bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health research knowledge translation into policy in Zambia: policy-maker and researcher perspectives
Authors: Malama Annie , Zulu Joseph Mumba , Nzala Selestine , Kombe Maureen Mupeta , Silumbwe Adam 
Published: March 2021

Abstract
Background
The translation of public health research evidence into policy is critical to strengthening the capacity of local health systems to respond to major health challenges. However, a limited amount of public health research evidence generated in developing countries is actually translated into policy because of various factors. This study sought to explore the process of health research knowledge translation into policy and to identify factors that facilitate or hinder the process in Zambia.

Methods
This work was an exploratory qualitative study comprising two phases. Firstly, a document review of health policies and strategic frameworks governing research was undertaken to understand the macro-environment for knowledge translation in Zambia. Secondly, key informant interviews were conducted with those responsible for health research and policy formulation. The study interviewed 15 key informants and a thematic analysis approach was used.

Results
The document review showed that there are policy efforts to promote knowledge translation through improvement of the research macro-environment. However, the interviews showed that coordination and linkage of the knowledge creation, translation and policy-making processes remains a challenge owing to lack of research knowledge translation capacity, limited resources and lack of knowledge hubs. Emerging local research leadership and the availability of existing stock of underutilized local health research data provide an opportunity to enhance knowledge translation to feed into policy processes in Zambia.

Conclusions
Public health research knowledge translation into policy remains a challenge in Zambia. To enhance the uptake of research evidence in policy-making, this study suggests the need for improved coordination, financing and capacity-building in knowledge translation processes for both health researchers and policy-makers.
A new type of flexible CP12 protein in the marine diatom Thalassiosira pseudonana
Authors: Shao Hui , Huang Wenmin , Avilan Luisana , Receveur-Bréchot Véronique , Puppo Carine , Puppo Rémy , Lebrun Régine , Gontero Brigitte , Launay Hélène 
Published: March 2021

Abstract
Background
CP12 is a small chloroplast protein that is widespread in various photosynthetic organisms and is an actor of the redox signaling pathway involved in the regulation of the Calvin Benson Bassham (CBB) cycle. The gene encoding this protein is conserved in many diatoms, but the protein has been overlooked in these organisms, despite their ecological importance and their complex and still enigmatic evolutionary background.

Methods
A combination of biochemical, bioinformatics and biophysical methods including electrospray ionization-mass spectrometry, circular dichroism, nuclear magnetic resonance spectroscopy and small X ray scattering, was used to characterize a diatom CP12.

Results
Here, we demonstrate that CP12 is expressed in the marine diatom Thalassiosira pseudonana constitutively in dark-treated and in continuous light-treated cells as well as in all growth phases. This CP12 similarly to its homologues in other species has some features of intrinsically disorder protein family: it behaves abnormally under gel electrophoresis and size exclusion chromatography, has a high net charge and a bias amino acid composition. By contrast, unlike other known CP12 proteins that are monomers, this protein is a dimer as suggested by native electrospray ionization-mass spectrometry and small angle X-ray scattering. In addition, small angle X-ray scattering revealed that this CP12 is an elongated cylinder with kinks. Circular dichroism spectra indicated that CP12 has a high content of α-helices, and nuclear magnetic resonance spectroscopy suggested that these helices are unstable and dynamic within a millisecond timescale. Together with in silico predictions, these results suggest that T. pseudonana CP12 has both coiled coil and disordered regions.

Conclusions
These findings bring new insights into the large family of dynamic proteins containing disordered regions, thus increasing the diversity of known CP12 proteins. As it is a protein that is more abundant in many stresses, it is not devoted to one metabolism and in particular, it is not specific to carbon metabolism. This raises questions about the role of this protein in addition to the well-established regulation of the CBB cycle.
Choregraphy of metabolism by CP12 proteins in Viridiplantae and Heterokonta.
While the monomeric CP12 in Viridiplantae is involved in carbon assimilation, regulating phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) through the formation of a ternary complex, in Heterokonta studied so far, the dimeric CP12 is associated with Ferredoxin-NADP reductase (FNR) and GAPDH. The Viridiplantae CP12 can bind metal ions and can be a chaperone, the Heterokonta CP12 is more abundant in all stresses (C, N, Si, P limited conditions) and is not specific to a metabolism.
Categorisation of lumbar spine MRI referrals in Denmark as compliant or non-compliant to international imaging guidelines: an inter-rater reliability study
Authors: Krogh Susanne Brogaard , Jensen Tue Secher , Rolving Nanna , Laursen Malene , Thomsen Janus Nikolaj Laust , Hansen Casper Brink , Werenberg Christoffer Høj , Rasmussen Erik , Carlson Rune , Jensen Rikke Krüger 
Published: March 2021

