bluuebunny/crossref_metadata_2025_split huggingface dataset:
N1-methyl-pseudouridine is incorporated with higher fidelity than pseudouridine in synthetic RNAs
Authors: Chen Tien-Hao , Potapov Vladimir , Dai Nan , Ong Jennifer L. , Roy Bijoyita 
Published: July 2022

AbstractIn vitro transcribed synthetic messenger RNAs (mRNAs) represent a novel therapeutic modality. To overcome the inherent immunogenicity, as well as to increase the therapeutic efficacy of the molecules, uridine analogs—such as pseudouridine (Ψ) and N1-methyl-pseudouridine (m1Ψ), are incorporated in the synthetic mRNA. To decipher the fidelity with which these modifications are incorporated during the in vitro transcription (IVT) process, we compared the incorporation fidelity of uridine analogs with different RNA polymerases. We demonstrate that m1Ψ is incorporated with higher fidelity than Ψ. The fidelity of nucleotide incorporation differs between RNA polymerases; however, the spectrum of mutations observed between the RNAPs is similar. We also show that the array of nucleotide misincorporation is not dependent on the template DNA sequence context and that the distribution of these misincorporated nucleotides is not localized to any specific region along the length of the RNA. Based on our findings, we introduce a novel method to improve uridine analog incorporation fidelity during IVT. Our proof-of-concept experiments for higher-fidelity incorporation of uridine analogs during IVT provide guidelines when choosing RNAPs for the generation of modified uridine-containing mRNAs in vitro.
Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA
Authors: Sánchez Ricardo , Dorado Sara , Ruíz-Heredia Yanira , Martín-Muñoz Alejandro , Rosa-Rosa Juan Manuel , Ribera Jordi , García Olga , Jimenez-Ubieto Ana , Carreño-Tarragona Gonzalo , Linares María , Rufián Laura , Juárez Alexandra , Carrillo Jaime , Espino María José , Cáceres Mercedes , Expósito Sara , Cuevas Beatriz , Vanegas Raúl , Casado Luis Felipe , Torrent Anna , Zamora Lurdes , Mercadal Santiago , Coll Rosa , Cervera Marta , Morgades Mireia , Hernández-Rivas José Ángel , Bravo Pilar , Serí Cristina , Anguita Eduardo , Barragán Eva , Sargas Claudia , Ferrer-Marín Francisca , Sánchez-Calero Jorge , Sevilla Julián , Ruíz Elena , Villalón Lucía , del Mar Herráez María , Riaza Rosalía , Magro Elena , Steegman Juan Luis , Wang Chongwu , de Toledo Paula , García-Gutiérrez Valentín , Ayala Rosa , Ribera Josep-Maria , Barrio Santiago , Martínez-López Joaquín 
Published: July 2022

AbstractThe screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.
Characterization and anti-biofilm activity of bacteriophages against urinary tract Enterococcus faecalis isolates
Authors: El-Atrees Doaa M. , El-Kased Reham F. , Abbas Ahmad M. , Yassien Mahmoud A. 
Published: July 2022

AbstractStrong biofilm-forming Enterococcus feacalis urinary tract pathogens (n = 35) were used to determine the lytic spectrum of six bacteriophages isolated from sewage samples. Only 17 Enterococcus feacalis isolates gave lytic zones with the tested bacteriophages from which five isolates were susceptible to all of them. The isolated enterococcal phages are characterized by wide range of thermal (30–90 °C) and pH (3–10) stability. They belong to order Caudovirales, from which four bacteriophages (EPA, EPB, EPD, EPF) belong to family Myoviridae and two (EPC, EPE) belong to family Siphoviridae. In addition, they have promising antibiofilm activity against the tested strong-forming biofilm E. faecalis isolates. The enterococcal phages reduced the formed and preformed biofilms to a range of 38.02–45.7% and 71.0–80.0%, respectively, as compared to the control. The same promising activities were obtained on studying the anti-adherent effect of the tested bacteriophages on the adherence of bacterial cells to the surface of urinary catheter segments. They reduced the number of adherent cells to a range of 30.8–43.8% and eradicated the pre-adherent cells to a range of 48.2–71.1%, as compared to the control. Overall, the obtained promising antibiofilm activity makes these phages good candidates for application in preventing and treating biofilm associated Enterococcus faecalis infections.
Combining multi-marker metabarcoding and digital holography to describe eukaryotic plankton across the Newfoundland Shelf
Authors: MacNeil Liam , Desai Dhwani K. , Costa Maycira , LaRoche Julie 
Published: July 2022

