bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical note on introducing a digital workflow for newborns with craniofacial anomalies based on intraoral scans - part I: 3D printed and milled palatal stimulation plate for trisomy 21
Authors: Xepapadeas Alexander B. , Weise Christina , Frank K. , Spintzyk S. , Poets C. F. , Wiechers C. , Arand J. , Koos B. 
Published: January 2020

AbstractBackgroundAdvanced digital workflows in orthodontics and dentistry often require a combination of different software solutions to create patient appliances, which may be a complex and time-consuming process. The main objective of this technical note is to discuss treatment of craniofacial anomalies using digital technologies. We present a fully digital, linear workflow for manufacturing palatal plates for infants with craniofacial anomalies based on intraoral scanning. Switching to intraoral scanning in infant care is advantageous as taking conventional impressions carries the risk of impression material aspiration and/or infections caused by material remaining in the oronasal cavity.Material and methodsThe fully digital linear workflow presented in this technical note can be used to design and manufacture palatal plates for cleft palate patients as well as infants with functional disorders. We describe the workflow implemented in an infant with trisomy 21. The maxilla was registered using a digital scanner and a stimulation plate was created using dental CAD software and an individual impression tray module on a virtual model. Plates were manufactured using both additive and subtractive methods. Methacrylate based light curing resin and Poly-Ether-Ether-Ketone were the materials used.ResultsThe palatal area was successfully scanned to create a virtual model. The plates fitted well onto the palatal area. Manual post-processing was necessary to optimize a functional ridge along the vestibular fold and remove support structures from the additively manufactured plate as well as the milled plate produced from a blank. The additively manufactured plate fitted better than the milled one.ConclusionImplementing a fully digital linear workflow into clinical routine for treatment of neonates and infants with craniofacial disorders is feasible. The software solution presented here is suitable for this purpose and does not require additional software for the design. This is the key advantage of this workflow, which makes digital treatment accessible to all clinicians who want to deal with digital technology. Whether additive or subtractive manufacturing is preferred depends on the appliance material of choice and influences the fit of the appliance.
Microbial contamination in herbal medicines: a serious health hazard to elderly consumers
Authors: de Sousa Lima Carolina Miranda , Fujishima Mayara Amoras Teles , de Paula Lima Bruno , Mastroianni Patrícia Carvalho , de Sousa Francisco Fábio Oliveira , da Silva Jocivânia Oliveira 
Published: January 2020

Abstract
Introduction
The use of herbal medicine is on the rise worldwide, and safety issues associated with herbal medicines may have an exacerbated impact in elderly because this population has an increased susceptibility and sensitivity to health complications due to the aging process.

Methods
This cross-sectional study was carried out at a primary health care unit in the city of Macapa, Brazil. The herbal medicines used and the sociodemographic characteristics of 123 voluntarily consenting participants were collected using a structured questionnaire. A total of 132 herbal medicines with oral or topical administration were donated by the elderly for microbial analysis before consumption, and 18 water samples used in the preparation of homemade herbal medicines were collected. Bacterial and fungal counts and identification of bacterial pathogens (Escherichia coli, Salmonella spp., Pseudomonas aeruginosa and Staphylococcus aureus) were performed according to the regulations of the Brazilian Pharmacopoeia and World Health Organization. Water analysis for the detection of coliforms and E. coli was carried out using Colilert® according to the manufacturer’s instructions and the techniques established by Standard Methods.

Results
Of the study participants, 78.8% were women. Bacterial growth was observed in samples from 51.5% of study and 35.6% had fungal growth. A total of 31.8% of the herbal medicine samples exceeded the safety limits (CFU/g ≤ 105), including 16.7% of the homemade herbal medicines and 15.1% of the commercial herbal medicines. It was also found that 31.0% of the samples exceeded the safety limit for fungal growth. The microorganisms most commonly isolated from the herbal medicines were S. aureus (49.2%), followed by Salmonella spp. (34.8%), E. coli (25.8%), and P. aeruginosa (14.4%). Of water samples analyzed, 77.8% were positive for total coliforms (1 ml) and in 66.7% water samples E. coli was detected (1 ml), making them unfit for consumption.

