bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone concentration regulates the cell cycle and transcription in early development
Authors: Chari Sudarshan , Wilky Henry , Govindan Jayalakshmi , Amodeo Amanda A. 
Published: September 2019

ABSTRACT
The early embryos of many animals, including flies, fish and frogs, have unusually rapid cell cycles and delayed onset of transcription. These divisions are dependent on maternally supplied RNAs and proteins including histones. Previous work suggests that the pool size of maternally provided histones can alter the timing of zygotic genome activation (ZGA) in frogs and fish. Here, we examine the effects of under- and overexpression of maternal histones in Drosophila embryogenesis. Decreasing histone concentration advances zygotic transcription, cell cycle elongation, Chk1 activation and gastrulation. Conversely, increasing histone concentration delays transcription and results in an additional nuclear cycle before gastrulation. Numerous zygotic transcripts are sensitive to histone concentration, and the promoters of histone-sensitive genes are associated with specific chromatin features linked to increased histone turnover. These include enrichment of the pioneer transcription factor Zelda, and lack of SIN3A and associated histone deacetylases. Our findings uncover a crucial regulatory role for histone concentrations in ZGA of Drosophila.
Assessing the development and implementation of the Global Trigger Tool method across a large health system in Sicily
Authors: Parrinello Vincenzo , Grasso Elena , Saglimbeni Giuseppe , Patanè Gabriella , Scalia Alma , Murolo Giuseppe , Lachman Peter 
Published: September 2019

Background: The Institute for Healthcare Improvement (IHI) has proposed a new method, the Global Trigger Tool (IHI GTT), to detect and monitor adverse events (AEs) and provide information to implement improvement. In 2015, the Sicilian Health System adopted IHI GTT to assess the number, types and severity levels of AEs. The GTT was implemented in 44 of 73 Sicilian public hospitals and 18,008 clinical records (CRs) were examined. Here we present the standardized application of the GTT and the preliminary results of 14,706 reviews of CRs. Methods: IHI GTT was adapted, developed and implemented to the local context. Reviews of CRs were conducted by 199 professionals divided into 71 review teams consisting of three individuals: two of whom had clinical knowledge and expertise, and a physician to authenticate the AE. The reviewers entered data into a dedicated IT-platform. All 44 of the public hospitals were included, with approximately 300,000 yearly inpatient admissions out of a population of approximately 5 million. In total, 14,706 randomized CRs of inpatients from medicine, surgery, obstetric and ICU wards, from June 2015 to June 2018 were reviewed. Results: In 975 (6.6%) CRs at least one AE was found. Approximately 20,000 patients of the 300,000 discharged each year in Sicily have at least one AE. In 5,574 (37.9%) CRs at least one trigger was found. A total of 1,542 AEs were found. The analysis of ROC curve shows that the presence of two triggers in a CR indicates with high probability the presence of an AE. The most frequent type of AE was in-hospital related infection. Conclusions: The GTT is an efficient method to identify AEs and to track improvement of care. The analysis and monitoring of some triggers is important to prevent AEs. However, it is a labor-intensive method, particularly if the CRs are paper-based.
Understanding life sciences data curation practices via user research
Authors: Venkatesan Aravind , Karamanis Nikiforos , Ide-Smith Michele , Hickford Jonathan , McEntyre Johanna 
Published: September 2019

