bluuebunny/crossref_metadata_2025_split huggingface dataset:
What helps and hinders the provision of healthcare that minimises treatment burden and maximises patient capacity? A qualitative study of stroke health professional perspectives
Authors: Kyle John , Skleparis Dimitris , Mair Frances S , Gallacher Katie I 
Published: March 2020

ObjectivesTreatment burden is the healthcare workload experienced by individuals with long-term conditions and the impact on well-being. Excessive treatment burden can negatively affect quality-of-life and adherence to treatments. Patient capacity is the ability of an individual to manage their life and health problems and is dependent on a variety of physical, psychological and social factors. Previous work has suggested that stroke survivors experience considerable treatment burden and limitations on their capacity to manage their health. We aimed to examine the potential barriers and enablers to minimising treatment burden and maximising patient capacity faced by health professionals and managers providing care to those affected by stroke.SettingPrimary and secondary care stroke services in a single health board area in Scotland.ParticipantsFace-to-face qualitative interviews with 21 participants including stroke consultants, nurses, physiotherapists, occupational therapists, speech and language therapists, psychologists, general practitioners and health-service managers.Outcome measuresData were analysed using thematic analysis to ascertain any factors that influence the provision of low-burden healthcare.ResultsBarriers and facilitators to the provision of healthcare that minimises treatment burden and maximises patient capacity were reported under five themes: healthcare system structure (e.g. care coordination and autonomous working); resources (e.g. availability of ward nurses and community psychologists); knowledge and awareness (e.g. adequate time and materials for optimal information delivery); availability of social care (e.g. waiting times for home adaptations or extra social support) and patient complexity (e.g. multimorbidity).ConclusionsOur findings have important implications for the design and implementation of stroke care pathways, emphasising the importance of removing barriers to health professional provision of person-centred care. This work can inform the design of interventions aimed at nurturing autonomous working by health professionals, improving communication and care coordination or ensuring availability of a named person throughout the patient journey.
Finding the right balance with participation in exercise and sport for individuals with multiple sclerosis: protocol for a pre and post intervention feasibility study
Authors: Smith Moira , Williams Gavin , Barker Ruth 
Published: March 2020

IntroductionIndividuals with minimal disability from multiple sclerosis (MS) requested advice on finding the right balance, between too much and too little exercise, when participating in their choice of sport or exercise. To optimise exercise participation during the early stages of the disease, a flexible exercise participation programme (FEPP) has been developed. The FEPP is novel because it provides guidance and support for individuals with MS to participate and progress in theirpreferredsport or exercise. The primary objective was to assess the feasibility of the FEPP. The secondary objective was to assess the feasibility of a larger trial to demonstrate the efficacy of the FEPP.Methods and analysisA stage I feasibility study of the FEPP, using a single group preintervention/post-intervention design, will be conducted with 16 participants with minimal disability from MS (Expanded Disability Status Scale level of 0–3.5). The 12-week FEPP will guide participants to independently participate in their preferred sport or exercise at a location of their choice. Exercise progression will be guided by individual energy levels and a weekly telephone coaching session with a physiotherapist. Participation in exercise or sport will be recorded in parallel with assessment of disease biomarkers (plasma cytokines interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumour necrosis factor (TNF)), subjective vitality and high-level mobility. Acceptability of the FEPP will be assessed using a sequential explanatory mixed methods design where the findings of a participant survey will inform the interview guide for a series of focus groups.Feasibility of a larger trial will be assessed via process, resources, management and scientific metrics. Progression to a larger trial will depend on the achievement of specified minimum success criteria.Ethics and disseminationEthical approval has been obtained for this study from the James Cook University Human Research Ethics Committee (H7956). Dissemination of findings is planned via peer-reviewed journals, conference presentations and media releases. The protocol date was 21 December 2019, V.1.Trial registration numberThe trial is registered with Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12620000076976.
Modified paediatric preoperative risk prediction score to predict postoperative ICU admission in children: a retrospective cohort study
Authors: Lian Chunwei , Wang Pei , Fu Qingxia , Du Xudong , Wu Junzheng , Lian Qingquan , ShangGuan Wangning 
Published: March 2020

