non-drinkers model achieved AUCs of 0.67 ± 0.02 in the internal cross-validation and 0.61–0.66 in the external validation datasets.

Conclusions
The outcomes of our internal and external validation demonstrate that the previously reported prediction models suffer from both overfitting and accuracy overestimation. Our results show that the previously proposed biomarkers are not yet sufficient for accurate and robust inference of alcohol consumption from blood. Overall, our findings imply that DNA methylation prediction biomarkers and models need to be improved considerably before epigenetic inference of alcohol consumption from blood can be considered for practical applications.
Successful treatment with radiation therapy for desmoid-type fibromatosis with unilateral hydronephrosis: a case report
Authors: Ishikawa Yojiro , Umezawa Rei , Yamamoto Takaya , Takahashi Noriyoshi , Takeda Kazuya , Suzuki Yu , Jingu Keiichi 
Published: October 2021

Abstract
Background
Desmoid-type fibromatosis is a rare disease that can result in hydronephrosis. Hydronephrosis associated with desmoid-type fibromatosis often requires surgery or ureteral stent insertion. Although radiation therapy is recommended for inoperable cases of desmoid-type fibromatosis, there has been no report of treatment for hydronephrosis associated with desmoid-type fibromatosis by radiation therapy alone. We herein report a case of successful treatment for inoperable recurrence of desmoid-type fibromatosis with unilateral hydronephrosis by radiation therapy alone.

Case presentation
A 43-year-old Japanese female underwent resection of desmoid-type fibromatosis in the right inguinal region and combined resection of the right external iliac vein 5 years before. Other treatment was not performed because of her pregnancy. Four years after surgery, desmoid-type fibromatosis recurred in the right pelvic wall. Cyclooxygenase-2 selective inhibitor treatment was given for 1 year, but her desmoid-type fibromatosis enlarged to more than 10 cm, and she had swelling of her right leg and hydronephrosis of her right kidney. The patient received 50.4 Gy in 28 fractions of prophylactic irradiation using 10 MV X-ray and 9 Gy in five fractions of a sequential boost for the recurrent desmoid-type fibromatosis. Although there was temporary tumor progression at 1 month after radiation therapy, slow regression of the tumor was seen. At 5 years after radiation therapy, there was no disease progression or severe complications.

Conclusion
We experienced successful treatment for an inoperable case of desmoid-type fibromatosis with hydronephrosis. Moderate-dose radiation therapy alone is an effective and feasible approach for the management of hydronephrosis associated with desmoid-type fibromatosis.
RETRACTED ARTICLE: Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage
Authors: Loiola Rodrigo Azevedo , García-Gabilondo Miguel , Grayston Alba , Bugno Paulina , Kowalska Agnieszka , Duban-Deweer Sophie , Rizzi Eleonora , Hachani Johan , Sano Yasuteru , Shimizu Fumitaka , Kanda Takashi , Mysiorek Caroline , Mazurek Maciej Piotr , Rosell Anna , Gosselet Fabien 
Published: October 2021

Abstract
Background
Cell-based therapeutic strategies have been proposed as an alternative for brain repair after stroke, but their clinical application has been hampered by potential adverse effects in the long term. The present study was designed to test the effect of the secretome of endothelial progenitor cells (EPCs) from stroke patients (scCM) on in vitro human models of angiogenesis and vascular barrier.

Methods
Two different scCM batches were analysed by mass spectrometry and a proteome profiler. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used for designing angiogenesis studies (proliferation, migration, and tubulogenesis) or in vitro models of EC monolayer (confluent monolayer ECs—CMECs) and blood–brain barrier (BBB; brain-like ECs—BLECs). Cells were treated with scCM (5 μg/mL) or protein-free endothelial basal medium (scEBM—control). CMECs or BLECs were exposed (6 h) to oxygen–glucose deprivation (OGD) conditions (1% oxygen and glucose-free medium) or normoxia (control—5% oxygen, 1 g/L of glucose) and treated with scCM or scEBM during reoxygenation (24 h).

Results

The analysis of different scCM batches showed a good reproducibility in terms of protein yield and composition. scCM increased CD34+-EC proliferation, tubulogenesis, and migration compared to the control (scEBM). The proteomic analysis of scCM revealed the presence of growth factors and molecules modulating cell metabolism and inflammatory pathways. Further, scCM decreased the permeability of CMECs and upregulated the expression of the junctional proteins such as occludin, VE-cadherin, and ZO-1. Such effects were possibly mediated through the activation of the interferon pathway and a moderate downregulation of Wnt signalling. Furthermore, OGD increased the permeability of both CMECs and BLECs, while scCM prevented the OGD-induced vascular leakage in both models. These effects were possibly mediated through the upregulation of junctional proteins and the regulation of MAPK/VEGFR2 activity.

