bluuebunny/crossref_metadata_2025 huggingface dataset:
Prodrugs of New Psychoactive Substances (NPS): A New Challenge
Authors: Elliott Simon P. , Holdbrook Tanith , Brandt Simon D.
Published: January 2020

The concept of a substance acting as a prodrug for an intended drug is not new and has been known and utilized with particular benefits within medicine for efficacy and patient safety. Prodrugs of psychoactive substances are also not particularly new but this has also extended to considerations of prodrugs of new psychoactive substances (NPS). The continuing evolution of NPS has been a constant forensic challenge. In some countries, this constant evolution has led to the introduction of various alternative methods of drug control. Whether for this reason or in the pursuit of user experimentation, prodrugs of NPS have been discussed, developed, and exploited, posing some distinct forensic challenges. This is especially the case within toxicological analysis of biological fluids and for some substances, also forensic chemical analysis, through inherent instability of the prodrug or metabolism in the body. Particular examples of NPS prodrugs include 1‐propanoyl‐LSD, 1‐butanoyl‐LSD, 1‐acetyl‐LSD, and 2C‐B‐AN. This is in addition to associated substances and medicines that may be used for an intended pharmacological effect. Various prodrugs for stimulant and hallucinogenic substances in particular have appeared in the literature and have been discussed within drug user forums and made available for purchase online. Presently, drug monitoring data from national and international systems indicate that prodrugs are not widely available or problematic. Nevertheless, it is important that there is sufficient awareness of the prodrug concept and potential impact and associated forensic implications, not just for chemical analysis but also for toxicological considerations when a substance has been used.
The impact of contaminants on the accuracy of genome skimming and the effectiveness of exclusion read filters
Authors: Rachtman Eleonora , Balaban Metin , Bafna Vineet , Mirarab Siavash
Published: January 2020

The ability to detect the identity of a sample obtained from its environment is a cornerstone of molecular ecological research. Thanks to the falling price of shotgun sequencing, genome skimming, the acquisition of short reads spread across the genome at low coverage, is emerging as an alternative to traditional barcoding. By obtaining far more data across the whole genome, skimming has the promise to increase the precision of sample identification beyond traditional barcoding while keeping the costs manageable. While methods for assembly‐free sample identification based on genome skims are now available, little is known about how these methods react to the presence of DNA from organisms other than the target species. In this paper, we show that the accuracy of distances computed between a pair of genome skims based on k‐mer similarity can degrade dramatically if the skims include contaminant reads; i.e., any reads originating from other organisms. We establish a theoretical model of the impact of contamination. We then suggest and evaluate a solution to the contamination problem: Query reads in a genome skim against an extensive database of possible contaminants (e.g., all microbial organisms) and filter out any read that matches. We evaluate the effectiveness of this strategy when implemented using Kraken‐II, in detailed analyses. Our results show substantial improvements in accuracy as a result of filtering but also point to limitations, including a need for relatively close matches in the contaminant database.
A PRISMA‐Drıven Systematıc Revıew for Determınıng Cross‐Cultural Mental Health Care
Authors: Üzar‐Özçetin Yeter Sinem , Tee Stephen
Published: January 2020

PURPOSE

The study aimed to determine how culture can affect mental healthcare delivery in order to make recommendations for improving care pathways supported by culturally competent care.

METHODS

Three international databases were systematically and independently searched by two researchers.

FİNDİNGS

The results were grouped under three themes—quality of cross‐cultural mental health care, expectations of people receiving cross‐cultural mental health care, and perspectives of healthcare providers on cross‐cultural mental health care.

CONCLUSİONS

The study indicates how important it is for nurses to understand the complex interplay between culture and mental health and to develop cultural awareness and sensitivity.

PRACTİCE IMPLİCATİONS

The study seeks to identify best practice and make recommendations for enhancing positive attitudes toward the cultural needs of people with mental health problems
Digital navigators to implement smartphone and digital tools in care
Authors: Wisniewski H. , Torous J.
Published: January 2020

While smartphone apps and other digital health tools have the clear potential to increase both quality of and access to care, actual successful implementation remains limited. Challenges often encountered in seeking to use apps in care include selecting safe/effective tools, spending clinical time troubleshooting technology instead of discussing health matters, and lack of time to check and review constant streams of data these digital tools can produce. In this ‘From Research to Clinical Practice’ piece, we focus on how a new care team member, the digital navigator, can help overcome these barriers through conducting evidence‐based app evaluation to help in selecting the right apps, troubleshooting technology outside of visits to improve the therapeutic alliance during, and finally summarizing digital data to facilitate clinical care that focus on actionable data.
A Multi‐Level Approach to Direct and Indirect Relationships between Organizational Voice Climate, Team Manager Openness, Implicit Voice Theories, and Silence
Authors: Knoll Michael , Neves Pedro , Schyns Birgit , Meyer Bertolt
Published: January 2020