Abstract
Background
Managing low back pain (LBP) often involves MRI despite the fact that international guidelines do not recommend routine imaging. To allow us to explore the topic and use this knowledge in further research, a reliable method to review the MRI referrals is needed. Consequently, this study aimed to assess the inter-rater reliability of a method evaluating lumbar spine MRI referrals’ appropriateness.

Methods
Four inexperienced students (chiropractic master’s students) and a senior clinician (chiropractor) were included as independent raters in this inter-rater reliability study. Lumbar spine MRI referrals from primary care on patients (> 18 years) with LBP with or without leg pain were included. The referrals were classified using a modified version of the American College of Radiology (ACR) imaging appropriateness criteria for LBP. Categories of appropriate referrals included; fractures, cancer, previous surgery, candidate for surgery or suspicion of cauda equina. Inappropriate referrals included lacking information on previous non-surgical treatment, no word on non-surgical treatment duration, or “other reasons” for inappropriate referrals.
After two rounds of training and consensus sessions, 50 lumbar spine MRI referrals were reviewed independently by the five raters. Inter-rater reliability was quantified using unweighted Kappa statistics, and the observed agreement was calculated with both a pairwise comparison and an overall five-rater comparison.

Results
Inter-rater reliability was substantial, with a Kappa value for appropriate vs. inappropriate referrals of 0.76 (95% CI: 0.55–0.89). When six and eight subcategories were evaluated, the Kappa values were 0.77 (95% CI: 0.58–0.91) and 0.82 (95% CI: 0.72–0.92), respectively.
The overall percentage of agreement for appropriate and inappropriate referrals was 92% and ranged from 88 to 98% for the pairwise comparisons of the five raters’ results. For the six and eight subcategories, the overall agreement was 92 and 88%, respectively, ranging from 88 to 98% and 84–92%, respectively, for the pairwise comparisons.

Conclusion
The inter-rater reliability of the evaluation of the appropriateness of lumbar spine MRI referrals, according to the modified ACR-appropriateness criteria, was found to range from substantial to almost perfect and can be used for research and quality assurance purposes.
All-arthroscopic repair of Atzei class II and III triangular fibrocartilage complex tears using the FasT-Fix suture device
Authors: Tsai Mengchun , Lin Yi-Hsuan , Chiu Chih-Hao , Cheng Chun-Ying , Chan Yi-Sheng , Chen Alvin Chao-Yu 
Published: March 2021

Abstract
Background
The study is aimed to propose an arthroscopic repair technique using a pre-tied suture device for peripheral TFCC (triangular fibrocartilage complex) tear with proximal component involvement.

Methods
Through a retrospective review in the medical records of patients who underwent unilateral arthroscopic repair for TFCC Palmer IB lesion between 2017 and 2019, 12 patients were arthroscopically diagnosed as proximal component tear and received more than 1 year follow-up postoperatively. The arthroscope was introduced from 6R portal to discriminate Atzei class II from III lesions by a “visualization test” and to supervise the repair procedure using pre-tied FasT-Fix suture device from 3-4 portal. Two poly-ether-ether-ketone (PEEK) blocks were further advanced along the device needle to finally seat outside the ulnar joint capsule, followed by gradually tightening the pre-tied suture loop until the TFCC periphery was securely repositioned and held stably.

