bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives of people with inherited retinal diseases on ocular gene therapy in Australia: protocol for a national survey
Authors: Mack Heather G , Chen Fred K , Grigg John , Jamieson Robyn , De Roach John , O’Hare Fleur , Britten-Jones Alexis Ceecee , McGuinness Myra , Tindill Nicole , Ayton Lauren 
Published: June 2021

IntroductionVoretigene neparvovec-rzyl (Luxturna) was approved by the Australian Therapeutic Goods Administration on 4 August 2020 for the treatment of biallelic mutations in theRPE65gene, a rare cause of congenital and adult-onset retinal dystrophy (predominantly Leber congenital amaurosis). Previous studies have shown that individuals who might participate in gene therapy trials overestimate clinical effect and underestimate risks. However, little is known about the perspectives of patients who may be offered approved gene therapy treatment for ocular conditions (as distinct from participating in clinical trials of gene therapy). The main objective of this study is to develop a tool to assess knowledge, attitudes and perceptions of approved and future genetic therapies among potential recipients of ocular gene therapy. In addition, we aim to assess the quality of life, attitudes towards clinical trials and vision-related quality of life among this cohort.Methods and analysisA new ‘Attitudes to Gene Therapy for the Eye’ tool will be developed following consultation with people with inherited retinal disease (IRD) and content matter experts. Australians with IRD or their guardians will be asked to complete an internet-based survey comprising existing quality of life and visual function instruments and items for the newly proposed tool. We expect to recruit 500 survey participants from patient support groups, the practices of Australian ophthalmologists who are specialists in IRD and Australian ophthalmic research institutions. Launch is anticipated early 2021. Responses will be analysed using item response theory methodology.Ethics and disseminationThis study has received ethics approval from the University of Melbourne (#2057534). The results of the study will be published in a peer-reviewed journal and will be presented at relevant conferences. Organisations involved in recruitment, and the Patient Engagement Advisory committee will assist the research team with dissemination of the study outcomes.
‘Well-being paradox’ revisited: a cross-sectional study of quality of life in over 4000 adults with congenital heart disease
Authors: Andonian Caroline Sophie , Freilinger Sebastian , Achenbach Stephan , Ewert Peter , Gundlach Ulrike , Hoerer Jürgen , Kaemmerer Harald , Pieper Lars , Weyand Michael , Neidenbach Rhoia Clara , Beckmann Jürgen 
Published: June 2021

ObjectiveThe present cross-sectional study investigated quality of life (QOL) in a large cohort of German adults with congenital heart disease (ACHDs) in association with patient-related and clinical variables.DesignCross-sectional survey.ParticipantsBetween 2016 and 2019, a representative sample of 4014 adults with various forms of congenital heart defect (CHD) was retrospectively analysed. Inclusion criteria were confirmed diagnosis of CHD; participant aged 18 years and older; and necessary physical, cognitive and language capabilities to complete self-report questionnaires.Primary and secondary outcome measuresQOL was assessed using the 5-level EQ-5D version (EQ-5D-5L). Sociodemographic and medical information was obtained by a self-devised questionnaire. Associations of QOL with patient-reported clinical and sociodemographic variables were quantified using multiple regression analysis and multiple ordinal logit models.ResultsOverall, ACHDs (41.8±17.2 years, 46.5% female) reported a good QOL comparable to German population norms. The most frequently reported complaints occurred in the dimensions pain/discomfort (mean: 16.3, SD: p<0.001) and anxiety/depression (mean: 14.3, p<0.001). QOL differed significantly within ACHD subgroups, with patients affected by pretricuspid shunt lesions indicating the most significant impairments (p<0.001). Older age, female sex, medication intake and the presence of comorbidities were associated with significant reductions in QOL (p<0.001). CHD severity was positively associated with QOL within the dimensions of self-care (OR 0.148, 95% CI 0.04 to 0.58) and mobility (OR 0.384, 95% CI 0.19 to 0.76).ConclusionCurrent findings temper widely held assumptions among clinicians and confirm that ACHDs experience a generally good QOL. However, specific subgroups may require additional support to cope with disease-related challenges. The negative correlation of QOL with age is especially alarming as the population of ACHDs is expected to grow older in the future.Trial registration numberDRKS00017699; Results.
Healthcare staff well-being and use of support services during COVID-19: a UK perspective
Authors: Petrella Anika R , Hughes Luke , Fern Lorna A , Monaghan Lisa , Hannon Benjamin , Waters Adam , Taylor Rachel M 
Published: June 2021

