bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antisense oligonucleotide treatment in CEP290‐related leber congenital amaurosis
Authors: Leroy Bart P , V Cideciyan Artur , Jacobson Samuel G , V Drack Arlene , Ho Allen C , Garafalo Alexandra , Roman Alejandro J , Schwartz Mike , Biasutto Patricia , de Wit Wilma , Cheetham Michael E , Adamson Peter S , Rodham David , Girach Aniz , De Zaeytijd Julie , Van Cauwenbergh Caroline , Russell Stephen R 
Published: December 2019

AbstractPurposeTo assess safety and efficacy of the antisense oligonucleotide (QR‐110) in LCA10 patients carrying the c.2991+1655A>G allele in the ciliopathy gene CEP290.MethodsIn a three‐center open‐label clinical trial (NCT03140969), subjects received intravitreal injections of QR‐110 in the worse seeing eye every three months. There were two combinations of loading/maintenance doses: 160/80 μg or 320/160 μg. Systemic and ocular safety was evaluated with standard methods. Efficacy was evaluated with visual acuity (VA), oculomotor control and instability (OCI), two‐colour full‐field stimulus test (FST), and mobility course testing among others. In a patient with an exceptional response, additional specialized tests of visual function were performed. Study was planned for 4 injections over one year but based on exceptional results in one patient an interim analysis was performed with the data cutoff date of Aug 2018. ResultsTen patients received at least 1 and up to 4 injections, and were followed for at least 1 and up to 9 months. At 3 months after the first (loading) injection, treated eyes were significantly improved compared to baseline by an average of 0.67 log (7 lines) in VA (P=0.022), 0.62 log in red FST (P=1E‐6) and 0.81 log in blue FST (P<2E‐16). At 3 months after the second (maintenance) injection, VA and FST results remained improved, and OCI results also demonstrated greater stability. Exceptional responder showed a VA improvement from light perception to 20/400, and large improvements in FST. Removing the exceptional responder from the analyses did not change the main statistical conclusion supporting significant improvements of vision at 3 months. Adverse events included cystoid macular oedema and cataract.ConclusionsPreliminary results with QR‐110 support an acceptable safety profile and potential for improvement of visual acuity and light sensitivity. Safety of the drug, and the efficacy and durability of the effect continue to be evaluated.
Can we quantify data on AngioOCT
Authors: Stalmans Ingeborg 
Published: December 2019

AbstractSince its inception, OCT angiography has moved from pretty images that were subjectively judged to a source of quantifiable vascular data. It has already proven itself as being able to detect glaucoma and it also shows promise as a useful tool for progression analysis. However, there is still controversy in published literature. This might be happening since several studies have been conducted with different approaches to this technology. These differences range from the acquisition stage to the analysis of captured data. Standardization might be key in leading this technology to the next level, allowing a more clear and accurate comparison of study results. Several approaches are being employed and this talk will present data from these attempts.
Evaluation of ganglion cell death: implications for therapy
Authors: Francesca Cordeiro M. 
Published: December 2019

AbstractGanglion cell death is implicated in several optic neuropathies, most commonly, glaucoma. Neuroprotective therapies have the potential to halt RGC loss through promoting cell survival. Mechanisms by which this may occur have been well‐researched over the years, and include neuroprotection. However, there until recently there were few methods of assessing the target organ – the ganglion cell. New and promising approaches to assessing the health and sicknes of retinal ganglion cells, including DARC, will be discussed. With these advances, it may be possible for the next wave of new glaucoma treatments in clinic to be assessed with theses promising biomarkers and surrogate endpoints.
Nerve regeneration in liquid cornea patches
Authors: Griffith May 
Published: December 2019

