bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 (SARS-CoV-2) lymphocyte responses are associated with inflammatory biomarkers in total joint replacement surgery candidates pre-operatively
Authors: Caicedo Marco S. , Flores Vianey , Padilla Alicia , Lauryn Samelko , Jacobs Joshua J. , Hallab Nadim J. 
Published: June 2021

Abstract
Background
Recent studies indicate that, in addition to antibody production, lymphocyte responses to SARS-CoV-2 may play an important role in protective immunity to COVID-19 and a percentage of the general population may exhibit lymphocyte memory due to unknown/asymptomatic exposure to SARS-CoV-2 or cross-reactivity to other more common coronaviruses pre-vaccination. Total joint replacement (TJR) candidates returning to elective surgeries (median age 68 years) may exhibit similar lymphocyte and/or antibody protection to COVID-19 prior to vaccination

Methods
In this retrospective study, we analyzed antibody titters, lymphocyte memory, and inflammatory biomarkers specific for the Spike and Nucleocapsid proteins of the SARS-CoV-2 virus in a cohort of n=73 returning TJR candidates (knees and/or hips) pre-operatively.

Results
Peripheral blood serum of TJR candidate patients exhibited a positivity rate of 18.4% and 4% for IgG antibodies specific for SARS-CoV-2 nucleocapsid and spike proteins, respectively. 13.5% of TJR candidates exhibited positive lymphocyte reactivity (SI > 2) to the SARS-CoV-2 nucleocapsid protein and 38% to the spike protein. SARS-CoV-2 reactive lymphocytes exhibited a higher production of inflammatory biomarkers (i.e., IL-1β, IL-6, TNFα, and IL-1RA) compared to non-reactive lymphocytes.

Conclusions
A percentage of TJR candidates returning for elective surgeries exhibit pre-vaccination positive SARS-CoV-2 antibodies and T cell memory responses with associated pro-inflammatory biomarkers. This is an important parameter for understanding immunity, risk profiles, and may aid pre-operative planning.

Trial registration
Retrospectively registered.
Performance of non-invasive prenatal testing for foetal chromosomal abnormalities in 1048 twin pregnancies
Authors: Cheng Yuan , Lu Xinran , Tang Junxiang , Li Jingran , Sun Yuxiu , Wang Chaohong , Zhu Jiansheng 
Published: June 2021

AbstractObjectiveTo investigate the clinical value of non-invasive prenatal testing (NIPT) to screen for chromosomal abnormalities in twin pregnancies and to provide further data on NIPT manifestations in twin pregnancies.Materials and methodsIn a 4-year period, 1048 women with twin pregnancies were voluntarily prospectively tested by NIPT to screen for chromosomal abnormalities by sequencing cell-free foetal DNA (cffDNA) in maternal plasma. Positive NIPT results were confirmed by karyotyping, while negative results were followed up 42 days after delivery.ResultsThirteen women had positive NIPT results as follows: 2 cases of trisomy 21 (T21), 1 of trisomy 18 (T18), 7 of sex chromosome aneuploidy (SCA), 1 of microdeletion, and 2 of microduplication. Of these 13 cases, 2 were true-positive cases confirmed by foetal karyotype analysis, namely, 1 case of T21 and 1 of microdeletion. Furthermore, the remaining 11 high-risk pregnant women were confirmed as false positive by foetal karyotyping. Thus, the combined positive predictive value (PPV) of NIPT screening for chromosomal abnormalities in twin pregnancies was 15.4% (2/13). There were no false-negative case via our follow-up results.ConclusionSafe and rapid NIPT has a certain clinical application value; however, the PPV is limited, and the screening efficiency is not stable. Careful use should be made in the screening of chromosomal abnormalities in twin pregnancies.
The effect of Melissa officinalis syrup on patients with mild to moderate psoriasis: a randomized, double-blind placebo-controlled clinical trial
Authors: Yargholi Alireza , Shirbeigi Leila , Rahimi Roja , Mansouri Parvin , Ayati Mohammad Hossein 
Published: June 2021

Abstract
Objective
Psoriasis is an immune-mediated inflammatory skin disease. It can involve any body skin area, particularly the scalp, lower back, elbows, and knees. There are several topical and systemic therapies for the treatment. Nowadays, herbal medicines are popular treatments for dermatologic conditions. This two-arm parallel, randomized placebo-controlled clinical trial was conducted to examine the hypothesis of the efficacy of Melissa officinalis syrup on patients with mild-to-moderate Plaque psoriasis.