Employee silence impedes sustainable organizational development, and it can conceal harm for internal and external stakeholders. Established approaches to overcoming silence in organizations draw on the assumption that employees withhold their views based on deliberate elaborations on the effectiveness and risks they associate with voice. Our research aims at complementing these approaches. Applying an information processing approach to culture and using implicit voice theories (IVTs; i.e., taken‐for‐granted beliefs about when and why speaking up at work is risky or inappropriate) as an example, we introduce a model proposing ways through which shared implicit knowledge structures emerge in teams and organizations, and how they affect motives to remain silent. We examine parts of the model with a sample of 696 employees nested in 129 teams and 67 organizations. Our findings show that IVTs can be shared at the team and organizational level, that shared IVTs explain variance in silence motives above and beyond perceptions of organizational climate and manager openness at the team and organization level, and that IVTs function as a mediator between team manager openness and silence motives. In sum, our findings point at shared IVTs as a way to conceptualize underlying basic assumptions of cultures of silence.
The Nuffield Council’s green light for genome editing human embryos defies fundamental human rights law
Authors: Drabiak Katherine
Published: January 2020

In July 2018, the Nuffield Council on Bioethics released the report Genome editing and human reproduction: Social and ethical issues, concluding that human germline modification of human embryos for implantation is not ‘morally unacceptable in itself’ and could be ethically permissible in certain circumstances once the risks of adverse outcomes have been assessed and the procedure appears ‘reasonably safe’. The Nuffield Council set forth two main principles governing anticipated uses and envisions applications that may include health enhancements as a public health measure. This essay provides a critique of three aspects in the Nuffield Council’s Report: its presumption of therapeutic efficacy, its inflation of parental rights to create a certain type of child, and its reliance on a specially commissioned report that appears to distort key definitions in international law.
A thymic stromal lymphopoietin polymorphism may provide protection from asthma by altering gene expression
Authors: Moorehead Amy , Hanna Raphael , Heroux Delia , Neighbour Helen , Sandford Andrew , Gauvreau Gail M. , Sommer Doron D. , Denburg Judah A. , Akhabir Loubna
Published: January 2020

Background

Genome‐wide association studies have identified associations of the single nucleotide polymorphism rs1837253 in the thymic stromal lymphopoietin (TSLP) gene with asthma, allergic disease and eosinophilia. The TSLP gene encodes two isoforms, long and short, and previous studies have indicated functional differences between these two isoforms.

Objective

We investigated the expression of these TSLP isoforms in response to a pro‐inflammatory signal, and the role of the rs1837253 genotype in gene isoform regulation.

Methods

We cultured nasal epithelial cells of asthmatic and non‐asthmatic subjects and evaluated poly(I:C)‐induced TSLP protein secretion using multiplex protein assays and gene expression profiles of the TSLP isoforms, and related genes using real‐time qPCR. We correlated these profiles with rs1837253 genotype.

Results

Asthmatic nasal epithelial cells exhibited increased TSLP protein secretion compared with nasal epithelial cells from healthy controls. The long TSLP isoform was more responsive to poly(I:C) stimulation. Additionally, the minor T allele of rs1837253 was less inducible than the major C allele, suggesting differential regulation; this may explain the “protective” effects of the T allele in asthma.

Conclusion

Our results provide important insights into the differential regulation and function of TSLP isoforms, including the role of TSLP rs1837253 polymorphisms in allergic inflammatory processes.

Clinical relevance

The key finding on the influence of TSLP genetic variation on disease expression/endotype could provide basis for investigation into targeted biologics for anti‐TSLP therapies.
Caregiver‐endorsed strategies to improving sexual health outcomes among foster youth
Authors: Albertson Katie , Crouch Julia M. , Udell Wadiya , Schimmel‐Bristow Allison , Serrano Jessica , Ahrens Kym R.
Published: January 2020

Foster youth are at an increased risk of unintended pregnancies and sexually transmitted infections (STIs) compared with peers. We conducted 11 semistructured focus groups with 86 foster and kinship caregivers in three child welfare jurisdictions to understand their strategies for monitoring and communicating with youth in foster care around sexual health topics, with the overall goal of developing a training for caregivers to reduce STI and unintended pregnancies among youth in foster care. We used thematic analysis to analyse the data. Three main themes emerged: (1) strategies to communicate with youth about sexual health (trust‐building, open/direct communication, tailoring information to each individual youth, creative conversation‐starters, and self‐education), (2) strategies for monitoring youth (e.g., tailoring monitoring to youth development/characteristics, clearly communicating rules, co‐development of rules, spending time with youth/friends/friends' parents, using technology, using a social support system), and (3) other strategies to promote positive youth development (advocating for youth, engaging youth in goal‐setting). Trainings that provide caregivers with (1) information on sexual health and normal adolescent development and (2) strategies and skills to help caregivers engage in open, evidence‐informed communication, and monitor youth in a tailored, developmentally‐informed manner are likely to improve reproductive health and other outcomes among youth in foster care.
Assessing stationarity in web analytics: A study of bounce rates
Authors: Poulos Marios , Korfiatis Nikolaos , Papavlassopoulos Sozon
Published: January 2020

