bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of soft skills development in a hard data world: learning from interviews with healthcare leaders
Authors: Abraham Traci H. , Stewart Greg L. , Solimeo Samantha L. 
Published: March 2021

Abstract
Background
Learning healthcare systems have invested heavily in training primary care staff to provide care using patient-centered medical home models, but less is known about how to effectively lead such teams to deliver high quality care. Research is needed to better understand which healthcare leadership skills are most utilized or in need of development through additional training.

Method
Semi-structured telephone interviews with healthcare leaders familiar with Patient-Aligned Care Teams (PACT) implementation in the U.S. Department of Veterans Affairs (VA). We interviewed sixteen (N = 16) physician, nursing, and administrative leaders at VA facilities located in the upper Midwestern United States. Content analysis of interviews transcripts using template techniques.

Results
Participants described instrumental challenges that they perceived hindered leadership effectiveness, including the supervisory structure; pace of change; complexity of the clinical data infrastructure; an over-reliance on technology for communication; and gaps in available leadership training. Factors perceived as facilitating effective leadership included training in soft skills, face-to-face communication, and opportunities for formal training and mentorship. A cross-cutting theme was the importance of developing “soft skills” for effective PACT leadership.

Conclusions
Although formal leadership training and development were perceived as beneficial, healthcare leaders familiar with PACT implementation in the VA described a mismatch between the skills and knowledge PACT leaders need to succeed and the training available to them. Closing this gap could improve retention of skilled and knowledgeable healthcare leaders, thereby reducing the costs associated with training and leading to improvements in healthcare delivery.
Vector incrimination and transmission of avian malaria at an aquarium in Japan: mismatch in parasite composition between mosquitoes and penguins
Authors: Inumaru Mizue , Yamada Atsushi , Shimizu Misa , Ono Ayana , Horinouchi Makiko , Shimamoto Tatsuki , Tsuda Yoshio , Murata Koichi , Sato Yukita 
Published: March 2021

Abstract
Background
Captive populations of penguins outside of their natural distributions are often maintained in outdoor facilities, such as zoos and aquariums. Consequently, such penguins in captivity are constantly exposed to mosquito vectors and risk of avian malarial infection during their active period from spring to autumn, which can be lethal to these naïve birds. Previous studies have investigated parasite prevalence in mosquitoes or penguins, but simultaneous investigations, which would be crucial to monitor the transmission dynamics and cycle within a facility, have not been done. To identify dominant lineages and trends, multiple-year surveys are recommended.

Methods
Avian malaria parasites (Plasmodium spp.) and related haemosporidia were tested in penguins and mosquitoes at an aquarium in Japan through multiple years from 2011 to 2018. Prevalence and dynamics were confirmed, and molecular analyses targeting the protozoal cytb gene were used to reveal the transmission cycle. Blood meals of mosquitoes were also identified using molecular methods.

Results
Parasite detection in penguins tended to fluctuate within an individual. Two Plasmodium lineages were consistently detected in mosquitoes that had fed on penguins and wild birds observed around the aquarium. Plasmodium lineage CXPIP09 was detected from both mosquitoes and penguins, suggesting active transmission at this facility. However, Plasmodium cathemerium PADOM02 was only detected in mosquitoes, which may be due to host, vector or parasite-related factors, or detection methods and their limits. Additionally, Haemoproteus larae SPMAG12 was detected from penguins, suggesting active transmission via biting midges.

Conclusions
The mismatch in parasite composition between penguins and mosquitoes shows that multiple aspects such as captive birds, wild birds and vector insects should be monitored in order to better understand and control avian malarial infection within ex-situ conservation facilities. Furthermore, morphological analyses would be needed to confirm competency and infection dynamics of avian malaria parasites.
27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial
Authors: Sandebring-Matton Anna , Goikolea Julen , Björkhem Ingemar , Paternain Laura , Kemppainen Nina , Laatikainen Tiina , Ngandu Tiia , Rinne Juha , Soininen Hilkka , Cedazo-Minguez Angel , Solomon Alina , Kivipelto Miia 
Published: March 2021

Abstract
Background
27-Hydroxycholesterol (27-OH), the main circulating oxysterol in humans and the potential missing link between peripheral hypercholesterolemia and Alzheimer’s disease (AD), has not been investigated previously in relation to cognition and neuroimaging markers in the context of preventive interventions.

