bluuebunny/crossref_metadata_2025 huggingface dataset:
Stigma and the Inverse Care Law: Experiences of ‘Care’ for People Living in Marginalised Conditions
Authors: Addison Michelle , Scott Steph , Bambra Clare , Lhussier Monique
Published: January 2025

This paper explores the connection between stigma and the Inverse Care Law (ICL) by focussing on the idea that people who have the greatest needs often have the least support from healthcare services. Twenty‐four semi‐structured interviews were undertaken with people who used class A & B illicit drugs, in the northeast of England. Many of the people in this study who used illicit drugs were not able to access quality healthcare in a timely way to meet their needs because of structural and relational stigma. We discuss four themes: (i) pressure on health services and long waiting lists, (ii) sensitivity to compassion fatigue from staff and impacts on engagement, (iii) complex systems that are difficult to navigate and (iv) stigma and drug use. These themes illuminate the harms of stigma and support Tudor Hart's ICL. Stigma is a key contributor to the inverse experience of good quality healthcare and requires greater attention from policymakers and practitioners. The structural and relational aspects of stigma embedded in healthcare are central to the ICL and reproduce inequities in access to and experience of good quality healthcare, which in turn impacts health inequalities.
The OnSPN2 from the nipa palm hispid beetle Octodonta nipae is a multipurpose defense tool against proteases from different peptidase families
Authors: Zhang Huajian , Xu Jiawei , Chen Mintao , Yin Jiawei , Hou Youming , Tang Baozhen
Published: January 2025

Serpins (serine protease inhibitors) constitute a superfamily of proteins with functional diversity and unusual conformational flexibility. In insects, serpins act as multiple inhibitors, by forming inactive acyl‐enzyme complexes, in regulating Spätzles activation, phenoloxidases (POs) activity, and other cytokines. In this study, we present the cloning and characterization of Octodonta nipae serpin2 (OnSPN2), a 415 residues protein homologous to Tenebrio molitor 42Dd‐like. Notably, OnSPN2 features an arginine residue (R364) at the P1 position, and additional arginine residues (R362, R367) at the P3 and P3′ positions, respectively which is crucial for protease inhibition. Immunohistochemistry (IHC) and Western blot analyses revealed that OnSPN2 is primarily synthesized in plasmatocytes and then released into the plasma to exert its function. RNA interference results indicated that OnSPN2 knockdown may depress serine protease in melanization and remarkably increase the transcript level of Attacin in hemolymph, but its messenger RNA levels were not changed upon immune induction. Reciprocal co‐immunoprecipitation assay results confirmed that OnSPN2 binds to OnPPAF1 and OnSP8, indicating its role as a negative regulator in the PO and AMP pathway. Intriguingly, several cathepsin‐L isoforms were identified in the OnSPN2 immunoprecipitated samples. The cathepsin‐L inhibition assays and protein–protein docking results, identified cathepsin‐L as a potential target of OnSPN2. These results indicate that OnSPN2 is produced as an intracellular resident and additionally is associated with the PO and AMP pathway. OnSPN2 represents a multiple defense tool that may provide multiple antiproteolytic functions.
High migratory potential of fall armyworm in West Africa despite stable temperatures and widely available year‐round habitats
Authors: Gao Fan‐Qi , Chen Hui , Kyerematen Rosina , Hu Gao , Early Regan , Chapman Jason W.
Published: January 2025

The fall armyworm (FAW), an important migratory pest native to the Americas, was first detected in a nonnative region (West Africa) in 2016. In the following years, it quickly spread to multiple regions worldwide. FAW exhibits long‐distance seasonal migration in both the Americas and Asia, primarily to take advantage of suitable seasonal habitats as they appear along the migratory pathways. Tropical West Africa experiences minimal annual temperature variation and has widely distributed potential year‐round habitats, leading us to hypothesize that the migration capacity of FAW populations in this region may be substantially reduced. To test our hypothesis, we assessed the flight performance of FAW collected from Ghana in West Africa with tethered flight mills and compared it to that of a FAW population from southern China. Additionally, we quantified the relationships between morphological characteristics and flight performance of the FAW from Ghana. Based on observed flight behaviors, we categorized FAW into migratory and non‐migratory types. The flight capabilities of first‐generation Ghanaian FAW bred in the laboratory were similar to that of the field population from Yunnan, Southwest China, with migrants making up the majority. However, after several generations of laboratory rearing, the flight capability of the Ghanaian population significantly declined, primarily due to a marked increase in the proportion of non‐migratory individuals. The low correlation between morphological variables and flight duration suggests that genetic factors likely determine most variations in flight propensity. The results of this study indicate that FAW with high migratory capacity in West Africa is likely to pose a threat to crops in eradication zones and neighboring uninvaded areas and may possibly be capable of crossing the Sahara Desert and invading Europe. Therefore, it is crucial to establish comprehensive pest early warning and management systems.
Fe3O4@SiO2/GO/HKUST‐1 nanocomposite for quercetin extraction and preconcentration followed by its determination using HPLC
Authors: Alavi Nikoo , Malekpour Akbar
Published: January 2025