AbstractThe planktonic diversity throughout the oceans is vital to ecosystem functioning and linked to environmental change. Plankton monitoring tools have advanced considerably with high-throughput in-situ digital cameras and genomic sequencing, opening new challenges for high-frequency observations of community composition, structure, and species discovery. Here, we combine multi-marker metabarcoding based on nuclear 18S (V4) and plastidial 16S (V4–V5) rRNA gene amplicons with a digital in-line holographic microscope to provide a synoptic diversity survey of eukaryotic plankton along the Newfoundland Shelf (Canada) during the winter transition phase of the North Atlantic bloom phenomenon. Metabarcoding revealed a rich eukaryotic diversity unidentifiable in the imaging samples, confirming the presence of ecologically important saprophytic protists which were unclassifiable in matching images, and detecting important groups unobserved or taxonomically unresolved during similar sequencing campaigns in the Northwest Atlantic Ocean. In turn, imaging analysis provided quantitative observations of widely prevalent plankton from every trophic level. Despite contrasting plankton compositions portrayed by each sampling method, both capture broad spatial differences between the northern and southern sectors of the Newfoundland Shelf and suggest complementary estimations of important features in eukaryotic assemblages. Future tasks will involve standardizing digital imaging and metabarcoding for wider use and consistent, comparable ocean observations.
Valorization of avocado seeds with antioxidant capacity using pressurized hot water extraction
Authors: Ong Eng Shi , Low Janelle , Tan Joseph Choon Wee , Foo Su Yi , Leo Chen Huei 
Published: July 2022

AbstractThe pulp of avocado (Persea Americana) is widely consumed as the primary food source, while the seed is often discarded as food waste. Increased consumption of avocado would inevitably results in production of waste by-products such as avocado seeds, hence the ability to extract phytochemicals from such waste, and upcycling to potential nutraceutical products is of great interest. The overall aim of this study is to explore avocado seeds as potential functional food through the combined use of a green extraction method, chemical standardization and pattern recognition tools, and biological characterization assays. Specifically, this study utilized an organic solvent-free extraction method, pressurized hot water extraction (PHWE) to extract phytochemicals from avocado seeds and liquid chromatography mass spectrometry (LCMS) was used to identify the phytochemicals present in the avocado seeds. Our results demonstrated that avocado seed extracts have antioxidant activity and inhibited oxidative stress-induced metabolomics changes in endothelial cells, suggesting that avocado seed extracts have vasoprotective actions.
Validation and advantages of using novel RT-qPCR melting curve analysis assays for the identification of SARS-CoV-2 variants
Authors: Juul Sebastian , Spiegelhauer Malene Roed , Petersen Mette Neve , Flugt Katharina Kirkegaard , Hansen Nikolaj Vestergaard , Larsen Helene , Jensen Per Bo , Christensen Ulf Bech , Petersen Rasmus Koefoed , Friis-Hansen Lennart 
Published: July 2022

AbstractReverse transcription quantitative PCR (RT-qPCR) assays are gold standard in diagnosing SARS-CoV-2 infection and play a major role in viral subtyping for rapid detection and monitoring of important mutations, containing the spread of new virus variants. We wanted to compare RT-qPCR melting curve analysis assays to Sanger Sequencing for detection of variants within the SARS-CoV-2 spike glycoprotein and examined their sensitivity and specificity. Samples positive for SARS-CoV-2 (n = 663 + 82) were subtyped using both Sanger sequencing and five RT-qPCR melting curve analysis assays specific for the mutations N501Y, P681H, E484K, K417N/T, and N439K. The results of the two methods were compared. The training cohort and the clinical validation cohort showed equally, or significantly better sensitivity of the assays compared to the Sanger sequencing. The agreement of the Sanger sequencing and the assays ranged from 92.6 to 100% for the training cohort and 99.4–100% for the clinical validation. The sensitivity, specificity, and turn-around time of the RT-qPCR melting curve analysis assays are well-suited for clinical monitoring of VOCs, making the assays an important tool in contact tracing and risk stratification. Furthermore, the assays were able to indicate the presence of new mutations in the complementary sequence to the mutation-specific probes.
Association of hormone replacement therapy with risk of gastric cancer: a systematic review and meta-analysis
Authors: Jang Yeu-Chai , Leung Chi Yan , Huang Hsi-Lan 
Published: July 2022

