bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and facilitators of germline genetic evaluation for prostate cancer
Authors: Loeb Stacy , Li Randall , Sanchez Nolasco Tatiana , Byrne Nataliya , Cheng Heather H. , Becker Daniel , Leader Amy E. , Giri Veda N. 
Published: May 2021

AbstractBackgroundGenetic counseling and germline testing have an increasingly important role for patients with prostate cancer (PCa); however, recent data suggests they are underutilized. Our objective was to perform a qualitative study of the barriers and facilitators of germline genetic evaluation among physicians who manage PCa.MethodsWe conducted semi‐structured interviews with medical oncologists, radiation oncologists, and urologists from different U.S. practice settings until thematic saturation was achieved at n = 14. The interview guide was based on the Tailored Implementation in Chronic Diseases Framework to identify key determinants of practice. Interview transcripts were independently coded by ≥2 investigators using a constant comparative method.ResultsThe decision to perform or refer for germline genetic evaluation is affected by factors at multiple levels. Although patient factors sometimes play a role, the dominant themes in the decision to conduct germline genetic evaluation were at the physician and organizational level. Physician knowledge, coordination of care, perceptions of the guidelines, and concerns about cost were most frequently discussed as the main factors affecting utilization of germline genetic evaluation.ConclusionsThere are currently numerous barriers to implementation of germline genetic evaluation for PCa. Efforts to expand physician education, to develop tools to enhance genetics in practice, and to facilitate coordination of care surrounding genetic evaluation are important to promote guideline‐concordant care.
Augmented Lagrangian method for spin‐coupled wave function
Authors: Sumita Masato , Yoshikawa Naruki 
Published: May 2021

AbstractWe applied augmented Lagrangian method coupled with derivative‐free methods to optimize molecular wave function based on non‐orthogonal orbitals, that is called spin‐coupled generalized valence bond (SCGVB), for its ground‐state energy. In contrast to the orthogonal‐orbital‐based electronic structure theory, the SCGVB includes spin eigenfunctions to satisfy the eigenstates as the operator of the square of the spin. To obtain the ground‐state energy of SCGVB, therefore, it is necessary to optimize the orbital and the spin‐coupling coefficients simultaneously. In this study, we validated feasibility of the derivative‐free augmented Lagrangian method for optimizing the spin‐coupling and the orbital coefficients with the constraint of normality of the wave function. We employed this SCGVB method to compute dissociative potential energy curves (PECs) of H2, , , and LiH. The obtained PECs by the SCGVB method are close to these by full configuration interaction theory. These results indicate that the augmented Lagrangian method is effective to optimize the wave function of SCGVB.
Analysis of vaginal and endometrial microbiota communities in infertile women with a history of repeated implantation failure
Authors: Ichiyama Takuhiko , Kuroda Keiji , Nagai Yoko , Urushiyama Daichi , Ohno Motoharu , Yamaguchi Takashi , Nagayoshi Motoi , Sakuraba Yoshiyuki , Yamasaki Fumio , Hata Kenichiro , Miyamoto Shingo , Itakura Atsuo , Takeda Satoru , Tanaka Atsushi 
Published: May 2021

AbstractPurposeTo identify specific bacterial communities in vaginal and endometrial microbiotas as biomarkers of implantation failure by comprehensively analyzing their microbiotas using next‐generation sequencing.MethodsWe investigated α‐ and β‐diversities of vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared their profiles between 145 women with repeated implantation failure (RIF) and 21 controls who lacked the factors responsible for implantation failure with a high probability of being healthy and fertile to identify specific bacteria that induce implantation failure.ResultsThe endometrial microbiotas had higher α‐diversities than did the vaginal microbiotas (P < .001). The microbiota profiles showed that vaginal and endometrial samples in RIF patients had significantly higher levels of 5 and 14 bacterial genera, respectively, than those in controls. Vaginal Lactobacillus rates in RIF patients were significantly lower at 76.4 ± 38.9% compared with those of the controls at 91.8 ± 22.7% (P = .018), but endometrial Lactobacillus rates did not significantly differ between the RIF patients and controls (56.2 ± 36.4% and 58.8 ± 37.0%, respectively, P = .79).ConclusionsImpaired microbiota communities containing specific bacteria in both the endometrium and vagina were associated with implantation failure. The vaginal Lactobacillus rates, but not the endometrial, may be a biomarker for RIF.
Nanoscale FasL Organization on DNA Origami to Decipher Apoptosis Signal Activation in Cells
Authors: Berger Ricarda M. L. , Weck Johann M. , Kempe Simon M. , Hill Oliver , Liedl Tim , Rädler Joachim O. , Monzel Cornelia , Heuer‐Jungemann Amelie 
Published: May 2021

