bluuebunny/crossref_metadata_2025_split huggingface dataset:
What is the significance of guidelines in the primary care setting?
Authors: Wangler Julian , Jansky Michael 
Published: June 2021

SummaryMedical guidelines aim to ensure that care processes take place in an evidence-based and structured manner. They are especially relevant in outpatient primary care due to the wide range of symptoms and clinical pictures. In German-speaking countries, there is a lack of current findings documenting general practitioners’ opinions and experiences regarding guidelines, their expectations and their views on what improvements could be made to increase the use of this type of evidence-based instrument in the primary care setting. Between April and August 2020, a total of 3098 general practitioners were surveyed in the states of Baden–Württemberg, Hesse and Rhineland–Palatinate via an online questionnaire. Alongside the descriptive evaluation, t‑testing was used to determine significant differences between two independent sampling groups. A factor analysis was also used to cluster the expectations of those surveyed regarding the fulfilment of requirements relating to guidelines. A total of 52% of those surveyed have a positive view of guidelines. Overall, guidelines are associated with an increased evidence-based approach (69%), standardisation of diagnosis and treatment (62%) and a reduction in overprovision or underprovision of care (57%). In all, 62% of the physicians who implemented guidelines observed positive effects on the quality of care provided, and 67% reported that the implementation of guidelines improved the quality of their diagnostic or therapeutic skills. However, implementation is often seen as being complicated (43%) and restricting the physician’s ability to act independently (63%). Survey participants suggested that guidelines could be optimised by giving greater consideration to nondrug alternatives (46%), focusing on issues related to quality of life (42%) and offering a comparative assessment of various treatment options (39%). In order to further promote the attractiveness of guidelines for primary care the design of guidelines should be oriented more towards their application; they should be well-presented to make them easier to implement. The scope of action available to the physician should be stressed. The guidelines should provide recommendations on opportunities for the delegation of tasks within practice teams.
Dysregulation of Notch-FGF signaling axis in germ cells results in cystic dilation of the rete testis in mice
Authors: Cao Yin , Liu Lingyun , Lin Jing , Sun Penghao , Guo Kaimin , Li Shengqiang , Li Xian , Lan Zi-jian , Wang Hongliang , Lei Zhenmin 
Published: June 2021

AbstractNumb (Nb) and Numb-like (Nbl) are functionally redundant adaptor proteins that critically regulate cell fate and morphogenesis in a variety of organs. We selectively deletedNbandNblin testicular germ cells by breedingNb/Nblfloxed mice with a transgenic mouse lineTex101-Cre. The mutant mice developed unilateral or bilateral cystic dilation in the rete testis (RT). Dye trace indicated partial blockages in the testicular hilum. Morphological and immunohistochemical evaluations revealed that the lining epithelium of the cysts possessed similar characteristics of RT epithelium, suggesting that the cyst originated from dilation of the RT lumen. Spermatogenesis and the efferent ducts were unaffected. In comparisons of isolated germ cells from mutants to control mice, the Notch activity considerably increased and the expression of Notch target geneHey1significantly elevated. Further studies identified that germ cellFgf4expression negatively correlated the Notch activity and demonstrated that blockade of FGF receptors mediated FGF4 signaling induced enlargement of the RT lumen in vitro. The crucial role of the FGF4 signaling in modulation of RT development was verified by the selective germ cellFgf4ablation, which displayed a phenotype similar to that of germ cellNb/Nblnull mutant males. These findings indicate that aberrant over-activation of the Notch signaling in germ cells due toNb/Nblabrogation impairs the RT development, which is through the suppressing germ cellFgf4expression. The present study uncovers the presence of a lumicrine signal pathway in which secreted/diffusible protein FGF4 produced by germ cells is essential for normal RT development.
An FDA Analysis of Inspected Entities After Receiving Official Action Indicated Letters for Good Clinical Practice Violations
Authors: Jung Miah , Swann Rachelle M. , Anantha Michelle S. , Jamali Faranak 
Published: June 2021

Abstract
Background
Limited research has been conducted to examine whether clinical investigators (CIs), sponsors (SPs), contract research organizations (CROs), and sponsor-investigators (SIs) continue conducting clinical trials following issuance of FDA Official Action Indicated (OAI) letters. FDA issues OAI letters for significant regulatory violations. The objective of this study was to evaluate the status of inspected entities who received OAI letters in the conduct of Center for Drug Evaluation and Research (CDER)-regulated clinical trials (CRCTs).