Result
Among 100 patients, 95 participants completed the trial and five of them withdrew. The mean pruritus intensity and PASI scores decreased significantly in the intervention group compared to the placebo group (P < 0.001). The DLQI score in the intervention group increased post-treatment compared to pre-treatment (P = 0.029); however, there was no significant difference between the intervention and control group at the end of the study (0.065).
Trial registration: The trial was registered in the Iranian registry of clinical trials on November 9th, 2019 (https://www.irct.ir/trial/43434; registration number: IRCT20191104045326N1).
A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer
Authors: Ylitalo Erik Bovinder , Thysell Elin , Landfors Mattias , Brattsand Maria , Jernberg Emma , Crnalic Sead , Widmark Anders , Hultdin Magnus , Bergh Anders , Degerman Sofie , Wikström Pernilla 
Published: June 2021

Abstract
Background
Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity.

Materials and methods
Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity.

Results
Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT.

Conclusions
A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.
Methylation status of genes escaping from X-chromosome inactivation in patients with X-chromosome rearrangements
Authors: Kawashima Sayaka , Hattori Atsushi , Suzuki Erina , Matsubara Keiko , Toki Machiko , Kosaki Rika , Hasegawa Yukihiro , Nakabayashi Kazuhiko , Fukami Maki , Kagami Masayo 
Published: June 2021

Abstract
Background
X-chromosome inactivation (XCI) is a mechanism in which one of two X chromosomes in females is randomly inactivated in order to compensate for imbalance of gene dosage between sexes. However, about 15% of genes on the inactivated X chromosome (Xi) escape from XCI. The methylation level of the promoter region of the escape gene is lower than that of the inactivated genes. Dxz4 and/or Firre have critical roles for forming the three-dimensional (3D) structure of Xi. In mice, disrupting the 3D structure of Xi by deleting both Dxz4 and Firre genes led to changing of the escape genes list. To estimate the impact for escape genes by X-chromosome rearrangements, including DXZ4 and FIRRE, we examined the methylation status of escape gene promoters in patients with various X-chromosome rearrangements.

Results
To detect the breakpoints, we first performed array-based comparative genomic hybridization and whole-genome sequencing in four patients with X-chromosome rearrangements. Subsequently, we conducted array-based methylation analysis and reduced representation bisulfite sequencing in the four patients with X-chromosome rearrangements and controls. Of genes reported as escape genes by gene expression analysis using human hybrid cells in a previous study, 32 genes showed hypomethylation of the promoter region in both male controls and female controls. Three patients with X-chromosome rearrangements had no escape genes with abnormal methylation of the promoter region. One of four patients with the most complicated rearrangements exhibited abnormal methylation in three escape genes. Furthermore, in the patient with the deletion of the FIRRE gene and the duplication of DXZ4, most escape genes remained hypomethylated.

Conclusion
X-chromosome rearrangements are unlikely to affect the methylation status of the promoter regions of escape genes, except for a specific case with highly complex rearrangements, including the deletion of the FIRRE gene and the duplication of DXZ4.
Predictors of physicians’ intentions to use clinical practice guidelines on antimicrobial in tertiary general hospitals of China: a structural equation modeling approach
Authors: Deng Qingwen , Zeng Zhichao , Zheng Yuhang , Lu Junhong , Liu Wenbin 
Published: June 2021

Abstract
Background
With inappropriate use of antimicrobials becoming a great public health concern globally, the issue of applying clinical practice guidelines (CPGs) to regulate the rational use of antimicrobials has attracted increasing attention. Taking tertiary general hospitals in China for example, this study aimed to identify factors to investigate the comprehensive influencing mechanism for physicians’ intention to use CPGs on antimicrobials.

Methods
Based on the integration of Theory of Planned Behavior (TPB), Technology Acceptance Model (TAM), and Technology-Organization-Environment framework (TOE), a questionnaire survey was conducted covering potential determinants of affecting physicians’ intentions to use CPGs on antimicrobials at the individual level (attitude, subjective norms and perceived risk), technical level (relative advantage and ease of use), and organizational level (top management support and organizational implementation). Data were collected from 644 physicians in tertiary general hospitals in eastern, central and western China, which were obtained by multi-stage random sampling. The structural equation modeling (SEM) was used to link three-level factors with physicians’ behavioral intentions.

Results
The majority of the participants (94.57%) showed a positive tendency toward intention to use CPGs on antimicrobials. The reliability and validity analysis showed the questionnaire developed from the theoretical model was acceptable. SEM results revealed physicians’ intentions to use CPGs on antimicrobials was associated with attitude (β = 0.166, p < 0.05), subjective norms (β = 0.244, p < 0.05), perceived risk (β = − 0.113, p < 0.05), relative advantage (β = 0.307, p < 0.01), top management support (β = 0.200, p < 0.05) and organizational implementation (β = 0.176, p < 0.05). Besides, subjective norms, perceived risk, relative advantage, ease of use, and top management support showed their mediating effects from large to small on the intentions, which were 0.215, 0.140, 0.103, 0.088, − 0.020, respectively.

