bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacy professionals’ views regarding the future of NHS patient medicines helpline services: a multimethod qualitative study
Authors: Williams Matt , Jordan Abbie , Scott Jenny , Jones Matthew D. 
Published: February 2021

AbstractBackgroundPatient medicines helpline services (PMHS) have been established at some National Health Service (NHS) hospitals, to provide patients with post-discharge medicines-related support. However, findings suggest that many PMHS are provided sub-optimally due to a lack of resources. This study sought to examine pharmacy professionals’ perceptions of the future of PMHS.MethodsParticipants comprised pharmacy professionals from NHS Trusts in England that provided a PMHS. Invitations to participate in a qualitative survey and then an interview were sent to pharmacy services at all NHS Trusts that provided a PMHS. This resulted in 100 survey participants and 34 interview participants. Data were analysed using Braun and Clarke’s inductive reflexive thematic analysis.ResultsTwo themes were generated:Enhancing value for service usersandImprovingefficiency.Enhancing value for service usersidentifies pharmacy professionals’ suggestions for improving the value of PMHS for service users. These include providing access methods extending beyond the telephone, and providing patients/carers with post-discharge follow-up calls from a pharmacist to offer medicines-related support.Improvingefficiencyidentifies that, in the future, and in line with NHS plans for efficiency and shared resources, PMHS may become centralised or provided by community pharmacies. Centralised services were considered to likely have more resources available to provide a patient medicines information service compared to hospital pharmacies. However, such a change was perceived to only increase efficiency if patient information can be shared between relevant healthcare settings.ConclusionsPMHS are perceived by pharmacy professionals as likely to become centralised in the future (i.e., provided regionally/nationally). However, such change is dependent upon the sharing of patients’ information between hospitals and the centralised hub/s or pharmacies. To enhance the value of PMHS for service users, providers should consider establishing other methods of access, such as email and video consultation. Considering the uncertainty around the future of PMHS, research should establish the best way to support all patients and carers regarding medicines following hospital discharge.
Characteristics and mortality rates among patients requiring intermediate care: a national cohort study using linked databases
Authors:   on behalf of SPACE, Evans Catherine J. , Potts Laura , Dalrymple Ursula , Pring Andrew , Verne Julia , Higginson Irene J. , Gao Wei 
Published: February 2021

Abstract
Background
Adults increasingly live and die with chronic progressive conditions into advanced age. Many live with multimorbidity and an uncertain illness trajectory with points of marked decline, loss of function and increased risk of end of life. Intermediate care units support mainly older adults in transition between hospital and home to regain function and anticipate and plan for end of life. This study examined the patient characteristics and the factors associated with mortality over 1 year post-admission to an intermediate care unit to inform priorities for care.

Methods
A national cohort study of adults admitted to intermediate care units in England using linked individual-level Hospital Episode Statistics and death registration data. The main outcome was mortality within 1 year from admission. The cohort was examined as two groups with significant differences in mortality between main diagnosis of a non-cancer condition and cancer. Data analysis used Kaplan-Meier curves to explore mortality differences between the groups and a time-dependant Cox proportional hazards model to determine mortality risk factors.

Results
The cohort comprised 76,704 adults with median age 81 years (IQR 70–88) admitted to 220 intermediate care units over 1 year in 2016. Overall, 28.0% died within 1 year post-admission. Mortality varied by the main diagnosis of cancer (total n = 3680, 70.8% died) and non-cancer condition (total n = 73,024, 25.8% died). Illness-related factors had the highest adjusted hazard ratios [aHRs]. At 0–28 days post-admission, risks were highest for non-cancer respiratory conditions (pneumonia (aHR 6.17 [95%CI 4.90–7.76]), chronic obstructive pulmonary disease (aHR 5.01 [95% CI 3.78–6.62]), dementia (aHR 5.07 [95% CI 3.80–6.77]) and liver disease (aHR 9.75 [95% CI 6.50–14.6]) compared with musculoskeletal disorders. In cancer, lung cancer showed largest risk (aHR 1.20 [95%CI 1.04–1.39]) compared with cancer ‘other’. Risks increased with high multimorbidity for non-cancer (aHR 2.57 [95% CI 2.36–2.79]) and cancer (aHR 2.59 [95% CI 2.13–3.15]) (reference: lowest).

