bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression gene drive in continuous space can result in unstable persistence of both drive and wild‐type alleles
Authors: Champer Jackson , Kim Isabel K. , Champer Samuel E. , Clark Andrew G. , Messer Philipp W. 
Published: January 2021

AbstractRapid evolutionary processes can produce drastically different outcomes when studied in panmictic population models vs. spatial models. One such process is gene drive, which describes the spread of “selfish” genetic elements through a population. Engineered gene drives are being considered for the suppression of disease vectors or invasive species. While laboratory experiments and modelling in panmictic populations have shown that such drives can rapidly eliminate a population, it remains unclear if these results translate to natural environments where individuals inhabit a continuous landscape. Using spatially explicit simulations, we show that the release of a suppression drive can result in what we term “chasing” dynamics, in which wild‐type individuals recolonize areas where the drive has locally eliminated the population. Despite the drive subsequently reconquering these areas, complete population suppression often fails to occur or is substantially delayed. This increases the likelihood that the drive is lost or that resistance evolves. We analyse how chasing dynamics are influenced by the type of drive, its efficiency, fitness costs, and ecological factors such as the maximal growth rate of the population and levels of dispersal and inbreeding. We find that chasing is more common for lower efficiency drives when dispersal is low and that some drive mechanisms are substantially more prone to chasing behaviour than others. Our results demonstrate that the population dynamics of suppression gene drives are determined by a complex interplay of genetic and ecological factors, highlighting the need for realistic spatial modelling to predict the outcome of drive releases in natural populations.
Dermatophytic melanonychia: A case series of an increasing disease
Authors: Starace Michela , Ambrogio Francesca , Bruni Francesca , Piraccini Bianca Maria , Alessandrini Aurora 
Published: January 2021

AbstractBackgroundMelanonychia refers to brown‐black colour pigmentation due to melanin or not‐melanin deposition in the nail plate. Onychoscopy allows to distinguish if the pigmentation is due by melanin or not.The main causes of non‐melanic pigmentation are subungual haematoma and pigmented onychomycosis. Fungal melanonychia (FM) is rare and may present as diffuse or longitudinal pigmentation. Differential diagnosis includes melanic activation, such as ethnic‐type nail pigmentation or frictional melanonychia, but also versus melanic proliferation, such as nevus or nail melanoma. Fungal melanonychia can be due to a colonisation by fungi with black variant or by melanin activation due to inflammation of fungal invasion.ObjectivesThe aim of paper is to increase clinical and dermoscopic knowledge of this increasingly frequent disease.MethodsIn this retrospective observational study, twenty patients with dermatophytic melanonychia were collected, with available clinical and dermoscopic pictures. The diagnosis of dermatophytic melanonychia was made based on clinical manifestation and mycological examination. KOH smear was performed in all cases. For each patient, clinical data included: age, gender, type of melanonychia and involved fingers.ResultsThis study aimed to show increased incidence of dermatophytic melanonychia and its correct management. In addition, we reviewed our collected cases and described the clinical and dermoscopic features of dermatophytic melanonychia.ConclusionsThe results of this study showed that physicians should keep in mind the diagnosis of this increasing disease, and that it cannot be performed relying only on clinical grounds. We would like to highlight the importance of tools as KOH examination, culture and dermoscopy.
Inflation volume‐balloon diameter and inflation pressure‐balloon diameter characteristics of commonly used bronchial blocker balloons for single‐lung ventilation in children
Authors: Goetschi Markus , Kemper Michael , Kleine‐Brueggeney Maren , Dave Mital H. , Weiss Markus 
Published: January 2021

