bluuebunny/crossref_metadata_2025_split huggingface dataset:
The handling oxygenation targets in the intensive care unit (HOT‐ICU) trial: Detailed statistical analysis plan
Authors: Schjørring Olav L. , Klitgaard Thomas L. , Perner Anders , Wetterslev Jørn , Lange Theis , Keus Frederik , Laake Jon H. , Morgan Matthew , Bäcklund Minna , Siegemund Martin , Thormar Katrin M. , Rasmussen Bodil S. 
Published: February 2020

BackgroundNo solid evidence exists on optimal oxygenation targets in intensive care patients. The handling oxygenation targets in the intensive care unit (HOT‐ICU) trial assesses the effects of a targeted arterial oxygen tension of 8 vs 12 kPa on 90‐day mortality in acutely admitted adult patients with hypoxaemic respiratory failure. This article describes the detailed statistical analysis plan for the predefined outcomes and supplementary analyses in the HOT‐ICU trial.MethodsThe trial will include 2928 patients to be able to detect or reject a true 20% relative risk reduction in the primary outcome of 90‐day all‐cause mortality with an α of 5% and a β of 10%. Analyses of the primary and secondary outcomes will be conducted according to the intention‐to‐treat principle and adjusted for stratification variables. The primary outcome and dichotomous secondary outcomes will be analysed using a generalised linear model with a log‐link and binomial error distribution. For the primary outcome, a 95% confidence interval (CI) not including 1.00 for the risk ratio will be considered statistically significant. Continuous secondary outcomes will be analysed using a generalised linear model or nonparametric test. CIs adjusted for the multiple secondary outcomes not including the null effect will be considered statistically significant. One planned interim analysis has been conducted.ConclusionsThe HOT‐ICU trial and the pre‐planned statistical analyses are designed to minimise bias and produce high quality data on the effects of a lower vs a higher oxygenation target throughout ICU admission in acutely admitted adult patients with hypoxaemic respiratory failure.RegistrationClinicalTrials.gov identifier: NCT03174002, date of registration: June 2, 2017. European clinical trials database, EudraCT number 2017‐000632‐34.
Evidence of distinct gene functional patterns in GC‐poor and GC‐rich isochores in Bos taurus
Authors: Arhondakis S. , Milanesi M. , Castrignanò T. , Gioiosa S. , Valentini A. , Chillemi G. 
Published: February 2020

SummaryVertebrate genomes are mosaics of megabase‐size DNA segments with a fairly homogeneous base composition, called isochores. They are divided into five families characterized by different guanine‐cytosine (GC) levels and linked to several functional and structural properties. The increased availability of fully sequenced genomes allows the investigation of isochores in several species, assessing their level of conservation across vertebrate genomes. In this work, we characterized the isochores in Bos taurus using the ARS‐UCD1.2 genome version. The comparison of our results with the well‐studied human isochores and those of other mammals revealed a large conservation in isochore families, in number, average GC levels and gene density. Exceptions to the established increase in gene density with the increase in isochores (GC%) were observed for the following gene biotypes: tRNA, small nuclear RNA, small nucleolar RNA and pseudogenes that have their maximum number in H2 and H1 isochores. Subsequently, we assessed the ontology of all gene biotypes looking for functional classes that are statistically over‐ or under‐represented in each isochore. Receptor activity and sensory perception pathways were significantly over‐represented in L1 and L2 (GC‐poor) isochores. This was also validated for the horse genome. Our analysis of housekeeping genes confirmed a preferential localization in GC‐rich isochores, as reported in other species. Finally, we assessed the SNP distribution of a bovine high‐density SNP chip across the isochores, finding a higher density in the GC‐rich families, reflecting a potential bias in the chip, widely used for genetic selection and biodiversity studies.
Testosterone replacement therapy
Authors: Barbonetti Arcangelo , D’Andrea Settimio , Francavilla Sandro 
Published: February 2020

