bluuebunny/crossref_metadata_2025 huggingface dataset:
Demystifying the nexus of audit committee characteristics and sustainability performance
Authors: Seth Himanshu , Saxena Akanksha
Published: January 2025

Purpose

To scrutinize the role of audit committee characteristics (i.e. audit committee independence, audit committee expertise and audit committee tenure) in attaining sustainability performance (i.e. environmental, social and governance performance).

Design/methodology/approach

Using a sample comprising 1,304 firm-year observations from Indian listed firms from 2018 to 2024, the current study performs baseline, robustness, additional and heterogeneity tests to examine the effect of audit committee characteristics on the environmental, social and governance performance.

Findings

Our findings reveal that audit committee independence and expertise are vital for achieving sustainability performance. Also, our results indicate that independence and expertise in audit committees reflect more inclination for environmental performance and governance performance than social performance. The outcomes further state that the audit committee tenure does not impact sustainability performance. Our results remain robust even after using different estimators. Additionally, the above findings are similar for industry-wise outcomes as well as during the COVID-19 phase and post-phase of the COVID-19 pandemic.

Originality/value

Our study makes a practical contribution by pioneering the attributes of audit committees in achieving sustainability performance from an emerging country perspective, such as India, which has not yet been done. The study holds great importance for managers, environmental activists, regulators and policymakers, reinforcing the belief that audit committee characteristics can be utilized in formulating policies for sustainability initiatives.
Clinical patterns of vitiligo in Japan: A descriptive study using the JMDC claims database
Authors: Tanemura Atsushi , Ma Yue , Sakaki‐Yumoto Masayo , Hiro Shintaro , Hirose Tomohiro , Suzuki Tamio
Published: January 2025

Vitiligo is a chronic autoimmune disorder that profoundly impacts patients' quality of life. Real‐world data on vitiligo in Japan are limited. This descriptive, cross‐sectional study used a claims database to evaluate vitiligo prevalence, patient demographics, treatments, and comorbidities in Japanese patients with vitiligo. Patients with claims for a vitiligo diagnosis in the JMDC database from January 2010 to December 2022 were included. Annual vitiligo prevalence, comorbidities, treatments, and medical facility visits were analyzed. Of 16 947 087 patients in the database during the 13‐year analysis period, a total of 26 358 patients (0.16%, 95% confidence interval 0.15–0.16) had a diagnosis of vitiligo. The standardized prevalence of vitiligo by sex and age in Japan remained generally consistent between 2010 (0.051%) and 2022 (0.056%). Atopic dermatitis was the most prevalent comorbidity. Comorbid atopic dermatitis prevalence increased between 2010 (21.8%) and 2022 (34.0%), and was highest among children aged 5–9 years. Other common comorbidities in 2022 included hypertension (10.4%), dyslipidemia (8.0%), anxiety disorder (7.4%), and psoriasis (7.0%). Topical corticosteroids were the most commonly used treatment throughout the period analyzed. Between 2010 and 2022, topical corticosteroid use decreased from 75.1% to 66.9%, and the use of narrowband ultraviolet B procedures increased from 19.2% to 28.1%. Mean duration of care was 12.9 months (standard deviation 20.5 months) and the median total number of outpatient medical facility visits was 3.0 (interquartile range 1.0–12.0). Key limitations include age and occupational biases in the JMDC database and potential misclassification of comorbidities due to off‐label treatment coding. Despite limitations in using a claims database, this study demonstrates consistent vitiligo prevalence in Japan, a high comorbidity burden, and evolving treatment patterns. Findings may guide clinical practice and treatment guidelines to improve management of vitiligo in Japanese patients.
Social skills in gifted students
Authors: Mendonça Lurian Dionizio , Capellini Vera Lucia Messias Fialho , Rodrigues Olga Maria Piazentin Rolim , Gastaldi Daniel German Ramos
Published: January 2025

People with high skills have a different behavioural repertoire and generally, such characteristics define their type of gifted. However, we do not have conclusive data regarding the characteristics of this population, since it is an area of study that generates many controversies, and when it comes to socio‐emotional characteristics, investigations are even more scarce and conflicting. Thus, the present study tried to describe and compare the behavioural characteristics and social abilities of students with high skills, before and after participating in enrichment activities. The Strengths and Difficulties Questionnaire (SDQ) was used, with the students themselves, their parents and teachers as informants. The results showed a good repertoire of social skills and few behaviour problems in these students, but there was no significant improvement in the second evaluation. As limitations, it was pointed out: the fact that the activities of curricular enrichment do not deal with the formal teaching of social skills; the reduced size of the sample and the lack of a control group to compare the results. As strong points, it was found that there are few studies that seek to describe the socio‐emotional characteristics of this population, neglecting other needs that need to be observed and met.
De‐implementing low‐value care in emergency medicine: A framework for sustainable improvement
Authors: Yousif Fahad , Bourke Elyssia M
Published: January 2025