AbstractBackgroundBalloon‐tipped bronchial blocker catheters are widely used in pediatric thoracic anesthesia to establish single‐lung ventilation. In clinical practice, their balloons demonstrate sudden expansion when inflated with air. In addition, there are concerns related to the high inflation pressures required to expand the balloons.MethodsThis in vitro study assessed inflation volume‐ and inflation pressure‐balloon diameter characteristics of the Fogarty arterial embolectomy catheters and Arndt endobronchial blockers. Balloon diameters were photographically assessed during unrestricted volume‐ and pressure‐guided inflation, using air up to the maximum allowed inflation volume as indicated by the manufacturers. Inflation pressures required to open the blocker balloons and inflation pressures needed to expand them to maximum indicated diameter were measured.ResultsVolume‐guided inflation demonstrated a late acute rise in diameter in Fogarty blocker balloons, whereas in the Arndt endobronchial blocker balloons almost linear inflation volume‐to‐diameter characteristics were observed. Pressure‐guided inflation on the other hand demonstrated low‐volume, high‐pressure characteristics in the Fogarty blocker balloons, with inflation pressures required to expand the balloons to maximum diameters ranging from (mean (SD)) 636 (75) to 947 (152) cmH2O. The inflation pressures required to open the Fogarty blocker balloons were even >1000 cmH2O. Inflation pressures required to expand the 5 F, 7 F, and 9 F Arndt endobronchial blocker balloons to maximum indicated diameter were much lower, namely at 218 (15), 252 (28), and 163 (8) cmH2O.ConclusionBased on these study findings, the balloons of Fogarty arterial embolectomy catheters represent high‐pressure devices and do not permit stepwise controlled bronchial blockage. The Arndt endobronchial blockers have some advantages over the Fogarty blocker devices, but also represent high‐pressure equipment and must be used with caution and limited duration. Manufacturers are asked to design pediatric endobronchial blocker catheters with truly high‐volume, low‐pressure balloons in accordance to age‐related pediatric airway dimensions.
Predictors of glucose metabolism and blood pressure among Ethiopian individuals with HIV/AIDS after one‐year of antiretroviral therapy
Authors: Amare Hiwot , Olsen Mette F. , Friis Henrik , Andersen Åse B. , Abdissa Alemseged , Yilma Daniel , Girma Tsinuel , Faurholt‐Jepsen Daniel 
Published: January 2021

AbstractObjectiveBetter understanding of glucose metabolism in patients with HIV after initiating antiretroviral therapy (ART) is important to target treatment and follow‐up for diabetes risk and other non‐communicable diseases in resource‐limited settings. The aim of this study was to assess the changes and predictors of glucose metabolism and blood pressure among patients with HIV on ART for 12 months.MethodsOne‐year follow‐up of Ethiopian patients with HIV after initiation of ART was done. Outcomes were changes in fasting plasma glucose (FPG), and 30‐minute (30mPG) and 2‐hour plasma glucose (2hPG) after oral glucose tolerance test, glycated haemoglobin (HbA1c), fasting plasma insulin (p‐insulin), homeostatic model assessment index for insulin resistance (HOMA‐IR) and blood pressure. ResultsThe mean age was 33 years, and the majority were women. During the first 12 months, levels of all plasma glucose parameters decreased, while p‐insulin (10B 3.1; 95% CI2.4, 4.0), HOMA‐IR (10B 3.1; 95% CI2.3, 4.0) and systolic blood pressure (B 4.0; 95% CI2.5, 5.5) increased. Fat‐free mass at baseline predicted higher increments in p‐insulin, HOMA‐IR and blood pressure; whereas, fat mass predicted higher increment in HbA1c.ConclusionsAmong Ethiopian patients with HIV, blood pressure and insulin increased, and all glucose parameters declined during 12‐month of ART. Only longer‐term follow‐up will tell us whether insulin increase is due to insulin resistance or from recovering β‐cells.
Genome Copy Number Regulates Inclusion Expansion, Septation, and Infectious Developmental Form Conversion in Chlamydia trachomatis
Authors: Brothwell Julie A. , Brockett Mary , Banerjee Arkaprabha , Stein Barry D. , Nelson David E. , Liechti George W. 
Published: January 2021

