bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B virus X protein promotes hepatocarcinogenesis via the activation of HMGA2/STC2 signaling to counteract oxidative stress-induced cell death
Authors: Huang Fung-Yu , Wong Danny Ka-Ho , Mak Lung-Yi , Cheung Tan-To , Seto Wai-Kay , Yuen Man-Fung 
Published: March 2022

Abstract
Chronic hepatitis B virus (HBV) infection can cause oxidative stress and induce cell death. The mechanisms by which cells overcome oxidative stress to survive remain largely unknown. Here, we used human sera, liver tissues and cell lines to study how HBV modulates cellular pathways to counteract oxidative stress-induced cell death. We found high-mobility group AT-hook 2 (HMGA2), an architectural transcription factor is upregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Elevated serum HMGA2 is significantly associated with viral load in HBV carriers, and HBV-related HCC. We showed that HBV X protein (HBx) encoded by HBV-induced cell growth via HMGA2 activation. The growth-promoting effect is abolished when HMGA2 is suppressed. Ectopic HBx expression induced DNA damage and oxidative stress. HMGA2 silencing reduced oxidative stress in HBx-expressing cells. Cytoprotective stanniocalcin 2 (STC2) protein is a downstream target of HMGA2. Consistent with the findings in HMGA2, STC2 mRNA and protein expression are upregulated in HCC tissues. Elevated serum STC2 is also associated with viral load in HBV carriers, and HCC. STC2 is transcriptionally upregulated by HBx and HMGA2 to elicit cytoprotection against apoptosis. STC2 knockdown disrupted Bax/Bcl-2 balance that increased cytochrome c release, caspase 3/7 activity and apoptosis, and thus abolished the growth-promoting effect of HMGA2. Clinical relevance of HBx/HMGA2/STC2 signaling is evidenced by the significant correlation of serum HMGA2/STC2 in active HBV infection and HCC. These findings reveal a novel HBx regulatory HMGA2/STC2 pathway in counteracting reactive oxygen species-induced cell death. HMGA2 and STC2 may be therapeutic targets for prevention of hepatocarcinogenesis in chronic HBV infection.
Targeted Metagenomic Sequencing-based Approach Applied to 2146 Tissue and Body Fluid Samples in Routine Clinical Practice
Authors: Flurin Laure , Wolf Matthew J , Mutchler Melissa M , Daniels Matthew L , Wengenack Nancy L , Patel Robin 
Published: March 2022

Abstract

Background
The yield of next-generation sequencing (NGS) added to a Sanger sequencing–based 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) assay was evaluated in clinical practice for diagnosis of bacterial infection.

Methods
PCR targeting the V1 to V3 regions of the 16S rRNA gene was performed, with amplified DNA submitted to Sanger sequencing and/or NGS (Illumina MiSeq) or reported as negative, depending on the cycle threshold value. A total of 2146 normally sterile tissues or body fluids were tested between August 2020 and March 2021. Clinical sensitivity was assessed in 579 patients from whom clinical data were available.

Results
Compared with Sanger sequencing alone (400 positive tests), positivity increased by 87% by adding NGS (347 added positive tests). Clinical sensitivity of the assay that incorporated NGS was 53%, which was higher than culture (42%, P &lt; .001), with an impact on clinical decision-making in 14% of infected cases. Clinical sensitivity in the subgroup that received antibiotics at sampling was 41% for culture and 63% for the sequencing assay (P &lt; .001).

Conclusions
Adding NGS to Sanger sequencing of the PCR-amplified 16S rRNA gene substantially improved test positivity. In the patient population studied, the assay was more sensitive than culture, especially in patients who had received antibiotic therapy.
Non-robotic minimally invasive mitral valve repair: a 20-year single-centre experience
Authors: Feirer Nina , Kornyeva Anastasiya , Lang Miriam , Sideris Konstantinos , Voss Bernhard , Krane Markus , Lange Rüdiger , Vitanova Keti 
Published: March 2022

Abstract

OBJECTIVES
Minimally invasive mitral valve repair (MVR) promises major advantages over median sternotomy regarding cosmetic results and faster recovery. However, the long-term functional outcome of minimally invasive MVR has been questioned by critics because the limited access may not exclusively promise high-quality repair. This study examines the long-term outcome regarding survival and reoperation rate.

