bluuebunny/crossref_metadata_2025_split huggingface dataset:
Views, knowledge, and practices of hospital pharmacists about using clinical pharmacokinetics to optimize pharmaceutical care services: a cross-sectional study
Authors: Shawahna Ramzi , Shraim Naser , Aqel Rafeef 
Published: March 2022

AbstractBackgroundPharmacokinetics (PK) is often used to optimize individualized dosing regimens of some drugs. This study was conducted to determine views, knowledge, and practices of hospital pharmacists in Palestine about using clinical PK to optimize pharmaceutical care services.MethodThis study was conducted in a cross-sectional design using a questionnaire. The questionnaire collected information about the nature of PK courses taught to hospital pharmacists, importance, relevance, effectiveness, adequacy, and depth of these courses, adequacy of PK skills, implementing PK knowledge/skills in current practice, and barriers limiting the implementation of PK to optimize pharmaceutical care services for hospitalized patients. The hospital pharmacists were visited in their places of work and were asked to complete the questionnaire in privacy. Categorical data were compared using Kruskal-Wallis test or Mann-WhitneyUtests.ResultsThe questionnaire was completed by 145 hospital pharmacists. Of the pharmacists, 84 (57.9%) received basic PK courses, 79 (54.5%) were taught integrated PK courses, and 94 (64.8%) agreed that the PK courses were important to their current practice. Similarly, 85 (57.9%) of the pharmacists were not satisfied with the teaching methods and contents of the PK courses. Pharmacists who obtained their degrees from Palestine were less satisfied with the methods of teaching compared to those who obtained their degrees from foreign countries (p-value = 0.006). Only 25 (17.2%) pharmacists reported frequent use of PK knowledge in their current practice. Lack of practical knowledge and continuing education, poor understanding of PK by pharmacists and other healthcare professionals were identified as barriers limiting the implementation of PK in optimizing pharmaceutical care services to hospitalized patients.ConclusionThe hospital pharmacists were generally not satisfied with the way PK courses were taught and expressed difficulty in implementing PK knowledge and skills to improve pharmaceutical care services to hospitalized patients. Integrating PK topics within other relevant courses and adopting more clinically oriented learning methods could improve understanding and implementing PK knowledge and skills in optimizing pharmaceutical services to hospitalized patients. Further studies are still needed to determine the optimal teaching/learning methods that can improve knowledge and skill acquisitions of pharmacists in the area of PK.
Navigating the care between two distinct cultures: a qualitative study of the experiences of Arabic-speaking immigrants in Norwegian hospitals
Authors: Alkhaled Tariq , Rohde Gudrun , Lie Birgit , Johannessen Berit 
Published: March 2022

Abstract
Background
During the past decades, there has been an increase in the number of immigrants to European and Scandinavian countries. This has challenged the health-care systems, which cater to the needs of patients despite their cultural and linguistic barriers, in these countries. Most studies on this topic have focused on the perspectives of health-care providers in delivering their service. The purpose of this qualitative study was to explore how hospitalized Arabic-speaking patients experienced their interaction with the Norwegian health-care system.

Methods
In-depth interviews with 20 participants and researcher’s participant observation were conducted to explore the idiosyncratic details and ascribed meanings that foreign-born patients attach to their everyday experience of the Norwegian health-care system. Thematic analysis was performed on the transcribed and translated versions of the in-depth interviews.

Results
The findings of this study indicated three interrelated core themes. Firstly, there exist challenges in understanding and being understood because of linguistic and cultural differences of newly migrated patients. Secondly, some patients missed the holistic and direct care available in their home countries. Finally, patients were satisfied with the Norwegian health-care system because of its compassion, care, and respect toward them as well as advanced health-care equipment.

Conclusion
Arabic-speaking patients in Norwegian hospitals experienced long waiting times and linguistic problems. Hence, a better and specialized interpreter service may resolve problems emanating from communication within the system and the subsequent delays in treatment. Compassionate care and the feeling of respect and love is the core strength of the Norwegian system as perceived by the patients.
A method for ultrafast tissue clearing that preserves fluorescence for multimodal and longitudinal brain imaging
Authors: Shan Qing-Hong , Qin Xin-Ya , Zhou Nan , Huang Chuan , Wang Yu , Chen Peng , Zhou Jiang-Ning 
Published: March 2022

Abstract
Background
Tissue-clearing techniques have recently been developed to make tissues transparent for three-dimensional (3D) imaging at different scales, including single-cell resolution. However, current tissue-clearing workflows have several disadvantages, including complex protocols, time-consuming application, and fluorescence quenching. Additionally, they can be used mainly for clearing larger-volume samples, preventing wide and easy applicability in conventional experimental approaches. In this study, we aimed to develop a versatile, fast, and convenient method for clearing thin and semi-thick samples, which can be used for three-dimensional imaging of experimental or even clinical samples.