Quercetin, a key flavonoid found in many fruits and vegetables, offers notable health benefits, including antioxidant, antiviral, and antitumor properties. Yet, isolating it from complex plant materials is challenging. This research aimed to develop a selective and efficient sorbent to clean up real sample matrices and pre‐concentrate quercetin, enhancing its detection using high‐performance liquid chromatography (HPLC). Several metal organic frameworks (MOFs) were synthesized and initially, their abilities to sorption of quercetin from aqueous and alcohol media were examined. Among them, HKUST‐1 showed the best performance. To improve the efficiency of this MOF, its composite with graphene oxide (GO) was prepared (Fe3O4@SiO2/GO/HKUST‐1) and was employed for quercetin extraction through magnetic dispersive micro solid‐phase extraction. The effect of different parameters was examined and the kinetic, thermodynamic, and isotherm of the sorption process was studied. The related results showed the system followed the pseudo‐second‐order kinetic model, with the Temkin and Langmuir isotherm models applicable in aqueous and methanol solutions, respectively. The method enabled rapid preconcentration and clean up within 20 min, with a 99.6% adsorption efficiency using just 5 mg of sorbent. The nanocomposite demonstrated an adsorption capacity of 29.3 mg/g and effectively extracted quercetin from red onion samples, achieving recovery rates between 75% and 98% for HPLC‐diode array detector analysis.

Practical Application

Quercetin is a common polyphenolic compound, which is widely found in plant materials such as onions. Owing to its medicinal effects including anti‐inflammatory, anti‐oxidant, anti‐cancer, cardioprotective, anti‐bacterial, anti‐viral, and anti‐allergic features, it has widespread usage in pharmacology and preparation of food preservers. In this study, Fe3O4@SiO2/GO/HKUST‐1 nanocomposite was synthesized for extraction and preconcentration of quercetin from an onion sample. Very low amounts of this sorbent indicated high adsorption percentage and adsorption capacity for quercetin. This method was simple, fast, cost‐effective, precise, and accurate, which exhibited a potential for extraction of quercetin in a large scale.
Determination of main lipids and volatile compounds in unconventional cold‐pressed seed oils through chromatographic techniques
Authors: Rigano Francesca , Vento Federica , Cafarella Cinzia , Trovato Emanuela , Trozzi Alessandra , Dugo Paola , Mondello Luigi
Published: January 2025

The purpose of this study was to characterize unconventional cold‐pressed seed oils (rosehip, strawberry, blackcurrant, carrot, plum, pomegranate, radish, and raspberry) as novel alternative edible oil source. A chemical characterization of different lipid components (total fatty acid composition, triacylglycerols, and vitamin E) and volatiles responsible for the particular aroma of these oils was reported. All the oils showed a content of unsaturated fatty acids, mainly oleic, linoleic, and α‐linolenic acid, that potentially contribute to the prevention of cardiovascular diseases, in the range of 80%–90%. Moreover, an isomer of α‐linolenic acid, namely, punicic acid, was quantified at a level of near to 40% in pomegranate seed oil. Triolein was the most abundant triacylglycerol in most of the analyzed seed oils, with the exception of raspberry and strawberry dominated by trilinolein and pomegranate seed oil, composed for almost 50% of tripunicine. The highest content of vitamin E was found in pomegranate oil (256 mg/100 g), while the lowest amount was found in strawberry (65 mg/100 g). Overall, >300 compounds were identified from volatile profile of oil samples. Among these, aldehydes were the predominant molecule class identified in plum, pomegranate, and strawberry oils, while terpenes were the main volatiles in blackcurrant, carrot, and rosehip oils. Extremely low values were obtained for atherogenicity (0.05–0.10) and thrombogenicity (0.07–0.30) nutritional indices in all the investigated oils. Principal component analysis of the lipid profile was used as strategy to discriminate and classify the samples, highlighting their similarity related to the presence of beneficial compounds.

Practical Application

Unconventional food products can find wide applicability in both cosmetic and food industry as alternative source that harmonize with consumers’ preferences for personal care and nutraceutical purpose. They often address food security, sustainability, and nutritional challenges. Within this context, the chemical characterization of both major (triacylglycerols and total fatty acid composition) and minor components (volatile compounds and vitamin E) was useful to demonstrate that the cold‐pressed seed oils here investigated are rich in essential nutrients. Hence, they can cater to specific dietary needs, thus creating new markets in food tech, agriculture, and biotechnology industries.
Simultaneous extraction and purification of polysaccharides and proteins from Pleurotus ostreatus using an aqueous two‐phase system
Authors: Yang Zhilai , Wang Jingkun , Wang Hongyu , Xie Huixian , Zhang Yingnan , Wang Meng
Published: January 2025

