bluuebunny/crossref_metadata_2025_split huggingface dataset:
Putative mobilized colistin resistance genes in the human gut microbiome
Authors: Andrade Bruno G. N. , Goris Tobias , Afli Haithem , Coutinho Felipe H. , Dávila Alberto M. R. , Cuadrat Rafael R. C. 
Published: July 2021

Abstract
Background
The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance (mcr) genes, poses an unprecedented threat to human health. Understanding the spread, evolution, and distribution of such genes among human populations will help in the development of strategies to diminish their occurrence. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome using a set of bioinformatics tools to screen the Unified Human Gastrointestinal Genome (UHGG) collection for the presence, synteny and phylogeny of putative mcr genes, and co-located antibiotic resistance genes.

Results
A total of 2079 antibiotic resistance genes (ARGs) were classified as mcr genes in 2046 metagenome assembled genomes (MAGs), distributed across 1596 individuals from 41 countries, of which 215 were identified in plasmidial contigs. The genera that presented the largest number of mcr-like genes were Suterella and Parasuterella. Other potential pathogens carrying mcr genes belonged to the genus Vibrio, Escherichia and Campylobacter. Finally, we identified a total of 22,746 ARGs belonging to 21 different classes in the same 2046 MAGs, suggesting multi-resistance potential in the corresponding bacterial strains, increasing the concern of ARGs impact in the clinical settings.

Conclusion
This study uncovers the diversity of mcr-like genes in the human gut microbiome. We demonstrated the cosmopolitan distribution of these genes in individuals worldwide and the co-presence of other antibiotic resistance genes, including Extended-spectrum Beta-Lactamases (ESBL). Also, we described mcr-like genes fused to a PAP2-like domain in S. wadsworthensis. These novel sequences increase our knowledge about the diversity and evolution of mcr-like genes. Future research should focus on activity, genetic mobility and a potential colistin resistance in the corresponding strains to experimentally validate those findings.
Identification of tomato accessions as source of new genes for improving heat tolerance: from controlled experiments to field
Authors: Gonzalo María José , Nájera Inmaculada , Baixauli Carlos , Gil David , Montoro Teresa , Soriano Vicky , Olivieri Fabrizio , Rigano Maria Manuela , Ganeva Daniela , Grozeva-Tileva Stanislava , Pevicharova Galina , Barone Amalia , Granell Antonio , Monforte Antonio José 
Published: July 2021

AbstractBackgroundDue to global warming, the search for new sources for heat tolerance and the identification of genes involved in this process has become an important challenge as of today. The main objective of the current research was to verify whether the heat tolerance determined in controlled greenhouse experiments could be a good predictor of the agronomic performance in field cultivation under climatic high temperature stress.ResultsTomato accessions were grown in greenhouse under three temperature regimes: control (T1), moderate (T2) and extreme heat stress (T3). Reproductive traits (flower and fruit number and fruit set) were used to define heat tolerance. In a first screening, heat tolerance was evaluated in 219 tomato accessions. A total of 51 accessions were identified as being potentially heat tolerant. Among those, 28 accessions, together with 10 accessions from Italy (7) and Bulgaria (3), selected for their heat tolerance in the field in parallel experiments, were re-evaluated at three temperature treatments. Sixteen tomato accessions showed a significant heat tolerance at T3, including five wild species, two traditional cultivars and four commercial varieties, one accession from Bulgaria and four from Italy. The 15 most promising accessions for heat tolerance were assayed in field trials in Italy and Bulgaria, confirming the good performance of most of them at high temperatures.Finally, a differential gene expression analysis in pre-anthesis (ovary) and post-anthesis (developing fruit) under heat stress among pairs of contrasting genotypes (tolerant and sensitive from traditional and modern groups) showed that the major differential responses were produced in post-anthesis fruit. The response of the sensitive genotypes included the induction of HSP genes, whereas the tolerant genotype response included the induction of genes involved in the regulation of hormones or enzymes such as abscisic acid and transferases.ConclusionsThe high temperature tolerance of fifteen tomato accessions observed in controlled greenhouse experiments were confirmed in agronomic field experiments providing new sources of heat tolerance that could be incorporated into breeding programs.A DEG analysis showed the complex response of tomato to heat and deciphered the different mechanisms activated in sensitive and tolerant tomato accessions under heat stress.
Primary care management of chronic insomnia: a qualitative analysis of the attitudes and experiences of Australian general practitioners
Authors: Haycock Jenny , Grivell Nicole , Redman Anne , Saini Bandana , Vakulin Andrew , Lack Leon , Lovato Nicole , Sweetman Alexander , Zwar Nicholas , Stocks Nigel , Frank Oliver , Mukherjee Sutapa , Adams Robert , McEvoy R. Doug , Hoon Elizabeth 
Published: July 2021