Background: Manual curation is a cornerstone of public biological data resources. However, it is a time-consuming process that urgently needs supportive technical solutions in the face of rapid data growth. Supporting scalable curation is a part of the mission of the Elixir Data Platform. Thus far, we have established infrastructure capable of ingesting and aggregating text-mined outputs from multiple providers and making these available via an API. This public API is used by Europe PMC to display specific entities and relationships on full text articles (via the SciLite application). Methods: To ensure that the future development of this infrastructure meets the needs of curators, we carried out a user research project to understand and identify common workflow patterns and practices via an observational study. Building on these outcomes, we then devised a curator community survey to more specifically understand which entity types, sections of a paper and tools are of top priority to address. Results: The main challenges faced by curators included the following: a) There is a need for ways to prioritise and identify relevant papers for curation as the volume of literature is large; b) Finding specific information can prove difficult; quick ways of filtering articles based on specific entities, such as experimental methods, species and other important entities, such as genes, cell lines and tissue samples, are required; and c) Transferring information from the search/annotation tools to the various curation workflows was also challenging. Conclusions: This study lays the foundation for identifying actionable items to orient the current infrastructure towards meeting the needs of curation community, by improving text-mined annotation quality and coverage and other engineering solutions; and reusing text-mined annotations and other metadata in Europe PMC for article triage. Furthermore, this study presents an opportunity to explore customisation of triage/ranking systems to suit different curation contexts.
The development of mouthwashes without anti-gonococcal activity for controlled clinical trials: an in vitro study
Authors: Van Dijck Christophe , Cuylaerts Vicky , Sollie Piet , Spychala Anna , De Baetselier Irith , Laumen Jolein , Crucitti Tania , Kenyon Chris 
Published: September 2019

Background: The oropharynx plays a major role in the development and spread of antimicrobial resistant Neisseria gonorrhoeae among men who have sex with men. Trials are currently assessing the efficacy of bactericidal mouthwashes as possible therapeutic or preventive options against these pharyngeal gonococcal infections. Controlled clinical trials require the use of a placebo mouthwash without anti-gonococcal activity. So far, no such mouthwash has been described. We describe the development of a mouthwash for this purpose. Methods: The in vitro anti-gonococcal activity of Corsodyl®, Listerine Cool Mint®, Biotene®, phosphate buffered saline and six in-house placebo mouthwashes was evaluated. Three gonococcal isolates from patients with pharyngeal infection were exposed to the mouthwashes for a duration ranging from 30 seconds to 60 minutes. Isolates were then plated onto blood agar (5% horse blood) and incubated for 24 hours (5-7% CO2, 35 ± 2°C). Growth of N. gonorrhoeae was scored on a five-point scale (0 to 4). All experiments were conducted in duplicate. Results: Corsodyl® and Listerine Cool Mint® were bactericidal to all isolates. For the other mouthwashes, the median growth score after 60 minutes of exposure was 4 (interquartile range 4-4) for phosphate buffered saline; 1 (interquartile range 1-3) for Biotene®; and ranged between 0 and 2 for the in-house composed mouthwashes. An in-house composed mouthwash (Placebo 6) performed best, with a growth score of 2 (interquartile range 2-3). Conclusions: All of the evaluated potential placebo mouthwashes were bacteriostatic after gonococcal exposure of 30 to 60 minutes. In-house composed Placebo 6 showed less inhibition on gonococcal growth than Biotene® and the other in-house placebos and demonstrates, in our opinion, a good trade-off between anti-gonococcal properties and taste.
Assessment of a neuro-developmental screening tool in children in Bhutan
Authors: Wong Brian , Grundy Sara , Tshering Lhab , Tshering Kinley , Mateen Farrah J. 
Published: September 2019