ABSTRACT

DNA replication is essential for the growth and development of
Chlamydia trachomatis
; however, it is unclear how this process contributes to and is controlled by the pathogen’s biphasic life cycle. While inhibitors of transcription, translation, cell division, and glucose-6-phosphate transport all negatively affect chlamydial intracellular development, the effects of directly inhibiting DNA polymerase have never been examined. We isolated a temperature-sensitive
dnaE
mutant (the

dnaE
ts

mutant) that exhibits an ∼100-fold reduction in genome copy number at the nonpermissive temperature (40°C) but replicates similarly to the parent at the permissive temperature of 37°C. We measured higher ratios of genomic DNA nearer the origin of replication than the terminus in the

dnaE
ts

mutant at 40°C, indicating that this replication deficiency is due to a defect in DNA polymerase processivity. The

dnaE
ts

mutant formed fewer and smaller pathogenic vacuoles (inclusions) at 40°C, and the bacteria appeared enlarged and exhibited defects in cell division. The bacteria also lacked both discernible peptidoglycan and polymerized MreB, the major cell division-organizing protein in
Chlamydia
responsible for nascent peptidoglycan biosynthesis. We also found that the absolute genome copy number, rather than active genome replication, was sufficient for infectious progeny production. Deficiencies in both genome replication and inclusion expansion were reversed when the

dnaE
ts

mutant was shifted from 40°C to 37°C early in infection, and intragenic suppressor mutations in

dnaE
ts

also restored genome replication and inclusion expansion in the

dnaE
ts

mutant at 40°C. Overall, our results show that genome replication in
C. trachomatis
is required for inclusion expansion, septum formation, and the transition between the microbe’s replicative and infectious forms.

IMPORTANCE
Chlamydiae transition between infectious, extracellular elementary bodies (EBs) and noninfectious, intracellular reticulate bodies (RBs). Some checkpoints that govern transitions in chlamydial development have been identified, but the extent to which genome replication plays a role in regulating the pathogen’s infectious cycle has not been characterized. We show that genome replication is dispensable for EB-to-RB conversion but is necessary for RB proliferation, division septum formation, and inclusion expansion. We use new methods to investigate developmental checkpoints and dependencies in
Chlamydia
that facilitate the ordering of events in the microbe’s biphasic life cycle. Our findings suggest that
Chlamydia
utilizes feedback inhibition to regulate core metabolic processes during development, likely an adaptation to intracellular stress and a nutrient-limiting environment.
The PROMISES study: a mixed methods approach to explore the acceptability of salivary progesterone testing for preterm birth risk among pregnant women and trained frontline healthcare workers in rural India
Authors: Ashworth Danielle , Sharma Pankhuri , Silverio Sergio A , Khan Simi , Kathuria Nishtha , Garg Priyanka , Ghule Mohan , Shivkumar V B , Tayade Atul , Mehra Sunil , Shivkumar Poonam V , Tribe Rachel M 
Published: January 2021

IntroductionIndia has an overall neonatal mortality rate of 28/1000 live births, with higher rates in rural India. Approximately 3.5 million pregnancies in India are affected by preterm birth (PTB) annually and contribute to approximately a quarter of PTBs globally. Embedded within the PROMISES study (which aims to validate a low-cost salivary progesterone test for early detection of PTB risk), we present a mixed methods explanatory sequential feasibility substudy of the salivary progesterone test.MethodsA pretraining and post-training questionnaire to assess Accredited Social Health Activists (ASHAs) (n=201) knowledge and experience of PTB and salivary progesterone sampling was analysed using the McNemar test. Descriptive statistics for a cross-sectional survey of pregnant women (n=400) are presented in which the acceptability of this test for pregnant women is assessed. Structured interviews were undertaken with ASHAs (n=10) and pregnant women (n=9), and were analysed using thematic framework analysis to explore the barriers and facilitators influencing the use of this test in rural India.ResultsBefore training, ASHAs’ knowledge of PTB (including risk factors, causes, postnatal support and testing) was very limited. After the training programme, there was a significant improvement in the ASHAs’ knowledge of PTB. All 400 women reported the salivary test was acceptable with the majority finding it easy but not quick or better than drawing blood. For the qualitative aspects of the study, analysis of interview data with ASHAs and women, our thematic framework comprised of three main areas: implementation of intervention; networks of influence and access to healthcare. Qualitative data were stratified and presented as barriers and facilitators.ConclusionThis study suggests support for ongoing investigations validating PTB testing using salivary progesterone in rural settings.
Treatable but not curable cancer in England: a retrospective cohort study using cancer registry data and linked data sets
Authors: White Rachel , Stanley Fintan , Than Jen , Macnair Archie , Pethick Joanna , Fallica Gregory , Hounsome Luke , Maher Jane 
Published: January 2021

