bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considering health literacy in cardiovascular disease management: a qualitative study on healthcare professionals’ and patients’ perspectives
Authors: Perrin Adèle , Damiolini Eléonore , Schott Anne-Marie , Zermati Jéremy , Bravant Estelle , Delahaye François , Dima Alexandra L. , Haesebaert Julie 
Published: September 2022

AbstractBackgroundImplementing practices adapted to patient health literacy (HL) is a promising avenue for improving their outcomes in the context of cardiovascular diseases (CVD). The health communication skills of healthcare professionals (HCPs) and the quality of information provided are essential for low-HL patients. We aimed to explore HCP knowledge about HL, patients’ and HCPs’ views on current practices regarding low-HL patients, and facilitators and barriers to adapting communication to patients’ HL level, in order to prepare the implementation of a complex intervention dedicated to improve CVD management for low-HL patients.MethodsWe conducted face-to-face semi-structured interviews with HCPs practicing in cardiology units and patients hospitalized for CVD. The study design and analysis were based on the Theory of Planned Behavior for HCPs and on the framework of Health Literacy and Health Action for patients. Deductive and inductive thematic analysis were used. Barriers and facilitators were structured into an Ishikawa fishbone diagram and implementation strategies were selected to address resulting themes from the Expert Recommendations for Implementing Change (ERIC).ResultsFifteen patients and 14 HCPs were interviewed. HCPs had partial knowledge of HL dimensions. Perceptions of HCPs and patients were not congruent regarding HCP-patient interactions and information provided by hospital and community HCPs. HCPs perceived they lacked validated tools and skills, and declared they adapted spontaneously their communication when interacting with low-HL patients. Patients expressed unmet needs regarding communication during hospital discharge and at return to home.ConclusionTo implement HL-tailored practices in this setting, our results suggest that several implementation strategies will be valuable at individual (engaging patients and their family), interactional (educating and training of HCPs about HL), and organizational levels (creating a multidisciplinary HCP interest group dedicated to HL).Trial registrationClinicalTrials.gov, (NCT number) NCT03949309, May 10, 2019.
Occult infection with hepatitis B virus PreS variants synergistically promotes hepatocellular carcinoma development in a high-fat diet context by generating abnormal ceramides
Authors: Liu Chang , Chen Kun , Zhao Fei , Xuan Lingling , Wang Yuting , Xu Chungui , Wu Zhiyuan , Wang Dongmei , Qu Chunfeng 
Published: September 2022

Abstract
Background
Some occult hepatitis B virus (HBV) infections are resulted from PreS mutations that reduce secretion of envelope protein (HBsAg). We investigated the ceramide amounts and species in hepatocytes infected with PreS variants that were isolated from HBsAg-seronegative patients with hepatocellular carcinoma (HCC) and the ceramide effects on autochthonous HCC development in murine models.

Methods
HBV PreS/S regions from 35 HBsAg-seronegative HCC patients were sequenced. Hepatocyte cell lines and male C57BL/6J mouse livers were transfected with two PreS variant representatives. The ceramides with variated lengths of fatty acyl chains were quantified. Tumour development was examined in the HBV-transfected mice fed different diet types.

Results
In HBsAg-seronegative HCC patients, nonneoplastic liver tissues harboured HBsAg and replication-competent HBV. The most frequently detected PreS/S variants carried mutations of altered amino acid properties in HBsAg compared with an isolate from one HBsAg-seronegative HCC patient. Hepatocyte infection with PreS variants caused HBsAg retention within the endoplasmic reticulum and generated more amounts of ceramides with C16:0 ceramide elevated the highest. Saturated fatty acids aggravated the PreS variant-infected hepatocytes to generate abnormal amounts and species of ceramides, which with HBV proteins synergistically activated NLRP3 inflammasome in liver inflammatory macrophages. Liver tumours were only detected in HBV-transfected mice fed high-fat diet, with higher tumour loads in the PreS variant-transfected, associated with abnormal ceramide generation.

