bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of choriocapillaris perfusion and choroidal layer changes in patients
with chronic central serous chorioretinopathy randomised to micropulse laser or
photodynamic therapy
Authors: Ho Mary , Lai Frank Hiu Ping , Ng Danny Siu Chun , Iu Lawrence Pui Leung , Chen Li Jia , Mak Andrew Chun Yue , Yip Yolanda , Cheung Carol , Young Alvin Lerrmann , Brelen Marten 
Published: June 2020

Purpose
The purpose of this study was to investigate the signal changes in
choriocapillaris flow deficits and choroidal thickness changes using
swept-source optical coherence tomography angiography (OCTA) following
different treatments.

Design
A double-blind, randomised controlled trial.

Methods
Patients with unilateral chronic central serous chorioretinopathy (CSC)
were randomised to receive subthreshold micropulse laser therapy (MLT) or
half-dose photodynamic therapy (PDT). Choroidal thickness and choriocapillaris
flow deficit signals were investigated.

Results
Eighteen patients were randomised into the MLT group and 15 patients into
the PDT group. Areas with flow deficit signals were identified in all baseline
OCTA images of the choriocapillaris, with mean areas of 0.420 and
0.465 mm2 in the MLT and PDT groups, respectively.
These flow deficit signal areas were significantly reduced at 6 months
(p=0.011) in the MLT group and at 3 months (p=0.008) in the PDT group. Patients
from the PDT group were shown to have smaller flow deficit areas than patients
from the MLT group at all time points after treatment (p=0.001, analyses of
variance). The mean choroidal volume of the fovea showed a significant
reduction at 1 month (p=0.003), 3 months (p=0.199) and 6 months (p=0.006) in
the PDT group.

Conclusion
The flow deficit areas identified in the choriocapillaris layer may
suggest possible relative choroidal ischaemia. With measurement of choroidal
volume reduction and faster rates of flow deficit area change, PDT has a
stronger effect than MLT in promoting choriocapillaris recovery.
Clinical outcomes in adult athletes with hypertrophic cardiomyopathy: a 7-year follow-up study
Authors: Pelliccia Antonio , Caselli Stefano , Pelliccia Matteo , Musumeci Maria Beatrice , Lemme Erika , Di Paolo Fernando M , Maestrini Viviana , Russo Domitilla , Limite Luca , Borrazzo Cristian , Autore Camillo 
Published: June 2020

Objective
Current guidelines recommend precautionary disqualification from competitive sports in patients with hypertrophic cardiomyopathy (HCM). We assessed the incidence of cardiovascular events in a cohort of patients with HCM engaged in long-term exercise programmes and competitive sport.

Methods
We reviewed data on 88 consecutive athletes diagnosed with HCM, from 1997 to 2017; 92% male, 98% Caucasian, median age 31 (IQR: 19–44) years. All participated in regular exercise programmes and competitive sport at study entry.
We performed follow-up evaluation after 7±5 (1–21) years. 61 (69%) of the athletes had substantially reduced or stopped exercise and sport (ie, HCM-detrained), and 27 had continued with regular training and sport competitions (HCM-trained). At baseline evaluation, both groups were similar for age, gender balance, symptoms, ECG abnormalities, extent of left ventricular hypertrophy, arrhythmias and risk profile for sudden cardiac death/arrest.

Results
During the follow-up period, two participants suffered sudden cardiac arrest or death (0.3% per year) both outside of sport participation. In addition, 19 (22%) reported symptoms (syncope in 3, palpitations in 10, chest pain in 4 and dyspnoea in 2). The Kaplan-Meier analyses of freedom from combined sudden cardiac arrest/death and symptoms (log-rank test p=0.264) showed no differences between HCM-trained and detrained patients.

