bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resisting recommended treatment for prostate cancer: a qualitative analysis of the lived experience of possible overdiagnosis
Authors: McCaffery Kirsten , Nickel Brooke , Pickles Kristen , Moynihan Ray , Kramer Barnett , Barratt Alexandra , Hersch Jolyn 
Published: May 2019

ObjectiveTo describe the lived experience of a possible prostate cancer overdiagnosis in men who resisted recommended treatment.DesignQualitative interview studySettingAustraliaParticipants11 men (aged 59–78 years) who resisted recommended prostate cancer treatment because of concerns about overdiagnosis and overtreatment.OutcomesReported experience of screening, diagnosis and treatment decision making, and its impact on psychosocial well-being, life and personal circumstances.ResultsMen’s accounts revealed profound consequences of both prostate cancer diagnosis and resisting medical advice for treatment, with effects on their psychological well-being, family, employment circumstances, identity and life choices. Some of these men were tested for prostate-specific antigen without their knowledge or informed consent. The men felt uninformed about their management options and unsupported through treatment decision making. This often led them to develop a sense of disillusionment and distrust towards the medical profession and conventional medicine. The findings show how some men who were told they would soon die without treatment (a prognosis which ultimately did not eventuate) reconciled issues of overdiagnosis and potential overtreatment with their own diagnosis and situation over the ensuing 1 to 20+ years.ConclusionsMen who choose not to have recommended treatment for prostate cancer may avoid treatment-associated harms like incontinence and impotence, however our findings showed that the impact of the diagnosis itself is immense and far-reaching. A high priority for improving clinical practice is to ensure men are adequately informed of these potential consequences before screening is considered.
Healthcare practitioners’ experiences of an intervention to detect and treat patients with liver disease (the LOCATE intervention): a qualitative process evaluation
Authors: Reinson Tina , Bradbury Katherine , Moore Michael , Sheron Nick 
Published: May 2019

ObjectivesThe local care and treatment of liver disease (LOCATE) intervention embedded specialist liver nurses in general practitioner (GP) practices to improve the identification of progressive liver disease, enabling earlier intervention. This current process evaluation examines GP practice staffs’ perceptions of the LOCATE intervention, in order to understand any potential barriers to successful implementation in clinical practice.Study design and settingA qualitative process evaluation nested within the LOCATE feasibility trial, using semistructured interviews with practice staff from five GP surgeries in the UK.ParticipantsA purposive sample of 29 interviews with practice staff (GPs, nurses, practice managers).Data collectionInterview transcripts were subjected to thematic analysis.FindingsThe intervention was found to be acceptable to practice staff and a number of barriers and facilitators to the success of the intervention were identified. However, interviews suggested that the intervention did not provide sufficient guidance for clinicians to be able to help patients make the behavioural changes needed to reduce risk factors associated with liver disease. The intervention did appear to improve clinician awareness and knowledge about liver disease, enabling GPs to feel more confident interpreting and managing liver function blood tests in order to identify the early signs of liver disease.ConclusionsThis study enabled identification of potential barriers to implementation of specialist nurses in primary care to identify progressive liver disease and enable earlier intervention. The next steps are to improve the intervention to make it more feasible to implement in practice and more likely to help patients to make the behavioural changes required to prevent a major liver event.Trial registration number13/SC/0012; Post-results.EthicsThis study was reviewed and approved by NRES Committee South Central—Hampshire A, Bristol Research Ethics Committee Centre, level 3, block B, Whitefriars, Lewins Mead Bristol BS1 2NT.
Football’s InfluencE on Lifelong health and Dementia risk (FIELD): protocol for a retrospective cohort study of former professional footballers
Authors: Russell Emma R , Stewart Katy , Mackay Daniel F , MacLean John , Pell Jill P , Stewart William 
Published: May 2019