Abstract
Background
Chronic insomnia is a highly prevalent disorder, with ten to thirty percent of Australian adults reporting chronic difficulties falling asleep and/or staying asleep such that it causes significant daytime impairment. Current Australian general practice guidelines recommend cognitive behavioural therapy for insomnia (CBTi) as first line treatment for insomnia, however research suggests that most general practice consultations for insomnia result in a prescription for hypnotic or sedative medicines. Although the first point of contact for patients experiencing symptoms of insomnia is often general practice, little is known about the current role, experiences and capacity of Australian general practitioners to manage insomnia. This study aimed to address that gap by exploring the attitudes and opinions of general practitioners regarding insomnia management, to inform the development and implementation of new models of best practice insomnia care within general practice.

Methods
A descriptive, pragmatic qualitative study. Purposive sampling was used to recruit practising Australian general practitioners, varying in age, years of experience and geographic location. Semi-structured interviews were conducted, and data analysed using thematic analysis.

Results
Twenty-eight general practitioners participated in the study. Three major themes were identified: 1) Responsibility for insomnia care; 2) Complexities in managing insomnia; and 3) Navigating treatment pathways. Whilst general practitioners readily accepted responsibility for the management of insomnia, provision of care was often demanding and difficult within the funding and time constraints of general practice. Patients presenting with comorbid mental health conditions and insomnia, and decision-making regarding long-term use of benzodiazepines presented challenges for general practitioners. Whilst general practitioners confidently provided sleep hygiene education to patients, their knowledge and experience of CBTi, and access and understanding of specialised referral pathways for insomnia was limited.

Conclusions
General practitioners report that whilst assessing and managing insomnia can be demanding, it is an integral part of general practice. Insomnia presents complexities for general practitioners. Greater clarity about funding options, targeted education about effective insomnia treatments, and referral pathways to specialist services, such as benzodiazepine withdrawal support and psychologists, would benefit insomnia management within general practice.
Transcriptome sequencing and multi-plex imaging of prostate cancer microenvironment reveals a dominant role for monocytic cells in progression
Authors: Mangiola Stefano , McCoy Patrick , Modrak Martin , Souza-Fonseca-Guimaraes Fernando , Blashki Daniel , Stuchbery Ryan , Keam Simon P. , Kerger Michael , Chow Ken , Nasa Chayanica , Le Page Melanie , Lister Natalie , Monard Simon , Peters Justin , Dundee Phil , Williams Scott G. , Costello Anthony J. , Neeson Paul J. , Pal Bhupinder , Huntington Nicholas D. , Corcoran Niall M. , Papenfuss Anthony T. , Hovens Christopher M. 
Published: July 2021

Abstract
Background
Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities.

Results
In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry.

Conclusions
This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation.
The effect of the universal two-child policy on medical insurance funds with a rapidly ageing population: evidence from China’s urban and rural residents’ medical insurance
Authors: Zhang Xinjie , Huang Jingru , Luo Ying 
Published: July 2021

Abstract
Background
With the rapid growth of the ageing population, the operating burden of China’s basic medical insurance fund is becoming increasingly heavy. To counter rapid population ageing and ameliorate a series of problems, China has adjusted its fertility policies several times. On January 1, 2016, the universal two-child policy was implemented. This study analysed the impacts of the adjustment to the fertility policy and potential improvements in fertility intention on the insured population and medical insurance fund sustainability.

Methods
We used an actuarial science method and took the urban and rural residents’ basic medical insurance (URRBMI) of China, which covers most urban and rural residents, as an example to build a dynamic forecast model of population growth and a dynamic actuarial model of medical insurance funds.

Results
Compared with the original policy, under the current fertility intention (40%) with the universal two-child policy, the ageing of the population structure of URRBMI participants will decline significantly after 2026, and individuals aged 65 and over will account for only 19.01% of the total participants in 2050. The occurrence of the current deficit and accumulated deficit of the URRBMI fund will be postponed for one year to 2022 and 2028, respectively. If fertility intentions continue to rise, the ageing degree of the population structure will decrease, and the deficit would be further delayed.

Conclusions
The universal two-child policy is conducive to improving the degree of overall population ageing, delaying the occurrence of a URRBMI fund deficit, and improving the sustainability of URRBMI funds. If fertility intention increases, the effects would be stronger. However, since the adjustment of the universal two-child policy has a certain time lag, it will take time to demonstrate this impact. Therefore, while actively promoting the universal two-child policy, other measures should be taken, such as improving the fertility desire among couples of childbearing age and reforming medical insurance payment methods.
Lung function, COPD and cognitive function: a multivariable and two sample Mendelian randomization study
Authors: Higbee Daniel H. , Granell Raquel , Hemani Gibran , Smith George Davey , Dodd James W. 
Published: July 2021

Abstract
Background
Observational studies show an association between reduced lung function and impaired cognition. Cognitive dysfunction influences important health outcomes and is a precursor to dementia, but treatments options are currently very limited. Attention has therefore focused on identifying modifiable risk factors to prevent cognitive decline and preserve cognition. Our objective was to determine if lung function or risk of COPD causes reduced cognitive function using Mendelian randomization (MR).