Results
Operation time averaged 87 min. Hook test and DRUJ arthroscopy confirmed proximal component tear in all 12 wrists. Four patients were diagnosed to be Atzei class II lesion as full thickness tear of distal component was arthroscopically identified from 6R portal while the other 8 exhibited partial thickness tear and were categorized as class III lesion. Follow-up averaged 15 months with a range of 12 to 24 months. Mayo modified wrist score improved from an average of 61.3 preoperatively to 90.4 at the latest visit.

Conclusions
A modified technique for diagnosis and all-arthroscopic repair in TFCC Atzei class II and III lesions using a pre-tied suture device is a feasible and safe option with promising results.
Circulating tumor cells and palbociclib treatment in patients with ER-positive, HER2-negative advanced breast cancer: results from a translational sub-study of the TREnd trial
Authors: Galardi Francesca , De Luca Francesca , Biagioni Chiara , Migliaccio Ilenia , Curigliano Giuseppe , Minisini Alessandro M. , Bonechi Martina , Moretti Erica , Risi Emanuela , McCartney Amelia , Benelli Matteo , Romagnoli Dario , Cappadona Silvia , Gabellini Stefano , Guarducci Cristina , Conti Valerio , Biganzoli Laura , Di Leo Angelo , Malorni Luca 
Published: March 2021

Abstract
Background
Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized patients with ABC to palbociclib alone or palbociclib plus the endocrine therapy received in the prior line of treatment. Moreover, we evaluated RB1 gene expression on CTCs and explored its prognostic role within the cTREnd subpopulation.

Methods
Forty-six patients with ER-positive, HER2-negative ABC were analyzed. Blood samples were collected before starting palbociclib treatment (timepoint T0), after the first cycle of treatment (timepoint T1), and at disease progression (timepoint T2). CTCs were isolated and counted by CellSearch® System using the CellSearch™Epithelial Cell kit. Progression-free survival (PFS), clinical benefit (CB) during study treatment, and time to treatment failure (TTF) after study treatment were correlated with CTC counts. Samples with ≥ 5 CTCs were sorted by DEPArray system® (DA). RB1 and GAPDH gene expression levels were measured by ddPCR.

Results
All 46 patients were suitable for CTCs analysis. CTC count at T0 did not show significant prognostic value in terms of PFS and CB. Patients with at least one detectable CTC at T1 (n = 26) had a worse PFS than those with 0 CTCs (n = 16) (p = 0.02). At T1, patients with an increase of at least three CTCs showed reduced PFS compared to those with no increase (mPFS = 3 versus 9 months, (p = 0.004). Finally, patients with ≥ 5 CTCs at T2 (n = 6/23) who received chemotherapy as post-study treatment had a shorter TTF (p = 0.02). Gene expression data for RB1 were obtained from 19 patients. CTCs showed heterogeneous RB1 expression. Patients with detectable expression of RB1 at any timepoint showed better, but not statistically significant, outcomes than those with undetectable levels.

Conclusions
CTC count seems to be a promising modality in monitoring palbociclib response. Moreover, CTC count at the time of progression could predict clinical outcome post-palbociclib. RB1 expression analysis on CTCs is feasible and may provide additional prognostic information. Results should be interpreted with caution given the small studied sample size.
Occurrence of Phlebotomine sand flies (Diptera: Psychodidae) in the northeastern plain of Italy
Authors: Michelutti Alice , Toniolo Federica , Bertola Michela , Grillini Marika , Simonato Giulia , Ravagnan Silvia , Montarsi Fabrizio 
Published: March 2021

Abstract
Background
Recent climate and environmental changes have resulted in the geographical expansion of Mediterranean Leishmania infantum vectors towards northern latitudes and higher altitudes in different European countries, including Italy, where new foci of canine leishmaniasis have been observed in the northern part of the country. Northern Italy is also an endemic area for mosquito-borne diseases. During entomological surveillance for West Nile virus, mosquitoes and other hematophagous insects were collected, including Phlebotomine sand flies. In this study, we report the results of Phlebotomine sand fly identification during the entomological surveillance conducted from 2017 to 2019.

