bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated knowledge translation to strengthen public policy research: a case study from experimental research on income assistance receipt among people who use drugs
Authors: Mendell Joanna , Richardson Lindsey 
Published: January 2021

Abstract
Background
Solutions to complex public health issues should be informed by scientific evidence, yet there are important differences between policy and research processes that make this relationship challenging. Integrated knowledge translation (IKT) is a strategy of sustained stakeholder engagement that intends to address barriers to evidence use. We highlight an example of an IKT project alongside a randomized controlled trial of a public policy intervention that tested different disbursement patterns of income assistance among people who use drugs in Vancouver, British Columbia.

Methods
A case study design was used where an IKT strategy led by a knowledge broker embedded within the research team acts as the case. This case study evaluates the process and effectiveness of the integrated knowledge translation project by measuring intermediate outcomes within a Theory of Change created to map pathways to impact. Content analysis was performed using an evaluation template through document review, post-event evaluations, and detailed tracking of media, knowledge translation activities and requests for information.

Results
A host of knowledge translation products synthesized existing research about the harms of synchronized income assistance disbursement and supported stakeholder engagement, facilitating conversation, relationship building and trust with stakeholders. Engagement improved knowledge of the contextual feasibility for system change, and contributed experiential knowledge to study findings. A combination of access to information and stakeholder and media engagement led to increased acknowledgement of the issue by policy makers directly involved in the income assistance system.

Conclusions
This project shows how a multipronged approach to IKT addressed barriers to evidence-informed public policy and successfully contributed to increased public discourse around income assistance policy reform. Additionally, sustained engagement with diverse stakeholders led to improved contextual knowledge and understanding of potential community level impacts that, along with scientific results, improved the evidence available to inform system change. This case study provides insight into the role IKT can play alongside research aimed at public policy improvements.

Trial registration
This IKT project was embedded within the study titled: The impact of Alternative Social Assistance Disbursement on Drug-Related Harm (TASA), known as Cheque Day Study, registered on ClinicalTrials.gov (NCT02457949) May 29, 2015.
COVID-19 outbreak in Brazil: adherence to national preventive measures and impact on people’s lives, an online survey
Authors: Faria de Moura Villela Edlaine , López Rossana Verónica Mendoza , Sato Ana Paula Sayuri , de Oliveira Fábio Morato , Waldman Eliseu Alves , Van den Bergh Rafael , Siewe Fodjo Joseph Nelson , Colebunders Robert 
Published: January 2021

AbstractBackgroundThe first case of COVID-19 infection was diagnosed in Brazil 26th February 2020. By March 16th, physical distancing and confinement measures were implemented by the Brazilian government. Little is known about how these measures were followed up by the Brazilian people and their impact on daily routine.MethodsIn early April 2020, using an online platform, we organized an online survey among adults living in Brazil about their COVID-19 preventive behavior and impact on their daily routine.ResultsData from 23,896 respondents were analyzed (mean age: 47.4 years). Due to COVID-19 restrictions, half (51.1%) of the professionals reported working from home. Regular handwashing was practiced by 98.7% of participants; 92.6% reported adhering to the 1.5-2 m physical distancing rule, but only 45.5% wore a face mask when going outside. While 29.3% of respondents found it relatively easy to stay at home, indoor confinement was extremely difficult for 7.9% of participants. Moreover, 11% of participants were extremely worried about their health during the COVID-19 epidemic. Younger people, male, persons living in a rural area/village or popular neighbourhoods, students and workers reported less preventive behaviour.ConclusionRestrictive measures markedly affected the daily and professional routines of Brazilians. Participants showed a satisfactory level of adherence to national COVID-19 prevention guidelines. Qualitative and follow-up studies are needed to monitor the impact of COVID-19 in the Brazilian society.
Antipsychotic medication adherence and preventive diabetes screening in Medicaid enrollees with serious mental illness: an analysis of real-world administrative data
Authors: Stockbridge Erica L. , Webb Nathaniel J. , Dhakal Eleena , Garg Manasa , Loethen Abiah D. , Miller Thaddeus L. , Nandy Karabi 
Published: January 2021

Abstract
Background
There is excess amenable mortality risk and evidence of healthcare quality deficits for persons with serious mental illness (SMI). We sought to identify sociodemographic and clinical characteristics associated with variations in two 2015 Healthcare Effectiveness Data and Information Set (HEDIS) measures, antipsychotic medication adherence and preventive diabetes screening, among Medicaid enrollees with serious mental illness (SMI).

Methods
We retrospectively analyzed claims data from September 2014 to December 2015 from enrollees in a Medicaid specialty health plan in Florida. All plan enrollees had SMI; analyses included continuously enrolled adults with antipsychotic medication prescriptions and schizophrenia or bipolar disorder. Associations were identified using mixed effects logistic regression models.