AbstractIn current clinical practice, corneas with perforations that are repaired by cyanoacrylate gluing and those with recurrent ulcerations are often treated by corneal grafting as the treatment to restore vision. However, there is a severe shortage of donor corneas worldwide. More importantly, when someone has a toothache and visits the dentist, the dentist removed the pathologic portions and fills the tooth. Corneal transplantation for a perforation or ulcer would be similar to extracting the tooth and replacing with an implant. Our objective was to develop a method for restoring pathologic corneas such as those with ulcers or perforations that avoids corneal transplantation. We have developed a Liquid Cornea Patch (LCP) that is based on a collagen‐like peptide conjugated to a polyethylene glycol backbone. The LCP is applied as a viscous liquid that polymerises in situ to form a hydrogel. We previously reported its efficacy in sealing large perforation in vitro (Samarawickrama et al. 2018). We also showed that the crosslinking agent used was non‐toxic to corneal epithelial and endothelial cells at doses used for hydrogel formation. Here, we report on a second‐generation patch which we successfully tested in vivo in rabbit and mini‐pig corneas. The LCP withstands bursting pressures up to 170 mm Hg. Although not as strong as cyanoacrylate glue, the bursting pressure is much higher than would be encountered in the human eye (where normal intraocular pressure is between 12 and 22 mm Hg). Over 12 months in mini‐pig corneas, the LCPs promoted regeneration of cornea tissue and nerves. We show that nerve in‐growth proceeded as per solid versions of collagen and collagen‐like peptide‐based implants.
Pharmacokinetics of retinal drug delivery
Authors: Urtti Arto 
Published: December 2019

AbstractThe Sight threatening changes of many ophthalmic diseases are present in the retina. Thus, retina is an important drug target, but it is not an easy tissue for drug delivery. Depending on the route of drug delivery (intravitreal, periocular, systemic) the retinal drug exposure is hampered by various physical barriers (vitreous, inner limiting membrane, retinal pigment epithelium and retinal capillaries) and blood flow factors. In this presentation, delivery aspects are discussed quantitatively utilizing modeling tools and addressing required dosing in different situations. Intravitreal, periocular and systemic routes of drug delivery will be discussed. Furthermore, scaling factors for drug doses between mouse, rabbit and humans are presented.
Where we stand with replacement and regeneration of blindness from optic neuropathy
Authors: Levin Leonard 
Published: December 2019

AbstractSome of the most dramatic changes in medical therapy of glaucoma have come from the realization that intraocular pressure lowering, which addresses the most treatable risk factor for glaucoma progression, is either insufficient, hard to achieve, or associated with adverse effects. In response, there has been a rebound in research at the basic science and clinical levels on neuroprotective therapies, and even institution of clinical trials for optic neuropathies. This presentation will address the breakthroughs over the past year.
OCT and OCT‐A based management of AMD. Present indications for the use of fluorescein angiography
Authors: Coscas Florence 
Published: December 2019

AbstractLate stage age‐related macular degeneration (AMD) has been described as the leading cause of blindness in industrialized countries. Neovascular AMD (nAMD) is characterized by the growth of abnormal blood vessels from the choroid through the Bruch’s membrane (CNV). Fluorescein angiography (FA) is historically considered the gold standard in the diagnosis and classification of CNV while indocyanine green angiography (ICGA) can be used to identify the entire extent of the CNV lesion.Once the diagnosis of CNV is established, the effect of anti‐VEGF therapy is efficiently monitored with non‐invasive Optical Coherence Tomography (OCT). So nowadays clinical practice mostly relies on structural OCT biomarkers of activity. However, conventional OCT devices do not allow direct visualization of the neovascular network and neovascular activity is inferred through indirect signs such as intraretinal fluid, subretinal fluid or pigment epithelial detachments. OCT‐angiography (OCT‐A) is the most recent advance of OCT technology and provides high resolution images of retinal and choroidal vasculature. It can CNV with the same sensitivity as contrast angiography and enables to evaluate morphological characteristics of neovascular networks. Previous works have demonstrated consistent qualitative features associated with exudation on structural OCT. For instance, exudative lesions were associated with a greater rate of small vessels branching and peripheral arcades and non‐exudative lesions with a dead‐tree appearance. On an attempt to eliminate subjectivity of qualitative evaluation, there has been a crescent effort to obtain quantitative features on neovascular networks, and the study of novel imaging biomarkers for nAMD disease activity has become a hot topic in research. The aim of this conference is to evaluate the current indications for FA use in nAMD and to provide an update on subjective and objective OCTA biomarkers in daily clinical practice.
What is the relationship between eye drops and women in science?
Authors: Kolko Miriam 
Published: December 2019

