bluuebunny/crossref_metadata_2025 huggingface dataset:
The landscape of metabolic pathway dependencies in cancer cell lines
Authors: Joly James H. , Chew Brandon T.L. , Graham Nicholas A.
Published: October 2020

The metabolic reprogramming of cancer cells creates metabolic vulnerabilities that can be therapeutically targeted. However, our understanding of metabolic dependencies and the pathway crosstalk that creates these vulnerabilities in cancer cells remains incomplete. Here, by integrating gene expression data with genetic loss-of-function and pharmacological screening data from hundreds of cancer cell lines, we identified metabolic vulnerabilities at the level of pathways rather than individual genes. This approach revealed that metabolic pathway dependencies are highly context-specific such that cancer cells are vulnerable to inhibition of one metabolic pathway only when activity of another metabolic pathway is altered. Notably, we also found that the no single metabolic pathway was universally essential, suggesting that cancer cells are not invariably dependent on any metabolic pathway. In addition, we confirmed that cell culture medium is a major confounding factor for the analysis of metabolic pathway vulnerabilities. Nevertheless, we found robust associations between metabolic pathway activity and sensitivity to clinically approved drugs that were independent of cell culture medium. Lastly, we used parallel integration of pharmacological and genetic dependency data to confidently identify metabolic pathway vulnerabilities. Taken together, this study serves as a comprehensive characterization of the landscape of metabolic pathway vulnerabilities in cancer cell lines.

Author Summary

Cancer cells rewire their metabolism, which creates targetable metabolic vulnerabilities. Previous analyses of metabolic vulnerabilities in cancer cells have been limited to the analysis ofindividualgenes or metabolites. However, metabolicpathwaysexhibit significant cross talk and compensation for one another. We developed a computational method to answer the question: when a metabolic pathway’s activity is high, which other metabolic pathways become more essential or less essential? By integrating genetic screen data with drug response data from FDA approved drugs, we identified cancer cell line dependence on metabolicpathwaysas opposed to individualgenes. For example, we found that identifying key regulators of metabolic pathways, such as the Pentose Phosphate Pathway, may serve as a biomarker to identify which patients may benefit from antifolate chemotherapies (e.g. methotrexate, 5-fluorouracil). The efforts outlined here serve as the first characterization of the landscape of metabolic pathway vulnerabilities in cancer cell lines. Our results demonstrate the benefit of analyzing dependencies on metabolic pathways as opposed to metabolic genes.
A potential impact of physical distancing on physical and mental health. A rapid narrative umbrella review of meta-analyses on the link between social isolation and health
Authors: Morina Nexhmedin , Kip Ahlke , Hoppen Thole H. , Priebe Stefan , Meyer Thomas
Published: October 2020

Background

The imperative for physical distancing during the coronavirus disease 2019 (COVID-19) pandemic may deteriorate physical and mental health. We aimed at summarizing the strength of evidence in the published literature on the association of social isolation and loneliness with physical and mental health.

Methods

We conducted a systematic search in April 2020 to identify meta-analyses using the Medline, PsycINFO, and Web of Science databases. The search strategy included terms of social isolation, loneliness, living alone, and meta-analysis. Eligible meta-analyses needed to report any sort of association between an indicator of social isolation and any physical or mental health outcome. The findings were summarized in a narrative synthesis.

Results

Twenty-five meta-analyses met our criteria, of which 10 focused on physical health and 15 on mental health outcomes. A total of more than 3 million individuals had participated in the 692 primary studies. The results suggest that social isolation is associated with chronic physical symptoms, frailty, coronary heart disease, malnutrition, hospital readmission, reduced vaccine uptake, early mortality, depression, social anxiety, psychosis, cognitive impairment in later life, and suicidal ideation.

Conclusions

The existing evidence clearly indicates that social isolation is associated with a range of poor physical and mental health outcomes. A potential negative impact on these outcomes needs to be considered in future decisions on physical distancing measures.

Strengths and limitations of this study

This rapid umbrella review focuses on a timely and societally relevant issue.

The systematic literature search was conducted in three major databases from inception up to April 2020 warranting an extensive and up-to-date overview on relevant meta-analyses in the field.

Quality of included meta-analyses was rated with a standardized measure.

Different indicators of social isolation were included.

The utilized method did not allow for a quantitative comparison of associations with health outcomes.
Increased microenvironment stiffness leads to altered aldehyde metabolism and DNA damage in mammary epithelial cells through a RhoA-dependent mechanism
Authors: Wood Amber , Sun Heyuan , Jones Matthew , Percival Hannah , Broadberry Eleanor , Zindy Egor , Lawless Craig , Streuli Charles , Swift Joe , Brennan Keith , Gilmore Andrew P.
Published: October 2020