AbstractBackgroundThe aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range. TRT has been used in the last 70 years, and overtime, numerous preparations and formulations have been developed to improve pharmacokinetics (PKs) and patient compliance. The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal and intramuscular (IM).ObjectivesThe aim of this narrative review was to describe and compare all available and approved testosterone preparations according to pharmacology, PKs and adverse effects.Materials and MethodsWe have performed an extensive PubMed review of the literature on TRT in clinical practice. Contraindications and monitoring of TRT were analyzed by comparing available guidelines released in the last five years. We provide a review of advantages and disadvantages of different modalities of TRT and how to monitor treatment to minimize the risks.ResultsTRT is associated with multiple benefits highly relevant to the patient. However, the recommendations given in different guidelines on TRT are based on data from a limited number of randomized controlled trials (RCTs), as well as non‐randomized clinical studies and observational studies. This is the case for the safety of a long‐term TRT in late‐onset hypogonadism (LOH). No evidence is provided indeed on the effects of TRT on endpoints such as deterioration of heart failure suggesting a cautious approach to T replacement in older men with a history of heart failure.ConclusionClinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of LOH in order to provide the safest and most beneficial results.
Pharmacokinetics, pharmacodynamics and safety of the inverse retinoic acid‐related orphan receptor γ agonist AZD0284
Authors: Asimus Sara , Palmér Robert , Albayaty Muna , Forsman Henrik , Lundin Christina , Olsson Marita , Pehrson Rikard , Mo John , Russell Muir , Carlert Sara , Close David , Keeling David 
Published: February 2020

AimsRetinoic acid‐related orphan receptor γ (RORγ), a master regulator of T‐helper 17 (Th17) cell function and differentiation, is an attractive target for treatment of Th17‐driven diseases. This first‐in‐human study aimed to investigate the pharmacokinetics, pharmacodynamics, safety and tolerability of the inverse RORγ agonist AZD0284.MethodsWe conducted a phase I, randomized, single‐blind, placebo‐controlled, two‐part, first‐in‐human study with healthy subjects receiving single (4–238 mg) or multiple (12–100 mg) oral doses of AZD0284 or placebo after overnight fasting. Subjects in the one single dose cohort additionally received a single dose of AZD0284 after a high‐calorie meal. AZD0284 plasma concentrations, as well as inhibition of ex vivo‐stimulated interleukin (IL)‐17A release in whole blood, were frequently measured after both single and multiple dosing.ResultsEighty‐three men participated in the study. AZD0284 was absorbed rapidly into plasma after oral dosing and exhibited a terminal half‐life of 13–16 hours. Both the area under the concentration‐time curve (AUC) and maximum concentration (Cmax) increased subproportionally with increasing dose (95% confidence intervals of slope parameter were 0.71–0.84 and 0.72–0.88 for AUC and Cmax, respectively). Food intake delayed the absorption of AZD0284 but did not affect the overall exposure or half‐life. AZD0284 showed dose‐dependent reduction of ex vivo‐stimulated IL‐17A release after both single and multiple doses. No significant safety concerns were identified in the study.ConclusionsAZD0284 was well tolerated, rapidly and dose‐dependently absorbed, and reduced stimulated IL‐17A release after single and multiple dosing. The results of this study support further clinical development of AZD0284.
A critical reflection on accessing women with learning disabilities to participate in research about sensitive subjects through organisational partnerships
Authors: Earle Sarah , Ledger Sue , Tilley Elizabeth , Walmsley Jan , Chapman Rohhss , Townson Lou 
Published: February 2020

Accessible summary

This article is about reaching out to people with learning disabilities to participate in research on sensitive topics, like contraception. Contraception is a way to prevent pregnancy.

The article shows that working with organisations can help to find and support people with learning disabilities to take part in research.

The article explores what research teams need to do when working with organisations to find and support research participants.