Conclusions
HBV PreS mutations which altered amino acid properties of envelope proteins inhibited HBsAg secretion. Hepatocyte infection with PreS variants generated abnormal ceramides which with HBV proteins coactivated NLRP3 inflammasome in liver macrophages to promote autochthonous HCC development.
Alpha-chloralose poisoning in cats in three Nordic countries - the importance of secondary poisoning
Authors: Windahl Ulrika , Tevell Åberg Annica , Kryuchkov Fedor , Lundgren Sandra , Tegner Cecilia , Dreimanis Kristoffer , Koivisto Sanna , Simola Outi , Sandvik Morten , Bernhoft Aksel 
Published: September 2022

Abstract
Background
Alpha-chloralose (AC) is a compound known to be toxic to various animal species and humans. In 2018 and 2019 an increase in suspected cases of AC poisoning in cats related to the use of AC as a rodenticide was reported to national veterinary and chemical authorities in Finland, Norway and Sweden by veterinarians working in clinical practices in respective country. The aims of this study were to prospectively investigate AC poisoning in cats, including possible secondary poisoning by consuming poisoned mice, and to study metabolism and excretion of AC in cats through analysis of feline urine.

Methods
Data on signalment, history and clinical findings were prospectively collected in Finland, Norway and Sweden from July 2020 until March of 2021 using a questionnaire which the attending veterinarian completed and submitted together with a serum sample collected from suspected feline cases of AC-poisoning. The diagnosis was confirmed by quantification of AC in serum samples. Content of AC was studied in four feline urine samples, including screening for AC metabolites by UHPLC-HRMS/MS. Bait intake and amount of AC consumed by mice was observed in wild mice during an extermination of a rodent infestation.

Results
In total, 59 of 70 collected questionnaires and accompanying serum samples were included, with 127 to 70 100 ng/mL AC detected in the serum. Several tentative AC-metabolites were detected in the analysed feline urine samples, including dechlorinated and oxidated AC, several sulfate conjugates, and one glucuronic acid conjugate of AC. The calculated amount of AC ingested by each mouse was 33 to 106 mg with a mean of 61 mg.

Conclusions
Clinical recognition of symptoms of AC poisoning in otherwise healthy cats roaming free outdoors and known to be rodent hunters strongly correlated with confirmation of the diagnosis through toxicological analyses of serum samples. The collected feline exposure data regarding AC show together with the calculation of the intake of bait and subsequent AC concentrations in mice that secondary poisoning from ingestion of mice is possible. The results of the screening for AC metabolites in feline urine confirm that cats excrete AC both unchanged and metabolized through dechlorination, oxidation, glucuronidation and sulfatation pathways.
Differences in l-arginine metabolism and asthma morbidity among asthma patients with and without obstructive sleep apnea
Authors: Althoff Meghan D. , Jimenez Guillermo , Peterson Ryan , Jin Ying , Grasemann Hartmut , Sharma Sunita , Federman Alex D. , Wisnivesky Juan P. , Holguin Fernando 
Published: September 2022

Abstract
Background
Imbalance in l-arginine and nitric oxide (NO) metabolism has been implicated in the pathophysiology of asthma and obstructive sleep apnea (OSA), and both diseases impact the other’s morbidity. We sought to determine whether l-arginine/NO metabolism differs between adults with asthma with or without comorbid OSA, and its association with asthma morbidity.

Methods
This is a cross-sectional study of 322 adults with asthma recruited in Denver, CO and New York City, NY. Data were collected on OSA status, spirometry, and metrics of asthma control and morbidity. l-Arginine metabolites were quantified in patient serum. Bivariate analyses and multiple regression were performed to determine differences between l-arginine metabolism, OSA and association with asthma morbidity.