The continued use of low‐value care interventions is a persisting challenge across the healthcare system despite targeted international efforts to reduce their use. These practices result in considerable economic and carbon costs. We present a model used to successfully de‐implement four low‐value care practices in a tertiary ED in Victoria, Australia. We outline the interventions and the proportions by which they were reduced. We provide a step‐by‐step framework that provides a model for other hospital departments or primary care centres to initiate their own de‐implementation process for low‐value care practices within their setting.
Role of mitochondrial complex I genes in host plant expansion of Bactrocera tau (Tephritidae: Diptera) by CRISPR/Cas9 system
Authors: Shi Wei , He Linsheng , Li Ruixiang , Cao Jun
Published: January 2025

Host expansion facilitates tephritid flies to expand their ranges. Unraveling the mechanisms of host expansion will help to efficiently control these pests. Our previous works showed mitochondrial complex I genes Ndufs1, Ndufs3, and Ndufa7 being upregulated during host expansion of Bactrocera tau (Walker), one of the highly hazardous species of tephritids. However, their roles in the host expansion of B. tau remain unknown. Here, using clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR‐associated nuclease 9 (Cas9) editing system for the first time, a stable homozygous Ndufa7 strain (Btndufa7−/−), heterozygous Ndufs1 (Btndufs1+/−), and Ndufs3 strains (Btndufs3+/−) were obtained from F3 generation of B. tau, after gene knockout. Reduced sizes of larvae and pupae of the Ndufa7 knockout strain were first observed. Notably, the mean values of fitness estimation (pupal numbers, single‐pupal weight and emergence rate) and Ndufa7 gene expression in the Ndufa7 knockout strain were slightly reduced on 2 native hosts (summer squash and cucumber), while it sharply decreased on the novel host banana and the potential host pitaya, compared with those of the wild‐type strain. Furthermore, the Ndufa7 knockout strain did not survive on the novel host guava. These results suggested that Ndufa7 disturbs the survival on native hosts, expansion to novel hosts, and further expansion to potential hosts of B. tau. Homozygous lethality occurred after the knockout of Ndufs1 or Ndufs3, suggesting that these 2 genes play a role in the early development of B. tau. This study revealed that Ndufa7 is a target gene for the management of tephritids and opens a new avenue for pest control research.
Fungi on the cuticle surface increase the resistance of Aedes albopictus to deltamethrin
Authors: Hu Ju‐Ping , Deng Si‐Jia , Gu Lin , Li Lin , Tu Lei , Li Ju‐Lin , Tang Jian‐Xia , Zhu Guo‐Ding
Published: January 2025

Aedes albopictus (Ae. albopictus) is widely distributed and can transmit many infectious diseases, and insecticide‐based interventions play an important role in vector control. However, increased insecticide resistance has become a severe public health problem, and the clarification of its detailed mechanism is a matter of urgence. This study found that target‐site resistance and metabolic resistance could not fully explain insecticide resistance in field Ae. albopictus, and there were likely other resistance mechanisms involved. The 16S and internal transcribed spacer sequencing revealed significant differences in the species compositions of the cuticle surface symbiotic bacteria and fungi between deltamethrin (DM)‐resistant (DR) and DM‐susceptible (DS) Ae. albopictus. Additionally, the abundances of Serratia spp. and Candida spp. significantly increased after DM treatment. Furthermore, 2 fungi (Rhodotorula mucilaginosa and Candida melibiosica) and 3 bacteria (Serratia marcescens, Klebsiella aerogenes, and Serratia sp.) isolated from DR Ae. albopictus can use DM as their sole carbon source. After reinoculation onto the cuticle surface of DS Ae. albopictus, R. mucilaginosa and C. melibiosica significantly enhanced the DM resistance of Ae. albopictus. Moreover, transcriptome sequencing of the surviving Ae. albopictus after DM exposure revealed that the gene expression of cytochrome P450 enzymes and glutathione‐S‐transferases increased, suggesting that besides the direct degradation, the candidate degrading microbes could also cause insecticide resistance via indirect enhancement of mosquito gene expression. In conclusion, we demonstrated that the cuticle surface symbiotic microbes were involved in the development of insecticide resistance in Ae. albopictus, providing novel and supplementary insights into insecticide resistance mechanisms.
Coagulation and platelet function in cold‐stored whole blood on missions in a helicopter emergency service
Authors: Sato Folatre José‐Gabriel , Wikman Agneta , Radulovic Vladimir , Sandström Göran , Skallsjö Gabriel , Arnell Per , Ricksten Sven‐Erik , Romlin Birgitta
Published: January 2025