AbstractBackgroundContraceptive use by women with learning disabilities differs from that of nondisabled women of a similar age. Women with learning disabilities start contraception earlier and often use it when they are not sexually active. Hence, there is a need to hear directly from these women about their experiences of contraceptive decision‐making. However, accessing women to discuss a sensitive topic such as contraception poses significant challenges to researchers.Materials and MethodsThe study was qualitative in nature and involved conducting semi‐structured interviews with 19 women. This paper reports on the methodological challenges and findings from the project which have wider implications for research on sensitive topics with hard‐to‐reach groups. It reflects critically on the challenges of accessing women with learning disabilities to participate in research on contraception.ResultsTwelve of the 19 participants in our project were recruited through two organisations. Working in partnership with organisations that had a keen interest in the research and endorsed it at senior level enabled us to overcome recruitment challenges. However, working in this way raised gatekeeping issues that impacted upon data collection and may have affected our substantive findings.ConclusionsWorking in partnership with organisations can be an effective and practical way of recruiting participants that researchers may otherwise find hard to reach. However, organisational partnerships can be hard to develop and take time. We argue that it is important to reflect openly and honestly about the methodological and ethical issues that may arise when working closely with organisations in sensitive research.
With a little help from my friends: Individual and collaborative performance during trail clearing in leaf‐cutting ants
Authors: Alma Andrea Marina , Farji‐Brener Alejandro G. , Elizalde Luciana 
Published: February 2020

AbstractSocial organisms express collaborative behaviors, allowing them to solve problems that exceed their individual capabilities. Group coordination and environmental context are some of the factors that may determine the performance of individual and collaborative strategies. Using the trail‐clearing behavior of leaf‐cutting ants, we evaluated experimentally for both strategies whether the success probability and clearing time depend on problem characteristics and context. We placed obstacles of different sizes and shapes (problem characteristics), in trails with different foragers' fluxes and soil roughness (context) in 10 field nests of Atta cephalotes, and compared removal success (i.e., if ants could remove obstacles) and time of individual and collaborative strategies. Very large obstacles could only be removed collaboratively, confirming individual limitations for transporting large objects. For all obstacle shapes, collaborative removals were more successful but took longer, suggesting that coordination among individuals delays these actions. Individual strategies were faster, regardless of ant flux. However, as ant flux increased, removal success was higher for collaborative than for individual removals. Lastly, trail roughness had no effect. This work highlights one advantage of sociality, the option of collaboratively solving problems that exceed the individual abilities. In addition, it reveals the associated costs of joint actions, since they can be time‐consuming presumably due to coordination problems.Abstract in Spanish is available with online material.
European Society of ColoProctology: guideline for haemorrhoidal disease
Authors: van Tol R. R. , Kleijnen J. , Watson A. J. M. , Jongen J. , Altomare D. F. , Qvist N. , Higuero T. , Muris J. W. M. , Breukink S. O. 
Published: February 2020

AbstractAimThe goal of this European Society of ColoProctology project was to establish a multidisciplinary, international guideline for haemorrhoidal disease (HD) and to provide guidance on the most effective (surgical) treatment for patients with HD.MethodsThe development process consisted of six phases. In phase one we defined the scope of the guideline. The patient population included patients with all stages of haemorrhoids. The target group for the guideline was all practitioners treating patients with haemorrhoids and, in addition, healthcare workers and patients who desired information regarding the treatment management of HD. The guideline needed to address both the diagnosis of and the therapeutic modalities for HD. Phase two consisted of the compilation of the guideline development group (GDG). All clinical members needed to have affinity with the diagnosis and treatment of haemorrhoids. Further, attention was paid to the geographical distribution of the clinicians. Each GDG member identified at least one patient in their country who could read English to comment on the draft guideline. In phase three review questions were formulated, using a reversed process, starting with possible recommendations based on the GDG’s knowledge. In phase four a literature search was performed in MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews. The search was focused on existing systematic reviews addressing each review question, supplemented by other studies published after the time frame covered by the systematic reviews. In phase five data of the included papers were extracted by the surgical resident (RT) and checked by the methodologist (JK) and the GDG. If needed, meta‐analysis of the systematic reviews was updated by the surgical resident and the methodologist using Review Manager. During phase six the GDG members decided what recommendations could be made based on the evidence found in the literature using GRADE.ResultsThere were six sections: (i) symptoms, diagnosis and classification; (ii) basic treatment; (iii) outpatient procedures; (iv) surgical interventions; (v) special situations; (vi) other surgical techniques. Thirty‐four recommendations were formulated.ConclusionThis international, multidisciplinary guideline provides an up to date and evidence based summary of the current knowledge of the management of HD and may serve as a useful guide for patients and clinicians.
Heidegger on Guilt: Reconstructing the Transcendental Argument in Being and Time
Authors: Elgat Guy 
Published: February 2020