Pleurotus ostreatus is a nutrient‐dense edible fungus renowned for its delicate texture, appealing flavor, and numerous potential health benefits. Simultaneous extraction within the framework of food resource processing facilitates the concurrent isolation and analysis of multiple target compounds. In this study, an ethanol/salt aqueous two‐phase system (ATPS) was employed to extract polysaccharides (PS) and proteins from P. ostreatus. The impacts of pH, inorganic salts, and temperature on ATPS phase formation were systematically evaluated. The ethanol/K₂HPO₄ system demonstrated superior selective extraction performance under optimal conditions: 25.16% ethanol (w/w), 15.91% K₂HPO₄ (w/w), and 24.11% crude extract (w/w) without pH adjustment. The highest recovery efficiency of PS and proteins were 90.29% ± 0.24% and 76.35% ± 0.15%, respectively. The simultaneous extraction efficiency of PS and proteins was 12.49% ± 0.14% and 20.34% ± 0.09%, respectively. As a comparison, hot water extraction and alkali extraction methods were performed to assess the impact of ATPS on the physicochemical properties of PS and proteins. SDS‐PAGE and HPLC analyses confirmed that the protein subunit distribution was consistent across different extraction methods, whereas the ATPS‐extracted PS exhibited characteristics of homogeneous heteropolysaccharides with a molecular weight of 28.8 × 10⁶ Da. Monosaccharides such as mannose, glucuronic acid, and glucose were identified in the PS hydrolysate. The results demonstrate that ATPS preserves the physicochemical integrity of the extracted substances. This method holds promise for unlocking new possibilities and has the potential to become an effective method for large‐scale extraction and purification of polysaccharides and proteins from edible fungi.

Practical Application

This work describes an efficient and straightforward aqueous two‐phase system (ATPS) method for simultaneously extracting polysaccharides and proteins from Pleurotus ostreatus. This approach offers advantages such as reduced operational time, lower toxicity solvents, and minimized byproduct waste for the extraction of bioactive substances from edible fungi. Additionally, the reduced residue levels help to shorten subsequent purification steps. This promising method has potential applications in the food, pharmaceutical, and health product industries.
Multispectral imaging‐based detection of apple bruises using segmentation network and classification model
Authors: Fang Yanru , Bai Hongyi , Sun Laijun , Hou Jingli , Che Yuhang
Published: January 2025

Bruises can affect the appearance and nutritional value of apples and cause economic losses. Therefore, the accurate detection of bruise levels and bruise time of apples is crucial. In this paper, we proposed a method that combines a self‐designed multispectral imaging system with deep learning to accurately detect the level and time of bruising on apples. To enhance the accuracy of extracting bruised regions with subtle features and irregular edges, an improved DeepLabV3+ was proposed. More specifically, depthwise separable convolution and efficient channel attention were employed, and the loss function was replaced with a focal loss. With these improvements, DeepLabV3+ achieved the maximum intersection over union of 95.5% and 91.0% for segmenting bruises on two types of apples in the test set, as well as maximum F1‐score of 97.5% and 95.2%. In addition, the spectral data of the bruised regions were extracted. After spectral preprocessing, EfficientNetV2, DenseNet121, and ShuffleNetV2 were utilized to identify the bruise levels and times and DenseNet121 exhibited the best performance. To improve the identification accuracy, an improved DenseNet121 was proposed. The learning rate was adjusted using the cosine annealing algorithm, and squeeze‐and‐excitation attention mechanism and the Gaussian error linear unit activation function were utilized. Test set results demonstrated that the accuracies of the bruising levels were 99.5% and 99.1%, and those of the bruise time were 99.0% and 99.3%, respectively. This provides a new method for detecting bruise levels and bruised time on apples.
DNA barcoding solves the mystery of the rainbow battleship caterpillar (Lepidoptera: Limacodidae) and reveals cryptic diversity in Australian slug moths
Authors: Cook Lyn G. , Thurman Jessa H. , Walker Andrew A.
Published: January 2025

Despite their striking appearance and abundance, the diversity and life‐histories of cup moths and their relatives (Lepidoptera: Limacodidae) in Australia are not well known. An example is a caterpillar commonly known as the rainbow battleship, or rainbow school bus. This caterpillar has been claimed to be the larva of Calcarifera ordinata (Butler, 1886), a wattle cup moth, but rearing experiments have recently shown that caterpillars of C. ordinata are not rainbow battleships. Here, we use DNA barcoding to identify the rainbow battleship by comparing the mitochondrial gene COI to sequences obtained from a DNA‐barcoding blitz at the Australian National Insect Collection. We positively identify the rainbow battleship caterpillar as the larva of Comana albibasis (Walker, 1862), an association not previously hypothesised. The COI barcode region appears to be a useful tool for identifying limacodids, including matching larval and adult forms. Divergence within some currently recognised species highlights the presence of potentially undescribed species diversity in Limacodidae.
Impacts of harmonic radar tagging on the flight ability of male Bactrocera tryoni and Bactrocera jarvisi (Diptera, Tephritidae)
Authors: Tomerini John M. , De Faveri Matthew G. , De Faveri Stefano G. , Wright Carole , Siderhurst Matthew S.
Published: January 2025