Conclusion
Our results suggest that scCM promotes angiogenesis and the maturation of newly formed vessels while restoring the BBB function in ischemic conditions. In conclusion, our results highlight the possibility of using EPC-secretome as a therapeutic alternative to promote brain angiogenesis and protect from ischemia-induced vascular leakage.
Decoding antibacterial and antibiofilm properties of cinnamon and cardamom essential oils: a combined molecular docking and experimental study
Authors: Pourkhosravani Elahe , Dehghan Nayeri Fatemeh , Mohammadi Bazargani Mitra 
Published: October 2021

AbstractThis study sets out to compare the antibacterial and antibiofilm profiles of Ci/Ca EOs alone and in combination together against infectious bacterial strains. MIC assay was carried out to survey the effectiveness of prepared EOs by two-fold serial dilution method and MTT evaluation. Synergic antibacterial properties of EOs against target strains were studied by using checkerboard titration method. Biofilm growth and development were evaluated using CV and XTT reduction assays. Antibacterial activity was observed for EOs against both bacterial strains with stronger activity for CiEO against both bacteria. The synergistic antibacterial effect was observed only against B. subtilis. Based on the FIC index, combinations could not inhibit the growth of E. coli. The pure EOs and their combination inhibited cell attachment for both studied bacteria with stronger effect on E. coli. CV and XTT reduction assays results showed that Ci EO and its combination with CaEO had the highest antibiofilm activity at lowest MIC value 0.08% and 0.04/0.02% against biofilm formed by E. coli and B. subtilis respectively, indicating a high antibiofilm potential. Computational docking analyses also postulated that the active constituents of evaluated EOs have the potential to interact with different bacterial targets, suggested binding mode of action of EOs metabolites. By and large, synergistic anti-biofilm properties of EOs may provide further options for developing novel formula to inhibit a variety of infectious clinical and industrial strains without (or less) toxicity effects on human body.
Graphical Abstract
Efficacy and safety of IL-6 inhibitors in patients with COVID-19 pneumonia: a systematic review and meta-analysis of multicentre, randomized trials
Authors: Belletti Alessandro , Campochiaro Corrado , Marmiere Marilena , Likhvantsev Valery , Yavorovskiy Andrey , Dagna Lorenzo , Landoni Giovanni , Zangrillo Alberto , Hajjar Ludhmila Abrahão 
Published: October 2021

Abstract
Purpose
COVID-19 is characterized by dysregulated immune response, respiratory failure and a relevant mortality rate among hospitalized patients. Interleukin-6 (IL-6) is involved in COVID-19-associated cytokine storm, and several trials investigated whether its inhibition could improve patients’ outcome. We performed a meta-analysis of randomized trials (RCT) to test this hypothesis.

Materials and methods
Two independent investigators searched PubMed, Scopus, ClnicalTrials.gov and medRxiv up to September 1st, 2021. Inclusion criteria were: administration of tocilizumab or sarilumab; COVID-19 adult patients with pneumonia; and being a RCT. Primary outcome was mortality at the longest follow-up. Secondary outcomes included intubation rate and incidence of adverse events. Two independent investigators extracted data from eligible trials.

Results
Of the 763 studies assessed, 15 RCTs were included (9,320 patients), all were multicentre, and the majority open-label vs standard treatment. IL-6 inhibitors were associated with reduced all-cause mortality at the longest follow-up (1315/5,380 [24.4%] in the IL-6 inhibitors group versus 1080/3,814 [28.3%] in the control group, RR = 0.90; 95% CI 0.84 to 0.96; p for effect = 0.003, I2 = 0%, with 13 studies included), with reduction in 28/30-day mortality and intubation rates, and with no increase in adverse events and secondary infections.

