bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Core Outcome Development for Carrier Screening (CODECS) Study: Protocol for Development of a Core Outcome Set
Authors: Richardson Ebony Joanne , McEwen Alison , Newton-John Toby , Manera Karine , Jacobs Chris 
Published: December 2020

Abstract
Background: Reproductive genetic carrier screening is a type of genetic testing available to those planning a pregnancy, or during their first trimester, to understand their risk of having a child with a severe genetic condition. There is a lack of consensus for ‘what to measure’ in studies on this intervention, leading to heterogeneity in choice of outcomes and methods of measurement. Such outcome heterogeneity has implications for the quality and comparability of these studies and has led to a lack of robust research evidence in the literature to inform policy and decision-making around the offer of this screening. As reproductive genetic carrier screening becomes increasingly accessible within the general population, it is timely to investigate the outcomes of this intervention. Objectives: The development of a core outcome set is an established methodology to address issues with outcome heterogeneity in research. We aim to develop a core outcome set for reproductive genetic carrier screening to clarify and standardise outcomes for research and practice.Methods: In accordance with guidance from the COMET (Core Outcome Measures in Effectiveness Trials) Initiative, this study will consist of five steps: i) A systematic review of quantitative studies, using narrative synthesis to identify previously reported outcomes, their definitions, and methods of measurement ii) A systematic review of qualitative studies using content analysis to identify excerpts related to patient experience and perspectives that can be interpreted as outcomes iii) Semi-structured focus groups and interviews with patients who have undertaken reproductive genetic carrier screening to identify outcomes of importance to them iv) Delphi survey of key stakeholders, including patients, clinicians, and researchers, to refine and prioritise the list of outcomes generated from the previous steps v) A virtual consensus meeting with a purposive sample of key stakeholders to finalise the core outcome set for reporting.Discussion: This protocol outlines the core outcome set development process and its novel application in the setting of genetic testing. This core outcome set will support the standardisation of outcome reporting in reproductive carrier screening research and contribute to an evolving literature on outcomes to evaluate genetic testing and genetic counselling as health interventions. COMET core outcome set registration: http://www.comet-initiative.org/Studies/Details/1381
TGR5 activation attenuates neuroinflammation via Pellino3 inhibition of Caspase-8/NLRP3 after middle cerebral artery occlusion in rats
Authors: Liang Hui , Matei Nathanael , Devin W. McBride , Xu Yang , Zhou Zhenhua , Tang Jiping , Luo Benyan , Zhang John H. 
Published: December 2020

Abstract
Background NLRP3 (nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3) plays an important role in mediating inflammatory responses during ischemic stroke. Bile acid receptor TGR5 has been identified as an important component in regulating inflammatory response in brain. In this study, we investigated the mechanism of TGR5 on alleviating neuroinflammation after middle cerebral artery occlusion (MCAO).Methods—Sprague-Dawley rats were subjected to MCAO and INT777 was administered intranasally 1 hour after MCAO. Small interfering RNA for TGR5 and Pellino3 were administered through intracerebroventricular injection 48 hours before MCAO. Infarct volumes, neurological scores, ELISA,flow cytometry༌ immunofluorescence staining, Western blot and co-immunoprecipitation were evaluated.Results— Endogenous TGR5 and Pellino3 expressions were increased after MCAO.TGR5 activation by INT777 significantly decreased pro-inflammatory cytokines levels, reduced cleaved caspase-8 and NLRP3 expressions, thereby reducing brain infarction, improving both short- and long-term neurobehavioral assessment. Ischemic damage induced interaction of TGR5 with Pellino3. Knockdown of either TGR5 or Pellino3 increased expressions of cleaved caspase-8 and NLRP3, aggravated brain impairments, abolished the anti-inflammatory effects of INT777 after MCAO.Conclusions—TGR5 activation attenuated brain injury by inhibiting neuroinflammation after MCAO, which may be mediated by Pellino3 inhibition of Caspase-8/NLRP3.
Systemic administration of β-glucan induces immune training in microglia
Authors: Heng Yang , Zhang Xiaoming , Borggrewe Malte , Weering Hilmar R.J. van , Brummer Maaike L. , Nijboer Tjalling W. , Joosten Leo A.B. , Netea Mihai G. , Boddeke Erik W.G.M. , Laman Jon D. , Eggen Bart J.L. 
Published: December 2020