Understanding the movement dynamics of fruit flies is critical to both surveillance and control strategies with much of what is known coming from mark–release–recapture or flight mill studies. However, recent studies have demonstrated the feasibility of field‐tracking fruit flies using harmonic radar (HR). In this study, the effects of attaching HR tags to Bactrocera tryoni and Bactrocera jarvisi were assessed in large indoor cages with both cultured and wild flies. The Queensland fruit fly, B. tryoni, is a major horticultural pest in the Northern Territory and east coast of Australia. Jarvis' fruit fly, B. jarvisi, is one of the lesser Australian fruit fly species, with a distribution in northern and eastern Australia. Three flight‐associated behavioural parameters were recorded: (1) flight success (proportion of flies that flew), (2) time to flight (period from release to take‐off) and (3) flight duration (period from take‐off to landing). Untagged flies were more likely to fly and also took flight more quickly than tagged flies with this result holding across fly species and fly origin (wild or cultured). Similarly, wild flies were more likely to fly than cultured flies, but no differences were observed between the flight successes of the two fruit fly species. For all tagged flies, mean time to flight increased with successive flight trials, while untagged flies mean time to flight over time varied with species and fly origin. The effect of tagging on flight duration varied by species (tagged > untagged for B. tryoni, tagged < untagged for B. jarvisi) but not by fly origin with species. Together, these results quantify the negative effects of HR tagging on B. tryoni and B. jarvisi flight behaviours that should be taken into account when interpreting the biological relevance of HR tracking studies. These results also suggest that HR tracking of fruit flies would benefit from the further development of smaller and lighter tags.
Patients’ Perceptions of the Efficacy, Safety, and Quality of the Evidence of Medicinal Cannabis: A Survey of Australian Cancer Patients
Authors: Taylor Joseph S. , Fradgley Elizabeth A. , Britton Ben Britton , Martin Jennifer H. , Lucas Catherine , Carlson Melissa A. , Bridge Paula , Morris Sarah , Watts Gareth , Lynam James
Published: January 2025

Introduction

Despite the increased demand for medical cannabis (MC), MASCC guidelines state that there is insufficient evidence of its efficacy and safety. Although research has explored medical professionals’ perceptions of MC, there is to our knowledge minimal research exploring patients’ perceptions, particularly in an Australian cancer setting.

Methods

A survey of Australian cancer patients attending oncology outpatient clinics was performed. Patients were ≥ 18 years and had a confirmed diagnosis of cancer (solid or hematological).

Results

A total of 413 patients were approached between April 2019 and March 2020 out of which 82% (350) consented to participate. A total of 19% (67/350) were using MC. Despite being used for symptom control, such as pain (61%), and, in some cases for perceived anticancer activity (12% to cure, and 16% to slow the cancer), only a minority of users believed that the evidence was of high quality for these indications (28% for physical benefits and 29% for anticancer activity). Nonusers were even more skeptical of the evidence for these indications (17% and 11%, respectively). Only a minority of patients (31% of users and 8% of nonusers) accessed information on MC from clinicians. Most instead relied on resources such as TV, friends, family, social media, and websites.

Conclusion

This study demonstrates current real‐world cancer patients’ perceptions on the evidence for MC, the sources of information used to shape their health beliefs, and compares users to nonusers. The results highlight the need for treating teams to combat potential misinformation that patients may be accessing about MC and provide information on treatments with stronger evidence.
Translational research in ophthalmology. Some examples
Authors: JImeno Jose Carlos Pator
Published: January 2025

Translational research is a bidirectional process that involves multidisciplinary integration among basic, clinical, practice, population, and policy‐based research. The goal of translational research is to speed up scientific discovery into patient and community benefit.

In my opinion, the most accessible research to a clinician like me is translational, and must be intimately linked to training and clinical practice. But the environment is very important and although our national health system has many benefits, research was not stimulated, at least in 1981 when I became a professor in Valladolid.

For this reason, and taking advantage of a reform of the University Law (LRU), in 1994 we created the IOBA. Thirty years later, we have our own building and more than 100 people work, 40 of whom are researchers.

Every five years we are evaluated by the University Quality System and in the last evaluation we obtained 88.5 points out of a total of 100. In 2003, we also took advantage of another reform of the University's Law, and created the first start‐up of the University of Valladolid, which 21 years later is still alive. And it allows us, among other things, to retain talented researchers until they find their place at the university.

And finally, in 2010 we stimulated the creation of a cluster dedicated to Ophthalmology and Vision Sciences called "Cluster4Eye". This cluster is currently focalized in the application of the so named Medical Device Regulation of the European Union which has been implemented affecting not only manufacturers but also sanitary personnel.

As an example of applied research, I will comment on some aspects of our research on the so‐called "endotamponades" in vitreoretinal surgery. Liquid perfluorocarbons and silicone oil.

In 2015 we took on the challenge of finding out why hundreds of people had irreparably lost vision in one eye after successful retinal detachment surgery. We were able to find out, we were part of the international ISO standards committee modifying the standard on ocular endotamponades and making an international patent and we are now part of the European Union's expert group for ocular medical devices.

Regarding silicone oil, I started working with Miguel Refojo in Boston in 1990 and we have continued to improve it continuously and produce improvements that have been incorporated into the market.
Translational experiences in ophthalmology
Authors: Cordeiro Maria Francesca
Published: January 2025

DARC (Detection of Apoptosing Retinal Cells) is a retinal imaging technology that has progressed from lab research to Phase 2 clinical trials. It uses ANX776 (fluorescently labelled Annexin A5) to detect stressed and apoptotic cells in the eye. The technology has undergone product optimization, GMP manufacturing, and preclinical testing, initially in models of glaucoma and optic neuropathy, and later in conditions like AMD, Alzheimer's, Parkinson's, and diabetes. Though the transition to clinical trials was slow, ANX776 has been found safe in around 400 clinical procedures around the world, with DARC showing promise in predicting disease activity in wet AMD, Geographic Atrophy, and glaucoma, aided by AI algorithms. Larger studies are needed to validate its use as an approved screening tool. This talk covers DARC's development and the challenges faced in advancing it to multiple clinical applications.
The need for standardization in methodologies for tear fluid biomarkers
Authors: Gijs Marlies
Published: January 2025

