bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults
Authors: Chahine Elias B.
Published: June 2020

Objective:

To review the efficacy and safety of the high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) in the prevention of influenza in older adults.

Data Sources:

A literature search was performed using PubMed and Google Scholar with the search terms high-dose, influenza vaccine, and quadrivalent. Other resources included the Centers for Disease Control and Prevention (CDC), the prescribing information, and the manufacturer’s website.

Study Selection and Data Extraction:

All relevant English-language articles of studies assessing the efficacy and safety of HD-IIV4 were included.

Data Synthesis:

HD-IIV4 is licensed by the Food and Drug Administration for the prevention of influenza in adults aged 65 years and older. The safety and immunogenicity of HD-IIV4 was demonstrated in a phase 3 trial, and the efficacy of the trivalent formulation (HD-IIV3) was demonstrated in a phase 3b-4 trial. HD-IIV4 carries a warning regarding the occurrence of Guillain-Barré syndrome. Adverse reactions, including injection-site pain and myalgia, were reported more frequently with HD-IIV4 than with HD-IIV3.

Relevance to Patient Care and Clinical Practice:

Although the CDC recommends any age-appropriate influenza vaccine for adults aged 65 years and older, HD-IIV4 was associated with improved immunogenicity against the added B strain and HD-IIV3 provided better protection against influenza than the standard-dose vaccine. Other influenza vaccines have weaker evidence of efficacy in older adults. Therefore, HDIIV4 should be recommended as the vaccine of choice in adults aged 65 years and older.

Conclusion:

HD-IIV4 has proven immunogenic, safe, and effective in preventing influenza in older adults and should be recommended as the vaccine of choice in this patient population.
The introduction of a third CDK4/6 inhibitor does not change the cost-effectiveness profile in first and subsequent-lines after progression or relapse during previous endocrine therapy in patients with hormone receptor positive (HR+)/human epidermal receptor-2 negative (HER-2) advanced or metastatic breast cancer
Authors: Giuliani Jacopo , Bonetti Andrea
Published: June 2020

The aim of this study was to assess the pharmacological costs of CDK4/6-inhibitors (palbociclib, ribociclib and abemaciclib) in hormone receptor positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer (BC). We have considered pivotal phase III randomized controlled trials (RCTs) of palbociclib, ribociclib and abemaciclib for the treatment of postmenopausal women with HR+/HER2- advanced or metastatic BC in first-line in association with letrozole or anastrozole (scenario 1) and in subsequent-lines after progression or relapse during previous endocrine therapy (scenario 2).The costs of drugs are at the Pharmacy of our Hospital and are expressed in euros (€). Six phase III RCTs, including 3843 patients, were considered. In the scenario 1, abemaciclib resulted the less expensive at the full dose, with 2246 € per month of progression free survival (PFS)-gained. Overall ribociclib resulted the less expensive considering the reduction in dosage (36.1% in MONALEESA-2 trial versus (vs). 36.0% of palbociclib in PALOMA-2 trial vs. 43.4% of abemaciclib in MONARCH-3 trial). The price was the same for palbociclib and abemaciclib both at full and with dose reduction. In the scenario 2, the situation was similar to the scenario 1, but with lowest costs for ribociclib per month PFS-gained both at full dose (2070 €) and at dose reduction (1391 € and 690 € at 400 mg and 200 mg, respectively). Combining pharmacological costs of drugs with the measure of efficacy represented by the PFS, ribociclib was the less expensive in both scenarios.
Veil of Darkness and Investigating Disproportionate Impact in Policing: When Researchers Disagree
Authors: Stacey Michele , Bonner Heidi S.
Published: June 2020

Disproportionate impact in policing has long been a concern for researchers and practitioners alike, with much of the focus on traffic stops. While there are many methods used to determine disproportionality in traffic stops, the veil of darkness (VOD) approach has increasingly become one of the most popular frameworks. Although there is consensus on certain aspects of the method, researchers utilizing VOD disagree on the appropriate sampling strategies. This research examines the original VOD method and three different sample restrictions proposed within the VOD literature to demonstrate the effect each has on the conclusions drawn. The results indicate that there is variation in the estimates of disproportionality depending on the sampling strategy used. As such, researchers using the VOD method must be cautious in their sampling decisions in mid-size jurisdictions due to the impact these such choices have on the conclusions drawn about disproportionate impact.
Inferring Causation in Yeast Gene Association Networks With Kernel Logistic Regression
Authors: Al-Aamri Amira , Taha Kamal , Maalouf Maher , Kudlicki Andrzej , Homouz Dirar
Published: June 2020