Background

Haemorrhage is a leading cause of morbidity and mortality in trauma, and prehospital transfusion of blood products is often necessary. Whole blood has been proposed to be the best alternative, but it is unclear whether, and how, storage and transport of the blood in a helicopter affects the blood units. We investigated the coagulation capacity and platelet function in whole blood at different time points during helicopter missions.

Methods

Twenty units of low‐titre group O RhD negative whole blood were collected from healthy volunteers and analysed before, during and after transport in a helicopter. Coagulation and platelet function, as measured by thromboelastography, and blood samples for pH, electrolytes, glucose and lactate were assessed at baseline and 24, 72 and 168 h after storage in the helicopter. Plasma concentrations of coagulation factors and haemoglobin and blood counts were measured at baseline and after 168 h.

Results

Plasma concentrations of coagulation factors and haemoglobin did not change during storage and transport. Platelet counts decreased from a baseline mean of 172 ± 29 × 109/L to a mean of 120 ± 28 × 109/L after 168 h, and platelet function worsened slightly but significantly by 8%–9% during storage and transport. pH and glucose decreased while potassium and lactate levels increased after 168 h compared with baseline.

Conclusion

Storage and transport of whole‐blood units in a rescue helicopter, for up to 168 h, had a slight impact on the blood quality. Storage of whole blood on board of the helicopter holds up to European standard, measured as temperature and haemolysis.
KIF9 Ameliorates Neuropathology and Cognitive Dysfunction by Promoting Macroautophagy in a Mouse Model of Alzheimer's Disease
Authors: Wang Maoju , Guo Song , Yi Lilin , Li Zhaolun , Shi Xiuyu , Fan YePeng , Luo Man , He Yan , Song Weihong , Du Yehong , Dong Zhifang
Published: January 2025

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the elderly. The imbalance of protein production and degradation processes leads to the accumulation of misfolded and abnormally aggregated amyloid‐beta (Aβ) in the extracellular space and forms senile plaques, which constitute one of the most critical pathological hallmarks of AD. KIF9, a member of the kinesin protein superfamily, mediates the anterograde transport of intracellular cargo along microtubules. However, the exact role of KIF9 in AD pathogenesis remains largely elusive. In this study, we reported that the expression of kinesin family member 9 (KIF9) in the hippocampus of APP23/PS45 double‐transgenic AD model mice declined in an age‐dependent manner, concurrent with macroautophagy dysfunction. Furthermore, we found that KIF9 mediated the transport of lysosomes through kinesin light chain 1 (KLC1), thereby participating in the degradation of amyloidogenic pathway‐related proteins of Aβ precursor protein (APP) in AD model cells through promoting the macroautophagy pathway. Importantly, genetic upregulation of KIF9 via adeno‐associated virus (AAV) diminished Aβ deposition and alleviated cognitive impairments in AD model mice by enhancing macroautophagy function. Collectively, our findings underscore the ability of KIF9 to promote macroautophagy through KLC1‐mediated anterograde transport of lysosomes, effectively ameliorating cognitive dysfunction in AD model mice. These discoveries suggest that KIF9 may represent a novel therapeutic target for the treatment of AD.
Is methamphetamine blood concentration in emergency department patients associated with the clinical picture?
Authors: McCutcheon David , Soderstrom Jessamine , Raghavan Mohan , Oosthuizen Francois , Douglas Bianca , Burrows Sally , Smith Jennifer L. , Fatovich Daniel
Published: January 2025

Aims

This study aimed to describe clinical features and outcomes of patients presenting to the emergency department with analytically confirmed methamphetamine intoxication, to determine the blood concentration of methamphetamine and to test its association with clinical findings.