METHODS
All patients undergoing minimally invasive MVR from February 2000 until March 2020 were included in this study. Baseline clinical and surgical characteristics were summarized from the internal database. Primary end points were survival and freedom from reoperation, analysed via Kaplan–Meier curves. Secondary end points were periprocedural complications after minimally invasive MVR and incidence for recurrent mitral regurgitation &gt;II°.

RESULTS
A total of 1194 patients underwent minimally invasive MVR, in 17 cases mitral valve replacement was required. The mean age was 55.1 years [47.6; 62.7]. The successful minimally invasive repair rate was 97%. The 30-day mortality was 0.6%. Survival was 96.7% [standard deviation (SD): 5.8%], 91.6% (SD: 1.1%) and 80.0% (SD: 11.2%) at 5, 10 and 20 years. The incidence of reoperation was 4.4% (SD: 3.2%), 10.3% (SD: 7.4%) and 16.7% (SD : 7.4%) at 5, 10 and 20 years, respectively. Concomitant procedures such as tricuspid valve repair and modified Cryo-maze procedure were performed in 263 cases.

CONCLUSIONS
Minimally invasive MVR for degenerative mitral regurgitation is safe, shows excellent functional long-term results and is associated with low perioperative and late mortality.
Towards a better understanding of the recoverability of physical property relationships from geophysical inversions of multiple potential-field data sets
Authors: Li Xinyan , Sun Jiajia 
Published: March 2022

SUMMRY
Collecting multiple potential-field data sets to image the subsurface has been popular in resource explorations. How to effectively integrate multiphysics data and extract useful information about the subsurface geology is an active area of research. Among existing approaches, geophysical inversions followed by geological classification has shown promising results. This procedure contains two steps. First, multiple geophysical data sets are inverted, either separately or jointly, to obtain their corresponding physical property models. Secondly, the inverted values are visualized in a scatterplot and classified into different groups, a process known as geology differentiation. The implicit assumption for geology differentiation is that the recovered physical property relationships are reliable. However, whether this assumption is generally valid or not remains unknown. Moreover, it is well known that the standard smooth inversion would underestimate the physical property values. On the other hand, the sparse inversion is able to recover compact anomalies with elevated magnitudes. However, it remains unclear as to how smooth and sparse inversions affect the recoverability. To understand the recoverability of physical property relationships, we have designed six geological scenarios with three geological anomalies located at different depths and assigned with different physical property values. For each scenario, we performed four inversions: both separate and joint inversions using smooth L2-norm and sparse mixed L12-norm regularizations. Each inversion is followed by geology differentiation. We have found (1) that the recovered physical property relationships from geophysical inversions are not always reliable, (2) the depths of the source bodies and inversion strategies significantly affect the recoverability, and (3) joint sparsity inversion consistently gives rise to the best recoverability.
Revisit NGC 5466 tidal stream withGaia, SDSS/SEGUE, and LAMOST
Authors: Yang Yong , Zhao Jing-Kun , Ishigaki Miho N , Zhou Jian-Zhao , Yang Cheng-Qun , Xue Xiang-Xiang , Ye Xian-Hao , Zhao Gang 
Published: March 2022

ABSTRACTBy mining the data from Gaia Early Data Release 3, Sloan Digital Sky Survey/Sloan Extension for Galactic Understanding and Exploration Data Release 16, and Large Sky Area Multi-Object Fiber Spectroscopic Telescope Data Release 8, 11 member stars of the NGC 5466 tidal stream are detected and 7 of them are newly identified. To reject contaminators, a variety of cuts are applied in sky position, colour–magnitude diagram, metallicity, proper motion, and radial velocity. We compare our data to a mock stream generated by modelling the cluster’s disruption under a smooth Galactic potential plus the Large Magellanic Cloud (LMC). The concordant trends in phase space between the model and observations imply that the stream might have been perturbed by the LMC. The two most distant stars among the 11 detected members trace the stream’s length to 60° of sky, supporting and extending the previous length of 45°. Given that NGC 5466 is so distant and potentially has a longer tail than previously thought, we expect that the NGC 5466 tidal stream could be a useful tool in constraining the Milky Way gravitational field.
The scaling relation between galaxy luminosity and WHIM density from EAGLE simulations with application to SDSS data
Authors: Holt Patrick , Tuominen Toni , Nevalainen Jukka , Bonamente Massimiliano , Kuutma Teet , Heinämäki Pekka , Tempel E 
Published: March 2022

