bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enabling visibility of the clinician-scientists’ knowledge broker role: a participatory design research in the Dutch nursing-home sector
Authors: Barry Margot , Kuijer Wietske , Persoon Anke , Nieuwenhuis Loek , Scherpbier Nynke 
Published: April 2021

Abstract
Background
A group of clinician-scientists and managers working within a Dutch academic network, experienced difficulties in clearly defining the knowledge broker role of the clinician-scientists. They found no role clarity in literature, nor did they find tools or methods suitable for clinician-scientists. Clarifying role expectations and providing accountability for funding these knowledge broker positions was difficult. The aim of this research was to design a theory-informed tool that allowed clinician-scientists to make their knowledge broker role visible.

Methods
A participatory design research was conducted in three phases, over a 21-month period, with a design group consisting of an external independent researcher, clinician-scientists and their managers from within the academic network. Phase 1 constituted a literature review, a context analysis and a needs analysis. Phase 2 constituted the design and development of a suitable tool and phase 3 was an evaluation of the tool’s perceived usefulness. Throughout the research process, the researcher logged the theoretic basis for all design decisions.

Results
The clinician-scientist’s knowledge broker role is a knowledge-intensive role and work-tasks associated with this role are not automatically visible (phase 1). A tool (the SP-tool) was developed in Microsoft Excel. This allowed clinician-scientists to log their knowledge broker activities as distinct from their clinical work and research related activities (phase 2). The SP-tool contributed to the clinician-scientists’ ability to make their knowledge broker role visible to themselves and their stakeholders (phase 3). The theoretic contribution of the design research is a conceptual model of professionalisation of the clinician-scientist’s knowledge broker role. This model presents the relationship between work visibility and the clarification of functions of the knowledge broker role. In the professionalisation of knowledge-intensive work, visibility contributes to the definition of clinician-scientists broker functions, which is an element necessary for the professionalisation of an occupation.

Conclusions
The SP-tool that was developed in this research, contributes to creating work visibility of the clinician-scientists’ knowledge broker role. Further research using the SP-tool could establish a clearer description of the knowledge broker role at the day-to-day professional level and improved ability to support this role within organisations.
The “Great Debate” at Immunotherapy Bridge 2020, December 3rd, 2020
Authors: Ascierto Paolo A. , Brody Joshua , Butterfield Lisa H. , Finn Olivera J. , Goldberg John , Perrone Francesco , Sullivan Ryan J. , Fox Bernard A. , Hwu Patrick , Puzanov Igor 
Published: April 2021

AbstractAs part of the 2020 Immunotherapy Bridge virtual congress (December 2nd–3rd, Italy), the Great Debate session featured counterpoint views from leading experts on three clinical questions in immunotherapy today. The first of these was whether antitumoral vaccination is still a treatment option. The second topic debated whether anti-programmed death (PD)-1/PD-ligand (L)1 blockade should be the backbone for immunotherapy combination. Finally, the use of innovative study designs and surrogate endpoints was considered from both an academic and industry perspective. For each topic, two experts presented the argument and counter-argument in support of two different points of view. As with previous Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their respective personal view. The views summarised in this article are based on available evidence but may reflect personal interpretation of these data, clinical experience and subjective opinion of the speaker.
Clinical validation of a commercially available deep learning software for synthetic CT generation for brain
Authors: Lerner Minna , Medin Joakim , Jamtheim Gustafsson Christian , Alkner Sara , Siversson Carl , Olsson Lars E. 
Published: April 2021

Abstract
Background
Most studies on synthetic computed tomography (sCT) generation for brain rely on in-house developed methods. They often focus on performance rather than clinical feasibility. Therefore, the aim of this work was to validate sCT images generated using a commercially available software, based on a convolutional neural network (CNN) algorithm, to enable MRI-only treatment planning for the brain in a clinical setting.

Methods
This prospective study included 20 patients with brain malignancies of which 14 had areas of resected skull bone due to surgery. A Dixon magnetic resonance (MR) acquisition sequence for sCT generation was added to the clinical brain MR-protocol. The corresponding sCT images were provided by the software MRI Planner (Spectronic Medical AB, Sweden). sCT images were rigidly registered and resampled to CT for each patient. Treatment plans were optimized on CT and recalculated on sCT images for evaluation of dosimetric and geometric endpoints. Further analysis was also performed for the post-surgical cases. Clinical robustness in patient setup verification was assessed by rigidly registering cone beam CT (CBCT) to sCT and CT images, respectively.