Methods
Single nucleotide polymorphisms from genome wide association studies of lung function and COPD were used as exposures. We examined their effect on general cognitive function in a sample of 132,452 individuals. We then performed multivariable MR (MVMR), examining the effect of lung function before and after conditioning for covariates.

Results
We found only weak evidence that reduced lung function (Beta − 0.002 (SE 0.02), p-value 0.86) or increased liability to COPD (− 0.008 (0.008), p-value 0.35) causes lower cognitive function. MVMR found both reduced FEV1 and FVC do cause lower cognitive function, but that after conditioning for height (− 0.03 (0.03), p-value 0.29 and − 0.01 (0.03) p-value 0.62, for FEV1 and FVC respectively) and educational attainment (− 0.03 (0.03) p-value 0.33 and − 0.01 (0.02), p-value 0.35) the evidence became weak.

Conclusion
We did not find evidence that reduced lung function or COPD causes reduced cognitive function. Previous observational studies are probably affected by residual confounding. Research efforts should focus on shared risk factors for reduced lung function and cognition, rather than lung function alone as a modifiable risk factor.
Effectiveness of zinc chloride mouthwashes on oral mucositis and weight of patients with cancer undergoing chemotherapy
Authors: Oshvandi Khodayar , Vafaei Seyed Yaser , Kamallan Seyed Ramesh , Khazaei Salman , Ranjbar Hossein , Mohammadi Fateme 
Published: July 2021

Abstract
Background
Oral mucositis is one of the most emerging and debilitating complications of chemotherapy during the treatment period, which strongly affects the nutritional status and physical and mental condition of these patients. Zinc increased protein synthesis and improved cell membrane stability so passible effective in prevent and treat oral mucositis and promote oral health. Therefore, this study aimed to evaluate the effect of zinc chloride mouthwash on the prevention, incidence, and severity of oral mucositis in cancer patients undergoing chemotherapy.

Methods
The present study was a randomized control trial study. 96 patients with a cancer diagnosis selected from one oncology clinic in the west of Iran. Then they assigned randomly to the zinc chloride group and placebo group. The patients in each group should rinse their mouths every 8 h two times and each time 2 min with 7.5 ml from mouthwash. The severity of mucositis and weight loss examined blindly at the baseline and 3-week follow-up.

Results
The incidence and severity of oral mucositis between groups were significant higher at the end of the second (p < 0.002) and third (p < 0.001) week. The mucositis severity decreased well during the third weeks in the zinc chloride group. The difference in the weight loss was significant higher between the zinc chloride and the placebo group (p < 0.01).

Conclusion
Zinc chloride mouthwash was effective in preventing and reducing the severity of oral mucositis and improving weight in patients undergoing chemotherapy.
Trial registration We can therefore recommend more studies examine the effects zinc chloride as preventive care at the beginning of chemotherapy to improve oral health and subsequently preventing weight loss in these patients.
Longitudinal team training program in a Norwegian surgical ward: a qualitative study of nurses’ and physicians’ experiences with implementation
Authors: Ballangrud Randi , Aase Karina , Vifladt Anne 
Published: July 2021

AbstractBackgroundTeam training interventions to improve team effectiveness within healthcare are widely used. However, in-depth knowledge of how healthcare professionals experience such team training curricula and their implementation processes, as well as how contextual factors impact implementation, is currently missing. The aim of this study is therefore to describe healthcare professionals’ experiences with the implementation of a longitudinal interprofessional team training program in a surgical ward.MethodsA descriptive design was applied based on qualitative semi-structured focus group interviews with 11 healthcare professionals. A convenience sample of physicians (n = 4), registered nurses (n = 4), and certified nursing assistants (n = 3) was divided into three professionally based focus groups, which were interviewed at three time intervals over a period of 1 year.InterventionThe validated and evidence-based team training program Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) was implemented in a surgical ward at a hospital between January 2016 and June 2017. The team training program included three phases: 1) assessment and planning, 2) training and implementation, and 3) sustainment.ResultsHealthcare professionals’ experiences with the content of the team training program varied from valuing the different elements of it to seeing the challenges in implementing the elements in clinical practice. A one-day training course was found to be especially beneficial for interprofessional collaboration at the ward. Over time, the nursing staff seemed to maintain their motivation for the implementation of the tools and strategies, while the physicians became less actively involved. Contextual ward factors influenced the adoption and utilization of the tools and strategies of the program both positively and negatively. The healthcare professionals’ experienced the implementation of the team training program as positive for the patient safety culture at the ward in the forms of increased awareness of teamwork and open communication.ConclusionsThe study suggests that the implementation of a team training program in a surgical ward is dependent on a set of factors related to content, process, context, and impact. Knowledge on how and why a team training program work supports the transferability to clinical practice in further planning of team training measures.Trial registrationThe study is part of a larger research project with a study protocol that was registered retrospectively on 05.30.17, with the trial registration numberISRCTN13997367.
Variability of multi-omics profiles in a population-based child cohort
Authors: Gallego-Paüls Marta , Hernández-Ferrer Carles , Bustamante Mariona , Basagaña Xavier , Barrera-Gómez Jose , Lau Chung-Ho E. , Siskos Alexandros P. , Vives-Usano Marta , Ruiz-Arenas Carlos , Wright John , Slama Remy , Heude Barbara , Casas Maribel , Grazuleviciene Regina , Chatzi Leda , Borràs Eva , Sabidó Eduard , Carracedo Ángel , Estivill Xavier , Urquiza Jose , Coen Muireann , Keun Hector C. , González Juan R. , Vrijheid Martine , Maitre Léa 
Published: July 2021