Conclusions
The use of homemade and commercial herbal medicines is a major risk to the health of elderly who use these therapies due to the lack of microbial quality standards. We observed levels of viable bacteria and fungi that were above safety limits; in addition, we were able to isolate pathogenic bacteria from these herbal medicines.
Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors
Authors: Lara Pablo , Palma-Florez Sujey , Salas-Huenuleo Edison , Polakovicova Iva , Guerrero Simón , Lobos-Gonzalez Lorena , Campos America , Muñoz Luis , Jorquera-Cordero Carla , Varas-Godoy Manuel , Cancino Jorge , Arias Eloísa , Villegas Jaime , Cruz Luis J. , Albericio Fernando , Araya Eyleen , Corvalan Alejandro H. , Quest Andrew F. G. , Kogan Marcelo J. 
Published: January 2020

Abstract
Background
Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy.

Results
We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules.

Conclusions
Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.
Time trends for pulmonary embolism incidence in Greece
Authors: Raptis Dimitrios G. , Gourgoulianis Konstantinos I. , Daniil Zoe , Malli Foteini 
Published: January 2020

Abstract
Background
Pulmonary embolism (PE) is a disease with a significant impact on public health. However, international epidemiological data are unclear and show considerable heterogeneity. The present study aims to investigate the incidence of PE at the Greek population and the associated demographic characteristics of patients with PE.

Methods
Data on hospital admissions for PE between 1999 and 2012 were provided by the Hellenic Statistical Authority of Greece. Data on age, gender and days of hospitalization from 1999 to 2007 were provided as well. The total population in each region was derived from the 1991, 2001, 2011 Census of the national statistical service of Greece.

Results
The mean annual incidence of PE during the study period was 18.5 per 100.000 population. The annual incidence of PE showed an upward trend ranging from 14 (1999) to 30 (2012) per 100.000 population. In the years before and after the economic crisis faced by Greece we observed statistically significant differences of PE incidence for the two different periods (1999–2008 versus 2009–2012, 14.49 versus 23.06 respectively, p = 0.002). The available data revealed a female predominance (16.48 cases for females per 100.000 population versus 13.69 cases for males per 100.000 population, p = 0.031). Incidence rate increased with age with a higher incidence in the “80–89” age group.

Conclusions
The incidence of PE appeared to increase in Greece, while it remains below the expected trend in an international context that may be attributed to Computed Tomography Pulmonary Angiography availability and/or PE awareness among clinicians.
Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
Authors: Mauriello Angela , Manolio Carmen , Cavalluzzo Beatrice , Avallone Antonio , Borrelli Marco , Morabito Alessandro , Iovine Emanuele , Chambery Angela , Russo Rosita , Tornesello Maria Lina , Buonaguro Franco M. , Tagliamonte Maria , Buonaguro Luigi 
Published: January 2020

Abstract
Background
We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant®, a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting.

Methods
PBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT). The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant®) was assessed using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4+ T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM.

Results
Treatment with RNAdjuvant® induced the strongest response in cancer patients in terms of activation of innate and adoptive immunity. Indeed, CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4+ T cell differentiation towards an effector phenotype. RNAdjuvant® was the only one to induce most of the cytokines/chemokines tested with a pronounced Th1 cytokine pattern. According to the different parameters evaluated in the study, no clear cut difference in immune response to adjuvants was observed between healthy subjects and cancer patients. Moreover, in the latter group, the chemotherapy treatment did not consistently correlate to a significant altered response in the different parameters.

Conclusions
The present study is the first analysis of immunological effects induced by adjuvants in cancer patients who undergo chemotherapy, who are enrolled in the currently ongoing cancer vaccine clinical trials. The results show that the RNAdjuvant® is a potent and Th1 driving adjuvant, compared to those tested in the present study. Most importantly, it is demonstrated that chemotherapy does not significantly impair the immune system, implying that cancer patients are likely to respond to a cancer vaccine even after a chemotherapy treatment.
Neuroprotective effect of microglia against impairments of auditory steady-state response induced by anti-P IgG from SLE patients in naïve mice
Authors: Wang Xuejiao , Li Yingzhuo , Li Zijie , Li Jinhong , Xu Jingyi , Yang Pingting , Qin Ling 
Published: January 2020

Abstract
Objective
Autoantibodies against ribosomal P proteins (anti-P antibodies) are strongly associated with the neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE). The present study was designed to assess whether anti-P antibodies can induce abnormal brain electrical activities in mice and investigate the potential cytopathological mechanism.