AbstractDespite the multifactorial nature of glaucoma, it is evident that treatments to lower the intraocular pressure (IOP) decrease the rate of glaucomatous progression. Within the available treatments, IOP‐lowering eye drops are the far most common strategy. In 2011, the most prescribed anti‐glaucomatous eye drops, Xalatan, went out of patent and since then multiple generic eye drops has entered the market. Although it is an obvious benefit to eradicate the monopoly, the minimum requirements for the introduction of generic eye drops are worrying. Thus, increasing evidence have shown significant differences between generic anti‐glaucomatous eye drops and their brand name products. Moreover, differences in‐between the generic eye drops exist. To complicate it even more, generic Xalatan has changed and is now different from its original form. Overall, it is a jungle and only by improving research, education, and behaviour, the availability of the various treatment options will be rewarding. With a humorous, but serious, angle, the jungle of current available anti‐glaucomatous eye drops will be compared to the challenging career path of women in science.
"My career in ophthalmology" ‐ by a non‐ophthalmologist
Authors: Kotecha Aachal 
Published: December 2019

AbstractDr. Aachal Kotecha PhD is an optometrist, whose research career started back in 1995 when she joined the team led by Professor (Sir) Peng Tee Khaw investigating antimetabolites in glaucoma filtration surgery at UCL Institute of Ophthalmology/Moorfields Eye Hospital. Since then her career has taken a very winding path, from being a senior lecturer at the City University, London, to a Senior Research Associate at UCL Institute of Ophthalmology, and Principal Optometrist in the Glaucoma Service at Moorfields Eye Hospital. She has now left academia and the NHS and works as a Clinical Development Scientist at Roche Products Ltd, UK, in late stage drug development.When asked to participate in this symposium, she asked ‘why me? I haven’t really achieved anything’ only to be given a lecture by the organizer about how that very question was so typical of women in science.She will share her experiences of working in research and academia, the challenges and joys it has brought along the way, and about her transition to industry.
Nystagmus videoocular mouvements recording in children with retinal diseases
Authors: Robert Matthieu 
Published: December 2019

AbstractIntroductionNystagmus is the main sign leading to the diagnosis of a retinal dystrophy in infants. It is often simply reported and described as a “nystagmus”, as if any nystagmus in an infant requested the same workup. Is it relevant to classify the nystagmus in an infant with a retinal disease? How can oculomotor recordings help doing so?ObjectiveTo answer these questions in a synthetic way.MethodsLiterature review using Pubmed and Google Scholar; chosen clinical case series.ResultsThree distinct varieties of nystagmus can be associated with retinal dysfunctions in children: infantile nystagmus syndrome, purely pendular nystagmus, and positional intermittent upbeat nystagmus. While some retinal stationary dysfunctions and dystrophies are specifically associated with one variety of nystagmus, most of them overlap across two varieties. However, it appears that the nature of the nystagmus does correlate with clinical and electroretinographic markers of severity of the retinal dysfunction.ConclusionsFormal oculomotor recordings therefore could be used as a non‐invasive, additional marker of the degree of retinal preservation, helping assess and better select the patients who could benefit from novel therapies for retinal dystrophies.
Allopurinol reduces oxidative stress and activates Nrf2/p62 to attenuate diabetic cardiomyopathy in rats
Authors: Luo Jierong , Yan Dan , Li Sisi , Liu Shiming , Zeng Fei , Cheung Chi Wai , Liu Hong , Irwin Michael G. , Huang Huansen , Xia Zhengyuan 
Published: December 2019