ObjectivesThis study estimates the prevalence of cancers that are categorised as treatable but not curable (TbnC) in England. It provides a quantification of the population and a framework to aid identification of this group to enable the design of tailored support services.DesignThrough consultation with clinical and data experts an algorithmic definition of TbnC was developed. Using cancer registry data sets, with five other linked data sets held by the National Disease Registration Service, the algorithm was applied as part of this retrospective cohort study to estimate the size and characteristics of the TbnC population.Setting and participantsThe health data records of 1.6 million people living with cancer in England in 2015, following a cancer diagnosis between 2001 and 2015, were retrospectively assessed for TbnC status.ResultsAn estimated 110 615 people in England were living with TbnC cancer at the end of 2015, following identification of TbnC cancer between 2012 and 2015. In addition, 51 946 people fit the initial search criteria but were found to have been in their last year of life at the end of 2015 and therefore considered separately here as end of life cases. A further 57 117 people in England were initially identified as being at high risk of recurrence or having their life being shortened by cancer but did not fit the TbnC conceptual framework and were excluded, but their results are also reported under ‘group B’.ConclusionsA population living with TbnC cancer can be identified using data currently collected on a national scale in England. This large population living with TbnC cancer requires personalised treatment and support.
Study protocol for a prospective, double-blinded, observational study investigating the diagnostic accuracy of an app-based diagnostic health care application in an emergency room setting: the eRadaR trial
Authors: Faqar-Uz-Zaman S Fatima , Filmann Natalie , Mahkovic Dora , von Wagner Michael , Detemble Charlotte , Kippke Ulf , Marschall Ursula , Anantharajah Luxia , Baumartz Philipp , Sobotta Paula , Bechstein Wolf O , Schnitzbauer Andreas A 
Published: January 2021

IntroductionOccurrence of inaccurate or delayed diagnoses is a significant concern in patient care, particularly in emergency medicine, where decision making is often constrained by high throughput and inaccurate admission diagnoses. Artificial intelligence-based diagnostic decision support system have been developed to enhance clinical performance by suggesting differential diagnoses to a given case, based on an integrated medical knowledge base and machine learning techniques. The purpose of the study is to evaluate the diagnostic accuracy of Ada, an app-based diagnostic tool and the impact on patient outcome.Methods and analysisThe eRadaR trial is a prospective, double-blinded study with patients presenting to the emergency room (ER) with abdominal pain. At initial contact in the ER, a structured interview will be performed using the Ada-App and both, patients and attending physicians, will be blinded to the proposed diagnosis lists until trial completion. Throughout the study, clinical data relating to diagnostic findings and types of therapy will be obtained and the follow-up until day 90 will comprise occurrence of complications and overall survival of patients. The primary efficacy of the trial is defined by the percentage of correct diagnoses suggested by Ada compared with the final discharge diagnosis. Further, accuracy and timing of diagnosis will be compared with decision making of classical doctor–patient interaction. Secondary objectives are complications, length of hospital stay and overall survival.Ethics and disseminationEthical approval was received by the independent ethics committee (IEC) of the Goethe-University Frankfurt on 9 April 2020 including the patient information material and informed consent form. All protocol amendments must be reported to and adapted by the IEC. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings.Trial registration numberDRKS00019098.
Group practice impacts on patients, physicians and healthcare systems: a scoping review
Authors: Zwiep Terry , Ahn San (Hilalion) , Brehaut Jamie , Balaa Fady , McIsaac Daniel I , Rich Susan , Wallace Tom , Moloo Husein 
Published: January 2021