Results
We developed an alkaline solution (AKS) containing a combination of 2,2′-thiodiethanol (TDE), DMSO, D-sorbitol, and Tris for tissue clearing, as the alkaline environment is suitable for maintaining the fluorescence of most commonly used fluorescence protein GFP and its variants, and tested its clearing effect on samples from mice and human brains. We assessed the clearing speed, the preservation of fluorescence protein and dyes, and the imaging depth and quality. The results showed that AKS treatment rapidly cleared 300-μm-thick brain slices and 1-mm-thick slices from different organs within 5 min and 1 h, respectively. Moreover, AKS was compatible with a variety of fluorescence proteins and dyes. Most importantly, AKS enhanced the fluorescence of YFP, in contrast to the majority of existing tissue-clearing methods which reduce the fluorescence intensity of fluorescent proteins. Using AKS, we performed long-time high-resolution imaging of weak fluorescent protein-labelled tissues, long-distance fibre tracking, larger-scale 3D imaging and cell counting of the entire brain area, neural circuit tracing, 3D neuromorphic reconstruction, and 3D histopathology imaging.

Conclusions
AKS can be used for simple and rapid clearing of samples from mice and human brains and is widely compatible with a variety of fluorescent dyes. Therefore, AKS has great potential to be used as a broad tissue-clearing reagent for biological optical imaging, especially for time-sensitive experiments.
Recovery of serum testosterone levels is an accurate predictor of survival from COVID-19 in male patients
Authors: Toscano-Guerra Emily , Martínez-Gallo Mónica , Arrese-Muñoz Iria , Giné Anna , Díaz-Troyano Noelia , Gabriel-Medina Pablo , Riveiro-Barciela Mar , Labrador-Horrillo Moisés , Martinez-Valle Fernando , Montalvá Adrián Sánchez , Hernández-González Manuel , Borrell Ricardo Pujol , Rodríguez-Frias Francisco , Ferrer Roser , Thomson Timothy M. , Paciucci Rosanna 
Published: March 2022

Abstract
Background
SARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients.

Methods
Biochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome.

Results
We have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes.

Conclusions
Recovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.
Integrative analyses of biomarkers and pathways for heart failure
Authors: Fan Shaowei , Hu Yuanhui 
Published: March 2022

Abstract
Background
Heart failure (HF) is the most common potential cause of death, causing a huge health and economic burden all over the world. So far, some impressive progress has been made in the study of pathogenesis. However, the underlying molecular mechanisms leading to this disease remain to be fully elucidated.

Methods
The microarray data sets of GSE76701, GSE21610 and GSE8331 were retrieved from the gene expression comprehensive database (GEO). After merging all microarray data and adjusting batch effects, differentially expressed genes (DEG) were determined. Functional enrichment analysis was performed based on Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, gene set enrichment analysis (GSEA), response pathway database and Disease Ontology (DO). Protein protein interaction (PPI) network was constructed using string database. Combined with the above important bioinformatics information, the potential key genes were selected. The comparative toxicological genomics database (CTD) is used to explore the interaction between potential key genes and HF.

Results
We identified 38 patients with heart failure and 16 normal controls. There were 315 DEGs among HF samples, including 278 up-regulated genes and 37 down-regulated genes. Pathway enrichment analysis showed that most DEGs were significantly enriched in BMP signal pathway, transmembrane receptor protein serine/threonine kinase signal pathway, extracellular matrix, basement membrane, glycosaminoglycan binding, sulfur compound binding and so on. Similarly, GSEA enrichment analysis showed that DEGs were mainly enriched in extracellular matrix and extracellular matrix related proteins. BBS9, CHRD, BMP4, MYH6, NPPA and CCL5 are central genes in PPI networks and modules.

