bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats
Authors: Bussi Simona , Coppo Alessandra , Celeste Roberto , Fanizzi Antonello , Fringuello Mingo Alberto , Ferraris Andrea , Botteron Catherine , Kirchin Miles A. , Tedoldi Fabio , Maisano Federico 
Published: February 2020

Abstract
Objectives
The purpose of this study was to compare Gd levels in rat tissues after cumulative exposure to four commercially available macrocyclic gadolinium-based contrast agents (GBCAs).

Methods
Sixty-five male Sprague-Dawley rats were randomized to four exposure groups (n = 15 per group) and one control group (n = 5). Animals in each exposure group received 20 GBCA administrations (four per week of ProHance®, Dotarem®, Clariscan™, or Gadovist® for 5 consecutive weeks) at a dose of 0.6 mmol/kg bodyweight. After 28-days’ recovery, animals were sacrificed and tissues harvested for Gd determination by inductively coupled plasma-mass spectroscopy (ICP-MS). Histologic assessment of the kidney tissue was performed for all animals.

Results
Significantly (p ≤ 0.005; all evaluations) lower Gd levels were noted with ProHance® than with Dotarem®, Clariscan™, or Gadovist® in all soft tissue organs: 0.144 ± 0.015 nmol/g vs. 0.342 ± 0.045, 0.377 ± 0.042, and 0.292 ± 0.047 nmol/g, respectively, for cerebrum; 0.151 ± 0.039 nmol/g vs. 0.315 ± 0.04, 0.345 ± 0.053, and 0.316 ± 0.040 nmol/g, respectively, for cerebellum; 0.361 ± 0.106 nmol/g vs. 0.685 ± 0.330, 0.823 ± 0.495, and 1.224 ± 0.664 nmol/g, respectively, for liver; 38.6 ± 25.0 nmol/g vs. 172 ± 134, 212 ± 121, and 294 ± 127 nmol/g, respectively, for kidney; and 0.400 ± 0.112 nmol/g vs. 0.660 ± 0.202, 0.688 ± 0.215, and 0.999 ± 0.442 nmol/g, respectively, for skin. No GBCA-induced macroscopic or microscopic findings were noted in the kidneys.

Conclusions
Less Gd is retained in the brain and body tissues of rats 28 days after the last exposure to ProHance® compared to other macrocyclic GBCAs, likely due to unique physico-chemical features that facilitate more rapid and efficient clearance.
Redefining the structure of structured reporting in radiology
Authors: Nobel J. Martijn , Kok Ellen M. , Robben Simon G. F. 
Published: February 2020

AbstractStructured reporting is advocated as a means of improving reporting in radiology to the ultimate benefit of both radiological and clinical practice. Several large initiatives are currently evaluating its potential. However, with numerous characterizations of the term in circulation, “structured reporting” has become ambiguous and is often confused with “standardization,” which may hamper proper evaluation and implementation in clinical practice. This paper provides an overview of interpretations of structured reporting and proposes a clear definition that differentiates structured reporting from standardization. Only a clear uniform definition facilitates evidence-based implementation, enables evaluation of its separate components, and supports (meta-)analyses of literature reports.
Protective properties of heme oxygenase-1 expressed in umbilical cord mesenchymal stem cells help restore the ovarian function of premature ovarian failure mice through activating the JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8+CD28− T cells
Authors: Yin Na , Wu Chenting , Qiu Jianping , Zhang Yueming , Bo Le , Xu Ying , Shi Mengdie , Zhu Songyue , Yang Guangzhao , Mao Caiping 
Published: February 2020

Abstract
Background
Umbilical cord-derived mesenchymal stem cell (UCMSCs) transplantation has been widely studied in premature ovarian failure (POF). However, the underlying mechanism remains elusive. This study aims to investigate the protective properties and mechanisms of heme oxygenase-1 (HO-1) expressed in UCMSCs in restoring the ovarian function of POF mice.

Methods
In in vitro and in vivo experiments, mice were treated with the presence or absence of the HO-1/shHO-1-transfected UCMSCs, and the administration of SP600125 or anisomycin, the inhibitor or activator of JNK. The viability and apoptosis of granulosa cells (GCs) at different time points of co-cultivation were assessed in vitro. In in vivo experiments, mouse ovarian function was assessed by detecting the serum levels of hormone and observing the ovarian morphological changes. Multiple molecular indices of JNK/Bcl-2 signal pathway were performed. And the autophagy changes in GCs were assessed by detecting the associated cytokines and observing the intracellular autophagosome accumulation. Additionally, the spleen levels of CD8+CD28− T cells and serum levels of interleukin 10 (IL-10) were tested to evaluate the immune mechanisms involved.