Tear fluid is a complex mixture of proteins, lipids, and other molecules essential for maintaining ocular surface health. In recent years, tear fluid has emerged as an invaluable source of biomarkers, reflecting not only ocular health, but also providing glimpses into systemic and neurological well‐being. Tears can be used to gather abundant molecular information that can be harnessed for diagnostic, monitoring, predictive, and prognostic purposes. The unique tear fluid molecular profile of each patient facilitates tailored interventions, enhancing treatment efficacy and minimizing adverse effects.

Besides being continuously accessible, tear fluid can be sampled in a non‐invasive and inexpensive way. This makes the sampling process patient friendly, thereby enhancing patient compliance and reducing the risk of potential complications associated with invasive sampling techniques. The non‐invasive nature of tear fluid sampling makes it suitable for repeated measurements over time, allowing for longitudinal studies and monitoring of dynamic changes in biomarkers. Additionally, tear fluid requires minimal storage requirements, as it can be collected and stored using simple and readily available equipment.

To date, hundreds of tear biomarkers have been discovered, but only a few have made it to the clinic. Major progress in translating newly discovered tear biomarkers into diagnostic tests is still missing because of the unique challenges that have yet to be addressed. Variability in tear fluid results poses a significant challenge in ocular research due to the lack of standardized methods for collection, analysis, interpretation, and reporting. This variation makes it difficult to draw consistent conclusions across different studies. Inconsistent research findings result from differences in methodologies and small sample sizes, leading to conflicting reports on disease‐specific tear proteins and outcomes. Moreover, the lack of standardization hampers our understanding of tear fluid physiology and its role in diseases, impeding the development of diagnostic tools and therapies. This lack of consensus also hinders the clinical translation of tear‐based diagnostics and therapies, potentially delaying accurate diagnoses and appropriate treatments for patients.

Recognizing the importance of methodological standardization, various initiatives have been proposed to address these challenges. Collaborative efforts involving researchers, clinicians, industry partners, and regulatory agencies aim to establish consensus guidelines for sample collection, processing, and analysis. These guidelines emphasize the importance of rigorous validation studies, quality control measures, and transparent reporting practices to enhance the reliability and reproducibility of tear fluid biomarker research. Through collaborative efforts and adherence to consensus guidelines, the field can realize the full potential of tear fluid biomarkers in revolutionizing the diagnosis, monitoring, and treatment of ocular diseases.
Tear biomarkers in daily practice – where are we?
Authors: Messmer Elisabeth M.
Published: January 2025

Dry Eye Disease (DED) and chronic ocular allergies are driven by chronic inflammation that causes measurable modifications in the tear film such as changes in osmolarity and inflammatory markers. Increased or decreased levels of protein biomarkers (eg. lactoferrin, S‐100), cytokines, chemokines, metalloproteinases, growth factors, and soluble receptors are observed in DED and chronic ocular allergies. To date only tests to measure MMP‐9 in the tear film, and bed side osmometers to test tear film osmolarity are available for daily patient care. The MMP‐9 point‐of‐care test is primarily a qualitative dichotomous test that stains positive if the value is above 40 ng/ml. It may be positive in DED, allergic conjunctivitis, and infection, and thus does not allow a differential diagnosis. Increased tear film osmolarity using the Tearlab® or the I‐pen®‐osmometer indicates DED. Normal tear film osmolarity is defined as < 300 mOsm/l in both eyes and an inter‐eye difference of < 8 mOsm/l. However, both techniques, the MMP‐9‐assay, and the tear film osmometry are far from being perfect tests. Their problems in daily care of ocular surface disease patients and developments for the future will be discussed.
Neurovascular coupling as measured by retinal vessel analyses
Authors: Castelo‐Branco Miguel
Published: January 2025

Neurovascular coupling is the intrinsic physiological mechanism by which neural activity in the retina is coupled to blood flow (and vessel dynamics) and metabolism. It enables the retina to regulate blood flow in response to neural activity and changes in metabolic demand. The measurement of thereof allows the study of ocular (and systemic) disease mechanisms and progression. Measuring the retinal vascular response to different visual stimuli such as flicker light alter the local metabolic demand of the retina enabling the assessment of neurovascular coupling in vivo. Impairment/ disruption of neurovascular coupling has also been documented in cerebral disease states. The anatomy and physiology of the retinal circulation resembles that of the brain; hence, observation of the retinal circulation therefore not only enables the study of retinal pathology but allows for indirect assessment of cerebrovascular disease states. The present talk gives and overview of how the measurement of retinal vessel dynamics in vivo provides some insight into retinal neurovascular coupling.
Bacterial keratitis
Authors: Modis Laszlo
Published: January 2025

The number of infectious keratitis cases is increasing worldwide. The vast majority of cases are bacterial in origin. Both gram positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae Corynebacterium diphtheriae) and gram negative (Pseudomonas aeruginosa, Acinetobacter species) bacteria can cause serious infections.

