bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating clinical pharmacists within general practice: protocol for a pilot cluster randomised controlled trial
Authors: Croke Aisling , Moriarty Frank , Boland Fiona , McCullagh Laura , Cardwell Karen , Smith Susan M , Clyne Barbara 
Published: March 2021

IntroductionManaging patients with multiple conditions (multimorbidity) is a major challenge for healthcare systems internationally, particularly in older patients. Multimorbidity and subsequent polypharmacy increase treatment burden and the risk of potentially inappropriate prescribing, and both are complex to manage in primary care. Limited evidence suggests integration of pharmacists into general practice teams could improve medication management for patients with multimorbidity and polypharmacy. Building on findings from a non-randomised, uncontrolled General Practice Pharmacist (GPP) feasibility study conducted in Irish primary care, the aim of this study is to conduct a pilot cluster randomised controlled trial (cRCT) of the GPP study, to assess feasibility, intervention impact, costs and appropriateness of continuing to a definitive cRCT.Methods and analysisThis pilot cRCT will involve 8 general practitioner (GP) practices and 120 patients. Practices will identify and recruit patients aged ≥65 years, who are taking ≥10 regular medications. Practices will be allocated to intervention or control after baseline data collection. Intervention practices will have a pharmacist integrated within their service, working with GPs, patients and practice staff to optimise prescribing and other medication-related activities. Control practices will provide standard GP care. The primary feasibility outcomes will include recruitment rate, uptake of medication reviews and study retention. For the primary clinical outcome, the number of potentially inappropriate prescribing incidences per patient will be collected. Secondary outcomes will include medication-related outcomes, patient-reported outcome measures, and data pertaining to the role and impact of the pharmacist on prescribing. In addition, economic and process evaluations will be conducted.Ethics and disseminationThis trial has been approved by the Irish College of General Practitioners Research Ethics Committee and will be performed in accordance with the Declaration of Helsinki. The results will be reported in peer-reviewed journals and be presented at national and international conferences.Trial registration numberISRCTN Registry (https://doi.org/10.1186/ISRCTN18752158).
Comorbidities and functional impairments in children with attention deficit hyperactivity disorder in China: a hospital-based retrospective cross-sectional study
Authors: Shi Xiaoyan , Ji Yiting , Cai Shizhong , Wu Ying , Zhang Lijun , Shen Ling , Jiang Zhiying , Chen Yan 
Published: March 2021

ObjectivesThe aim of this study was to assess comorbidity patterns and functional impairment in children with and without attention deficit hyperactivity disorder (ADHD).DesignHospital-based retrospective cross-sectional study; data collection occurred between 2016 and 2019.Settings and patientsA total of 8256 children and adolescents, 6–17 years of age, with suspected ADHD agreed to participate in this hospital-based cross-sectional study over a 4-year period in China. Comorbidities and social functions were assessed according to the scales Vanderbilt ADHD Diagnostic Parent Rating Scale and Weiss Functional Impairment Rating Scale-Parent Form, which were completed by the parents of the study participants.ResultsOf the 8256 children, 5640 were diagnosed with ADHD. Other 2616 children who did not meet the ADHD diagnostic criteria were classified as the N-ADHD group . The proportion of comorbidities (47.4%) and functional impairments (84.5%) in the ADHD group were higher than the N-ADHD group (p≤0.001). The functional impairment scores in all of the six domains, including family, academic, life skills, self-concept, social activities and risky activities, were significantly higher in the ADHD group than the N-ADHD group (p≤0.001). The functional impairment in ADHD group with comorbidities was more severe than those without comorbidities (p≤0.001). Comorbidities and core symptoms both can affect the functions of children with ADHD. Logistics regression analysis indicated that in all of the six functional domains, the effect of comorbidities on functional impairment exceeded the effects of ADHD core symptoms.ConclusionsComorbidities had the greatest influence on different areas of adaptive functioning in children with ADHD. Clinical management of children suspected to have ADHD should address multiple comorbidities and functional impairments assessment, as well as core symptom analysis.
Stakeholders’ views on the organisational factors affecting application of artificial intelligence in healthcare: a scoping review protocol
Authors: Lebcir Reda , Hill Tetiana , Atun Rifat , Cubric Marija 
Published: March 2021