AbstractIn the chapter on conscience and guilt in Being and Time, Heidegger makes transcendental claims to the effect that Dasein's Being‐guilty is the condition of possibility of factical guilt—guilt for specific misdeeds. In this article, I reconstruct Heidegger's transcendental argument. To do so, I distinguish factical guilt from (what I call) ontic guilt and ontological guilt and explain why Dasein's ontic guilt is a necessary condition of possibility of Dasein's factical guilt and why ontic guilt, in turn, is necessarily conditioned by Dasein's ontological guilt, or Dasein's ownmost Being‐guilty. In the process, I provide an interpretation of the two “nullities” that constitute Dasein's Being‐guilty according to Heidegger. I end the paper with thoughts on why Dasein's Being‐guilty is only a necessary yet not a sufficient condition of factical guilt in general and factical moral guilt in particular.
Age‐specific findings on endodontic treatments performed by private dentists in Finland in 2012 and 2017: a nationwide register‐based observation
Authors: Vehkalahti M. M. , Palotie U. , Valaste M. 
Published: February 2020

AbstractAimTo evaluate age‐specific aspects and changes in volume and content of endodontic treatment for adults visiting private dentists in Finland in 2012 and 2017.MethodologyThis study utilized register‐based data of private dental care. The observation unit of the aggregated macro‐level data was age group, with 5‐year age groups from 20 to 24 years onwards and the oldest group combining all patients aged 90 years and over. Data from years 2012 and 2017 included all the oral health care of 2.04 million patients receiving reimbursement for treatment by private dentists; a total of 183 932 patients received at least one endodontic treatment and were analysed. The number of teeth receiving endodontic treatment was counted separately as pulp cappings, pulpotomies and root canal fillings according to number of canals filled per tooth. Statistical associations were assessed as correlation coefficients.ResultsThe mean age of endodontic patients was 53.6 years in 2012 and 55.9 years in 2017. In both years, 38% were aged from 50 to 64 years. In 2012, 9.9%, and in 2017, 8.0% of patients received at least one endodontic treatment; the older the patients, the fewer received endodontic treatment (r = −0.9). From 2012 to 2017, numbers of all patients and treatments decreased, endodontic patients and treatments even more notably, and in all age groups. Per thousand patients in 2017, 62.1 teeth received root canal treatment and 14.9 pulp capping. Pulp capping comprised 19.2%, pulpotomies 0.8% and root canal fillings 80.0% of teeth receiving endodontic treatment. Of root filled teeth, 45.1% received filling in one canal, 17.0% in two and 37.9% in three or more canals, multi‐canal options being less frequent in older patients (r = −0.94).ConclusionsEndodontic treatment, received by 9% of adult patients visiting private dentists in Finland, was strongly age‐dependent, showing a decreasing trend with age and time.
The transcription factor ICE1 functions in cold stress response by binding to the promoters of CBF and COR genes
Authors: Tang Kai , Zhao Lun , Ren Yuying , Yang Shuhua , Zhu Jian‐Kang , Zhao Chunzhao 
Published: February 2020