Computational prediction of gene-gene associations is one of the productive directions in the study of bioinformatics. Many tools are developed to infer the relation between genes using different biological data sources. The association of a pair of genes deduced from the analysis of biological data becomes meaningful when it reflects the directionality and the type of reaction between genes. In this work, we follow another method to construct a causal gene co-expression network while identifying transcription factors in each pair of genes using microarray expression data. We adopt a machine learning technique based on a logistic regression model to tackle the sparsity of the network and to improve the quality of the prediction accuracy. The proposed system classifies each pair of genes into either connected or nonconnected class using the data of the correlation between these genes in the whole Saccharomyces cerevisiae genome. The accuracy of the classification model in predicting related genes was evaluated using several data sets for the yeast regulatory network. Our system achieves high performance in terms of several statistical measures.
Real-world disability improvement in patients with relapsing–remitting multiple sclerosis treated with natalizumab in the Tysabri Observational Program
Authors: Wiendl Heinz , Spelman Tim , Butzkueven Helmut , Kappos Ludwig , Trojano Maria , Su Ray , Campbell Nolan , Ho Pei-Ran , Licata Stephanie
Published: June 2020

Background:

Natalizumab has been associated with disability improvement as indicated by a confirmed Expanded Disability Status Scale (EDSS) score decrease.

Objective:

The aim of this study was to characterize disability improvement in patients in the Tysabri Observational Program (TOP), an ongoing observational study of relapsing–remitting multiple sclerosis patients initiating natalizumab in clinical practice.

Methods:

TOP data as of November 2018 were included. Confirmed disability improvement (CDI) was defined as a decrease ⩾1.0 confirmed 24 weeks later from a baseline EDSS score ⩾2.0. Confirmed functional system (FS) improvement was defined as a decrease ⩾1.0 confirmed 24 weeks later from a baseline score ⩾1.0 in that FS.

Results:

Of 5384 patients, 1287 (23.9%) had CDI; 51.8% experienced CDI in the first treatment year. Among patients with CDI, 56.6% had CDI ⩾1.5 points; 34.4% had CDI ⩾2.0 points. The cumulative probability of maintaining improvement 8 years after the CDI event was 52.6%. At treatment initiation, 5363 patients (85.2%) had impairment in ⩾1 FS. At 8 years, the cumulative probability of confirmed improvement in any FS was 88.8% and ranged from 38.3% to 58.6% in individual FS.

Conclusion:

These results highlight disability improvement as a potential benefit of natalizumab treatment. Improvements across all FS demonstrate the range of functional improvement.
Constrained or sustained by demands? Perceptions of professional autonomy in early childhood education
Authors: Oosterhoff Arda , Oenema-Mostert Ineke , Minnaert Alexander
Published: June 2020

Early childhood teachers worldwide feel that their ability to act according to their professional knowledge and values is constrained. This sense of constraint is commonly attributed to the pressures of accountability policies, aimed at ensuring and improving educational quality. By law, Dutch schools are free to choose how they design their teaching practices. Nevertheless, efforts by the government to control daily teaching practices are encountered in Dutch schools. The generally recognized importance of teachers’ professional autonomy led the authors to conduct an in-depth study on this topic in Dutch early childhood education. They interviewed experienced early childhood teachers in open one-on-one interviews to explore their lived realities. The findings contribute to the discourse on three topics: first, the generally felt forces of accountability stemming from a variety of actors in the school environment; second, the impact of these forces on daily education practice, as well as on teachers’ emotions; and third, the role of the head teacher, who appears to be able to either enforce or inhibit these impacts. The results of the study show that where external forms of regulation and accountability measures are passed on by the head teacher, the negative emotional impact of the pressures is high. For head teachers, however, operating in a position between multiple fields of professional influence also seems to offer opportunities for maintaining a healthy balance between regulation and freedom.
Engagement in Household Chores in Youth With Chronic Conditions: Health care Transition Implications
Authors: Richards Jordan , Nazareth Meaghan , van Tilburg Miranda A. L. , Jain Nina , Hart Laura , Faldowski Richard A. , Coltrane Chad , Hooper Stephen R. , Ferris Maria , Rak Eniko
Published: June 2020

This study examined associations between chores engagement, self-management, and transition readiness in youth with chronic conditions. Youths with various chronic conditions attending a therapeutic camp, and their parents participated. Responses of 165 campers and their parents were analyzed (mean camper age 12.3 ± 2.6 years, 47.9% males, 79.4% White). The most common diagnoses were diabetes, spina bifida, cerebral palsy, and sickle cell anemia. Youth who completed chores manifested higher overall health care transition readiness ([Formula: see text] = 5.17, p = .026) and better communication with providers ([Formula: see text] = 2.98, p = .006) than youth who completed no chores. Higher chores frequency was not more predictive of higher health care transition readiness scores above and beyond the effects of having chores at all. These results suggest that responsible health care behaviors are related to similar actions in other areas of life. Assignment of chores may promote self-management and health care transition readiness in youth with chronic conditions.
Dual-energy computed-tomography-based discrimination between basic calcium phosphate and calcium pyrophosphate crystal deposition in vivo
Authors: Pascart Tristan , Falgayrac Guillaume , Norberciak Laurène , Lalanne Clément , Legrand Julie , Houvenagel Eric , Ea Hang-Korng , Becce Fabio , Budzik Jean-François
Published: June 2020

Background:

Dual-energy computed tomography (DECT) is being considered as a non-invasive diagnostic and characterization tool in calcium crystal-associated arthropathies. Our objective was to assess the potential of DECT in distinguishing between basic calcium phosphate (BCP) and calcium pyrophosphate (CPP) crystal deposition in and around joints in vivo.