Methods
This cross-sectional study included an analysis of inspectional data from CDER’s Good Clinical Practice (GCP) inspections for OAI letters issued from October 1, 2010, to September 30, 2015, with an in-depth analysis of post-OAI status of inspected entities, including OAI follow-up inspections.

Results
Of the 2248 GCP letters issued during this period, 104 (4.6%) OAI letters were sent: 95 (4.2%) to CIs (91% of OAIs), 7 (0.3%) to SPs (7% of OAIs), and 2 (0.08%) to SIs (2% of OAIs). Majority of OAI letters were issued as a result of a for-cause inspection. Five CIs were excluded from analysis. No OAI letters were sent to CROs. Only 30% of CIs (27 out of 90) continued to conduct CRCTs. OAI follow-up inspections were completed for these CIs resulting in 16 No Action Indicated (NAI), 11 Voluntary Action Indicated (VAI), and no OAI letters. Majority (64%) of the VAI letters noted repeated but not significant violations.

Conclusions
Majority (70%) of CIs who received an OAI letter were no longer conducting CRCTs at the time of follow-up. Of the 27 CIs continuing CRCTs, 16 (59%) OAI follow-up inspections resulted in NAI classifications and 11 (41%) in VAI.
The Promise of Disease Detection Dogs in Pandemic Response: Lessons Learned From COVID-19
Authors: Otto Cynthia M. , Sell Tara Kirk , Veenema Tener Goodwin , Hosangadi Divya , Vahey Rachel A. , Connell Nancy D. , Privor-Dumm Lois 
Published: June 2021

Abstract
One of the lessons learned from the coronavirus disease 2019 (COVID-19) pandemic is the utility of an early, flexible, and rapidly deployable disease screening and detection response. The largely uncontrolled spread of the pandemic in the United States exposed a range of planning and implementation shortcomings, which, if they had been in place before the pandemic emerged, may have changed the trajectory. Disease screening by detection dogs show great promise as a noninvasive, efficient, and cost-effective screening method for COVID-19 infection. We explore evidence of their use in infectious and chronic diseases; the training, oversight, and resources required for implementation; and potential uses in various settings. Disease detection dogs may contribute to the current and future public health pandemics; however, further research is needed to extend our knowledge and measurement of their effectiveness and feasibility as a public health intervention tool, and efforts are needed to ensure public and political support.
Observations of Children With Disability During Arts-Based Multisensory Story and Rhyme Activities: Is It All Just Chimes and Perfumes?
Authors: O’Rourke John , Main Susan , Gray Christina , Lovering Christine 
Published: June 2021

AbstractIt is generally acknowledged that alternative strategies are required to enable children with disability to access storytelling activities. In this study, we sought to analyse the benefits of one such strategy: an arts-based multisensory story and rhyme program delivered to children with Down syndrome and autism spectrum disorder. In order to determine the engagement and impact of the program on the participants, data were collected through a series of multisensory session observations, focus group interviews with parents of participants, and interviews with performing artists delivering the program. The findings of this study revealed multiple benefits of using sensory stimuli to engage children with disability in storytelling processes, including increased engagement, focus, and interaction with other children and family members. The performing artists used their knowledge and skills to create an engaging environment that was responsive to the children’s needs. It was observed that language development could be further enhanced by integrating written text into the performance and increasing the use of nonverbal communication methods. Further, the engagement of siblings without disability in this program suggested that it could be developed to be inclusive of children with and without disability.
Physical and mental health in young adults with heart disease – a national survey of Norwegian university students
Authors: Leirgul Elisabeth , Hysing Mari , Greve Gottfried , Sivertsen Børge 
Published: June 2021