Background:Developmental screening tools are designed to fit the cultural context in which they are utilized, yet often find a wider international audience. This study evaluates the efficacy of one such tool, the Parental Evaluation of Developmental Status: Developmental Milestones (PEDS:DM), developed in the United States and tested in the lower income Asian country of Bhutan. We aimed to test the PEDS:DM instrument to measure neurodevelopmental delay in children in Bhutan.Methods:In total, 96 community-dwelling Bhutanese children (3-7 years old) without diagnosed neurocognitive conditions were recruited from ambulatory clinics in urban Bhutan in 2016 as part of a larger study on retinal imaging and cognitive and growth parameters. Scoring was based on neurocognitive domains (gross and fine motor, receptive and expressive speech, self-help, social-emotional). Rates of failure (meant to indicate delay) within domains were calculated.Results:Modifications of some standard questions were deemed necessary by the study staff to suit the cultural context, such as replacing kickball with football in a question regarding games played with rules to maintain local relevance. In a modified PEDS:DM test with these improvised modifications, the mean percentage of age-appropriate domains failed was 58.8% and the mean percent delay was 12.3% (range 0-41.4%, available in n=83). The highest prevalence of failures was 59.4% for receptive language and 76.3% for expressive language, much higher than the lowest rate of failure seen in self-help (5.4%). Conclusions:The PEDS:DM requires further modifications and validation studies before it can be reliably implemented to assess developmental delay in children in Bhutan. In this pilot study, the rate of delay as reported by the PEDS:DM would be scored as markedly elevated, especially when compared to available epidemiologic studies in the region.
Visualizing participant experiences in maternal and child nutrition studies using timeline mapping
Authors: Sankaran Deepa , Sharma Priyanshu , Lazarus Lisa , Swain Tapaswini , Pilli Bhanu , Kumar P. Manish , Namasivayam Vasanthakumar , Blanchard James , Moses Stephen 
Published: September 2019

Iron and folic acid (IFA) supplementation is one of the most cost-effective interventions to prevent and treat anemia during pregnancy. Despite having the highest global burden of anemia among pregnant women, rates of IFA uptake in pregnancy in India are still very low, particularly in the state of Uttar Pradesh. Timeline maps were developed as a visual qualitative tool to explore the nuances of health behaviors among pregnant women with respect to antenatal care (ANC) services, including IFA consumption. Timeline maps were used to elicit and visually document critical events pertaining to ANC services chronologically, including details on contact points with the health system and events specific to IFA distribution, consumption and counselling. The tool consists of a horizontal straight line with nine suspended boxes corresponding to each month of pregnancy, with legends on how to illustrate IFA receipt and consumption. In this instance, the woman’s last menstrual period and expected date of delivery were used as a frame of reference for the duration of pregnancy. Six research assistants (RAs) were trained on how to use timeline maps to elicit and record participant narratives. The RAs later participated in a focus group discussion to gain insight about their experiences using the tool. The timeline maps were easy-to-use and facilitated in-depth conversations with participants. RAs were able to actively engage the participants in co-creating the maps. The visual nature of the tool prompted participants’ recall of key pregnancy events and reflexivity. Challenges reported with the tool/process included recollection of past events and potential misrepresentation of information. These highlight a need to restructure training processes. Our findings indicate that timeline maps have the potential to be used in a variety of other program contexts, and merit further exploration.
Frailty and physical performance in the context of extreme poverty: a population-based study of older adults in rural Burkina Faso
Authors: Witham Miles D. , Davies Justine I. , Bärnighausen Till , Bountogo Mamadou , Manne-Goehler Jennifer , Payne Collin F. , Ouermi Lucienne , Sie Ali , Siedner Mark J. , Harling Guy 
Published: September 2019

Background: Little is known about the prevalence of frailty and about normal values for physical performance among older individuals in low-income countries, in particular those in sub-Saharan Africa. We describe the prevalence of phenotypic frailty, and values and correlates of several physical performance measures in a cohort of middle-aged and older people living in rural Burkina Faso, one of the world’s poorest communities. Methods: We analysed data collected from participants aged over 40 in Nouna district, Burkina Faso. We measured handgrip strength, four metre walk speed, chair rise time, and derived the Fried frailty score based on grip strength, gait speed, body mass index, self-reported exhaustion, and physical activity. Frailty and physical performance indicators were then correlated with health and sociodemographic variables including comorbid disease, marital status, age, sex, wealth and activity impairment. Results: Our sample included 2973 individuals (1503 women), mean age 54 years. 1207 (43%) were categorised as non-frail, 1324 (44%) as prefrail, 212 (7%) as frail, and 167 (6%) were unable to complete all five frailty score components. Lower grip strength, longer chair stand time, lower walk speed and prevalence of frailty rose with age. Frailty was more common in women than men (8% vs 6%, p=0.01) except in those aged 80 and over. Frailty was strongly associated with impairment of activities of daily living and with lower wealth, being widowed, diabetes mellitus, hypertension, and self-reported diagnoses of tuberculosis or heart disease. With the exception of grip strength, which was higher in women than prior international normative values, women had greater deficits than men in physical performance. Conclusions: Phenotypic frailty and impaired physical performance were associated as expected with female sex, co-morbidities, increasing age and impaired activities of daily living. These results support the use of frailty measurements for classification of ageing related syndromes in this setting.
The Effect of the Microsoft Excel based Interactive Learning Media on the Physics Problem Solving
Authors: Astuti Irnin Agustina Dwi , Bhakti Yoga Budi 
Published: September 2019