Results
UCMSCs transfected with shHO-1 or treated with SP600125 inhibited GCs’ viability and promoted its apoptosis in a time-dependent manner in vitro. In in vivo experiments, mice in both groups showed little therapeutic efficiency which presented as the increased extent of ovarian fibrosis with decreased number of functional follicles, and disordered hormone production. Additionally, the JNK/Bcl-2-associated cytokines were obviously declined. The inhibited autophagy-related cytokines, the chromatin condensation and abound vacuolar autophagosome in GCs, and weakened fluorescence intensity by MDC were observed. The downregulated levels of CD8+CD28− T cells and serum levels of IL-10 were also detected. The damages above can be alleviated with HO-1-MSCs treatment or anisomycin administration.

Conclusions
HO-1 expressed in UCMSCs is critical in restoring the ovarian function in POF mice with UCMSC transplantation, which is mediated by the activation of JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8+CD28− T cells.
Working towards a better understanding of type 2 diabetes care organization with First Nations communities: a qualitative assessment
Authors: Wozniak Lisa A. , Johnson Jeffrey A. , Eurich Dean T. 
Published: February 2020

AbstractBackgroundDiabetes care is suboptimal in First Nations populations. Innovative and culturally-relevant approaches are needed to promote proactive organization of diabetes care for diabetes patients on-reserve in Canada. The Reorganizing the Approach to Diabetes care through the Application of Registries (RADAR) model is one strategy to improve care: an integrated disease registry and electronic health record for community healthcare workers with centralized care coordination. The aim of this study was to qualitatively assess the organization of type 2 diabetes care in participating communities in Alberta, Canada, at baseline prior to implementing RADAR.MethodsUsing qualitative description, we purposefully sampled healthcare workers involved in diabetes care at each health center. We used the 5Rs framework (i.e., Recognize, Register, Resource, Relay, Recall) to inform the baseline assessment and conducted group interviews in 6 communities with 16 healthcare workers. Detailed notes were taken and validated by participants. Data was managed using ATLAS.ti 8 and analyzed using content analysis.ResultsWe found strong commitment and effort by local healthcare workers to support people living with type 2 diabetes in their communities. However, healthcare workers were limited in their ability to identify (i.e., recognize), track (i.e., register and relay) and manage (i.e., resource and recall) people with type 2 diabetes as proposed by the 5Rs framework. The organization of diabetes care was often reactive and dependent on patients’ abilities to navigate the health system. Interestingly, participants talked about the 5Rs in relationship to one another, not in a linear or isolated manner.ConclusionsOverall, the organization of diabetes care in participating communities did not align with the recommended approach of the 5Rs framework. In addition, we propose “reimagining” the 5Rs to reflect the interdependence and mediation of components situated within human and financial resources. This will better equip healthcare workers to assess, plan and execute organized and proactive diabetes care. However, the onus on people living with type 2 diabetes to engage with healthcare services remains a concern.Trial registrationISRCTN.com,ISRCTN14359671.
Complementary horse-assisted therapy for substance use disorders: a randomized controlled trial
Authors: Gatti Francesca , Walderhaug Espen , Kern-Godal Ann , Lysell Jeanette , Arnevik Espen Ajo 
Published: February 2020

Abstract
Background
Treatment completion is the greatest challenge for the treatment of substance use disorders (SUDs). A previous investigation showed that complementary horse-assisted therapy (cHAT) was associated with higher retention in treatment and completion than standard treatment alone. This randomized controlled trial further explored the benefits of cHAT for patients with SUDs.

Methods
Fifty patients in residential SUD treatment at the Department of Addiction Treatment, Oslo University Hospital, were randomly allocated to either cHAT (cHAT group) or treatment as usual alone (TAU-only group). The primary end-point was treatment completion. Secondary end-points were dropout, transfer to another treatment, and time in treatment.

Results
The multinomial logistic regression analysis found no statistically significant association between intervention (cHAT) and treatment outcome (completion, dropout, transferred) among the 37 participants who were ultimately recruited to the study. Some unforeseen challenges were encountered in the study: a high number of subjects transferred to another treatment, variable attendance at cHAT sessions, and long temporary exits. Nevertheless, 44% of participants in the cHAT group completed their treatment, compared with 32% in the TAU-only group; this observation encourages further investigation in a larger sample.