Results
Among the 322 participants, 92 (28.5%) had OSA. The cohort was 81.6% female, 23.4% identified as Black and 30.6% as Latino. Patients with asthma and OSA had significantly higher serum concentrations of NO synthase inhibitor asymmetric dimethylarginine (ADMA) (p-value = 0.019), lower L-arginine to ornithine ratios (p-value = 0.003), and increased ornithine (p-value = 0.001) and proline levels (p-value < 0.001) compared to those without OSA. In adjusted models, OSA was associated with worse asthma control, adjusted mean difference in asthma control questionnaire of 0.36 (95% confidence interval [CI]: 0.06 to 0.65), and asthma quality of life questionnaire, adjusted mean difference: − 0.53 (95% CI: − 0.85 to − 0.21), after adjusting for relevant covariates including body mass index and L-arginine metabolites.

Conclusions
Adults with asthma and OSA had increased ADMA, an inhibitor of nitric oxide synthase, and greater metabolism of l-arginine via the arginase pathway compared to those with asthma alone, indicating a possible shared pathophysiological mechanism of these diseases.
Steric accessibility of the N-terminus improves the titer and quality of recombinant proteins secreted from Komagataella phaffii
Authors: Dalvie Neil C. , Naranjo Christopher A. , Rodriguez-Aponte Sergio A. , Johnston Ryan S. , Christopher Love J. 
Published: September 2022

Abstract
Background
Komagataella phaffii is a commonly used alternative host for manufacturing therapeutic proteins, in part because of its ability to secrete recombinant proteins into the extracellular space. Incorrect processing of secreted proteins by cells can, however, cause non-functional product-related variants, which are expensive to remove in purification and lower overall process yields. The secretion signal peptide, attached to the N-terminus of the recombinant protein, is a major determinant of the quality of the protein sequence and yield. In K. phaffii, the signal peptide from the Saccharomyces cerevisiae alpha mating factor often yields the highest secreted titer of recombinant proteins, but the quality of secreted protein can vary highly.

Results
We determined that an aggregated product-related variant of the SARS-CoV-2 receptor binding domain is caused by N-terminal extension from incomplete cleavage of the signal peptide. We eliminated this variant and improved secreted protein titer up to 76% by extension of the N-terminus with a short, functional peptide moiety or with the EAEA residues from the native signal peptide. We then applied this strategy to three other recombinant subunit vaccine antigens and observed consistent elimination of the same aggregated product-related variant. Finally, we demonstrated that this benefit in quality and secreted titer can be achieved with addition of a single amino acid to the N-terminus of the recombinant protein.

Conclusions
Our observations suggest that steric hindrance of proteases in the Golgi that cleave the signal peptide can cause unwanted N-terminal extension and related product variants. We demonstrated that this phenomenon occurs for multiple recombinant proteins, and can be addressed by minimal modification of the N-terminus to improve steric accessibility. This strategy may enable consistent secretion of a broad range of recombinant proteins with the highly productive alpha mating factor secretion signal peptide.
circ_0061265 competitively binds to microRNA-885-3p to promote the development of gastric cancer by upregulating AURKA expression
Authors: Fei Qian , Lin Yuhe , Zhang Mi , Guo Jinshuai , Liang Yuan 
Published: September 2022

Abstract
Background
Circular RNAs (circRNAs) represent a class of newly identified transcripts that act as competing endogenous RNAs (ceRNAs) to modulate gene expression by competing for the shared microRNAs (miRNAs) in humans. In this study, we set out to investigate the role of the circRNA-miRNA-mRNA ceRNA network in gastric cancer (GC).

Methods
A differential analysis on GC-related circRNAs, miRNAs and mRNAs was performed utilizing the R language “limma” package, followed by GO and KEGG enrichment analyses. The Cytoscape visualization software was used to construct the circRNA-miRNA-mRNA ceRNA network. RT-qPCR, Western blot assay, immunohistochemistry, RNA pull down, RIP and dual luciferase gene reporter assay were conducted to verify the expression of the related circRNA, miRNA and mRNA and their interaction in GC tissues and cells.