Results
All sCT images were successfully generated. Areas of bone resection due to surgery were accurately depicted. Mean absolute error of the sCT images within the body contour for all patients was 62.2 ± 4.1 HU. Average absorbed dose differences were below 0.2% for parameters evaluated for both targets and organs at risk. Mean pass rate of global gamma (1%/1 mm) for all patients was 100.0 ± 0.0% within PTV and 99.1 ± 0.6% for the full dose distribution. No clinically relevant deviations were found in the CBCT-sCT vs CBCT-CT image registrations. In addition, mean values of voxel-wise patient specific geometric distortion in the Dixon images for sCT generation were below 0.1 mm for soft tissue, and below 0.2 mm for air and bone.

Conclusions
This work successfully validated a commercially available CNN-based software for sCT generation. Results were comparable for sCT and CT images in both dosimetric and geometric evaluation, for both patients with and without anatomical anomalies. Thus, MRI Planner is feasible to use for radiotherapy treatment planning of brain tumours.
Pulmonary infection after cardiopulmonary bypass surgery in children: a risk estimation model in China
Authors: Ren Chunnian , Wu Chun , Pan Zhengxia , Wang Quan , Li Yonggang 
Published: April 2021

Abstract
Objectives
The occurrence of pulmonary infection after congenital heart disease (CHD) surgery can lead to significant increases in intensive care in cardiac intensive care unit (CICU) retention time, medical expenses, and risk of death risk. We hypothesized that patients with a high risk of pulmonary infection could be screened out as early after surgery. Hence, we developed and validated the first risk prediction model to verify our hypothesis.

Methods
Patients who underwent CHD surgery from October 2012 to December 2017 in the Children’s Hospital of Chongqing Medical University were included in the development group, while patients who underwent CHD surgery from December 2017 to October 2018 were included in the validation group. The independent risk factors associated with pulmonary infection following CHD surgery were screened using univariable and multivariable logistic regression analyses. The corresponding nomogram prediction model was constructed according to the regression coefficients. Model discrimination was evaluated by the area under the receiver operating characteristic curve (ROC) (AUC), and model calibration was conducted with the Hosmer-Lemeshow test.

Results
The univariate and multivariate logistic regression analyses identified the following six independent risk factors of pulmonary infection after cardiac surgery: age, weight, preoperative hospital stay, risk-adjusted classification for congenital heart surgery (RACHS)-1 score, cardiopulmonary bypass time and intraoperative blood transfusion. We established an individualized prediction model of pulmonary infection following cardiopulmonary bypass surgery for CHD in children. The model displayed accuracy and reliability and was evaluated by discrimination and calibration analyses. The AUCs for the development and validation groups were 0.900 and 0.908, respectively, and the P-values of the calibration tests were 0.999 and 0.452 respectively. Therefore, the predicted probability of the model was consistent with the actual probability.

Conclusions
Identified the independent risk factors of pulmonary infection after cardiopulmonary bypass surgery. An individualized prediction model was developed to evaluate the pulmonary infection of patients after surgery. For high-risk patients, after surgery, targeted interventions can reduce the risk of pulmonary infection.
A framework for the evaluation of patients with congenital facial weakness
Authors: Webb Bryn D. , Manoli Irini , Engle Elizabeth C. , Jabs Ethylin W. 
Published: April 2021

AbstractThere is a broad differential for patients presenting with congenital facial weakness, and initial misdiagnosis unfortunately is common for this phenotypic presentation. Here we present a framework to guide evaluation of patients with congenital facial weakness disorders to enable accurate diagnosis. The core categories of causes of congenital facial weakness include: neurogenic, neuromuscular junction, myopathic, and other. This diagnostic algorithm is presented, and physical exam considerations, additional follow-up studies and/or consultations, and appropriate genetic testing are discussed in detail. This framework should enable clinical geneticists, neurologists, and other rare disease specialists to feel prepared when encountering this patient population and guide diagnosis, genetic counseling, and clinical care.
Economic burden in the management of transfusion-dependent thalassaemia patients in Malaysia from a societal perspective
Authors: Shafie Asrul Akmal , Wong Jacqueline Hui Yi , Ibrahim Hishamshah Mohd , Mohammed Noor Syahireen , Chhabra Irwinder Kaur 
Published: April 2021

