bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 450 million years long latitudinal gradient in age‐dependent extinction
Authors: Silvestro Daniele , Castiglione Silvia , Mondanaro Alessandro , Serio Carmela , Melchionna Marina , Piras Paolo , Di Febbraro Mirko , Carotenuto Francesco , Rook Lorenzo , Raia Pasquale 
Published: December 2019

AbstractLeigh Van Valen famously stated that under constant conditions extinction probability is independent of species age. To test this 'law of constant extinction', we developed a new method using deep learning to infer age‐dependent extinction and analysed 450 myr of marine life across 21 invertebrate clades. We show that extinction rate significantly decreases with age in > 90% of the cases, indicating that most species died out soon after their appearance while those which survived experienced ever decreasing extinction risk. This age‐dependent extinction pattern is stronger towards the Equator and holds true when the potential effects of mass extinctions and taxonomic inflation are accounted for. These results suggest that the effect of biological interactions on age‐dependent extinction rate is more intense towards the tropics. We propose that the latitudinal diversity gradient and selection at the species level account for this exceptional, yet little recognised, macroevolutionary and macroecological pattern.
Local thermal adaptation and limited gene flow constrain future climate responses of a marine ecosystem engineer
Authors: Miller Adam D. , Coleman Melinda A. , Clark Jennifer , Cook Rachael , Naga Zuraya , Doblin Martina A. , Hoffmann Ary A. , Sherman Craig D. H. , Bellgrove Alecia 
Published: December 2019

AbstractRising ocean temperatures and extreme temperature events have precipitated declines and local extinctions in many marine species globally, but patterns of loss are often uneven across species ranges for reasons that are poorly understood. Knowledge of the extent of local adaptation and gene flow may explain such patterns and help predict future trajectories under scenarios of climate change. We test the extent to which local differentiation in thermal tolerance is influenced by gene flow and local adaptation using a widely distributed intertidal seaweed (Hormosira banksii) from temperate Australia. Population surveys across ~2,000 km of the species range revealed strong genetic structuring at regional and local scales (global FST = 0.243) reflecting extremely limited gene flow, while common garden experiments (14‐day exposures to 15, 18, 21°C) revealed strong site differences in early development and mortality in response to elevated temperature. Embryos from many sites spanning a longitudinal thermal gradient showed suppressed development and increased mortality to elevated water temperatures, but populations originating from warmer and more variable thermal environments tended to be less susceptible to warming. Notably, there was significant local‐scale variation in the thermal responses of embryos within regions which was corroborated by the finding of small‐scale genetic differences. We expect the observed genetic and phenotypic differentiation to lead to uneven responses to warming sea surface temperatures in this important marine foundation species. The study highlights the challenges of predicting species responses to thermal stress and the importance of management strategies that incorporate evolutionary potential for “climate‐proofing” marine ecosystems.
Urate‐induced immune programming: Consequences for gouty arthritis and hyperuricemia
Authors: Cabău Georgiana , Crișan Tania O. , Klück Viola , Popp Radu A. , Joosten Leo A. B. 
Published: December 2019

AbstractTrained immunity is a process in which innate immune cells undergo functional reprogramming in response to pathogens or damage‐associated molecules leading to an enhanced non‐specific immune response to subsequent stimulation. While this capacity to respond more strongly to stimuli is beneficial for host defense, in some circumstances it can lead to maladaptive programming and chronic inflammation. Gout is characterized by persistent low‐grade inflammation and is associated with an increased number of comorbidities. Hyperuricemia is the main risk factor for gout and is linked to the development of comorbidities. Several experimental studies have shown that urate can mechanistically alter the inflammatory capacity of myeloid cells, while observational studies have indicated an association of hyperuricemia to a wide spectrum of common adult inflammatory diseases. In this review, we argue that hyperuricemia is a main culprit in the development of the long‐term systemic inflammation seen in gout. We revisit existing evidence for urate‐induced transcriptional and epigenetic reprogramming that could lead to an altered functional state of circulating monocytes consisting in enhanced responsiveness and maladaptive immune responses. By discussing specific functional adaptations of monocytes and macrophages induced by soluble urate or monosodium urate crystals and their contribution to inflammation in vitro and in vivo, we further enforce that urate is a metabolite that can induce innate immune memory and we discuss future research and possible new therapeutic approaches for gout and its comorbidities.
A randomised clinical trial to compare octyl cyanoacrylate with absorbable monofilament sutures for the closure of laparoscopic cholecystectomy port incisions
Authors: Ben Safta Yacine , Maatouk Mohamed , Bouzidi Mohamed T. , Sakly Nabil , Mabrouk Aymen , Bouafif Marwa , Sghaier Sarra , Maghraoui Hamida , Dziri Chadli , Ben Moussa Mounir 
Published: December 2019