AbstractAllopurinol (ALP) attenuates oxidative stress and diabetic cardiomyopathy (DCM), but the mechanism is unclear. Activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) following the disassociation with its repressor Keap1 under oxidative stress can maintain inner redox homeostasis and attenuate DCM with concomitant attenuation of autophagy. We postulated that ALP treatment may activate Nrf2 to mitigate autophagy over‐activation and consequently attenuate DCM. Streptozotocin‐induced type 1 diabetic rats were untreated or treated with ALP (100 mg/kg/d) for 4 weeks and terminated after heart function measurements by echocardiography and pressure‐volume conductance system. Cardiomyocyte H9C2 cells infected with Nrf2 siRNA or not were incubated with high glucose (HG, 25 mmol/L) concomitantly with ALP treatment. Cell viability, lactate dehydrogenase, 15‐F2t‐Isoprostane and superoxide dismutase (SOD) were measured with colorimetric enzyme‐linked immunosorbent assays. ROS, apoptosis, was assessed by dihydroethidium staining and TUNEL, respectively. The Western blot and qRT‐PCR were used to assess protein and mRNA variations. Diabetic rats showed significant reductions in heart rate (HR), left ventricular eject fraction (LVEF), stroke work (SW) and cardiac output (CO), left ventricular end‐systolic volume (LVVs) as compared to non‐diabetic control and ALP improved or normalized HR, LVEF, SW, CO and LVVs in diabetic rats (all P < .05). Hearts of diabetic rats displayed excessive oxidative stress manifested as increased levels of 15‐F2t‐Isoprostane and superoxide anion production, increased apoptotic cell death and cardiomyocytes autophagy that were concomitant with reduced expressions of Nrf2, heme oxygenase‐1 (HO‐1) and Keap1. ALP reverted all the above‐mentioned diabetes‐induced biochemical changes except that it did not affect the levels of Keap1. In vitro, ALP increased Nrf2 and reduced the hyperglycaemia‐induced increases of H9C2 cardiomyocyte hypertrophy, oxidative stress, apoptosis and autophagy, and enhanced cellular viability. Nrf2 gene silence cancelled these protective effects of ALP in H9C2 cells. Activation of Nrf2 subsequent to the suppression of Keap1 and the mitigation of autophagy over‐activation may represent major mechanisms whereby ALP attenuates DCM.
Platinum‐based combination chemotherapy triggers cancer cell death through induction of BNIP3 and ROS, but not autophagy
Authors: Chung Ling‐Yen , Tang Shye‐Jye , Wu Yi‐Ching , Yang Kai‐Chi , Huang Hui‐Ju , Sun Guang‐Huan , Sun Kuang‐Hui 
Published: December 2019

AbstractThese days, cancer can still not be effectively cured because cancer cells readily develop resistance to anticancer drugs. Therefore, an effective combination of drugs with different mechanisms to prevent drug resistance has become a very important issue. Furthermore, the BH3‐only protein BNIP3 is involved in both apoptotic and autophagic cell death. In this study, lung cancer cells were treated with a chemotherapy drug alone or in combination to identify the role of BNIP3 and autophagy in combination chemotherapy for treating cancer. Our data revealed that various combinational treatments of two drugs could increase cancer cell death and cisplatin in combination with rapamycin or LBH589, which triggered the cell cycle arrest at the S phase. Cells with autophagosome and pEGFP‐LC3 puncta increased when treated with drugs. To confirm the role of autophagy, cancer cells were pre‐treated with the autophagy inhibitor 3‐methyladenine (3‐MA). 3‐MA sensitized cancer cells to chemotherapy drug treatments. These results suggest that autophagy may be responsible for cell survival in combination chemotherapy for lung cancer. Moreover, BNIP3 was induced and localized in mitochondria when cells were treated with drugs. The transfection of a dominant negative transmembrane deletion construct of BNIP3 (BNIP3ΔTM) and treatment of a reactive oxygen species (ROS) inhibitor suppressed chemo drug‐induced cell death. These results indicate that BNIP3 and ROS may be involved in combination chemo drug‐induced cell death. However, chemo drug‐induced autophagy may protect cancer cells from drug cytotoxicity. As a result, inhibiting autophagy may improve the effects of combination chemotherapy when treating lung cancer.
Endothelial S1pr1 regulates pressure overload‐induced cardiac remodelling through AKT‐eNOS pathway
Authors: Liu Xiuxiang , Wu Jinjin , Zhu Chenying , Liu Jie , Chen Xiaoli , Zhuang Tao , Kuang Yashu , Wang Yanfang , Hu Hao , Yu Ping , Fan Huimin , Zhang Yuzhen , Liu Zhongmin , Zhang Lin 
Published: December 2019