AbstractA recent paper by Kidokoro et al. (2020) in The Plant Cell reported a transgene‐dependent transcriptional silencing phenomenon in the dominant ice1‐1 Arabidopsis mutant containing the CBF3‐LUC reporter, and questioned whether ICE1 may regulate CBF genes and may be involved in plant cold response. Here, we evaluate available evidence supporting the involvement of ICE1 in plant cold response, and provide ChIP‐seq data showing ICE1 binding to the promoters of CBF genes and other regulatory genes known to be critical for cold response as well as to the promoters of some COR genes.
Toward a conceptual framework for the interdisciplinary function‐focused care in nursing homes
Authors: Kim Mi So , Lee Su Jung , Park Min Sun , Jeong Eun‐hye , Chang Sung Ok 
Published: February 2020

AbstractAimTo develop a conceptual framework to structure the shared roles and tasks of interdisciplinary teams for efficient function‐focused care of nursing home (NH) residents.MethodsA qualitative study using focus groups. Two focus group interviews were conducted on NH practitioners and professors. Focus group 1 consisted of six practitioners with more than 5 years of practical experience in NHs. Focus group 2 consisted of six professors with more than 5 years of educational experience in geriatrics or gerontology and who are capable of adopting theoretical approaches to older adults’ functions.ResultsThe post‐acute care‐rehabilitation quality framework furnished the underlying structure for the focus group interview questionnaire to develop the shared interdisciplinary function‐focused care framework. The focus of the framework is how resident care processes should be based on individuality of the residents and include holistic continuous assessments, integration of care, and professional interventions by each discipline. An interdisciplinary process involves setting shared goals, communicating and coordinating roles and tasks of interdisciplinary teams, and providing complementary care. Shared final outcomes are defined as improving residents' independence and quality of life and reducing hospital transfer and admission rates.ConclusionIn this study, we have developed the first conceptual framework of interdisciplinary function‐focused care in NHs, which will provide an evidence‐based foundation for integrated and continuous function‐focused care for NH residents. The results of this study will contribute to efficient communication among the interdisciplinary teams and improvement of the outcomes of function‐focused care subjects.
Cell proliferation and neurogenesis alterations in Alzheimer’s disease and diabetes mellitus mixed murine models
Authors: Hierro‐Bujalance Carmen , del Marco Angel , José Ramos‐Rodríguez Juan , Infante‐Garcia Carmen , Bella Gomez‐Santos Sara , Herrera Marta , Garcia‐Alloza Monica 
Published: February 2020

AbstractThe classic neuropathological features of Alzheimer's disease (AD) are accompanied by other complications, including alterations in adult cell proliferation and neurogenesis. Moreover recent studies have shown that traditional markers of the neurogenic process, such as doublecortin (DCX), may also be expressed in CD8+ T cells and ionized calcium‐binding adaptor molecule 1 (Iba1+) microglia, in the close proximity to senile plaques, increasing the complexity of the condition. Altered glucose tolerance, observed in metabolic alteratioins, may accelerate the neurodegenerative process and interfere with normal adult cell proliferation and neurogenesis. To further explore the role of metabolic disease in AD, we analyzed cell proliferation and neurogenesis using 5’‐bromo‐2’‐deoxyuridine and DCX immunohistochemistry in three different mouse models of AD and metabolic alterations: APP/PS1xdb/db mice, APP/PS1 mice on a long‐term high‐fat diet, and APP/PS1 mice treated with streptozotozin. As reported previously, an overall reduction in cell proliferation and neurogenesis was observed after streptozotocin administration. In contrast, an increase in cell proliferation and neurogenesis was detected in neurogenic niches in 14‐ and 26‐week‐old APP/PS1xdb/db mice, accompanied by a slight increase in cortical cell proliferation. While a similar trend was observed in animals on a high‐fat diet, differences were not statistically significant. We observed very few DCX+/CD8+ cells and no DCX+/Iba1+ cells were observed in the close proximity to senile plaques in any of the groups. Interestingly, metabolic parameters such as body weight and glucose and insulin levels were identified as reliable predictors of cell proliferation and neurogenesis in APP/PS1xdb/db mice. Furthermore, metabolic parameters were also associated with altered Aβ levels in the cortex and hippocampus of APP/PS1xdb/db mice. Altogether, our data suggest that metabolic disease may also interfere with central complications in AD.
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