AbstractHormone replacement therapy (HRT) is widely used to relieve menopausal symptoms; however, it remains unclear whether the use of HRT was associated with gastric cancer. We conducted a systematic review and meta-analysis to synthesize available evidence. This study followed the PRISMA guideline to report meta-analysis. PubMed, Embase, and Cochrane library were searched from conception through 23 February 2022. Eligible studies reporting risk of gastric cancer after HRT were screened and accessed by two independent reviewers. Random-effects meta-analysis was used to calculate pooled risk estimate as relative risk (RR, 95% CI). Pre-established review protocol was registered in PROSPERO (CRD42021281260). Among the 1095 articles identified, we included 11 studies with 1,919,089 women in this meta-analysis. The combined risk estimate (RR, 0.72; 95% CI 0.64–0.81; I2 = 2%) indicated that the use of HRT was associated with a 28% reduction in risk of gastric cancer compared with those who had no HRT exposure. The narrow prediction interval (0.62–0.84) for gastric cancer risk suggested a low between-study variance. In subgroup analysis defined by HRT formulation, there were reduction in risks of gastric cancer after the use of estrogen-only therapy (Pooled RR, 0.63; 95% CI 0.51–0.77, I2 = 0%) and estrogen-progestin therapy (Pooled RR, 0.70; 95% CI 0.57–0.87; I2 = 0%), as compared with non-users. In this systematic review and meta-analysis, the use of HRT was associated with a reduced gastric cancer risk regardless of HRT formulation. Further investigations are warranted to confirm underlying mechanisms.
Collagen-depletion strategies in dentin as alternatives to the hybrid layer concept and their effect on bond strength: a systematic review
Authors: H. S. Delgado António , Belmar Da Costa Madalena , Polido Mário Cruz , Mano Azul Ana , Sauro Salvatore 
Published: July 2022

AbstractStrategies aiming to improve the longevity of resin–dentin adhesive interface developed so far have only been able to retard the problem. Different approaches are thus needed. The objective of this review was to determine whether the use of collagen-depletion strategies after acid-etching procedures may improve the bond strength of resin-based materials to dentin. A systematic review was planned following 2021 PRISMA statement guidelines, with a search strategy performed in five electronic databases: PubMed/Medline, Scopus, EMBASE, SciELO and IADR Abstract Archive (last search: 17/01/2022). Inclusion criteria encompassed studies which evaluated a collagen-depletion strategy in acid-etched human dentin and tensile/shear bond strength tests. Risk of bias assessment was carried out by two reviewers, working independently on an adapted five-domain risk of bias (RoB) checklist for laboratory studies. Results were synthesized qualitatively, as a meta-analysis was not possible due to limited number of studies and their RoB. A total of eight studies were eligible for inclusion in the systematic review after inclusion/exclusion criteria application. Out of these, two evaluated the effect of using NaOCl followed by an antioxidant, and the remaining six evaluated different enzymatic treatments (bromelain, chondroitinase ABC, papain, and trypsin). None of the studies reported a decrease of bond strength when a collagen-depletion strategy was used, in comparison to traditional hybrid layers (control). All enzymatic treatment studies which respected the inclusion criteria improved the bond strength to dentin. Some specific collagen-depletion strategies seem to play a favorable role in improving immediate bond strengths to dentin. Further research with sound methodology is required to consolidate these findings, since limitations in RoB and a low number of studies were found. The assessment of further proteolytic agents and long-term outcomes is also required.
Brillouin light scattering in niobium doped lead zirconate single crystal
Authors: Kajewski D. , Oh S. H. , Ko J.-H. , Majchrowski A. , Bussmann-Holder A. , Sitko R. , Roleder K. 
Published: July 2022