BackgroundThe COVID-19 pandemic has drastically increased demands on healthcare workers (HCWs) leaving them vulnerable to acute psychological distress, burnout and post-traumatic stress. In response, supportive services in a central London hospital mobilised mental health support specifically for HCWs.AimsThis rapid evaluation assessed HCW psychological welfare during the acute phase of the COVID-19 pandemic and their use of supportive services made available.MethodsDuring the acute phase of COVID-19 (April to May 2020) all staff working for the hospital were invited to complete an online survey assessing well-being (self-rated health, moral distress exposure, symptoms of burnout and psychological distress) and use of available supportive services (awareness of, use and perceived helpfulness). Associations among personal characteristics and psychological well-being were explored using correlations and linear regression.ResultsA total of 1127 staff participated in the rapid evaluation. On average, psychological distress was high (mean (SD): 22 (7.57)) regardless of role, with 84% of this sample scoring above the general population mean (14.5). Nearly half of the sample reported feeling emotionally drained and a profile emerged displaying higher levels of psychological distress and burnout in those who were younger and exposed to morally distressing situations, with this group also exhibiting greater support service use. Greater levels of burnout were associated with increased psychological distress when controlling for personal factors. During this acute phase of the pandemic, majority of staff used at least one service and rated it as helpful.ConclusionHCWs experienced high levels of psychological distress requiring continued support as the COVID-19 pandemic evolved. Although HCWs were aware of supportive services, uptake varied. In order to mitigate the risk of burnout and post-traumatic stress, long-term, effective strategies that facilitate staff accessing support are urgently required.
Circulating myeloid-derived suppressor cells and regulatory T cells as immunological biomarkers in refractory/relapsed diffuse large B-cell lymphoma: translational results from the R2-GDP-GOTEL trial
Authors: Jiménez-Cortegana Carlos , Palazón-Carrión Natalia , Martin Garcia-Sancho Alejandro , Nogales-Fernandez Esteban , Carnicero-González Fernando , Ríos-Herranz Eduardo , de la Cruz-Vicente Fatima , Rodríguez-García Guillermo , Fernández-Álvarez Rubén , Rueda Dominguez Antonio , Casanova-Espinosa Maria , Martínez-Banaclocha Natividad , Gumà-Padrò Josep , Gómez-Codina José , Labrador Jorge , Salar-Silvestre Antonio , Rodriguez-Abreu Delvys , Galvez-Carvajal Laura , Provencio Mariano , Sánchez-Beato Margarita , Guirado-Risueño María , Espejo-García Pablo , Lejeune Marylene , Álvaro Tomás , Sánchez-Margalet Victor , de la Cruz-Merino Luis 
Published: June 2021

BackgroundThe search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator.MethodsBlood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations.ResultsIn this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival.ConclusionsIn conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.
Endovascular treatment of anterior cerebral artery occlusions
Authors: Goyal Mayank , Cimflova Petra , Ospel Johanna Maria , Chapot René 
Published: June 2021

There are limited data on endovascular treatment (EVT) for anterior cerebral artery (ACA) occlusions. This review focuses on aspects related to ACA EVT: ACA anatomy, clinical and imaging findings, prognosis of ACA stroke, and ACA thrombectomy techniques. The ACA anatomy, and the regions supplied by the ACA, are highly variable; frequent anatomical variants include azygos ACA, triplicated ACA and fenestrations of the anterior communicating artery. ACA occlusions can be classified based on occlusion location, their continuity with other vessel occlusions (isolated ACA occlusion vs ACA occlusion as part of a carotid T occlusion) and etiology (primary—spontaneous ACA occlusion, vs secondary—spontaneous or iatrogenic due to clot fragmentation/migration). Symptoms of ACA stroke differ in severity and nature due to large inter-individual variations in territorial ACA blood supply. Generally, ACA strokes are severely disabling, and the typical clinical hallmark is a motor deficit of the contralateral lower extremity. Advanced imaging (CT perfusion, multiphase CT angiography) increases the likelihood of the correct diagnosis of ACA stroke and should be obtained on routine basis.Available data for ACA EVT suggest its feasibility and safety while clinical outcomes are often unfavorable with conservative management. Therefore, the potential benefit of EVT seems obvious. An optimized endovascular approach for ACA thrombectomy comprises the development and use of smaller and softer devices that can be delivered through small microcatheters with an optimized vector of force. Ultimately, generating high-level evidence for ACA EVT from randomized trials remains warranted.
Exact solutions of (deformed) Jackiw–Teitelboim gravity
Authors: Momeni Davood , Channuie Phongpichit 
Published: June 2021

AbstractIt is well known that Jackiw–Teitelboim (JT) gravity posses the simplest theory on 2-dimensional gravity. The model has been fruitfully studied in recent years. In the present work, we investigate exact solutions for both JT and deformed JT gravity recently proposed in the literature. We revisit exact Euclidean solutions for Jackiw-Teitelboim gravity using all the non-zero components of the dilatonic equations of motion using proper integral transformation over Euclidean time coordinate. More precisely, we study exact solutions for hyperbolic coverage, cusp geometry and another compact sector of the AdS$$_2$$