Methods
The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older individuals (60–77 years) at increased risk for dementia but without dementia or substantial cognitive impairment from the general population. Participants were randomized to a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice) in a 1:1 ratio. Outcome assessors were masked to group allocation. This FINGER exploratory sub-study included 47 participants with measures of 27-OH, cognition, brain MRI, brain FDG-PET, and PiB-PET. Linear regression models were used to assess the cross-sectional and longitudinal associations between 27-OH, cognition, and neuroimaging markers, considering several potential confounders/intervention effect modifiers.

Results
27-OH reduction during the intervention was associated with improvement in cognition (especially memory). This was not observed in the control group. The intervention reduced 27-OH particularly in individuals with the highest 27-OH levels and younger age. No associations were found between changes in 27-OH levels and neuroimaging markers. However, at baseline, a higher 27-OH was associated with lower total gray matter and hippocampal volume, and lower cognitive scores. These associations were unaffected by total cholesterol levels. While sex seemed to influence associations at baseline, it did not affect longitudinal associations.

Conclusion
27-OH appears to be a marker not only for dementia/AD risk, but also for monitoring the effects of preventive interventions on cholesterol metabolism.

Trial registration
ClinicalTrials.gov, NCT01041989. Registered on 4 January 2010
Hippocampal neurons isolated from rats subjected to the valproic acid model mimic in vivo synaptic pattern: evidence of neuronal priming during early development in autism spectrum disorders
Authors: Traetta Marianela Evelyn , Codagnone Martín Gabriel , Uccelli Nonthué Alejandra , Ramos Alberto Javier , Zárate Sandra , Reinés Analía 
Published: March 2021

AbstractBackgroundAutism spectrum disorders (ASD) are synaptopathies characterized by area-specific synaptic alterations and neuroinflammation. Structural and adhesive features of hippocampal synapses have been described in the valproic acid (VPA) model. However, neuronal and microglial contribution to hippocampal synaptic pattern and its time-course of appearance is still unknown.MethodsMale pups born from pregnant rats injected at embryonic day 10.5 with VPA (450 mg/kg, i.p.) or saline (control) were used. Maturation, exploratory activity and social interaction were assessed as autistic-like traits. Synaptic, cell adhesion and microglial markers were evaluated in the CA3 hippocampal region at postnatal day (PND) 3 and 35. Primary cultures of hippocampal neurons from control and VPA animals were used to study synaptic features and glutamate-induced structural remodeling. Basal and stimuli-mediated reactivity was assessed on microglia primary cultures isolated from control and VPA animals.ResultsAt PND3, before VPA behavioral deficits were evident, synaptophysin immunoreactivity and the balance between the neuronal cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) were preserved in the hippocampus of VPA animals along with the absence of microgliosis. At PND35, concomitantly with the establishment of behavioral deficits, the hippocampus of VPA rats showed fewer excitatory synapses and increased NCAM/PSA-NCAM balance without microgliosis. Hippocampal neurons from VPA animals in culture exhibited a preserved synaptic puncta number at the beginning of the synaptogenic period in vitro but showed fewer excitatory synapses as well as increased NCAM/PSA-NCAM balance and resistance to glutamate-induced structural synaptic remodeling after active synaptogenesis. Microglial cells isolated from VPA animals and cultured in the absence of neurons showed similar basal and stimuli-induced reactivity to the control group. Results indicate that in the absence of glia, hippocampal neurons from VPA animals mirrored the in vivo synaptic pattern and suggest that while neurons are primed during the prenatal period, hippocampal microglia are not intrinsically altered.ConclusionsOur study suggests microglial role is not determinant for developing neuronal alterations or counteracting neuronal outcome in the hippocampus and highlights the crucial role of hippocampal neurons and structural plasticity in the establishment of the synaptic alterations in the VPA rat model.
Effect of fibronectin, FGF-2, and BMP4 in the stemness maintenance of BMSCs and the metabolic and proteomic cues involved
Authors: Chen Lingling , Carlton Morgan , Chen Xiaodan , Kaur Navdeep , Ryan Hollie , Parker Tony J , Lin Zhengmei , Xiao Yin , Zhou Yinghong 
Published: March 2021