Methods
The northeastern plain of Italy was divided by a grid with a length of 15 km, and a CO2-CDC trap was placed in each geographical unit. The traps were placed ~ 15 km apart. For each sampling site, geographical coordinates were recorded. The traps were operated every two weeks, from May to November. Sand flies collected by CO2-CDC traps were identified by morphological and molecular analysis.

Results
From 2017 to 2019, a total of 303 sand flies belonging to the species Phlebotomus perniciosus (n = 273), Sergentomyia minuta (n = 5), P. mascittii (n = 2) and P. perfiliewi (n = 2) were collected, along with 21 unidentified specimens. The trend for P. perniciosus collected during the entomological surveillance showed two peaks, one in July and a smaller one in September. Sand flies were collected at different altitudes, from −2 m above sea level (a.s.l.) to 145 m a.s.l. No correlation was observed between altitude and sand fly abundance.

Conclusions
Four Phlebotomine sand fly species are reported for the first time from the northeastern plain of Italy. Except for S. minuta, the sand fly species are competent vectors of Leishmania parasites and other arboviruses in the Mediterranean Basin. These findings demonstrate the ability of sand flies to colonize new environments previously considered unsuitable for these insects. Even though the density of the Phlebotomine sand fly population in the plain areas is consistently lower than that observed in hilly and low mountainous areas, the presence of these vectors could herald the onset of epidemic outbreaks of leishmaniasis and other arthropod-borne diseases in areas previously considered non-endemic.

Graphical Abstract
A novel fungal metabolite inhibits Plasmodium falciparum transmission and infection
Authors: Niu Guodong , Wang Xiaohong , Hao Yue , Kandel Shambhu , Niu Guomin , Raptis Raphael G. , Li Jun 
Published: March 2021

Abstract
Background
Malaria transmission depends on infected mosquitoes and can be controlled by transmission-blocking drugs. The recently discovered FREP1-mediated malaria transmission pathway is an excellent target to screen drugs for limiting transmission.

Methods
To identify candidate small molecules, we used an ELISA-based approach to analyze extracts from a fungal library for inhibition of the FREP1–parasite interaction. We isolated and determined one active compound by chromatography and crystallography, respectively. We measured the effects of the bioactive compound on malaria transmission to mosquitoes through standard membrane-feeding assays (SMFA) and on parasite proliferation in blood by culturing.

Results
We discovered the ethyl acetate extract of the fungus Purpureocillium lilacinum that inhibited Plasmodium falciparum transmission to mosquitoes. Pre-exposure to the extract rendered Anopheles gambiae resistant to Plasmodium infection. Furthermore, we isolated one novel active compound from the extract and identified it as 3-amino-7,9-dihydroxy-1-methyl-6H-benzo[c]chromen-6-one, or “pulixin.” Pulixin prevented FREP1 from binding to P. falciparum-infected cell lysate. Pulixin blocked the transmission of the parasite to mosquitoes with an EC50 (the concentration that gave half-maximal response) of 11 µM based on SMFA. Notably, pulixin also inhibited the proliferation of asexual-stage P. falciparum with an EC50 of 47 nM. The compound did not show cytotoxic effects at a concentration of 116 µM or lower.

Conclusion
By targeting the FREP1–Plasmodium interaction, we discovered that Purpureocillium lilacinum extract blocked malaria transmission. We isolated and identified the bioactive agent pulixin as a new compound capable of stopping malaria transmission to mosquitoes and inhibiting parasite proliferation in blood culture.

Graphical Abstract
Lower extremity compression garments use by athletes: why, how often, and perceived benefit
Authors: Franke Thierry P. C. , Backx Frank J. G. , Huisstede Bionka M. A. 
Published: March 2021

Abstract
Background
Studies on the benefits of lower extremity compression garments (CGs) have focused on their effects on post-exercise recovery and performance improvement. Less is known about why athletes actually use CGs, the frequency with which they use them, and perceived benefits from using CGs. The purpose of this study was to investigate which athletes use CGs, why athletes use CGs, when CGs are worn by athletes, and, in case of an injury or injury prevention, for which injuries CGs are used.