Conclusions
This study revealed the significance of multifaceted factors to enhance the intention to use CPGs on antimicrobials. These findings will not only contribute to the development of targeted intervention strategies on promoting the use of CPGs on antimicrobials, but also provide insights for future studies about physicians’ adoption behaviors on certain health services or products.
Small quantities of respiratory syncytial virus RNA only in large droplets around infants hospitalized with acute respiratory infections
Authors: Kutter Jasmin S. , de Meulder Dennis , Bestebroer Theo M. , van Kampen Jeroen J. A. , Molenkamp Richard , Fouchier Ron A. M. , Wishaupt Jérôme O. , Fraaij Pieter L. A. , Herfst Sander 
Published: June 2021

Abstract
Background
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in young children. The predominant transmission routes for RSV are still a matter of debate. Specifically, it remains unclear if RSV can be transmitted through the air and what the correlation is between the amount of RSV in nasopharynx samples and in the air.

Methods
The amount of RSV in the air around hospitalized RSV infected infants in single-patient rooms was quantified using a six-stage Andersen cascade impactor that collects and fractionates aerosols and droplets according to size. RSV shedding in the nasopharynx of patients was followed longitudinally by quantifying RSV RNA levels and infectious virus in nasopharyngeal aspirates. Nose and throat swabs of parents and swabs of the patient’s bedrail and a datalogger were also collected.

Results
Patients remained RSV positive during the air sampling period and infectious virus was isolated up to 9 days post onset of symptoms. In three out of six patients, low levels of RSV RNA, but no infectious virus, were recovered from impactor collection plates that capture large droplets > 7 μm. For four of these patients, one or both parents were also positive for RSV. All surface swabs were RSV-negative.

Conclusions
Despite the prolonged detection of infectious RSV in the nasopharynx of patients, only small amounts of RSV RNA were collected from the air around three out of six patients, which were primarily contained in large droplets which do not remain suspended in the air for long periods of time.
Combined antibiotic stewardship and infection control measures to contain the spread of linezolid-resistant Staphylococcus epidermidis in an intensive care unit
Authors: Papan Cihan , Schröder Matthias , Hoffmann Mathias , Knoll Heike , Last Katharina , Albrecht Frederic , Geisel Jürgen , Fink Tobias , Gärtner Barbara C. , Mellmann Alexander , Volk Thomas , Berger Fabian K. , Becker Sören L. 
Published: June 2021

AbstractBackgroundThe unrestricted use of linezolid has been linked to the emergence of linezolid-resistantStaphylococcus epidermidis(LRSE). We report the effects of combined antibiotic stewardship and infection control measures on the spread of LRSE in an intensive care unit (ICU).MethodsMicrobiological data were reviewed to identify all LRSE detected in clinical samples at an ICU in southwest Germany. Quantitative data on the use of antibiotics with Gram-positive coverage were obtained in defined daily doses (DDD) per 100 patient-days (PD). In addition to infection control measures, an antibiotic stewardship intervention was started in May 2019, focusing on linezolid restriction and promoting vancomycin, wherever needed. We compared data from the pre-intervention period (May 2018–April 2019) to the post-intervention period (May 2019–April 2020). Whole-genome sequencing (WGS) was performed to determine the genetic relatedness of LRSE isolates.ResultsIn the pre-intervention period, LRSE were isolated from 31 patients (17 in blood cultures). The average consumption of linezolid and daptomycin decreased from 7.5 DDD/100 PD and 12.3 DDD/100 PD per month in the pre-intervention period to 2.5 DDD/100 PD and 5.7 DDD/100 PD per month in the post-intervention period (p = 0.0022 and 0.0205), respectively. Conversely, vancomycin consumption increased from 0.2 DDD/100 PD per month to 4.7 DDD/100 PD per month (p < 0.0001). In the post-intervention period, LRSE were detected in 6 patients (4 in blood cultures) (p = 0.0065). WGS revealed the predominance of one single clone.ConclusionsComplementing infection control measures by targeted antibiotic stewardship interventions was beneficial in containing the spread of LRSE in an ICU.
An SPH framework for fluid–solid and contact interaction problems including thermo-mechanical coupling and reversible phase transitions
Authors: Fuchs Sebastian L. , Meier Christoph , Wall Wolfgang A. , Cyron Christian J. 
Published: June 2021