Abstract
Background
Growing evidence suggests that the pluripotent state of mesenchymal stem cells (MSCs) relies on specific local microenvironmental cues such as adhesion molecules and growth factors. Fibronectin (FN), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein 4 (BMP4) are the key players in the regulation of stemness and lineage commitment of MSCs. Therefore, this study was designed to investigate the pluripotency and multilineage differentiation of bone marrow-derived MSCs (BMSCs) with the introduction of FN, FGF-2, and BMP4 and to identify the metabolic and proteomic cues involved in stemness maintenance.

Methods
To elucidate the stemness of BMSCs when treated with FN, FGF-2, and BMP4, the pluripotency markers of OCT4, SOX2, and c-MYC in BMSCs were monitored by real-time PCR and/or western blot. The nuclear translocation of OCT4, SOX2, and c-MYC was investigated by immunofluorescence staining. Multilineage differentiation of the treated BMSCs was determined by relevant differentiation markers. To identify the molecular signatures of BMSC stemness, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and bioinformatics analysis were utilized to determine the metabolite and protein profiles associated with stem cell maintenance.

Results
Our results demonstrated that the expression of stemness markers decreased with BMSC passaging, and the manipulation of the microenvironment with fibronectin and growth factors (FGF2 and BMP4) can significantly improve BMSC stemness. Of note, we revealed 7 differentially expressed metabolites, the target genes of these metabolites may have important implications in the maintenance of BMSCs through their effects on metabolic activity, energy production, and potentially protein production. We also identified 21 differentially abundant proteins, which involved in multiple pathways, including metabolic, autophagy-related, and signaling pathways regulating the pluripotency of stem cells. Additionally, bioinformatics analysis comfirned the correlation between metabolic and proteomic profiling, suggesting that the importance of metabolism and proteome networks and their reciprocal communication in the preservation of stemness.

Conclusions
These results indicate that the culture environment supplemented with the culture cocktail (FN, FGF2, and BMP4) plays an essential role in shaping the pluripotent state of BMSCs. Both the metabolism and proteome networks are involved in this process and the modulation of cell-fate decision making. All these findings may contribute to the application of MSCs for regenerative medicine.
Ability of procalcitonin to distinguish between bacterial and nonbacterial infection in severe acute exacerbation of chronic obstructive pulmonary syndrome in the ICU
Authors:   from the PROCALCIVIR and BPCTrea study group, Daubin Cédric , Fournel François , Thiollière Fabrice , Daviaud Fabrice , Ramakers Michel , Polito Andréa , Flocard Bernard , Valette Xavier , Du Cheyron Damien , Terzi Nicolas , Fartoukh Muriel , Allouche Stephane , Parienti Jean-Jacques 
Published: March 2021

Abstract
Background
To assess the ability of procalcitonin (PCT) to distinguish between bacterial and nonbacterial causes of patients with severe acute exacerbation of COPD (AECOPD) admitted to the ICU, we conducted a retrospective analysis of two prospective studies including 375 patients with severe AECOPD with suspected lower respiratory tract infections. PCT levels were sequentially assessed at the time of inclusion, 6 h after and at day 1, using a sensitive immunoassay. The patients were classified according to the presence of a documented bacterial infection (including bacterial and viral coinfection) (BAC + group), or the absence of a documented bacterial infection (i.e., a documented viral infection alone or absence of a documented pathogen) (BAC- group). The accuracy of PCT levels in predicting bacterial infection (BAC + group) vs no bacterial infection (BAC- group) at different time points was evaluated by receiver operating characteristic (ROC) analysis.