Methods:

A total of 13 patients with calcific periarthritis and 11 patients with crystal-proven CPPD were recruited prospectively to undergo DECT scans. Samples harvested from BCP and CPP calcification types were analyzed using Raman spectroscopy and validated against synthetic crystals. Regions of interest were placed in BCP and CPP calcifications, and the following DECT attenuation parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (Rho), and effective atomic number ( Zeff). These DECT attenuation parameters were compared and validated against crystal calibration phantoms at two known equal concentrations. Receiver operating characteristic (ROC) curves were plotted to determine the highest accuracy thresholds for DEI and Zeff.

Results:

Raman spectroscopy enabled chemical fingerprinting of BCP and CPP crystals both in vitro and in vivo. DECT was able to distinguish between HA and CPP in crystal calibration phantoms at two known equal concentrations, most notably by DEI (200 mg/cm3: 0.037 ± 0 versus 0.034 ± 0, p = 0.008) and Zeff (200 mg /cm3: 9.4 ± 0 versus 9.3 ± 0, p = 0.01) analysis. Likewise, BCP calcifications had significantly higher DEI (0.041 ± 0.005 versus 0.034 ± 0.005, p = 0.008) and Zeff (9.5 ± 0.2 versus 9.3 ± 0.2, p = 0.03) than CPP crystal deposits with comparable CT numbers in patients. With an area under the ROC curve of 0.83 [best threshold value = 0.0 39, sensitivity = 90. 9% (81.8, 97. 7%), specificity = 64.6% (50.0, 64. 6%)], DEI was the best parameter in distinguishing between BCP and CPP crystal depositions.

Conclusion:

DECT can help distinguish between crystal-proven BCP and CPP calcification types in vivo and, thus, aid in the diagnosis of challenging clinical cases, and in the characterization of CPP and BCP crystal deposition occurring in osteoarthritis.
Creativity for the Group: Distinctive Feminists Engage in Divergent Thinking When Acting on Behalf of Women
Authors: van Breen J. A. , Gocłowska M. A. , de Lemus S. , Baas M. , Kelleci B. , Spears R.
Published: June 2020

For feminists, a core goal is to promote the interests of women as a group. Across three studies, we examined whether the pursuit of such goals can lead feminists to use more divergent thinking styles. We measured identification with feminists, identification with women, and manipulated the extent to which a divergent thinking task was congruent with the goal of promoting women’s interests. Results showed that—when given the opportunity to promote the interests of women—feminist identification was associated with greater divergent thinking. This effect was observed only in feminists who identified less strongly with women as a group (“distinctive feminists”). We conclude that distinctive feminists draw on divergent thinking to promote the interests of women as a group.
Understanding new actors in European Arrest Warrant cases concerning detention conditions: The role, powers and functions of prison inspection and monitoring bodies
Authors: Aizpurua Eva , Rogan Mary
Published: June 2020

Prison inspection and monitoring bodies are becoming central players in European Arrest Warrant (EAW) decision-making. These bodies write reports on prison conditions and examine their compliance with fundamental rights. Now that poor prison conditions can be a basis to refuse an EAW’s execution, these bodies are becoming increasingly important actors in EAW decision-making process. While this is so, there is a remarkable lack of analysis on the legal structures and activities of such bodies. This article addresses this absence by presenting findings from the first European Union (EU)-wide study of prison inspection and monitoring bodies, providing new insights into the nature of these bodies. It provides both empirical insights into these structures for overseeing detention conditions and doctrinal analysis. It assesses the implications of an increased role for such bodies in the Area of Freedom, Security and Justice.
#digitalnomads, #solotravellers, #remoteworkers: A Cultural Critique of the Traveling Entrepreneur on Instagram
Authors: Bozzi Nicola
Published: June 2020

As opposed to traditional nomads, backpackers, or tourists, digital nomads are defined as Internet-enabled remote workers, who maintain a focus on connectivity and productivity even in leisure. This essay discusses the relationship between Instagram and the digital nomad from a theoretical perspective, proposing a critique of the aesthetics and urban politics that underlie this figure. Inspired by recent theories that combine geopolitical and technological insight with a speculative approach, the article positions the digital nomad as a cultural avatar of contemporary neoliberalism, which celebrates a depoliticized aesthetics of work and helps establish a material geography of globalization through social media. In particular, the essay leverages the concept of tagging (not only intended as the use of hashtags like #digitalnomad, #solotraveller, or #remotework, but also geotagging) as a tool for cultural critique, discussing Instagram as a key site of intersection between the imaginary appeal of the traveling entrepreneur and the material effects of globalized gentrification. The conclusion provocatively suggests that, with the increasing economic and geopolitical influence of digital nomadism, Instagram might become a site of negotiation of the figure’s culture and aesthetics, potentially steering them toward a more radical re-imagination of borders and life beyond work. By offering a cultural critique of the digital nomad, the essay contributes to critical discourse on Instagram as a cultural platform.
Dry Taps? A Synthesis of Alternative “Wash” Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings
Authors: Kivuti-Bitok Lucy W. , Chepchirchir Angeline , Waithaka Peter , Ngune Irene
Published: June 2020

Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.
“Planned Benefits” Can Be Misleading in Digital Transformation Projects: Insights From a Case Study of Human Resource Information Systems Implementation in Healthcare
Authors: Tursunbayeva Aizhan , Bunduchi Raluca , Pagliari Claudia
Published: June 2020

Human Resources Information Systems (HRIS) are being implemented in many organizations but, like other technology projects, translating their potential benefits into meaningful improvements can be challenging. So-called “planned benefits” approaches are designed to aid this translation, but little is known about their success in HRIS projects. This study examined how a planned benefits approach was manifested in a national-scale HRIS implementation program. The results point to the importance of reviewing the benefits plan at regular intervals, to ensure the project can adapt to changing circumstances, and considering benefits at the level of individual modules and user groups, as well as for the organization as a whole. Adequate data preparation, training, effective communication, and process analysis were identified as key actions necessary for successful HRIS implementation and benefit realization.
Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria
Authors: Moxon Christopher A. , Alhamdi Yasir , Storm Janet , Toh Julien M. H. , McGuinness Dagmara , Ko Joo Yeon , Murphy George , Lane Steven , Taylor Terrie E. , Seydel Karl B. , Kampondeni Sam , Potchen Michael , O’Donnell James S. , O’Regan Niamh , Wang Guozheng , García-Cardeña Guillermo , Molyneux Malcolm , Craig Alister G. , Abrams Simon T. , Toh Cheng-Hock
Published: June 2020

Microvascular thrombosis and blood–brain barrier (BBB) breakdown are key components of cerebral malaria (CM) pathogenesis in African children and are implicated in fatal brain swelling. How Plasmodium falciparum infection causes this endothelial disruption and why this occurs, particularly in the brain, is not fully understood. In this study, we have demonstrated that circulating extracellular histones, equally of host and parasite origin, are significantly elevated in CM patients. Higher histone levels are associated with brain swelling on magnetic resonance imaging. On postmortem brain sections of CM patients, we found that histones are colocalized with P falciparum–infected erythrocytes sequestered inside small blood vessels, suggesting that histones might be expelled locally during parasite schizont rupture. Histone staining on the luminal vascular surface colocalized with thrombosis and leakage, indicating a possible link between endothelial surface accumulation of histones and coagulation activation and BBB breakdown. Supporting this, patient sera or purified P falciparum histones caused disruption of barrier function and were toxic to cultured human brain endothelial cells, which were abrogated with antihistone antibody and nonanticoagulant heparin. Overall, our data support a role for histones of parasite and host origin in thrombosis, BBB breakdown, and brain swelling in CM, processes implicated in the causal pathway to death. Neutralizing histones with agents such as nonanticoagulant heparin warrant exploration to prevent brain swelling in the development or progression of CM and thereby to improve outcomes.
Desquamative interstitial pneumonia: a systematic review of its features and outcomes
Authors: Hellemons Merel E. , Moor Catharina C. , von der Thüsen Jan , Rossius Mariska , Odink Arlette , Thorgersen Laila Haugen , Verschakelen Johny , Wuyts Wim , Wijsenbeek Marlies S. , Bendstrup Elisabeth
Published: June 2020

Background

Desquamative Interstitial Pneumonia (DIP) is a rare form of idiopathic interstitial pneumonia (IIP). Data on clinical features, aetiology, prognosis and effect of treatment strategies are limited. We aimed to collect all published cases to better characterise DIP.

Methods

A systematic literature search was performed for all original cases of adult patients with histopathologically-confirmed DIP. Individual patient data were extracted and summarised.

Results

We included 68 individual cases and 13 case series reporting on 294 cases. Most common presenting symptoms were dyspnoea and cough. Pulmonary function showed a restrictive pattern (71%) with decreased diffusion capacity. We found a high incidence (81%) of ever smoking in patients with DIP and 22% of patients had other (occupational) exposures. Characteristic features on high-resolution computed tomography (HRCT) scan were bilateral ground-glass opacities with lower lobe predominance (92%). Treatment and duration of treatment widely varied. Initial response to treatment was generally good, but definitely not uniformly so. A significant proportion of patients died (25% of individual cases) or experienced a relapse (18% of individual cases).