Conclusion
IL-6 inhibitors reduced longest follow-up mortality and intubation in COVID-19 patients. Findings need to be confirmed in high-quality RCTs.
Influence of citrate buffer and flash heating in enhancing the sensitivity of ratiometric genosensing of Hepatitis C virus using plasmonic gold nanoparticles
Authors: Prakash Hrishikesh Shashi , Maroju Pranay Amruth , Boppudi Naga Sai Sriteja , Balapure Aniket , Ganesan Ramakrishnan , Ray Dutta Jayati 
Published: October 2021

AbstractGold nanoparticles (Au NPs) based technology has been shown to possess enormous potential in the viral nucleic acid diagnosis. Despite significant advancement in this domain, the existing literature reveals the diversity in the conditions employed for hybridization and tagging of thiolated nucleic acid probes over the Au NPs. Here we employ the probe sequence derived from the Hepatitis C virus to identify the optimal hybridization and thiol-Au NP tagging conditions. In a typical polymerase chain reaction, the probes are initially subjected to flash heating at elevated temperatures to obtain efficient annealing. Motivated by this, in the current study, the hybridization between the target and the antisense oligonucleotide (ASO) has been studied at 65 °C with and without employing flash heating at temperatures from 75 to 95 °C. Besides, the efficiency of the thiolated ASO’s tagging over the Au NPs with and without citrate buffer has been explored. The study has revealed the beneficial role of flash heating at 95 °C for efficient hybridization and the presence of citrate buffer for rapid and effective thiol tagging over the Au NPs. The combinatorial effect of these conditions has been found to be advantageous in enhancing the sensitivity of ratiometric genosensing using Au NPs.
Bioactive compounds from an endophytic fungi Nigrospora aurantiaca
Authors: Safwan Safwan , Hsiao George , Lee Tzong-Huei , Lee Ching-Kuo 
Published: October 2021

Abstract
Background
Many groups of fungi live as an endophyte in plants. Both published and undiscovered bioactive compounds can be found in endophytic fungi. Various biological activities of bioactive compounds from endophytic fungi had been reported, including anti-inflammatory and anticancerous effects.
The chemical investigation of biologically active compounds from endophytic fungi Melaleuca leucadendra Linn. have not yet been stated.

Results
One new compound, namely nigaurdiol (1), along with five known compounds, xyloketal K (2), bostrycin (3), deoxybostrycin (4), xylanthraquinone (5), and ergosterol (6), were isolated from the Melaleuca leucadendra Linn. associated fungal strain Nigrospora aurantiaca#TMU062. Their chemical structures were elucidated by spectroscopic data and compared with literature. All isolated compounds were evaluated for inhibitory effect of NO production in LPS-activated microglial BV-2 cells.

Conclusions
Compound 6 exhibited considerable inhibitory effect on NO production with IC50 values of 7.2 ± 1.4 µM and the survival rate of the cells was 90.8 ± 6.7% at the concentration of 10 µM.
Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management
Authors: Crippa Ilaria Alice , Vincent Jean-Louis , Zama Cavicchi Federica , Pozzebon Selene , Annoni Filippo , Cotoia Antonella , Njimi Hassane , Gaspard Nicolas , Creteur Jacques , Taccone Fabio Silvio 
Published: October 2021

Abstract
Background
Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients’ outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome.

Methods
Retrospective analysis of prospectively collected data. Inclusion criteria: adult cardiac arrest survivors treated by targeted temperature management (TTM). Exclusion criteria: trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3–5 assessed 3 months after CA defined unfavorable neurological outcome (UO).

Results
We included 50 patients (Jan 2015–Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10–35] min. HT (core body temperature 33.7 [33.2–34] °C) lasted for 24 [23–28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6–37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11–0.58] vs. 0.58 [0.30–0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43–0.83] vs. 0.31 [− 0.01–0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO.

Conclusions
CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.
Potential of megathrust earthquakes along the southern Ryukyu Trench inferred from GNSS data
Authors: Kano Masayuki , Ikeuchi Aoi , Nishimura Takuya , Miyazaki Shin’ichi , Matsushima Takeshi 
Published: October 2021