ABSTRACT
This paper presents an updated scaling relation between the optical luminosity density (LD) of galaxies in the r band and the density of the warm–hot intergalactic medium (WHIM) in cosmic filaments, using the high-resolution EAGLE simulations. We find a strong degree of correlation between the WHIM density and the galaxy luminosity density, resulting in a scaling relation between the two quantities that permits us to predict the WHIM density of filaments with a scatter of less than $\frac {1}{2}$ dex in a broad range of smoothed filament luminosity densities. In order to estimate the performance of the simulation-based calibration of the LD–WHIM density relation, we applied it to a sample of low-redshift filaments detected with the Bisous method in the Legacy Survey SDSS DR12 data. In the volume covered by the SDSS data, our relation predicts a WHIM density amounting to 31 ± 7 ± 12 per cent (statistical errors followed by systematic) of cosmic baryon density. This agrees, albeit within the large uncertainties, with the current estimates of the cosmological missing baryon fraction, implying that our LD–WHIM density relation may be a useful tool in the search for the missing baryons. This method of analysis provides a new promising avenue to study the physical properties of the missing baryons, using an observable that is available for large volumes of the sky, complementary and independent from WHIM searches with absorption-line systems in the FUV or X-rays.
CRISPR–Cas9 gRNA efficiency prediction: an overview of predictive tools and the role of deep learning
Authors: Konstantakos Vasileios , Nentidis Anastasios , Krithara Anastasia , Paliouras Georgios 
Published: March 2022

Abstract
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has become a successful and promising technology for gene-editing. To facilitate its effective application, various computational tools have been developed. These tools can assist researchers in the guide RNA (gRNA) design process by predicting cleavage efficiency and specificity and excluding undesirable targets. However, while many tools are available, assessment of their application scenarios and performance benchmarks are limited. Moreover, new deep learning tools have been explored lately for gRNA efficiency prediction, but have not been systematically evaluated. Here, we discuss the approaches that pertain to the on-target activity problem, focusing mainly on the features and computational methods they utilize. Furthermore, we evaluate these tools on independent datasets and give some suggestions for their usage. We conclude with some challenges and perspectives about future directions for CRISPR–Cas9 guide design.
Immunoglobulin M seroneutralization for improved confirmation of Japanese encephalitis virus infection in a flavivirus-endemic area
Authors: Bharucha Tehmina , Ayhan Nazli , Pastorino Boris , Rattanavong Sayaphet , Vongsouvath Manivanh , Mayxay Mayfong , Changthongthip Anisone , Sengvilaipaseuth Onanong , Phonemixay Ooyanong , Pommier Jean-David , Gorman Christopher , Zitzmann Nicole , Newton Paul N , de Lamballerie Xavier , Dubot-Pérès Audrey 
Published: March 2022

Abstract

Background
The mainstay of diagnostic confirmation of acute Japanese encephalitis (JE) involves detection of anti-JE virus (JEV) immunoglobulin M (IgM) by enzyme-linked immunosorbent assay (ELISA). Limitations in the specificity of this test are increasingly apparent with the introduction of JEV vaccinations and the endemicity of other cross-reactive flaviviruses. Virus neutralization testing (VNT) is considered the gold standard, but it is challenging to implement and interpret. We performed a pilot study to assess IgG depletion prior to VNT for detection of anti-JEV IgM neutralizing antibodies (IgM-VNT) as compared with standard VNT.

Methods
We evaluated IgM-VNT in paired sera from anti-JEV IgM ELISA-positive patients (JE n=35) and negative controls of healthy flavivirus-naïve (n=10) as well as confirmed dengue (n=12) and Zika virus (n=4) patient sera. IgM-VNT was subsequently performed on single sera from additional JE patients (n=76).

Results
Anti-JEV IgG was detectable in admission serum of 58% of JE patients. The positive, negative and overall percentage agreement of IgM-VNT as compared with standard VNT was 100%. A total of 12/14 (86%) patient samples were unclassified by VNT and, with sufficient sample available for IgG depletion and IgG ELISA confirming depletion, were classified by IgM-VNT. IgM-VNT enabled JE case classification in 72/76 (95%) patients for whom only a single sample was available.