ObjectiveTo identify the advantages and disadvantages that group practices have on patients, physicians and healthcare systems.Study designA scoping review was performed based on the methodology proposed by Arksey and O’Malley, and refined by Levac et al. Titles and abstracts were screened by two reviewers. A quantitative analysis was performed to assess the type, year and region of publication, as well as the population studied. A qualitative descriptive analysis was performed to identify common themes.Study settingMEDLINE, EMBASE and Cochrane databases were searched from database inception to October 2018 for papers which assessed outcomes relevant to the research question.ResultsOur search strategy returned 2408 papers and 98 were included in the final analysis. Most papers were from the USA, were surveys and assessed physician outcomes. Advantages of group practices for patients included improved satisfaction and quality of care. Studies of physicians reported improved quality of life and income, while disadvantages included increased stress due to poor interpersonal relationships. Studies of healthcare systems reported improved efficiency and better utilisation of resources.ConclusionsGroup practices have many benefits for patients and physicians. However, further work needs to be done assessing patient outcomes and establishing the elements that make a group practice successful.
Physical frailty and health-related quality of life among Chinese rural older adults: a moderated mediation analysis of physical disability and physical activity
Authors: Hao Wenting , Li Jie , Fu Peipei , Zhao Dan , Jing Zhengyue , Wang Yi , Yu Caiting , Yuan Yemin , Zhou Chengchao 
Published: January 2021

ObjectivesThe purpose of this study is to explore the mediating effect of physical disability as well as the role of physical activity (PA) as a moderator in the relationship between physical frailty and health-related quality of life (HRQoL) among rural older adults in China.DesignCross-sectional analysis.SettingRural households in Shandong of China (Rushan, Qufu, Laolin).Participants and methodsA survey was conducted among 3243 rural older adults. The data were collected using questionnaires measuring physical frailty, physical disability, HRQoL and PA. Bootstrap analyses were employed to explore the mediating effect of physical disability and also the moderating role of PA on physical frailty and HRQoL.ResultsAfter controlling for age and education, physical disability partially mediated the effect of physical frailty on HRQoL (indirect effect=−0.143, 95% CI −0.175 to –0.113), with the mediating effect accounting for 33.71% of the total effect. PA moderated the relationship between physical frailty and physical disability as well as the relationship between physical disability and HRQoL. Specifically, the interaction term between physical frailty and PA significantly predicted physical disability (β=−0.120, t=−7.058, p<0.001), and the interaction term between physical disability and PA also had a significant predictive effect on HRQoL (β=0.115, t=6.104, p<0.001).ConclusionsPA appears to moderate the indirect effect of physical disability on the association between physical frailty and HRQoL. This study provides support for potential mechanisms in the association between physical frailty and HRQoL. Encouraging rural older adults to increase PA appropriately might improve HRQoL for older adults with physical frailty and physical disability problems.
Factors affecting consultant attitudes to undertaking undergraduate medical student teaching in the UK: a systematic review
Authors: Harris Isobel Marion , McNeilly Heather , Benamer Hani , Ward Derek J , Sitch Alice J , Parry Jayne 
Published: January 2021

ObjectiveThis systematic review aimed to explore consultant attitudes towards teaching undergraduate medical students in the UK.DesignSystematic review.MethodologyStandard systematic review methodology was followed. MEDLINE, EMBASE and OpenGrey were searched from inception to August 2019 to identify studies exploring senior doctors’ attitudes towards teaching undergraduate medical students. Two reviewers independently carried out key methodological steps including study screening/selection, quality assessment and data extraction. A narrative synthesis was undertaken.ResultsFive studies were included in the review dating 2003–2015. Two studies used questionnaires, and three used focus groups/semistructured interviews. Key findings identified across all studies were consultants generally found teaching undergraduate medical students enjoyable, and consultants identified time constraints as a barrier to teaching. Other findings were consultants feeling there was a lack of recognition for time spent teaching, and a lack of training/guidance regarding teaching students.ConclusionsThis is the first systematic review to explore senior hospital doctors’ attitudes towards teaching undergraduate medical students. Despite these five studies spanning 12 years, the same attitudes and issues regarding teaching are identified by all, suggesting lack of time particularly is a persistent problem regarding consultant-based teaching. An anecdotal impression is that consultants are no longer as enthusiastic about teaching as they once were, but it is evident over the 12 years of these studies that enjoyment levels, and presumably enthusiasm, have not changed significantly.