Conclusions
One in four patients died within 1 year. Indicators for palliative care assessment are respiratory conditions, dementia, liver disease, cancer and rising multimorbidity. The traditional emphasis on rehabilitation and recovery in intermediate care units has changed with an ageing population and the need for greater integration of palliative care.
The role of viral and bacterial infections in the pathogenesis of IPF: a systematic review and meta-analysis
Authors: Mostafaei Shayan , Sayad Babak , Azar Maryam Ebadi Fard , Doroudian Mohammad , Hadifar Shima , Behrouzi Ava , Riahi Parisa , Hussen Bashdar Mahmud , Bayat Bahareh , Nahand Javid Sadri , Moghoofei Mohsen 
Published: February 2021

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. Several risk factors such as smoking, air pollution, inhaled toxins, high body mass index and infectious agents are involved in the pathogenesis of IPF. In the present study, this meta-analysis study investigates the prevalence of viral and bacterial infections in the IPF patients and any possible association between these infections with pathogenesis of IPF.

Methods
The authors carried out this systematic literature review from different reliable databases such as PubMed, ISI Web of Science, Scopus and Google Scholar to December 2020.Keywords used were the following “Idiopathic pulmonary fibrosis”, “Infection”, “Bacterial Infection” and “Viral Infection”, alone or combined together with the Boolean operators "OR”, “AND” and “NOT” in the Title/Abstract/Keywords field. Pooled proportion and its 95% CI were used to assess the prevalence of viral and bacterial infections in the IPF patients.

Results
In this systematic review and meta-analyses, 32 studies were selected based on the exclusion/inclusion criteria. Geographical distribution of included studies was: eight studies in American people, 8; in European people, 15 in Asians, and one in Africans. The pooled prevalence for viral and bacterial infections w ere 53.72% (95% CI 38.1–69.1%) and 31.21% (95% CI 19.9–43.7%), respectively. The highest and lowest prevalence of viral infections was HSV (77.7% 95% CI 38.48–99.32%), EBV (72.02%, 95% CI 44.65–90.79%) and Influenza A (7.3%, 95% CI 2.66–42.45%), respectively. Whereas the highest and lowest prevalence in bacterial infections were related to Streptococcus sp. (99.49%, 95% CI 96.44–99.9%) and Raoultella (1.2%, 95% CI 0.2–3.08%), respectively.

Conclusions
The results of this review were confirmed that the presence of viral and bacterial infections are the risk factors in the pathogenesis of IPF. In further analyses, which have never been shown in the previous studies, we revealed the geographic variations in the association strengths and emphasized other methodological parameters (e.g., detection method). Also, our study supports the hypothesis that respiratory infection could play a key role in the pathogenesis of IP.
Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma
Authors: Yu Kai , Yang Huan , Lv Qiao-li , Wang Li-chong , Tan Zi-long , Zhang Zhe , Ji Yu-long , Lin Qian-xia , Chen Jun-jun , He Wei , Chen Zhen , Shen Xiao-li 
Published: February 2021

Abstract
Background
Glioblastoma is the most common primary malignant brain tumor. Because of the limited understanding of its pathogenesis, the prognosis of glioblastoma remains poor. This study was conducted to explore potential competing endogenous RNA (ceRNA) network chains and biomarkers in glioblastoma by performing integrated bioinformatics analysis.

Methods
Transcriptome expression data from The Cancer Genome Atlas database and Gene Expression Omnibus were analyzed to identify differentially expressed genes between glioblastoma and normal tissues. Biological pathways potentially associated with the differentially expressed genes were explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and a protein-protein interaction network was established using the STRING database and Cytoscape. Survival analysis using Gene Expression Profiling Interactive Analysis was based on the Kaplan–Meier curve method. A ceRNA network chain was established using the intersection method to align data from four databases (miRTarBase, miRcode, TargetScan, and lncBace2.0), and expression differences and correlations were verified by quantitative reverse-transcription polymerase chain reaction analysis and by determining the Pearson correlation coefficient. Additionally, an MTS assay and the wound-healing and transwell assays were performed to evaluate the effects of complement C1s (C1S) on the viability and migration and invasion abilities of glioblastoma cells, respectively.