Conclusions
Though no association was identified between cHAT and treatment retention or completion, our study may have been underpowered. Further work in a larger clinical population is needed; observational studies with repeated measures may also be useful for investigating whether cHAT increases retention in treatment or rates of completion, two important factors for successful SUD treatment.
Trial registration The trial was registered and approved on 14 October 2011 by the Regional Committee for Medical and Health Research Ethics with registration number 2011/1642 and registered at ClinicalTrials.gov on 21 February 2013 with registration number NCT01795755
Urbanicity, hypothalamic-pituitary-adrenal axis functioning, and behavioral and emotional problems in children: a path analysis
Authors: Evans B. E. , van der Ende J. , Greaves-Lord K. , Huizink A. C. , Beijers R. , de Weerth C. 
Published: February 2020

AbstractBackgroundUrbanization is steadily increasing worldwide. Previous research indicated a higher incidence of mental health problems in more urban areas, however, very little is known regarding potential mechanisms underlying this association. We examined whether urbanicity was associated with mental health problems in children directly, and indirectly via hypothalamic-pituitary-adrenal (HPA)-axis functioning.MethodsUtilizing data from two independent samples of children we examined the effects of current urbanicity (n = 306, ages seven to 12 years) and early childhood urbanicity (n = 141, followed from birth through age 7 years). Children’s mothers reported on their mental health problems and their family’s socioeconomic status. Salivary cortisol samples were collected during a psychosocial stress procedure to assess HPA axis reactivity to stress, and at home to assess basal HPA axis functioning. Neighborhood-level urbanicity and socioeconomic conditions were extracted from Statistics Netherlands. Path models were estimated using a bootstrapping procedure to detect indirect effects.ResultsWe found no evidence for a direct effect of urbanicity on mental health problems, nor were there indirect effects of urbanicity through HPA axis functioning. Furthermore, we did not find evidence for an effect of urbanicity on HPA axis functioning or effects of HPA axis functioning on mental health problems.ConclusionsPossibly, the effects of urbanicity on HPA axis functioning and mental health do not manifest until adolescence. An alternative explanation is a buffering effect of high family socioeconomic status as the majority of children were from families with an average or high socioeconomic status. Further studies remain necessary to conclude that urbanicity does not affect children’s mental health via HPA axis functioning.
Cyclosporine-a attenuates retinal inflammation by inhibiting HMGB-1 formation in rats with type 2 diabetes mellitus
Authors: Wang Peng , Chen Fei , Zhang Xuedong 
Published: February 2020

Abstract
Background
Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy.

Methods
Male Sprague-Dawley rats were established to type 2 diabetic model. After 6 weeks, diabetic rats and normal controls were intravitreally injected with. Cs-A (42 ng/2 μL) to the left eye, and 2 μL DMSO to the right eye for the control.. Another group of normal wild-type rats was subjected to intravitreal injections into. The left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus. Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with. Hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were. Detected by immunohistochemistry, ELISA or Western blot or RT-PCR.

Results
Retinal expression levels of IL-1β and TNF-α were upregulated in type 2. diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were. Attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in. diabetic retina and relieved the retinopathy in type 2 diabetic rats.

Conclusions
Intravitreal administration of Cs-A showed a protective effect on retina. of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α. via the suppression of HMGB-1.
Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity
Authors: Kaalund Sanne Simone , Passamonti Luca , Allinson Kieren S. J. , Murley Alexander G. , Robbins Trevor W. , Spillantini Maria Grazia , Rowe James B. 
Published: February 2020

AbstractThe locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson’s syndrome. We test the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP.We used immunohistochemistry in post mortem tissues from 31 patients with a clinical diagnosis of PSP (22 with Richardson’s syndrome) and 6 control cases. We quantified the presence of hyperphosphorylated tau, the number of pigmented cells indicative of noradrenergic neurons, and the percentage of pigmented neurons with tau-positive inclusions. Ante mortem assessment of clinical severity using the PSP rating scale was available within 1.8 (±0.9) years for 23 patients.We found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was negatively associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions.Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.
Tau-tubulin kinase 1 and amyloid-β peptide induce phosphorylation of collapsin response mediator protein-2 and enhance neurite degeneration in Alzheimer disease mouse models
Authors: Ikezu Seiko , Ingraham Dixie Kaitlin L. , Koro Lacin , Watanabe Takashi , Kaibuchi Kozo , Ikezu Tsuneya 
Published: February 2020