AbstractCell signaling is initiated by characteristic protein patterns in the plasma membrane, but tools to decipher their molecular organization and activation are hitherto lacking. Among the well‐known signaling pattern is the death inducing signaling complex with a predicted hexagonal receptor architecture. To probe this architecture, DNA origami‐based nanoagents with nanometer precise arrangements of the death receptor ligand FasL are introduced and presented to cells. Mimicking different receptor geometries, these nanoagents act as signaling platforms inducing fastest time‐to‐death kinetics for hexagonal FasL arrangements with 10 nm inter‐molecular spacing. Compared to naturally occurring soluble FasL, this trigger is faster and 100× more efficient. Nanoagents with different spacing, lower FasL number or higher coupling flexibility impede signaling. The results present DNA origami as versatile signaling scaffolds exhibiting unprecedented control over molecular number and geometry. They define molecular benchmarks in apoptosis signal initiation and constitute a new strategy to drive particular cell responses.
Architecture violations detection and visualization in the continuous integration pipeline
Authors: Mendoza Camilo , Bocanegra José , Garcés Kelly , Casallas Rubby 
Published: May 2021

AbstractNew code in projects can introduce violations that deviate the code implementation from the intended architecture. This process is known as architecture erosion. In this article, we propose an approach for recovering the implemented architecture, and detecting violations when comparing it with the intended architecture. Given a code repository, the continuous integration pipeline calls the solution to detect the incidences of architecture violations as well as some quality and social metrics. This data is presented in metric‐centered views that help development teams to manage architecture erosion. Our approach is based on model‐driven engineering techniques since models serve to represent the code, and a model‐based pattern language helps us to automate the search for violation occurrences and execute corresponding actions (e.g., creation/assignment of issues). We confirm the approach benefits in a real project implemented by a software developing company, in a sample project available on the internet, and in a software development course, including 20 projects, where every single project decreases its architecture violations density through time.
The potential of trans‐local policy networks for contributing to sustainable food systems—The Dutch City Deal: Food on the Urban Agenda
Authors: Sibbing Lara , Candel Jeroen , Termeer Katrien 
Published: May 2021

AbstractTo foster more sustainable food systems, collaboration between local governments for knowledge exchange and cooperation is essential. Trans‐local food policy networks potentially serve this purpose but their functioning and outcomes remain largely unexplored. We address this gap by analyzing collaboration and its outcomes for one of the first trans‐local food policy networks in the Netherlands: City Deal: Food on the Urban Agenda. We use Ansell and Gash's collaborative governance model as an ideal type to analyze the City Deal drawing on two rounds of semi‐structured interviews with civil servants and politicians in 2016 and 2019 resulting in a total of 37 interviews with 49 unique respondents. The collaborative process was a continuous searching and negotiating for roles, goals, and activities, on the one hand, combined with great eagerness among participants to collaborate and improve local food systems on the other. Although this process led to collective identity building and learning, it resulted in limited collaborative action between participants or tangible results on the ground. The main outcomes were the active network itself, which fostered the strengthening of connections, exchanging knowledge, learning, and agenda setting. Based on our findings, we identify five key points of attention for successful food policy collaboration: ensuring stakeholder commitment, striking a balance between a sectoral and holistic focus, avoiding too abstract ambitions, fostering interdependence, and investing in political commitment.
Antimicrobial use in poultry flocks in Austria between 2013 and 2019
Authors: Griesbacher Antonia , Schließnig Harald , Weber Stefan , Fuchs Klemens 
Published: May 2021