Conclusion
In this adult cohort of low-risk HCM athletes, voluntary decision to pursue in participation in competitive sport events was not associated with increased risk for major cardiac events or clinical worsening compared with decision to reduce or withdraw from exercise programmes and sport. Similar results may not be seen in younger or racially diverse athlete populations, or in patients with more severe HCM phenotypes.
Elicitation of Norwegian EQ-5D-5L values for hypothetical and experience-based health states based on the EuroQol Valuation Technology (EQ-VT) protocol
Authors: Hansen Tonya Moen , Helland Ylva , Augestad Liv Ariane , Rand Kim , Stavem Knut , Garratt Andrew 
Published: June 2020

IntroductionNorway is one of several European countries that lacks a national value set and scoring algorithm for the EuroQol five dimensions (EQ-5D). Recent studies have found differences between countries in terms of health values or preferences for health states described by instruments such as the EQ-5D. The project aims to model a national value set for the five level version of the EQ-5D based on values elicited from a representative sample of the Norwegian adult general population in terms of region, age, sex and level of education. Using a sampling strategy supporting the collection of values for both hypothetical and experienced health states, the study will have the additional aim of assessing the feasibility of collecting experience-based values in accordance with the latest EQ-5D valuation study protocol, and comparing values with those given for hypothetical health states.Methods and analysisMultistage random sampling and quota-sampling will contribute to representativeness. To increase the number of valuations of experienced health states, those with less than perfect health will be oversampled, increasing the total number of interviews from 1000 to 1300–1500. The most recent EQ-5D valuation protocol will be followed which includes computer assisted face-to-face, one-to-one interviews and use of composite time trade-off and discrete choice experiments.Ethics and disseminationThe study has been reviewed and found to be outside of the scope of the ethics committee and thus not in need of ethical approval. The study findings will be disseminated through peer-reviewed publications, conference presentations and summaries for key stakeholders and partners in the field. The scoring algorithms will be available for widely used statistical software.
Does meeting physical activity recommendations ameliorate association between television viewing with cardiovascular disease risk? A cross-sectional, population-based analysis
Authors: Patterson Freda , Mitchell Jonathan A , Dominick Gregory , Lozano Alicia J , Huang Liming , Hanlon Alexandra L 
Published: June 2020

ObjectivesAs a common form of sedentary behaviour, television viewing is associated with an increase in body mass index (BMI) as well as overall cardiovascular disease (CVD) risk. This study examined the extent to which meeting the recommended volume of weekly physical activity (PA) reduced the association between television viewing with the outcomes of BMI and CVD risk. A second aim was to determine the number of hours (ie, cut-point) of daily television viewing that conferred a higher BMI and CVD risk for a large population-based sample of adults.DesignPopulation-based, cross-sectional study.SettingUK Biobank recruited across 35 centres in the UK between 2006 and 2010.Primary outcomeCVD risk, as measured by the 30-year Framingham risk score.ResultsLinear regression models indicated that every additional hour of television viewing per day was associated with a 3% increase in CVD risk (aCoeff=0.03, d=0.16, p<0.0001); the interaction between television viewing with meeting PA guidelines was marginally associated with CVD risk (aCoeff=0.0010, d=0.01, p=0.014). Each additional hour of television viewing per day was associated with a 0.54 increase in BMI (aCoeff=0.54, d=0.13, p<0.0001); the interaction between television viewing with meeting PA guidelines was not significantly associated with BMI. Regression tree models of the study outcomes revealed that 2.5 hours of television viewing was associated with pronounced increases in BMI and CVD risk.ConclusionsThese data underscore the independent association between television viewing with cardiovascular risk and suggest that reducing television viewing to less than 2.5 hours per day, even in physically active adults, is a clinical and public health priority.
Why managing sciatica is difficult: patients’ experiences of an NHS sciatica pathway. A qualitative, interpretative study
Authors: Ryan Clare , Pope Catherine J , Roberts Lisa 
Published: June 2020