ObjectiveTo integrate intrinsic surgical risk into the paediatric preoperative risk prediction score (PRPS) model to construct a more comprehensive risk scoring system (modified PRPS) and improve the prediction accuracy of postoperative intensive care unit (ICU) admission in paediatric patients.DesignThis was a retrospective study conducted between 1 January and 30 December 2016. Data on age, American Society of Anaesthesiology physical status (ASA-PS), oxygen saturation, prematurity, non-fasted status, severity of surgery and immediate transfer to the ICU after surgery were collected. The modified PRPS was developed by logistic regression in the derivation cohort; it was tested and compared with the paediatric PRPS and ASA-PS by the Hosmer-Lemeshow test, the receiver operating characteristic (ROC) curve and Kappa analysis in the validation cohort.SettingHospital-based study in China.ParticipantsPaediatric patients (≤14 years) who underwent surgery under general anaesthesia were included, and those who needed reoperation due to surgical complications or stayed in the ICU preoperatively were excluded.Main outcome measureICU admission rate, defined as any patients’ direct disposition from the operating room to the ICU immediately after the surgery.ResultsA total of 9261 paediatric patients were included in this study, with 418 patients admitted to the ICU. In the validation cohort, the modified PRPS model fit the test data well (deciles of risk goodness-of-fit χ2=6.84, p=0.077). The area under the ROC curve of the modified PRPS, paediatric PRPS and ASA-PS were 0.963, 0.941 and 0.870, respectively (p<0.05), and the Kappa values were 0.620, 0.286 and 0.267. Analyses in the cohort indicated that the modified PRPS was superior to the paediatric PRPS and ASA-PS.ConclusionsThe modified PRPS integrating intrinsic surgical risk shows better prediction accuracy than the previous PRPS.
The impact of level of neonatal care provision on outcomes for preterm babies born between 27 and 31 weeks of gestation, or with a birth weight between 1000 and 1500 g: a review of the literature
Authors: Ismail Abdul Qader Tahir , Boyle Elaine M , Pillay Thillagavathie 
Published: March 2020

ObjectiveThere is evidence that birth and care in a maternity service associated with a neonatal intensive care unit (NICU) is associated with improved survival in preterm babies born at <27 weeks of gestation. We conducted a systematic review to address whether similar gains manifested in babies born between 27+0 and 31+6 weeks (hereafter 27 and 31 weeks) of gestation, or in those with a birth weight between 1000 and 1500 g.MethodsWe searched Embase, Medline and CINAHL databases for studies comparing outcomes for babies born between 27 and 31 weeks or between 1000 and 1500 g birth weight, based on designation of the neonatal unit where the baby was born or subsequently cared for (NICU vs non-NICU setting). A modified QUIPS (QUality In Prognostic Studies) tool was used to assess quality.ResultsNine studies compared outcomes for babies born between 27 and 31 weeks of gestation and 11 studies compared outcomes for babies born between 1000 and 1500 g birth weight. Heterogeneity in comparator groups, birth locations, gestational age ranges, timescale for mortality reporting, and description of morbidities facilitated a narrative review as opposed to a meta-analysis.ConclusionDue to paucity of evidence, significant heterogeneity and potential for bias, we were not able to answer our question—does place of birth or care affect outcomes for babies born between 27 and 31 weeks? This supports the need for large-scale research to investigate place of birth and care for babies born in this gestational age range.
Medical-attention injuries in community cricket: a systematic review
Authors: McLeod Geordie , O’Connor Siobhán , Morgan Damian , Kountouris Alex , Finch Caroline F , Fortington Lauren V 
Published: March 2020

ObjectivesThe aim was to identify and describe outcomes from original published studies that present the number, nature, mechanism and severity of medically treated injuries sustained in community-level cricket.DesignSystematic review.MethodsNine databases were systematically searched to December 2019 using terms “cricket*” and “injur*”. Original, peer-reviewed studies reporting injury for at least one injury descriptor (body region, nature of injury and/or mechanism of injury) in community-level cricketers of all ages were included. Qualitative synthesis, critical appraisal and descriptive summary results are reported within the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.ResultsSix studies were included: five reported hospital-treated data and one reported insurance claims data. Two had a low risk of bias. In hospital-based studies, fractures were the most frequent injury type. Upper and lower limb injuries (age ≥15 years) and injuries to the head (age <15 years) were the most common body region injured. Being struck by the ball was the most common mechanism for injury presenting to hospitals. Children were also commonly struck by equipment. One study using insurance claims data reported soft tissue injuries as the main of injury type.ConclusionHospital treatment data were most prominent, which emphasised injuries of a more serious nature or requiring acute care. These injuries were primarily fractures, dislocation/sprain and strains, bruising and open wounds with the majority resulting from players being struck by the ball. Research into whether properly fitted protective equipment, at an approved standard, is worn and is effective, is recommended.
Pterostilbene improves cardiac function in a rat model of right heart failure through modulation of calcium handling proteins and oxidative stress
Authors: Lacerda Denise , Türck Patrick , Campos-Carraro Cristina , Hickmann Alexandre , Ortiz Vanessa , Bianchi Sara , Belló-Klein Adriane , de Castro Alexandre Luz , Bassani Valquiria Linck , Araujo Alex Sander da Rosa 
Published: March 2020