AbstractBackground: The increase in bacteria that are resistant to antimicrobials—often selected for a high level of antimicrobial uses (AMUs) in human beings or food‐producing animals—is a global concern. The Austrian Poultry Health Service (QGV) has established a database containing comprehensive information on poultry flocks in Austria.Methods: AMU in 32,411 broiler flocks and 2946 turkey flocks between 2013 and 2019 is analysed by calculating different metrics, including the treatment incidence TI1000. Furthermore, the Austrian benchmarking system for poultry is introduced.Results: Annual AMU in broilers decreased from 1030.8 kg of active ingredient to 762.5 kg between 2013 and 2016 but rose again to 1165.0 kg in 2019; while for turkeys annual AMU dropped from 1196.4 kg to 569.0 kg between 2013 and 2019. At the same time, the proportion of treated flocks decreased from 34.2% to 24.8% for broilers and from 54.3% to 44.0% for turkeys. In both broilers and turkeys, the most frequently used antimicrobial class, according to the TI1000 unit, in broilers and turkeys is polymyxins.Conclusion: Calculating different metrics enables a deeper insight into AMU. Total AMU reduced without legislation but the increase of AMU in broiler production needs further investigation.
Imaging features of unilateral renal T‐cell lymphoma occurring simultaneously in the urinary bladder wall and contralateral ureter with secondary polycythaemia in a dog
Authors: Soler Marta , García‐Martinez Juan , Barge Pablo , Belda Eliseo , Agut Amalia 
Published: May 2021

AbstractA six‐year‐old neutered male Labrador Retriever was presented with haematuria and inappetence of one‐week duration. Physical examination revealed mild abdominal pain and the blood cell count showed moderate polycythaemia, with a slight increase of the erythropoietin levels. Urinalysis demonstrated proteinuria, haematuria and isosthenuria and urinary sediment revealed mild amount of lymphoid cells. After performing a complete imaging study (radiographs, ultrasound and CT scan), a unilateral renal lymphoma with secondary extranodal lymphoma of the urinary tract (bladder wall and left ureter) was suspected. Fine‐needle aspirates of both kidneys, ureter and bladder masses were obtained, and a tentative diagnosis of lymphoma was made. Positive PCR antigen receptor rearrangement indicated a T‐cell origin. The owners opted for euthanasia and declined necropsy. CT was essential for the evaluation of this case – it not only depicted renal lesions, but also identified accurately extension to adjacent anatomic structures helping to determine the systemic spread of the disease.
Combination therapy with mycophenolate mofetil and prednisone for exfoliative cutaneous lupus erythematosus in a German shorthaired pointer dog
Authors: Eberhardy Aurrielle , Heinrich Nicole , McFadden Rendina , Reiter Lisa 
Published: May 2021

AbstractExfoliative cutaneous lupus erythematosus (ECLE) of the German shorthaired pointer dog is an autoimmune disease characterized by generalized scaling, crusting, follicular casting and incomplete alopecia affecting the head, trunk, and limbs. Affected dogs often develop arthralgia and peripheral lymphadenopathy. Diagnosis is achieved with history, signalment, physical exam, skin biopsies, and genetic analysis. ECLE is often refractory to commonly used immunosuppressant therapies, and reliable treatment protocols have not been established. This case report describes successful treatment of ECLE with a combination of mycophenolate mofetil and prednisone.
Notfälle in der Augenheilkunde: Vermittlung anhand interaktiver Key-feature-Fälle für Medizinstudierende
Authors: Müller Andreas , Wagner Felix M. , Schuster Alexander K. , Günal Betül , Pfeiffer Norbert , Schmidt Franziska , Prokosch Verena 
Published: May 2021

Zusammenfassung
Hintergrund
Wichtiges Ziel eines Curriculums für Medizinstudierende ist, die Fähigkeit zum selbstständigen Erkennen und Einordnen von Notfällen zu vermitteln. Die Augenheilkunde steht hierbei aufgrund fachspezifischer „red flags“, also Warnsymptomen und -zeichen, vor der Herausforderung, dass solche selten von anderen Organsystemen hierauf übertragen werden können. Um Medizinstudierende dabei zu fördern, die „red flags“ der Augenheilkunde in ihrer späteren Tätigkeit zu erkennen, entwickelten wir für unser eLearning-Angebot leitsymptomorientierte interaktive Fallvignetten.

Material und Methoden
Es wurden 7 interaktive Fallvignetten zu potenziell bedrohlichen ophthalmologischen Symptomen und Zeichen wie „schmerzloser Visusverlust“ oder „rotes Auge“ entwickelt. Hierbei werden Studierende mit Bild und Text durch einen Fall geführt und zu entscheidenden Aspekten („key features“) mit verschiedenen Frageformaten geprüft. Die interaktiven Fälle wurden mithilfe von eLearning-Authoring-Software umgesetzt und als Lernmodule in der Learning-Management-Präsenz der Augenklinik integriert. Die Patientenfälle waren Teil unseres Praktikums der Augenheilkunde. Die Fälle wurden im Anschluss von den Studierenden evaluiert.