IntroductionArtificial intelligence (AI) offers great potential for transforming healthcare delivery leading to better patient-outcomes and more efficient care delivery. However, despite these advantages, integration of AI in healthcare has not kept pace with technological advancements. Previous research indicates the importance of understanding various organisational factors that shape integration of new technologies in healthcare. Therefore, the aim of this study is to provide an overview of the existing organisational factors influencing adoption of AI in healthcare from the perspectives of different relevant stakeholders. By conducting this review, the various organisational factors that facilitate or hinder AI implementation in healthcare could be identified.Methods and analysisThis study will follow the Joanna Briggs Institute framework, which includes the following stages: (1) defining and aligning objectives and questions, (2) developing and aligning the inclusions criteria with objectives and questions, (3) describing the planned approach to evidence searching and selection, (4) searching for the evidence, (5) selecting the evidence, (6) extracting the evidence, (7) charting the evidence, and summarising the evidence with regard to the objectives and questions.The databases searched will be MEDLINE (Ovid), CINAHL (Plus), PubMed, Cohrane Library, Scopus, MathSciNet, NICE Evidence, OpenGrey, O’REILLY and Social Care Online from January 2000 to June 2021. Search results will be reported based on The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines. The review will adopt diffusion of innovations theory, technology acceptance model and stakeholder theory as guiding conceptual models. Narrative synthesis will be used to integrate the findings.Ethics and disseminationEthics approval will not be sought for this scoping review as it only includes information from previously published studies. The results will be disseminated through publication in a peer-reviewed journal. In addition, to ensure its findings reach relevant stakeholders, they will be presented at relevant conferences.
Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis
Authors: Zhang Lijuan , Song Yanli , Jiang Nan , Huang Yaqi , Dong Bo , Li Wei , He Yanze , Chen Yun , Liu Haibin , Yu Rui 
Published: March 2021

ObjectivesDespite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC.DesignMeta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.SettingRCTs from any country and healthcare setting.ParticipantsPatients with OC.InterventionsCombination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC.Primary and secondary outcome measuresOverall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures.ResultsIn total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p<0.00001), ORR (relative risk (RR): 1.33, 95% CI 1.16 to 1.52, p<0.0001) and DCR (RR: 1.22, 95% CI 1.11 to 1.34, p<0.0001) but not PFS (HR: 0.91, 95% CI 0.76 to 1.08, p=0.26). Anti-EGFR treatment was significantly associated with higher incidences of myelosuppression, diarrhoea, acne-like rash and hypomagnesaemia.ConclusionsOverall, anti-EGFR agents have positive effects on OS, the ORR and DCR in OC. However, considering the high incidence of adverse effects, such as myelosuppression, diarrhoea, acne-like rashes and hypomagnesaemia, careful monitoring of patients with OC is recommended during anti-EGFR treatment.Trial registration numberCRD42020169230.
Risk factors for SARS-CoV-2 infection and course of COVID-19 disease in patients with IBD in the Veterans Affair Healthcare System
Authors: Khan Nabeel , Mahmud Nadim , Trivedi Chinmay , Reinisch Walter , Lewis James D 
Published: March 2021