Microenvironmental stiffness regulates the behaviour of both normal and cancer cells. In breast tissue, high mammographic density (HMD), which reflects greater organisation and stiffness of the periductal collagen, represents a significant risk factor for cancer. However, the mechanistic link between extracellular matrix (ECM) stiffness and increased risk of breast tumour initiation remains unclear. In particular, how increased ECM stiffness might promote genomic damage, leading to the acquisition of transforming mutations, remains to be determined. Here we determine that ECM stiffness induces changes in mammary epithelial cell (MEC) metabolism that drive genomic damage. Using a 3D-culture model, we demonstrate that genome-wide transcriptional changes in response to increased ECM stiffness impair the ability of MECs to remove reactive aldehyde species, resulting in greater accumulation of DNA damage in a RhoA-dependent manner. Together, our results provide a mechanistic link between increased ECM stiffness and the genomic damage required for breast cancer initiation.
Development of a three-compartmentin vitrosimulator of the Atlantic Salmon GI tract and associated microbial communities: SalmoSim
Authors: Kazlauskaite R. , Cheaib B. , Heys C. , Ijaz U. , Connelly S. , Sloan W.T. , Russell J. , Martinez-Rubio L. , Sweetman J. , Kitts A. , McGinnity P. , Lyons P. , Llewellyn M.
Published: October 2020

Atlantic salmon are a species of major economic importance. Intense innovation is underway to improve salmon feeds and feed additives to enhance fish performance, welfare, and the environmental sustainability of the industry. Several gut models targeted at monogastric vertebrates are now in operation. Here we report progress in the development of an Atlantic salmonin vitrogut model, SalmoSim, to simulate three gut compartments (stomach, pyloric caecum and mid gut) and associated microbial communities. The artificial gut model was established in a series of linked bioreactors seeded with biological material derived for adult marine phase salmon. In biological triplicate, the response of thein vitrosystem to two distinct dietary formulations (fish meal and fish meal free) was compared to a parallelin vivotrial over forty days. 16S rDNA sequencing, qPCR, ammoniacal nitrogen and volatile fatty acid measurements were undertaken to survey microbial community dynamics and function. SalmoSim communities were indistinguishable (p=0.230) from their founding inocula at 20 days and most abundant genera (e.g.Psycrobacter, Staphylococcus, Pseudomonas) proliferated thein vitrosystem. Real salmon and SalmoSim responded similarly to the introduction of the novel feed, with most taxa (96% Salmon, 97% SalmoSim) unaffected, while a subset of taxa was affected non-identically across both systems. Consistent with a low impact of the novel feed on microbial community function, VFA profiles were not significantly different in SalmoSim pre and post the switch feed. This study represents an important first-step in the development of anin vitrogut system as a tool for the improvement of salmon nutrition.
The transcription factor BCL11A defines a distinctive subset of dopamine neurons in the developing and adult midbrain
Authors: Tolve Marianna , Ulusoy Ayse , Islam Khondker Ushna Sameen , Bodea Gabriela O. , Öztürk Ece , Broske Bianca , Mentani Astrid , Wagener Antonia , van Loo Karen , Britsch Stefan , Liu Pengtao , Khaled Walid , Baader Stephan , Di Monte Donato A. , Blaess Sandra
Published: October 2020

Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, impact on behavior and susceptibility to neurodegeneration. Little is known about the molecular mechanisms that establish this diversity in mDA neurons during development. We find that the transcription factor Bcl11a defines a subset of mDA neurons in the developing and adult murine brain. By combining intersectional labeling and viral-mediated tracing we show that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the dopaminergic system. We demonstrate that Bcl11a-expressing mDA neurons in the substantia nigra (SN) are particularly vulnerable to neurodegeneration in an α-synuclein overexpression model of Parkinson’s disease. Inactivation of Bcl11a in developing mDA neurons results in anatomical changes, deficits in motor learning and a dramatic increase in the susceptibility to α-synuclein-induced degeneration in SN-mDA neurons. In summary, we identify an mDA subpopulation with highly distinctive characteristics defined by the expression of the transcription factor Bcl11a already during development.
RNA polymerase clamp conformational dynamics: long-lived states and modulation by crowding, cations, and nonspecific DNA binding
Authors: Mazumder Abhishek , Wang Anna , Uhm Heesoo , Ebright Richard H. , Kapanidis Achillefs N.
Published: October 2020

The RNA polymerase (RNAP) clamp, a mobile structural element conserved in RNAP from all domains of life, has been proposed to play critical roles at different stages of transcription. In previous work, we demonstrated using single-molecule Förster resonance energy transfer (smFRET) that RNAP clamp interconvert between three short-lived conformational states (lifetimes ∼ 0.3-0.6 s), that the clamp can be locked into any one of these states by small molecules, and that the clamp stays closed during initial transcription and elongation. Here, we extend these studies to obtain a comprehensive understanding of clamp dynamics under conditions RNAP may encounter in living cells. We find that the RNAP clamp can populate long-lived conformational states (lifetimes >1.0 s) and can switch between these long-lived states and the previously observed short-lived states. In addition, we find that clamp motions are increased in the presence of molecular crowding, are unchanged in the presence of elevated monovalent-cation concentrations, and are reduced in the presence of elevated divalent-cation concentrations. Finally, we find that RNAP bound to non-specific DNA predominantly exhibits a closed clamp conformation. Our results raise the possibility of additional regulatory checkpoints that could affect clamp dynamics and consequently could affect transcription and transcriptional regulation.
North American fireflies host low bacterial diversity
Authors: Green Emily A. , Smedley Scott R. , Klassen Jonathan L.
Published: October 2020