AbstractBackgroundMultiple omics technologies are increasingly applied to detect early, subtle molecular responses to environmental stressors for future disease risk prevention. However, there is an urgent need for further evaluation of stability and variability of omics profiles in healthy individuals, especially during childhood.MethodsWe aimed to estimate intra-, inter-individual and cohort variability of multi-omics profiles (blood DNA methylation, gene expression, miRNA, proteins and serum and urine metabolites) measured 6 months apart in 156 healthy children from five European countries. We further performed a multi-omics network analysis to establish clusters of co-varying omics features and assessed the contribution of key variables (including biological traits and sample collection parameters) to omics variability.ResultsAll omics displayed a large range of intra- and inter-individual variability depending on each omics feature, although all presented a highest median intra-individual variability. DNA methylation was the most stable profile (median 37.6% inter-individual variability) while gene expression was the least stable (6.6%). Among the least stable features, we identified 1% cross-omics co-variation between CpGs and metabolites (e.g. glucose and CpGs related to obesity and type 2 diabetes). Explanatory variables, including age and body mass index (BMI), explained up to 9% of serum metabolite variability.ConclusionsMethylation and targeted serum metabolomics are the most reliable omics to implement in single time-point measurements in large cross-sectional studies. In the case of metabolomics, sample collection and individual traits (e.g. BMI) are important parameters to control for improved comparability, at the study design or analysis stage. This study will be valuable for the design and interpretation of epidemiological studies that aim to link omics signatures to disease, environmental exposures, or both.
Causes of altered ventricular mechanics in hypertrophic cardiomyopathy: an in-silico study
Authors: Kovacheva Ekaterina , Gerach Tobias , Schuler Steffen , Ochs Marco , Dössel Olaf , Loewe Axel 
Published: July 2021

AbstractBackgroundHypertrophic cardiomyopathy (HCM) is typically caused by mutations in sarcomeric genes leading to cardiomyocyte disarray, replacement fibrosis, impaired contractility, and elevated filling pressures. These varying tissue properties are associated with certain strain patterns that may allow to establish a diagnosis by means of non-invasive imaging without the necessity of harmful myocardial biopsies or contrast agent application. With a numerical study, we aim to answer: how the variability in each of these mechanisms contributes to altered mechanics of the left ventricle (LV) and if the deformation obtained in in-silico experiments is comparable to values reported from clinical measurements.MethodsWe conducted an in-silico sensitivity study on physiological and pathological mechanisms potentially underlying the clinical HCM phenotype. The deformation of the four-chamber heart models was simulated using a finite-element mechanical solver with a sliding boundary condition to mimic the tissue surrounding the heart. Furthermore, a closed-loop circulatory model delivered the pressure values acting on the endocardium. Deformation measures and mechanical behavior of the heart models were evaluated globally and regionally.ResultsHypertrophy of the LV affected the course of strain, strain rate, and wall thickening—the root-mean-squared difference of the wall thickening between control (mean thickness 10 mm) and hypertrophic geometries (17 mm) was >10%. A reduction of active force development by 40% led to less overall deformation: maximal radial strain reduced from 26 to 21%. A fivefold increase in tissue stiffness caused a more homogeneous distribution of the strain values among 17 heart segments. Fiber disarray led to minor changes in the circumferential and radial strain. A combination of pathological mechanisms led to reduced and slower deformation of the LV and halved the longitudinal shortening of the LA.ConclusionsThis study uses a computer model to determine the changes in LV deformation caused by pathological mechanisms that are presumed to underlay HCM. This knowledge can complement imaging-derived information to obtain a more accurate diagnosis of HCM.