The physics problem solving is needed students to overcome the phenomenon of physics. The development of technology in physics learning is able to explain the concept of abstract physics. This study aims to know effect of use interactive learning media based Microsoft Excel on the physics problem solving. The subject on this media is Heat and Temperature. The research method used is pretest-postest controlled group design. The analysis technique is used t-test with SPSS 16.0 with a margin of error of 5%. The results of this study showed that the mean scores of post-test treatment class students significantly better than the average score post-test control class indicated by the average score of students' post-test treatment class at 80.26 and scores the average post-test control class at 68.00 and with SPSS analyze sig value is 0.000. While the average score gain results-physics students learn physics class treatment significantly better than the average score gain results Physics students learn physics-control class indicated by the average score of physics problem solving gain of 0.77 and the treatment class the average score gain control class student physics problem solving of 0.63.
Preoperative oral antibiotic bowel preparation in elective resectional colorectal surgery reduces rates of surgical site infections: a single-centre experience with a cost-effectiveness analysis
Authors: Vadhwana B , Pouzi A , Surjus Kaneta G , Reid V , Claxton D , Pyne L , Chalmers R , Malik A , Bowers D , Groot-Wassink T 
Published: September 2019

Introduction Surgical site infections cause considerable postoperative morbidity and mortality. The aim of this study was to determine the effect on surgical site infection rates following introduction of a departmental oral antibiotic bowel preparation protocol. Methods A prospective single-centre study was performed for elective colorectal resections between May 2016-April 2018; with a control group with mechanical bowel preparation and treatment group with oral antibiotic bowel preparation (neomycin and metronidazole) and mechanical bowel preparation. The primary outcome of surgical site infection and secondary outcomes of anastomotic leak, length of stay and mortality rate were analysed using Fisher’s exact test and independent samples t-tests. A cost-effectiveness analysis was also performed. Results A total of 311 patients were included; 156 in the mechanical bowel preparation group and 155 in the mechanical bowel preparation plus oral antibiotic bowel preparation group. The study included 180 (57.9%) men and 131 (42.1%) women with a mean age of 68 years. There was a significant reduction in surgical site infection rates (mechanical bowel preparation 16.0% vs mechanical bowel preparation plus oral antibiotic bowel preparation 4.5%; P = 0.001) and mean length of stay (mechanical bowel preparation 10.2 days vs mechanical bowel preparation plus oral antibiotic bowel preparation 8.2 days; P = 0.012). There was also a reduction in anastomotic leak and mortality rates. Subgroup analyses demonstrated significantly reduced surgical site infection rates in laparoscopic resections (P = 0.008). There was an estimated cost saving of £239.13 per patient and £37,065 for our institution over a one-year period. Conclusion Oral antibiotic bowel preparation is a feasible and cost-effective intervention shown to significantly reduce the rates of surgical site infection and length of stay in elective colorectal surgery.
Postnatal Development of Functional Projections from Parasubiculum and Presubiculum to Medial Entorhinal Cortex in the Rat
Authors: Canto Cathrin B. , Koganezawa Noriko , Lagartos-Donate Mariá José , O'Reilly Kally C. , Mansvelder Huibert D. , Witter Menno P. 
Published: September 2019