Results
Data for 5502 enrollees were analyzed. Substance use disorders, depression, and having both schizophrenia and bipolar disorder diagnoses were associated with both HEDIS measures but the direction of the associations differed; each was significantly associated with antipsychotic medication non-adherence (a marker of suboptimal care quality) but an increased likelihood of diabetes screening (a marker of quality care). Compared to whites, blacks and Hispanics had a significantly greater risk of medication non-adherence. Increasing age was significantly associated with increasing medication adherence, but the association between age and diabetes screening varied by sex. Other characteristics significantly associated with quality variations according to one or both measures were education (associated with antipsychotic medication adherence), urbanization (relative to urban locales, residing in suburban areas was associated with both adherence and diabetes screening), obesity (associated with both adherence and diabetes screening), language (non-English speakers had a greater likelihood of diabetes screening), and anxiety, asthma, and hypertension (each positively associated with diabetes screening).

Conclusions
The characteristics associated with variations in the quality of care provided to Medicaid enrollees with SMI as gauged by two HEDIS measures often differed, and at times associations were directionally opposite. The variations in the quality of healthcare received by persons with SMI that were identified in this study can guide quality improvement and delivery system reform efforts; however, given the sociodemographic and clinical characteristics’ differing associations with different measures of care quality, multidimensional approaches are warranted.
Doxorubicin treatment modulates chemoresistance and affects the cell cycle in two canine mammary tumour cell lines
Authors: Levi Michela , Salaroli Roberta , Parenti Federico , De Maria Raffaella , Zannoni Augusta , Bernardini Chiara , Gola Cecilia , Brocco Antonio , Marangio Asia , Benazzi Cinzia , Muscatello Luisa Vera , Brunetti Barbara , Forni Monica , Sarli Giuseppe 
Published: January 2021

Abstract
Background
Doxorubicin (DOX) is widely used in both human and veterinary oncology although the onset of multidrug resistance (MDR) in neoplastic cells often leads to chemotherapy failure. Better understanding of the cellular mechanisms that circumvent chemotherapy efficacy is paramount. The aim of this study was to investigate the response of two canine mammary tumour cell lines, CIPp from a primary tumour and CIPm, from its lymph node metastasis, to exposure to EC50(20h) DOX at 12, 24 and 48 h of treatment. We assessed the uptake and subcellular distribution of DOX, the expression and function of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), two important MDR mediators. To better understand this phenomenon the effects of DOX on the cell cycle and Ki67 cell proliferation index and the expression of p53 and telomerase reverse transcriptase (TERT) were also evaluated by immunocytochemistry (ICC).

Results
Both cell lines were able to uptake DOX within the nucleus at 3 h treatment while at 48 h DOX was absent from the intracellular compartment (assessed by fluorescence microscope) in all the surviving cells. CIPm, originated from the metastatic tumour, were more efficient in extruding P-gp substrates. By ICC and qRT-PCR an overall increase in both P-gp and BCRP were observed at 48 h of EC50(20h) DOX treatment in both cell lines and were associated with a striking increase in the percentage of p53 and TERT expressing cells by ICC. The cell proliferation fraction was decreased at 48 h in both cell lines and cell cycle analysis showed a DOX-induced arrest in the S phase for CIPp, while CIPm had an increase in cellular death without arrest. Both cells lines were therefore composed by a fraction of cells sensible to DOX that underwent apoptosis/necrosis.

Conclusions
DOX administration results in interlinked modifications in the cellular population including a substantial effect on the cell cycle, in particular arrest in the S phase for CIPp and the selection of a subpopulation of neoplastic cells bearing MDR phenotype characterized by P-gp and BCRP expression, TERT activation, p53 accumulation and decrease in the proliferating fraction. Important information is given for understanding the dynamic and mechanisms of the onset of drug resistance in a neoplastic cell population.
Evaluation of hematological alteration of vector‐borne pathogens in cats from Bangkok, Thailand
Authors: Do Thom , Kamyingkird Ketsarin , Chimnoi Wissanuwat , Inpankaew Tawin 
Published: January 2021

Abstract
Background
Cats can be carriers of infected arthropods and be infected with several vector-borne pathogens (VBPs) but there is limited knowledge about their pathogenic role in cats. This study aimed to assess the prevalence of some feline vector-borne agents by molecular technique and to characterize the hematological findings associated with these infections in a cat population from Bangkok Thailand.