AbstractThe accumulation of phosphorylated tau protein (pTau) in the entorhinal cortex (EC) is the earliest tau pathology in Alzheimer’s disease (AD). Tau tubulin kinase-1 (TTBK1) is a neuron-specific tau kinase and expressed in the EC and hippocampal regions in both human and mouse brains. Here we report that collapsin response mediator protein-2 (CRMP2), a critical mediator of growth cone collapse, is a new downstream target of TTBK1 and is accumulated in the EC region of early stage AD brains. TTBK1 transgenic mice show severe axonal degeneration in the perforant path, which is exacerbated by crossing with Tg2576 mice expressing Swedish familial AD mutant of amyloid precursor protein (APP). TTBK1 mice show accumulation of phosphorylated CRMP2 (pCRMP2), in the EC at 10 months of age, whereas age-matched APP/TTBK1 bigenic mice show pCRMP2 accumulation in both the EC and hippocampal regions. Amyloid-β peptide (Aβ) and TTBK1 suppress the kinetics of microtubule polymerization and TTBK1 reduces the neurite length of primary cultured neurons in Rho kinase-dependent manner in vitro. Silencing of TTBK1 or expression of dominant-negative Rho kinase demonstrates that Aβ induces CRMP2 phosphorylation at threonine 514 in a TTBK1-dependent manner, and TTBK1 enhances Aβ-induced CRMP2 phosphorylation in Rho kinase-dependent manner in vitro. Furthermore, TTBK1 expression induces pCRMP2 complex formation with pTau in vitro, which is enhanced upon Aβ stimulation in vitro. Finally, pCRMP2 forms a complex with pTau in the EC tissue of TTBK1 mice in vivo, which is exacerbated in both the EC and hippocampal tissues in APP/TTBK1 mice. These results suggest that TTBK1 and Aβ induce phosphorylation of CRMP2, which may be causative for the neurite degeneration and somal accumulation of pTau in the EC neurons, indicating critical involvement of TTBK1 and pCRMP2 in the early AD pathology.
A novel to perform a thermoelastic analysis using digital image correlation and the boundary element method
Authors: Oberg Matheus B. A. M. , de Oliveira Daniel F. , Goulart Jhon N. V. , Anflor Carla T. M. 
Published: February 2020

AbstractThis work aims for a novel thermoelastic analysis methodology based on experimental steady-state temperature data and numerical displacement evaluation. The temperature data was acquired using thermal imaging and used as the input for a boundary element method (BEM) routine to evaluate its consequent thermoelastic displacement. The thermoelastic contribution to the resultant displacement arises in the BEM formulation as a domain integral, which compromises the main benefits of the BEM. To avoid the necessity of domain discretization, the radial integration method (RIM) was applied to convert the thermoelastic domain integral into an equivalent boundary integral. Due to its mathematical development, the resultant formulation from RIM requires the temperature difference to be input as a function. The efficacy of the proposed methodology was verified based on experimental displacement fields obtained via digital image correlation (DIC) analysis. For this purpose, a CNC (computer numerical control) marker was developed to print the speckle pattern instead of preparing the specimen by using manual spray paint or using commercially available pre-painted adhesives. The good agreement observed in the comparison between the numerical and experimental displacements indicates the viability of the proposed methodology.
Development and proof-of-concept of a multicenter, patient-centered cancer registry for breast cancer patients with metastatic disease—the “Breast cancer care for patients with metastatic disease” (BRE-4-MED) registry
Authors: Stangl Stephanie , Haas Kirsten , Eichner Felizitas A. , Grau Anna , Selig Udo , Ludwig Timo , Fehm Tanja , Stüber Tanja , Rashid Asarnusch , Kerscher Alexander , Bargou Ralf , Hermann Silke , Arndt Volker , Meyer Martin , Wildner Manfred , Faller Hermann , Schrauder Michael G. , Weigel Michael , Schlembach Ulrich , Heuschmann Peter U. , Wöckel Achim 
Published: February 2020

Abstract
Background
Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus on controlling for disease symptoms and maintaining high quality of life. Information on individual needs of patients and their relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or are not routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adapted for these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data.

Methods
The concept for patient-centered “Breast cancer care for patients with metastatic disease” (BRE-4-MED) registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germany comprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information including routine data from established Cancer Registries in different federal states, treating physicians in hospital as well as in outpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancer registry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-based questionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitor needs, progression, and therapy change of individual patients. Patient’s acceptance and feasibility of data collection in clinical routine was assessed within a proof-of-concept study.

Results
The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018. In total n = 31 patients were included in the pilot study, n = 22 patients were followed up after 1 month. Record linkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n = 7 participants. The feasibility of the registry concept in clinical routine was positively evaluated by the participating hospitals.

Conclusion
The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needs of family members, and raising clinical parameters from primary and secondary data sources as well as m-health applications are feasible and accepted in an incurable cancer collective.