Methods
This cross-sectional study involved 512 athletes who used lower extremity CGs. Athletes completed a questionnaire on the type of CGs they used, and when and why they used them. They also reported their sports participation, past and current sports injuries, and the perceived benefits of using CGs.

Results
88.1% (n=451) of the athletes were endurance athletes and 11.9% (n=61) were non-endurance athletes. Endurance and non-endurance athletes reported running (84.7%, n=382) and obstacle course racing (24.6%, n=15) the most frequently as primary sports, respectively. The most-used CG was the compression sock (59.2%, n=303). In total, 47.5% (n=246) of the athletes used a CG primarily to prevent re-injury and 14.5% (n=74) to reduce symptoms of a current sports injury. Other primary reported aims were primary prevention (13.6%), post-exercise recovery (14.3%), sports performance improvement (8.8%), and to look good (0.2%). The point prevalence of past and current sports injuries among all athletes was 84.2 and 20.2%, respectively. The most common current sports injuries were shin and calf injuries. Many athletes “always” or “often” used their CGs during training (56.8%, n=279) and competitions (72.9%, n=264). Furthermore, almost 90% of the athletes that aimed to prevent re-injury by using CGs reported that CGs contributed to secondary injury prevention.

Conclusion
88% of the CG-users were endurance athletes, of which 85% were runners. All athletes mainly used CGs to prevent injury recurrence, but also to reduce symptoms of a current sports injury. A majority of the athletes reported positive perceived effects from the CGs. CGs were used more during than after sports participation.
Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization
Authors: Dong Bing , Wang Chao , Zhang Jing , Zhang Jinrong , Gu Yinuo , Guo Xiaoping , Zuo Xu , Pan He , Hsu Alan Chen-Yu , Wang Guoqiang , Wang Fang 
Published: March 2021

Abstract
Background
Severe, steroid-resistant asthma (SSRA) is a serious clinical problem in asthma management. Affected patients have severe clinical symptoms, worsened quality of life, and do not respond to steroid, a mainstay steroid treatment of asthma. Thus, effective therapies are urgently needed. Exosomes derived from mesenchymal stem cell (MSC-Exo) has become attractive candidates for the lung inflammatory diseases through its immunomodulatory effects. In this study, we explored the therapeutic effects of MSC-Exo in SSRA and identified the therapeutic mechanism of MSC-Exo.

Method
Exosomes from human umbilical cord mesenchymal stem cell (hUCMSC) were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis and flow cytometry analysis. Effects of MSC-Exo on airway hyper responsiveness (AHR), inflammation, histopathology, and macrophage polarization in SSRA in mice were evaluated. Systematic depletion of macrophages determined the role of macrophages in the therapeutic effect of SSRA in mice. LPS-stimulated RAW 264.7 cell model was constructed to determine the underlying mechanism of MSC-Exo on macrophage polarization. qRT-PCR, Western blotting, immunofluorescence, and flow cytometry were performed to evaluate the expression of M1 or M2 markers. Tandem mass tags (TMT)-labeled quantitative proteomics were applied to explore the central protein during the regulation effect of MSC-Exo on macrophage polarization. Knockdown and overexpression of TRAF1 were used to further clarify the role of the central protein on macrophage polarization.

Result
We successfully isolated and characterized exosomes from hUCMSCs. We verified that the intratracheal administration of MSC-Exo reversed AHR, histopathology changes, and inflammation in SSRA mice. Systematic depletion of macrophages weakened the therapeutic effect of MSC-Exo. We found that MSC-Exo treatment inhibited M1 polarization and promoted M2 polarization in LPS-stimulated RAW 264.7 cells. Subsequently, tumor necrosis factor receptor-associated factor 1 (TRAF1) was determined as the central protein which may be closely related to the regulation of macrophage polarization from TMT-labeled quantitative proteomics analysis. Knockdown and overexpression of TRAF1 demonstrated that the effect of MSC-Exo treatment on macrophage polarization, NF-κB and PI3K/AKT signaling was dependent on TRAF1.

Conclusion
MSC-Exo can ameliorate SSRA by moderating inflammation, which is achieved by reshaping macrophage polarization via inhibition of TRAF1.