ObjectivesAmid a political agenda for integrated, high-value care, the UK is implementing its Low Back and Radicular Pain Pathway. To align care with need, it is imperative to understand the patients’ perspective. The purpose of this study was, therefore, to explore how people experience being managed for sciatica within an National Health Service (NHS) pathway.DesignQualitative interpretative study.SettingMusculoskeletal Service in an NHS, Primary Care Trust, UK.ParticipantsThe sample comprised 14 people aged ≥18 years with a clinical presentation of sciatica, who were currently under the care of a specialist physiotherapist (the specialist spinal triage practitioner), had undergone investigations (MRI) and received the results within the past 6 weeks. People were excluded if they had previously undergone spinal surgery or if the suspected cause of symptoms was cauda equina syndrome or sinister pathology. Participants were sampled purposively for variation in age and gender. Data were collected using individual semi-structured interviews (duration: 38–117 min; median: 82.6 min), which were audio-recorded and transcribed verbatim. Data were analysed thematically.ResultsA series of problems with the local pathway (insufficient transparency and information; clinician-led decisions; standardised management; restricted access to specialist care; and a lack of collaboration between services) made it difficult for patients to access the management they perceived necessary. Patients were therefore required to be independent and proactive or have agency. This was, however, difficult to achieve (due to the impact of sciatica and because patients lacked the necessary skills, funds and support) and together with the pathway issues, this negated patients’ capability to manage sciatica.ConclusionsThis novel paper explores how patients experience the process of being managed within a sciatica pathway. While highlighting the need to align with recommended best practice, it shows the need to be more person-centred and to support and empower patient agency.Trial registration numberClinicalTrials.gov reference (UOS-2307-CR); Pre-results.
What narrative devices do people with systemic sclerosis use to describe the experience of pain from digital ulcers: a multicentre focus group study at UK scleroderma centres
Authors: Jones Jennifer , Hughes Michael , Pauling John , Gooberman-Hill Rachael , Moore Andrew J 
Published: June 2020

ObjectivesDigital ulcers (DUs) are a common complication in systemic sclerosis (SSc). No existing studies have specifically reported on the qualitative patient experience of DU pain, and our current patient-reported outcome measure (PROM) does not capture the multifaceted painful experience of SSc-DU. Our aim was to examine the patient experience of SSc-DU pain.DesignFocus groups with people diagnosed with SSc who had experienced DUs were conducted using a topic guide developed by people with SSc, experts in SSc and experienced qualitative researchers. Focus groups were continued until data saturation had been reached. The focus groups were audio recorded, transcribed verbatim, anonymised and analysed using inductive thematic analysis. Our current study is an integration of the data from these focus groups to specifically examine the patient experience of DU pain.SettingThree specialist scleroderma units across the UK (Bath, Manchester and London).ParticipantsFour focus groups were undertaken; 29 adults (20 women, 9 men) with SSc and a spectrum of historical DUs participated. We included participants with a diverse demographic (including ethnic) background and disease-related characteristics.ResultsFive narrative devices were identified, which encompass how people describe the pain from SSc-DUs: ‘Words to express DU-associated pain’, ‘Descriptions of physical and psychological reactions to pain’, ‘Comparisons with other painful events’, ‘Descriptions of factors that exacerbate pain’ and ‘Descriptions of strategies for coping with the pain’.ConclusionThe experience of SSc-DU pain leads to the use of graphic language and rich description by participants in the focus group setting. Existing SSc-DU outcomes do not adequately capture the patient experiences of SSc-DU pain. Our findings further highlight the multifaceted nature of SSc-DUs and will hopefully support the development of a novel PROM to assess the severity and impact of SSc-DUs.
IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment
Authors: Desbois Mélanie , Béal Coralie , Charrier Mélinda , Besse Benjamin , Meurice Guillaume , Cagnard Nicolas , Jacques Yannick , Béchard David , Cassard Lydie , Chaput Nathalie 
Published: June 2020