AbstractTissue adhesives have gained increasing use as a possible method of wound closure. We compared the use of 2‐octyl cyanoacrylate (OCA) or subcuticular suture in incisions sutures for the closure of laparoscopic cholecystectomy port incisions. A prospective randomised controlled trial was performed. Patients were randomised to have closure of laparoscopic port sites using either OCA or sutures. Patients were reviewed at 24 hours and returned for follow‐up 1 week and 1 month after postoperatively. At these times, different wound characteristics were documented: Two tools were used to measure the cosmetic result using Hollander wound evaluation scale (HWES) and the patient and observer scar assessment scale (POSAS). A total of 70 patients, 35 in each group were enrolled. The wounds were closed significantly faster in the OCA group (mean 229.16 [±43.7] seconds versus 258.82 [±51.7] seconds, P = .01). Statistically significant difference in favour of using OCA was found for dehiscence (17.1% versus none in the suture group, P = .025) after 1 week. However, no difference was found for wound dehiscence after 1 month. OCA and suture groups did not differ significantly on patient satisfaction. There were no differences in the percentage of wounds achieving optimal scores on the HWES (suture 85.7% versus OCA 74.2%, P = .169). Nerveless, wound evolution was judged to be significantly better in the OCA group using POSAS. Patients' median POSAS was 9.45 (6–11) and 11.43 (10–13) in the OCA and suture groups, respectively (P = .005), and surgeon's median POSAS was 9.42 (6–11) and 11.48 (10–13) in the OCA and suture groups, respectively (P = .006). N‐butyl‐cyanoacrylate tissue adhesive is an acceptable technique for the closure of laparoscopic wounds with less operative time, and cosmetic results are comparable to suturing.
Analysis of transcription by ChIP‐seq in the eye: Progress and challenges
Authors: Cvekl Ales 
Published: December 2019

AbstractPurposeChIP‐seq experiments are designed to map in vivo localization of DNA‐binding transcription factors, their associated chromatin remodeling enzymes, RNA polymerase, and histone posttranslational modifications, at the genome scale. The results, coupled with analysis of gene loss‐of‐function studies by RNA‐seq, are used to reconstruct gene regulatory networks (GRNs) that govern cellular development and differentiation. In the eye, the majority of available data include lens and retina. Although some of the chromatin‐based assays can be conducted at single cell level (e.g. ATAC‐seq), mapping of transcription factors and modified histones require large numbers of cells.MethodsStandard ChIP‐seq experiments require millions of cells. In contrast, recent modifications allow the use of <100 000 cells. Complementary ATAC‐seq experiments employ 1–50 000 individual cells. RNA‐seq experiments are included in the analysis to distinguish directly and indirectly regulated specific targets of these transcription factors.ResultsIn lens, standard ChIP‐seq data exist for Pax6, H3K4me1, H3K4me3, H3K27ac, H3K27me3, and RNA polymerase II. Using ATAC‐seq, we found that Pax6 was bound both in “open” and “closed” lens chromatin domains in agreement with its dual roles as transcriptional activator and repressor.ConclusionsReconstructions of GRNs that govern lens and retinal morphogenesis are in progress and require joint efforts of multiple research teams. Ongoing studies to use smaller numbers of cells will be reported. Together, these data open the field for mechanistic studies of lens‐ and retinal‐specific promoters and enhancers.
Ocular thermography in keratoconus
Authors: Szentmáry Nóra , Németh Orsolya , Lepper Sabine , Milioti Georgia , Abdin Aladin , Eppig Timo , Zsolt Nagy Zoltán , Langenbucher Achim , Seitz Berthold 
Published: December 2019