ObjectiveOur aim was to explore the risk of infection with all classes of inflammatory bowel disease (IBD) medications and the impact of these medications on the disease course in a nationwide cohort of patients with IBD.DesignThis was a retrospective national cohort study of patients with IBD in the Veterans Affairs Healthcare System. We categorised IBD medication use immediately prior to the COVID-19 pandemic and used survival analysis methods to study associations with SARS-CoV-2 infection, as well as a combined secondary outcome of COVID-19 hospitalisation or COVID-19-related mortality.ResultsThe analytical cohort of 30 911 patients was primarily male (90.9%), white (78.6%) and with ulcerative colitis (58.8%). Over a median follow-up of 10.7 months, 649 patients (2.1%) were diagnosed with SARS-CoV-2 infection and 149 (0.5%) met the combined secondary outcome. In adjusted models, vedolizumab (VDZ) use was significantly associated with infection relative to mesalazine alone (HR 1.70, 95% CI 1.16 to 2.48, p=0.006). Patients on no IBD medications had increased risk of the combined secondary outcome relative to mesalazine alone (sub-HR 1.64, 95% CI 1.12 to 2.42, p=0.01), however, no other IBD medication categories were significantly associated with this outcome, relative to mesalazine alone (each p>0.05). Corticosteroid use was independently associated with both SARS-CoV-2 infection (HR 1.60, 95% CI 1.23 to 2.09, p=0.001) and the combined secondary outcome (sub-HR 1.90, 95% CI 1.14 to 3.17, p=0.01).ConclusionVDZ and corticosteroid were associated with an increased risk of SARS-CoV-2 infection. Except for corticosteroids no medications including mesalazine were associated with an increased risk of severe COVID-19.
Rising of LOXHD1 as a signature causative gene of down-sloping hearing loss in people in their teens and 20s
Authors: Kim Bong Jik , Jeon Hyoung Won , Jeon Woosung , Han Jin Hee , Oh Jayoung , Yi Nayoung , Kim Min Young , Kim Minah , Kim Justin Namju , Kim Bo Hye , Hyon Joon Young , Kim Dongsup , Koo Ja-Won , Oh Doo-Yi , Choi Byung Yoon 
Published: March 2021

BackgroundDown-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype–phenotype correlation of lipoxygenase homology domain 1 (LOXHD1) in down-sloping SNHL through a cohort study.MethodsBased on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the ‘SNUBH Teenager–Young Adult Down-sloping SNHL’ cohort (10–35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed.ResultsLOXHD1 accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype–phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing.ConclusionsLOXHD1 exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype–phenotype correlation.
Improvement of root morphological characteristics on water percolation rate in grassland soils of Yellow River riparian buffer strips
Authors: Yang Xiaoyan , Gu Haiping , Fan Zihao , Guo Erhui 
Published: March 2021

Soil water percolation is an important process required to meet plant water needs, determine soil water storage, and affect soil water quality in riparian buffer strips. However, the effects of plant roots on soil percolation in riparian buffer strips are not totally understood, and contradictory results have been carried out on the effects of the root system on soil percolation rates. This study aimed to investigate soil percolation in natural grasslands and evaluate the relationships between root morphological characteristics and percolation rates. Path analysis was used to provide information on the relative contribution of root characteristics on soil percolation rates. Three mixed grasslands (Imperata cylindrica + Phragmites australis, I. cylindrica + Cynodon dactylon, and I. cylindrica + Juncellus serotinus) were selected in the Yellow River wetland natural reserves of Zhengzhou. Soil percolation rates (initial, average, and steady infiltration rates) were measured by using double-ring methods, and plant root morphological characteristics were analyzed. Soil percolation rates and plant root characteristic parameters of I. cylindrica + P. australis and I. cylindrica + C. dactylon were higher than those of I. cylindrica + J. serotinus. Initial percolation rate of I. cylindrica + P. australis and I. cylindrica + C. dactylon at 0–10 cm depth was 58.06% and 95.55% higher than that of I. cylindrica + J. serotinus, respectively. Percolation rates had a significant positive correlation with root characteristic parameters, and the main factor controlling soil percolation rates was root volume density (RVD). Mixed natural grasslands with more RVD improved soil infiltration and percolation rates.
Probing nuclear cluster symmetries through the harmonic oscillator
Authors: Freer Martin , Canavan Rhiann , Marsh Thomas , Souter James 
Published: March 2021