Although there are numerous studies of firefly mating flashes, lantern bioluminescence, and anti-predation lucibufagin metabolites, almost nothing is known about their microbiome. We therefore used 16S rRNA community amplicon sequencing to characterize the gut and body microbiomes of four North American firefly taxa:Ellychnia corrusca, thePhoturis versicolorspecies complex,Pyractomena borealis, andPyropyga decipiens. These firefly microbiomes all have very low species diversity, often dominated by a single species, and each firefly type has a characteristic microbiome. Although the microbiomes of male and female fireflies did not differ from each other,Ph. versicolorgut and body microbiomes did, with their gut microbiomes being enriched inPseudomonasandAcinetobacter.Ellychnia corruscaegg and adult microbiomes were unique except for a single egg microbiome that shared a community type withE.corruscaadults, which could suggest microbial transmission from mother to offspring. Mollicutes that had been previously isolated from fireflies were common in our firefly microbiomes. These results set the stage for further research concerning the function and transmission of these bacterial symbionts.
Helicobacter pyloriaccelerates KRAS-dependent gastric dysplasia
Authors: O’Brien Valerie P. , Koehne Amanda , Dubrulle Julien , Rodriguez Armando E. , Leverich Christina K. , Kong Paul , Campbell Jean S. , Pierce Robert H. , Goldenring James R. , Choi Eunyoung , Salama Nina R.
Published: October 2020

More than 80% of gastric cancer is attributable to stomach infection withHelicobacter pylori(Hp), even though the bacterium is not always present at time of diagnosis. Infection is thought to lead to cancer by promoting the accumulation of oncogenic mutations downstream of inflammation; once oncogenic pathways become activated, infection may become dispensable for cancer development. Gastric preneoplastic progression involves sequential changes to the tissue, including loss of parietal cells, spasmolytic polypeptide-expressing metaplasia (SPEM), intestinal metaplasia (IM) and dysplasia. In mice, active KRAS expression recapitulates these tissue changes in the absence ofHpinfection. This model provides an experimental system to investigate whetherHpinfection has additional roles in preneoplastic progression, beyond initiating inflammation. Mice were assessed by evaluating tissue histology, gene expression changes, the immune cell repertoire, and expression of metaplasia and dysplasia markers. Compared toHp-/KRAS+ mice,Hp+/KRAS+ mice had i) severe T cell infiltration and altered macrophage polarization; ii) altered expression of metaplasia markers, including increased expression of CD44v9 (SPEM) and decreased expression of TFF3 (IM); iii) more dysplastic (TROP2+) glands; and iv) greater proliferation of metaplastic and dysplastic glands.Hpwas able to persistently colonize the stomach during the onset of these tissue changes, and eradication ofHpwith antibiotics prevented metaplastic, dysplastic and proliferation marker changes. Collectively, these results suggest that gastric preneoplastic progression differs betweenHp+ andHp-cases, and that sustainedHpinfection can promote the later stages of gastric preneoplastic progression, in addition to its established role in initiating chronic inflammation.
Effective resource utilization in Arkansas public schools
Authors: Sanders Ryan , Zhang Shengfan
Published: October 2020

Purpose

Teacher pay in Arkansas public schools varies widely from district to district across the state. This pay discrepancy is driven by both the funds available to a district and by how these funds are allocated. A standard per student budget is given to districts across the state, but this budget can be supplemented by additional property taxes collected on property within a district. This leaves districts with more highly valued property at an advantage. Districts are free to allocate their budget for teacher pay as they see fit, with constraints on number of students per teacher and minimum teacher salary.

Design/methodology/approach

Using public data available through the Arkansas Department of Education, this research investigates what variables affect student performance in Arkansas public schools using feature selection and predictive modelling and determine the cost-effectiveness associated with changing possible decision variables in terms of improving student performance.

Findings

It was found that the most cost-effective ways for districts to increase student performance are to (1) increase average teacher salary and (2) increase average years of teacher experience. This result is validated by education research, as both of these methods have been identified in literature as being effective ways to increase teacher quality and increase student performance. Furthermore, districts should consider increasing student–teacher ratio and applying the resulting savings toward teacher salaries.

Originality/value

This methodology gives a fresh perspective on the most cost-effective use of resources in publicly funded schools.
Contractual procurement alternatives of air force contingency pharmaceuticals: a cost-benefit analysis
Authors: Brubakken Adam J. , Dickens John M. , Anderson Jason , Cunningham William
Published: October 2020

Purpose

This paper aims to explore effective supply chain principles, through the theory of transaction cost economics, as measures to improve current contingency pharmaceutical item shortfalls in the Air Force Medical Service (AFMS) Contingency Pharmaceutical Programme.

Design/methodology/approach

In this research, AFMS contingency pharmaceutical data was collected from various databases, including the Joint Medical Asset Repository, Medical Contingency Requirements Workflow and the Medical Requirements List. Through the methodology of cost-benefit analysis, alternative sourcing and fulfilment practices are evaluated.

Findings

The findings of this research indicate that the application of centralized purchasing principles, in an effort to leverage prime vendor contract fill rates for shortage items, can lead to 12%–17% increases in pharmaceutical material availability across the programme.

Originality/value

This research clearly shows that consolidating demand for shortage items across Active Duty War Reserve Material assemblages, though applications of centralized purchasing principles that leverage prime vendor contract fill rates, can lead to substantial increases in material availability at costs that justify the calculated benefits.
Interpreting plant root responses to nutrients, neighbours and pot volume depends on researchers’ assumptions
Authors: McNickle Gordon G.
Published: October 2020

Some plants respond to both neighbours and nutrient levels below‐ground independently, while others respond only to nutrients. These responses have important ecological implications, but debate about the appropriate control treatments used in experiments has led many to debate results.