This study explored the effect of pterostilbene (PTS) complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on right heart function, glutathione and glutaredoxin systems, and the expression of redox-sensitive proteins involved with regulation calcium levels in the experimental model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). After 7 days of PAH induction, rats received daily doses of the PTS:HPβCD complex (corresponding to 25, 50, or 100 mg·kg−1of PTS) or vehicle (control group, CTR0) (an aqueous solution containing HPβCD; CTR0 and MCT0 (MCT group that did not receive PTS treatment)) via oral administration for 2 weeks. The results showed that the PTS:HPβCD complex increased the content of reduced glutathione and the activity of glutathione-S-transferase and glutaredoxin in the right ventricle (RV) of MCT-treated rats in a dose-dependent manner. Additionally, at higher doses, it also prevented the reduction of stroke volume and cardiac output, prevented myocardial performance index (MPI) increase, reduced lipoperoxidation, reduced total phospholamban, and increased the expression of sarcoplasmic reticulum calcium ATPase in the RV of MCT-treated rats. These results demonstrate that the PTS:HPβCD complex has a dose-dependent antioxidant mechanism that results in improved cardiac function in experimental right heart failure. Our results open a field of possibilities to PTS administration as new therapeutic approach to conventional therapy for right ventricular dysfunction.Novelty Pterostilbene complexed with hydroxypropyl-β-cyclodextrin could be a new therapeutic approach. Pterostilbene complexed with hydroxypropyl-β-cyclodextrin reestablishes redox homeostasis through glutathione metabolism modulation, leading to an improved MPI in pulmonary arterial hypertension-provoked right heart failure.
Towards high-order calculations of three-nucleon scattering in chiral effective field theory
Authors: Epelbaum E. , Golak J. , Hebeler K. , Kamada H. , Krebs H. , Meißner U.-G. , Nogga A. , Reinert P. , Skibiński R. , Topolnicki K. , Volkotrub Yu. , Witała H. 
Published: March 2020

AbstractWe discuss the current status of chiral effective field theory in the three-nucleon sector and present selected results for nucleon–deuteron scattering observables based on semilocal momentum-space-regularized chiral two-nucleon potentials together with consistently regularized three-nucleon forces up to third chiral order. Using a Bayesian model for estimating truncation errors, the obtained results are found to provide a good description of the experimental data. We confirm our earlier findings that a high-precision description of nucleon–deuteron scattering data below pion production threshold will require the theory to be pushed to fifth chiral order. This conclusion is substantiated by an exploratory study of selected short-range contributions to the three-nucleon force at that order, which, as expected, are found to have significant effects on polarization observables at intermediate and high energies. We also outline the challenges that will need to be addressed in order to push the chiral expansion of three-nucleon scattering observables to higher orders.
Targeting of CD38 by the Tumor Suppressor miR-26a Serves as a Novel Potential Therapeutic Agent in Multiple Myeloma
Authors: Hu Yi , Liu Huimin , Fang Chuanfeng , Li Chen , Xhyliu Fjorela , Dysert Hayley , Bodo Juraj , Habermehl Gabriel , Russell Benjamin E. , Li Wenjun , Chappell Marcia , Jiang Xiaofeng , Ondrejka Sarah L. , Hsi Eric D. , Maciejewski Jaroslaw P. , Yi Qing , Anderson Kenneth C. , Munshi Nikhil C. , Ao Geyou , Valent Jason N. , Lin Jianhong , Zhao Jianjun 
Published: March 2020

