bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beware of pharyngeal Fusobacterium nucleatum in COVID-19
Authors: Bao Lirong , Zhang Cheng , Lyu Jinglu , Yan Caixia , Cao Ranran , Pan Ming , Li Yan 
Published: October 2021

Abstract
Background
Fusobacterium nucleatum (F. n) is an important opportunistic pathogen causing oral and gastrointestinal disease. Faecalibacterium prausnitzii (F. p) is a next-generation probiotic and could serve as a biomarker of gut eubiosis/dysbiosis to some extent. Alterations in the human oral and gut microbiomes are associated with viral respiratory infection. The aim of this study was to characterise the oral and fecal bacterial biomarker (i.e., F. n and F. p) in COVID-19 patients by qPCR and investigate the pharyngeal microbiome of COVID-19 patients through metagenomic next-generation sequencing (mNGS).

Results
Pharyngeal F. n was significantly increased in COVID-19 patients, and it was higher in male than female patients. Increased abundance of pharyngeal F. n was associated with a higher risk of a positive SARS-CoV-2 test (adjusted OR = 1.32, 95% CI = 1.06 ~ 1.65, P < 0.05). A classifier to distinguish COVID-19 patients from the healthy controls based on the pharyngeal F. n was constructed and achieved an area under the curve (AUC) of 0.843 (95% CI = 0.688 ~ 0.940, P < 0.001). However, the level of fecal F. n and fecal F. p remained unaltered between groups. Besides, mNGS showed that the pharyngeal swabs of COVID-19 patients were dominated by opportunistic pathogens.

Conclusions
Pharyngeal but not fecal F. n was significantly increased in COVID-19 patients, clinicians should pay careful attention to potential coinfection. Pharyngeal F. n may serve as a promising candidate indicator for COVID-19.
Use of health and aged care services in Australia following hospital admission for myocardial infarction, stroke or heart failure
Authors: Hsu Benjumin , Korda Rosemary J. , Lindley Richard I. , Douglas Kirsty A. , Naganathan Vasi , Jorm Louisa R. 
Published: October 2021

AbstractBackgroundCardiovascular diseases (CVD), including myocardial infarction (MI), stroke and heart failure (HF) are the leading cause of death amongst the older population worldwide. The aim of this study is to investigate trajectories of use of health and aged care services after hospital admission for MI, stroke or HF among community-dwelling people not previously receiving aged care services.MethodsThe study population comprised people aged 65+ years from the 45 and Up Study with linked records for hospital stays, aged care services and deaths for the period 2006–14. Among those with an index hospital admission for MI, stroke or HF, we developed Sankey plots to describe and visualize sequences and trajectories of service use (none, re-hospitalization, community care, residential care, death) in the 12 months following discharge. We used Cox proportional hazards models to estimate hazard ratios (HRs), for commencing community care and entering residential care (and the other outcomes) within 3, 6 and 12 months, compared to a matched group without MI, stroke or HF.ResultsTwo thousand six hundred thirty-nine, two thousand five hundred and two thousand eight hundred seventy-three people had an index hospitalization for MI, stroke and HF, respectively. Within 3 months of hospital discharge, 16, 32 and 29%, respectively, commenced community care (multivariable-adjusted HRs: 1.26 (95%CI:1.18–1.35), 1.53 (95%CI:1.44–1.64) and 1.39 (95%CI:1.32–1.48)); and 7, 18 and 14%, respectively, entered residential care (HRs: 1.25 (95%CI:1.12–1.41), 2.65 (95%CI:2.42–2.91) and 1.50 (95%CI:1.37–1.65)). Likewise, 26, 15 and 28%, respectively, were rehospitalized within 3 months following discharge (multivariable-adjusted HRs: 4.78 (95%CI:4.31–5.32), 3.26 (95%CI:2.91–3.65) and 4.94 (95%CI:4.47–5.46)).ConclusionsOlder people hospitalized for major CVD may be vulnerable to transition-related risks and have poor health trajectories, thus emphasizing the value of preventing such events and care strategies targeted towards this at-risk group.
Developing a model for estimating infarction onset time based on computed tomography radiomics in patients with acute middle cerebral artery occlusion
Authors: Wen Xuehua , Shu Zhenyu , Li Yumei , Hu Xingfei , Gong Xiangyang 
Published: October 2021

Abstract
Background
Radiomics analysis is a newly emerging quantitative image analysis technique. The aim of this study was to extract a radiomics signature from the computed tomography (CT) imaging to determine the infarction onset time in patients with acute middle cerebral artery occlusion (MCAO).

