bluuebunny/crossref_metadata_2025 huggingface dataset:
How much do the conventional parameters contribute to the biological toxicity of surface water in different types of villages?
Authors: Shao Ying , Fan Yueting , Yang Yinjie , Zhou Min , Li Tingting , Fang Fang , Wang Chenchen , Jiang Yanxue , Chen Zhongli , Guo Jinsong
Published: June 2021

Background

In rural areas, the surface water quality is seriously threatened by pollution from agriculture, breeding, industrial and tourism activities. Even though many strategies and programs were launched for rural environment management, it is challenging to tackle the serious surface water pollution in villages. Since pollution status varies with the type of villages, there is no single parameter that defines environment quality completely. Until recently, most of rural surface water quality monitoring programs focus only on the conventional parameters, while can these conventional parameters reflect comprehensive status of water quality? To study how much the conventional parameters contribute to biological toxicity of surface water in villages, the in situ parameters of pH, DO, EC, ORP, laboratorial parameters of COD, TN, NO3−-N, NO2−-N, NH4+-N, TP, and PO43−-P and acute toxicity were analyzed for the surface water samples those were collected from six types of villages, named breeding, agricultural, handicraft, industrial, agricultural and breeding, and tourism. The correlation analysis was applied to establish the linkages and contributions of each parameter.

Results

The results showed that all detected surface waters were alkaline, and the concentration of TN and most of COD concentrations in all six types of villages were higher than the Class V limits specified in environmental quality standards for surface water (GB3838-2002). Pearson’s correlation analysis showed that significantly positive correlations were found for the acute toxicity effects and laboratorial parameters of NO2−-N, NH4+-N and PO43−-P in agricultural villages, and negative correlations were found for the acute toxicity effects and laboratorial parameters of TN and NO3−-N. No significant correlation was observed in breeding villages and industrial villages.

Conclusion

The problems of nitrogen pollution and aerobic pollution are still serious in villages, and more attention should be paid in further rural environment management. NH4+-N could contribute to the acute toxicity of surface water in the most of investigated villages, while no significant correlation was observed between acute toxicity and conventional parameters in industrial villages and tourism villages. Environmental monitoring programs focusing just on the classical conventional parameters are far from sufficient, since the main toxic contributors are quite different in diverse villages. The outcomes of the present study contribute to demonstrate the performance and usefulness of bioanalytical techniques for water quality assessment.
Effects of different vasopressors on the contraction of the superior mesenteric artery and uterine artery in rats during late pregnancy
Authors: Wang Tingting , Liao Limei , Tang Xiaohui , Li Bin , Huang Shaoqiang
Published: June 2021

Background

Hypotension after neuraxial anaesthesia is one of the most common complications during caesarean section. Vasopressors are the most effective method to improve hypotension, but which of these drugs is best for caesarean section is not clear. We assessed the effects of vasopressors on the contractile response of uterine arteries and superior mesenteric arteries in pregnant rats to identify a drug that increases the blood pressure of the systemic circulation while minimally affecting the uterine and placental circulation.

Methods

Isolated ring segments from the uterine and superior mesenteric arteries of pregnant rats were mounted in organ baths, and the contractile responses to several vasopressor agents were studied. Concentration-response curves for norepinephrine, phenylephrine, metaraminol and vasopressin were constructed.

Results

The contractile response of the mesenteric artery to norepinephrine, as measured by the pEC50 of the drug, was stronger than the uterine artery (5.617 ± 0.11 vs. 4.493 ± 1.35, p = 0.009), and the contractile response of the uterine artery to metaraminol was stronger than the mesenteric artery (pEC50: 5.084 ± 0.17 vs. 4.92 ± 0.10, p = 0.007). There was no statistically significant difference in the pEC50 of phenylephrine or vasopressin between the two blood vessels.