BackgroundAs the immune system is compromised in patients with cancer, therapeutic strategies to stimulate immunity appear promising, to avoid relapse and increase long-term overall survival. Interleukin-15 (IL-15) has similar properties to IL-2, but does not cause activation-induced cell death nor activation and proliferation of regulatory T cells (Treg), which makes it a serious candidate for anticancer immunotherapy. However, IL-15 has a short half-life and high doses are needed to achieve responses. Designed to enhance its activity, receptor-linker-IL-15 (RLI) (SO-C101) is a fusion molecule of human IL-15 covalently linked to the human IL-15Rα sushi+ domain currently assessed in a phase I/Ib clinical trial on patients with advanced/metastatic solid cancer.MethodsWe investigated the antimetastatic activity of RLI in a 4T1 mouse mammary carcinoma that spontaneously metastasizes and evaluated its immunomodulatory role in the metastatic lung microenvironment. We further characterized the proliferation, maturation and cytotoxic functions of natural killer (NK) cells in tumor-free mice treated with RLI. Finally, we explored the effect of RLI on human NK cells from healthy donors and patients with non-small cell lung cancer (NSCLC).ResultsRLI treatment displayed antimetastatic properties in the 4T1 mouse model. By characterizing the lung microenvironment, we observed that RLI restored the balance between NK cells and neutrophils (CD11b+Ly6GhighLy6Clow) that massively infiltrate lungs of 4T1-tumor bearing mice. In addition, the ratio between NK cells and Treg was strongly increased by RLI treatment. Further pharmacodynamic studies in tumor-free mice revealed superior proliferative and cytotoxic functions on NK cells after RLI treatment compared with IL-15 alone. Characterization of the maturation stage of NK cells demonstrated that RLI favored accumulation of CD11b+CD27highKLRG1+mature NK cells. Finally, RLI demonstrated potent immunostimulatory properties on human NK cells by inducing proliferation and activation of NK cells from healthy donors and enhancing cytotoxic responses to NKp30 crosslinking in NK cells from patients with NSCLC.ConclusionsCollectively, our work demonstrates superior activity of RLI compared with rhIL-15 in modulating and activating NK cells and provides additional evidences for a therapeutic strategy using RLI as antimetastatic molecule.
Risk perception, safer sex practices and PrEP enthusiasm: barriers and facilitators to oral HIV pre-exposure prophylaxis in Black African and Black Caribbean women in the UK
Authors: Nakasone Sarah E , Young Ingrid , Estcourt Claudia S , Calliste Josina , Flowers Paul , Ridgway Jessica , Shahmanesh Maryam 
Published: June 2020

ObjectivesUK Black African/Black Caribbean women remain disproportionately affected by HIV. Although oral pre-exposure prophylaxis (PrEP) could offer them an effective HIV prevention method, uptake remains limited. This study examined barriers and facilitators to PrEP awareness and candidacy perceptions for Black African/Black Caribbean women to help inform PrEP programmes and service development.MethodsUsing purposive sampling through community organisations, 32 in-depth, semi-structured interviews were conducted with Black African/Black Caribbean women living in London and Glasgow between June and August 2018. Participants (aged 19–63) included women of varied HIV statuses to explore perceptions of sexual risk and safer sex, sexual health knowledge and PrEP attitudes. A thematic analysis guided by the Social Ecological Model was used to explore how PrEP perceptions intersected with wider safer sex understandings and practices.ResultsFour key levels of influence shaping safer sex notions and PrEP candidacy perceptions emerged: personal, interpersonal, perceived environment and policy. PrEP-specific knowledge was low and some expressed distrust in PrEP. Many women were enthusiastic about PrEP for others but did not situate PrEP within their own safer sex understandings, sometimes due to difficulty assessing their own HIV risk. Many felt that PrEP could undermine intimacy in their relationships by disrupting the shared responsibility implicit within other HIV prevention methods. Women described extensive interpersonal networks that supported their sexual health knowledge and shaped their interactions with health services, though these networks were influenced by prevailing community stigmas.ConclusionsDifficulty situating PrEP within existing safer sex beliefs contributes to limited perceptions of personal PrEP candidacy. To increase PrEP uptake in UK Black African/Black Caribbean women, interventions will need to enable women to advance their knowledge of PrEP within the broader context of their sexual health and relationships. PrEP service models will need to include trusted ‘non-sexual health-specific’ community services such as general practice.
Association between COPD exacerbations and lung function decline during maintenance therapy
Authors: Kerkhof Marjan , Voorham Jaco , Dorinsky Paul , Cabrera Claudia , Darken Patrick , Kocks Janwillem WH , Sadatsafavi Mohsen , Sin Don D , Carter Victoria , Price David B 
Published: June 2020