Abstract
BackgroundAn innate immune memory response can manifest in two ways: immune training and immune tolerance, which refers to an enhanced or suppressed immune response to a second challenge, respectively. Exposing monocytes to moderate-to-high amounts of bacterial lipopolysaccharide (LPS) induces immune tolerance, whereas fungal β-glucan (BG) induces immune training. In microglia, it has been shown that different LPS inocula in vivo can induce either immune training or tolerance. Few studies focused on impact of BG on microglia and were only performed in vitro. The aim of the current study was to determine whether BG activates and induces immune memory in microglia upon peripheral administration in vivo.MethodsTwo experimental designs were used. In the acute design, mice received an intraperitoneal (i.p.) injection with PBS, 1 mg/kg LPS or 20 mg/kg BG and were terminated after 3 h, 1 or 2 days. In the preconditioning design, animals were first challenged i.p. with PBS, 1 mg/kg LPS or 20 mg/kg BG. After 2, 7 or 14 days, mice received a second injection with PBS or 1 mg/kg LPS and were sacrificed 3 h later. Microglia were isolated by fluorescence-activated cell sorting, and cytokine gene expression levels were determined. In addition, a self-developed program was used to analyze microglia morphological changes. Cytokine concentrations in serum were determined by a cytokine array.ResultsMicroglia exhibited a classical inflammatory response to LPS, showing significant upregulation of Tnf, Il6, Il1β, Ccl2, Ccl3 and Csf1 expression, three h after injection, and obvious morphological changes 1 and 2 days after injection. With an interval of 2 days between two challenges, both BG and LPS induced immune training in microglia. The training effect of LPS changed into immune tolerance after a 7-day interval between 2 LPS challenges. Preconditioning with BG and LPS resulted in increased morphological changes in microglia in response to a systemic LPS challenge compared to naïve microglia.ConclusionsOur results demonstrate that preconditioning with BG and LPS both induced immune training of microglia at two days after the first challenge. However, with an interval of 7 days between the first and second challenge, LPS-preconditioning resulted in immune tolerance in microglia.
Activated STAT3 Signaling Pathway by Ligature-induced Periodontitis Could Contribute to Neuroinflammation and Cognitive Impairment in Rats
Authors: Hu Yi , Zhang Xu , Zhang Jing , Xia Xinyi , Li Huxiao , Qiu Che , Liao Yue , Chen Huiwen , He Zhiyan , Song Zhongchen , Zhou Wei 
Published: December 2020