One of the most common causes is related to contact lens wear. This can be in connection with overwear, overnight wear (orthokeratology), inadequate lens cleaning with tap water, lack of hygiene, and contamination of different solutions. Uncontrolled use of lenses ordered from the internet is also a source of danger. The other main cause is trauma, resulting from surface injuries (e.g. nails, plants), foreign bodies, mechanical and chemical injuries. Certain ophthalmological conditions also predispose to bacterial keratitis, such as dry eye, blepharitis, non‐healing ulceration, and previous eye surgery. Immunosuppressive treatment, autoimmune diseases, diabetes mellitus may also result in development of infection.

In serious cases patients typically complain of pain, sensitivity to light, blurred vision, tearing, yellowish purulent discharge and various degree of visual loss. Clinical appearance includes epithelial defect and erosions, ulceration, stromal infiltrates with indistinct margins. In serious forms Descemetocele, even perforation can be present. Hypopyon may also appear in the anterior chamber.

Diagnosis is based on the clinical picture. Culturing and smear sampling are necessary when the infiltrate is large and central, when there in contact lens wear in the history, the process is resistant to therapy, and appearance is atypical.

Most cases can be successfully treated with empiric therapy. The first choice of treatment is usually fluroquinolone therapy. In severe cases moxifloxacin or cefazolin with tobramycin or gentamycin is advised. Eye drops in every hour should be applied both day and night for the first 48 hours as saturation dose. If there is no improvement in the clinical picture after 48 hours, repeat sampling for microbiological culture recommended. Corticosteroids may be considered after 2 days when the infective organism is identified, and the keratitis is responding to therapy. Cycloplegia may also decrease pain as well as synechia formation. In therapy resistant cases crosslinking may be an additional option if herpetic origin can be excluded. Amniotic membrane transplantation is recommended for non‐healing epithelial defects. In cases of non‐healing and rapidly progressive cases therapeutic corneal transplantation is recommended. However, surgery has a better prognosis in quiet eye.
Integrated approach to uncover regulatory networks in eye development and disease
Authors: Lachke Salil A.
Published: January 2025

It is challenging to identify/prioritize genes involved in development of the eye and its associated defects. The application of genome‐level transcript profiling (transcriptomics) to examine eye tissues and cell types has facilitated ocular gene discovery. To maximally utilize the large transcriptome data, there is a need to perform meta‐analysis of independently generated public data and to present it a user‐friendly and freely accessible platform. Toward these goals, we developed a web‐resource tool called iSyTE (integrated Systems Tool for Eye gene discovery; https://research.bioinformatics.udel.edu/iSyTE/). iSyTE has effectively expedited eye gene discovery, leading to the identification of several genes (Caprin2, Celf1, Elavl1, Ell2, Mafg, Mafk, Pvrl3, Rbm24, Sep15, Tdrd7, etc.) associated with lens defects and/or cataract and has contributed to the understanding of many other important lens regulatory pathways (e.g. Foxe3, Frfr2, n‐Myc, Prox1, Sip1 (Zeb2), CBP, p300, etc.). To update iSyTE, we have now meta‐analyzed transcriptome data from isolated lens epithelium and fiber cells as the lens develops from early embryonic stages through aging. Further, we have applied single nucleus (sn) multiomics approach using snRNA‐seq and ATAC‐seq to characterize early postnatal lens development. These new analysis have identified potential new genes and pathways in lens development and cataract.
Cellular insights and new therapeutic approaches for limbal stem cell deficiency
Authors: Lagali Neil
Published: January 2025

Several rare diseases of the ocular surface are characterized by a full, partial, or temporary inflammation and neovascularization of the cornea, which occurs because of an insufficiency in the limbal stem cells and their niche in maintaining a corneal epithelial phenotype. In models of corneal neovascularization and aniridia‐associated keratopathy, we have examined the cellular‐level changes arising with the progressive pathology, giving us insights into various cell types and transcripts regulating the loss of corneal epithelial phenotype. Alongside a better understanding of the pathological mechanisms, we have examined pharmacotherapy approaches in the form of eye drop treatments, to address this limbal stem cell insufficiency. In models of inflammation, corneal neovascularization and aniridia‐associated keratopathy, we have applied novel pharmacotherapies to partially rescue the inflammatory, neovascular, and conjunctival phenotype and restore the status of a functioning corneal epithelium and thereby corneal homeostasis. Here, insights will be presented into specific pathways influenced by these therapies and their regulation in various corneal cell subpopulations, highlighting the importance of treating inflammation and neovascular phenotypes to address rare diseases characterized by limbal stem cell deficiency.
Underground drivers
Authors: Garrido‐Mercado Rafaela
Published: January 2025

Introduction: Some professional occupations have visual requirements. For underground drivers, requirements include good photopic visual acuity, color vision, stereopsis, and normal campimetry. However, there are other visual functions that may be important in this occupation, especially mesopic tests, as their work is done in darkness, and they are the first functions to be altered with age.

Our objective was to describe the state of different visual functions in a population of underground drivers.