Neurons in parasubiculum (PaS), presubiculum (PrS), and medial entorhinal cortex (MEC) code for place (grid cells) and head direction. Directional input has been shown to be important for stable grid cell properties in MEC, and PaS and PrS have been postulated to provide this information to MEC. In line with this, head direction cells in those brain areas are present at postnatal day 11 (P11), having directional tuning that stabilizes shortly after eye opening, which is before premature grid cells emerge in MEC at P16. Whether functional connectivity between these structures exists at those early postnatal stages is unclear. Using anatomical tracing, voltage-sensitive dye imaging and single-cell patch recordings in female and male rat brain slices between P2 and P61, we determined when the pathways from PaS and PrS to MEC emerge, become functional, and how they develop. Anatomical connections from PaS and PrS to superficial MEC emerge between P4 and P6. Monosynaptic connectivity from PaS and PrS to superficial MEC was measurable from P9 to P10 onward, whereas connectivity with deep MEC was measurable from P11 to P12. From P14/P15 on, reactivity of MEC neurons to parasubicular and presubicular inputs becomes adult-like and continues to develop until P28-P30. The maturation of the efficacy of both inputs between P9 and P21 is paralleled by maturation of morphological properties, changes in intrinsic properties of MEC principal neurons, and changes in the GABAergic network of MEC. In conclusion, synaptic projections from PaS and PrS to MEC become functional and adult-like before the emergence of grid cells in MEC.SIGNIFICANCE STATEMENTHead direction information, crucial for grid cells in medial entorhinal cortex (MEC), is thought to enter MEC via parasubiculum (PaS) and presubiculum (PrS). Unraveling the development of functional connections between PaS, PrS, and MEC is key to understanding how spatial navigation, an important cognitive function, may evolve. To gain insight into the development, we used anatomical tracing techniques, voltage-sensitive dye imaging, and single-cell recordings. The combined data led us to conclude that synaptic projections from PaS and PrS to MEC become functional and adult-like before eye opening, allowing crucial head direction information to influence place encoding before the emergence of grid cells in rat MEC.
Impact of obesity and diabetes on the incidence of kidney and bladder cancers: a nationwide cohort study
Authors: Ko Seung Hyun , Han Kyung Do , Yun Jae Seung , Chung Sungjin , Koh Eun Sil 
Published: September 2019

Objective
Obesity and type 2 diabetes are becoming increasingly prevalent worldwide and are both associated with the increased incidence of kidney and bladder cancers. However, previous reports have provided conflicting results. We investigated the impact of body mass index (BMI) and diabetes on the incidence of both cancers in the general population.

Methods
Using nationally representative data from the Korean National Health Insurance System, 9,777,133 subjects without any malignancy who underwent health examinations in 2009 were followed to the end of 2017.

Results
After a median follow-up period of 8.32 years, 12,544 incidents of kidney cancer and 15,137 incidents of bladder cancer were identified. The hazard ratio (HR) for kidney cancer was the lowest in people with a BMI <18.5 kg/m2 (HR: 0.82, 95% confidence interval (CI): 0.72–0.94) and the highest in those with a BMI ≥30 kg/m2 (HR: 1.71, 95% CI: 1.57–1.87) compared to a reference BMI group (18.5–23 kg/m2). In subjects with diabetes, obesity was associated with increased risk of kidney cancer, although the HRs were lower than observed in those without diabetes. Otherwise, there was a reduction in risk of bladder cancer with obesity in men and the HR for bladder cancer was not affected by BMI increase in women. There was a strongly positive association between diabetes and bladder cancer in the total study population.

Conclusions
Obesity was a strong risk factors for kidney cancer, whereas the association between obesity and bladder cancer differed by gender. The subjects with diabetes had a higher risk for both cancers than those without diabetes.