When plants ignore neighbours, and only respond to nutrient levels this is sometimes called an ideal‐free distribution (IFD). When individual plants respond to neighbours by increasing root production to pre‐empt the uptake of neighbours, and do so at the expense of reproduction, this has become known as a tragedy of the commons (TOC). Here, I describe how the history of competition experiments has largely been a history of experiments that only control two of three critical variables: (a) total nutrients per plant; (b) soil nutrient concentration and (c) pot volume. These confounding effects are the source of debate about results.

In one study, split‐root pea plants were grown with and without a below‐ground neighbour at many pot volumes with equal total nutrients per‐plant. The researchers explicitly argued that plant growth responses would not be affected by the concentration of nutrients in soil, and therefore they explicitly confounded soil nutrient concentration with neighbour presence. Here, I reanalyse a subset of their data, controlling for soil nutrient concentration, but confounding pot volume with neighbour presence.

When I controlled for soil nutrient concentration, the presence of a below‐ground neighbour had no effects on plant size, or allocation, and the effects of volume also disappeared. The reanalysis suggests that the behaviour of peas in this study was consistent with an IFD model, and that the previously reported volume and neighbour responses may have been due to the confounding of nutrient concentration.

The results of the study in question depend very much on whether one does analyses that control for pot volume or whether one does analyses that control for soil nutrient concentration. Ultimately, these analyses lead to two different interpretations of the data. New experimental designs are emerging that fully control pot volume and nutrients across competition treatment, and I discuss possible paths forward in this ongoing debate.
The analysis of plant root responses to nutrient concentration, soil volume and neighbour presence: Different statistical approaches reflect different underlying basic questions
Authors: Chen Bin J. W. , During Heinjo J. , Vermeulen Peter J. , de Kroon Hans , Poorter Hendrik , Anten Niels P. R.
Published: October 2020

To investigate the responses of plants to their below‐ground neighbours independently of nutrient availability, experiments generally require a solitary treatment with one plant grown alone with one unit of nutrients, and a neighbour treatment with two plants grown together with two units of nutrients. This can either be done by doubling nutrient concentration (C) or by doubling soil volume (V) in the neighbour treatment as compared to the solitary treatment.

Statistically analysing the same dataset from an experiment that grew plants in solitary or neighbour treatment with a series of V given a fixed amount of nutrients per plant (e.g. 1 g), Chen et al. (2015a) found significant neighbour effects when they controlled for V, while McNickle (2020) found the effects to be insignificant when he controlled for C.

The discrepancy in the results of the two studies is caused by a difference in their analytical approaches. This includes (a) different choices of data transformation for the controlling factor, and (b) a mathematical deviation of model structures between V‐based and C‐based analyses, due to the different inversely proportional V‐C relationships between solitary and neighbour treatments.

Choices for either V or C as a controlling factor in the analyses for ‘neighbour effect’ are based on two different perspectives, focussing either on neighbour‐induced nutrient depletion (like McNickle, 2020) or on identity recognition (like Chen et al., 2015a).

We also raise concerns about the use of mesh‐divided root interaction design and replacement series design in the studies of plant–plant root interactions. We propose to adjust the experimental designs and analytical methods based on the focal perspectives of neighbour effect.
Comparison of 6‐mm and 11‐mm dental implants in the posterior region supporting fixed dental prostheses: 5‐year results of an open multicenter randomized controlled trial
Authors: Guljé Felix L. , Meijer Henny J. A. , Abrahamsson Ingemar , Barwacz Christopher A. , Chen Stephen , Palmer Paul J. , Zadeh Homayoun , Stanford Clark M.
Published: October 2020

Objective

The aim of this multicenter, randomized controlled trial was to compare the clinical and radiographic outcomes of 6‐mm or 11‐mm implants, placed in the posterior maxilla and mandible, during a 5‐year follow‐up period.

Materials and methods

Ninety‐five patients with adequate bone height for 11‐mm implants, were randomly allocated to a 6‐mm group (test group with short implants) or an 11‐mm group (control group with standard‐length implants). Two or three implants of the same length were placed in each patient and after 6 weeks loaded with a splinted provisional restoration. This was followed by definitive splinted restoration 6 months after implant placement. Clinical and radiographic parameters, including the occurrence of complications were recorded.

Results

A total of 49 patients were enrolled to receive 6‐mm implants (n = 108) and 46 patients to receive 11‐mm implants (n = 101). Three implants (two of 6 mm and one of 11 mm in length) were lost before loading and one 6‐mm implant after 15 months of function, and one 11‐mm implant was lost during the first year of function. The 5‐year survival rates were 96.0% and 98.9% in the 6‐mm and 11‐mm group, respectively. The mean marginal bone level changes 5 years post‐loading were 0.01 ± 0.45 mm (bone gain) in the 6‐mm group and −0.12 ± 0.93 mm (bone loss) in the 11‐mm group (p = .7670). Clinical parameters, including plaque, bleeding on probing and pocket probing depth were not significantly different between the groups, and also technical complications were low.