Results
The bioinformatics analysis screened 13 circRNAs, 241 miRNAs and 7483 mRNAs related to GC. Ten DEmRNAs (AURKA, BUB1, CCNF, FEN1, FGF2, ITPKB, CDKN1A, TRIP13, KNTC1 and KIT) were identified from the constructed PPI network and module analysis, among which AURKA was the most critical. A circ_0061265-miRNA-885-3p-AURKA ceRNA network was constructed. In vitro cell experiment demonstrated significantly upregulated circ_0061265 and AURKA, but downregulated miR-885-3p in GC. Moreover, circ_0061265 promoted the occurrence of GC by competitively binding to miRNA-885-3p to regulate AURKA expression.

Conclusion
Our work validated that circ_0061265 may increase AURKA expression by competitively binding to miRNA-885-3p, thereby promoting GC development.
Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer
Authors: Lei Kunjian , Luo Min , Tu Zewei , Lv Shigang , Liu Junzhe , Gong Chuandong , Ye Minhua , Wu Miaojing , Sheng Yilei , Long Xiaoyan , Li Jingying , Zhu Xingen , Huang Kai 
Published: September 2022

Abstract
Background
The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored.

Methods
We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx).

Results
Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells.

Conclusions
Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.
Prostate cancer in omics era
Authors: Gholami Nasrin , Haghparast Amin , Alipourfard Iraj , Nazari Majid 
Published: September 2022

AbstractRecent advances in omics technology have prompted extraordinary attempts to define the molecular changes underlying the onset and progression of a variety of complex human diseases, including cancer. Since the advent of sequencing technology, cancer biology has become increasingly reliant on the generation and integration of data generated at these levels. The availability of multi-omic data has transformed medicine and biology by enabling integrated systems-level approaches. Multivariate signatures are expected to play a role in cancer detection, screening, patient classification, assessment of treatment response, and biomarker identification. This review reports current findings and highlights a number of studies that are both novel and groundbreaking in their application of multi Omics to prostate cancer.
Challenges to the right to health in sub-Saharan Africa: reflections on inequities in access to dialysis for patients with end-stage kidney failure
Authors: Ashu James Tataw , Mwangi Jackline , Subramani Supriya , Kaseje Daniel , Ashuntantang Gloria , Luyckx Valerie A. 
Published: September 2022

AbstractRealization of the individual’s right to health in settings such as sub-Saharan Africa, where health care adequate resources are lacking, is challenging. This paper demonstrates this challenge by illustrating the example of dialysis, which is an expensive but life-saving treatment for people with kidney failure. Dialysis resources, if available in sub-Saharan Africa, are generally limited but in high demand, and clinicians at the bedside are faced with deciding who lives and who dies. When resource limitations exist, transparent and objective priority setting regarding access to such expensive care is required to improve equity across all health needs in a population. This process however, which weighs individual and population health needs, denies some the right to health by limiting access to health care.This paper unpacks what it means to recognize the right to health in sub-Saharan Africa, acknowledging the current resource availability and scarcity, and the larger socio-economic context. We argue, the first order of the right to health, which should always be realized, includes protection of health, i.e. prevention of disease through public health and health-in-all policy approaches. The second order right to health care would include provision of universal health coverage to all, such that risk factors and diseases can be effectively and equitably detected and treated early, to prevent disease progression or development of complications, and ultimately reduce the demand for expensive care. The third order right to health care would include equitable access to expensive care. In this paper, we argue that recognition of the inequities in realization of the right to health between individuals with “expensive” needs versus those with more affordable needs, countries must determine if, how, and when they will begin to provide such expensive care, so as to minimize these inequities as rapidly as possible. Such a process requires good governance, multi-stakeholder engagement, transparency, communication and a commitment to progress. We conclude the paper by emphasizing that striving towards the progressive realization of the right to health for all people living in SSA is key to achieving equity in access to quality health care and equitable opportunities for each individual to maximize their own state of health.
Migrants in Swedish sexual and reproductive health and rights related policies: a critical discourse analysis
Authors: Amroussia Nada , Holmström Charlotta , Ouis Pernilla 
Published: September 2022

Abstract
Background
Previous research has shown that migrants in Sweden are disadvantaged in terms of sexual and reproductive health and rights (SRHR). SRHR policies might play a crucial role in shaping migrants’ SRHR outcomes. The purpose of the study was to critically examine: a) how migrants were represented in the discourses embedded within Swedish SRHR-related policies, and b) how migrants’ SRHR-related issues were framed and addressed within these discourses.