AbstractBackground:Young adults with heart disease constitute a growing group with the risk of cognitive and physical impairment. The knowledge of their academic performance and mental and physical health is, however, scant. This study aimed to compare young adults with CHDs or arrhythmia with their peers.Methods:Information on physical health (Somatic Symptom Scale-8), mental health problems (Hopkins Symptoms Checklist-25), quality of life (Satisfaction With Life Scale), physical activity, and academic performance was collected online in a national cross-sectional survey in Norway among students in higher education (the SHoT2018 study).Results:Among 50,054 students, 172 (0.34%) reported CHD and 132 (0.26%) arrhythmias. Students reporting arrhythmias scored significantly higher than the control group on somatic symptoms (OR = 2.3 (95% CI: 1.62–3.27)), anxiety (OR = 1.60 (1.08–2.37)), depression (OR = 1.49 (1.05–2.11)), self-harm, and suicide attempt (OR = 2.72 (1.56–4.75)), and lower quality of life (OR 1.64 (1.16–2.32)) and more loneliness (OR = 1.99 (1.28–3.10)) compared to participants without heart disease. Participants with CHD reported an increased somatic symptom burden (OR = 1.58 (1.16–2.16)). Despite a tendency to a higher score, this group did not differ significantly from the control group on anxiety or depression, quality of life, or loneliness. However, the risk of self-harm thoughts and suicidality was significantly increased (OR for suicide attempt 2.22 (1.3–3.77)). There was no difference between the groups on academic performance.Conclusions:Although Norwegian students with heart disease reported more somatic symptoms, their academic progress was not reduced compared to students without heart disease. Students with CHD or arrhythmias showed an increased risk of self-harm thoughts and suicidality.
Das Intensiv-Trauma unserer Kinder
Authors: Kaiser Marvin , Rixe Jacqueline , Wabnitz Pascal 
Published: June 2021

Was ist zu diesem Thema bekannt? Das Überleben einer kritischen Erkrankung ist bei Kindern und Jugendlichen häufig mit einer starken psychotraumatischen Erfahrung verbunden, was ganze Familiensysteme über viele Jahre hinweg belasten kann. Wie wird eine neue Perspektive eingebracht? Da diese Thematik in der intensivmedizinischen und psychiatrischen Praxis nur selten berücksichtigt wird, bietet diese Arbeit einen ersten Überblick. Gleichzeitig soll diese Arbeit für einen sorgsamen Umgang mit Überlebenden einer kritischen Erkrankung und deren Familien sensibilisieren. Was sind die Auswirkungen für die Praxis? Da weder Risiko- noch Schutzfaktoren ausreichend untersucht sind, braucht es zu diesem Thema dringend weiterführende Forschung.
Ein Verständnis der eigenen Erkrankung erarbeiten
Authors: Nienaber André , Bötel Nora , Schulz Michael , Wabnitz Pascal , Jørgensen Rikke 
Published: June 2021

Was ist zu diesem Thema bekannt? Guided Self-Determination (GSD) ist ursprünglich für die Zusammenarbeit in der Behandlung von Menschen mit der Diagnose Diabetes mellitus Typ 1 entwickelt worden. GSD hat sich auch in der Begleitung von Menschen mit anderen chronischen Erkrankungen als hilfreich erwiesen. Wie wird eine neue Perspektive eingebracht? Im Zentrum von GSD steht ein gemeinsamer und geleiteter Reflexionsprozess, in dem strukturiert anhand von Arbeitsblättern an individuellen und komplexen Problemstellungen gearbeitet wird – mit dem Ziel einer personenzentrierten, ressourcenorientierten, und realitätsnahen Lösung. Was sind die Auswirkungen für die Praxis? Menschen in komplexen Problemlagen, die durch eine Erkrankung mit langfristigem Verlauf ausgelöst oder beeinflusst sind, können mit GSD gemeinsam mit professionell Helfenden strukturiert, individuell und ergebnisorientiert ihre Situation reflektieren und zu ihren Bedürfnissen passende Lösungsmöglichkeiten entwickeln.
Results of the Electron Drift Instrument on Cluster
Authors: Paschmann G. , Quinn J. M. , Torbert R. B. , McIlwain C. E. , Vaith H. , Haaland S. , Matsui H. , Kletzing C. A. , Baumjohann W. , Haerendel G. 
Published: June 2021