AbstractThe present contribution explores the symmetries of the deformed harmonic oscillator for both prolate and oblate deformations. It demonstrates the emergence of clustering from the degeneracies of the deformed harmonic oscillator and the appearance of the cluster structures in the associated densities. The universality of molecular structures is presented, demonstrating that molecular-like exchange of protons and neutrons is encoded into the mean-field. The nature of oblate-like structures is also explored.
CPTM symmetry, closed time paths and cosmological constant problem in the formalism of extended manifold
Authors: Bondarenko S. 
Published: March 2021

AbstractThe problem of the cosmological constant is considered in the formalism of an extended space-time consisting of the extended classical solution of Einstein equations. The different regions of the extended manifold are proposed to be related by the charge, parity, time and mass (CPTM) reversal symmetry applied with respect to the metric fields of the manifolds. There are interactions between the points of the extended manifold provided by scalar fields present separately in the different patches of the extended solution. The value of the constant is obtained equal to zero at the classical level due the mutual contribution of the fields in the vacuum energy, it’s non-zero value is due the quantum interactions between the fields. There are few possible scenario for the actions of the fields are discussed. Each from the obtained variants is similar to the closed time path approach of non-equilibrium condensed matter physics and among these possibilities for the closed paths, there is a variant of the action equivalent to the formalism of Keldysh. Accordingly, we consider and shortly discuss the application of the proposed formalism to the problem of smallness of the cosmological constant and singularities problem.
Chapter 5.3b Mount Early and Sheridan Bluff: petrology
Authors: Panter Kurt S. , Reindel Jenna , Smellie John L. 
Published: March 2021

Abstract

This study discusses the petrological and geochemical features of two monogenetic Miocene volcanoes, Mount Early and Sheridan Bluff, which are the above-ice expressions of Earth's southernmost volcanic field located at
c.
87° S on the East Antarctic Craton. Their geochemistry is compared to basalts from the West Antarctic Rift System to test affiliation and resolve mantle sources and cause of melting beneath East Antarctica. Basaltic lavas and dykes are olivine-phyric and comprise alkaline (hawaiite and mugearite) and subalkaline (tholeiite) types. Trace element abundances and ratios (e.g. La/Yb, Nb/Y, Zr/Y) of alkaline compositions resemble basalts from the West Antarctic rift and ocean islands (OIB), while tholeiites are relatively depleted and approach the concentrations levels of enriched mid-ocean ridge basalt (E-MORB). The magmas evolved by fractional crystallization with contamination by crust; however, neither process can adequately explain the contemporaneous eruption of hawaiite and tholeiite at Sheridan Bluff. Our preferred scenario is that primary magmas of each type were produced by different degrees of partial melting from a compositionally similar mantle source. The nearly simultaneous generation of lower degrees of melting to produce alkaline types and higher degrees of melting forming tholeiite was most likely to have been facilitated by the detachment and dehydration of metasomatized mantle lithosphere.
Pacritinib Combined with Sirolimus and Low-Dose Tacrolimus for GVHD Prevention after Allogeneic Hematopoietic Cell Transplantation: Preclinical and Phase I Trial Results
Authors: Pidala Joseph , Walton Kelly , Elmariah Hany , Kim Jongphil , Mishra Asmita , Bejanyan Nelli , Nishihori Taiga , Khimani Farhad , Perez Lia , Faramand Rawan G. , Davila Marco L. , Nieder Michael L. , Sagatys Elizabeth M. , Holtan Shernan G. , Lawrence Nicholas J. , Lawrence Harshani R. , Blazar Bruce R. , Anasetti Claudio , Sebti Said M. , Betts Brian C. 
Published: March 2021

Abstract

Purpose:
In this first-in-human, phase I, GVHD prevention trial (NCT02891603), we combine pacritinib (PAC), a JAK2 inhibitor, with sirolimus to concurrently reduce T-cell costimulation via mTOR and IL6 activity. We evaluate the safety of pacritinib when administered with sirolimus plus low-dose tacrolimus (PAC/SIR/TAC) after allogeneic hematopoietic cell transplantation.