Conclusions
The novel approach has been readily adapted for high-throughput testing of single patient samples and it holds promise for incorporation into algorithms for use in reference centres.
Real-World Comparison of Isavuconazole and Voriconazole in Terms of the Need for Dosage Adjustments Guided by Clinical Pharmacological Advice During Primary Prophylaxis of Invasive Fungal Infections in Pediatric Patients with Hemato-Oncological Malignancies
Authors: Gatti Milo , Campoli Caterina , Belotti Tamara , Cojutti Pier Giorgio , Masetti Riccardo , Pession Andrea , Viale Pierluigi , Pea Federico 
Published: March 2022

Background:
Limited evidence concerning optimal azole dosing regimens currently exists for antifungal prophylaxis in hemato-oncological pediatric patients.

Methods:
Hemato-oncological children receiving intravenous or oral isavuconazole or voriconazole for primary antifungal prophylaxis at IRCCS Azienda Ospedaliero–Universitaria of Bologna during November 2020 to October 2021 and undergoing CPA programs based on real-time therapeutic drug monitoring (TDM) were retrospectively analyzed. CPAs for isavuconazole and voriconazole and the number of dosage adjustments were collected. Normalized trough concentrations [(Cmin)/dose/kg] were calculated for both drugs at each TDM assessment, and the coefficient of variation was determined. The efficacy and safety of the drugs were evaluated.

Results:
Sixteen hemato-oncological pediatric patients received azole prophylaxis (mean age and weight: 9.1 ± 4.9 years and 32.6 ± 16.0 kg; 6 isavuconazole and 10 voriconazole). Sixty and 89 CPAs were delivered as isavuconazole and voriconazole, respectively. Dosage adjustments were needed in 3.3% of cases for isavuconazole and 53.9% of cases for voriconazole (P < 0.001). At first TDM, achievement of the desired target during standard dosing regimens was higher for isavuconazole (83.3%) than for voriconazole (10.0%; P = 0.008). Dispersion of normalized concentrations was higher for voriconazole (CV = 139.1% vs. CV = 79.4%). Elevation of ALT and aspartate aminotransferase levels between baseline and the third month was higher in patients receiving voriconazole (median, 28 vs. 90 U/L; P = 0.038, and 19 vs. 65.5 U/L; P = 0.002).

Conclusions:
Our findings suggest that there is limited variability in isavuconazole exposure in hemato-oncological pediatric patients receiving azole prophylaxis, resulting in a low need for CPA-guided dosage adjustments.
Predictors of Implicit and Explicit Internalized Stigma in a Sample With Different Mental Illness Diagnoses
Authors: González-Sanguino Clara , Muñoz Manuel 
Published: March 2022

Abstract
This research aimed to study implicit and explicit internalized stigma and its relationship with other variables in a sample of people with distinct mental illness diagnoses (N = 160). Descriptive analysis, mean differences, correlations, and stepwise regression models were conducted. Implicit and explicit internalized stigma was found throughout the sample with differences depending on certain sociodemographic variables. Regression models revealed symptomatology, physical environment, personality traits, references to mental illness, and the time taken to seek professional help as predictors of explicit internalized stigma. At the implicit level, only self-esteem was found as a predictor explaining a low percentage of the variance. The results obtained underline the differences between implicit and explicit stigma, suggesting different relevant variables for interventions focused on prevention and internalized stigma reduction.
Nitratireductor rhodophyticola sp. nov., isolated from marine red algae
Authors: Kim Kyung Hyun , Kristyanto Sylvia , Kim Hyung Min , Kim Kyeong Ryeol , Jeon Che Ok 
Published: March 2022

Two Gram-stain-negative, strictly aerobic bacteria, strains L1-7-SET and R6, isolated from marine red algae, were characterized. They shared 99.9 % 16S rRNA gene sequence similarity and a 100 % digital DNA–DNA hybridization (DDH) value, representing members of a single species. Cells of strains L1-7-SET and R6 were catalase- and oxidase-positive motile rods with a single polar flagellum. Strains L1-7-SET and R6 optimally grew at 30–35 °C, pH 7.0–8.0 and with 1.0–2.0 % (w/v) NaCl. Ubiquinone-10 was the sole isoprenoid quinone and C19 : 0 cyclo ω8c and summed feature 8 (comprising C18 : 1
ω7c and/or C18 : 1
ω6c) were detected as the major cellular fatty acids. The DNA G+C contents of strains L1-7-SET and R6 were both 61.62 mol%. The polar lipids of strain L1-7-SET consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and two unidentified polar lipids. Phylogenetic analyses based on 16S rRNA gene and 120 protein marker sequences revealed that strains L1-7-SET and R6 formed a phyletic lineage within the genus