AbstractThe electron drift instrument (EDI) on Cluster pioneered a new method of measuring electric fields, using a beam of electrons to sample the drift velocity over a km‐scale gyro orbit. The technique is especially well suited to measuring weak, sub‐mV/m, convection fields due to its sensitivity (to both components in the plane perpendicular to B) and because it is unaffected by the anomalous local electric fields that are generated by spacecraft‐plasma interactions. Because EDI requires exquisite beam pointing with active tracking of the firing directions, measurements are less regular, or even impossible, in rapidly varying electric and magnetic fields; however, in the many regimes where tracking is successful the resulting measurements are reliably accurate. We review the EDI technique and instrumentation, and present six areas of investigation using Cluster data: (1) Detailed comparisons of EDI data with the electric field and waves double probe measurements show excellent agreement in many cases but identify large discrepancies where strong ion outflow in the polar regions creates local spacecraft wake effects. (2) The wake effect is exploited to infer quantitative ion outflow rates. Detailed convection patterns in the (3) polar cap, (4) lobe, and (5) inner magnetosphere are derived under various driver conditions using statistical analyses of long term measurements during the Cluster mission. (6) EDI's large geometric‐factor detector is used for extremely high time resolution measurements of electrons at a specified energy and pitch angle.
Cluster Multi‐Probing of the Aurora During Two Decades
Authors: Marklund Göran , Lindqvist Per‐Arne 
Published: June 2021

AbstractThe Cluster spacecraft, launched in the year 2000, were pioneers using multi‐point measurements to explore the dynamic space plasma environment of Earth. This capability offered a new, powerful approach to study in situ fundamental space plasma processes of the solar‐terrestrial interaction. Although not a major science objective of the mission, the aurora and associated processes proved to be a very fruitful target for exploration by the Cluster fleet. Here, results are presented from a selection of Cluster auroral studies using the multi‐point measurements capability to further our understanding on various open issues on the aurora. These include the nature and properties of the auroral acceleration region, in particular the altitude distribution of the quasi‐static parallel electric field and potential, the auroral density cavity and its relation to the acceleration region, the role of and relative contribution by quasi‐static and Alfvénic acceleration processes in producing aurora. A related topic addressed by Cluster is acceleration processes and dynamics of the downward current region and its relation to black aurora. To get a broader perspective on these phenomena, event and statistical studies were used, supported by, in a few cases, numerical simulation studies.
Effects of renal transplantation on erectile dysfunction: a systematic review and meta-analysis
Authors: Rahman Irham Arif , Rasyid Nur , Birowo Ponco , Atmoko Widi 
Published: June 2021

AbstractErectile dysfunction (ED) is a major global health burden commonly observed in patients with end-stage renal disease (ESRD). Although renal transplantation improves the problem in some patients, it persists in ≈20–50% of recipients. Studies regarding the effects of kidney transplantation on ED present contradictory findings. We performed a systematic review to summarise the effects of kidney transplantation on ED. A systematic literature search was performed across PubMed, Cochrane, and Scopus databases in April 2020. We included all prospective studies that investigated the pre and posttransplant international index of erectile function (IIEF-5) scores in recipients with ED. Data search in PubMed and Google Scholar produced 1326 articles; eight were systematically reviewed with a total of 448 subjects. Meta-analysis of IIEF-5 scores showed significant improvements between pre and post transplantation. Our findings confirm that renal transplantation improves erectile function. Furthermore, transplantation also increases testosterone level. However, the evidence is limited because of the small number of studies. Further studies are required to investigate the effects of renal transplantation on erectile function.
Detection of carbapenemase producing enterobacteria using an ion sensitive field effect transistor sensor
Authors: Kotsakis Stathis D. , Miliotis Georgios , Tzelepi Eva , Tzouvelekis Leonidas S. , Miriagou Vivi 
Published: June 2021

AbstractThe timely and accurate detection of carbapenemase-producing Enterobacterales (CPE) is imperative to manage this worldwide problem in an effective fashion. Herein we addressed the question of whether the protons produced during imipenem hydrolysis could be detected using an ion sensitive field effect transistor (ISFET). Application of the methodology on enzyme preparations showed that the sensor is able to detect carbapenemases of the NDM, IMP, KPC and NMC-A types at low nanomolar concentrations while VIM and OXA-48 responded at levels above 100 nM. Similar results were obtained when CPE cell suspensions were tested; NDM, IMP, NMC-A and KPC producers caused fast reductions of the output potential. Reduction rates with VIM-type and especially OXA-48 producing strains were significantly lower. Based on results with selected CPEs and carbapenemase-negative enterobacteria, a threshold of 10 mV drop at 30 min was set. Applying this threshold, the method exhibited 100% sensitivity for NDM, IMP and KPC and 77.3% for VIM producers. The OXA-48-positive strains failed to pass the detection threshold. A wide variety of carbapenemase-negative control strains were all classified as negative (100% specificity). In conclusion, an ISFET-based approach may have the potential to be routinely used for non OXA-48-like CPE detection in the clinical laboratory.
Local and systemic inflammation after implantation of a novel iron based porous degradable bone replacement material in sheep model
Authors: Wegener Bernd , Behnke Maik , Milz Stefan , Jansson Volkmar , Redlich Christian , Hermanns Walter , Birkenmaier Christof , Pieper Korbinian , Weißgärber Thomas , Quadbeck Peter 
Published: June 2021