Evidence‐based methods for evaluating marketing interventions such as A/B testing have become standard practice. However, the pitfalls associated with the misuse of this decision‐making instrument are not well understood by managers and analytics professionals. In this study, we assess the impact of stationarity on the validity of samples from conditioned time series, which are abundant in web metrics. Such a prominent metric is the bounce rate, which is prevalent in assessing engagement with web content as well as the performance of marketing touchpoints. In this study, we show how to control for stationarity using an algorithmic transformation to calculate the optimum sampling period. This distance is based on a novel stationary ergodic process that considers that a stationary series presents reversible symmetric features and is calculated using a dynamic time warping algorithm in a self‐correlation procedure. This study contributes to the expert and intelligent systems literature by demonstrating a robust method for sub‐sampling time‐series data, which are critical in decision making.
Knowledge, attitudes, and practices of community pharmacists toward the management of acne vulgaris in Palestine: a cross‐sectional study
Authors: Ghanem Rania E. , Mostafa Saja H. , Abu Hamamda Najla K. , Khdour Maher R.
Published: January 2020

Background

Acne vulgaris (AV) is a common dermatological disease affecting almost 85% of teenagers. Patients with AV usually present at community pharmacies during the early stages of their disease.

Aim

The aim of this study was to assess community pharmacists' knowledge, attitudes, and practice toward AV management in West Bank in Palestine.

Methods

This study was a cross‐sectional questionnaire‐based study. The questionnaire included four sections: 1) demographic, 2) knowledge, 3) attitude and practice items related causes, and 4) treatment options and counseling during management of patients with AV. A convenience sampling method was implemented in this study. Parametric and non‐parametric tests were used to compare different issues as appropriate. P < 0.05 were considered significant.

Result

A total of 270 community pharmacists were interviewed, and more than half (54.1%) were males. The study revealed that community pharmacists had an inadequate level of knowledge on management of AV; only 7.7% had high levels of knowledge. Pharmacists have positive attitude regarding AV management, but inadequate knowledge was reflected on their treatment practices; only 10% of participants independently dealt with AV without referral. Pharmacists with a low level of knowledge showed five times more referrals than those with a high level of knowledge (OR: 5.3; P < 0.001), and those with a bachelor degree showed three times more referrals than postgraduates (OR: 3.3; P < 0.001).

Conclusion

There is a demand to update dermatological knowledge of community pharmacists and encourage them to attend structured training programs about the management of AV.
Structures and properties of chicken myofibrillar protein gel induced by microwave heating
Authors: Wei Sumeng , Yang Yuling , Feng Xiao , Li Shanshan , Zhou Lei , Wang Jingyu , Tang Xiaozhi
Published: January 2020

Structures and properties of myofibrillar protein gel prepared at different power (300–800 W) were evaluated. Amino acid analysis demonstrated that changes in microwave power did not alter primary structure of gel. However, an increase in microwave power could change higher structures of gel. As microwave power increased, α‐helix content decreased and β‐sheet content increased. Increased microwave power probably facilitated protein to unfold and expose the internal groups, causing surface hydrophobicity and the formation of disulphide bonds were enhanced, which indicated changes in tertiary and quaternary structures of protein. At 500 W, gel had the best ultrastructure where surface morphology, springiness and water holding capacity reached the optimum. Our findings suggested that microwave at an appropriate power (500 W) could change higher structures of myofibrillar protein gel to achieve desired processing and quality protein gel characteristics.
Why do cognitive prompts hurt learning in older adults?
Authors: Kraiger Kurt , Cavanagh Thomas M. , Willis Colin M. G.
Published: January 2020

The purposes of the present investigation were to attempt to replicate the negative effects for learning prompts in older adults reported by Cavanagh, Kraiger and Peters (2016), determine if the impact of learning prompts depends on type of prompt, and investigate the two possible explanations of the negative impact of prompts – increased cognitive load and higher negative affect. Learning prompts refer to short text inserted into training content to encourage trainees to rehearse new content or engage in meta‐cognitive activity. Although learning prompts generally lead to greater learning in training, Cavanagh et al. reported a negative impact for prompts on measures of recall and transfer. Using similar training materials and learning outcome measures, we conducted two studies using both elaboration and meta‐cognitive prompts in online training. In the first, older adults (N = 194) between 55 and 70 years and younger adults (N = 218) were randomly assigned to either a meta‐cognitive, elaboration or no prompts (control) condition. Older adults learned less and reported greater mental effort than younger learners, but these effects were not moderated by prompt condition. In the second, N = 57 older adults were randomly assigned to the same three prompts conditions listed above. Older adults learned less with prompts than without, but there were no differences between conditions in mental effort or negative affect. In sum, we found negative effects for learning prompts in older adults in two studies, but found no evidence to suggest that these effects were due to either increased cognitive load or greater negative affect.
Detection of major weather patterns reduces number of simulations in climate impact studies
Authors: Ababaei Behnam , Najeeb Ullah
Published: January 2020