Conclusions

In vitro experiments showed that norepinephrine contracts peripheral blood vessels more strongly and had the least effect on uterine artery contraction. These findings support the use of norepinephrine in mothers between the time of neuraxial anaesthesia and the delivery of the foetus.
A national survey on COVID-19 second-wave lockdowns on older adults’ mental wellbeing, health-seeking behaviours and social outcomes across Australia
Authors: Siette Joyce , Seaman Karla , Dodds Laura , Ludlow Kristiana , Johnco Carly , Wuthrich Viviana , Earl Joanne K. , Dawes Piers , Strutt Paul , Westbrook Johanna I.
Published: June 2021

Background

The impact of severe second lockdown measures on older adults’ wellbeing is unknown. We aimed to (i) identify the impact of the second lockdown that resulted from the second wave of COVID-19 cases on older Australians’ quality of life; (ii) compare the impact of second wave lockdowns in Victoria, Australia’s second most populous State, to those in other States and Territories not in lockdown.

Methods

A national cross-sectional study of community-dwelling older adults completed online questionnaires for quality of life, social networks, healthcare access, and perceived impact of COVID-19 between July to September 2020. Tobit regression was used to measure the relationships of healthcare service access and social networks with quality of life of older adults in Victoria compared to those in the rest of Australia.

Results

A total of 2,990 respondents (mean [SD] age, 67.3 [7.0]; 66.8 % female) participated. At time of data collection, Victoria’s second COVID-19 lockdown had been in force for an average 51.7 days. Median quality of life scores were significantly higher in Victoria compared to the rest of Australia (t2,827=2.25 p = 0.025). Being female (95 % CI, -0.051–0.020), having lower educational attainment (95 % CI, -0.089–-0.018), receiving government benefits (95 % CI, -0.054–-0.024), having small social networks (95 % CI, 0.006–0.009) and self-reported physical chronic health conditions were all independent predictors of lower quality of life.

Conclusions

Longer-term studies are required to provide more robust evidence of the impact as restrictions lift and normal social conventions return.
Increased cerebrospinal fluid adenosine 5'-triphosphate in patients with amyotrophic lateral sclerosis
Authors: Nukui Takamasa , Matsui Atsushi , Niimi Hideki , Sugimoto Tomoyuki , Hayashi Tomohiro , Dougu Nobuhiro , Konishi Hirofumi , Yamamoto Mamoru , Anada Ryoko , Matsuda Noriyuki , Kitajima Isao , Nakatsuji Yuji
Published: June 2021

Background

Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined cerebrospinal fluid (CSF) ATP levels in patients with ALS whether it can be a useful biomarker in ALS.

Methods

Forty-eight CSF samples from 44 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated.

Results

CSF ATP levels were significantly higher in patients with ALS than in the iNPH (716 ± 411 vs. 3635 ± 5465 pmol/L, p < 0.01). CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. ALS functional rating scale-revised (ALSFRS-R) (37.9 ± 5.7 vs. 42.4 ± 2.8, p < 0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis adjusted for age and sex (r = -0.3, p = 0.08).

Conclusions

Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.
Timing of initiation of breastfeeding and its determinants at a tertiary hospital in Ghana: a cross-sectional study
Authors: Boakye-Yiadom Adwoa Pokua , Nguah Samuel Blay , Ameyaw Emmanuel , Enimil Anthony , Wobil Priscilla Naa Lomle , Plange-Rhule Gyikua
Published: June 2021

Background

Early initiation of breastfeeding (EIBF), breastfeeding within first hour after birth, is known to have major benefits for both the mother and newborn. EIBF rates, however, tends to vary between and within countries. This study set out to determine the prevalence of EIBF at the Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana, and to evaluate the determinants of EIBF and time to initiation of breastfeeding.

Methods

A cross-sectional study was conducted at the KATH postnatal wards between August and October 2014. Three hundred and eighty-two mothers delivering at KATH were recruited and data on time to initiation of breastfeeding, antenatal, delivery and immediate postnatal periods were collected. Data analyses using both binary and ordinal logistic regressions with stepwise elimination were used to determine the relationship between EIBF and time to initiation of breastfeeding on one side, and the maternal, pregnancy, delivery and neonatal associated factors.