AbstractCardiac vascular microenvironment is crucial for cardiac remodelling during the process of heart failure. Sphingosine 1‐phosphate (S1P) tightly regulates vascular homeostasis via its receptor, S1pr1. We therefore hypothesize that endothelial S1pr1 might be involved in pathological cardiac remodelling. In this study, heart failure was induced by transverse aortic constriction (TAC) operation. S1pr1 expression is significantly increased in microvascular endothelial cells (ECs) of post‐TAC hearts. Endothelial‐specific deletion of S1pr1 significantly aggravated cardiac dysfunction and deteriorated cardiac hypertrophy and fibrosis in myocardium. In vitro experiments demonstrated that S1P/S1pr1 praxis activated AKT/eNOS signalling pathway, leading to more production of nitric oxide (NO), which is an essential cardiac protective factor. Inhibition of AKT/eNOS pathway reversed the inhibitory effect of EC‐S1pr1‐overexpression on angiotensin II (AngII)‐induced cardiomyocyte (CM) hypertrophy, as well as on TGF‐β‐mediated cardiac fibroblast proliferation and transformation towards myofibroblasts. Finally, pharmacological activation of S1pr1 ameliorated TAC‐induced cardiac hypertrophy and fibrosis, leading to an improvement in cardiac function. Together, our results suggest that EC‐S1pr1 might prevent the development of pressure overload‐induced heart failure via AKT/eNOS pathway, and thus pharmacological activation of S1pr1 or EC‐targeting S1pr1‐AKT‐eNOS pathway could provide a future novel therapy to improve cardiac function during heart failure development.
Risk of mycosis fungoides in psoriatic patients: a critical review
Authors: Biondo G. , Cerroni L. , Brunasso A.M.G. , Sola S. , Cota C. , Javor S. , Massone C. 
Published: December 2019

AbstractPsoriasis has been controversially associated with risk of non‐Hodgkin lymphoma (NHL) and mycosis fungoides (MF). Also patients who developed MF after systemic treatment for psoriasis have been reported, and some authors suggested that the association between MF and psoriasis is not infrequent. We performed an extensive literature review in order to examine the risk of developing MF in psoriatic patients with a systematic search of the English‐language databases. An increased risk for lymphoma overall in psoriatic patients has been found only by three out of seven studies. The risk of developing MF in psoriatic patients has been investigated by different studies in different populations and with different methodologies presenting bias and limitations, and it seems reasonable that misclassification between psoriasis and MF may explain the association reported. In contrast to the large number of psoriatic patients treated with biologicals, only 27 case reports of MF after biological therapy for psoriasis have been reported, and in 10 cases, the initial psoriasis diagnoses were then revised as MF. A true association between MF and psoriasis is possible, but the real incidence and prevalence are still unknown. The reported higher risk of developing MF in psoriatic patients should be reconsidered in the light of the bias of misclassification and the low magnitude reported in previous studies. There is not enough evidence to support a causal relation among biological therapies and MF in psoriatic patients.
Ulcus vulvae acutum Lipschütz: a systematic literature review and a diagnostic and therapeutic algorithm
Authors: Sadoghi B. , Stary G. , Wolf P. , Komericki P. 
Published: December 2019

AbstractThe case report literature on ulcus vulvae acutum Lipschütz (UVAL) is scant, and specific guidelines on its diagnosis and treatment are lacking. Our study's aim was to perform a systematic literature review of UVAL in order to formulate a diagnostic and therapeutic algorithm. Using the PRISMA criteria, we searched PubMed and MEDLINE for the terms ‘ulcus vulvae acutum’, ‘Lipschütz ulcer’ and ‘acute genital ulcer AND vulva’. We extracted relevant data on ‘type of article’, ‘patients’ age’, ‘amount and localization of ulcers’, ‘presence of flu‐like symptoms’, ‘prior sexual contacts’, ‘diagnostic workup’ (including histology, blood count and serology such as Epstein–Barr virus testing) and ‘treatment/outcome’. Data were meta‐analysed and comparative analyses were discussed in order to create a diagnostic algorithm and recommendations for management. Twenty‐one publications reporting a total of 60 cases of UVAL were included for analysis. On this basis, we formulated a diagnostic and therapeutic algorithm defined by two major and four minor criteria. The major criteria were (i) acute onset of one or more painful ulcerous lesions in the vulvar region and (ii) exclusion of infectious and non‐infectious causes for the ulcer. The minor criteria were (i) localization of ulcer at vestibule or labia minora, (ii) no sexual intercourse ever (i.e. patient was a virgin) or within the last 3 months, (iii) flu‐like symptoms and/or (iv) systemic infection within 2–4 weeks prior to onset of vulvar ulcer. Use of a symptom‐based treatment algorithm based on our proposed major and minor criteria will improve the diagnosis and management of UVAL.