AbstractDespite the high potential of healthy bone to regenerate, the reconstruction of large bone defects remains a challenge. Due to the lack of mechanical stability of existing bone substitutes, recently developed degradable metallic alloys are an interesting alternative providing higher load-bearing capabilities. Degradable iron-based alloys therefore might be an attractive innovation. To test the suitability of a newly-designed iron-based alloy for such applications, an animal experiment was performed. Porous iron-based degradable implants with two different densities and a control group were tested. The implants were positioned in the proximal tibia of Merino sheep. Over a period of 6 and 12 months, blood and histological parameters were monitored for signs of inflammation and degradation. In the histological evaluation of the implants` environment we found degraded alloy particles, but no inflammatory reaction. Iron particles were also found within the popliteal lymph nodes on both sides. The serum blood levels of phosphorus, iron and ferritin in the long term groups were elevated. Other parameters did not show any changes. Iron-based degradable porous bone replacement implants showed a good biocompatibility in this experiment. For a clinical application, however, the rate of degradation would have to be significantly increased. Biocompatibility would then have to be re-evaluated.
Weather constraints on global drone flyability
Authors: Gao Mozhou , Hugenholtz Chris H. , Fox Thomas A. , Kucharczyk Maja , Barchyn Thomas E. , Nesbit Paul R. 
Published: June 2021

AbstractSmall aerial drones are used in a growing number of commercial applications. However, drones cannot fly in all weather, which impacts their reliability for time-sensitive operations. The magnitude and global variability of weather impact is poorly understood. We explore weather-limited drone flyability (the proportion of time drones can fly safely) by comparing historical wind speed, temperature, and precipitation data to manufacturer-reported thresholds of common commercial and weather-resistant drones with a computer simulation. We show that global flyability is highest in warm and dry continental regions and lowest over oceans and at high latitudes. Median global flyability for common drones is low: 5.7 h/day or 2.0 h/day if restricted to daylight hours. Weather-resistant drones have higher flyability (20.4 and 12.3 h/day, respectively). While these estimates do not consider all weather conditions, results suggest that improvements to weather resistance can increase flyability. An inverse analysis for major population centres shows the largest flyability gains for common drones can be achieved by increasing maximum wind speed and precipitation thresholds from 10 to 15 m/s and 0–1 mm/h, respectively.
Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart
Authors: Ton Anh Tuan , Nguyen William , Sweat Katrina , Miron Yannick , Hernandez Eduardo , Wong Tiara , Geft Valentyna , Macias Andrew , Espinoza Ana , Truong Ky , Rasoul Lana , Stafford Alexa , Cotta Tamara , Mai Christina , Indersmitten Tim , Page Guy , Miller Paul E. , Ghetti Andre , Abi-Gerges Najah 
Published: June 2021

AbstractLate sodium current (late INa) inhibition has been proposed to suppress the incidence of arrhythmias generated by pathological states or induced by drugs. However, the role of late INa in the human heart is still poorly understood. We therefore investigated the role of this conductance in arrhythmias using adult primary cardiomyocytes and tissues from donor hearts. Potentiation of late INa with ATX-II (anemonia sulcata toxin II) and E-4031 (selective blocker of the hERG channel) slowed the kinetics of action potential repolarization, impaired Ca2+ homeostasis, increased contractility, and increased the manifestation of arrhythmia markers. These effects could be reversed by late INa inhibitors, ranolazine and GS-967. We also report that atrial tissues from donor hearts affected by atrial fibrillation exhibit arrhythmia markers in the absence of drug treatment and inhibition of late INa with GS-967 leads to a significant reduction in arrhythmic behaviour. These findings reveal a critical role for the late INa in cardiac arrhythmias and suggest that inhibition of this conductance could provide an effective therapeutic strategy. Finally, this study highlights the utility of human ex-vivo heart models for advancing cardiac translational sciences.