Methods
A total of 123 patients with acute MCAO in the M1 segment (85 patients in the development cohort and 38 patients in the validation cohort) were enrolled in the present study. Clinicoradiological profiles, including head CT without contrast enhancement and computed tomographic angiography (CTA), were collected. The time from stroke onset (TFS) was classified into two subcategories: ≤ 4.5 h, and > 4.5 h. The middle cerebral artery (MCA) territory on CT images was segmented to extract and score the radiomics features associated with the TFS. In addition, the clinicoradiological factors related to the TFS were identified. Subsequently, a combined model of the radiomics signature and clinicoradiological factors was constructed to distinguish the TFS ≤ 4.5 h. Finally, we evaluated the overall performance of our constructed model in an external validation sample of ischemic stroke patients with acute MCAO in the M1 segment.

Results
The area under the curve (AUC) of the radiomics signature for discriminating the TFS in the development and validation cohorts was 0.770 (95% confidence interval (CI): 0.665–0.875) and 0.792 (95% CI: 0.633–0.950), respectively. The AUC of the combined model comprised of the radiomics signature, age and ASPECTS on CT in the development and validation cohorts was 0.808 (95% CI: 0.701–0.916) and 0.833 (95% CI: 0.702–0.965), respectively. In the external validation cohort, the AUC of the radiomics signature was 0.755 (95% CI: 0.614–0.897), and the AUC of the combined model was 0.820 (95% CI: 0.712–0.928).

Conclusions
The CT-based radiomics signature is a valuable tool for discriminating the TFS in patients with acute MCAO in the M1 segment, which may guide the use of thrombolysis therapy in patients with indeterminate stroke onset time.
Identification of a novel RHO heterozygous nonsense mutation in a Chinese family with autosomal dominant retinitis pigmentosa
Authors: Liu Wei , Guo Ruru , Hao Huijie , Ji Jian 
Published: October 2021

Abstract
Background
To explore the molecular genetic cause of a four-generation autosomal dominant retinitis pigmentosa family in China.

Methods
Targeted region sequencing was performed to detect the potential mutation, and Sanger sequencing was used to validate the mutation. Multiple sequence alignment from different species was performed by CLUSTALW. The structures of wild-type and the mutant RHO were modeled by Swiss-Model Server and shown using a PyMOL Molecular Graphic system.

Results
A novel heterozygous nonsense mutation (c.1015 A > T, p.Lys339Ter, p.K339X) within RHO, which cosegregated with retinitis pigmentosa phenotype was detected in this family. Bioinformatics analysis showed the mutation was located in a highly conserved region, and the mutation was predicted to be pathogenic.

Conclusions
We identified a novel heterozygous nonsense mutation of RHO gene in a Chinese family with retinitis pigmentosa by target region sequencing and our bioinformatics analysis indicated that the mutation is pathogenic. Our results can broaden the spectrum of RHO gene mutation and enrich the phenotype-genotype correlation of retinitis pigmentosa.
Microspheres present comparable efficacy and safety profiles compared with polyvinyl alcohol for bronchial artery embolization treatment in hemoptysis patients
Authors: Fu Zhigang , Li Xun , Cai Fei , Yuan Yinpeng , Zhang Xiaolin , Qin Jingxia , Liang Yonghui 
Published: October 2021

Abstract
Background
The present study aimed to compare the efficacy and safety profiles of microspheres versus (vs.) polyvinyl alcohol (PVA) for bronchial artery embolization (BAE) treatment in patients with hemoptysis.

Methods
Totally, 152 patients with hemoptysis who were about to receive BAE treatment were consecutively enrolled and divided into microspheres group (N = 62) and PVA group (N = 90). Technical success and clinical success were assessed after BAE procedure, and the hemoptysis-recurrence status, survival status and adverse events were recorded during follow-up.

Results
Technical success rates were both 100% in microspheres group and PVA group; clinical success rate (96.8% vs. 100.0%, P = 0.165), 6-month (9.7% vs. 7.8%, P = 0.681) and 1-year (9.7% vs. 8.9%, P = 0.869) hemoptysis recurrence rate, 6-month (4.8% vs. 2.2%, P = 0.374) and 1-year (4.8% vs. 3.3%, P = 0.639) mortality were similar between microspheres group and PVA group. Furthermore, hemoptysis-free survival (P = 0.488) and overall survival (P = 0.321) were of no difference between two groups. In addition, all adverse events were mild, and there was no difference of adverse events between two groups (all P > 0.05). These data were validated by further multivariate regression analysis.