Methods
Critical discourse analysis (CDA) was used to analyze a total of 54 policy documents. Following Jäger’s approach to CDA, discourse strands and entanglements between different discourse strands were examined.

Results
Our findings consisted of three discourse strands: 1) “Emphasizing vulnerability”, 2) “Constructing otherness”, and 3) “Prioritizing the structural level or the individual level?”.
Migrants’ representation in Swedish SRHR-related policies is often associated with the concept of vulnerability, a concept that can hold negative connotations such as reinforcing social control, stigma, and disempowerment. Alongside the discourse of vulnerability, the discourse of otherness appears when framing migrants’ SRHR in relation to what is defined as honor-related violence and oppression. Furthermore, migrant SRHR issues are occasionally conceptualized as structural issues, as suggested by the human rights-based approach embraced by Swedish SRHR-related policies. Relevant structural factors, namely migration laws and regulations, are omitted when addressing, for example, human trafficking and HIV/AIDS.

Conclusions
We conclude that the dominant discourses favor depictions of migrants as vulnerable and as the Other. Moreover, despite the prevailing human rights-based discourse, structural factors are not always considered when framing and addressing migrants’ SRHR issues. This paper calls for a critical analysis of the concept of vulnerability in relation to migrants’ SRHR. It also highlights the importance of avoiding othering and paying attention to the structural factors when addressing migrants’ SRHR.
Diagnosis of pathogens causing bacterial meningitis using Nanopore sequencing in a resource-limited setting
Authors: Pallerla Srinivas Reddy , Van Dong Do , Linh Le Thi Kieu , Van Son Trinh , Quyen Dao Thanh , Hoan Phan Quoc , Trung Ngo Tat , The Nguyen Trong , Rüter Jule , Boutin Sébastien , Nurjadi Dennis , Sy Bui Tien , Kremsner Peter G. , Meyer Christian G. , Song Le Huu , Velavan Thirumalaisamy P. 
Published: September 2022

Abstract
Aim
The aim of the present study is to compare the performance of 16S rRNA Nanopore sequencing and conventional culture in detecting infectious pathogens in patients with suspected meningitis in a resource-limited setting without extensive bioinformatics expertise.

Methods
DNA was isolated from the cerebrospinal fluid (CSF) of 30 patients with suspected bacterial meningitis. The isolated DNA was subjected to 16S sequencing using MinION™. The data were analysed in real time via the EPI2ME cloud platform. The Nanopore sequencing was done in parallel to routine microbiological diagnostics.

Results
Nanopore sequencing detected bacterial pathogens to species level in 13 of 30 (43%) samples. CSF culture showed 40% (12/30) positivity. In 21 of 30 patients (70%) with suspected bacterial meningitis, both methods yielded concordant results. About nine of 30 samples showed discordant results, of these five were false positive and four were false negative. In five of the culture negative results, nanopore sequencing was able to detect pathogen genome, due to the higher sensitivity of the molecular diagnostics. In two other samples, the CSF culture revealed Cryptococcus neoformans and Streptococcus pneumoniae, which were not detected by Nanopore sequencing. Overall, using both the cultures and 16S Nanopore sequencing, positivity rate increased from 40% (12/30) to 57% (17/30).

Conclusion
Next-generation sequencing could detect pathogens within six hours and could become an important tool for both pathogen screening and surveillance in low- and middle-income countries (LMICs) that do not have direct access to extensive bioinformatics expertise.