Abstract

Multiple myeloma is an incurable refractory hematologic malignancy arising from plasma cells in the bone marrow. Here we investigated miR-26a function in multiple myeloma and tested single-wall carbon nanotube delivery of miR-26a in vitro and in vivo. miR-26a was downregulated in patients with multiple myeloma cells compared with plasma cells from healthy donors. miR-26a overexpression inhibited proliferation and migration and induced apoptosis in multiple myeloma cell lines. To identify the targets of miR-26a, RPMI8226-V-miR-26-GFP and RPMI8226-V-GFP cells were cultured using stable isotope labeling by amino acids in cell culture (SILAC) medium, followed by mass spectrometry analysis. In multiple myeloma cells overexpressing miR-26a, CD38 protein was downregulated and subsequently confirmed to be a direct target of miR-26a. Depletion of CD38 in multiple myeloma cells duplicated the multiple myeloma inhibition observed with exogenous expression of miR-26a, whereas restoration of CD38 overcame the inhibition of miR-26a in multiple myeloma cells. In a human multiple myeloma xenograft mouse model, overexpression of miR-26a inhibited CD38 expression, provoked cell apoptosis, and inhibited cell proliferation. Daratumumab is the first CD38 antibody drug for monotherapy and combination therapy for patients with multiple myeloma, but eventually resistance develops. In multiple myeloma cells, CD38 remained at low level during daratumumab treatment, but a high-quality response is sustained. In daratumumab-resistant multiple myeloma cells, CD38 expression was completely restored but failed to correlate with daratumumab-induced cell death. Therefore, a therapeutic strategy to confer selection pressure to maintain low CD38 expression in multiple myeloma cells may have clinical benefit.

Significance:
These results highlight the tumor suppressor function of miR-26a via its targeting of CD38 and suggest the therapeutic potential of miR-26a in patients with multiple myeloma.
B Cells Improve Overall Survival in HPV-Associated Squamous Cell Carcinomas and Are Activated by Radiation and PD-1 Blockade
Authors: Kim Sangwoo S. , Shen Sarek , Miyauchi Sayuri , Sanders P. Dominick , Franiak-Pietryga Ida , Mell Loren , Gutkind J. Silvio , Cohen Ezra E.W. , Califano Joseph A. , Sharabi Andrew B. 
Published: March 2020

AbstractPurpose:To characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on B-cell populations.Experimental Design:Tumor RNA-sequencing data from over 800 patients with head and neck squamous cell carcinoma (HNSCC) and cervical cancer, including a prospective validation cohort, was analyzed to study the impact of B-cell gene expression on overall survival (OS). A novel murine model of HPV+ HNSCC was used to study the effects of PD-1 blockade and radiotherapy on B-cell activation, differentiation, and clonality including analysis by single-cell RNA-sequencing and B-cell receptor (BCR)-sequencing. Human protein microarray was then used to quantify B-cell–mediated IgG and IgM antibodies to over 16,000 proteins in the serum of patients treated on a clinical trial with PD-1 blockade.Results:RNA-sequencing identified CD19 and IGJ as novel B-cell prognostic biomarkers for 3-year OS (HR, 0.545; P &lt; 0.001). PD-1 blockade and radiotherapy enhance development of memory B cells, plasma cells, and antigen-specific B cells. BCR-sequencing found that radiotherapy enhances B-cell clonality, decreases CDR3 length, and induces B-cell somatic hypermutation. Single-cell RNA-sequencing identified dramatic increases in B-cell germinal center formation after PD-1 blockade and radiotherapy. Human proteome array revealed enhanced IgG and IgM antibody responses in patients who derived clinical benefit but not those with progressive disease after treatment with PD-1 blockade.Conclusions:These findings establish a key role for B cells in patient outcomes and responses to PD-1 blockade in HPV-associated squamous cell carcinomas and demonstrate the need for additional diagnostics and therapeutics targeting B cells.
A Phase I/II Study of Neoadjuvant Cisplatin, Docetaxel, and Nintedanib for Resectable Non–Small Cell Lung Cancer
Authors: Cascone Tina , Sepesi Boris , Lin Heather Y. , Kalhor Neda , Parra Edwin R. , Jiang Mei , Godoy Myrna C.B. , Zhang Jianjun , Fossella Frank V. , Tsao Anne S. , Lam Vincent K. , Lu Charles , Mott Frank E. , Simon George R. , Antonoff Mara B. , Mehran Reza J. , Rice David C. , Behrens Carmen , Weissferdt Annikka , Moran Cesar , Vaporciyan Ara A. , Lee J. Jack , Swisher Stephen G. , Gibbons Don L. , Wistuba Ignacio I. , William William N. , Heymach John V. 
Published: March 2020

Abstract

Purpose:
Nintedanib enhances the activity of chemotherapy in metastatic non–small cell lung cancer (NSCLC). In this phase I/II study, we assessed safety and efficacy of nintedanib plus neoadjuvant chemotherapy, using major pathologic response (MPR) as primary endpoint.