With climate change posing a serious threat to food security, there has been an increased interest in simulating its impact on cropping systems. Crop models are useful tools to evaluate strategies for adaptation to future climate; however, the simulation process may be infeasible when dealing with a large number of G × E × M combinations. We proposed that the number of simulations could significantly be reduced by clustering weather data and detecting major weather patterns. Using 5, 10 and 15 clusters (i.e., years representative of each weather pattern), we simulated phenology, cumulative transpiration, heat‐shock‐induced yield loss (heat loss) and grain yield of four Australian cultivars across the Australian wheatbelt over a 30‐year period under current and future climates. A strong correlation (r2≈1) between the proposed method and the benchmark (i.e., simulation of all 30 years without clustering) for phenology suggested that average duration of crop growth phases could be predicted with substantially fewer simulations as accurately as when simulating all 30 seasons. With mean absolute error of 0.64 days for phenology when only five clusters were identified, this method had a deviation considerably lower than the reported deviations of calibrated crop models. Although the proposed method showed higher deviations for traits highly sensitive to temporal climatic variability such as cumulative transpiration, heat loss and grain yield when five clusters were used, significantly strong correlations were achieved when 10 or 15 clusters were identified. Furthermore, this method was highly accurate in reproducing site‐level impact of climate change. Less than 7% of site × general circulation model (GCM) combinations (zero for phenology) showed incorrect predication of the direction (+/−) of climate change impact when only five clusters were identified while the accuracy further increased at the regional level and with more clusters. The proposed method proved promising in predicting selected traits of wheat crops and can reduce number of simulations required to predict crop responses to climate/management scenarios in model‐aided ideotyping and climate impact studies.
Epidemiology and clinical characteristics of atrial fibrillation in patients with inherited heart diseases
Authors: Butters Alexandra , Isbister Julia C. , Medi Caroline , Raju Hariharan , Turner Christian , Sy Raymond W. , Semsarian Christopher , Ingles Jodie
Published: January 2020

Background

The prevalence and clinical course of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) is well described, though less so for other inherited cardiomyopathies (familial dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction); and inherited arrhythmia syndromes (long QT syndrome, Brugada syndrome or catecholaminergic polymorphic ventricular tachycardia [CPVT]). We examined the frequency, clinical characteristics and AF‐related management and outcomes amongst this patient population.

Methods

We retrospectively studied consecutive probands with inherited cardiomyopathy (n = 962) and inherited arrhythmia syndromes (n = 195) evaluated between 2002 and 2018.

Results

AF was observed in 5% to 31% of patients, with the highest frequency in HCM. Age of AF onset was 45.8 ± 21.9 years in the inherited arrhythmia syndromes compared with 53.3 ± 15.3 years in the inherited cardiomyopathies, with four CPVT patients developing AF at a median age of 20 years. Overall, 11% of patients with AF had a transient ischemic attack or stroke of which a total of 80% were anticoagulated; with 48% of events occurring at a CHA2DS2‐VASc < 2. Amongst sarcomere‐positive HCM, AF was independently associated with age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02‐1.08; P = .0014), left atrial area (OR, 1.11; 95% CI, 1.05‐1.17; P = .0005) and MYH7 variants (OR, 2.55; 95% CI, 1.16‐5.61; P = .020).

Conclusion

Up to one‐third of inherited heart disease patients will develop AF. While common general population risk factors are key in patients with HCM, the genotype is independently associated with AF. Amongst inherited arrhythmia syndromes, AF is less common, though often occurs below the age of 50 years.
Defined host factors support HBV infection in non‐hepatic 293T cells
Authors: Yang Xiaoqiang , Cai Weiwen , Sun Xiaoyue , Bi Yanwei , Zeng Chui , Zhao XiaoYu , Zhou Qi , Xu Tian , Xie Qingdong , Sun Pingnan , Zhou Xiaoling
Published: January 2020

Hepatitis B virus (HBV) is a human hepatotropic virus. However, HBV infection also occurs at extrahepatic sites, but the relevant host factors required for HBV infection in non‐hepatic cells are only partially understood. In this article, a non‐hepatic cell culture model is constructed by exogenous expression of four host genes (NTCP, HNF4α, RXRα and PPARα) in human non‐hepatic 293T cells. This cell culture model supports HBV entry, transcription and replication, as evidenced by the detection of HBV pgRNA, HBV cccDNA, HBsAg, HBeAg, HBcAg and HBVDNA. Our results suggest that the above cellular factors may play a key role in HBV infection of non‐hepatic cells. This model will facilitate the identification of host genes that support extrahepatic HBV infection.
SIRT3, PP2A and TTP protein stability in the presence of TNF‐α on vincristine‐induced apoptosis of leukaemia cells
Authors: Wang Liang‐Jun , Chiou Jing‐Ting , Lee Yuan‐Chin , Huang Chia‐Hui , Shi Yi‐Jun , Chang Long‐Sen
Published: January 2020