AbstractBrillouin light scattering experiments were performed for lead zirconate single crystals doped with niobium. Special attention was paid to the elastic mode softening near phase transition temperatures. The results are compared with data obtained by Raman light scattering experiments. We observed that the interaction between acoustic and optic modes is responsible for symmetry breaking far above TC, leading to polar regions' appearance. No changes in the acoustic mode frequency and its damping are observed at TC, where ε(T) exhibits a maximum value. The absence of these changes and the central peak observed in Raman experiments suggest that the phase transition at TC is mainly of the order–disorder type. The origin of other phase transitions is discussed as well.
The circulating 70 kDa heat shock protein (HSPA1A) level is a potential biomarker for breast carcinoma and its progression
Authors: de Freitas Gabriela Boufelli , Penteado Laura , Miranda Mila Meneguelli , Filassi José Roberto , Baracat Edmund Chada , Linhares Iara Moreno 
Published: July 2022

AbstractThe early diagnosis of breast cancer can improve treatment and prognosis. We sought to evaluate whether the serum concentration of the 70 kDa heat shock protein (HSPA1A) was elevated in Brazilian women with breast cancer, and if levels correlated with tumor characteristics. This was a cross-sectional, analytical, case–control exploratory study performed at The University of São Paulo School of Medicine. From September 2017 to December 2018, 68 women with breast cancer and 59 controls were recruited. The HSPA1A concentration in serum samples was determined by ELISA by individuals blinded to the clinical data. The mean ages in the study and control groups were 54.9 and 52.0 years, respectively. The median serum levels of HSPA1A were elevated in women with breast cancer (1037 pg/ml) compared with controls (300 pg/ml) (p < 0.001). Elevated HSPA1A levels were associated with advanced histological tumor grade (p < 0.001) and with the cell proliferation index (KI67) (p = 0.0418). The HSPA1A concentration was similar in women with different histological subtypes, nuclear grade, hormone receptor expression, HER2 status and the presence or absence of angiolymphatic invasion. Elevated serum HSPA1A in Brazilian women with advanced histological grade and proliferation index breast cancer supports the potential value of additional investigation on larger and more varied populations to verify the value of HSPA1A detection as a component of breast cancer diagnosis and progression.
The abundance of bifidobacterium in relation to visceral obesity and serum uric acid
Authors: Gong Hualan , Gao Hainv , Ren Qingye , He Jia 
Published: July 2022

AbstractGut microbiome has been shown to play a role in the development of obesity in recent studies. Most of these studies on obesity were based on the BMI classification criteria, which doesn't distinguish Visceral adipose tissue (VAT) from subcutaneous adipose tissue (SAT). Some studies showed that VAT has a higher risk of inducing metabolic diseases than SAT. This study focused on the visceral obesity defined by increased visceral fat area. The present study was designed to investigate the association of visceral obesity with gut predominant microbiota and metabolic status. This study included 372 healthy individuals from medical examination center in Shulan Hangzhou Hospital. Quantitative polymerase chain reaction (q-PCR) technique was used to detect ten kinds of gut predominant bacteria in fresh feces. Visceral fat area (VFA) was measured by the bioimpedance analyzer (INBODY720, Korea). The abundance of Bifidobacterium significantly decreased in the visceral obesity group. Compared with the lean group, Visceral obesity group had significantly higher levels of LDL, TG, FBG, serum uric acid (SUA) and lower levels of HDL. SUA was an independent impact factor for Bifidobacterium. SUA was negatively correlated with Bifidobacterium and positively correlated with VFA. In the mediation analysis, SUA showed significant mediation effect. SUA may be a mediating factor between decreased Bifidobacterium and increased VAT.
Prevalence and predictors of difficult vascular anatomy in forearm artery access for coronary angiography and PCI
Authors: Roeschl Tobias , Jano Anas M. , Fochler Franziska , Grewe Mona M. , Wacker Marlis , Meier Kirstin , Schmidt Christian , Maier Lars , Grewe Peter H. 
Published: July 2022