Methods: A total of 430 randomly selected underground drivers, aged between 27 and 65, participated in the study. 94,41% were males. High and low‐contrast monocular best corrected visual acuity (VA) was tested using EDTRS charts under photopic and mesopic conditions. Photopic (cone‐enhanced) and mesopic (rod‐enhanced) flicker modulation thresholds (FMT) were measured at the fovea and at an eccentricity of 5° in each of the four quadrants using the Flicker‐Plus test (Advance Vision and Optometric test, City Occupational Ltd, London). Subjective refraction and stereopsis were also measure. Myopia was defined as the spherical equivalent ≤ ‐0.5 D.

The study was conducted at the Optometry Clinic of the Complutense University of Madrid, Spain.

Results: 32.8% of the subjects had myopia, most of which (23.3%) were less than 3 D. 1.63% of the subjects had no stereopsis. For the analysis of the results, we divided the subjects into those under or ≥50 years of age. Mean high contrast photopic visual acuity was ‐0.13 logMAR in subjects under 50 years of age and ‐0.1 logMAR in those over 50, with a significant difference between the two groups (p = 0.004). Mean mesopic visual acuity was 0.05 logMAR in subjects under 50 years of age and 0.07 logMAR in the older group (p = 0.048). None of the subjects had mesopic VA values > 0.3 logMAR. Results of low‐contrast VA showed a mean under photopic conditions of 0.05 logMAR in those under 50 years of age and 0.08 logMAR in those older. Under mesopic conditions, the mean was 0.38 logMAR and 0.41 logMAR in both groups, respectively. In both conditions there were significant differences between the groups (p = 0.04 and 0.03). The median central threshold of Flicker‐plus test under photopic conditions was 4.1 in those under 50 years of age and 5.37 in those over 50. Under mesopic conditions, median values were 8.18 and 10.18 respectively. Values were different between groups (both p < 0.001). Median photopic threshold values for parafovea were 3.93 in those under 50 years of age, and 4.56 in those over 50. Under mesopic conditions, medians were 6.16 and 7.75 in both groups, respectively. Significant differences were found between the groups (both, p < 0.001). We did not find differences in the values of AV or FMT depending on the years of work in the underground.

Conclusions: We found good results for visual acuity and flicker modulation thresholds in this population of underground drivers, both in photopic and mesopic conditions. It does not appear that working conditions have influenced the outcome.
Tips to improve ocular surface problems in patients using glaucoma medication
Authors: ∅yo‐Szerenyi Karin
Published: January 2025

Ocular surface disease is a frequently met challenge in our daily ophthalmology practice; even more so in glaucoma patients, who often need long term topical medication. The risk factors for ocular surface disease are many, including age, systemic disease, drug side effects, ocular conditions and lifestyle habits, such as smoking or computer use. More often than not, our glaucoma therapy is worsening the symptoms.

Knowing the different effects and side effects of our therapy will help us chose the optimal local agents for our individual patients and, by addressing this issue with the patient, we can ensure a better adherence to our therapy and find an optimal and tolerable daily regimen for the necessary treatment of glaucoma.
Deciphering the differentiation of human induced pluripotent stem cell‐derived corneal stem cells by gene regulatory networks analysis
Authors: Cunha Dulce Lima , Vatulainen Meri , Arts Julian , Melin Outi , Ilmarinen Tanja , Skottman Heli , Zhou Jo
Published: January 2025

The cornea is the transparent tissue situated at the surface of the eye, with crucial protective and light refraction properties. Limbal epithelial stem cells (LESC), residing in the limbus in the peripheral cornea, play a crucial role in sustaining corneal clarity by continuously renewing the corneal epithelium. Due to this regenerative capacity, LESC loss or malfunction result in limbal stem cell deficiency (LSCD) and subsequent corneal opacity. Therefore, elucidating LESC development and lineage determination is paramount for the advancement and refinement of LESC‐based therapies.

In this project, we have differentiated induced pluripotent stem cells (iPSC) into LESC using established in‐house protocols spanning a 25‐day period. Subsequently, we conducted single‐cell Assay for Transposase‐Accessible Chromatin with high‐throughput sequencing (scATACseq) at three distinct stages of differentiation (days 0, 11, and 25) to examine chromatin accessibility changes throughout the process. These findings were integrated with previously conducted single‐cell RNA sequencing (scRNAseq) on cells at equivalent differentiation stages. Analysis revealed six distinct cell populations based on overall chromatin accessibility profiles, aligning with the major cell clusters identified in scRNA‐seq data. We are currently conducting gene regulatory network analysis using both scATACseq and scRNAseq data to pinpoint the critical transcription factors driving LESC fate and comprehend the mechanisms underlying cellular heterogeneity during differentiation.