Results
Regarding the entire cohort (n = 375), at any time, the PCT levels significantly differed between groups (Kruskal–Wallis test, p < 0.001). A pairwise comparison showed that PCT levels were significantly higher in patients with bacterial infection (n = 94) than in patients without documented pathogens (n = 218) (p < 0.001). No significant difference was observed between patients with bacterial and viral infection (n = 63). For example, the median PCT-H0 levels were 0.64 ng/ml [0.22–0.87] in the bacterial group vs 0.24 ng/ml [0.15–0.37] in the viral group and 0.16 ng/mL [0.11–0.22] in the group without documented pathogens. With a c-index of 0.64 (95% CI; 0.58–0.71) at H0, 0.64 [95% CI 0.57–0.70] at H6 and 0.63 (95% CI; 0.56–0.69) at H24, PCT had a low accuracy for predicting bacterial infection (BAC + group).

Conclusion
Despite higher PCT levels in severe AECOPD caused by bacterial infection, PCT had a poor accuracy to distinguish between bacterial and nonbacterial infection. Procalcitonin might not be sufficient as a standalone marker for initiating antibiotic treatment in this setting.
Collaborating in a penta-helix structure within a community based participatory research programme: ‘Wrestling with hierarchies and getting caught in isolated downpipes’
Authors: Sjögren Forss Katarina , Kottorp Anders , Rämgård Margareta 
Published: March 2021

AbstractBackgroundIn the light of the existence of social inequalities in health, a CBPR (Community Based Participatory Research) programme for health promotion started in Malmö, Sweden, in 2017. The programme was based on a penta-helix structure and involved a strategic steering group with representatives from academia, voluntary organisations, the business sector, the public sector, and citizens from the community where the programme took place. The aim of this study was to explore how the penta-helix collaboration worked from the perspectives of all partners, including the citizens.MethodsIndividual interviews, that were based on a guide for self-reflection and evaluation of CBPR partnerships, were conducted with the representatives (N = 13) on three occasions, during the period 2017–2019. A qualitative content analysis was used to analyse the interviews.ResultsSix themes emerged from the analysis, including Challenges for the partners in the penta-helix collaboration; Challenges for the professionals at the local level; Citizen-driven processes are important for the penta-helix collaboration; Health promoters are essential to build trust between different sectors of society; Shift of power; and System changes take time. The analysis shows that the penta-helix collaboration worked well at the local level in a governance-related model for penta-helix cooperation. In the overall cooperation it was the citizen-driven processes that made the programme work. However, the findings also indicated an inflexibility in organisations with hierarchical structures that created barriers for citizen involvement in the penta-helix collaboration.ConclusionThe main issue uncovered in this study is the problem of vertically organised institutions where discovery and innovation processes flow down from the top, thereby eliminating the essential input of the people and community that they are supposed to serve. The success of the programme was based on an interprofessional cooperation at a local level, where local professions worked together with voluntary organisations, social workers, CBPR researchers from the university, citizens and local health promoters.
Species Distribution Modelling performance and its implication for Sentinel-2-based prediction of invasive Prosopis juliflora in lower Awash River basin, Ethiopia
Authors: Ahmed Nurhussen , Atzberger Clement , Zewdie Worku 
Published: March 2021