Results

EIBF was done in 39.4% (95%CI: 34.3–44.5) of the newborns with breastfeeding initiated between 1 to 6 h for 19.7%, 6 to 11 h in 4.8%, 11 to 16 h in 4.8% and after 16 h in 28.5% of the deliveries. A higher number of antenatal care visits (AOR = 1.14, 95%CI: 1.04–1.25, p = 0.006), delivery by caesarean section (AOR = 0.07, 95%CI: 0.01–0.79, p = 0.031) and infant rooming-in with mother (AOR: 31.67, 95%CI: 5.59–179.43, p <  0.001) were significantly and independently associated with EIBF. Factors independently associated with longer time to initiation of breastfeeding were older maternal age (AOR = 1.04, 95%CI: 1.00–1.09, p = 0.039), Akan ethnicity (AOR = 1.92, 95%CI: 1.14–3.22, p = 0.014), first-born child (AOR = 2.06, 95%CI: 1.18–3.58, p = 0.011), mother rooming-in with newborn (AOR = 0.01. 95%CI: 0.00–0.02, p <  0.001), increasing fifth minute APGAR score (AOR = 0.73, 95%CI: 0.58–0.93, p = 0.010) and using prelacteals (AOR = 2.42, 95%CI: 1.34–4.40, p = 0.004).

Conclusions

The low EIBF rate and prolonged time to initiation of breastfeeding at a major tertiary health facility is a major concern. Key interventions will need to be implemented at KATH and possibly other tertiary healthcare facilities in Ghana and beyond to improve EIBF rate and time to breastfeeding.
BCL-xL is correlated with disease severity in neonatal infants with early sepsis
Authors: Wenshen Wu , Qi Peng , Tianli Huang , Jinfeng Liao , Ning Li
Published: June 2021

Background

Sepsis is the most common cause of morbidity and mortality in neonatal infants. It is essential to find an accurate and sensitive biomarker to confirm and treat neonatal sepsis in order to decrease the rate of mortality. The aim of this study was to investigate the association between disease severity in patients with sepsis and TNF-α, B cell lymphoma-extra-large (BCL-xL), and serum Mitochondrial membrane potential (MMP).

Methods

We investigated the correlation between SNAP-II score and levels of TNF-α, BCL-xL, and MMP-index, respectively. The receiver-operating characteristics (ROC) was to assess the diagnostic value of the the Bcl-xL in the diagnosis of the of septic shock.

Results

A total of 37 infants were diagnosed with sepsis. SNAP-II was positively correlated with the level of BCL-xL (r = 0.450, P = 0.006). The area under the BCL-xL curve was 83.0 %, and the 95 % CI was 67.1–93.3 %. The septic shock threshold was > 3.022 ng/mL, and the sensitivity and specificity were 75.0 and 95.2 %, respectively. The positive predictive value was 92.3 %, and the negative predictive value was 83.3 %. Furthermore, the level of SNAP-II was > 10, and BCL-xL was > 3.022 ng/mL as the threshold, and the sensitivity, specificity, positive predictive value, and negative predictive value of septic shock were 93.8 %, 95.2 %, 93.8 %, and 95.2 %, respectively.

Conclusions

BCL-xL is associated with the progression of sepsis. The combination of BCL-xL and SNAP-II could be early predicte the severity of the disease.
A systems pharmacology approach based on oncogenic signalling pathways to determine the mechanisms of action of natural products in breast cancer from transcriptome data
Authors: Odongo Regan , Demiroglu-Zergeroglu Asuman , Çakır Tunahan
Published: June 2021

Background

Narrow spectrum of action through limited molecular targets and unforeseen drug-related toxicities have been the main reasons for drug failures at the phase I clinical trials in complex diseases. Most plant-derived compounds with medicinal values possess poly-pharmacologic properties with overall good tolerability, and, thus, are appropriate in the management of complex diseases, especially cancers. However, methodological limitations impede attempts to catalogue targeted processes and infer systemic mechanisms of action. While most of the current understanding of these compounds is based on reductive methods, it is increasingly becoming clear that holistic techniques, leveraging current improvements in omic data collection and bioinformatics methods, are better suited for elucidating their systemic effects. Thus, we developed and implemented an integrative systems biology pipeline to study these compounds and reveal their mechanism of actions on breast cancer cell lines.