AbstractThe present work proposes an approach for fluid–solid and contact interaction problems including thermo-mechanical coupling and reversible phase transitions. The solid field is assumed to consist of several arbitrarily-shaped, undeformable but mobile rigid bodies, that are evolved in time individually and allowed to get into mechanical contact with each other. The fluid field generally consists of multiple liquid or gas phases. All fields are spatially discretized using the method of smoothed particle hydrodynamics (SPH). This approach is especially suitable in the context of continually changing interface topologies and dynamic phase transitions without the need for additional methodological and computational effort for interface tracking as compared to mesh- or grid-based methods. Proposing a concept for the parallelization of the computational framework, in particular concerning a computationally efficient evaluation of rigid body motion, is an essential part of this work. Finally, the accuracy and robustness of the proposed framework is demonstrated by several numerical examples in two and three dimensions, involving multiple rigid bodies, two-phase flow, and reversible phase transitions, with a focus on two potential application scenarios in the fields of engineering and biomechanics: powder bed fusion additive manufacturing (PBFAM) and disintegration of food boluses in the human stomach. The efficiency of the parallel computational framework is demonstrated by a strong scaling analysis.
The roles of ribosomal proteins in nasopharyngeal cancer: culprits, sentinels or both
Authors: Sim Edmund Ui-Hang , Lee Choon-Weng , Narayanan Kumaran 
Published: June 2021

AbstractRibosomal protein genes encode products that are essential for cellular protein biosynthesis and are major components of ribosomes. Canonically, they are involved in the complex system of ribosome biogenesis pivotal to the catalysis of protein translation. Amid this tightly organised process, some ribosomal proteins have unique spatial and temporal physiological activity giving rise to their extra-ribosomal functions. Many of these extra-ribosomal roles pertain to cellular growth and differentiation, thus implicating the involvement of some ribosomal proteins in organogenesis. Consequently, dysregulated functions of these ribosomal proteins could be linked to oncogenesis or neoplastic transformation of human cells. Their suspected roles in carcinogenesis have been reported but not specifically explained for malignancy of the nasopharynx. This is despite the fact that literature since one and half decade ago have documented the association of ribosomal proteins to nasopharyngeal cancer. In this review, we explain the association and contribution of dysregulated expression among a subset of ribosomal proteins to nasopharyngeal oncogenesis. The relationship of these ribosomal proteins with the cancer are explained. We provide information to indicate that the dysfunctional extra-ribosomal activities of specific ribosomal proteins are tightly involved with the molecular pathogenesis of nasopharyngeal cancer albeit mechanisms yet to be precisely defined. The complete knowledge of this will impact future applications in the effective management of nasopharyngeal cancer.
Diffusion modeling reveals effects of multiple release sites and human activity on a recolonizing apex predator
Authors: Eisaguirre Joseph M. , Williams Perry J. , Lu Xinyi , Kissling Michelle L. , Beatty William S. , Esslinger George G. , Womble Jamie N. , Hooten Mevin B. 
Published: June 2021

AbstractBackgroundReintroducing predators is a promising conservation tool to help remedy human-caused ecosystem changes. However, the growth and spread of a reintroduced population is a spatiotemporal process that is driven by a suite of factors, such as habitat change, human activity, and prey availability. Sea otters (Enhydra lutris) are apex predators of nearshore marine ecosystems that had declined nearly to extinction across much of their range by the early 20th century. In Southeast Alaska, which is comprised of a diverse matrix of nearshore habitat and managed areas, reintroduction of 413 individuals in the late 1960s initiated the growth and spread of a population that now exceeds 25,000.MethodsPeriodic aerial surveys in the region provide a time series of spatially-explicit data to investigate factors influencing this successful and ongoing recovery. We integrated an ecological diffusion model that accounted for spatially-variable motility and density-dependent population growth, as well as multiple population epicenters, into a Bayesian hierarchical framework to help understand the factors influencing the success of this recovery.ResultsOur results indicated that sea otters exhibited higher residence time as well as greater equilibrium abundance in Glacier Bay, a protected area, and in areas where there is limited or no commercial fishing. Asymptotic spread rates suggested sea otters colonized Southeast Alaska at rates of 1–8 km/yr with lower rates occurring in areas correlated with higher residence time, which primarily included areas near shore and closed to commercial fishing. Further, we found that the intrinsic growth rate of sea otters may be higher than previous estimates suggested.ConclusionsThis study shows how predator recolonization can occur from multiple population epicenters. Additionally, our results suggest spatial heterogeneity in the physical environment as well as human activity and management can influence recolonization processes, both in terms of movement (or motility) and density dependence.