AbstractKeratoconus (KC) is defined as a non‐inflammatory corneal disease, however, recent studies discuss a potential inflammatory origin. 251 eyes of 132 patients with KC (TKC ‘0‐1’ to ‘4’; age 37.1 ± 13.2 years, 65.7% males) and 75 eyes of 39 healthy subjects (TKC ‘‐’, age 35.4 ± 12.8 years, 43.6% males) were examined. KC was diagnosted using slitlamp examination and corneal topo‐ (TMS‐5, Tomey, Erlangen‐Tennenlohe, Germany) and tomography (Pentacam, Wetzlar, Germany). The patients filled the Ocular Surface Disease Index (OSDI) questionnaire (score ranges for normal 0–12; mild 13–22; moderate 23–32; severe 33–100 ocular surface disease) and were examined by the Ocular Surface Thermographer TG‐1000 (Tomey, Erlangen‐Tennenlohe, Germany). Main outcome measures beside OSDI were mean corneal surface temperature (CST) at the center and 2 mms from the center nasally, temporally, superiorly and inferiorly, during 10 seconds of sustained eye opening, after blinking.OSDI Score was significantly higher in KC (30.4 ± 21.5) as in normal subjects (14.6 ± 15.3) (p < 0.001). There was no significant difference in central (34.2 ± 0.6 vs 34.2 ± 0.6), nasal (34.2 ± 0.6 vs 34.1 ± 0.6), temporal (34.1 ± 0.6 vs 34.2 ± 0.6) and superior (34.1 ± 0.6 vs 34.1 ± 0.6) CST between both groups (p > 0.75). OSDI Score was correlated with surface asymmetry index (SAI) and surface regularity index (SRI) of topographer and with TKC of tomographer (p < 0.006), however did not correlate with CST at the corneal center (p = 0.80). CST at corneal center was also not correlated with SAI, SRI and TKC (p > 0.18).An increased OSDI Score may refer to corneal surface irregularity in KC, which is not accompanied by an increased CST. Further studies are necessary to clarify the potential inflammatory origin of KC.
Scanning laser ophthalmoscopy – basic optical principles
Authors: Irsch Kristina 
Published: December 2019

AbstractScanning Laser Ophthalmoscopy (SLO) produces an ocular fundus image by moving a focused laser beam via scanning mirrors over the retina in a grid pattern and registering the reflected light from each scanned point. In confocal SLO, a pinhole is placed in front of the detector to cut off scattered or defocused light coming from outside the point of interest, which otherwise can blur the image. This results in a focused, high‐contrast image of a single tissue layer located at the focal plane. Tomographic information can be extracted by moving the plane of the pinhole. The use of various wavelengths allows for different applications, such as fluorescein angiography, indocyanine green angiography, and autofluorescence imaging. This lecture will present the basic principles of SLO, as well as discuss notable applications and variants of the technology.
Optical coherence tomography ‐ machine learning
Authors: Bernardes Rui 
Published: December 2019

AbstractMachine learning is a method of data analysis. It gives computers the ability to learn from data and to build models from which predictions can be made. Even though OCT (Optical Coherence Tomography) is mainly used to visualize retinal structures and compute thickness maps, it conveys information on subtle changes within the retina before structural ones can be identified. Exposing the machine learning model to a set of examples allows it to build a model from which predictions can be made on new data and explain differences between groups. This lecture will explain the underlying principles of machine learning and discuss potential applications in ophthalmology and CNS disorders through the imaging of the retina.
Muller glia as endogenous neuroprotectors of the retina
Authors: Vecino Elena 
Published: December 2019

AbstractEndogenous cellular protective mechanisms may help in the development of therapies in order to achieve progress in the treatment of neuroprotection of the retinal cells. Exposure to high IOP induces changes in the endogenous neurotrophins from different retinal cells. In particular we found a transient increase of BDNF synthesis by RGCs after IOP increase that could be implicated in their neuroprotective transient responses endogenously or by acting through Müller glia. A possible proposed mechanism of action on Müller glia is through inhibiting the osmotic swelling and by up regulating the glutamate/aspartate transporter (GLAST) and Glutamine Synthetase (GS) expression in Müller glia. Moreover, we have demonstrated that Müller glia protects RGCs by several secreted factors as determined by proteomic analysis from their condition media. We will present the last studies showing how Müller glia protects RGCs.
The cis‐regulatory logic of photoreceptors and bipolar cells
Authors: Corbo Joseph 
Published: December 2019

