bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitation as a component of evidence implementation: a multinational perspective
Authors: Lizarondo Lucylynn , McArthur Alexa , Moola Sandeep , Albornos-Muñoz Laura , Badeaux Jennifer , Bennett Marsha , Püschel Vilanice Alves de Araújo , González-Monasterio Emilia Irene , Mwita Clifford , Perrenoud Beatrice , Porche Demetrius , Rodrigues Rogério , Stannard Daphne 
Published: August 2022

Background:
Facilitation is a key component of JBI's approach to evidence implementation along with context analysis and evaluation of process and outcomes. Although the role of facilitation is recognized as a critical component of evidence implementation, what constitutes effective facilitation is poorly understood.

Aim:
This article presents a descriptive exploration of facilitation as it occurs in evidence implementation initiatives conducted in various healthcare and geographical contexts. All projects used the JBI approach to evidence implementation.

Methods:
To provide a multinational perspective on how facilitation was operationalized to promote positive changes in clinical practice and health outcomes, five case studies of evidence implementation projects are presented.

Results:
The cases highlighted that facilitation is a multifaceted process that can be met through a variety of roles that address aspects of education and capacity building, partnerships, action planning, problem solving and evaluation. Facilitation in all cases appeared to be collaborative, with multiple ‘players’ within and outside of the health organization being involved in the process. Although there are similarities in activities, facilitation involved some level of local contextualization where there were unique or additional activities performed to accommodate the local needs and requirements of the health organization involved in each case. Numerous contextual factors influenced the success of the implementation initiative.

Conclusion:
The cases emphasized the complex nature of facilitation as a strategy for evidence implementation, indicating that contextual attributes and features define the range of knowledge, skills, and activities that should take place in order for facilitation to be effective. Although there appears to be some core components, tailoring and adaptation of the facilitation process (or roles) is required.
Heterologous vaccination as a strategy to minimize inequity in COVID-19 vaccine access: A modeling study in Thailand
Authors: Anupong Suparinthon , Chantanasaro Tanakorn , Wilasang Chaiwat , Jitsuk Natcha C. , Sararat Chayanin , Sornbundit Kan , Pattanasiri Busara , Chadsuthi Sudarat , Modchang Charin 
Published: August 2022

AbstractBackgroundVaccinations are the best hope to control the COVID-19 pandemic and save lives. Due to the high demand and failure to share vaccines equitably, there were not enough vaccine supplies to cover the majority of people in low- and middle-income countries during the early stage of vaccination. To cope with this problem, Thailand, an upper-middle-income country, decided to employ a heterologous vaccination strategy as the primary COVID-19 vaccination regimen in the country. The CoronaVac (CV) vaccine was administered as the first dose, followed by the ChAdOx1 nCoV-19 (AZ) vaccine as the second dose. However, there is no study to assess the effectiveness of the heterologous vaccination employed in Thailand compared to the standard homologous vaccination.MethodsWe delineated the course and timeline of COVID-19 vaccination in Thailand. An age-structured compartmental model for COVID-19 transmission and vaccination was constructed and employed to assess the effectiveness of the heterologous vaccination strategy. The impact of the vaccine prioritization strategies on COVID-19 mortality and infections was also investigated.ResultsWe found that the CV+AZ heterologous vaccination strategy outperforms the separate CV and AZ homologous vaccinations in reducing cumulative cases and deaths when combined with other non-pharmaceutical interventions. Furthermore, the results suggested that prioritizing vaccines for the elderly could be optimal in reducing COVID-19 mortality for a wide range of vaccination rates and disease transmission dynamics.ConclusionsOur modeling results suggested that to minimize the impacts of inequity in early COVID-19 vaccine access in low- and middle-income countries, those countries may use early accessible but maybe lower-efficacy vaccines as the first dose of heterologous vaccination in combination with higher-efficacy vaccines as the second dose when they are available.
Genome-wide characterization of the common bean kinome: catalog and insights into expression patterns and genetic organization
Authors: Aono Alexandre Hild , Pimenta Ricardo José Gonzaga , Dambroz Caroline Marcela da Silva , Costa Francisco Cleilson Lopes , Kuroshu Reginaldo Massanobu , de Souza Anete Pereira , Pereira Welison Andrade 
Published: August 2022