Patients and Methods:
The preclinical efficacy and immune modulation of PAC/SIR were investigated in xenogeneic GVHD. Our phase I trial followed a 3+3 dose-escalation design, including dose level 1 (pacritinib 100 mg daily), level 2 (pacritinib 100 mg twice daily), and level 3 (pacritinib 200 mg twice daily). The primary endpoint was to identify the lowest biologically active and safe dose of pacritinib with SIR/TAC (n = 12). Acute GVHD was scored through day +100. Allografts included 8/8 HLA-matched related or unrelated donor peripheral blood stem cells.

Results:
In mice, we show that dual JAK2/mTOR inhibition significantly reduces xenogeneic GVHD and increases peripheral regulatory T cell (Treg) potency as well as Treg induction from conventional CD4+ T cells. Pacritinib 100 mg twice a day was identified as the minimum biologically active and safe dose for further study. JAK2/mTOR inhibition suppresses pathogenic Th1 and Th17 cells, spares Tregs and antileukemia effector cells, and exhibits preliminary activity in preventing GVHD. PAC/SIR/TAC preserves donor cytomegalovirus (CMV) immunity and permits timely engraftment without cytopenias.

Conclusions:
We demonstrate that PAC/SIR/TAC is safe and preliminarily limits acute GVHD, preserves donor CMV immunity, and permits timely engraftment. The efficacy of PAC/SIR/TAC will be tested in our ongoing phase II GVHD prevention trial.
Radium-223 Treatment Increases Immune Checkpoint Expression in Extracellular Vesicles from the Metastatic Prostate Cancer Bone Microenvironment
Authors: Vardaki Ioulia , Corn Paul , Gentile Emanuela , Song Jian H. , Madan Namrata , Hoang Anh , Parikh Nila , Guerra Leah , Lee Yu-Chen , Lin Song-Chang , Yu Guoyu , Santos Elmer , Melancon Marites P. , Troncoso Patricia , Navone Nora , Gallick Gary E. , Efstathiou Eleni , Subudhi Sumit K. , Lin Sue-Hwa , Logothetis Christopher J. , Panaretakis Theocharis 
Published: March 2021

Abstract

Purpose:
Radium-223 prolongs survival in a fraction of men with bone metastatic prostate cancer (PCa). However, there are no markers for monitoring response and resistance to Radium-223 treatment. Exosomes are mediators of intercellular communication and may reflect response of the bone microenvironment to Radium-223 treatment. We performed molecular profiling of exosomes and compared the molecular profile in patients with favorable and unfavorable overall survival.

Experimental Design:
We performed exosomal transcriptome analysis in plasma derived from our preclinical models (MDA-PCa 118b tumors, TRAMP-C2/BMP4 PCa) and from the plasma of 25 patients (paired baseline and end of treatment) treated with Radium-223. All samples were run in duplicate, and array data analyzed with fold changes +2 to −2 and P &lt; 0.05.

Results:
We utilized the preclinical models to establish that genes derived from the tumor and the tumor-associated bone microenvironment (bTME) are differentially enriched in plasma exosomes upon Radium-223 treatment. The mouse transcriptome analysis revealed changes in bone-related and DNA damage repair–related pathways. Similar findings were observed in plasma-derived exosomes from patients treated with Radium-223 detected changes. In addition, exosomal transcripts detected immune-suppressors (e.g., PD-L1) that were associated with shorter survival to Radium-223. Treatment of the Myc-CaP mouse model with a combination of Radium-223 and immune checkpoint therapy (ICT) resulted in greater efficacy than monotherapy.

Conclusions:
These clinical and coclinical analyses showed that RNA profiling of plasma exosomes may be used for monitoring the bTME in response to treatment and that ICT may be used to increase the efficacy of Radium-223.