2

spacetime manifold.
Semi-compactness and multiple oscillating pulses in kink scattering
Authors: Bazeia D. , Gomes Adalto R. , Simas Fabiano C. 
Published: June 2021

AbstractIn this work we consider models of asymmetric kinks, where the behavior of the solution in one side is different from the other side. Also, the models depend of an integer n and, with the increase of n, the constructed kink assumes a hybrid character: a compactlike profile on one side and a kinklike profile on the other side. We investigate numerically the kink-antikink and antikink-kink dynamics, with the aim to understand the effect of the transition of the usual kink to the semi-compacton structure. The kink-antikink process shows the formation of one-bounce windows for small values of n. The increase of n favors the breaking this structure and the appearance of oscillatory modes. For antikink-kink collisions we report the appearance of two-bounce windows for small values of the parameter. We also found an intricate structure of two-oscillation windows.
Langevin dynamics of heavy quarks in a soft-hard factorized approach
Authors: Li Shuang , Sun Fei , Xie Wei , Xiong Wei 
Published: June 2021

AbstractBy utilizing a soft-hard factorized model, which combines a thermal perturbative description of soft scatterings and a perturbative QCD-based calculation for hard collisions, we study the energy and temperature dependence of the heavy quark diffusion coefficients in Langevin dynamics. The adjustable parameters are fixed from the comprehensive model-data comparison. We find that a small value of the spatial diffusion coefficient at transition temperature is preferred by data $$2\pi TD_{s}(T_{c}) \simeq 6$$

2
π
T

D
s

(

T
c

)

≃
6

. With the parameter-optimized model, we are able to describe simultaneously the prompt $$D^{0}$$

D
0

$$R_{\mathrm{AA}}$$

R
AA

and $$v_{\mathrm{2}}$$

v
2

data at $$p_{\mathrm{T}}\le 8$$

p
T

≤
8

GeV in Pb–Pb collisions at $$\sqrt{s_{\mathrm{NN}}}=2.76$$

s
NN

=
2.76

and $$\sqrt{s_{\mathrm{NN}}}=5.02$$

s
NN

=
5.02

TeV. We also make predictions for non-prompt $$D^{0}$$

D
0

meson for future experimental tests down to the low momentum region.
Fokker–Planck approach to neural networks and to decision problems
Authors: Vellmer Sebastian , Lindner Benjamin 
Published: June 2021

AbstractWe review applications of the Fokker–Planck equation for the description of systems with event trains in computational and cognitive neuroscience. The most prominent example is the spike trains generated by integrate-and-fire neurons when driven by correlated (colored) fluctuations, by adaptation currents and/or by other neurons in a recurrent network. We discuss how for a general Gaussian colored noise and an adaptation current can be incorporated into a multidimensional Fokker–Planck equation by Markovian embedding for systems with a fire-and-reset condition and how in particular the spike-train power spectrum can be determined by this equation. We then review how this framework can be used to determine the self-consistent correlation statistics in a recurrent network in which the colored fluctuations arise from the spike trains of statistically similar neurons. We then turn to the popular drift-diffusion models for binary decisions in cognitive neuroscience and demonstrate that very similar Fokker–Planck equations (with two instead of only one threshold) can be used to study the statistics of sequences of decisions. Specifically, we present a novel two-dimensional model that includes an evidence variable and an expectancy variable that can reproduce salient features of key experiments in sequential decision making.
Semi-supervised Heterogeneous Defect Prediction with Open-source Projects on GitHub
Authors: Sun Ying , Jing Xiao-Yuan , Wu Fei , Dong Xiwei , Sun Yanfei , Wang Ruchuan 
Published: June 2021

The heterogeneous defect prediction (HDP) technique can predict defects in a target company using heterogeneous metric data from external company, which has received substantial research attention. However, existing HDP methods assume that source data is labeled but labeling data is expensive. Semi-supervised defect prediction technique can perform defect prediction with few labeled data. In this paper, we investigate a new problem — semi-supervised HDP (SHDP). To solve this problem, we propose a new approach named cost-sensitive kernel semi-supervised correlation analysis (CKSCA) as a solution of SHDP problem. It introduces unified metric representation and canonical correlation analysis to make the data distributions of different company projects more similar. CKSCA also designs a cost-sensitive kernel semi-supervised discriminant analysis mechanism to utilize the limited labeled data and sufficient real-life unlabeled data from different companies. Besides we collect lots of open-source projects from GitHub website to construct a new large-scale unlabeled dataset called GITHUB dataset. It contains 26,407 modules and is greater than each public project dataset. It has been public online and can be extended continuously. Experiments on the GITHUB dataset and other public datasets indicate that unlabeled GITHUB data can help prediction model improve prediction performance, and CKSCA is effective and efficient for solving SHDP problem.
DNAPK Inhibition Preferentially Compromises the Repair of Radiation-induced DNA Double-strand Breaks in Chronically Hypoxic Tumor Cells in Xenograft Models
Authors: Jiang Yanyan , Willmore Elaine , Wedge Stephen R. , Ryan Anderson J. 
Published: June 2021