AbstractBackgroundTransfusion-dependent thalassaemia (TDT) is a hereditary blood disorder in which blood transfusion is the mainstay treatment to prolong survival and improve quality of life. Patients with this disease require blood transfusion at more than 100 ml/kg annually and iron-chelating therapy (ICT) to prevent iron overload (IOL) complications. There are substantial numbers of TDT patients in Malaysia, but limited data are available regarding the economic burden associated with this disease. The purpose of this study was to determine the lifetime cost of TDT from a societal perspective and identify potential factors increasing patient and family expenditures among thalassaemia populations.MethodsThe total lifetime cost per TDT patient (TC1) is the sum of lifetime healthcare cost (TC2) and lifetime patient and family healthcare expenditure (TC3). TC2 was simulated using the Markov model, taking into account all costs subsidized by the government, and TC3 was estimated through a cross-sectional health survey approach. A survey was performed using a two-stage sampling method in 13 thalassaemia centres covering all regions in Malaysia.ResultsA TDT patient is expected to incur TC2 of USD 561,208. ICT was the main driver of cost and accounted for 56.9% of the total cost followed by blood transfusion cost at 13.1%. TC3 was estimated to be USD 45,458. Therefore, the estimated TC1 of a TDT patient was USD 606,665. Sensitivity analyses showed that if all patients were prescribed oral ICT deferasirox for their lifetime, the total healthcare cost would increase by approximately 65%. Frequency of visits to health facilities for blood transfusion/routine monitoring and patients who were prescribed desferrioxamine were observed to be factors affecting patient and family monthly expenses.ConclusionThe lifetime cost per TDT patient was USD 606,665, and this result may be useful for national health allocation planning. An estimation of the economic burden will provide additional information to decision makers on implementing prevention interventions to reduce the number of new births and medical service reimbursement.
Data silos are undermining drug development and failing rare disease patients
Authors: Denton Nathan , Molloy Monique , Charleston Samantha , Lipset Craig , Hirsch Jonathan , Mulberg Andrew E. , Howard Paul , Marsh Eric D. 
Published: April 2021

AbstractData silos are proliferating while research and development activity explode following genetic and immunological advances for many clinically described disorders with previously unknown etiologies. The latter event has inspired optimism in the patient, clinical, and research communities that disease-specific treatments are on the way. However, we fear the tendency of various stakeholders to balkanize databases in proprietary formats, driven by current economic and academic incentives, will inevitably fragment the expanding knowledge base and undermine current and future research efforts to develop much-needed treatments. The proliferation of proprietary databases, compounded by a paucity of meaningful outcome measures and/or good natural history data, slows our ability to generate scalable solutions to benefit chronically underserved patient populations in ways that would translate to more common diseases. The current research and development landscape sets too many projects up for unnecessary failure, particularly in the rare disease sphere, and does a grave disservice to highly vulnerable patients. This system also encourages the collection of redundant data in uncoordinated parallel studies and registries to ultimately delay or deny potential treatments for ostensibly tractable diseases; it also promotes the waste of precious time, energy, and resources. Groups at the National Institutes of Health and Food and Drug Administration have started programs to address these issues. However, we and many others feel there should be significantly more discussion of how to coordinate and scale registry efforts. Such discourse aims to reduce needless complexity and duplication of efforts, as well as promote a pre-competitive knowledge ecosystem for rare disease drug development that cultivates and accelerates innovation.
Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy
Authors:   ATTRv Collaborators, Magliano Lorenza , Obici Laura , Sforzini Claudia , Mazzeo Anna , Russo Massimo , Cappelli Francesco , Fenu Silvia , Luigetti Marco , Tagliapietra Matteo , Gemelli Chiara , Leonardi Luca , Tozza Stefano , Pradotto Luca Guglielmo , Citarelli Giulia , Mauro Alessandro , Manganelli Fiore , Antonini Giovanni , Grandis Marina , Fabrizi Gian Maria , Sabatelli Mario , Pareyson Davide , Perfetto Federico , Merlini Giampaolo , Vita Giuseppe 
Published: April 2021

Abstract
Background
Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient’s functional autonomy negatively affects the patient’s quality of life and requires increasing involvement of relatives in the patient’s daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients’ and relatives’ socio-demographic variables, patients’ clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives.

Methods
The study was carried out on symptomatic patients included in the ATTRv Italian national registry and living with at least one adult relative not suffering from severe illness and being free from ATTRv symptoms. Patients and relatives’ assessments were performed using validated self-reported tools.

Results
Overall, 141 patients and 69 relatives were evaluated. Constraints of leisure activities, feelings of loss and worries for the future were the consequences of ATTRv most frequently reported by patients and relatives. Both in patients and their relatives, the burden increased with the duration of symptoms and the level of help in daily activities needed by the patient. In the 69 matched patient-relative pairs, the practical burden was significantly higher among the patients than among their relatives, while the psychological burden was similar in the two groups. Moreover, compared to their relatives, patients with ATTRv reported higher levels of professional and social network support.