Conclusion

The clinical and radiographic outcomes of 6‐mm short and 11‐mm standard‐length implants were not different during a 5‐year evaluation period.
The evolution of reversed sex roles and classical polyandry: Insights from coucals and other animals
Authors: Safari Ignas , Goymann Wolfgang
Published: October 2020

In most animals, competition for mating opportunities is higher among males, whereas females are more likely to provide parental care. In few species, though, these "conventional" sex roles are reversed such that females compete more strongly for matings and males provide most or all parental care. This "reversal" in sex roles is often combined with classical polyandry—a mating system in which a female forms a harem with several males. Here, we review the major hypotheses relating such role reversals to evolutionary and behavioural traits (anisogamy, phylogenetic history, sexy males, parental care, genetic paternity, trade‐off between mating and parenting, adult sex ratio) and to ecological factors (food supply, offspring predation). We evaluate each hypothesis in relation to coucals (Centropodinae), a group of nesting cuckoos of great interest for mating system and parental care theory. The black coucal (Centropus grillii) is the only known bird combining classical polyandry with altricial development of young, a costly trait with regard to parental care. Our long‐term study offers a unique possibility to compare the strongly polyandrous black coucal with a monogamous close relative breeding in the same area and habitat, the white‐browed coucal (C. superciliosus). We show that the evolution of sex roles in coucals and other animals has many different facets. Whereas phylogenetic constraints are important, confidence in genetic paternity is not. In combination with facilitating ecological conditions, adult sex ratios are key to understanding sex roles in coucals, shorebirds, and most likely also other animals. We plead for more studies including experimental tests to understand how biased adult sex ratios emerge and whether they drive sexual selection or vice versa. How do sex ratios and sexual selection interact and feedback on each other? Answers to these questions will be fundamental for understanding the evolution of sex roles in mating and parenting in coucals and other species.
Cohort study of sleep quality in adult patients with acute pulmonary exacerbations of cystic fibrosis
Authors: Henderson Daniel , Moore Vanessa , MacMorran Kate , Castellini Julieta , Hay Karen , Keegan Vernon , Reid David , Curtin Deanne , Tay George
Published: October 2020

Background

The impact of an acute pulmonary exacerbation of cystic fibrosis (CF) on sleep quality has not been established. Patients have greater burden of symptoms, higher intensity of therapy and are often admitted to hospital outside of their usual sleeping environment.

Aims

To evaluate the prevalence of, and factors associated with, poor sleep quality in adult patients admitted to hospital with an acute exacerbation of CF lung disease.

Methods

This prospective, observational study determined the prevalence of impaired sleep quality and associated factors in adult patients admitted to a single CF unit with an acute pulmonary exacerbation of CF. Sleep quality was defined by the Pittsburgh Sleep Quality Index (PSQI), with >5 indicating poor sleep quality. Data were obtained through patient questionnaires, chart review and examination.

Results

Sixty‐six percent of patients had impaired sleep quality. Patients with poor sleep had more sleep disruption due to pain (median response ‘mild sleep disruption’ vs ‘no sleep disruption’; P = 0.003) and insomnia (mean Insomnia Severity Index (ISI) 13 vs 5; P < 0.001). In patients with symptoms of restless legs, poor sleepers had worse symptoms (mean International Restless Legs Severity Score (IRLSS) 15 vs 5; P = 0.029).

Univariate modelling showed relationships between PSQI and symptoms of depression and anxiety as well as with sleep disruption due to pain, general noise and nursing observations. In a multivariable model, ISI was the only variable that remained significantly associated with PSQI. Mean PSQI score increased 0.58 units for each 1 unit increase in ISI (95% CI 0.42–0.73; P < 0.001).

Conclusions

Poor sleep quality is common among patients admitted with an acute exacerbation of CF and is strongly associated with insomnia symptoms in this cohort.
Epidemiology of 2017 influenza outbreaks in nine Australian Aged care facilities
Authors: Hooshmand Elmira , Moa Aye , Trent Mallory , Kunasekaran Mohana , Poulos Christopher J. , Chughtai Abrar Ahmad , MacIntyre C. Raina
Published: October 2020

Background

The 2017 A/H3N2 influenza season was the most severe season since the 2009 influenza pandemic. There were over 591 influenza outbreaks in institutions across the state of New South Wales (NSW) in Australia.

Aim

To describe the epidemiology of influenza outbreaks in nine Sydney aged care facilities in 2017.

Methods

Study data were collected from nine Sydney aged care facilities for 2017 influenza season. Descriptive epidemiological analysis was conducted.

Results

From the nine sites included, with a total of 716 residents, four sites reported laboratory‐confirmed influenza outbreaks during the study period, with an attack rate in residents ranging from 6% to 29%. The outbreaks resulted in lockdowns in two facilities and hospitalisation of seven residents. No deaths were reported as a result of influenza infection. Influenza A was the most common influenza type reported across the facilities. The duration of outbreak lasted for 1‐4 weeks varied by site.