Abstract
Background
Species Distribution Modelling (SDM) coupled with freely available multispectral imagery from Sentinel-2 (S2) satellite provides an immense contribution in monitoring invasive species. However, attempts to evaluate the performances of SDMs using S2 spectral bands and S2 Radiometric Indices (S2-RIs) and biophysical variables, in particular, were limited. Hence, this study aimed at evaluating the performance of six commonly used SDMs and one ensemble model for S2-based variables in modelling the current distribution of Prosopis juliflora in the lower Awash River basin, Ethiopia. Thirty-five variables were computed from Sentinel-2B level-2A, and out of the variables, twelve significant variables were selected using Variable Inflation Factor (VIF). A total of 680 presence and absence data were collected to train and validate variables using the tenfold bootstrap replication approach in the R software “sdm” package. The performance of the models was evaluated using sensitivity, specificity, True Skill Statistics (TSS), kappa coefficient, area under the curve (AUC), and correlation.

Results
Our findings demonstrated that except bioclim all machine learning and regression models provided successful prediction. Among the tested models, Random Forest (RF) performed better with 93% TSS and 99% AUC followed by Boosted Regression Trees (BRT), ensemble, Generalized Additive Model (GAM), Support Vector Machine (SVM), and Generalized Linear Model (GLM) in decreasing order. The relative influence of vegetation indices was the highest followed by soil indices, biophysical variables, and water indices in decreasing order. According to RF prediction, 16.14% (1553.5 km2) of the study area was invaded by the alien species.

Conclusions
Our results highlighted that S2-RIs and biophysical variables combined with machine learning and regression models have a higher capacity to model invasive species distribution. Besides, the use of machine learning algorithms such as RF algorithm is highly essential for remote sensing-based invasive SDM.
Prior National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder trials as background and rationale for NIDA CTN-0100 “optimizing retention, duration and discontinuation strategies for opioid use disorder pharmacotherapy (RDD)”
Authors: Shulman Matisyahu , Weiss Roger , Rotrosen John , Novo Patricia , Costello Elizabeth , Nunes Edward V. 
Published: March 2021

AbstractOpioid use disorder continues to be a significant problem in the United States and worldwide. Three medications—methadone, buprenorphine, and extended-release injectable naltrexone,— are efficacious for treating opioid use disorder (OUD). However, the utility of these medications is limited, in part due to poor rates of retention in treatment. In addition, minimum recovery milestones and other factors that influence when and whether individuals can safely discontinue medications are unknown. The National Drug Abuse Treatment Clinical Trials Network (CTN) study “Optimizing Retention, Duration, and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy” (RDD; CTN-0100) will be among the largest clinical trials on treatment of OUD yet conducted, consisting of two phases, the Retention phase, and the Duration-Discontinuation phase. The Retention phase, open to patients initiating treatment, will test different doses and formulations of buprenorphine (standard dose sublingual, high dose sublingual, or extended-release injection), and a digital therapeutic app delivering contingency management and cognitive behavioral counseling on the primary outcome of retention in treatment. The Discontinuation phase, open to patients in stable remission from OUD and choosing to discontinue medication (including participants from the Retention phase or from the population of patients treated at the clinical site, referred by an outside prescriber or self-referred) will study different tapering strategies for buprenorphine (sublingual taper vs taper with injection buprenorphine), and a digital therapeutic app which provides resources to promote recovery, on the primary outcome of relapse-free discontinuation of medication. This paper describes how the RDD trial derives from two decades of research in the CTN. Initial trials (CTN-0001; CTN-0002; CTN-0003) focused on opioid detoxification, showing buprenorphine-naloxone was effective for detoxification, but that acute detoxification did not appear to be an effective treatment strategy. Trials on comparative effectiveness of medications for opioid use disorder (MOUD) (CTN-0027; CTN-0030; and CTN-0051) highlighted the problem of dropout from treatment and few trials defined retention on MOUD as the primary outcome. Long-term follow-up studies on those patient samples demonstrated the importance of long-term continuation of medication for many patients to sustain remission. Overall, these trials highlight the potential of a stable research infrastructure such as CTN to advance treatment effectiveness through a programmatic succession of large clinical trials.