IntroductionIn the past decade, evidence has emerged suggesting a potential link between contact sport participation and increased risk of late neurodegenerative disease, in particular chronic traumatic encephalopathy. While there remains a lack of clear evidence to test the hypothesis that contact sport participation is linked to an increased incidence of dementia, there is growing public concern regarding the risk. There is, therefore, a pressing need for research to gain greater understanding of the potential risks involved in contact sports participation, and to contextualise these within holistic health benefits of sport.Methods and analysisFootball’s InfluencE on Lifelong health and Dementia risk is designed as a retrospective cohort study, with the aim to analyse data from former professional footballers (FPF) in order to assess the incidence of neurodegenerative disease in this population. Comprehensive electronic medical and death records will be analysed and compared with those of a demographically matched population control cohort. As well as neurodegenerative disease incidence, all-cause, and disease-specific mortality, will be analysed in order to assess lifelong health. Cox proportional hazards models will be run to compare the data collected from FPFs to matched population controls.Ethics and disseminationApprovals for study have been obtained from the University of Glasgow College of Medical, Veterinary and Life Sciences Research Ethics Committee (Project Number 200160147) and from National Health Service Scotland’s Public Benefits and Privacy Panel (Application 1718-0120).
Putting out fires: a qualitative study exploring the use of patient complaints to drive improvement at three academic hospitals
Authors: Liu Jessica J , Rotteau Leahora , Bell Chaim M , Shojania Kaveh G 
Published: May 2019

Background and objectivesRecent years have seen increasing calls for more proactive use of patient complaints to develop effective system-wide changes, analogous to the intended functions of incident reporting and root cause analysis (RCA) to improve patient safety. Given recent questions regarding the impact of RCAs on patient safety, we sought to explore the degree to which current patient complaints processes generate solutions to recurring quality problems.Design/settingQualitative analysis of semistructured interviews with 21 patient relations personnel (PRP), nursing and physician leaders at three teaching hospitals (Toronto, Canada).ResultsChallenges to using the patient complaints process to drive hospital-wide improvement included: (1) Complaints often reflect recalcitrant system-wide issues (eg, wait times) or well-known problems which require intensive efforts to address (eg, poor communication). (2) The use of weak change strategies (eg, one-off educational sessions). (3) The handling of complaints by unit managers so they never reach the patient relations office. PRP identified giving patients a voice as their primary goal. Yet their daily work, which they described as ‘putting out fires’, focused primarily on placating patients in order to resolve complaints as quickly as possible, which may in effect suppress the patient voice.ConclusionsUsing patient complaints to drive improvement faces many of the challenges affecting incident reporting and RCA. The emphasis on ‘putting out fires’ may further detract from efforts to improve care for future patients. Systemically incorporating patients’ voices in clinical operations, as with co-design and other forms of authentic patient engagement, may hold greater promise for meaningful improvements in the patient experience than do RCA-like analyses of patient complaints.
Performing diagnostic radial access coronary angiography on uninterrupted direct oral anticoagulant therapy: a prospective analysis
Authors: Chongprasertpon Napohn , Zebrauskaite Aiste , Coughlan John Joseph , Ibrahim Abdalla , Arnous Samer , Hennessy Terence , Kiernan Thomas John 
Published: May 2019