The contribution of vincristine (VCR)‐induced microtubule destabilization to evoke apoptosis in cancer cells remains to be resolved. Thus, we investigated the cytotoxic mechanism of VCR on U937 and HL‐60 human leukaemia cell lines. We discovered that VCR treatment resulted in the up‐regulation of TNF‐α expression and activation of the death receptor pathway, which evoked apoptosis of U937 cells. Moreover, VCR induced microtubule destabilization and mitotic arrest. VCR treatment down‐regulated SIRT3, and such down‐regulation caused mitochondrial ROS to initiate phosphorylation of p38 MAPK. p38 MAPK suppressed MID1‐modulated degradation of the protein phosphatase 2A (PP2A) catalytic subunit. The SIRT3‐ROS‐p38 MAPK‐PP2A axis inhibited tristetraprolin (TTP)‐controlled TNF‐α mRNA degradation, consequently, up‐regulating TNF‐α expression. Restoration of SIRT3 and TTP expression, or inhibition of the ROS‐p38 MAPK axis increased the survival of VCR‐treated cells and repressed TNF‐α up‐regulation. In contrast to suppression of the ROS‐p38 MAPK axis, overexpression of SIRT3 modestly inhibited the effect of VCR on microtubule destabilization and mitotic arrest in U937 cells. Apoptosis of HL‐60 cells, similarly, went through the same pathway. Collectively, our data indicate that the SIRT3‐ROS‐p38 MAPK‐PP2A‐TTP axis modulates TNF‐α expression, which triggers apoptosis of VCR‐treated U937 and HL‐60 cells. We also demonstrate that the apoptotic signalling is not affected by VCR‐elicited microtubule destabilization.
Commentary: Enabling efficient and full application of prevention strategies for population mental health — reflections on Dodge (2020)
Authors: Tolan Patrick
Published: January 2020

Dodge (2020) provides a challenging and compelling formulation for more systematic determination of prevention component selection. The essay reminds us that population impact should be front and center in prevention specifically and public health organization in general. Dodge brings forth numerous issues in the science and the application of knowledge about prevention that warrant more research support and study. These issues include the need to recognize the existence of and increase the number of proven programs, the need for better and more extensive knowledge about impact variation across populations, and more attention to strengths and capabilities as guides for prevention. His essay also reminds us of the nuance and complexities in attempting to compare effect sizes and cost–benefit ratios of universal versus selective efforts. In addition, he provides compelling rationale for formalization of how prevention is organized and implemented in local community efforts. Further, in refocusing on the centrality of population effects in intervention application, Dodge also reminds us of the attendant principles of health equity and social justice in how we implement and judge the benefits of interventions. This essay provides a compelling argument for a strategy to realize the potential of the accumulating evidence of prevention as vital for addressing mental health and development.
Materials in digital dentistry—A review
Authors: Sulaiman Taiseer A.
Published: January 2020

Objective

To review materials available in computer‐aided design/computer‐aided manufacturing (CAD/CAM), their various properties and accuracy are compared to conventional materials/methods when available.

Overview

CAD/CAM in dentistry is constantly growing and becoming a user‐ and patient‐friendly technology and service using intraoral scanners and laboratory/chairside milling units to manufacture dental restorations and appliances from multiple materials including wax, metals, composite resins, and ceramics. Properties of these materials may vary when compared to restorations prepared from conventional and additive manufacturing methods. Understanding the differences in these properties is important for material and fabrication method selection. Additive manufacturing is becoming an alternative to subtractive manufacturing in many applications. However, chemical composition, mechanical and physical properties of these materials are still lacking. 3D printed materials require a considerable amount of research and time to prove their clinical efficacy.

Conclusion

The current developments in, and possibilities of, CAD/CAM technology is exciting and is transforming restorative dentistry. With all this excitement, it is crucially important to ensure that proper testing and evaluation of the various materials are warranted before making definite claims and decisions to replace conventionally prepared materials.

Clinical Significance

CAD/CAM materials are versatile and emerging as the material of choice for many restorations and appliances. For recently introduced CAD/CAM materials, it is important to ensure that proper clinical‐ and research‐based evidence confirming the success and durability of these materials are available before recommending them in patient care.
The experiences of Dutch fathers on fathering children with disabilities: ‘Hey, that is a father and his daughter, that is it’
Authors: Schippers A. , Berkelaar M. , Bakker M. , Van Hove G.
Published: January 2020

Background

Due to a predominant focus on mothers, fathers of children with disabilities are greatly overlooked in research. One could argue that there is a lack of research on the multifaceted nature of fatherhood altogether. Therefore, this study aims to gain insight into the perceived experiences of fathers of children with disabilities.

Methods

These perceptions were studied by analysing data generated through semi‐structured interviews, which were conducted with 12 Dutch fathers of children or young adults with disabilities.