Results
PCR was positive with at least one pathogen in 237 out of 372 subjects (63.7%), with prevalence of 39.5% (147/372) for Babesia spp., 36.9% (137/372) for hemoplasmas and 3.2% (12/372) for Hepatozoon spp. The cats older than 1 year were at significantly greater risk for VBPs infection (P = 0.001; OR = 1.43; 95% CI: 1.12 – 1.81) and hemoplasmas infection (χ2 = 10.8, df = 1; P < 0.0001; OR = 2.45; 95% CI: 1.49 – 4.01). A significant association between hematological findings and hemoplasma infection were identified in the present study. Besides, VBPs infection revealed more frequent in male cats (χ2= 6.38, df = 1, P = 0.01). Macrocytic hypochromic type of anemia was observed in cats infested with blood-sucking arthropods compared to the non-infested cats presented.

Conclusions
The current study confirmed that Babesia, Hepatozoon and hemoplasmas had infected semi-domesticated cats in Bangkok, Thailand, with Babesia and hemoplasmas being dominant in prevalence. Some hematological findings were significantly associated with cats infected with vector-borne pathogens in this study including leukocyte count and platelets count that may help support veterinary technicians in diagnosis and appropriate treatment. Campaigns of VBPs monitoring in Bangkok emphasizing on the investigation of vectors and possible routes of the infection in animals should be conducted to prevent the transmission of the pathogens.
MERS-CoV: epidemiology, molecular dynamics, therapeutics, and future challenges
Authors: Rabaan Ali A. , Al-Ahmed Shamsah H. , Sah Ranjit , Alqumber Mohammed A. , Haque Shafiul , Patel Shailesh Kumar , Pathak Mamta , Tiwari Ruchi , Yatoo Mohd. Iqbal , Haq Abrar Ul , Bilal Muhammad , Dhama Kuldeep , Rodriguez-Morales Alfonso J. 
Published: January 2021

AbstractThe Severe Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has gained research attention worldwide, given the current pandemic. Nevertheless, a previous zoonotic and highly pathogenic coronavirus, the Middle East Respiratory Syndrome coronavirus (MERS-CoV), is still causing concern, especially in Saudi Arabia and neighbour countries. The MERS-CoV has been reported from respiratory samples in more than 27 countries, and around 2500 cases have been reported with an approximate fatality rate of 35%. After its emergence in 2012 intermittent, sporadic cases, nosocomial infections and many community clusters of MERS continued to occur in many countries. Human-to-human transmission resulted in the large outbreaks in Saudi Arabia. The inherent genetic variability among various clads of the MERS-CoV might have probably paved the events of cross-species transmission along with changes in the inter-species and intra-species tropism. The current review is drafted using an extensive review of literature on various databases, selecting of publications irrespective of favouring or opposing, assessing the merit of study, the abstraction of data and analysing data. The genome of MERS-CoV contains around thirty thousand nucleotides having seven predicted open reading frames. Spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins are the four main structural proteins. The surface located spike protein (S) of betacoronaviruses has been established to be one of the significant factors in their zoonotic transmission through virus-receptor recognition mediation and subsequent initiation of viral infection. Three regions in Saudi Arabia (KSA), Eastern Province, Riyadh and Makkah were affected severely. The epidemic progression had been the highest in 2014 in Makkah and Riyadh and Eastern Province in 2013. With a lurking epidemic scare, there is a crucial need for effective therapeutic and immunological remedies constructed on sound molecular investigations.
Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer
Authors: Wu Shaocong , Luo Min , To Kenneth K. W. , Zhang Jianye , Su Chaoyue , Zhang Hong , An Sainan , Wang Fang , Chen Da , Fu Liwu 
Published: January 2021

Abstract
Background
Epidermal growth factor receptor (EGFR)-mutated lung cancer constitutes a major subgroup of non-small cell lung cancer (NSCLC) and osimertinib is administrated as first-line treatment. However, most patients with osimertinib treatment eventually relapse within one year. The underlying mechanisms of osimertinib resistance remain largely unexplored.

Methods
Exosomes isolation was performed by differential centrifugation. Co-culture assays were conducted to explore the alteration of drug sensitivity by cell viability and apoptosis assays. Immunofluorescence and flow cytometry were performed to visualize the formation or absorption of exosomes. Exosomes secretion was measured by Nanoparticle Tracking Analysis or ELISA. The xenograft tumor model in mice was established to evaluate the effect of exosomes on osimertinib sensitivity in vivo.

Results
Intercellular transfer of exosomal wild type EGFR protein confers osimertinib resistance to EGFR-mutated sensitive cancer cells in vitro and in vivo. Co-culture of EGFR-mutated sensitive cells and EGFR-nonmutated resistant cells promoted osimertinib resistance phenotype in EGFR-mutated cancer cells, while depletion of exosomes from conditioned medium or blockade of exosomal EGFR by neutralizing antibody alleviated this phenotype. Mechanistically, osimertinib promoted the release of exosomes by upregulated a Rab GTPase (RAB17). Knockdown of RAB17 resulted in the decrease of exosomes secretion. Moreover, exosomes could be internalized by EGFR-mutated cancer cells via Clathrin-dependent endocytosis and then the encapsulated exosomal wild type EGFR protein activated downstream PI3K/AKT and MAPK signaling pathways and triggered osimertinib resistance.