This research aims to unveil novel epigenetic mechanisms and crucial factors potentially implicated in the dynamic process of LESC lineage determination, potentially benefiting the generation of LESC populations suitable for transplantation as well as providing novel insights for LSCD treatment options.
Objective assessment of corneal transparency using densitometry distribution analysis
Authors: Consejo Alejandra
Published: January 2025

Advancing the assessment of eye diseases necessitates novel biomarkers that surpass conventional morphological analysis. Historically, the exploration of microstructural details in corneal research has heavily relied on histological examination, a process necessitating post‐mortem tissue samples and inapplicable in vivo. The cornea comprises densely arranged collagen fibers and specialized cell types including keratocytes, endothelial cells, and epithelial cells. These intricate details are inaccessible through widely used clinical instrumentation, such as Scheimpflug or OCT imaging. However, it is possible to analyze in‐vivo microstructure indirectly using Densitometry Distribution Analysis (DDA). This method involves extracting microstructure‐related biomarkers, such as tissue transparency and homogeneity, from low‐resolution clinical corneal images using image processing supported by artificial intelligence. Indirect in‐vivo microstructure analysis requires evaluating the distribution of pixel intensities. In ophthalmic instruments, image formation is influenced by how light, after being emitted from the source, backscatters upon interacting with the cornea. Given the cornea's nonhomogeneous nature, its internal arrangement affects how light traverses through different layers and regions. This variation in light propagation leads to differing pixel intensities in the resultant images. By examining these intensity variations, we can derive microstructure‐related biomarkers, such as tissue transparency and homogeneity.

In this talk, we will describe the DDA methodology and revisit its early successes in detecting eye diseases such as keratoconus before any clinical signs are apparent, with a 97% success rate, and up to 100% if clinical signs are observed. The DDA has also been used for early glaucoma detection, with a success rate of over 80%. Additionally, the DDA has been successfully applied to study the effects of contact lens wear on our eyes and to investigate certain rare genetic disorders affecting the cornea.
Insights into myopia from electrophysiology and from rare inherited retinal diseases
Authors: Mahroo Omar
Published: January 2025

Eye growth is driven by retinal signalling. The first part of the talk will discuss a common genetic myopia‐risk polymorphism near the GJD2 gene and recent findings that have found an association between allelic identity at this locus and retinal cone‐driven OFF pathway responses as detected in the full‐field electroretinogram (ERG). Results will be presented from investigations of standard and experimental ERG protocols and also from analysis of ERG components that are not conventionally quantified. The second part of the talk will present axial length distributions in a range of rare monogenic retinal diseases. These distributions will be compared with reference datasets and possible insights into mechanisms of emmetropisation will be discussed.
What gass did not say: how many ways to create a macular hole
Authors: Hsieh Yi‐Ting
Published: January 2025

Thanks to Dr. Gass' proposal for staging macular holes, we could have insights into the pathogenesis and progression of idiopathic macular holes back in the era without optical coherence tomography (OCT). This staging system is based on the foveal appearance, the size of the macular hole, and the presence or absence of vitreous separation as observed through biomicroscopy. According to the staging progression, anteroposterior traction from the posterior hyaloid plays a significant role in the development of a macular hole. Although most of Dr. Gass' descriptions remain relevant after the development of OCT, we have observed some cases of macular holes that do not fit into the Gass’ classification. The International Vitreomacular Traction Study (IVTS) Group has developed a new classification system based on OCT findings, such as macular hole size and the vitreomacular relationship. However, this system still considers partial or complete vitreomacular separation a necessary condition for the development of a macular hole. Interestingly, we have noticed that in some cases, there is no vitreomacular separation at the macular area, whereas in others, the macular hole develops only after posterior hyaloid detachment. These observations suggest that some macular holes might not develop through the classical route described by Dr. Gass. The traction force resulting in macular hole formation may be tangential, originating either from the undetached posterior hyaloid, the internal limiting membrane, or the epiretinal membrane. In this talk, we will explore aspects of the pathogenesis of idiopathic macular holes that Dr. Gass did not say.
CXL: Challenges and updates
Authors: Doroodgar Farideh
Published: January 2025

Corneal cross‐linking (CXL) is a critical treatment for keratoconus that combines UVA light and riboflavin (vitamin B2). This procedure received FDA approval in 2016 based on studies by Sykakis et al. (2015) which indicated that CXL could stabilize keratoconus, prevent myopia progression, and improve uncorrected distance visual acuity (UDVA). Despite the promising results, the studies had potential biases and a low number of randomized controlled trials (RCTs).

The two primary methods of CXL are epithelium‐off (epi‐off) and epithelium‐on (epi‐on or transepithelial). Epi‐off CXL involves removing the corneal epithelium to allow riboflavin penetration, whereas epi‐on CXL retains the epithelium, reducing patient discomfort but potentially being less effective. NG et al. (2021) found no significant difference in outcomes between these methods, though epi‐on showed fewer side effects such as corneal haze.

Accelerated CXL protocols have been developed to increase efficiency. Karam et al. (2023) compared these protocols, revealing that a 10‐minute protocol with 9 mW/cm2 UVA exposure provided better outcomes than a 5‐minute protocol with 18 mW/cm2. Accelerated methods are becoming more common due to their reduced treatment time.

In pediatric cases, both conventional and accelerated CXL are effective, although the transepithelial method had a lesser impact, as concluded by Mahdavi Fard et al. (2020). Additionally, combined procedures known as CXL+ integrate CXL with other treatments like laser ablation. The Athens Protocol, developed by Dr. Kanellopoulos, combines topography‐guided laser ablation with CXL to address irregular astigmatism and coma in keratoconus patients.

New riboflavin formulations and delivery methods, such as isotonic riboflavin and iontophoresis, have been developed to enhance riboflavin penetration and effectiveness. Glaukos' (Avedro) Mosaic System and the "sub400" protocol for ultrathin corneas are notable advancements, offering customized treatments based on individual corneal characteristics.