Results

Categories found during our data analysis were similar to those illustrated in the ‘conceptual framework on responsible fathering’ by including role identification, commitment, employment characteristics, cultural expectations and social support.

Conclusions

Overall, the fathers in this study reported similar experiences, but this study identified new life perspective as an additional category, which might be specific for fathers of children with disabilities. This new life perspective included a positive attitude, living in the moment, appreciation of the little things and transformation of expectations. Some fathers expressed that their child(ren) has enriched their lives, which positively influenced their fathering experience.
Relationships between quality of life and skin toxicities of epidermal growth factor receptor inhibitors in cancer patients: A literature review
Authors: Hirayama Kengo , Su Ya , Chiba Megumi , Izutsu Miku , Yuki Michiko
Published: January 2020

Aim

Epidermal growth factor receptor (EGFR) inhibitors are used as treatments for various cancers, but the associated skin toxicities affect quality of life (QoL). The aim of this review is to document the relationship between skin toxicity and QoL of cancer patients, and to identify implications for clinical practice and subjects for future studies.

Methods

Electronic databases were searched systematically and all studies examining aspects of health‐related QoL in patients receiving EGFR inhibitor treatments for cancer.

Results

A total of 25 published studies met the criteria for inclusion. Some cancer patients maintained their health conditions by recognizing that skin toxicities are correlated with the efficacy of EGFR inhibitor therapy, yet QoL declined in all functional evaluations. In particular, QoL was low in patients above 81 years of age and in those under 50 years of age.

Conclusion

Improved understanding of the pain due to skin toxicity is required in all age groups, particularly in elderly and young cancer patients. In addition, further studies are required to define long‐term changes in QoL among patients receiving EGFR inhibitors for cancer. Healthcare professionals need to help patients to maintain subjective health conditions by understanding relationships between skin toxicity and therapeutic effects. To this end, assessments of patients who are prone to QoL decline due to skin toxicity are critical so that skin management can be started during early stages.
Combining tensile testing and microscopy to address a diverse range of questions
Authors: ROBINSON SARAH , DURAND‐SMET PAULINE
Published: January 2020

Both plants and animals sense and respond to mechanical stresses that arise internally or are externally imposed. In many cases, tissues respond by changing their gene expression or their mechanical properties, which has an impact on how they develop. Many tools have been developed to measure mechanical properties and to investigate responses to mechanical stress. Here we review the state of microscope‐coupled tensile testing at the single‐cell and tissue scale and give a view on future opportunities for extending the technology. Uniaxial tensile testing involves quantifying the deformation of a sample when a force is applied. By varying the amount of force, the speed at which the force is applied or the length of time that it is applied for, many characteristics of the mechanical properties of the sample can be calculated. Tensile testing has been used extensively to measure the mechanical properties of whole tissues or organs. The need for higher resolution data resulted in more researchers using indentation tests to measure mechanical properties instead. Indentation tests provide information at a different scale and are not suitable for answering the same type of questions as tensile testing. Here we discuss that by coupling tensile‐testing machinery with microscopes such as is the case for the Automated Confocal Micro‐Extensometer (ACME) it is possible to obtain tissue‐scale measurements of mechanical properties with cellular resolution. Moreover, to understand and identify the biological processes cells and tissues use to respond to mechanical stress, we need to be able to apply mechanical perturbations to plant samples while recording the induced biological changes with microscopy.

Lay Description

Plants, like most living organisms, are sensitive to their environment. This includes mechanical stresses imposed upon them by gravity or wind. Mechanical stress can also arise from internal tissue tension, which can build up if different parts of a tissue grow at different rates. In many cases, the cells respond to mechanical stress by changing their mechanical properties, which can affect their growth and their final shape. There is thus a critical need to develop tools for measuring mechanical properties and the response to mechanical stress. Mechanical properties cannot be visualised directly but must be inferred by looking at how a tissue deforms when a force is applied or vice versa. This is more challenging when one wishes to achieve this at the cellular scale, as the forces and deformations are much smaller. There are a range of methods available that have advantages and disadvantages. Here we review some of these methods. In particular, we focus on methods that cause deformation in the main axis of the tissue. This type of test can be coupled with conventional and state‐of‐the‐art microscopes. Coupling with microscopes increases the resolution of the tests that can be performed and facilitates the simultaneous observation of responses to the mechanical stresses.
Endometrial stromal cells treated by tumor necrosis factor‐α stimulate macrophages polarized toward M2 via interleukin‐6 and monocyte chemoattractant protein‐1
Authors: Li Min‐Zhen , Wu Ya‐Hong , Ali Maria , Wu Xian‐Qing , Nie Mei‐Fang
Published: January 2020

Aim

This study aimed to investigate the effects of endometrial stromal cells (ESC)‐derived interleukin (IL)‐6 and monocyte chemoattractant protein (MCP)‐1 on macrophage polarization in endometriosis.