Methods

Transcriptome data from compound-treated breast cancer cell lines, representing triple negative (TN), luminal A (ER+) and HER2+ tumour types, were mapped on human protein interactome to construct targeted subnetworks. The subnetworks were analysed for enriched oncogenic signalling pathways. Pathway redundancy was reduced by constructing pathway-pathway interaction networks, and the sets of overlapping genes were subsequently used to infer pathway crosstalk. The resulting filtered pathways were mapped on oncogenesis processes to evaluate their anti-carcinogenic effectiveness, and thus putative mechanisms of action.

Results

The signalling pathways regulated by Actein, Withaferin A, Indole-3-Carbinol and Compound Kushen, which are extensively researched compounds, were shown to be projected on a set of oncogenesis processes at the transcriptomic level in different breast cancer subtypes. The enrichment of well-known tumour driving genes indicate that these compounds indirectly dysregulate cancer driving pathways in the subnetworks.

Conclusion

The proposed framework infers the mechanisms of action of potential drug candidates from their enriched protein interaction subnetworks and oncogenic signalling pathways. It also provides a systematic approach for evaluating such compounds in polygenic complex diseases. In addition, the plant-based compounds used here show poly-pharmacologic mechanism of action by targeting subnetworks enriched with cancer driving genes. This network perspective supports the need for a systemic drug-target evaluation for lead compounds prior to efficacy experiments.
Genetic aetiology of primary adrenal insufficiency in Chinese children
Authors: Chang Zhuo , Lu Wei , Zhao Zhuhui , Xi Li , Li Xiaojing , Ye Rong , Ni Jinwen , Pei Zhou , Zhang Miaoying , Cheng Ruoqian , Zheng Zhangqian , Sun Chengjun , Wu Jing , Luo Feihong
Published: June 2021

Background

Primary adrenal insufficiency (PAI) is life-threatening, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features.

Methods

Seventy children were enrolled in this cross-sectional study. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants.

Results

Among the 70 children, 84.3% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and 21-hydroxylase deficiency (21-OHD) was genetically confirmed in 91.5% of these cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.1% (39/59), 30.5% (18/59), and 3.4% (2/59) of the cases, respectively. The 17-hydroxyprogesterone (17-OHP) and testosterone (TES) levels were significantly higher in children with SW than with SV. The 17-OHP and cortisol levels in female SW patients were significantly higher than those in males. The 17-OHP, cortisol, dehydroepiandrosterone (DHEAS) and TES levels in female SW patients were significantly higher than those in female SV patients. Additionally, 72.7% (8/11) of uncharacterized PAI patients had positive genetic findings. Among all the patients, two novel variants in the CYP21A2 gene (c.833dupT and c.651 + 2T > G) were found. A microdeletion (Xp21.2–21.3) and five novel variants, including 2 in the NR0B1 gene (c.323–324CG > GA and c.1231_1234delCTCA), 2 in the AAAS gene (c.399 + 1G > A and c.250delT) and 1 in the NNT gene (c.2274delT), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 skipping during mRNA transcription and produce a truncated ALADIN protein.

Conclusions

We found ethnicity-based differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and TES levels, which warrants caution in relation to the effects of virilization. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of PAI, however, further improvement of genetic testing tools beyond our protocol are still needed to uncover the complete aetiology of PAI in children.
Relationship between polymorphism of receptor SCARB2 gene and clinical severity of enterovirus-71 associated hand-foot-mouth disease
Authors: Wang Xia , Liu Hong , Li Ying , Su Rui , Liu Yamin , Qiao Kunyan
Published: June 2021

Background

To investigate the relationship between polymorphism of scavenger receptor class B member 2 (SCARB2) gene and clinical severity of enterovirus (EV)-71 associated hand-foot-mouth disease (HFMD).