Results
We detected 2842 differentially expressed (DE) mRNAs, 2577 DE long non-coding RNAs (lncRNAs), and 309 DE microRNAs (miRNAs) that were dysregulated in glioblastoma. The final ceRNA network consisted of six specific lncRNAs, four miRNAs, and four mRNAs. Among them, four DE mRNAs and one DE lncRNA were correlated with overall survival (p < 0.05). C1S was significantly correlated with overall survival (p= 0.015). In functional assays, knockdown of C1S inhibited the proliferation and invasion of glioblastoma cell lines.

Conclusions
We established four ceRNA networks that may influence the occurrence and development of glioblastoma. Among them, the MIR155HG/has-miR-129-5p/C1S axis is a potential marker and therapeutic target for glioblastoma. Knockdown of C1S inhibited the proliferation, migration, and invasion of glioblastoma cells. These findings clarify the role of the ceRNA regulatory network in glioblastoma and provide a foundation for further research.
Down‐regulation of the Sp1 transcription factor by an increase of microRNA-4497 in human placenta is associated with early recurrent miscarriage
Authors: Tang Huaiyun , Pan Linqing , Xiong Yun , Wang Leilei , Cui Yugui , Liu Jiayin , Tang Lisha 
Published: February 2021

Abstract
Background
The pathophysiological mechanism of recurrent miscarriage (RM) is unclear. The goals of this study were to determine the role of microRNA-4497 overexpression in placental villus tissues in early RM; To identify the potential target mRNAs of miRNA-4497; And to investigate the microRNA-4497-mediated regulatory mechanisms in placental trophoblasts.

Methods
Bioinformatics analysis was performed to identify the candidate target genes of miRNA-4497. The protein expression of Sp1 transcription factor (SP1), chemokine (C-X-C motif) receptor 5 (CXCR5) and bone morphogenetic protein 8a (BMP8A) were determined in the villus tissues of the RM and normal groups by Western blotting and immunohistochemistry. Cultured 293T cells were co-transfected with the miRNA-4497 agomir or luciferase reporter vectors containing the wild-type or mutant 3’-UTRs of the target mRNAs to verify the regulatory role of miRNA-4497.

Results
Bioinformatics analysis suggested that SP1, CXCR5 and BMP8A mRNAs are potential targets of miRNA-4497. The expression of SP1, CXCR5 and BMP8A proteins in the chorionic villus tissues of RM placentas were significantly decreased compared to those in the normal controls. Moreover, SP1 protein levels were inversely correlated with the levels of miRNA-4497 in the placentas of RM patients and normal controls. The expression of SP1 mRNA and protein were down-regulated in HTR-8/SVneo cells after forced overexpression of the miRNA-4497 agomir. The results of the co-transfection assay showed that mutation of the miRNA-4497-binding sites in the 3’-untranslated region (3’-UTR) of SP1 led to a recovery of luciferase activity upon overexpression of miRNA-4497, suggesting that SP1 could be a direct target of miRNA-4497.

Conclusions
An increased miRNA-4497 level in the placental villus tissues associated with recurrent miscarriage may down-regulate SP1 expression. The negative regulation of SP1 by miRNA-4497 may potentially contribute to the pathogenesis of recurrent miscarriage through promotion of trophoblast apoptosis. These findings provide novel information on the regulation of placental trophoblast apoptosis, and could be useful for the development of new therapeutic strategies for better management of recurrent miscarriage.
Baicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation
Authors: Sonawane Shweta Kishor , Uversky Vladimir N. , Chinnathambi Subashchandrabose 
Published: February 2021

Abstract
Background
Amyloid aggregate deposition is the key feature of Alzheimer’s disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (Aβ) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable of preventing the aggregation of these intrinsically disordered proteins by inhibiting the early stages of their pathological transformations. Polyphenols are known to be neuroprotective agents with the noticeable potential against many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Prion diseases.