Abstract
Background: Increasing evidence suggests a causal link between periodontitis and cognitive disorders. Systemic inflammation initiated by periodontitis may mediate the development of cognitive impairment. Our study aims to investigate the effect of ligature-induced periodontitis on cognitive function and the role of Signal transducers and activators of transcription 3 (STAT3) in this process.Materials and Methods: Ligature-induced periodontitis was established, and the rats were treated intraperitoneally with/without the pSTAT3 inhibitor cryptotanshinone (CTS). Alveolar bone resorption and periodontal inflammation were detected by micro-computed tomography (micro-CT) analysis and histopathological evaluation. Locomotor activity and cognitive function were evaluated by the Open field test (OFT) and the Morris water maze test (MWM), respectively. The activation of microglia and astrocytes in hippocampus and cortex was assessed by immunohistochemistry (IHC). The expression of interleukins (IL-1β, IL-6, IL-8, IL-21) in both periphery and cortex was evaluated by RT-PCR and ELISA. The expression of pSTAT3 and the activation of the STAT3 signaling pathway (JAK2, STAT3, and pSTAT3) in both oral cavity and cortex was assessed by IHC and Western blotting. The expression of amyloid precursor protein (APP) and its key secretase enzymes were evaluated by RT-PCR. The level of amyloid β-protein (Aβ) and the ratio of Aβ1-40/1-42 were measured via ELISA in plasma and cortex while IHC was used to detect the level of Aβ1-42 in brain.Results: In periodontal ligature rats, significant alveolar bone resorption and local inflammatory cell infiltration were present. Apparent increases in inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-21) were detected. in both periphery and brain. Additionally, spatial learning and memory ability was impaired, while locomotor activity was not affected. Activated microglia and astrocytes were found in the cortex and hippocampus, presenting as enlarged cell bodies and irregular protrusions. The STAT3 signaling pathway was activated in both oral cavity and cortex and the processing of APP by β- and γ-secretases was promoted. Change mentioned above could be relieved by the pSTAT3 inhibitor CTS. Conclusions: Ligature-induced periodontitis in rats resulted in systemic inflammation and further abnormal APP processing, leading to cognitive impairments. In this progress, the activation of the STAT3 signaling pathway may play an important role by increasing inflammatory load and promoting neuroinflammation.
Drug Resistance Profile and Clonality of Plasmodium Falciparum Parasites in Cape Verde: The 2017 Malaria Outbreak
Authors: Leal Silvânia da Veiga , Ward Daniel , Campino Susana , Benavente Ernest Diez , Ibrahim Amy , Andrade Tânia , Varela Isaías , Clark Taane G. , Monteiro Davidson , Gonçalves Luzia , Valdez Tomas , Lima Maria da Luz Mendonça , Silveira Henrique , Nogueira Fatima 
Published: December 2020

Abstract
BackgroundCape Verde is an archipelago located off the West African coast, and is in a pre-elimination phase of malaria control. Since 2010, less than 20 Plasmodium falciparum malaria cases have been reported annually, except in 2017, when an outbreak in Praia before the rainy season led to 423 autochthonous cases. It is important to understand the genetic diversity of circulating P. falciparum to inform on drug resistance, potential transmission networks, and sources of infection, including parasite importation.MethodsEnrolled subjects involved malaria patients admitted to Dr. Agostinho Neto Hospital at Praia city, Santiago island, Cape Verde, between July and October 2017. Neighbours and family members of enrolled cases were assessed for the presence of anti-P. falciparum antibodies. Sanger sequencing and real time PCR was used to identify SNPs in genes associated with drug resistance (e.g. pfdhfr, pfdhps, pfmdr1, pfk13, pfcrt), and whole genome sequencing data was generated to investigate the population structure of P. falciparum parasites.ResultsWe analysed 190 parasite samples, 187 indigenous and three from imported infections. Malaria cases were distributed throughout Praia city. There were no cases of severe malaria, and all patients had an adequate clinical and parasitological response after treatment. Anti-P. falciparum antibodies were not detected in the 137 neighbours and family members tested. No mutations were detected in pfdhps. The triple mutation S108N/N51I/C59R in pfdhfr and the chloroquine resistant CVIET haplotype in the pfcrt gene were detected in almost all samples. Variations in pfk13 were identified in only one sample (R645T, E668K). The haplotype NFD for pfmdr1 was detected in the majority of samples (89.7%).ConclusionsPolymorphisms in pfk13 associated with ACTs tolerance in Southeast Asia were not detected, but the majority of the tested samples carried the pfmdr1 haplotype NFD and antimalarial associated mutations in the the pfcrt and pfdhfr genes. We performed the first WGS for Cape Verdean parasites that showed that the samples cluster together, have a very high level of similarity and are close to other parasites populations from West Africa.
Do Clinicians in Areas of Declining Malaria Transmission Adhere to Malaria Diagnosis Guidelines? A Cross-sectional Study From Kampala, Uganda.
Authors: Angella Atukunda , Deogratius Mwaka Amos , Arinaitwe Emmanuel , Orishaba Phillip , Kamya Moses R. , Nankabirwa Joaniter I. 
Published: December 2020