AbstractMulticellular organisms evolved via repeated functional divergence and subspecialization of transcriptionally related, but distinct sister cell types. In this talk, I describe the cis‐regulatory logic of two canonical sister cell types in the retina: photoreceptors and bipolar cells. Although these cell types have highly divergent transcriptional profiles and open chromatin maps, they share remarkably similar cis‐regulatory grammars. I present evidence that the presence/absence of a single key transcription factor binding site motif played a key role in the evolutionary divergence of the bipolar transcriptome from that of photoreceptors.
Ocular thermography in normal subjects
Authors: Moussa Sarah 
Published: December 2019

AbstractIn healthy subjects, corneal surface temperature measured by the Ocular Surface Thermographer TG‐1000 (Tomey, Germany) does not change diurnally and is warmer nasally than centrally and temporally during the interblinking interval. This leads to the assumption that diurnal changes of corneal temperature indicate ocular surface abnormality or corneal pathology.
Investigations of Uveitis
Authors: James Teifi 
Published: December 2019

AbstractTeifi James discusses an investigation strategy explaining how to investigate patients presenting with uveitis and associated clinical problems. Starting with the history and the clinical examination he gives a logical and straightforward progression of investigations which are chosen according to the clinical situation. He will explain the wisdom of first doing simple investigations like dipstick testing of urine, chest X‐ray and Full Blood Count, but explain when and why it is appropriate to conduct more elaborate tests. Think before requesting any investigation – why am I doing this test?
Pearls and pitfalls
Authors: Kivelä Tero 
Published: December 2019

AbstractThe speaker will highlight some pearls and pitfalls in statistics that both authors and readers benefit from knowing, based on his personal experience as a writer, reviewer and editorial board member. The items discussed, based on examples from recent literature, will include: (1) How to avoid giving a false impression of precision when reporting key results, (2) How to communicate effect size; (3) How to differentiate statistical from clinical significance, (4) How to communicate statistically non‐significant results, and (5) How to recognise multiple comparisons and adjust for them. Clear reporting of basic statistics is not difficult as long as one is aware of some basic rules. Putting them into action may improve your manuscripts and reading skills when scanning published evidence to base your practice on.
Ex vivo expansion of human labial mucosal epithelium for corneal surface reconstruction
Authors: Gerasimov Maxim , Borzenok Sergey A. , Malyugin Boris E. , Ostrovskiy Dmitriy S. 
Published: December 2019

AbstractPurposeTo achieve ex vivo expansion of human labial mucosal epithelium using the explant method and simplified formulation of the culture media.MethodsLabial mucosa was obtained from six patients during conjunctival fornix reconstruction after signing informed contest. The substantia propria was severed, and the remaining tissue was into 1 × 1 mm explants. Explants were cultured in EpiLife (0.06 mM Ca) and DMEM/F12 (1:1) (1.05 mM Ca) media supplemented with 5% fetal bovine serum, hydrocortisone 5 µg/mL, human recombinant epidermal growth factor (hrEGF) 10 ng/ml, insulin 5 µg/ml, and standard antifungal‐antibiotic. Besides routine monitoring, primary cells were double stained with anti‐p75/p63, anti‐integrin b1/vimentin, and anti‐ZO‐1/CK10 antibodies.ResultsExplant outgrowths had cobblestone epithelial phenotype in all samples in both media; however, cell growths were delayed in the low‐Ca medium. In the high‐Ca medium, all the cultures had more unfastened cells and debris. Integrin b1, CK10, and p75 had no expression in all the primary cultures. p63 expression was registered in 39.2% and 34.7% (median, n = 3, ns) cells for EpiLife and DMEM/F12 media respectively. Expression of vimentin was found as very low in both media. ZO‐1 expression was calculated as 5.18 and 17.5 mkm (median, n = 3, ns) length per cells for EpiLife and media respectively.ConclusionsIt was confirmed that human labial mucosal epithelium could be cultured from a small biopsy without feeder cells in the culture media contained only three specific growth factors. Better cell morphology and lowered differentiation status were obtained in the 0.06Ca medium. Thus it was considered that the cell source, culture technique, and media formulations are suitable for autologous transplantation of cultured labial mucosal epithelium in patients with limbal stem cell deficiency.
Longitudinal changes in peripapillary retinal nerve fiber layer thickness in hypertension
Authors: Kim Jung Yeul 
Published: December 2019