Abstract
Radiation-induced DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR) and nonhomologous end joining (NHEJ). Recently, it has been found that chronic tumor hypoxia compromises HR repair of DNA DSBs but activates the NHEJ protein DNAPK. We therefore hypothesized that inhibition of DNAPK can preferentially potentiate the sensitivity of chronically hypoxic cancer cells to radiation through contextual synthetic lethality in vivo. In this study, we investigated the impact of DNAPK inhibition by a novel selective DNAPK inhibitor, NU5455, on the repair of radiation-induced DNA DSBs in chronically hypoxic and nonhypoxic cells across a range of xenograft models. We found that NU5455 inhibited DSB repair following radiation in both chronically hypoxic and nonhypoxic tumor cells. Most importantly, the inhibitory effect was more pronounced in chronically hypoxic tumor cells than in nonhypoxic tumor cells. This is the first in vivo study to indicate that DNAPK inhibition may preferentially sensitize chronically hypoxic tumor cells to radiotherapy, suggesting a broader therapeutic window for transient DNAPK inhibition combined with radiotherapy.
A Novel Nrf2 Pathway Inhibitor Sensitizes Keap1-Mutant Lung Cancer Cells to Chemotherapy
Authors: Zhang Di , Hou Zhilin , Aldrich Kelly E. , Lockwood Lizbeth , Odom Aaron L. , Liby Karen T. 
Published: June 2021

Abstract
The nuclear factor erythroid-2-related factor 2 (Nrf2)–Keap1–ARE pathway, a master regulator of oxidative stress, has emerged as a promising target for cancer therapy. Mutations in NFE2L2, KEAP1, and related genes have been found in many human cancers, especially lung cancer. These mutations lead to constitutive activation of the Nrf2 pathway, which promotes proliferation of cancer cells and their resistance to chemotherapies. Small molecules that inhibit the Nrf2 pathway are needed to arrest tumor growth and overcome chemoresistance in Nrf2-addicted cancers. Here, we identified a novel small molecule, MSU38225, which can suppress Nrf2 pathway activity. MSU38225 downregulates Nrf2 transcriptional activity and decreases the expression of Nrf2 downstream targets, including NQO1, GCLC, GCLM, AKR1C2, and UGT1A6. MSU38225 strikingly decreases the protein level of Nrf2, which can be blocked by the proteasome inhibitor MG132. Ubiquitination of Nrf2 is enhanced following treatment with MSU38225. By inhibiting production of antioxidants, MSU38225 increases the level of reactive oxygen species (ROS) when cells are stimulated with tert-butyl hydroperoxide (tBHP). MSU38225 also inhibits the growth of human lung cancer cells in both two-dimensional cell culture and soft agar. Cancer cells addicted to Nrf2 are more susceptible to MSU38225 for suppression of cell proliferation. MSU38225 also sensitizes human lung cancer cells to chemotherapies both in vitro and in vivo. Our results suggest that MSU38225 is a novel Nrf2 pathway inhibitor that could potentially serve as an adjuvant therapy to enhance the response to chemotherapies in patients with lung cancer.
Arid5a: A Missing Link between EMT and Tumoral Immune Resistance
Authors: Van den Eynde Benoit J. 
Published: June 2021

Abstract
Epithelial-to-mesenchymal transition (EMT) endows tumor cells with the ability to invade and migrate, and to suppress antitumor immunity. In this issue, Parajuli and colleagues report that EMT tumors often express the RNA-binding protein AT-rich interactive domain 5a (Arid5a), which they find stabilizes the mRNAs encoding indoleamine 2,3 dioxygenase (IDO1) and CCL2. As a new link between EMT and tumoral immune resistance, Arid5a represents a therapeutic target of interest.
See related article by Parajuli et al., p. 862 (4).
Low Carotid Flow Pulsatility Index Correlates With the Presence of Unruptured Intracranial Aneurysms
Authors: Igase Michiya , Igase Keiji , Okada Yoko , Ochi Masayuki , Tabara Yasuharu , Sadamoto Kazuhiko , Ohyagi Yasumasa 
Published: June 2021

Background
We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors.

Methods and Results
The data of 1376 healthy older subjects (age range, 31–91 years) without cerebro‐ or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial‐ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0–8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low‐density lipoprotein cholesterol.

Conclusions
The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low‐density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low‐density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.