AbstractThe protein kinase (PK) superfamily is one of the largest superfamilies in plants and is the core regulator of cellular signaling. Even considering this substantial importance, the kinome of common bean (Phaseolus vulgaris) has not been profiled yet. Here, we identified and characterised the complete set of kinases of common bean, performing an in-depth investigation with phylogenetic analyses and measurements of gene distribution, structural organization, protein properties, and expression patterns over a large set of RNA-Sequencing data. Being composed of 1,203 PKs distributed across all P. vulgaris chromosomes, this set represents 3.25% of all predicted proteins for the species. These PKs could be classified into 20 groups and 119 subfamilies, with a more pronounced abundance of subfamilies belonging to the receptor-like kinase (RLK)-Pelle group. In addition to provide a vast and rich reservoir of data, our study supplied insights into the compositional similarities between PK subfamilies, their evolutionary divergences, highly variable functional profile, structural diversity, and expression patterns, modeled with coexpression networks for investigating putative interactions associated with stress response.
Molecular underpinnings of programming by early-life stress and the protective effects of early dietary ω6/ω3 ratio, basally and in response to LPS: hippocampal mRNA-miRNAs integrated approach
Authors: Reemst Kitty , Lopizzo Nicola , Abbink Maralinde R. , Engelenburg Hendrik J. , Cattaneo Annamaria , Korosi Aniko 
Published: August 2022

AbstractEarly-life stress (ELS) exposure increases the risk for mental disorders, including cognitive impairments later in life. We have previously demonstrated that a dietary low ω6/ω3 polyunsaturated fatty acid (PUFA) ratio protects against ELS-induced cognitive impairments. Several studies have implicated the neuroimmune system in the ELS and diet mediated effects, but currently the molecular pathways via which ELS and early diet exert their long-term impact are not yet fully understood. Here we study the effects of ELS and dietary PUFA ratio on hippocampal mRNA and miRNA expression in adulthood, both under basal and inflammatory conditions.Male mice were exposed to chronic ELS by the limiting bedding and nesting material paradigm from postnatal day(P)2 to P9, and provided with a diet containing a high (15:1.1) or low (1.1:1) ω6 linoleic acid to ω3 alpha-linolenic acid ratio from P2 to P42. At P120, memory was assessed using the object location task. Subsequently, a single lipopolysaccharide (LPS) injection was given and 24 hours later hippocampal genome-wide mRNA and microRNA (miRNA) expression was measured using microarray.An integrated miRNA – mRNA analysis revealed that ELS and early diet induced miRNA driven mRNA expression changes into adulthood. Under basal conditions both ELS and the diet affected molecular pathways related to hippocampal plasticity, with a low ω6/ω3 ratio diet specific activation of molecular pathways associated with improved hippocampal plasticity and learning and memory in mice previously exposed to ELS (e.g., CREB signaling and endocannabinoid neuronal synapse pathway). LPS induced miRNA and mRNA expression was strongly influenced by both ELS and early diet. In mice fed the high ω6/ω3 diet, LPS increased miRNA expression leading to activation of inflammatory pathways. In contrast, in mice fed the low ω6/ω3 diet, LPS reduced miRNA expression and altered target mRNA expression ultimately leading to limited activation of inflammatory signaling pathways and inhibition of pathways associated with hippocampal plasticity which was especially apparent in mice previously exposed to ELS.This data provides molecular insights into how the low ω6/ω3 diet during development could exert its long-lasting beneficial effects on hippocampal plasticity and learning and memory especially in a vulnerable population exposed to stress early in life, providing the basis for the development of intervention strategies.
Hepatocyte Differentiation From Mouse Liver Ductal Organoids By Transducing Four Liver-Specific Transcription Factors
Authors: Tomofuji Katsuhiro , Kondo Jumpei , Onuma Kunishige , Oyama Koki , Miyoshi Eiji , Fukumitsu Ken , Ishii Takamichi , Hatano Etsuro , Inoue Masahiro 
Published: August 2022