Methods

Macrophage polarization was measured in eutopic endometrium of control participants (‘normal endometrium’), eutopic endometrium of patients with endometriosis (‘eutopic endometrium’) and ectopic endometrium of endometriosis patients (‘ectopic endometrium’) by immunohistochemical staining. Expression of IL‐6 and MCP‐1 were measured in the eutopic and ectopic endometrium through enzyme‐linked immunosorbent assays. Expression of CD163 was measured in human acute monocytic leukemia (THP‐1) cell‐derived macrophages that were treated with conditional medium induced by tumor necrosis factor (TNF)‐α, TNF‐α + anti‐IL‐6 or TNF‐α + anti‐MCP‐1 via flow cytometry.

Results

The ratio of CD163+/CD68+ macrophages in the normal endometrium was higher than that in the eutopic endometrium, while differences between the eutopic and ectopic endometrium were not statistically significant. IL‐6 and MCP‐1 exhibited enhanced expression in the ectopic endometrium group and decreased expression in the eutopic endometrium group. TNF‐α could promote the expression of ESC‐derived IL‐6 and MCP‐1. Intervention with TNF‐α‐induced conditioned medium resulted in the upregulation of CD163 in THP‐1 cells, while conditional medium induced with IL‐6 and MCP‐1 neutralizing antibodies decreased the proportion of CD163+ macrophages significantly.

Conclusion

In endometriosis patients, the macrophages of the eutopic endometrium polarize toward M1 compared with the normal endometrium, and those of the ectopic endometrium were mainly M2‐polarized. Under the action of TNF‐α, ESC‐derived IL‐6 and MCP‐1 could stimulate peritoneal macrophages toward M2‐polarization, which could modulate endometriosis.
Cytolysin‐positive Enterococcus faecalis is not increased in patients with non‐alcoholic steatohepatitis
Authors: Lang Sonja , Demir Münevver , Duan Yi , Martin Anna , Schnabl Bernd
Published: January 2020

Several studies show associations between gut bacterial dysbiosis and chronic liver diseases, but causative mechanisms are largely unclear. We recently identified cytolysin, a bacterial exotoxin expressed and secreted by Enterococcus faecalis to cause liver damage in the setting of alcohol‐related liver disease. Cytolysin was increased and highly correlated with liver disease severity and mortality in alcoholic hepatitis patients. In this study, we investigated if faecal cytolysin‐positivity can be linked to non‐alcoholic fatty liver disease, a highly prevalent disease where new biomarkers and treatment targets are urgently needed. In contrast to what we observed in alcoholic hepatitis, only seven out of 96 non‐alcoholic fatty liver disease patients were cytolysin‐positive, and these patients did not have increased liver disease activity compared with cytolysin‐negative patients. These results indicate that the association of cytolysin carriage with worse clinical outcome might be specific for alcoholic hepatitis.
The associations of economic growth and anaemia for school‐aged children in China
Authors: Luo Dongmei , Xu Rongbin , Ma Jun , Yan Xiaojin , Hu Peijin , Song Yi , Jan Catherine , Raat Hein , Patton George C.
Published: January 2020

Economic growth has brought improvements in many areas of child health, but its effects on anaemia among school‐aged children remain unknown. However, this is important because iron deficiency anaemia is common and is the main cause of disability‐adjusted life years for school‐aged children. In this study, we included 429,222 Chinese children aged 7–17 years from five consecutive national cross‐sectional surveys during 1995–2014. Using altitude‐adjusted haemoglobin concentration measured from capillary blood samples, we defined anaemia status according to World Health Organization's recommendation. We used logistic regressions weighted by provincial population to examine the association between provincial gross domestic product (GDP) per capita and anaemia, adjusting for sex, age, urban–rural location, regional socio‐economic status (SES), fixed effect of province, and clustering of schools. We used generalised additive mixed models to evaluate a potentially non‐linear relationship. For each 100% growth in GDP per capita, there was a 40% (odds ratio [OR] = 0.60; 95% confidence interval [CI; 0.56, 0.65]) reduction in anaemia. However, the association was weaker for girls and in cities with a lower SES. The association was weaker across 2005–2014 (OR = 0.75, 95% CI [0.62, 0.90]) compared with 1995–2005 (OR = 0.52; 95% CI [0.44, 0.61]), reflecting a weaker association when GDP per capita reaches around $2,000. The results were similar for moderate‐to‐severe anaemia. We concluded that economic growth has been associated with reductions in anaemia among school‐aged children in China but with fewer benefits for girls and those in poorer settings. Further economic development in China is unlikely to bring similar reductions in anaemia, suggesting that additional population level and targeted interventions will be needed.
Professional and non‐professional sources of formula feeding advice for parents in the first six months
Authors: Appleton Jessica , Fowler Cathrine , Laws Rachel , Russell Catherine Georgina , Campbell Karen J. , Denney‐Wilson Elizabeth
Published: January 2020