AbstractPurposeTo determine longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) thickness in patients with hypertension (HTN).DesignA prospective observational study.ParticipantsParticipants without any ophthalmic disease were divided into two groups: a HTN group (50 eyes) that included patients with HTN for ≥5 years and a control group.MethodsAfter the initial visit, pRNFL thicknesses were measured four more times at 1‐year intervals using spectral‐domain optical coherence tomography. The pRNFL thickness was fitted using linear mixed models. Univariate and multivariate generalized linear mixed models were used to determine factors associated with pRNFL reductions over time.Main Outcome MeasuresThe pRNFL thickness and rate of pRNFL thickness reduction.ResultsThe mean ages of the HTN and control groups were 62.9 ± 6.2 and 60.7 ± 6.1 years, respectively, and they were not significantly different (P = 0.089). The baseline mean pRNFL thicknesses were 90.50 ± 8.31 and 93.90 ± 8.77 μm; they were significantly different (P = 0.049). The mean pRNFL reduction rate was −1.14 and −0.40 μm/year in the HTN and control groups, respectively; the interaction between group and duration was significant (P < 0.001). In the HTN group, all sectors showed a significant reduction over time, but in the control group, only the superior sector showed a significant reduction over time. In the linear mixed model determination of factors associated with pRNFL reduction, there was no significant factor in the control group. In the HTN group, age, and axial length showed significant results in both univariate and multivariate analyses (estimate: −0.43 and −3.59; P = 0.016 and 0.005, respectively).ConclusionsPatients with HTN had a significantly greater decrease in pRNFL than normal individuals. Additionally, age and axial length significantly affected the reduction in pRNFL in HTN patients.
Longitudinal changes in the ganglion cell – inner plexus layer thickness in hypertension: A prospective observational study
Authors: Hyuk Lee Woo , Lim Hyung‐Bin , Shin Yong‐Il , Kim Jung‐Yeul 
Published: December 2019

AbstractPurposeTo determine longitudinal changes in the ganglion cell‐inner plexus layer (GC‐IPL) thickness in patients with hypertension (HTN).DesignA prospective observational study.ParticipantsParticipants without any ophthalmic disease and systemic except HTN were divided into two groups: a HTN group (49 eyes) and a control group (56 eyes).MethodsAfter the initial visit, GC‐IPL thicknesses were measured four more times at 1‐year intervals using spectral‐domain optical coherence tomography. The GC‐IPL thickness was fitted using linear mixed models. Univariate and multivariate generalized linear mixed models were used to determine factors associated with GC‐IPL reductions over time.Main outcome measuresThe GC‐IPL thickness and redcution rate.ResultsThe mean ages of the HTN and control groups were 60.3 ± 9.7 and 57.7 ± 7.9 years, respectively, and they were not significantly different (p = 0.137). The baseline average GC‐IPL thicknesses were 81.84 ± 6.67 and 84.86 ± 4.39 μm; they were significantly different (p = 0.008). The average GC‐IPL reduction rate was −0.64 and −0.19 μm/year in the HTN and control groups, respectively; the interaction between group and duration was significant (p < 0.001). In the HTN group, all sectors showed a significant reduction over time, but in the control group, the superior, inferior, inferonasal and superonasal sector showed a significant reduction over time. In the linear mixed model determination of factors associated with GC‐IPL reduction, there was no significant factor in the control group. In the HTN group, age showed significant results in both univariate and multivariate analyses (estimate: −0.24, p = 0.009). In minimum parameter age and mean IOP showed significant (estimate: −0.30 and −1.38, all p = 0.043)ConclusionsPatients with HTN had a significantly reduction in GC‐IPL than normal individuals. Additionally, age and IOP affected the reduction in GC‐IPL in HTN patients.