PurposeWe sought to assess the safety of performing diagnostic radial access coronary angiography with uninterrupted anticoagulation on patients receiving direct oral anticoagulant therapy.BackgroundDirect oral anticoagulants have become a popular choice for the prevention of thromboembolism. Risk factors for thromboembolism are common among cardiovascular conditions and indications for direct oral anticoagulant therapy as well as coronary angiography often overlap in patients. It has been hypothesised that uninterrupted direct oral anticoagulant therapy would increase haemorrhagic and access site complications, however data in this area is limited.MethodsThis was a prospective observational analysis of 49 patients undergoing elective diagnostic coronary angiography while receiving uninterrupted anticoagulation with direct oral anticoagulants. This population was compared with a control group of 49 unselected patients presenting to the cardiology service for elective diagnostic coronary angiography. Continuous variables were analysed using the independent samples t-test and categorical variables using Pearson’s χ2test.ResultsThe mean duration of radial compression for the control group was 235.8±62.8 min and for the uninterrupted direct oral anticoagulant group was 258.4±56.5 min. There was no significant difference in mean duration of radial compression (p=0.07; 95% CI=-1.4 to 46.5). There was also no difference in the complication rate between the two groups (p=1).ConclusionsWe observed similar complication rates and radial artery compression time postangiography in both groups. This small prospective observational study suggests that uninterrupted continuation of direct oral anticoagulants during coronary angiography is safe. Larger randomised control studies in this area would be beneficial.
Coronary artery calcium, HIV and inflammation in Uganda compared with the USA
Authors: Alencherry Ben , Erem Geoffrey , Mirembe Grace , Ssinabulya Isaac , Yun Chun-Ho , Hung Chung-Lieh , Siedner Mark J , Bittencourt Marcio , Kityo Cissy , McComsey Grace A , Longenecker Chris T 
Published: May 2019

ObjectivesTo compare the prevalence of detectable coronary artery calcium (CAC) among higher risk, older people living with HIV (PLWH) and uninfected persons in Uganda versus the USA, and second to explore associations of CAC with HIV-specific variables and biomarkers of inflammation.MethodsThis cross-sectional study of 430 total subjects compared 100 PLWH on antiretroviral therapy and 100 age-matched and sex-matched HIV-uninfected controls in Uganda with 167 PLWH on antiretroviral therapy and 63 uninfected controls in the USA. Multivariable logistic regression was used to examine associations with detectable CAC (CAC >0).ResultsCompared with US subjects, Ugandans were older (mean age 56 vs 52 years) and were more likely to have diabetes (36% vs 3%) and hypertension (85% vs 36%), but were less likely to be male (38% vs 74%) or smokers (4% vs 56%). After adjustment for HIV serostatus, age, sex and traditional risk factors, Ugandans had substantially lower odds of CAC >0 (adjusted OR 0.07 (95% CI 0.03 to 0.17), p<0.001). HIV was not associated with CAC >0 in either country (p>0.1). Among all PLWH, nadir CD4 count was associated with the presence of CAC, and among Ugandans soluble intercellular adhesion molecule (p=0.044), soluble CD163 (p=0.004) and oxidised low-density lipoprotein (p=0.043) were all associated with the presence of CAC.ConclusionsUgandans had a dramatically lower prevalence of any coronary calcification compared with US subjects. The role of HIV infection and inflammation as risk factors for subclinical coronary disease in sub-Saharan Africa merits further investigation.
Identifying the source of illicit gold from South America
Authors: Dixon Roger D. , Merkle Roland K. W. 
Published: May 2019

Abstract
Illicit trade in gold, mainly sourced from South America and Africa, is used to fund criminal activities such as the drug trade. Laundering money through the purchase of illicit gold, then having it refined and being paid for in clean funds is a major problem, and drives further growth in illicit mining. In order to restrict the influx of illicit gold into the legal domain, it is necessary to be able to identify the traded item as being of a licit or illicit nature. The only way that this can be done with any certainty is by determining, from its chemical composition, the source of the gold and the means by which it has been processed and upgraded. The example dealt with here shows how the use of compositional, processing and geological knowledge is able to discriminate gold from different origins. Data derived from a physical sample is far better able to constrain the source than a paper trail of certification, which can be manipulated.
Impact of different temperature stimuli on the expression of myosin heavy chain isoforms during recovery from bupivacaine-induced muscle injury in rats
Authors: Shibaguchi Tsubasa , Hoshi Mizuki , Yoshihara Toshinori , Naito Hisashi , Goto Katsumasa , Yoshioka Toshitada , Sugiura Takao 
Published: May 2019