Methods
Affinity-purified human anti-ribosomal P antibodies were injected intravenously into mice after blood–brain barrier (BBB) disruption. The auditory steady-state response (ASSR) was evaluated based on electroencephalography (EEG) signals in response to 40-Hz click-train stimuli, which were recorded from electrodes implanted in the skull of mice. Immunofluorescence staining was used to examine the morphology and density of neurons and glia in the hippocampus and cortex. The presence of apoptosis in the brain tissues was studied using the TUNEL assay. A PLX3397 diet was used to selectively eliminate microglia from the brains of mice.

Results
Circulating anti-P antibodies caused an enhancement of the ASSR and the activation of microglia through the disrupted BBB, while no obvious neural apoptosis was observed. In contrast, when microglia were depleted, anti-P antibodies induced a serious reduction in the ASSR and neural apoptosis.

Conclusion
Our study indicates that anti-P antibodies can directly induce the dysfunction of auditory-evoked potentials in the brain and that microglia are involved in the protection of neural activity after the invasion of anti-P antibodies, which could have important implications for NPSLE.
A comprehensive reproductive health program for vulnerable adolescent girls
Authors: Pourkazemi Razieh , Janighorban Mojgan , Boroumandfar Zahra , Mostafavi Firoozeh 
Published: January 2020

Abstract
Background
Reproductive health of vulnerable adolescent girls is a top priority in global programs. Alcohol consumption, drug abuse, high risk sexual behaviors, sexually transmitted diseases, sexual assault, escape from home, unrestrained sex in the family, history of robbery, imprisonment and living in drug hangouts expose adolescents to different sorts of damage and injury. These adolescent girls are at risk of AIDS and other STDs, unwanted pregnancies, illegal and unsafe abortions, unplanned pregnancy and childbirth, and unsafe motherhood. Therefore, assessing these girls’ reproductive health needs and designing programs to improve their sexual and reproductive health seem to be essential. This study will be conducted to design a comprehensive program for improving the reproductive health of vulnerable adolescent girls.

Methods
The present study is an exploratory sequential mixed methods study (Qual-Quan) designed in three phases. In the first phase, a qualitative study will be used to describe the reproductive health needs of vulnerable adolescent girls, identify facilitating and inhibiting factors, and explain the strategies of reproductive health programs for these girls. Participants will be selected in this phase using purposive sampling method, and the data will be collected through semi-structured interviews. The obtained data will be analyzed using conventional qualitative content analysis. In the second phase, through a quantitative study, the strategies obtained from the qualitative study and review of the literature will be provided to reproductive health care providers, experts, policymakers, and planners to prioritize and select the best strategies. In the third phase, the initial draft of the program will be formulated based on prioritized strategies and will be proposed in a panel comprised of specialists in the areas of reproductive and sexual health, health promotion, social injuries and a psychiatrist. Finally, the final program will be developed and presented after obtaining the agreement and approval of the panel members.

Discussion
Designing a program based on a qualitative study, review of the existing evidence and programs, and using the opinions of experts in different areas can lead to different aspects of reproductive and sexual health of vulnerable adolescent girls. On the other hand, taking into account all cultural sensitivities and taboos as well as political, economic and social barriers, the development of such a program can provide the appropriate possibility of presenting comprehensive reproductive and sexual health services to vulnerable adolescent girls and achieve the goals agreed universally.
Joining forces: the need to combine science and ethics to address problems of validity and translation in neuropsychiatry research using animal models
Authors: Meijboom Franck L. B. , Kostrzewa Elzbieta , Leenaars Cathalijn H. C. 
Published: January 2020