Methods
We analyzed the capability of Baicalein to inhibit aggregation of human Tau protein by a multifactorial analysis that included several biophysical and biochemical techniques.

Results
The potency of Baicalein, a polyphenol from the Scutellaria baicalensis Georgi, against in vitro Tau aggregation and PHF dissolution has been screened and validated. ThS fluorescence assay revealed the potent inhibitory activity of Baicalein, whereas ANS revealed its mechanism of Tau inhibition viz. by oligomer capture and dissociation. In addition, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action. Tau oligomers formed by Baicalein were non-toxic to neuronal cells, highlighting its role as a potent molecule to be screened against AD.

Conclusion
In conclusion, Baicalein inhibits aggregation of hTau40 by enhancing the formation of SDS-stable oligomers and preventing fibril formation. Baicalein-induced oligomers do not affect the viability of the neuroblastoma cells. Therefore, Baicalein can be considered as a lead molecule against Tau pathology in AD.
The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia
Authors: Han Caixia , He Shujiao , Wang Ruiqi , Gao Xuefeng , Wang Hong , Qiao Jingqiao , Meng Xiangyu , Li Yonghui , Yu Li 
Published: February 2021

AbstractBackgroundRho GTPase activating protein 9 (ARHGAP9) is expressed in various types of cancers and can inactivate Rho GTPases that mainly regulate cytoskeletal dynamics. However, the exact role of ARHGAP9 in acute myeloid leukemia (AML) has yet to be clarified.MethodsWe compared the transcriptional expression, prognosis, differentially expressed genes, functional enrichment, and hub genes in AML patients on the basis of the data published in the following databases: UALCAN, GEPIA, Gene Expression Omnibus, the Human Protein Atlas, Cancer Cell Line Encyclopedia, LinkedOmics, Metascape, and String. Data from the Cancer Genome Atlas database was used to evaluate the correlations between ARHGAP9 expression and various clinicopathological parameters, as well as the significantly different genes associated with ARHGAP9 expression.ResultsWe found that ARHGAP9 expression was higher in the tissues and cell lines extracted from patients with AML than corresponding control tissues and other cancer types. ARHGAP9 overexpression was associated with decreased overall survival (OS) in AML. Compared with the ARHGAP9lowgroup, the ARHGAP9highgroup, which received only chemotherapy, showed significantly worse OS and event-free survival (EFS); however, no significant difference was observed after treatment with autologous or allogeneic hematopoietic stem cell transplantation (auto/allo-HSCT). The ARHGAP9highpatients undergoing auto/allo-HSCT also had a significantly better prognosis with respect to OS and EFS than those receiving only chemotherapy. Most overlapping genes of the significantly different genes and co-expression genes exhibited enriched immune functions, suggesting the immune regulation potential of ARHGAP9 in AML. A total of 32 hub genes were identified from the differentially expressed genes, within which the KIF20A had a significant prognostic value for AML.ConclusionsARHGAP9 overexpression was associated with poor OS in AML patients and can be used as a prognostic biomarker. AML patients with ARHGAP9 overexpression can benefit from auto/allo-HSCT rather than chemotherapy.
Changes in cannabis use, exposure, and health perceptions following legalization of adult recreational cannabis use in California: a prospective observational study
Authors: Gali Kathleen , Winter Sandra J. , Ahuja Naina J. , Frank Erica , Prochaska Judith J. 
Published: February 2021

Abstract
Background
Most U.S. states have legalized cannabis for medical and/or recreational use. In a 6-month prospective observational study, we examined changes in adult cannabis use patterns and health perceptions following broadened legalization of cannabis use from medical to recreational purposes in California.

Methods
Respondents were part of Stanford University’s WELL for Life registry, an online adult cohort concentrated in Northern California. Surveys were administered online in the 10 days prior to state legalization of recreational use (1/1/18) and 1-month (2/1/18–2/15/18) and 6-months (7/1/2018–7/15/18) following the change in state policy. Online surveys assessed self-reported past 30-day cannabis use, exposure to others’ cannabis use, and health perceptions of cannabis use. Logistic regression models and generalized estimating equations (GEE) examined associations between participant characteristics and cannabis use pre- to 1-month and 6-months post-legalization.