Limited information exists regarding the impact of different temperature stimuli on myosin heavy chain (MyHC) expression in skeletal muscle during recovery from injury. Therefore, this experiment investigated the impact of both cold and heat exposure on the MyHC isoform profile in the rat soleus during recovery from injury. Male Wistar rats were randomly divided into control, bupivacaine-injected (BPVC), BPVC with icing, and BPVC with heat stress groups. Muscle injury was induced by intramuscular injection of bupivacaine into soleus muscles of male Wistar rats. Icing treatment (0°C for 20 min) was performed immediately after the injury. Intermittent heat stress (42°C for 30 min on alternating days) was carried out during 2–14 days after bupivacaine injection. In response to injury, a transient increase in developmental, IId/x, and IIb MyHC isoforms, as well as various types of hybrid fibers, followed by the recovery of the MyHC profile toward the control level, was noted in the regeneration of the soleus. The restoration of the MyHC profile in the regenerating muscle at whole-muscle and individual myofiber levels was partially delayed by icing but facilitated by heat stress. In addition, the application of repeated heat stress promoted the recovery of soleus muscle mass toward the control level following injury. We conclude that compared with acute and immediate cold (icing) treatment, chronic and repeated heat stress may be a more appropriate treatment for the enhancement of both normalization of the MyHC profile and restoration of muscle mass following injury.NEW & NOTEWORTHY Cold exposure (icing), but not heat exposure, has been well accepted as a first-aid treatment for accidental and/or sports-related injuries. However, recent evidence suggests the negative impact of icing treatment on skeletal muscle regeneration following injury. Here, we demonstrated that acute/immediate icing treatment delayed the restoration of the myosin heavy chain (MyHC) profile, but intermittent hyperthermia, repeated for several days, facilitated the recovery of both muscle mass and the MyHC profile in the regeneration of skeletal muscle following injury.
Differential Activity of ATR and WEE1 Inhibitors in a Highly Sensitive Subpopulation of DLBCL Linked to Replication Stress
Authors: Young Lucy A. , O'Connor Lenka Oplustil , de Renty Christelle , Veldman-Jones Margaret H. , Dorval Thierry , Wilson Zena , Jones David R. , Lawson Deborah , Odedra Rajesh , Maya-Mendoza Apolinar , Reimer Corinne , Bartek Jiri , Lau Alan , O'Connor Mark J. 
Published: May 2019

Abstract

DNA damage checkpoint kinases ATR and WEE1 are among key regulators of DNA damage response pathways protecting cells from replication stress, a hallmark of cancer that has potential to be exploited for therapeutic use. ATR and WEE1 inhibitors are in early clinical trials and success will require greater understanding of both their mechanism of action and biomarkers for patient selection. Here, we report selective antitumor activity of ATR and WEE1 inhibitors in a subset of non-germinal center B-cell (GCB) diffuse large B-cell lymphoma (DLBCL) cell lines, characterized by high MYC protein expression and CDKN2A/B deletion. Activity correlated with the induction of replication stress, indicated by increased origin firing and retardation of replication fork progression. However, ATR and WEE1 inhibitors caused different amounts of DNA damage and cell death in distinct phases of the cell cycle, underlying the increased potency observed with WEE1 inhibition. ATR inhibition caused DNA damage to manifest as 53BP1 nuclear bodies in daughter G1 cells leading to G1 arrest, whereas WEE1 inhibition caused DNA damage and arrest in S phase, leading to earlier onset apoptosis. In vivo xenograft DLBCL models confirmed differences in single-agent antitumor activity, but also showed potential for effective ATR inhibitor combinations. Importantly, insights into the different inhibitor mechanisms may guide differentiated clinical development strategies aimed at exploiting specific vulnerabilities of tumor cells while maximizing therapeutic index. Our data therefore highlight clinical development opportunities for both ATR and WEE1 inhibitors in non-GCB DLBCL subtypes that represent an area of unmet clinical need.