Breastfeeding is beneficial to both the mother and infant, yet many infants are either partially or fully fed with formula milk. Those parents feeding with formula receive less support from professional sources than those breastfeeding and may rely on more non‐professional sources for advice, and this contributes to negative emotional experiences such as guilt. This paper explores the sources of advice for formula feeding, factors associated with using professional or non‐professional sources and compares these sources with those used for breastfeeding advice. A secondary analysis of Australian survey data from 270 mothers was performed. Mothers of six‐month‐old infants participated in an online survey, providing information on advice they received or read about formula feeding and/or breastfeeding from professional and non‐professional sources. A fifth of mothers who were formula feeding did not receive any formula feeding advice from professional sources, and only a small fraction (4.5%) of mothers breastfeeding did not received any breastfeeding advice from professional sources. Compared with those mothers breastfeeding receiving breastfeeding advice, fewer mothers formula feeding receive formula feeding advice from both professional and non‐professional sources. The tin of formula was the most used source of formula advice. Mothers feeding with formula at six months were more likely to have received formula feeding advice from professional sources if they had been fully formula feeding before their infant was under the age of three months. Further research is needed to understand the specific barriers to accessing formula feeding advice and what other factors influence access to formula feeding advice.
Evolutionary signal in the gut microbiomes of 74 bird species from Equatorial Guinea
Authors: Capunitan Darien C. , Johnson Oscar , Terrill Ryan S. , Hird Sarah M.
Published: January 2020

How the microbiome interacts with hosts across evolutionary time is poorly understood. Data sets including many host species are required to conduct comparative analyses. Here, we analyzed 142 intestinal microbiome samples from 92 birds belonging to 74 species from Equatorial Guinea, using the 16S rRNA gene. Using four definitions for microbial taxonomic units (97%OTU, 99%OTU, 99%OTU with singletons removed, ASV), we conducted alpha and beta diversity analyses. We found that raw abundances and diversity varied between the data sets but relative patterns were largely consistent across data sets. Host taxonomy, diet and locality were significantly associated with microbiomes, at generally similar levels using three distance metrics. Phylogenetic comparative methods assessed the evolutionary relationship between the microbiome as a trait of a host species and the underlying bird phylogeny. Using multiple ways of defining “microbiome traits”, we found that a neutral Brownian motion model did not explain variation in microbiomes. Instead, we found a White Noise model (indicating little phylogenetic signal), was most likely. There was some support for the Ornstein‐Uhlenbeck model (that invokes selection), but the level of support was similar to that of a White Noise simulation, further supporting the White Noise model as the best explanation for the evolution of the microbiome as a trait of avian hosts. Our study demonstrated that both environment and evolution play a role in the gut microbiome and the relationship does not follow a neutral model; these biological results are qualitatively robust to analytical choices.
Mystagogy and Cyrillian Orthodoxy: Christology as Fidelity to a Carnal Presence
Authors: Riches Aaron
Published: January 2020

Henry Chadwick’s contention that the “nerve‐center” of Cyril’s Christology is the Eucharist reconfigures the urgency of his polemic against Nestorius: it is not a question of abstract doctrine, but of the mystery encountered in the liturgy. This contention has been corroborated by patrologists, but its theological implication has not been fully drawn – viz. that mystagogy is the basis of Cyrillian orthodoxy. When this implication is grasped, it entails that the orthodox doctrine of the “unity of Christ” concerns not merely the unity of the historical Jesus with the Logos, but the unity of the encounter with Christ: “mystical union” is not an addendum to the doctrine of the “hypostatic unity,” it is basic to it.
A spatial ecology study in a high‐diversity host community to understand blood‐feeding behaviour in Phlebotomus sandfly vectors of Leishmania
Authors: Pérez‐Cutillas P. , Muñoz C. , Martínez‐De La Puente J. , Figuerola J. , Navarro R. , Ortuño M. , Bernal L. J. , Ortiz J. , Soriguer R. C. , Berriatua E.
Published: January 2020

Molecular studies indicate that Phlebotomine sandflies (Diptera: Psychodidae) blood feed on many vertebrate species, of which only a few are proven parasite reservoirs. Investigating sandfly vector feeding preferences is therefore important and requires taking into account the availability and accessibility of host species. In terms of the latter, it is necessary to consider the metabolic cost to the insect of reaching the host and moving on to a suitable breeding site. The present study used statistical modelling to compare the feeding patterns of Phlebotomus perniciosus (n = 150), Phlebotomus papatasi (n = 35) and Phlebotomus ariasi (n = 7) on each of an average of 30 host species in a wildlife park in Murcia, Spain. Sandfly feeding movement costs were estimated as a function of the distance and altitude gradients saved by the insect, assuming that they displayed ‘site fidelity’. Most (87%) engorged females were caught <100 m from the host on which they had fed. Although the percentage of bloodmeals was highest on fallow deer (Dama dama) (30%) and red deer (Cervus elaphus) (26%), the predicted feeding probability after considering movement cost was highest for red deer and common eland (Taurotragus oryx), and positively associated with host census. These results suggest that, under similar circumstances, sandflies prefer to feed on some host species more than on others.