AbstractThe southern part of the Ryukyu subduction zone has recorded tsunami events with a recurrence interval of several hundred years. Although their source is controversial, one model suggests that the last 1771 Yaeyama tsunami was caused by a shallow megathrust earthquake with a magnitude of 8. However, the current knowledge on interplate coupling based on recent geodetic data is limited. Here, a time series of Global Navigation Satellite System data from January 2010 to February 2021 was analyzed, including newly installed stations by Kyoto and Kyushu Universities, to obtain the distance changes between stations and vertical secular velocities. The distance changes ranged from 2.4 mm/year in contraction and to 4.7 mm/year in extension, and the vertical velocities exhibited no clear uplift or subsidence, with − 2.4 to 1.1 mm/year. The back slip inversion results indicated a slip deficit of 17–47 mm/year to the south of the Yaeyama Islands. The large slip deficit area is complementarily intervened between the shallower source area of low-frequency earthquakes and the deeper slow slip region, suggesting the spatial heterogeneity of frictional properties along the plate interface. If the large slip deficit area accumulates stress in the same rate since the last 1771 earthquake, it could result in a megathrust event with a moment magnitude greater than 7.5. Because the limited onshore data cannot resolve the slip deficit on the shallow plate interface, seafloor geodetic observations are essential to clarify the detailed spatial distribution of the slip deficit and discuss its earthquake and tsunami potential.
Graphical Abstract
The SREBP (Sterol Regulatory Element-Binding Protein) pathway: a regulatory bridge between carotenogenesis and sterol biosynthesis in the carotenogenic yeast Xanthophyllomyces dendrorhous
Authors: Gómez Melissa , Baeza Marcelo , Cifuentes Víctor , Alcaíno Jennifer 
Published: October 2021

AbstractXanthophyllomyces dendrorhous is a basidiomycete yeast that naturally produces the red–orange carotenoid astaxanthin, which has remarkable antioxidant properties. The biosynthesis of carotenoids and sterols share some common elements that have been studied in X. dendrorhous. For example, their synthesis requires metabolites derived from the mevalonate pathway and in both specific pathways, cytochrome P450 enzymes are involved that share a single cytochrome P450 reductase, CrtR, which is essential for astaxanthin biosynthesis, but is replaceable for ergosterol biosynthesis. Research on the regulation of carotenoid biosynthesis is still limited in X. dendrorhous; however, it is known that the Sterol Regulatory Element-Binding Protein (SREBP) pathway, which is a conserved regulatory pathway involved in the control of lipid metabolism, also regulates carotenoid production in X. dendrorhous. This review addresses the similarities and differences that have been observed between mammal and fungal SREBP pathways and what it is known about this pathway regarding the regulation of the production of carotenoids and sterols in X. dendrorhous.
Effects of Greater Central Arterial Stiffness on Cardiovagal Baroreflex Sensitivity in Resistance-Trained Men
Authors: Nakamura Nobuhiro , Muraoka Isao 
Published: October 2021

Abstract
Background
Compared with age-matched untrained men, resistance-trained men who have undergone long duration training (> 2 years) at a high frequency (> 5 days/week) may be lower cardiovagal baroreflex sensitivity (BRS) because of central arterial stiffening. Therefore, the purpose of this study was to examine the effect of greater central arterial stiffness in resistance-trained men on cardiovagal BRS in a cross-sectional study to compare resistance-trained men with age-matched untrained men.

Methods
This cross-sectional study included resistance-trained men (n = 20; age: 22 ± 3; body mass index: 26.7 ± 2.2) and age-matched untrained men (control group: n = 20; age: 25 ± 2; body mass index: 23.7 ± 2.4). The β-stiffness index and arterial compliance were assessed at the right carotid artery using a combination of a brightness mode ultrasonography system for the carotid artery diameter and applanation tonometry for the carotid blood pressure. And, the cardiovagal BRS was estimated by the slope of the R–R interval and systolic blood pressure during Phase II and IV of Valsalva maneuver (VM). The participants maintained an expiratory mouth pressure of 40 mmHg for 15 s in the supine position.

Results
The β-Stiffness index was significantly higher in the resistance-trained group than in the control group (5.9 ± 1.4 vs. 4.4 ± 1.0 a.u., P < 0.01). In contrast, the resistance-trained group had significantly lower arterial compliance (0.15 ± 0.05 vs. 0.20 ± 0.04 mm2/mmHg, P < 0.01) and cardiovagal BRS during Phase IV of VM (9.0 ± 2.5 vs. 12.9 ± 5.4 ms/mmHg, P < 0.01) than the control group and. Moreover, cardiovagal BRS during Phase IV of VM was inversely and positively correlated with the β-stiffness index (r = − 0.59, P < 0.01) and arterial compliance (r = 0.64, P < 0.01), respectively.

Conclusion
Resistance-trained group had greater central arterial stiffness and lower cardiovagal BRS Phase IV compared with control group. Moreover, the central arterial stiffening was related to cardiovagal BRS Phase IV. These results suggest that greater central arterial stiffness in resistance-trained men may be associated with lower cardiovagal BRS.
Trial Registration University hospital Medical Information Network (UMIN) in Japan, UMIN000038116. Registered on September 27, 2019.