Conclusions
Microspheres present comparable efficacy and safety profiles compared with PVA for the BAE treatment in patients with hemoptysis, providing evidence for embolic agent selection.
Positive feedback between lncRNA FLVCR1-AS1 and KLF10 may inhibit pancreatic cancer progression via the PTEN/AKT pathway
Authors: Lin Jiewei , Zhai Shuyu , Zou Siyi , Xu Zhiwei , Zhang Jun , Jiang Lingxi , Deng Xiaxing , Chen Hao , Peng Chenghong , Zhang Jiaqiang , Shen Baiyong 
Published: October 2021

Abstract
Background
FLVCR1-AS1 is a key regulator of cancer progression. However, the biological functions and underlying molecular mechanisms of pancreatic cancer (PC) remain unknown.

Methods
FLVCR1-AS1 expression levels in 77 PC tissues and matched non-tumor tissues were analyzed by qRT-PCR. Moreover, the role of FLVCR1-AS1 in PC cell proliferation, cell cycle, and migration was verified via functional in vitro and in vivo experiments. Further, the potential competitive endogenous RNA (ceRNA) network between FLVCR1-AS1 and KLF10, as well as FLVCR1-AS1 transcription levels, were investigated.

Results
FLVCR1-AS1 expression was low in both PC tissues and PC cell lines, and FLVCR1-AS1 downregulation was associated with a worse prognosis in patients with PC. Functional experiments demonstrated that FLVCR1-AS1 overexpression significantly suppressed PC cell proliferation, cell cycle, and migration both in vitro and in vivo. Mechanistic investigations revealed that FLVCR1-AS1 acts as a ceRNA to sequester miR-513c-5p or miR-514b-5p from the sponging KLF10 mRNA, thereby relieving their suppressive effects on KLF10 expression. Additionally, FLVCR1-AS1 was shown to be a direct transcriptional target of KLF10.

Conclusions
Our research suggests that FLVCR1-AS1 plays a tumor-suppressive role in PC by inhibiting proliferation, cell cycle, and migration through a positive feedback loop with KLF10, thereby providing a novel therapeutic strategy for PC treatment.
Societal and equity challenges for Brain Health Services. A user manual for Brain Health Services—part 6 of 6
Authors: Milne Richard , Altomare Daniele , Ribaldi Federica , Molinuevo José Luis , Frisoni Giovanni B. , Brayne Carol ,   on behalf of the European Task Force for Brain Health Services
Published: October 2021

AbstractBrain Health Services are a novel approach to the personalized prevention of dementia. In this paper, we consider how such services can best reflect their social, cultural, and economic context and, in doing so, deliver fair and equitable access to risk reduction. We present specific areas of challenge associated with the social context for dementia prevention. The first concentrates on how Brain Health Services engage with the “at-risk“ individual, recognizing the range of factors that shape an individual’s risk of dementia and the efficacy of risk reduction measures. The second emphasizes the social context of Brain Health Services themselves and their ability to provide equitable access to risk reduction. We then elaborate proposals for meeting or mitigating these challenges. We suggest that considering these challenges will enable Brain Health Services to address two fundamental questions: the balance between an individualized “high-risk” and population focus for public health prevention and the ability of services to meet ethical standards of justice and health equity.
Individual and collective human intelligence in drug design: evaluating the search strategy
Authors: Cincilla Giovanni , Masoni Simone , Blobel Jascha 
Published: October 2021

AbstractIn recent years, individual and collective human intelligence, defined as the knowledge, skills, reasoning and intuition of individuals and groups, have been used in combination with computer algorithms to solve complex scientific problems. Such approach was successfully used in different research fields such as: structural biology, comparative genomics, macromolecular crystallography and RNA design. Herein we describe an attempt to use a similar approach in small-molecule drug discovery, specifically to drive search strategies of de novo drug design. This is assessed with a case study that consists of a series of public experiments in which participants had to explore the huge chemical space in silico to find predefined compounds by designing molecules and analyzing the score associate with them. Such a process may be seen as an instantaneous surrogate of the classical design-make-test cycles carried out by medicinal chemists during the drug discovery hit to lead phase but not hindered by long synthesis and testing times. We present first findings on (1) assessing human intelligence in chemical space exploration, (2) comparing individual and collective human intelligence performance in this task and (3) contrasting some human and artificial intelligence achievements in de novo drug design.
Decontaminating N95/FFP2 masks for reuse during the COVID-19 epidemic: a systematic review
Authors: Peters Alexandra , Lotfinejad Nasim , Palomo Rafael , Zingg Walter , Parneix Pierre , Ney Hervé , Pittet Didier 
Published: October 2021

Abstract
Background
With the current COVID-19 pandemic, many healthcare facilities have been lacking a steady supply of filtering facepiece respirators. To better address this challenge, the decontamination and reuse of these respirators is a strategy that has been studied by an increasing number of institutions during the COVID-19 pandemic.