Ergebnisse
Die Fälle wurden im Mittel mit einer Note von 1,51 ± 0,68 (Mittelwert ± Standardabweichung) bewertet (n = 163). Auf einer Likert-Skala wurden sie mit 1,60 ± 0,81 als hilfreich für das eigene Lernen empfunden (1 = sehr hilfreich, 7 = gar nicht hilfreich; n = 164). Die Informationsmenge und Auswahl der Szenarien wurden ebenfalls positiv evaluiert.

Diskussion
Um Studierenden im engen zeitlichen Rahmen eines Kurses mehr Sicherheit im Erkennen und der primären Versorgung von augenärztlichen Notfällen verschaffen zu können, können praxisorientierte Key-feature-Fälle Bestandteil eines eLearning-Angebotes sein.
Barriers to successful dichoptic treatment for amblyopia in young children
Authors: Kadhum Aveen , Tan Emily T. C. , Levi Dennis M. , Colpa Linda , Fronius Maria , Simonsz Huibert J. , Loudon Sjoukje E. 
Published: May 2021

Abstract
Purpose
In an ongoing randomised clinical trial comparing dichoptic VR video games with patching for amblyopia, we evaluated any potential barriers to successful use of this novel amblyopia treatment method.

Methods
From December 2017, all newly diagnosed amblyopic children were recruited. Excluded were children under age 4 and patients with strabismus exceeding 30PD. The video game was played for 1 h per week at the outpatient clinic under direct supervision. Records were kept of difficulties encountered during treatment and categorised into domains. Factors influencing the successful completion of this treatment were identified and related to patient characteristics.

Results
Ninety-one children were recruited for the trial, 20 parents refused participation before randomisation, because of the logistical challenges the outpatient dichoptic treatment would cause them. Of the 17 children who commenced dichoptic treatment (median age 6.2 years; IQR 4.9–8.4 years), 10 did not complete treatment. Children under age 5.5 years were unable to comprehend the game settings or the game itself. Older children (N = 7; 41%) were less willing to comply with the video game. Loss of interest in the game (N = 8; 47%) was found to be a limiting factor at all ages.

Conclusion
Half of the children failed to complete VR dichoptic treatment, mainly due to young age. In countries with nationwide screening where amblyopia is detected before age 6, the applicability of such dichoptic treatment is limited.
Formal semantics and high performance in declarative machine learning using Datalog
Authors: Wang Jin , Wu Jiacheng , Li Mingda , Gu Jiaqi , Das Ariyam , Zaniolo Carlo 
Published: May 2021

AbstractWith an escalating arms race to adopt machine learning (ML) in diverse application domains, there is an urgent need to support declarative machine learning over distributed data platforms. Toward this goal, a new framework is needed where users can specify ML tasks in a manner where programming is decoupled from the underlying algorithmic and system concerns. In this paper, we argue that declarative abstractions based on Datalog are natural fits for machine learning and propose a purely declarative ML framework with a Datalog query interface. We show that using aggregates in recursive Datalog programs entails a concise expression of ML applications, while providing a strictly declarative formal semantics. This is achieved by introducing simple conditions under which the semantics of recursive programs is guaranteed to be equivalent to that of aggregate-stratified ones. We further provide specialized compilation and planning techniques for semi-naive fixpoint computation in the presence of aggregates and optimization strategies that are effective on diverse recursive programs and distributed data platforms. To test and demonstrate these research advances, we have developed a powerful and user-friendly system on top of Apache Spark. Extensive evaluations on large-scale datasets illustrate that this approach will achieve promising performance gains while improving both programming flexibility and ease of development and deployment for ML applications.
Highly parallelized human embryonic stem cell differentiation to cardiac mesoderm in nanoliter chambers on a microfluidic chip
Authors: Vollertsen Anke R. , Den Simone A. ten , Schwach Verena , van den Berg Albert , Passier Robert , van der Meer Andries D. , Odijk Mathieu 
Published: May 2021