Abstract
Background: Uganda clinical management guidelines recommend a malaria laboratory test in all patients presenting with fever, and only those with a positive test receive antimalarial treatment. However, the current practice in areas with declining malaria transmission remains unknown. We assessed the clinicians’ diagnostic practices, the factors associated with recommending a test, and the risk of missing a malaria case when a test is not recommended in patients presenting with fever in Kampala, an area of declining malaria transmission in Uganda. Methods: Between January and March 2020, 383 participants aged > 12 years and presenting to Kisenyi Health Centre IV with fever were enrolled in the study. A questionnaire was administered during exit interviews, routine diagnostic practices were recorded from participant clinical notes, and a research blood slide was obtained for later reading. Results: Of the enrolled participants, 356 (93%) had a malaria diagnostic test recommended by the managing clinician. Factors associated with increasing prevalence of having a test recommended included; history of overnight travel (adjusted prevalence ratio [aPR] 1.07, 95% confidence interval [CI] 1.02 – 1.13, p=0.011), being married (aPR=1.07, 95% CI 1.01 – 1.13, p=0.022), and having tertiary education (aPR=1.09 95% CI 1.01 – 1.17, p=0.031). Among the 27 participants where a malaria diagnostic test was not recommended, 4 (14.8%) had a positive study smear. Conclusion: Despite having significant declines in malaria transmission in Kampala in the last decade, clinicians at the study health facility highly adhered to the clinical management guidelines, recommending a malaria test in almost all patients presenting with fever. However, a significant proportion of malaria cases was missed when a test was not recommended. These results highlight the importance of laboratory testing for malaria in all patients who present with fevers and live in endemic setting even when transmission has significantly declined.
Arthroscopy Mini-plate Fixation with the Posterior Trans-septal Portal for Treating Posterior Cruciate Ligament Tibial Avulsion Fractures
Authors: Wang Chunlei , Zhang Haisen , Li Longjie , Chen Si , Liu Chang 
Published: December 2020

Abstract
Background Posterior cruciate ligament (PCL) avulsion fractures are rare and difficult to treat. The present work aimed to examine the effect of an innovative arthroscopy method for the treatment of PCL tibial avulsion fractures using mini-plate reduction and fixation through two tibial tunnels and the posterior trans-septal portal.Methods Totally 19 patients (median age, 33 years; range, 23–43 years) with PCL tibial avulsion fractures who underwent treatment with an arthroscopic suture bridge method were retrospectively assessed. Knee function pre-operation and at last follow up was assessed via Lysholm and Tegner scores. A KT-2000 arthrometer was employed for determining knee stability, the range of motion (ROM), and side-to-side differences. Plain radiography and International Knee Documentation Committee (IKDC) exams were performed for patient evaluation.Results No patient was switched to conventional open surgery due to difficult intraoperative procedures. Mean post-surgical Lysholm and Tegner scores (P < 0.001) were significantly improved in comparison with presurgical values. KT-2000 examination revealed markedly reduced side-to-side differences at last follow-up than observed preoperatively (1.2 ± 0.6 VS. 9.3 ± 2.2; P < 0.001). Radiography at the final follow up revealed solid union at the fracture site in the totality of 19 cases.Conclusions This new arthroscopy mini-plate fixation and posterior trans-septal method for posterior cruciate ligament tibial avulsion fractures resulted in good clinico-radiological outcomes, with adequate stability and fracture site healing. It could be employed to repair avulsion fragments of various sizes.Level of evidence IV
Relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors at the unit level: A correlational study
Authors: Nurmeksela Anu , Mikkonen Santtu , Kinnunen Juha , Kvist Tarja 
Published: December 2020