Conclusion

DIP remains an uncommon disease, frequently but not always related to smoking or other exposures. Furthermore, DIP behaves as a progressive disease more often than generally thought, possibly associated with different underlying aetiology.
Transitioning to lead-free ammunition use in hunting: socio-economic and regulatory considerations for the European Union and other jurisdictions
Authors: Kanstrup Niels , Thomas Vernon G.
Published: June 2020

Background

Hunting throughout the European Union (EU) has left an accumulating legacy of spent lead ammunition that has deleterious toxic effects upon the environment, wildlife, and humans who consume hunted game meat. Non-toxic lead substitutes for both rifle and shotgun ammunition have been developed and are required in some EU jurisdictions. Within the EU, at least 28 companies make or distribute non-lead shotgun ammunition, and a further 14 companies distribute non-lead rifle ammunition. However, a broad transition to the use of these products has been resisted by the hunting and ammunition-making communities.

Results and conclusions

It is in the self-interest of these communities to recognize the consequences of externalizing the effects of spent lead ammunition to society, and to make hunting more sustainable and socially acceptable. The paper endorses the ongoing process under the European Commission (EC) to introduce wide and fundamental restrictions on the use, trade and possession of lead ammunition for all types of hunting within 3 years, and within 5 years for clay target shooting. This would align EC regulations on lead from ammunition with lead from other anthropogenic sources, and EC regulations that protect the natural environment, especially the conservation of wild birds. Simultaneous EC regulation of lead in marketed game meats would provide extra health protection and assure a safe source of game meat products for consumers.
Construction situation, costs and charges associated with pharmacy intravenous admixture services: multi-center cross-sectional survey based on 137 medical institutions in mainland China
Authors: Yang Chunsong , Kang Bing Yao , Zhang Lingli , Yu Dan
Published: June 2020

Background

To investigate the construction situation, costs and charges associated with pharmacy intravenous admixture services (PIVAS) to provide references for the construction and development of PIVAS in mainland China.

Methods

A multi-center cross-sectional survey was conducted via a WeChat Group targeting PIVAS leaders in hospitals to investigate the basic situation of PIVAS, including opening time, area, number of PIVAS, equipment, management mode, PIVAS costs and charges, as well as numbers of beds, open wards, and staff, and analyze differences in PIVAS construction at different provincial and hospital levels.

Results

137 questionnaires were collected from 29 provinces, representing a response rate of 99.3%. Most participants (88.4%) were from Level III Hospitals. The number of years of operations of PIVAS ranged from 1 to 22 (median: 6). PIVAS site area ranged between 100 and 1973 m2; daily average infusion volume was concentrated in the ranges 0–1000 bags (29.9%, 41/137) and 1001–2000 bags (26.3%, 36/137). In terms of PIVAS management mode, the vast majority used separate pharmacy management (65.0%, 89/137). Only 52.6% (72/137) of PIVAS have standardized charges, and 70.1% (96/137) operate at a loss. The median costs of mixed tumor chemotherapy drugs, total parenteral nutrition, general medicine, antibiotics were 20, 35, 4 and 5 RMB, respectively. With the exception of a few features, PIVAS construction does not obviously differ among different regions and hospital levels.

Conclusions

In recent years, PIVAS in China has developed rapidly and become relatively large. The main problems are that most provinces lack standards for charges and PIVAS construction differs among hospitals. Therefore, standards for PIVAS construction and charges should be developed to provide a reference for the future development of PIVAS.
Correction to: The one-in-all diagnostic value of 99mTcMDP bone scan combining with singlephoton emission tomography (SPECT)/CT imaging in spinal osteoblastoma
Authors: Ma Wenhui , Quan Zhiyong , Wang Jing , Li Xiangdong , Li Guoquan
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples
Authors: Russano Marco , Napolitano Andrea , Ribelli Giulia , Iuliani Michele , Simonetti Sonia , Citarella Fabrizio , Pantano Francesco , Dell’Aquila Emanuela , Anesi Cecilia , Silvestris Nicola , Argentiero Antonella , Solimando Antonio Giovanni , Vincenzi Bruno , Tonini Giuseppe , Santini Daniele
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
cfNOMe — A single assay for comprehensive epigenetic analyses of cell-free DNA
Authors: Erger Florian , Nörling Deborah , Borchert Domenica , Leenen Esther , Habbig Sandra , Wiesener Michael S. , Bartram Malte P. , Wenzel Andrea , Becker Christian , Toliat Mohammad R. , Nürnberg Peter , Beck Bodo B. , Altmüller Janine
Published: June 2020

Cell-free DNA (cfDNA) analysis has become essential in cancer diagnostics and prenatal testing. We present cfNOMe, a two-in-one method of measuring cfDNA cytosine methylation and nucleosome occupancy in a single assay using non-disruptive enzymatic cytosine conversion and a custom bioinformatic pipeline. We show that enzymatic cytosine conversion better preserves cfDNA fragmentation information than does bisulfite conversion. Whereas previously separate experiments were required to study either epigenetic marking, cfNOMe delivers reliable results for both, enabling more comprehensive and inexpensive epigenetic cfDNA profiling. cfNOMe has the potential to advance biomarker discovery and diagnostic usage in diseases with systemic perturbations of cfDNA composition.
A comparison of epigenetic mitotic-like clocks for cancer risk prediction
Authors: Teschendorff Andrew E.
Published: June 2020

Background

DNA methylation changes that accrue in the stem cell pool of an adult tissue in line with the cumulative number of cell divisions may contribute to the observed variation in cancer risk among tissues and individuals. Thus, the construction of epigenetic “mitotic” clocks that can measure the lifetime number of stem cell divisions is of paramount interest.