Conclusion

The 2017 season was a severe influenza season recorded in Australia. About half of the facilities studied experienced outbreaks of influenza, with a high attack rate among residents. Infection prevention and control measures and outbreak management plans are crucial for aged care facilities, including vaccination of staff and visitors to prevent outbreaks among the vulnerable residents.
Up‐regulation of CDHR5 expression promotes malignant phenotype of pancreatic ductal adenocarcinoma
Authors: Gao Junyi , Wang Mengyi , Li Tong , Liu Qiaofei , You Lei , Liao Quan
Published: October 2020

CDHR5 has been reported to play key roles in carcinogenesis of various cancers, but its roles in pancreatic cancer have not been reported. The present study was designed to investigate its clinical value in pancreatic ductal adenocarcinoma (PDAC). Tissue microarray‐based immunohistochemistry was performed to analyse the correlation between CDHR5 expression and clinical and pathological features of PDAC, as well as the CDHR5 expression during tumour progression. Cell function assays were performed to investigate CDHR5’s effects on PDAC cells. Moreover, qRT‐PCR was applied to investigate the expression of CDHR5 isoforms in PDAC cells. Expression of CDHR5 was higher on the membrane of PDAC cells. This high expression level was associated with shorter overall survival of PDAC patients and was identified as an independent prognostic factor for overall survival by multivariate Cox regression analysis. In addition, expression level of CDHR5 presented an increased trend in the occurrence and progression of PDAC. Cell experiment suggested that CDHR5 could notably promote invasion and migration of PDAC cells. Moreover, analysis of CDHR5 isoforms indicated CDHR5‐L was the major isoform expressed in PDAC cell lines. CDHR5 appears to be a promising and novel prognostic factor for PDAC, and its promotion in PDAC metastasis might be ascribed to the isoform CDHR5‐L.
Growth inhibition of foodborne pathogens by co‐microencapsulation of lactobacilli cell free and propolis extracts
Authors: Burgut Aykut
Published: October 2020

Cell free extracts (CFE) obtained from Lactobacillus plantarum FI 8595 and Lactobacillus reuteri ATCC 55730 alone or in combination with propolis ethanolic or water extracts (1%) were microencapsulated with maltodextrin (25%) before the subsequent spray drying process. They were morphologically characterized by scanning electron microscope. Chemical compositions of pure extracts were identified by gas chromatography–mass spectrometry. Antimicrobial activities of pure and microencapsulated extracts against four foodborne pathogens (Staphylococcus aureus ATCC29213, Listeria monocytogenes ATCC19112, Klebsiella pneumoniae ATCC700603 and Salmonella Paratyphi A NCTC13) were determined using agar well diffusion, broth microdilution and time kill assays. CFE from L. reuteri and L. plantarum consisted of acetic acid, pyrrolo[1,2‐a]pyrazine‐1,4‐dione, hexahydro‐3‐(phenylmethyl)‐, 2,3,4‐trihydroxybenzaldehyde and 9‐octadecenoic acid. The results also indicated the presence of two respective major compounds, namely, 2‐methoxy‐4‐vinylphenol (19.03%) and trans‐cinnamic acid (27.67%) in water and ethanolic propolis extracts. Presence of propolis extracts mainly ethanolic extract in microencapsulation led to higher inhibition zones against all foodborne pathogens (p < .05). The co‐microencapsulation of CFE from L. reuteri in combination with ethanolic or water extract of propolis resulted in 2.34‐ and 2.2‐fold higher inhibition zone towards L. monocytogenes. Pure and microencapsulated CFE from L. reuteri resulted in 2.89 and 2.14 log cfu/ml reduction in growth of S. Paratyphi A at 3 hr, respectively. The co‐microencapsulation of CFE from lactobacilli and propolis extracts mainly ethanolic extract could be suggested as a novel antimicrobial on inhibition of food pathogens, as they contain abundant bioactive substances.
Development and evolution of the notarium in Pterosauria
Authors: Aires Alex Schiller , Reichert Leici Machado , Müller Rodrigo Temp , Pinheiro Felipe Lima , Andrade Marco Brandalise
Published: October 2020

The notarium is the structure formed by fusion of the dorsal vertebrae which occurred independently in pterosaurs and birds. This ankylosis usually involves two to six elements and in many cases, also includes the last cervical vertebra. Fusion can occur in different degrees, uniting the vertebral centra, the neural spines, the transverse processes, the ventral processes, or a combination of these sites. A detailed assessment of the fusion process of pterosaur dorsal vertebrae is still lacking. Here we identify the fusion sequence of pterosaur notarial elements, demonstrating the order of ossification in vertebral bodies and neural spines based on fossils and extant birds. In both Pterosauria and Aves, the notarium generally develops in a antero‐posterior direction, but the actual order of each fusion locus may present slight variations. Based on our data, we were able to identify seven developmental stages in the notarium formation, with broad implications for the prediction of ontogenetic stages for the Pterosauria. In addition, we report the occurrence of a notarium in Ardeadactylus longicollum (Kimmeridgian, Southern Germany), the oldest occurrence of this structure in pterosaurs.
The global trends and regional differences in incidence of HEV infection from 1990 to 2017 and implications for HEV prevention
Authors: Jing Wenzhan , Liu Jue , Liu Min
Published: October 2020

Background/Aims

Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis worldwide, but it is long‐neglected. We aimed to understand the global trends and regional differences in the incidence of HEV infection, thereby making global tailored prevention strategies.

Methods

This study is a post‐hoc analysis of the data from Global Burden of Disease Study 2017. Annual HEV incident cases and incidence rates from 1990 to 2017 were collected. Changes in incident cases and estimated annual percentage changes (EAPCs) of age‐standardized incidence rates (ASRs) were calculated to quantify the temporal trends of HEV infection.