Methods
We conducted a systematic literature review in PubMed, PubMed Central, Embase, and Google Scholar. Studies were eligible when (electronically or in print) up to 17 June 2020, and published in English, French, German, or Spanish. The primary outcome was reduction of test viruses or test bacteria by log3 for disinfection and log6 for sterilization. Secondary outcome was physical integrity (fit/filtration/degradation) of the respirators after reprocessing. Materials from the grey literature, including an unpublished study were added to the findings.

Findings
Of 938 retrieved studies, 35 studies were included in the analysis with 70 individual tests conducted. 17 methods of decontamination were found, included the use of liquids (detergent, benzalkonium chloride, hypochlorite, or ethanol), gases (hydrogen peroxide, ozone, peracetic acid or ethylene oxide), heat (either moist with or without pressure or dry heat), or ultra violet radiation (UVA and UVGI); either alone or in combination. Ethylene oxide, gaseous hydrogen peroxide (with or without peracetic acid), peracetic acid dry fogging system, microwave-generated moist heat, and steam seem to be the most promising methods on decontamination efficacy, physical integrity and filtration capacity.

Interpretation
A number of methods can be used for N95/FFP2 mask reprocessing in case of shortage, helping to keep healthcare workers and patients safe. However, the selection of disinfection or sterilization methods must take into account local availability and turnover capacity as well as the manufacturer; meaning that some methods work better on specific models from specific manufacturers.

Systematic registration number

CRD42020193309.
Application of modified Michaelis – Menten equations for determination of enzyme inducing and inhibiting drugs
Authors: Saganuwan Saganuwan Alhaji 
Published: October 2021

Abstract
Background
Pharmacokinetics (PK) is the process of absorption, distribution, metabolism and elimination (ADME) of drugs. Some drugs undergo zero-order kinetics (ethyl alcohol), first order kinetics (piroxicam) and mixed order kinetics (ascorbic acid). Drugs that undergo Michaelis-Menten metabolism are characterized by either increased or decreased metabolism constant (Km) and maximum velocity (Vmax) of enzyme reaction. Hence literatures were searched with a view to translating in vitro-in vivo enzyme kinetics to pharmacokinetic/pharmacodynamic parameters for determination of enzyme inducing and inhibiting drugs, in order to achieve optimal clinical efficacy and safety.

Methods
A narrative review of retrospective secondary data on drugs, their metabolites, Vmax and Km, generated in the laboratory and clinical environments was adopted, using inclusion and exclusion criteria. Key word search strategy was applied, to assess databases of published articles on enzyme inducing and inhibiting drugs, that obey Michaelis-Menten kinetics. In vitro and in vivo kinetic parameters, such as concentration of substrate, rate of endogenous substrate production, cellular metabolic rate, initial velocity of metabolism, intrinsic clearance, percent saturation and unsaturation of the enzyme substrate, were calculated using original and modified formulas. Years and numbers of searched publications, types of equations and their applications were recorded.

Results
A total of fifty-six formulas both established and modified were applied in the present study. Findings have shown that theophylline, voriconazole, phenytoin, thiopental, fluorouracil, thyamine and thymidine are enzyme inducers whereas, mibefradil, metronidazole, isoniazid and puromicin are enzyme inhibitors. They are metabolized and eliminated according to Michaelis-Menten principle. The order could be mixed but may change to zero or first order, depending on drug concentration, frequency and route of drug administration.