AbstractBackgroundCurrent policies regulating the use of animals for scientific purposes are based on balancing between potential gain of knowledge and suffering of animals used in experimentation. The balancing process is complicated, on the one hand by plurality of views on our duties towards animals, and on the other hand by more recent discussions on uncertainty in the probability of reaching the final aim of the research and problems of translational failure.MethodsThe study combines ethical analysis based on a literature review with neuropsychiatry-related preclinical research as a case study.ResultsBased on the analysis and the case study we show that neuropsychiatry-related preclinical research is an especially interesting case from an ethical perspective. The 3R principles (Replacement, Reduction and Refinement) are used to minimize the negative consequences for the animals used in research. However, neuropsychiatric research is characterized by specific challenges in assessing the probability of success of reaching the final aim, due to our limited mechanistic knowledge of human neuropsychiatric illness. Consequently, the translational value of the currently used animal models may be difficult to prove, which undermines the validity of these models and complicated the ethical assessment.ConclusionsWe conclude that a combined approach that deals with both science and the ethical dimensions is necessary to address the problems of validity and translation in neuropsychiatry-related preclinical research. We suggest this approach to comprise first, improved experimental methods, e.g. by using systematic reviews, second, a more patients-based approach that leads to models that reflect interindividual variation better, and third, more interdisciplinary cooperation.
“Becoming myself”: how participants in a longitudinal substance use disorder recovery study experienced receiving continuous feedback on their results
Authors: Svendsen Thomas Solgaard , Bjornestad Jone , Slyngstad Tale Ekeroth , McKay James R. , Skaalevik Aleksander Waagan , Veseth Marius , Moltu Christian , Nesvaag Sverre 
Published: January 2020

AbstractBackgroundBeing a participant in longitudinal follow-up studies is not commonly a factor considered when investigating useful self-change aspects for individuals attempting recovery from substance use disorder (SUD). This study reports on how ongoing monitoring, and feedback on data results in a longitudinal follow-up study of SUD recovery were perceived by individuals who had achieved long-term abstinence and social recovery.MethodsInterviewers with first-hand experience with the topic conducted interviews with 30 participants and analysed the data using a thematic analytic approach within an interpretative–phenomenological framework.ResultsAnalyses resulted in the following themes. 1) Ongoing short text messaging (SMS) monitoring: helped participants by offering recovery milestones and reminders of the past. 2) Feedback on data results helped participants track physical and cognitive recovery: “I am more like myself”. 3) Using feedback in treatment: understanding the importance of a functional brain to participants may help with long-term retention in treatment.ConclusionsSelf-changes that were challenging to detect on a day-to-day basis were available for reflection through longitudinal study participation, including ongoing monitoring and feedback on the results, allowing personal consolidation of change processes. Clinical services could benefit from continuing development and implementation of such technology for ongoing monitoring and feedback on assessments to motivate self-change in SUD recovery. The development of guidelines for providing the results of research assessments to individuals could help reduce attrition in research projects and support recovery and healthy choices for study participants.
Expression of xylosyltransferases I and II and their role in the pathogenesis of arthrofibrosis
Authors: Bernstein Anke , Reichert Sven N. A. , Südkamp Norbert P. , Hernandez Sergio Latorre , Nerlich Andreas G. , Kühle Jan , Mayr Hermann O. 
Published: January 2020

Abstract
Background
Arthrofibrosis is a painful and restraining complication that occurs after about 10% of total knee arthroplasty and cruciate ligament surgery. The pathogenesis of arthrofibrosis has not yet been fully understood. Stress signals stimulate immune cells, and fibroblast differentiates into myofibroblast, which produce a large amount of collagen. Xylosyltransferases also appear to be involved in these pathways. They catalyze proteoglycan biosynthesis, which is involved in tissue remodeling and myofibroblast differentiation. The aim of this study was to investigate the relationship between the disease arthrofibrosis and the expression of the two isoforms of xylosyltransferases I and II.

Methods
Tissue samples from 14 patients with arthrofibrosis were compared with tissue samples from seven healthy controls. The xylosyltransferases were detected by immunohistochemistry. The tissues were divided into four different areas of interest: vessels, synovialis, cell-poor and cell-rich fibrosis, or cell-poor and cell-rich areas in the control group. A quantification of the results was performed by modification of the immunoreactive score according to Remmele and Stegner.

Results
Xylosyltransferase I was expressed in the various tissue types at varying rates. Xylosyltransferase I expression was considerably and significantly stronger than that of xylosyltransferase II. The following sequences of xylosyltransferase I and xylosyltransferase II expression were determined as follows: vessels >> cell-rich fibrosis > cell-poor fibrosis > synovialis. A positive correlation between the number of positive fibroblasts and the immunoreactive scoring system (IRS) was documented.

Conclusions
The significant positive correlation of xylosyltransferase -I expression with increasing number of fibroblasts demonstrates a high myofibroblast differentiation rate, which implies a gradual event as the pathogenesis of arthrofibrosis.