Abstract
Background Nurse managers play a critical role in enhancing nursing and patient outcomes. A nurse manager’s work, which can be described as a middle-manager at a health care organization, is complex and changes from day to day. Only a few studies have clarified how nurse managers divide their time across various work activities. This study aimed to describe the relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors at the hospital unit level. Methods A cross-sectional and correlational study design was used. The data were collected from nurse managers (n= 29), nursing staff (n=306), and patients (n=651) from 28 units across three Finnish acute care hospitals between April and November in year 2017. In addition, data concerning medication errors over one calendar year (2017) were acquired from the hospitals’ incident reporting register. Analysis of covariance (ANCOVA) was used to estimate relationships between data from subareas of Nurse Managers’ Work Content Questionnaire, Kuopio University Hospital Job Satisfaction Scale, and Revised Humane Caring Scale, along with medication errors reports. Significance level of 95% was used to estimate strength of covariances. Unstandardized coefficients (B) estimates were used to explain the relationship of variables.Results Multiple relationships between nurse managers’ work activities, nurses’ job satisfaction, patient satisfaction, and medication errors were identified. Nurse managers’ work activities had both positive and negative relationships on the other studied variables. The Requiring factors of work (p< .001) subarea of nurses’ job satisfaction, total patient satisfaction (p< .001), and medication errors (p< .001) were found to be the variables most significantly affected by other factors.Conclusions The findings suggest that nurse managers should focus on improving nursing practices by managing and organizing nurses’ work in a way that makes their employees feel supported, motivated and secure. Furthemore, nurse managers should adopt a leadership style that emphasizes safe and patient-centered care. The results also suggest that the administration of today’s health care organizations should actively evaluate nurse managers’ share of work activities to ensure that their daily work is in line with the organizational goals.
Possible associations between callers’ degree-of-worry and their socioeconomic status when contacting out-of-hours services: a prospective cohort study
Authors: Thilsted Sita LeBlanc , Gamst-Jensen Hejdi , Folke Fredrik , Tolstrup Janne S. , Thygesen Lau Caspar 
Published: December 2020

Abstract
Background: Telephone triage within out-of-hours (OOH) services aims to ascertain the urgency of a caller’s medical condition in order to determine the correct type of health care needed, ensuring patient safety. To improve the triage process by increasing patient‐centred communication, a triage tool has been developed, whereby callers are asked to rate their degree-of-worry (DOW) as a measure of self-evaluated urgency. Studies show that low socioeconomic status (SES), being single and non-Western ethnicity are associated to low self-rated health and morbidity and these factors may also be associated with high DOW. The aim of this paper was to examine if low SES, being single and non-Western ethnicity were associated to high DOW of callers contacting OOH services. Methods: A prospective cohort study design, at the OOH services for the Capital Region of Denmark. Over two weeks, 6,869 of 38,787 callers met the inclusion criteria: ³18 years, patients themselves or close relative/friend, reported DOW, had a valid personal identification number and gave informed consent. Callers were asked to report their DOW (1=minimal worry to 5=maximal worry), which was dichotomized into low (1-3) and high (4-5) DOW and linked to data from electronical medical records and Statistics Denmark. Socioeconomic factors (education and annual household income), marital status and ethnicity were assessed in relation to DOW by logistic regression.Results: High DOW was reported by 38.2% of the participants. Low SES (low educational level; OR 1.5, 95% CI 1.3-1.7 and low annual household income; 1.5, 1.3-1.6) was associated with high DOW and so too was being single; 1.2, 1.1-1.3 and of non-Western ethnicity; 2.9, 2.5-3.4.Conclusions: Knowledge of the association of low SES, marital status as single and non-Western ethnicity with high DOW among callers to OOH services may give call handlers a better understanding of callers’ DOW. If this does not correspond to the call handler’s perception of urgency, this knowledge may further encourage patient-centred communication, aid the triage process and increase patient safety. A better understanding of socioeconomic variables and their relation to callers’ DOW gives direction for future research to improve telephone triage of OOH services.