Conclusions
Intercellular transfer of exosomal wild type EGFR promotes osimertinib resistance in NSCLC, which may represent a novel resistant mechanism of osimertinib and provide a proof of concept for targeting exosomes to prevent and reverse the osimertinib resistance.
STED lithography in microfluidics for 3D thrombocyte aggregation testing
Authors: Buchegger Bianca , Tanzer Alexander , Posch Sandra , Gabriel Christian , Klar Thomas A. , Jacak Jaroslaw 
Published: January 2021

AbstractThree-dimensional photopolymerization techniques such as multiphoton polymerization lithography (MPL) and stimulated emission depletion (STED) lithography are powerful tools for fabricating structures in the sub-µm range. Combining these techniques with microfluidics enables us to broaden the range of their applications. In this study, we show a microfluidic device enhanced with MPL structures carrying STED-lithographically written nanoanchors that promote binding of the von Willebrand factor (vWF). The density of vWF is adjusted by varying the number of the nanoanchors on the 3D structures. This allows us to study the impact of the density of vWF on the activation of thrombocytes. The activation of the thrombocytes seems to decrease with the density of vWF on the 3D scaffolds inside the microfluidic channels.
Prioritizing knowledge translation in low- and middle-income countries to support pandemic response and preparedness
Authors: Mahendradhata Yodi , Kalbarczyk Anna 
Published: January 2021

AbstractThe COVID-19 pandemic has created urgent demand around the world for knowledge generation about a novel coronavirus, its transmission, and control, putting academic institutions at the frontline of politics. While many academic institutions are well poised to conduct research, there are well-documented barriers for these institutions, particularly in low- and middle-income countries (LMICs), to further conduct strategic synthesis and dissemination to promote knowledge utilization among policy-makers. These systemic barriers to knowledge translation (KT) pose significant challenges for academic institutions seeking to take advantage of unprecedented policy windows to inform evidence-based decision-making. Global health funding organizations should prioritize the support of academic institutions’ activities along the KT pathway, including both knowledge generation and strategic dissemination, to improve knowledge uptake for decision-making to improve health. Institutional capacity-building initiatives for KT have the potential to profoundly impact responses to this and future pandemics.
Mixed method evaluation of the CEBHA+ integrated knowledge translation approach: a protocol
Authors: Pfadenhauer Lisa M. , Grath Tanja , Delobelle Peter , Jessani Nasreen , Meerpohl Joerg J. , Rohwer Anke , Schmidt Bey-Marrié , Toews Ingrid , Akiteng Ann R. , Chapotera Gertrude , Kredo Tamara , Levitt Naomi , Ntawuyirushintege Seleman , Sell Kerstin , Rehfuess Eva A. 
Published: January 2021

AbstractBackgroundThe Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA+) is a research consortium concerned with the prevention, diagnosis and treatment of non-communicable diseases. CEBHA+ seeks to engage policymakers and practitioners throughout the research process in order to build lasting relationships, enhance evidence uptake, and create long-term capacity among partner institutions in Ethiopia, Malawi, Rwanda, South Africa and Uganda in collaboration with two German universities. This integrated knowledge translation (IKT) approach includes the formal development, implementation and evaluation of country specific IKT strategies.MethodsWe have conceptualised the CEBHA+ IKT approach as a complex intervention in a complex system. We will employ a comparative case study (CCS) design and mixed methods to facilitate an in-depth evaluation. We will use quantitative surveys, qualitative interviews, quarterly updates, and a policy document analysis to capture the process and outcomes of IKT across the African CEBHA+ partner sites. We will conduct an early stage (early 2020) and a late-stage evaluation (early 2022), triangulate the data collected with various methods at each site and subsequently compare our findings across the five sites.DiscussionEvaluating a complex intervention such as the CEBHA+ IKT approach is complicated, even more so when undertaken across five diverse countries. Despite conceptual, methodological and practical challenges, our comparative case study addresses important evidence gaps: While involving decision-makers in the research process is gaining traction worldwide, we still know very little regarding (i) whether this approach really makes a difference to evidence uptake, (ii) the mechanisms that make IKT successful, and (iii) relevant differences across socio-cultural contexts. The evaluation described here is intended to provide relevant insights on all of these aspects, notably in countries in Sub-Saharan Africa, and is expected to contribute to the science of IKT overall.