Results

Globally, HEV ASRs decreased by an average 0.16% (95% CI: 0.14%‐0.17%) per year from 279.79 per 100 000 in 1990 to 269.70 per 100 000 in 2017; however, the number of HEV incident cases increased by 17.63% from 16.53 million in 1990 to 19.44 million in 2017. Against the global trend of ASR falling, an increasing trend was reported in Oceania (EAPC = 0.03; 95% CI: 0.03‐0.04) and Western Europe (EAPC = 0.02; 95% CI: 0.01‐0.03). The number of HEV incident cases increased remarkably in low (63.07%) and low‐middle (37.46%) Socio‐Demographic Index (SDI) regions between 1990 and 2017. Additionally, the number of HEV incident cases increased by 4.63% in high SDI regions, mainly in 40 plus age group. Surprisingly, more than 40% of HEV incident cases in Western Europe in 2017 were over 40 years old.

Conclusions

HEV is still pending in hyperendemic regions, and it is emerging in low endemic regions, suggesting more efforts should be done to make targeted prevention strategies.
Charisma and communities of feeling
Authors: Uzelac Gordana
Published: October 2020

Theories of nations and nationalism have serious problems when dealing with the concept of charisma. Besides frequent conceptual confusion, the concept of charisma is predominantly observed from either the structuralist position or the perspective of psychological reductionism. Charisma is so often sought in the properties of an office, within an ideology, character of a leader or general socio‐economic circumstances of an epoch. In the example of the commonly examined case—that of Hitler—this article argues that charisma is a property of experience and it is the emotional reaction of the audience that validates it. This article builds on Erika Fischer‐Lichte's theory of performance to argue that successful performances of charisma create a type of community that is not based solely on common beliefs but more importantly on shared emotions and experiences. Studying charisma as a property of experience is a step toward understanding the emotional character of nationalism itself.
Unusual findings in ultrasound screening for carpal tunnel syndrome in a patient with acromegaly: Bifid median nerve and persistent median artery
Authors: Cüce İsa , Beke Sinem Kübra , Veziroğlu Enes , Demir Hüseyin , Bayram Fahri
Published: October 2020

Carpal tunnel syndrome (CTS) is a common complication in acromegaly and is often associated with enlargement of the median nerve. Morphological changes in the median nerve and surrounding tissues can be visualized easily by ultrasound (US) scanning in suspected patients. Ultrasonography also offers priceless contributions to visualization of anatomical variations and pathological conditions that may potentially be associated with CTS. We present the presence of bifid median nerve and persistent median artery, which are both unusual findings, during the US screening for CTS in a 36‐year‐old male patient with acromegaly.
Inhaled hypertonic saline after pediatric lung transplant—Caution required?
Authors: Shkurka Emma , Spencer Helen
Published: October 2020

Management of pulmonary infection following lung transplant is multifaceted and includes respiratory physiotherapy. Inhaled hypertonic saline (HTS) has been introduced as an adjunct to physiotherapy in pediatric transplant patients. There are no published studies investigating the use of HTS in this population. This study aimed to evaluate the effect of inhaled HTS, in the acute post‐operative period, in pediatric lung transplant patients. A retrospective case‐note review was completed at a single UK pediatric transplant center. An intervention group who received HTS was compared to a historical control group. Participants were frequency matched for age, gender, and diagnosis (14 per group); median age in years was 13.7(IQR 12.7‐15.3) in the controls and 14.8(IQR 12.4‐16.1) in the intervention group. Primary outcome was the requirement of invasive and non‐invasive ventilation. Secondary outcomes included oxygen use and length of stay. Median days of invasive ventilation were shorter in the control group (1, 95% CI 1‐1) compared to the intervention group (2, 95% CI 1‐2.5) (P < .05). Days of non‐invasive ventilation and oxygen were higher in the HTS group, but this was not statistically significant. The controls displayed shorter median length of stay (23 days, 95% CI 20‐24) compared to the intervention group (31 days, 95% CI 24.5‐39) (P < .05). The results of this small study provide uncertainty regarding the safety of inhaled hypertonic saline after lung transplant. There was a trend of poorer acute outcomes in patients who received HTS. However, the findings should be interpreted with caution and further investigation using larger samples is required.
Restoration of nocturnal blood pressure dip and reduction of nocturnal blood pressure with evening anti‐hypertensive medication administration in pediatric kidney transplant recipients: A pilot randomized clinical trial
Authors: Sethna Christine B. , Grossman Lindsay G. , Dhanantwari Preeta , Gurusinghe Shari , Laney Nina , Frank Rachel , Meyers Kevin E.
Published: October 2020

Non‐dipping and nocturnal hypertension are commonly found during ABPM in pediatric kidney transplant recipients. These entities are independently associated with increased cardiovascular disease risk in adults. Kidney transplant recipients aged 5‐21 years with eGFR > 30 mL/min/1.73 m2 and ABPM demonstrating non‐dipping status and normal daytime BP were randomized to intervention (short acting BP medication added in the evening) or control (no medication change) in this pilot, randomized, open‐label, blinded end‐point clinical trial. ABPM, echocardiography, and PWV were performed at baseline, 3 months, and 6 months. The trial included 17 intervention and 16 control participants. Conversion to dipper status occurred in 53.3% vs 7.7% (P = .01) at 6 months for intervention and controls, respectively. Systolic dip was greater in the intervention group compared to controls (10.9 ± 4.5 vs 4.2 ± 4.6, P = .001), and average systolic nighttime BP was significantly lower in the intervention group (106 ± 8.3 vs 114.9 ± 9.5 mm Hg, P = .01) at 6 months. There were no significant differences in LVMI, PWV, or eGFR between groups. Within‐group changes in the intervention group demonstrated improvements in non‐dippers, dipping, systolic nighttime BP and nighttime BP load. Restoration of nocturnal dip and improvement in nocturnal BP were observed in the population following chronotherapy. Future studies are needed with larger sample sizes over a longer period of time to delineate the long‐term effect of improved nocturnal dip on target organ damage.
Using Symmetries à Rebours
Authors: Pucci Edvige , Saccomandi Giuseppe
Published: October 2020