Results
The sample (N = 429, 51% female, 55% non-Hispanic White, age mean = 56 ± 14.6) voted 58% in favor of state legalization of recreational cannabis use, with 26% opposed, and 16% abstained. Cannabis use in the past 30-days significantly increased from pre-legalization (17%) to 1-month post-legalization (21%; odds ratio (OR) = 1.28, p-value (p) = .01) and stayed elevated over pre-legalization levels at 6-months post-legalization (20%; OR = 1.28, p = .01). Exposure to others’ cannabis use in the past 30 days did not change significantly over time: 41% pre-legalization, 44% 1-month post-legalization (OR = 1.18, p = .11), and 42% 6-months post-legalization (OR = 1.08, p = .61). Perceptions of health benefits of cannabis use increased from pre-legalization to 6-months post-legalization (OR = 1.19, p = .02). Younger adults, those with fewer years of education, and those reporting histories of depression were more likely to report recent cannabis use pre- and post-legalization. Other mental illness was associated with cannabis use at post-legalization only. In a multivariate GEE adjusted for sociodemographic characteristics and diagnoses, favoring legalization and the interaction of time and positive health perceptions were associated with a greater likelihood of using cannabis.

Conclusions
Legalized recreational cannabis use was associated with greater self-reported past 30-day use post-legalization, and with more-positive health perceptions of cannabis use. Future research is needed to examine longer-term perceptions and behavioral patterns following legalization of recreational cannabis use, especially among those with mental illness.
Validation of the 5-domain Niemann-Pick type C Clinical Severity Scale
Authors: Patterson Marc C. , Lloyd-Price Lucy , Guldberg Christina , Doll Helen , Burbridge Claire , Chladek Michael , íDali Christine , Mengel Eugen , Symonds Tara 
Published: February 2021

AbstractBackgroundNiemann-Pick disease type C (NPC) is an ultra-rare, progressive, genetic disease leading to impaired lysosomal function and neurodegeneration causing serious morbidity and shortened life expectancy.The Niemann-Pick type C Clinical Severity Scale (NPCCSS) is a 17 domain, disease-specific, clinician-reported outcome measure of disease severity and progression. An abbreviated 5-domain NPCCSS scale has been developed (measuring Ambulation, Swallow, Cognition, Speech, and Fine Motor Skills) and the scale reliability has been established. Additional psychometric properties and meaningful change of the scale need, however, to be assessed.MethodsMixed method studies were conducted to ascertain which NPCCSS domains were most important, as well as to explore meaningful change: 1) surveys in caregivers/patients (n = 49) and 2) interviews with clinicians (n = 5) as well as caregivers/patients (n = 28). Clinical trial data (n = 43) assessed construct validity and meaningful change through an anchor-based approach.ResultsDomains identified as most important by clinicians, caregivers, and patients (independent of current age, age of onset, and disease severity) were Ambulation, Swallow, Cognition, Speech, and Fine Motor Skills, indicating content validity of the 5-domain NPCCSS.Criterion validity was shown with the 5-domain NPCCSS being highly correlated with the 17-item NPCCSS total score (excluding hearing domains), r2 = 0.97. Convergent validity was demonstrated against the 9 Hole Peg Test, r2 = 0.65 (n = 31 patients), and the Scale for Assessment and Rating of Ataxia (SARA), r2 = 0.86 (n = 49 patients). Any change was seen as meaningful by patients/caregivers across domains. Meaningful change using trial data and interviews with NPC experts (n = 5) and patients/caregivers (n = 28) suggested that a 1-category change on a domain is equivalent to 1-point change or greater in the 5-domain NPCCSS total score.ConclusionsQualitative and quantitative data support content and construct validity of the 5-domain NPCCSS score as a valid endpoint in NPC trials. A 1-category change on any domain is equivalent to 1-point change or greater in the 5 domain NPCCSS total score, representing a clinically meaningful transition and reflecting loss of complex function and increased disability.Trial registrationNCT02612129. Registered 23 November 2015,https://clinicaltrials.gov/ct2/show/NCT02612129