Methods

Among the 100 recruited cases, 56 were in the severe HFMD group (case group) and 44 were in the general HFMD group (control group). By screening functional single nucleotide polymorphisms (SNPs) and hot SNPs, and performing SNP site optimization, some SNP sites of SCARB2 gene were selected for analysis. Genotyping was performed using a MassArray platform. PLINK software was used for statistical processing and analysis of the correlation differences between the mutant genotypes in the severe and general HFMD groups. The relationship between the SNPs and clinical severity of enterovirus (EV)-71 associated HFMD was assessed.

Results

28 SNPs in SCARB2 were selected by site optimization. Then three loci were not in agreement with the minor allele frequency (MAF) in the 1000 Han Chinese in Beijing (CHB) dataset. Another three loci could not be detected. Nine loci were not suitable for further analysis (MAF < 0.01 and Hardy–Weinberg [HWE] P < 0.001). A total of 13 sites were subsequently analyzed. Through Fisher analysis, the frequency of the rs6812193 T allele was 0.134 and 0.034 in the severe and general HFMD groups, respectively (P 0.023 < 0.05, odds ratio [OR] 4.381 > 1). Logistic regression analysis of rs6812193 T alleles between the severe and general HFMD groups, respectively (P 0.023 < 0.05, OR 4.412 > 1, L95 1.210 > 1). Genotype logistic regression analysis of the rs6812193 alleles CT + TT versus CC gave an OR of 4.56 (95% confidence interval [95% CI] 1.22–17.04, P = 0.012).

Conclusion

The rs6812193 T allele was a susceptibility SNP for SHFMD, and the rs6812193 polymorphism might be significantly associated with the susceptibility to EV-71 infection.
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

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

Objective

To 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 methods

In 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.

Results

Thirteen 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.

Conclusion

Safe 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

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

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

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

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

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

Background

The 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).

Methods

Microbiological 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.

Results

In 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.

Conclusions

Complementing 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

The 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

Ribosomal 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

Background

Reintroducing 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.

Methods

Periodic 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.

Results

Our 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.

Conclusions

This 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.
The Quantification of Acceleration Events in Elite Team Sport: a Systematic Review
Authors: Delves Robert I. M. , Aughey Robert J. , Ball Kevin , Duthie Grant M.
Published: June 2021

Background

Wearable tracking devices are commonly utilised to quantify the external acceleration load of team sport athletes during training and competition. The ability to accelerate is an important attribute for athletes in many team sports. However, there are many different acceleration metrics that exist in team sport research. This review aimed to provide researchers and practitioners with a clear reporting framework on acceleration variables by outlining the different metrics and calculation processes that have been adopted to quantify acceleration loads in team sport research.

Methods

A systematic review of three electronic databases (CINAHL, MEDLINE, SPORTDiscus), was performed to identify peer-reviewed studies that published external acceleration load in elite team sports during training and/or competition. Articles published between January 2010 and April 2020 were identified using Boolean search phrases in relation to team sports (population), acceleration/deceleration (comparators), and competition and/or training (outcome). The included studies were required to present external acceleration and/or deceleration load (of any magnitude) from able-bodied athletes (mean age ≥ 18 years) via wearable technologies.

Results

A total of 124 research articles qualified for inclusion. In total, 113/124 studies utilised GPS/GNSS technology to outline the external acceleration load of athletes. Count-based metrics of acceleration were predominant of all metrics in this review (72%). There was a lack of information surrounding the calculation process of acceleration with 13% of studies specifying the filter used in the processing of athlete data, whilst 32% outlined the minimum effort duration (MED). Markers of GPS/GNSS data quality, including horizontal dilution of precision (HDOP) and the average number of satellites connected, were outlined in 24% and 27% of studies respectively.

Conclusions

Team sport research has predominantly quantified external acceleration load in training and competition with count-based metrics. Despite the influence of data filtering processes and MEDs upon acceleration, this information is largely omitted from team sport research. Future research that outlines acceleration load should present filtering processes, MEDs, HDOP, and the number of connected satellites. For GPS/GNSS systems, satellite planning tools should document evidence of available satellites for data collection to analyse tracking device performance. The development of a consistent acceleration filtering method should be established to promote consistency in the research of external athlete acceleration loads.