Conclusions
The enrichment pathway of DEGs and GO may reveal the molecular mechanism of HF. Among them, target genes EIF1AY, RPS4Y1, USP9Y, KDM5D, DDX3Y, NPPA, HBB, TSIX, LOC28556 and XIST are expected to become new targets for heart failure. Our findings provide potential biomarkers or therapeutic targets for the further study of heart failure and contribute to the development of advanced prediction, diagnosis and treatment strategies.
Biomimetic GBM-targeted drug delivery system boosting ferroptosis for immunotherapy of orthotopic drug-resistant GBM
Authors: Liu Bao , Ji Qifeng , Cheng Ying , Liu Miao , Zhang Bangle , Mei Qibing , Liu Daozhou , Zhou Siyuan 
Published: March 2022

Abstract
Background
Clinical studies have shown that the efficacy of programmed cell death receptor-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors on glioblastoma (GBM) is much lower than what is expected because of the low immunogenicity of GBM. Ferroptosis of cancer cells can induce the maturation of dendritic cells (DC cells) and increase the activity of T cell. The activated T cells release IFN-γ, which subsequently induces the ferroptosis of cancer cells. Thus, the aim of this paper is to set up a new GBM-targeted drug delivery system (Fe3O4-siPD-L1@M-BV2) to boost ferroptosis for immunotherapy of drug-resistant GBM.

Results
Fe3O4-siPD-L1@M-BV2 significantly increased the accumulation of siPD-L1 and Fe2+ in orthotopic drug-resistant GBM tissue in mice. Fe3O4-siPD-L1@M-BV2 markedly decreased the protein expression of PD-L1 and increased the ratio between effector T cells and regulatory T cells in orthotopic drug-resistant GBM tissue. Moreover, Fe3O4-siPD-L1@M-BV2 induced ferroptosis of GBM cells and maturation of DC cell, and it also increased the ratio between M1-type microglia and M2-type microglia in orthotopic drug-resistant GBM tissue. Finally, the growth of orthotopic drug-resistant GBM in mice was significantly inhibited by Fe3O4-siPD-L1@M-BV2.

Conclusion
The mutual cascade amplification effect between ferroptosis and immune reactivation induced by Fe3O4-siPD-L1@M-BV2 significantly inhibited the growth of orthotopic drug-resistant GBM and prolonged the survival time of orthotopic drug-resistant GBM mice.

Graphical Abstract
Service utilization patterns and characteristics among clients of integrated supervised consumption sites in Toronto, Canada
Authors: Nassau Tanner , Kolla Gillian , Mason Kate , Hopkins Shaun , Tookey Paula , McLean Elizabeth , Werb Dan , Scheim Ayden 
Published: March 2022

Abstract
Introduction
Supervised consumption services (SCS), intended to reduce morbidity and mortality among people who inject drugs, have been implemented in a variety of delivery models. We describe and compare access to and uptake of co-located and external services among clients accessing harm reduction-embedded (HR-embedded) and community health center-embedded (CHC-embedded) SCS models.

Methods
Cross-sectional baseline data were collected between November 2018 and March 2020 as part of a cohort of people who inject drugs in Toronto, Canada designed to evaluate one HR-embedded and two CHC-embedded SCS. This analysis was restricted to clients who reported accessing these SCS more than once in the previous 6 months. Participants were classified as HR-embedded or CHC-embedded SCS clients based on self-reported usage patterns. Client characteristics, as well as access to onsite services and referral and uptake of external services, were compared by SCS model.

Results
Among 469 SCS clients, 305 (65.0%) primarily used HR-embedded SCS and 164 (35.0%) primarily used CHC-embedded SCS. Compared to clients accessing CHC-embedded SCS, clients accessing HR-embedded SCS were somewhat younger (37.6 vs. 41.4, p < 0.001), more likely to report fentanyl as their primary injected drug (62.6% vs. 42.7%, p < 0.001), and visited SCS more often (49.5% vs. 25.6% ≥ daily, p < 0.001). HR-embedded SCS clients were more likely to access harm reduction services onsite compared to CHC-embedded SCS clients (94.8% vs. 89.6%, p = 0.04), while CHC-embedded SCS clients were more likely to access non-harm reduction services onsite (57.3% vs. 26.6%, p < 0.001). For external services, HR-embedded SCS clients were more likely to receive a referral (p = 0.03) but less likely to report referral uptake (p = 0.009).