Design

The Western Australian Illicit Substance Evaluation (WISE) study is a prospective observational cohort study.

Setting

Royal Perth Hospital Emergency Department, Perth, Australia, between 2016 and 2018.

Participants

Patients suspected to be intoxicated with a stimulant, hallucinogenic or cannabinoid substance and who required intravenous access or blood tests as part of standard care. Those predominantly alcohol intoxicated, behaviourally disturbed or opioid intoxicated were excluded. The 431 participants with detectable methamphetamine (> 0.001 mg/l) included in this analysis had a mean age of 33.2 (9.4) years and 286/431 (66.4%) were male.

Measurements

Concentration was reported for methamphetamine and other illicit drugs detected. Univariate associations of symptoms and signs, and physiological and laboratory parameters with methamphetamine concentration were determined and used to develop a multivariable model.

Findings

The median concentration of methamphetamine was 0.12 mg/L [Q1,Q3: 0.05, 0.27]. Psychotic symptoms were seen in 265/431 (61.5%) patients and intravenous or intramuscular sedation was required in 280/431 (65.0%). Mean heart rate was elevated at 105.9 (21.5) beats per minute, but other mean or median physiological parameters were within normal limits. A multivariable model showed that methamphetamine concentration was 27% lower in males (P = 0.026), 60% higher in those with palpitations (P = 0.013), 62% higher in those with choreoathetoid movements (P = 0.002) and increased by 1% for each unit (μg/L) increment in creatinine (P = 0.001).

Conclusions

In a cohort of emergency department patients with methamphetamine exposure, a multivariable model inferred a significant association between higher methamphetamine concentration and female sex, the presence of palpitations and choreoathetoid movements and creatinine concentration. The model showed no significant association with agitation, psychotic symptoms or other physiological or clinical parameters.
A Newly Discovered Symbiotic Relationship Between Giant Cowbirds (Molothrus oryzivorus) and South American Tapirs (Tapirus terrestris) in Suriname
Authors: Backshall Steve J. , Dunn Christian , Mainwaring Mark C.
Published: January 2025

Interspecific interactions are a common occurrence in nature, and, in some instances, two species form very close associations. Such symbiotic relationships vary, though, in terms of the relative advantages and disadvantages accrued by both species during interspecific interactions. Symbiotic relationships whereby both species benefit are thought to occur between oxpeckers and large mammals in Africa because while oxpeckers benefit by preying upon ticks and blood‐sucking flies on the mammal's bodies, the mammals also benefit from the removal of ticks and flies. However, there is also evidence that the interactions between oxpeckers and mammals may not benefit both species because oxpeckers may not significantly reduce the abundance of ticks and may also deliberately keep wounds open, making such interactions harmful for mammals. Here, we respond to calls for further observations to help clarify the nature of such interactions by reporting a newly discovered symbiotic relationship between giant cowbirds (Molothrus oryzivorus) and South American tapirs (Tapirus terrestris) in Suriname. The cowbirds were observed feeding on ticks on the bodies of the tapirs and while it appeared that the tapirs were generally tolerant of the cowbirds, we did observe the tapirs attempting to repel the cowbirds when they appeared to target wounds on their bodies. The interactions we observed therefore appeared to benefit the cowbirds by providing them with prey and while the tapirs benefit from a reduction in tick abundance, the cowbirds did appear to target wounds on their bodies. Consequently, we tentatively conclude that the relationship between giant cowbirds and South American tapirs that we observed was beneficial to the birds and yet potentially harmful to the mammals and so further observations are needed to confirm if such interactions are context dependent. The interactions between giant cowbirds and South American tapirs provide an interesting opportunity to examine the nature of the evolutionary causes and ecological consequences of symbiotic interactions between birds and mammals.
Homozygous multiple‐insecticide resistance in Australian invasive serpentine leafminer Liriomyza huidobrensis (Blanchard) (Diptera: Agromyzidae)
Authors: Chen Yizhou , Nguyen Duong T. , Webster John , Nguyen Thi Hong Tham , Herron Grant A.
Published: January 2025