AbstractHuman stem cell-derived cells and tissues hold considerable potential for applications in regenerative medicine, disease modeling and drug discovery. The generation, culture and differentiation of stem cells in low-volume, automated and parallelized microfluidic chips hold great promise to accelerate the research in this domain. Here, we show that we can differentiate human embryonic stem cells (hESCs) to early cardiac mesodermal cells in microfluidic chambers that have a volume of only 30 nanoliters, using discontinuous medium perfusion. 64 of these chambers were parallelized on a chip which contained integrated valves to spatiotemporally isolate the chambers and automate cell culture medium exchanges. To confirm cell pluripotency, we tracked hESC proliferation and immunostained the cells for pluripotency markers SOX2 and OCT3/4. During differentiation, we investigated the effect of different medium perfusion frequencies on cell reorganization and the expression of the early cardiac mesoderm reporter MESP1mCherry by live-cell imaging. Our study demonstrates that microfluidic technology can be used to automatically culture, differentiate and study hESC in very low-volume culture chambers even without continuous medium perfusion. This result is an important step towards further automation and parallelization in stem cell technology.
Diesel exhaust exposure alters the expression of networks implicated in neurodegeneration in zebrafish brains
Authors: Jami M. Saeid , Murata Hiromi , Barnhill Lisa M. , Li Sharon , Bronstein Jeff M. 
Published: May 2021

AbstractNeurodegenerative diseases are a major cause of disability in the world, but their etiologies largely remain elusive. Genetic factors can only account for a minority of risk for most of these disorders, suggesting environmental factors play a significant role in the development of these diseases. Prolonged exposure to air pollution has recently been identified to increase the risk of Alzheimer’s and Parkinson’s diseases, but the molecular mechanisms by which it acts are not well understood. Zebrafish embryos exposed to diesel exhaust particle extract (DEPe) lead to dysfunctional autophagy and neuronal loss. Here, we exposed zebrafish embryos to DEPe and performed high throughput proteomic and transcriptomic expression analyses from their brains to identify pathogenic pathways induced by air pollution. DEPe treatment altered several biological processes and signaling pathways relevant to neurodegenerative processes, including xenobiotic metabolism, phagosome maturation, and amyloid processing. The biggest induction of gene expression in brains was in Cyp1A (over 30-fold). The relevance of this expression change was confirmed by blocking induction using CRISPR/Cas9, which resulted in a dramatic increase in sensitivity to DEPe toxicity, confirming that Cyp1A induction was a compensatory protective mechanism. These studies identified disrupted molecular pathways that may contribute to the pathogenesis of neurodegenerative disorders. Ultimately, determining the molecular basis of how air pollution increases the risk of neurodegeneration will help in the development of disease-modifying therapies.
Graphical abstract
How patients being treated for non-small cell lung cancer value treatment benefit despite side effects
Authors: Martin Mona L. , Correll Julia , Walding Andrew , Rydén Anna 
Published: May 2021

Abstract
Purpose
To describe symptoms and side effects experienced by patients with advanced non-small cell lung cancer (NSCLC), assess how patients allocate sensations (i.e. symptoms or side effects) to either the disease or its treatment, and evaluate how patients balance side effects with treatment benefits.

Methods
Qualitative sub-studies were conducted as part of two clinical trials in patients treated for advanced NSCLC (AURA [NCT01802632]; ARCTIC [NCT02352948]).

Results
Interviews were conducted with 23 patients and 19 patients in the AURA and ARCTIC sub-studies, respectively. The most commonly experienced symptoms/side effects were respiratory (81% of patients), digestive (76%), pain and discomfort (76%), energy-related (71%), and sensory (62%). Patients identified a sensation as a treatment side effect if they had not experienced it before, if there was a temporal link between the sensation and receipt of treatment, and/or if their doctors consistently told or asked them about it in relation to side effects. Themes that emerged when patients talked about their cancer treatment and its side effects related to the serious nature of their advanced disease and their treatment expectations. Patients focused on treatment benefits, wanting a better quality of life, being hopeful, not really having a choice, and not thinking about side effects.

Conclusions
In these two qualitative sub-studies, patients with advanced NSCLC valued the benefits of their treatment regardless of side effects that they experienced. Patients weighed their options against the seriousness of their disease and expressed their willingness to tolerate their side effects in return for receiving continued treatment benefits.