Nitratireductor

and they were most closely related to

Nitratireductor aquibiodomus

NL21T and

Nitratireductor kimnyeongensis

KY 101T with both 98.8 % 16S rRNA gene sequence similarities. Digital DDH values between strain L1-7-SET and the type strains of

N. aquibiodomus

and

N. kimnyeongensis

were 60.3 and 29.5 %, respectively. The phenotypic, chemotaxonomic and molecular features support that strains L1-7-SET and R6 represents a novel species of the genus

Nitratireductor

, for which the name Nitratireductor rhodophyticola sp. nov. is proposed. The type strain is L1-7-SET (=KACC 19076T=KCTC 92231T=JCM 31802T).
Dynamic analysis of sequestration-based feedbacks in cellular and biomolecular circuits
Authors: Dey Supravat , Vargas-Garcia Cesar A. , Singh Abhyudai 
Published: March 2022

AbstractNonlinear feedback controllers are ubiquitous features of biological systems at different scales. A key motif arising in these systems is a sequestration-based feedback. As a physiological example of this type of feedback architecture, platelets (specialized cells involved in blood clotting) differentiate from stem cells, and this process is activated by a protein called Thrombopoietin (TPO). Platelets actively sequester and degrade TPO, creating negative feedback whereby any depletion of platelets increases the levels of freely available TPO that upregulates platelet production. We show similar examples of sequestration-based feedback in intracellular biomolecular circuits involved in heat-shock response and microRNA regulation. Our systematic analysis of this feedback motif reveals that platelets induced degradation of TPO is critical in enhancing system robustness to external disturbances. In contrast, reversible sequestration of TPO without degradation results in poor robustness to disturbances. We develop exact analytical results quantifying the limits to which the sensitivity to disturbances can be attenuated by sequestration-based feedback. Next, we consider the stochastic formulation of the circuit that takes into account low-copy number fluctuations in feedback components. Interestingly, our results show that the extent of random fluctuations are enhanced with increasing feedback strength, but can exhibit local maxima and minima across parameter regimes. In summary, our systematic analysis highlights design principles for enhancing the robustness of sequestration-based feedback mechanisms to external disturbances and inherent noise in molecular counts.
Characteristics of N6-methyladenosine modification during sexual reproduction of Chlamydomonas reinhardtii
Authors: Lv Ying , Han Fei , Liu Mengxia , Zhang Ting , Cui Guanshen , Wang Jiaojiao , Yang Ying , Yang Yun-Gui , Yang Wenqiang 
Published: March 2022

AbstractThe unicellular green alga Chlamydomonas reinhardtii (referred to as Chlamydomonas throughout) is an ideal model organism which possesses both plant and animal attribute for studying the fundamental processes such as photosynthesis, sexual reproduction and life cycle etc. N6-methyladenosine (m6A) is the most prevalent mRNA modification and plays important roles during sexual reproduction in animals and plants. However, the pattern and function of m6A modification during Chlamydomonas sexual reproduction is still unknown. Here, we performed transcriptome and MeRIP sequencing on the six samples from different stages during sexual reproduction of Chlamydomonas life cycle. The results showed that m6A occurs widely at the main motif of UGKAM (K= U/G, M= A/C) in Chlamydomonas mRNA. Moreover, m6A peak in Chlamydomonas mRNA is mainly enriched in the 3’UTR region and negatively correlated with the abundance of the transcripts at each stage. Especially, genes in microtubule-associated pathway showed a significant negative correlation between gene expression level and m6A level, indicating the influences of m6A modification on sexual reproduction and life cycle of Chlamydomonas through regulating microtubule-based movement. In summary, our findings first demonstrate the distributions and the functions of m6A modification in Chlamydomonas and provide new insights into the understandings of m6A modification in the process of sexual reproduction in other plant organisms evolutionarily.