AbstractBackground & AimsHepatocyte sources that are expandable in vitro are required for liver regenerative medicine and to elucidate the mechanisms underlying the physiological functions of the liver. Liver ductal organoids (LDOs) comprise liver tissue stem cells with a bipotential capacity to differentiate into hepatocyte and cholangiocyte lineages, and can thus serve as a hepatocyte source. However, using current differentiation methods LDOs differentiate into immature hepatocytes while retaining strong cholangiocyte characteristics. We thus investigated an alternative differentiation method for LDOs to achieve hepatocyte maturation.MethodsWe extracted 12 candidate transcription factors to induce hepatocyte differentiation by comparing their gene expression in LDOs and liver tissues. After evaluating the effects of these transcription factors on LDOs, we analyzed the comprehensive gene expression profile, protein expression, and hepatic function in the transduced organoids.ResultsWe identified a combination of four transcription factors, Hnf4a, Foxa1, Prox1, and Hlf, which upregulated hepatic lineage markers and downregulated cholangiocyte markers. Differentiation-induced LDOs showed more hepatocyte-specific characteristics than those with the conventional method, enhancing the transition from cholangiocyte to hepatocyte lineage and hepatic functions, such as liver-specific protein synthesis, lipid droplet deposition, and ammonia detoxification.ConclusionTransduction of the four transcription factors (Hnf4a, Foxa1, Prox1, Hlf) is a promising strategy to promote the differentiation of LDOs to obtain mature hepatocyte-like cells with better functionality.
A unified analysis of atlas single cell data
Authors: Chen Hao , Nguyen Nam D. , Ruffalo Matthew , Bar-Joseph Ziv 
Published: August 2022

AbstractRecent efforts to generate atlas-scale single cell data provide opportunities for joint analysis across tissues and across modalities. Most of the existing methods for single cell atlas analysis use cells as the reference unit to combine datasets. However, such methods suffer from the inability to effectively integrate cross-modality data, hindering downstream gene-based analysis, and loss of genuine biological variations. Here we present a new data integration method, GIANT, which is for the first time designed for the atlas-scale analysis from the gene perspective. GIANT first converts datasets from different modalities into gene graphs, and then recursively embeds genes in the graphs into a latent space without additional alignment. Applying GIANT to the HuBMAP datasets creates a unified gene embedding space across multiple human tissues and data modalities, where gene representations reflect the functions of genes in their cells. Further evaluations demonstrate the usefulness of GIANT in discovering diverse gene functions, and underlying gene regulations in cells of different tissues.
LRIT3 expression in cone photoreceptors restores post-synaptic bipolar cell signalplex assembly and function in Lrit3-/- mice
Authors: Gregg Ronald G. , Hasan Nazarul , Borghuis Bart G. 
Published: August 2022

SUMMARYComplete congenital stationary night blindness (cCSNB) is a heterogeneous disorder characterized by poor dim light vision, myopia, and nystagmus, that is caused by mutations in genes critical for signal transmission between photoreceptors and depolarizing bipolar cells (DBCs). One such gene, LRIT3, is required for assembly of the post-synaptic signaling complex (signalplex) at the dendritic tips of DBCs, although the number of signalplex components impacted is greater in cone DBCs than in rod bipolar cells. This difference raises the possibility that LRIT3 is expressed both pre- and post-synaptically at cone terminals. Here we show that rAAV-mediated expression of LRIT3 in cones results in robust rescue of cone DBC signalplex components and restores downstream visual function, as measured by the light adapted ERG b-wave and electrophysiological recordings of BCs and RGCs. These data show that LRIT3 successfully restores function to cone DBCs in a trans-synaptic manner, potentially paving the way for therapeutic intervention in LRIT3-associated cCSNB.
Integrative genetic and genomic networks identify microRNA associated with COPD and ILD
Authors: Pavel Ana B. , Garrison Carly , Luo Lingqi , Liu Gang , Taub Daniel , Xiao Ji , Juan-Guardela Brenda , Tedrow John , Alekseyev Yuriy O. , Yang Ivana V. , Geraci Mark W. , Sciurba Frank , Schwartz David A. , Kaminski Naftali , Beane Jennifer , Spira Avrum , Lenburg Marc E. , Campbell Joshua D. 
Published: August 2022

ABSTRACTChronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) are clinically and molecularly heterogeneous diseases. We utilized clustering and integrative network analyses to elucidate roles for microRNAs (miRNAs) and miRNA isoforms (isomiRs) in COPD and ILD pathogenesis. Short RNA sequencing was performed on 351 lung tissue samples of COPD (n=145), ILD (n=144) and controls (n=64). Five distinct subclusters of samples were identified including 1 COPD-predominant cluster and 2 ILD-predominant clusters which associated with different clinical measurements of disease severity. Utilizing 262 samples with gene expression and SNP microarrays, we built disease-specific genetic and expression networks to predict key miRNA regulators of gene expression. Members of miR-449/34 family, known to promote airway differentiation by repressing the Notch pathway, were among the top connected miRNAs in both COPD and ILD networks. Genes associated with miR-449/34 members in the disease networks were enriched among genes that increase in expression with airway differentiation at an air-liquid interface. A highly expressed isomiR containing a novel seed sequence was identified at the miR-34c-5p locus. 47% of the anticorrelated predicted targets for this isomiR were distinct from the canonical seed sequence for miR-34c-5p. Overexpression of the canonical miR-34c-5p and the miR-34c-5p isomiR with an alternative seed sequence down-regulated NOTCH1 and NOTCH4. However, only overexpression of the isomiR down-regulated genes involved in Ras signaling such as CRKL and GRB2. Overall, these findings elucidate molecular heterogeneity inherent across COPD and ILD patients and further suggest roles for miR-34c in regulating disease-associated gene-expression.
The prognostic value of transthoracic echocardiography findings in hospitalized adult patients with COVID-19: A single-center retrospective analysis
Authors: Muliawan Hary Sakti , Agarwal Raksheeth , Nugraha Raka Aldy , Priyonugroho Gatut , Hertine Siti , Wicaksono Sony Hilal , Almazini Prima , Zamroni Dian 
Published: August 2022

AbstractBackgroundCardiac involvement in coronavirus disease 2019 (COVID-19) is associated with poor outcomes. Transthoracic echocardiography (TTE) can be used to assess cardiac structure and function non-invasively, and has been shown to influence management in COVID-19.ObjectivesWe aim to investigate the prognostic value of TTE findings in hospitalized adults with confirmed COVID-19.MethodsAll consecutive hospitalized adult patients with confirmed COVID-19 who underwent TTE assessment between 3rd April 2020 – 6th April 2021 were included. Comprehensive clinical data including TTE findings were collected from electronic medical records. Patients with mild-moderate and severe-critical COVID-19 were compared. Within the severe-critical group, patients who survived hospitalization and died were compared. Further analyses were conducted after matching for age >60 years, obesity, and diabetes.ResultsA total of 488 COVID-19 patients were included in this study; 202 with mild-moderate and 286 severe-critical disease. All mild-moderate patients and 152 severe-critical patients survived hospitalization. In the matched cohorts, TTE findings associated with severe-critical COVID-19 included left ventricular (LV) hypertrophy (OR: 1.91; CI: 1.21 – 3.02), LV diastolic dysfunction (OR: 1.55; CI: 1.00 – 2.38), right ventricular (RV) dysfunction (OR: 3.86; CI: 1.06 – 14.08), wall motion abnormalities (WMAs) (OR: 2.76; CI: 1.28 – 5.96), and any TTE abnormalities (OR: 2.99; CI: 1.73 – 5.17). TTE findings associated with mortality included RV dysfunction (OR: 3.53; CI: 1.12 – 11.19) and WMAs (OR: 2.63; CI: 1.26 – 5.49).ConclusionTTE is a non-invasive modality that can potentially be used for risk-stratification of hospitalized COVID-19 patients. These findings must be confirmed in larger prospective studies.
Autonomous Screening for Diabetic Macular Edema Using Deep Learning Processing of Retinal Images
Authors: Bressler Idan , Aviv Rachelle , Margalit Danny , Cohen Gal Yaakov , Ianchulev Tsontcho , Savant Shravan V. , Ramsey David J. , Dvey-Aharon Zack 
Published: August 2022