BackgroundLittle is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study.MethodsThe study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsOf 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS.ConclusionExacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.
The shadow of dark matter as a shadow of string theory: string origin of the dipole term
Authors: Dick Rainer 
Published: June 2020

AbstractWe point out that the Kalb–Ramond field can couple to the Ramond and Neveu–Schwarz fields of superstring theory in a way that can generate a coupling of the Kalb–Ramond field to dark matter dipole moments. Electroweak dipole dark matter could then arise from the Ramond sector of superstrings with low string scale $$M_s\lesssim 120$$Ms≲120 TeV.
PESM: A novel approach of tumor purity estimation based on sample specific methylation sites
Authors: Pang Shanchen , Wang Lihua , Wang Shudong , Zhang Yuanyuan , Wang Xinzeng 
Published: June 2020

Background: Tumor purity is of great significance for the study of tumor genotyping and the prediction of recurrence, which is significantly affected by tumor heterogeneity. Tumor heterogeneity is the basis of drug resistance in various cancer treatments, and DNA methylation plays a core role in the generation of tumor heterogeneity. Almost all types of cancer cells are associated with abnormal DNA methylation in certain regions of the genome. The selection of tumor-related differential methylation sites, which can be used as an indicator of tumor purity, has important implications for purity assessment. At present, the selection of information sites mostly focuses on inter-tumor heterogeneity and ignores the heterogeneity of tumor growth space that is sample specificity. Results: Considering the specificity of tumor samples and the information gain of individual tumor sample relative to the normal samples, we present an approach, PESM, to evaluate the tumor purity through the specificity difference methylation sites of tumor samples. Applied to more than 200 tumor samples of Prostate adenocarcinoma (PRAD) and Kidney renal clear cell carcinoma (KIRC), it shows that the tumor purity estimated by PESM is highly consistent with other existing methods. In addition, PESM performs better than the method that uses the integrated signal of methylation sites to estimate purity. Therefore, different information sites selection methods have an important impact on the estimation of tumor purity, and the selection of sample specific information sites has a certain significance for accurate identification of tumor purity of samples.
Approximating Spanners and Directed Steiner Forest
Authors: Chlamtáč Eden , Dinitz Michael , Kortsarz Guy , Laekhanukit Bundit 
Published: June 2020

It was recently found that there are very close connections between the existence of
additive spanners
(subgraphs where all distances are preserved up to an additive stretch),
distance preservers
(subgraphs in which demand pairs have their distance preserved exactly), and
pairwise spanners
(subgraphs in which demand pairs have their distance preserved up to a multiplicative or additive stretch) [Abboud-Bodwin SODA’16 8 J.ACM’17, Bodwin-Williams SODA’16]. We study these problems from an optimization point of view, where rather than studying the existence of extremal instances, we are given an instance and are asked to find the sparsest possible spanner/preserver. We give an
O
(
n
3/5 + ε
)-approximation for distance preservers and pairwise spanners (for arbitrary constant ε > 0). This is the first nontrivial upper bound for either problem, both of which are known to be as hard to approximate as Label Cover. We also prove Label Cover hardness for approximating additive spanners, even for the cases of additive 1 stretch (where one might expect a polylogarithmic approximation, since the related multiplicative 2-spanner problem admits an
O
(log
n
)-approximation) and additive polylogarithmic stretch (where the related multiplicative spanner problem has an
O
(1)-approximation).

Interestingly, the techniques we use in our approximation algorithm extend beyond distance-based problem to pure connectivity network design problems. In particular, our techniques allow us to give an
O
(
n
3/5 + ε
)-approximation for the Directed Steiner Forest problem (for arbitrary constant ε > 0) when all edges have uniform costs, improving the previous best
O
(
n
2/3 + ε
)-approximation due to Berman et al. [ICALP’11] (which holds for general edge costs).