AbstractTransradial access has established as preferred access for cardiac catheterization. Difficult vascular anatomy (DVA) is a noticeable threat to procedural success. We retrospectively analyzed 1397 consecutive cardiac catheterizations to estimate prevalence and identify predictors of DVA. In the subclavian-innominate-aortic-region (SIAR), DVA was causing failure in 2.4% during right-sided vs. 0.7% in left-sided forearm-artery-access (FAA) attempts (χ2 = 5.1, p = 0.023). Independent predictors were advanced age [odds ratio (OR) 1.44 per 10-year increase, 95% confidence interval (CI) 1.15 to 1.80, p = 0.001] and right FAA (OR 2.52, 95% CI 1.72 to 3.69, p < 0.001). In the radial-ulnar-brachial region (RUBR), DVA was causing failure in 2.5% during right-sided vs. 1.7% in left-sided FAA (χ2 = 0.77, p = 0.38). Independent predictors were age (OR 1.28 per 10-year increase, 95% CI 1.01 to 1.61, p = 0.04), lower height (OR 1.56 per 10-cm decrease, 95% CI 1.13 to 2.15, p = 0.008) and left FAA (OR 2.15, 95% CI 1.45 to 3.18, p < 0.001). Bilateral DVA was causing procedural failure in 0.9% of patients. The prevalence of bilateral DVA was rare. Predictors in SIAR were right FAA and advanced age and in RUBR, left FAA, advanced age and lower height. Gender, arterial hypertension, body mass, STEMI and smoking were not associated with DVA.
Stochastic models of Mendelian and reverse transcriptional inheritance in state-structured cancer populations
Authors: Bukkuri Anuraag , Pienta Kenneth J. , Austin Robert H. , Hammarlund Emma U. , Amend Sarah R. , Brown Joel S. 
Published: July 2022

AbstractRecent evidence suggests that a polyaneuploid cancer cell (PACC) state may play a key role in the adaptation of cancer cells to stressful environments and in promoting therapeutic resistance. The PACC state allows cancer cells to pause cell division and to avoid DNA damage and programmed cell death. Transition to the PACC state may also lead to an increase in the cancer cell’s ability to generate heritable variation (evolvability). One way this can occur is through evolutionary triage. Under this framework, cells gradually gain resistance by scaling hills on a fitness landscape through a process of mutation and selection. Another way this can happen is through self-genetic modification whereby cells in the PACC state find a viable solution to the stressor and then undergo depolyploidization, passing it on to their heritably resistant progeny. Here, we develop a stochastic model to simulate both of these evolutionary frameworks. We examine the impact of treatment dosage and extent of self-genetic modification on eco-evolutionary dynamics of cancer cells with aneuploid and PACC states. We find that under low doses of therapy, evolutionary triage performs better whereas under high doses of therapy, self-genetic modification is favored. This study generates predictions for teasing apart these biological hypotheses, examines the implications of each in the context of cancer, and provides a modeling framework to compare Mendelian and non-traditional forms of inheritance.
[18F]-Labeled PARP-1 PET imaging of PSMA targeted alpha particle radiotherapy response
Authors: Zhang Hanwen , Abou Diane , Lu Peng , Hasson Abbie Meghan , Villmer Alexandria , Benabdallah Nadia , Jiang Wen , Ulmert David , Carlin Sean , Rogers Buck E. , Turtle Norman F. , McDevitt Michael R. , Baumann Brian , Simons Brian W. , Dehdashti Farrokh , Zhou Dong , Thorek Daniel L. J. 
Published: July 2022

AbstractThe growing interest and clinical translation of alpha particle (α) therapies brings with it new challenges to assess target cell engagement and to monitor therapeutic effect. Noninvasive imaging has great potential to guide α-treatment and to harness the potential of these agents in the complex environment of disseminated disease. Poly(ADP) ribose polymerase 1 (PARP-1) is among the most abundantly expressed DNA repair enzymes with key roles in multiple repair pathways—such as those induced by irradiation. Here, we used a third-generation PARP1-specific radiotracer, [18F]-PARPZ, to delineate castrate resistant prostate cancer xenografts. Following treatment with the clinically applied [225Ac]-PSMA-617, positron emission tomography was performed and correlative autoradiography and histology acquired. [18F]-PARPZ was able to distinguish treated from control (saline) xenografts by increased uptake. Kinetic analysis of tracer accumulation also suggests that the localization of the agent to sites of increased PARP-1 expression is a consequence of DNA damage response. Together, these data support expanded investigation of [18F]-PARPZ to facilitate clinical translation in the ⍺-therapy space.