AbstractBackgroundDiabetic Macular Edema (DME) is a complication of diabetes which, when untreated, leads to vision loss. Screening for signs of diabetic eye disease, including DME, is recommended for all patients with diabetes at least every one to two years, however, compliance with this standard is low.MethodsA deep learning model was trained for DME detection using the EyePACS dataset. Data was randomly assigned, by participant, into development (n= 14,246) and validation (n= 1,583) sets. Analysis was conducted on the single image, eye, and patient levels. Model performance was evaluated using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). Independent validation was further performed on the IDRiD dataset, as well as new data.FindingsAt the image level, sensitivity of 0.889 (CI 95% 0.878, 0.900), specificity of 0.889 (CI 95% 0.877, 0.900), and AUC of 0.954 (CI 95% 0.949, 0.959) were achieved. At the eye level, sensitivity of 0.905 (CI 95% 0.890, 0.920), specificity of 0.902 (CI 95% 0.890, 0.913), and AUC of 0.964 (CI 95% 0.958, 0.969) were achieved. At the patient level, sensitivity of 0.901 (CI 95% 0.879, 0.917), specificity of 0.900 (CI 95% 0.883, 0.911), and AUC of 0.962 (CI 95% 0.955, 0.968) were achieved.InterpretationDME can be detected from color fundus imaging with high performance on all analysis metrics. Automatic DME detection may simplify screening, leading to more encompassing screening for diabetic patients. Further prospective studies are necessary.FundingFunding was provided by AEYE Health Inc.
Persistent Presence of Spike protein and Viral RNA in the Circulation of Individuals with Post-Acute Sequelae of COVID-19
Authors: Craddock Vaughn , Mahajan Aatish , Krishnamachary Balaji , Spikes Leslie , Chalise Prabhakar , Dhillon Navneet K. 
Published: August 2022

ABSTRACTSARS-CoV-2, the causative agent of COVID-19 disease has resulted in the death of millions worldwide since the beginning of the pandemic in December 2019. While much progress has been made to understand acute manifestations of SARS-CoV-2 infection, less is known about post-acute sequelae of COVID-19 (PASC). We investigated the levels of circulating SARS-CoV-2 components, Spike protein and viral RNA, in patients hospitalized with acute COVID-19 and in patients with and without PASC. In hospitalized patients with acute COVID-19 (n=116), we observed a positive correlation of Spike protein with D-dimer, length of hospitalization, and peak WHO score while viral RNA correlated with a tissue injury marker, lactate dehydrogenase (LDH). When comparing patients with post-COVID symptoms (n=33) and patients without (n=14), we found that Spike protein and viral RNA were more likely to be present in patients with PASC and in some cases at higher levels compared to acute COVID-19 patients. We also observed that the percent positivity of circulating viral RNA increased in the PASC positive individuals compared to acute COVID-19 group while Spike protein positivity remained the same. Additionally, we report that part of the circulating Spike protein is linked to extracellular vesicles without any presence of viral RNA in these vesicles. In conclusion, our findings suggest that Spike protein and/or viral RNA fragments persist in the recovered COVID-19 patients with PASC, regardless of their presence or absence during the acute COVID-19 phase. These results may help in understanding the reason(s) for why patients experience PASC symptoms and may offer potential therapeutic targets.
NO2 pollution decrease in big cities of Latin America during COVID-19 pandemic
Authors: Poullain Matias , Guerrieri Juan Martin , Miller Manuel Eduardo , Utgés María Eugenia , Santini María Soledad , Acosta Mariana Manteca , Fernández Agustín , Marsico Franco Leonel 
Published: August 2022

AbstractNO2 is a mainly anthropogenic gas that affects population health and its exposure is associated with several respiratory diseases. Its tropospheric concentration is associated with vehicle emissions. During 2020, COVID-19 lockdowns have impeded population’s mobility, hence constructing an almost ideal situation to study their relationship with tropospheric NO2 concentration. We used TROPOMI (TROPOspheric Monitoring Instrument) satellite images, Google mobility reports and vehicule count in order to study these relationships in six big Latin American metropolitan areas: México DF, São Paulo, Buenos Aires, Rio de Janeiro, Lima and Bogotá. In all of them, tropospheric NO2 concentration decreased during 2020 compared to 2019, particularly during April 2020. Temperature differences alone could not explain the NO2 concentration differences between February and April 2020. The daily vehicle count in Buenos Aires was a significantly important variable in order to explain NO2 concentration variations (p < 0.001) and it could be replaced by the daily Google’s residential variation without significant information loss (p ≃ 1). This study strengthens previous research findings about NO2 concentration reduction during COVID-19 lockdowns and shows the relationship between human mobility and air pollution in the particular context of Latin America big cities.