Patients and Methods:
Eligible patients had stage IB (≥4 cm)–IIIA resectable NSCLC. A safety run-in phase was followed by an expansion phase with nintedanib 200 mg orally twice a day (28 days), followed by three cycles of cisplatin (75 mg/m2), docetaxel (75 mg/m2) every 21 days plus nintedanib, followed by surgery. With 33 planned patients, the study had 90% power to detect an MPR increase from 15% to 35%.

Results:
Twenty-one patients (stages I/II/III, N = 1/8/12) were treated. One of 15 patients treated with nintedanib 200 mg achieved MPR [7%, 95% confidence interval (CI), 0.2%–32%]. Best ORR in 20 evaluable patients was 30% (6/20, 95% CI, 12%–54%). Twelve-month recurrence-free survival and overall survival were 66% (95% CI, 47%–93%) and 91% (95% CI, 79%–100%), respectively. Most frequent treatment-related grade 3–4 toxicities were transaminitis and electrolyte abnormalities. On the basis of an interim analysis the study was discontinued for futility. Higher levels of CD3+ and cytotoxic CD3+CD8+ T cells were found in treated tumors of patients who were alive than in those who died (652.8 vs. 213.4 cells/mm2, P = 0.048; 142.3 vs. 35.6 cells/mm2, P = 0.018).

Conclusions:
Although tolerated, neoadjuvant nintedanib plus chemotherapy did not increase MPR rate compared with chemotherapy historical controls. Additional studies of the combination in this setting are not recommended. Posttreatment levels of tumor-infiltrating T cells were associated with patient survival. Use of MPR facilitates the rapid evaluation of neoadjuvant therapies.
See related commentary by Blakely and McCoach, p. 3499
Endogenous PAD4 in Breast Cancer Cells Mediates Cancer Extracellular Chromatin Network Formation and Promotes Lung Metastasis
Authors: Shi Lai , Yao Huanling , Liu Zheng , Xu Ming , Tsung Allan , Wang Yanming 
Published: March 2020

Abstract

Peptidyl arginine deiminase 4 (PAD4/PADI4) is a posttranslational modification enzyme that converts protein arginine or mono-methylarginine to citrulline. The PAD4-mediated hypercitrullination reaction in neutrophils causes the release of nuclear chromatin to form a chromatin network termed neutrophil extracellular traps (NET). NETs were first described as antimicrobial fibers that bind and kill bacteria. However, it is not known whether PAD4 can mediate the release of chromatin DNA into the extracellular space of cancer cells. Here, we report that murine breast cancer 4T1 cells expressing high levels of PADI4 can release cancer extracellular chromatin networks (CECN) in vitro and in vivo. Deletion of Padi4 using CRISPR/Cas9 abolished CECN formation in 4T1 cells. Padi4 deletion from 4T1 cells also reduced the rate of tumor growth in an allograft model, and decreased lung metastasis by 4T1 breast cancers. DNase I treatment, which degrades extracellular DNA including CECNs, also reduced breast to lung metastasis of Padi4 wild-type 4T1 cells in allograft experiments in the Padi4-knockout mice. We further demonstrated that DNase I treatment in this mouse model did not alter circulating tumor cells but decreased metastasis through steps after intravasation. Taken together, our genetic studies show that PAD4 plays a cell autonomous role in cancer metastasis, thus revealing a novel strategy for preventing cancer metastasis by inhibiting cancer cell endogenous PAD4.

Implications:
This study shows that PADI4 can mediate the formation of CECNs in 4T1 cells, and that endogenous PADI4 plays an essential role in breast cancer lung metastasis.

Visual Overview:
http://mcr.aacrjournals.org/content/molcanres/18/5/735/F1.large.jpg.