Methods

Building upon a dynamic model of DNA methylation gain in unmethylated CpG-rich regions, we here derive a novel mitotic clock (“epiTOC2”) that can directly estimate the cumulative number of stem cell divisions in a tissue. We compare epiTOC2 to a different mitotic model, based on hypomethylation at solo-WCGW sites (“HypoClock”), in terms of their ability to measure mitotic age of normal adult tissues and predict cancer risk.

Results

Using epiTOC2, we estimate the intrinsic stem cell division rate for different normal tissue types, demonstrating excellent agreement (Pearson correlation = 0.92, R2 = 0.85, P = 3e−6) with those derived from experiment. In contrast, HypoClock’s estimates do not (Pearson correlation = 0.30, R2 = 0.09, P = 0.29). We validate these results in independent datasets profiling normal adult tissue types. While both epiTOC2 and HypoClock correctly predict an increased mitotic rate in cancer, epiTOC2 is more robust and significantly better at discriminating preneoplastic lesions characterized by chronic inflammation, a major driver of tissue turnover and cancer risk. Our data suggest that DNA methylation loss at solo-WCGWs is significant only when cells are under high replicative stress and that epiTOC2 is a better mitotic age and cancer risk prediction model for normal adult tissues.

Conclusions

These results have profound implications for our understanding of epigenetic clocks and for developing cancer risk prediction or early detection assays. We propose that measurement of DNAm at the 163 epiTOC2 CpGs in adult pre-neoplastic lesions, and potentially in serum cell-free DNA, could provide the basis for building feasible pre-diagnostic or cancer risk assays. epiTOC2 is freely available from 10.5281/zenodo.2632938
A video protocol for rapid dissection of mouse dorsal root ganglia from defined spinal levels
Authors: Sleigh James N. , West Steven J. , Schiavo Giampietro
Published: June 2020

Objective

Dorsal root ganglia (DRG) are heterogeneous assemblies of assorted sensory neuron cell bodies found in bilateral pairs at every level of the spinal column. Pseudounipolar afferent neurons convert external stimuli from the environment into electrical signals that are retrogradely transmitted to the spinal cord dorsal horn. To do this, they extend single axons from their DRG-resident somas that then bifurcate and project both centrally and distally. DRG can be dissected from mice at embryonic stages and any age post-natally, and have been extensively used to study sensory neuron development and function, response to injury, and pathological processes in acquired and genetic diseases. We have previously published a step-by-step dissection method for the rapid isolation of post-natal mouse DRG. Here, the objective is to extend the protocol by providing training videos that showcase the dissection in fine detail and permit the extraction of ganglia from defined spinal levels.

Results

By following this method, the reader will be able to swiftly and accurately isolate specific lumbar, thoracic, and cervical DRG from mice. Dissected ganglia can then be used for RNA/protein analyses, subjected to immunohistochemical examination, and cultured as explants or dissociated primary neurons, for in-depth investigations of sensory neuron biology.
The influence of surficial features in lava flow modelling
Authors: Tsang Sophia W. R. , Lindsay Jan M. , Coco Giovanni , Deligne Natalia I.
Published: June 2020

Lava flows can cause substantial and immediate damage to the built environment and affect the economy and society over days through to decades. Lava flow modelling can be undertaken to help stakeholders prepare for and respond to lava flow crises. Traditionally, lava flow modelling is conducted on a digital elevation model, but this type of representation of the surface may not be appropriate for all settings. Indeed, we suggest that in urban areas a digital surface model may more accurately capture all of the obstacles a lava flow would encounter. We use three effusive eruption scenarios in the well-studied Auckland Volcanic Field (New Zealand) to demonstrate the difference between modelling on an elevation model versus on a surface model. The influence of surficial features on lava flow modelling results is quantified using a modified Jaccard coefficient. For the scenario in the most urbanised environment, the Jaccard coefficient is 40%, indicating less than half of the footprints overlap, while for the scenario in the least urbanised environment, the Jaccard coefficient is 90%, indicating substantial overlap. We find that manmade surficial features can influence the hazard posed by lava flows and that a digital surface model may be more applicable in highly modified environments.
Country-level interventions for the prevention and management of hypertension through the modification of social determinants of health: a systematic review protocol
Authors: Arabi Basharic Fateme , Janati Ali , Pezeshki Mohammad Zakaria , Khodayari-Zarnaq Rahim , Sadeghi-Ghyassi Fatemeh , Gholizadeh Masoumeh
Published: June 2020

Background

Hypertension is one of the public health challenges. Various risk factors are associated with hypertension, including social demographics, geographical location, health behaviours, and social stress. Interventions in the social determinants of health can improve hypertension and health promotion. Accordingly, different sectors such as agriculture, housing, education, and transportation should cooperate. This systematic review examines policies as a set of activities and actions/interventions aimed at the modification of the social determinants of health to prevent hypertension.