Conclusions
Clients accessing HR-embedded and CHC-embedded SCS were largely demographically similar but had different drug and SCS use patterns, with CHC-embedded SCS clients using the site less frequently. While clients of CHC-embedded SCS reported greater access to ancillary health services onsite, external service use remained moderate overall, underscoring the importance of co-location and support for clients with system navigation. Importantly, lack of capacity in services across the system may impact ability of staff to make referrals and/or the ability of clients to take up a referral.
Identification of blood-based key biomarker and immune infiltration in Immunoglobulin A nephropathy by comprehensive bioinformatics analysis and a cohort validation
Authors: Xu Jie , Shen Xiahong , Wei Xing , Ding Jie , Yuan Jiaojiao , Weng Zhen , He Yang 
Published: March 2022

Abstract
Background
To identify the critical genes in the onset and progression of Immunoglobulin A nephropathy (IgAN) and to explore its immune cell infiltration feature.

Methods
Differentially expressed genes (DEGs) were firstly screened from 1 blood-derived dataset GSE73953 and a glomerulus derived dataset GSE93798 through limma analysis, overlap genes omitting and weighted gene correlation network analysis (WGCNA) and further reduced according to expression pattern and correlation with the clinical features: eGFR and proteinuria, followed by external validation using the GSE37460 dataset and an IgAN cohort. In addition, the CIBERSORT tool for immune cell infiltration analysis, ceRNA network construction and Connectivity Map (CMAP) were also performed.

Results
A total of 195 DEGs were found, and among them, 3 upregulated (ORMDL2, NRP1, and COL4A1) and 3 downregulated genes (ST13, HSPA8 and PKP4) are verified to correlate clinically, and finally ORMDL2, NRP1 and COL4A1 were validated in patient cohort and with the ability of IgAN discrimination (highest AUC was COL4A1: 97.14%). The immune cell infiltration results revealed that significant differences could be found on resting memory CD4 T cells, activated NK cells, and M2 macrophages between control and IgAN.

Conclusions
Our results demonstrated here that significantly upregulated DEGs: ORMDL2, NRP1 and COL4A1, could be served as the diagnostic marker for IgAN, and dysregulated immune cell infiltration hinted possible the immune system intervention point in the setting of IgAN.
Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control
Authors: Moyano Ana , Blanch-Lombarte Oscar , Tarancon-Diez Laura , Pedreño-Lopez Nuria , Arenas Miguel , Alvaro Tamara , Casado Concepción , Olivares Isabel , Vera Mar , Rodriguez Carmen , del Romero Jorge , López-Galíndez Cecilio , Ruiz-Mateos Ezequiel , Prado Julia G. , Pernas María 
Published: March 2022

Abstract
Background
Long-Term Non-Progressors (LTNPs) are untreated Human Immunodeficiency virus type 1 (HIV-1) infected individuals able to control disease progression for prolonged periods. However, the LTNPs status is temporary, as viral load increases followed by decreases in CD4 + T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers, have been associated with effective immunodominant HIV-1 Gag-CD8 + T-cell responses restricted by protective HLA-B alleles. Individuals carrying HLA-B*14:02 control HIV-1 infection is related to an immunodominant Env-CD8 + T-cell response. Limited data are available on the contribution of HLA-B*14:02 CD8 + T -cells in LTNPs.

Results
In this study, we performed a virological and immunological detailed analysis of an HLA-B*14:02 LNTP individual that lost viral control (LVC) 27 years after HIV-1 diagnosis. We analysed viral evolution and immune escape in HLA-B*14:02 restricted CD8 + T -cell epitopes and identified viral evolution at the Env-EL9 epitope selecting the L592R mutation. By IFN-γ ELISpot and immune phenotype, we characterized HLA- B*14:02 HIV-1 CD8 + T cell responses targeting, Gag-DA9 and Env-EL9 epitopes before and after LVC. We observed an immunodominant response against the Env-EL9 epitope and a decreased of the CD8 T + cell response over time with LVC. Loss of Env-EL9 responses was concomitant with selecting K588R + L592R mutations at Env-EL9. Finally, we evaluated the impact of Env-EL9 escape mutations on HIV-1 infectivity and Env protein structure. The K588R + L592R escape variant was directly related to HIV-1 increase replicative capacity and stability of Env at the LVC.

Conclusions
These findings support the contribution of immunodominant Env-EL9 CD8 + T-cell responses and the imposition of immune escape variants with higher replicative capacity associated with LVC in this LNTP. These data highlight the importance of Env-EL9 specific-CD8 + T-cell responses restricted by the HLA-B*14:02 and brings new insights into understanding long-term HIV-1 control mediated by Env mediated CD8 + T-cell responses.