Significance:
ATR and WEE1 inhibitors demonstrate effective antitumor activity in preclinical models of DLBCL associated with replication stress, but new mechanistic insights and biomarkers of response support a differentiated clinical development strategy.
Pathogen Molecular Pattern Receptor Agonists: Treating Cancer by Mimicking Infection
Authors: Aleynick Mark , Svensson-Arvelund Judit , Flowers Christopher R. , Marabelle Aurélien , Brody Joshua D. 
Published: May 2019

Abstract
Immunotherapies such as checkpoint blockade have achieved durable benefits for patients with advanced stage cancer and have changed treatment paradigms. However, these therapies rely on a patient's own a priori primed tumor-specific T cells, limiting their efficacy to a subset of patients. Because checkpoint blockade is most effective in patients with inflamed or “hot” tumors, a priority in the field is learning how to “turn cold tumors hot.” Inflammation is generally initiated by innate immune cells, which receive signals through pattern recognition receptors (PRR)–a diverse family of receptors that sense conserved molecular patterns on pathogens, alarming the immune system of an invading microbe. Their immunostimulatory properties can reprogram the immune suppressive tumor microenvironment and activate antigen-presenting cells to present tumors antigens, driving de novo tumor-specific T-cell responses. These features, among others, make PRR-targeting therapies an attractive strategy in immuno-oncology. Here, we discuss mechanisms of PRR activation, highlighting ongoing clinical trials and recent preclinical advances focused on therapeutically targeting PRRs to treat cancer.
Recent Developments of Novel Pharmacologic Therapeutics for Prevention of Chemotherapy-Induced Peripheral Neuropathy
Authors: Hu Shuiying , Huang Kevin M. , Adams Elizabeth J. , Loprinzi Charles L. , Lustberg Maryam B. 
Published: May 2019

Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting toxicity, negatively affecting both quality of life and disease outcomes. To date, there is no proven preventative strategy for CIPN. Although multiple randomized trials have evaluated a variety of pharmacologic interventions for the treatment of CIPN, only duloxetine has shown clear efficacy in a phase III study. The National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee has identified CIPN as a priority for translational research in cancer care. Promising advances in preclinical research have identified several novel preventative and therapeutic targets, which have the potential to transform the care of patients with this debilitating neurotoxicity. Here, we provide an overarching view of emerging strategies and therapeutic targets that are currently being evaluated in CIPN.
NME1 Drives Expansion of Melanoma Cells with Enhanced Tumor Growth and Metastatic Properties
Authors: Wang Ying , Leonard M. Kathryn , Snyder Devin E. , Fisher Matthew L. , Eckert Richard L. , Kaetzel David M. 
Published: May 2019

Abstract

Melanoma is a lethal skin cancer prone to progression and metastasis, and resistant to therapy. Metastasis and therapy resistance of melanoma and other cancers are driven by tumor cell plasticity, largely via acquisition/loss of stem-like characteristics and transitions between epithelial and mesenchymal phenotypes (EMT/MET). NME1 is a metastasis suppressor gene that inhibits metastatic potential when its expression is enforced in melanoma and other cancers. Herein, we have unmasked a novel role for NME1 as a driver of melanoma growth distinct from its canonical function as a metastasis suppressor. NME1 promotes expansion of stem-like melanoma cells that exhibit elevated expression of stem cell markers (e.g., Sox2, Sox10, Oct-4, KLF4, and Ccnb-1), enhanced growth as melanoma spheres in culture, and enhanced tumor growth and lung colonizing activities in vivo. In contrast, NME1 expression did not affect the proliferation of melanoma cell lines in monolayer culture conditions. Silencing of NME1 expression resulted in a dramatic reduction in melanoma sphere size, and impaired tumor growth and metastatic activities of melanoma sphere cells when xenografted in immunocompromised mice. Individual cells within melanoma sphere cultures displayed a wide range of NME1 expression across multiple melanoma cell lines. Cell subpopulations with elevated NME1 expression were fast cycling and displayed enhanced expression of stem cell markers.

Implications:
Our findings suggest the current model of NME1 as a metastasis-suppressing factor requires refinement, bringing into consideration its heterogeneous expression within melanoma sphere cultures and its novel role in promoting the expansion and tumorigenicity of stem-like cells.