Methods

A systematic search will be conducted in Medline (via Ovid), PubMed, EMBASE, Cochrane Library, ProQuest Dissertations & Theses, and scientific Persian databases including SID and Magiran. There will be no time restriction. The quality of selected studies will be assessed using an appropriate Joanna Briggs Institute (JBI) Critical Appraisal Checklists according to the type of studies. Two independent researchers will carry out screening and quality assessment. Disagreement between two researchers will be resolved by a third party.

Discussion

Recommendations will be made for policymakers in order to make better evidence-based decisions about the prevention and management of hypertension with regard to the social determinants of health.

Systematic review registration

PROSPERO CRD42020152298
Modified Chebyshev collocation method for delayed predator–prey system
Authors: Dengata J. , Ma Shufang
Published: June 2020

In this study, the approximate solutions of the predator–prey system with delay have been obtained by using the modified Chebyshev collocation method. The main technique is that this method transforms the original problem into a system of nonlinear algebraic equations. By using the residual function of the operator equations, error differential equations are constructed and thus the approximate solutions are corrected. A numerical example is given to confirm the reliability and applicability of the method, and comparisons with existing results are given. The numerical results show that the obtained solutions are in good agreement with earlier studies.
A Simplified Method to Predict Damage of Axially-Loaded Circular RC Columns Under Lateral Impact Loading
Authors: Liu Bin , Fan Wei , Huang Xu , Shao Xudong , Kang Lijing
Published: June 2020

Detailed finite element (FE) models are often employed to predict the impact responses of reinforced concrete (RC) columns. However, they always require substantial investments of time and effort in modeling and analysis so that they are not widely used in practice, particularly in preliminary designs. Moreover, although some simplified models have been established for beams and slabs under impact loading, few attempts have been made on modeling RC columns. For these reasons, this paper proposes a simplified modeling method to accurately capture the impact-induced response and damage of circular RC columns. In the proposed method, a two-degree-of-freedom (DOF) system was used to describe the interaction between the impactor and the impacted column. The formulas, and procedure to estimate the force–deformation relationship with strain-rate effects were presented according to the section-based analysis. The influence of the unloading stiffness on the residual deformation was addressed, and the method to determine the unloading stiffness of circular columns was proposed. Furthermore, a fiber-based beam-column element modeling method was developed to estimate the force–deformation relationship of the columns with strain-rate effects. The proposed simplified method was demonstrated by the drop-hammer impact tests to be capable of predicting the impact response of RC columns well. Its accuracy in the residual deformation is superior to that of the detailed FE simulation. Parametric studies were performed to investigate the damage characteristics of axially-loaded circular RC columns under various impact scenarios.
A randomised controlled pilot trial of two interventions to manage dry mouth in pre-operative elective surgical patients
Authors: Morton Leesa , Siu Amanda Tsan Yue , Fowler Samuel , Zhou Chen , Nixon Christopher , Campbell Doug
Published: June 2020

Background

Dry mouth is a common perioperative patient complaint. There are a number of treatments used for dry mouth in other settings which are effective. None have been tested previously in the perioperative setting. Interventions to Manage Dry mouth (IM DRY) compared the effect of water and a saliva substitute on mouth dryness. The primary objective was to demonstrate the feasibility of conducting a large randomised controlled trial and secondary scientific aims were to assess treatment potential efficacy.

Methods

Single blind, pilot randomised controlled trial (RCT) of 101 pre-operative elective surgical patients who were randomised to water or saliva substitute (Biotene oral rinse, GlaxoSmithKline, Australia) at a tertiary, university hospital. Dry mouth was assessed by 100 mm visual analogue scale (VAS) and 5-point Likert score.

Results

One hundred participants completed follow-up and comprised the analysis dataset. All feasibility outcomes were achieved (recruitment rate > 5 participants a week, >95% completeness of the dataset, study protocol acceptability to staff, acceptability to participants > 66% and adherence to time limits within the protocol). Mean recruitment rate was 6 participants per week. These data were 99% complete. There were no adverse side effects or complications noted. There were no concerns raised by staff regarding acceptability. Overall, there was a mean of 30 min (± SD 5 min) between delivery of the intervention and the assessment, 30 min being the target time. The difference in VAS post intervention was − 11.2 mm (95% CI − 17.3 to − 5.1 mm) for water and − 12.7 mm (95% CI − 18.7 to − 6.7 mm) for saliva substitute. The proportion of patients who had improved dry mouth increased from 52% for water to 62% for saliva substitute.