Conclusions
These results show that ATTRv is a disease affecting quality of life of both patients and their families. Supporting interventions should be guaranteed to patients, to facilitate their adaptation to the disease, and to their families, to cope as best as possible with the difficulties that this pathology may involve.
Mapping geographical areas at risk for tick-borne encephalitis (TBE) by analysing bulk tank milk from Swedish dairy cattle herds for the presence of TBE virus–specific antibodies
Authors: Blomqvist Gunilla , Näslund Katarina , Svensson Linda , Beck Cécile , Valarcher Jean Francois 
Published: April 2021

Abstract
Background
The vector-borne human viral zoonosis tick-borne encephalitis (TBE) is of growing concern in Sweden. The area where TBE is considered endemic has expanded, with an increasing geographical distribution of Ixodes ricinus as the tick vector and a rising number of reported TBE cases in humans. Efforts to map TBE risk areas have been carried out by sentinel monitoring, mainly based on individual sampling and analysis of wild and domestic animals, as well as ticks, for tick-borne encephalitis virus (TBEV). However, the interpretation of the geographical distribution has been hampered by the patchy and focal nature of TBEV occurrence. This study presents TBEV surveillance data based on antibody analysis of bulk tank milk collected from dairy herds located throughout Sweden before (May) and after (November) the vector season. A commercial TBEV antibody ELISA was modified and evaluated for use in this study.

Results
The initial comparative TBEV antibody analysis revealed a good correlation between milk and serum antibody levels from individually sampled cows. Also, the TBEV-antibody levels for the mean-herd serum showed good comparability with TBEV antibody levels from bulk tank milk, thus indicating good predictability of seroprevalence when analysing bulk tank milk from a herd.
Analyses of bulk tank milk samples collected from 616 herds in May and 560 herds in November showed a geographical distribution of TBEV seropositive herds that was largely consistent with reported human TBE cases. A few TBEV-reactive herds were also found outside known locations of human TBE cases.

Conclusion
Serological examination of bulk tank milk from dairy cattle herds may be a useful sentinel surveillance method to identify geographical presence of TBEV. In contrast to individual sampling this method allows a large number of animals to be monitored. TBEV seropositive herds were mainly found in coastal areas of southern Sweden similar to human TBE cases. However, some antibody-reactive herds were found outside known TBE areas at the time of the study.
Working short and working long: can primary healthcare be protected as a public good in Lebanon today?
Authors: Hamadeh Randa Sami , Kdouh Ola , Hammoud Rawan , Leresche Enrica , Leaning Jennifer 
Published: April 2021

AbstractIn this commentary we propose four questions to be addressed while building a meaningful public primary healthcare response in Lebanon today. These questions emerge from two imperatives: the necessity to consider both short- and longer-term struggles in a context of protracted conflict and the need to protect public health as a public good whilst the public Primary Healthcare Network (PHCN) is facing the Covid19 pandemic. In order to identify how these questions are related to the need to be working short and long, we look at the imprints left by past and present shocks. Profound shocks of the past include the Lebanese civil war and the Syrian refugee crisis. We analyse how these shocks have resulted in the PHCN developing resilience mechanisms in order to ensure a space for healthcare provision that stands public in Lebanon today. Then, we consider how two present shocks -- the economic breakdown and the blast of ammonium nitrate in Beirut port -- are affecting and threatening the progress made by the PHCN to ensure that primary healthcare remains a public good, a fragile space acquired with difficulty in the past half century. We identify what questions emerge from the combined consequences of such traumas, when the immediate constraints of the present meet the impediments of the past. We consider what such questions mean more broadly, for the people living in Lebanon today, and for the PHCN ability to respond to the Covid 19 pandemic in a relevant way. Our hypothesis is that in a protracted conflict, such as the one defining the circumstances of Lebanon now, public access to primary healthcare might persist for the people as one safeguard, in which social and moral continuity can be anchored to protect a sense of public good.
Targeting neddylation E2s: a novel therapeutic strategy in cancer
Authors: Zheng Yi-Chao , Guo Yan-Jia , Wang Bo , Wang Chong , Mamun M. A. A. , Gao Ya , Liu Hong-Min 
Published: April 2021

AbstractUbiquitin-conjugating enzyme E2 M (UBE2M) and ubiquitin-conjugating enzyme E2 F (UBE2F) are the two NEDD8-conjugating enzymes of the neddylation pathway that take part in posttranslational modification and change the activity of target proteins. The activity of E2 enzymes requires both a 26-residue N-terminal docking peptide and a conserved E2 catalytic core domain, which is the basis for the transfer of neural precursor cell-expressed developmentally downregulated 8 (NEDD8). By recruiting E3 ligases and targeting cullin and non-cullin substrates, UBE2M and UBE2F play diverse biological roles. Currently, there are several inhibitors that target the UBE2M-defective in cullin neddylation protein 1 (DCN1) interaction to treat cancer. As described above, this review provides insights into the mechanism of UBE2M and UBE2F and emphasizes these two E2 enzymes as appealing therapeutic targets for the treatment of cancers.