Conclusion
Hence, pharmacokinetic-pharmacodynamic translation can be optimally achieved by incorporating, newly modified Michaelis-Menten equations into pharmacokinetic formulas for clinical efficacy and safety of the enzyme inducing and inhibiting therapeutic agents used in laboratory and clinical settings.
Melanin-based structural coloration of birds and its biomimetic applications
Authors: Jeon Deok-Jin , Paik Suejeong , Ji Seungmuk , Yeo Jong-Souk 
Published: October 2021

AbstractMelanin has been a widely researched pigment by scientists for decades as it is undoubtedly the most ubiquitous and ancient pigment found in nature. Melanin plays very significant roles in structural plumage colors in birds: it has visible light-absorbing capabilities, and nanoscale structures can be formed by self-assembling melanin granules. Herein, we review recent progress on melanin-based structural coloration research. We hope that this review will provide current understanding of melanin’s structural and optical properties, natural coloration mechanisms, and biomimetic methods to implement artificial melanin-based structural colors.
Life-cycle cost analysis of bridges subjected to fatigue damage
Authors: Sacconi Stefano , Ierimonti Laura , Venanzi Ilaria , Ubertini Filippo 
Published: October 2021

AbstractLife-cycle cost analysis (LCCA) is a decision-making tool particularly useful for the design of bridges as it predicts lifetime expenses and supports the inspections management and the maintenance activities. LCCA allows to consider uncertainties on loads, resistances, degradation and on the numerical modelling and structural response analysis. It also permits to consider different limit states and different types of damage in a unified framework. Among the types of damages that can occur to steel and steel-concrete composite bridges, fatigue is one of the most dangerous ones, as it may lead to sudden and fragile rupture, even at operational traffic levels. In this context, the present paper proposes a framework for LCCA based on the use of the Pacific Earthquake Engineering Research (PEER) equation which is for the first time utilized for fragility and cost analysis of bridges subjected to fatigue, highlighting the possibility of treating the problem of fatigue damage estimation with an approach similar to the one currently adopted for damage induced by other hazards, like earthquake and wind. To this aim, a damage index computed through the Palmgren-Miner’s rule is adopted as engineering demand parameter. The framework is applied to a composite steel-reinforced concrete multi-span roadway bridge by evaluating the fatigue limit state from different traffic load models, i.e. a Technical Code-based model and a model based on results of Weigh in Motion monitoring system. The evolution over time of the probability of failure and the life-cycle costs due to fatigue damage induced by heavy traffic loads are investigated for different probability distributions of the engineering demand parameter and for different fragility models. The comparison between the fatigue failure probabilities and the life-cycle costs obtained with the two traffic models, encourages the adoption of traffic monitoring systems for a correct damage estimation.
Regulation of rose petal dehydration tolerance and senescence by RhNAP transcription factor via the modulation of cytokinin catabolism
Authors: Zou Jing , Lü Peitao , Jiang Liwei , Liu Kun , Zhang Tao , Chen Jin , Yao Yi , Cui Yusen , Gao Junping , Zhang Changqing 
Published: October 2021

AbstractPetals and leaves share common evolutionary origins but have different phenotypic characteristics, such as the absence of stomata in the petals of most angiosperm species. Plant NAC transcription factor, NAP, is involved in ABA responses and regulates senescence-associated genes, and especially those that affect stomatal movement. However, the regulatory mechanisms and significance of NAP action in senescing astomatous petals is unclear. A major limiting factor is failure of flower opening and accelerated senescence. Our goal is to understand the finely regulatory mechanism of dehydration tolerance and aging in rose flowers. We functionally characterized RhNAP, an AtNAP-like transcription factor gene that is induced by dehydration and aging in astomatous rose petals. Cytokinins (CKs) are known to delay petal senescence and we found that a cytokinin oxidase/dehydrogenase gene 6 (RhCKX6) shares similar expression patterns with RhNAP. Silencing of RhNAP or RhCKX6 expression in rose petals by virus induced gene silencing markedly reduced petal dehydration tolerance and delayed petal senescence. Endogenous CK levels in RhNAP- or RhCKX6-silenced petals were significantly higher than those of the control. Moreover, RhCKX6 expression was reduced in RhNAP-silenced petals. This suggests that the expression of RhCKX6 is regulated by RhNAP. Yeast one-hybrid experiments and electrophoresis mobility shift assays showed that RhNAP binds to the RhCKX6 promoter in heterologous in vivo system and in vitro, respectively. Furthermore, the expression of putative signal transduction and downstream genes of ABA-signaling pathways were also reduced due to the repression of PP2C homolog genes by RhNAP in rose petals. Taken together, our study indicates that the RhNAP/RhCKX6 interaction represents a regulatory step enhancing dehydration tolerance in young rose petals and accelerating senescence in mature petals in a stomata-independent manner.