Conclusions

IM DRY successfully achieved its primary feasibility aims: recruitment rate, completeness of these, acceptability and protocol adherence. Saliva substitutes, used in the perioperative management of dry mouth, may be a simple, inexpensive, and low risk solution to help alleviate this common complaint. A large randomised controlled trial is feasible and is currently recruiting (ANZCTR 12619000132145).

Ethics and Trial registration

Northern A New Zealand Health and Disability Ethics Committee (reference 17/NTA/152). Australian New Zealand Clinical Trials Registry (Number: 12618001270202). Registered retrospectively 18 October 2018.
Prioritising target non-pharmacological interventions for research in Parkinson’s disease: achieving consensus from key stakeholders
Authors: Bogosian Angeliki , Rixon Lorna , Hurt Catherine S.
Published: June 2020

Background

In 2014 Parkinson’s UK conducted a research prioritisation exercise with stakeholders highlighting important clinical research questions. The exercise highlighted the need for effective interventions to be developed and tested to tackle a range of non-motor symptoms including: sleep quality, stress and anxiety, mild cognitive impairment, dementia and urinary problems. The present work set out to build on this exercise by prioritising types of non-pharmacological interventions to be tested to treat the identified non-motor symptoms.

Methods

A Patient and Public Involvement exercise was used to reach consensus on intervention priorities for the treatment of non-motor symptoms. A Delphi structure was used to support the feedback collected. A first-round prioritisation survey was conducted followed by a panel discussion. Nineteen panellists completed the first-round survey (9 people with Parkinson’s and 10 professionals working in Parkinson’s) and 16 participated in the panel discussion (8 people with Parkinson’s and 8 professionals working in Parkinson’s). A second-round prioritization survey was conducted after the panel discussion with 13 people with Parkinson’s.

Results

Physical activity, third wave cognitive therapies and cognitive training were rated as priority interventions for the treatment of a range of non-motor symptoms. There was broad agreement on intervention priorities between health care professionals and people with Parkinson’s. A consensus was reached that research should focus on therapies which could be used to treat several different non-motor symptoms. In the context of increasing digitisation, the need for human interaction as an intervention component was highlighted.

Conclusion

Bringing together Parkinson’s professionals and people with Parkinson’s resulted in a final treatment priority list which should be both feasible to carry out in routine clinical practice and acceptable to both professionals and people with Parkinson’s. The workshop further specified research priorities in Parkinson’s disease based on the current evidence base, stakeholder preferences, and feasibility. Research should focus on developing and testing non-pharmacological treatments which could be effective across a range of symptoms but specifically focusing on tailored physical activity interventions, cognitive therapies and cognitive training.
18F-FDG PET-guided diffusion tractography reveals white matter abnormalities around the epileptic focus in medically refractory epilepsy: implications for epilepsy surgical evaluation
Authors: Poirier Stefan E. , Kwan Benjamin Y. M. , Jurkiewicz Michael T. , Samargandy Lina , Steven David A. , Suller-Marti Ana , Lam Shin Cheung Victor , Khan Ali R. , Romsa Jonathan , Prato Frank S. , Burneo Jorge G. , Thiessen Jonathan D. , Anazodo Udunna C.
Published: June 2020

Background

Hybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning.

Methods

FDG-PET and diffusion MRI of 14 MRI-negative or equivocal MRE patients were used to retrospectively pilot the PET/DTI approach. We used asymmetry index (AI) mapping of FDG-PET to detect the EF as brain areas showing the largest decrease in FDG uptake between hemispheres. Seed-based WM fiber tracking was performed on DTI images with a seed location in WM 3 mm from the EF. Fiber tractography was repeated in the contralateral brain region (opposite to EF), which served as a control for this study. WM fibers were quantified by calculating the fiber count, mean fractional anisotropy (FA), mean fiber length, and mean cross-section of each fiber bundle. WM integrity was assessed through fiber visualization and by normalizing ipsilateral fiber measurements to contralateral fiber measurements. The added value of PET/DTI in clinical decision-making was evaluated by a senior neurologist.

Results

In over 60% of the patient cohort, AI mapping findings were concordant with clinical reports on seizure-onset localization and lateralization. Mean FA, fiber count, and mean fiber length were decreased in 14/14 (100%), 13/14 (93%), and 12/14 (86%) patients, respectively. PET/DTI improved diagnostic confidence in 10/14 (71%) patients and indicated that surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery.

Conclusions

We demonstrate here the utility of AI mapping in detecting the EF based on brain regions showing decreased FDG-PET activity and, when coupled with DTI, could be a powerful tool for detecting EF and assessing WM integrity in MRI-negative epilepsy. PET/DTI could be used to further enhance clinical decision-making in epilepsy surgery.