We consider nonclassical symmetries of partial differential equations (PDEs) in dimensions. Given a th‐order ordinary differential equation in the unknown we are able to find the most general scalar PDE of a given order which can be reduced via a nonclassical symmetry to .
The roles of small‐molecule inflammatory mediators in rheumatoid arthritis
Authors: Cheng Qi , Wu Huaxiang , Du Yan
Published: October 2020

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Although great progress has been made in the treatment of RA with antagonists of pro‐inflammatory cytokines such as TNF‐α, IL‐6 and IL‐1, the disease remains refractory in some patients. Previous studies have found that small‐molecule inflammatory mediators, such as prostaglandins, leukotrienes, reactive oxygen species, nitric oxide, lipoxins and platelet‐activating factor, play a significant role in the development of RA. Such compounds help to induce, maintain or reduce inflammation and could therefore be potential therapeutic targets. In this review, we describe the roles of various classes of small‐molecule inflammatory mediators in RA and discuss the effects of some drugs that modulate their activity. Many drugs targeting these mediators have demonstrated good efficacy in mouse models of RA but not in patients. However, it is clear that many small‐molecule inflammatory mediators play key roles in the pathogenesis of RA, and a better understanding of the underlying molecular pathways may assist in the development of targeted therapies that are efficacious in RA patients.
Genomic full‐length sequence of the HLA‐B*40:01:43 allele was identified by full‐length group‐specific sequencing
Authors: An Run , Jiao Shuxian , Chi Xiaoyun , Pang Shutao
Published: October 2020

Genomic full‐length sequence of HLA‐B*40:01:43 was identified by group‐specific sequencing in a Chinese individual.
Stability of TiO2-coated ZnO photocatalytic thin films for photodegradation of methylene blue
Authors: Butalid Rogel Jan B. , Cristobal Anna Patricia S. , Montallana Arantxa Danielle S. , Vasquez Magdaleno R.
Published: October 2020

Investigations on the stability of titanium dioxide (TiO2)-coated zinc oxide (ZnO) thin films upon repeated uses for methylene blue (MB) degradation were conducted. Photocorrosion of ZnO, upon exposure to light in aqueous media, can affect the photocatalytic performance due to loss of material. Hence, coating with a more stable metal oxide was seen as a way to suppress the effects of photocorrosion. In this study, homogeneous wurtzite ZnO nanostructured thin films were obtained from thermal oxidation of sputter-deposited Zn films on glass substrates. TiO2 was subsequently deposited onto the ZnO nanostructured thin films using a reactive magnetron sputtering system in an admixture of argon and oxygen gases. After deposition, the thin films were annealed at 500 °C for 1 h. The photocatalytic efficiency and stability of the thin films were investigated after multiple degradation cycles. The addition of a TiO2 film increased the surface roughness and blueshifted the absorption edge of the ZnO thin films. The coated films obtained up to 94.3% degradation efficiency of MB after a 180-min exposure cycle using a solar light simulator. After three cycles, degradation efficiency decreased for the uncoated ZnO photocatalysts. Analysis of the MB solution after one degradation cycle revealed the presence of Zn2+ ions attributed to the effects of photocorrosion. Higher Zn2+ concentrations were observed when the ZnO surface is uncoated. This study showed that the addition of a thin, antiphotocorrosion material such as TiO2 layer decreased the dissolution of ZnO caused by photocorrosion without a significant reduction in the photodegradation efficiency.
Self-standing and flexible covalent organic framework (COF) membranes for molecular separation
Authors: Liu Jiangtao , Han Gang , Zhao Dieling , Lu Kangjia , Gao Jie , Chung Tai-Shung
Published: October 2020

2D COFs fabricated from interface-confined reaction have the honeycomb lattice for nanofiltration.
A unique route of colloidal phase separation yields stress-free gels
Authors: Tsurusawa Hideyo , Arai Shunto , Tanaka Hajime
Published: October 2020

We show a unique route of colloid gelation where topological percolation generates little mechanical stress.
A sleep-like state in
Hydra
unravels conserved sleep mechanisms during the evolutionary development of the central nervous system
Authors: Kanaya Hiroyuki J. , Park Sungeon , Kim Ji-hyung , Kusumi Junko , Krenenou Sofian , Sawatari Etsuko , Sato Aya , Lee Jongbin , Bang Hyunwoo , Kobayakawa Yoshitaka , Lim Chunghun , Itoh Taichi Q.
Published: October 2020

The brain-less freshwater polyp
Hydra
controls sleep-wake cycles by mechanisms conserved or reprogrammed among animal species.