In October 2020, Liriomyza huidobrensis (serpentine leafminer [SLM]) was first detected in Western Sydney, New South Wales (NSW), and subsequently Southern Queensland (QLD). Control failures were reported, and insecticide resistance was confirmed via bioassay, but mechanisms causing resistance remained unknown. We characterised the complete mRNA sequence of eight insecticide target genes of L. huidobrensis using RNA sequencing. We found that the Australian SLM carries three mutations (I129V, G227A and F331W) of the acetylcholinesterase (AChE) gene, causing resistance to mode of action (MOA) 1 chemicals; one mutation (A301S) of the gamma‐aminobutyric acid receptor subunit beta (GABAR), causing resistance to MOA 2 chemicals; and two mutations (M918T and L1014L) of the voltage‐gated sodium channel (VGSC) gene, causing resistance to MOA 3 chemicals. We consequently developed a multiamplicon‐sequencing panel to screen 234 Australian field‐collected SLM samples using next‐generation sequencing. The multiplex panel includes mitochondrial cytochrome oxidase subunit 1 (COI) for species identification and AChE, VGSC, glutamate‐gated chloride channel (GluCl) and chitin synthase 1 (CHS1) gene mutations. We confirm that all the individuals carry the multi‐resistance alleles in a homozygous and fixed state. This is a rare phenomenon for a single individual to be homozygous for multiple resistance mutations, with only a few studies documenting such multi‐resistance at the population level. Such resistance mechanism detection raises concern that there are limited chemical options for the control of invasive SLM in Australia.
IL‐25 Enhances B Cell Responses in Type 2 Inflammation Through IL‐17RB Receptor
Authors: Abdu Semah , Xia Jiao , Yuan Huihui , Tan Tiak Ju , Layhadi Janice A. , Shamji Mohamed H. , McKenzie Andrew N. J. , Haloob Nora , Hopkins Claire , Woszczek Grzegorz , Till Stephen J.
Published: January 2025

Background

Alarmin cytokine IL‐25 promotes type 2 inflammatory responses in disorders such as asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and known targets include ILC2 and Th2 cells. However, other cellular targets for IL‐25 remain poorly defined.

Objective

To investigate induction and expression of IL‐25 receptor (IL‐17RB) by B cells and evaluate responsiveness of IL‐17RB‐expressing B cells to IL‐25 in vitro.

Methods

IL‐17RB expression, regulation and function on B cells were evaluated in peripheral blood‐derived B cells by flow cytometry and RT‐PCR, including in response to IgE‐inducing stimuli (anti‐CD40 mAb and IL‐4). Single‐cell RNA sequencing was used to compare IL‐17RB+ and IL‐17RB‐activated peripheral blood‐derived B cells. To evaluate B cell IL‐17RB expression within type 2 inflamed tissue, B cells were compared from nasal polyps, control turbinate tissue and matched peripheral blood.

Results

Activation of B cells with anti‐CD40 and IL‐4 increased IL‐17RB expression at both protein and mRNA level, which was further upregulated by IL‐25. B cells induced to express IL‐17RB responded to IL‐25 with enhanced antibody production. Single‐cell RNA‐sequencing showed that IL17RB+ activated B cells expressed higher levels of IGHE, CCL17 and CCL22 compared to IL17RB‐ B cells. B cells from nasal polyp tissue expressed higher levels of surface IL‐17RB compared with control tissue, correlating with patient‐reported CRSwNP severity (SNOT‐22).

Conclusion

Peripheral blood B cells activated under IgE‐inducing conditions express surface IL‐17RB, and tissue IL‐17RB+ B cells are increased in type 2 inflammation. IL‐17RB+ cells have a distinct transcriptional profile and respond to IL‐25 with enhanced antibody production, highlighting the IL‐25/IL‐17RB pathway as a potential therapeutic target for CRSwNP and other type 2 inflammatory disorders.
The impact of complement factor H Y402H polymorphism on the retina
Authors: Ferrington Deborah A. , Shang Peng , Shen Shichen , Qu Jun
Published: January 2025

Genome‐wide association studies of AMD patients have identified single nucleotide polymorphisms (SNP) in 34 high‐risk loci involving different biological pathways, suggesting that different mechanisms can lead to the clinical diagnosis of AMD. Our study defines how the high‐risk SNP for complement factor H (CFH) alters cellular processes in the retinal pigment epithelium at early AMD and with progressive disease severity. Using label‐free ultrahigh resolution mass spectrometry, we analyzed the content of ~6000 proteins in RPE isolated from human donors that were genotyped for the CFH risk alleles (CC, high risk; TT, low risk; CT, mixed risk) and phenotyped for AMD severity. There were significant differences in the RPE proteome even in the absence of AMD, which may provide insight into why this single amino acid change in CFH confer high risk for AMD. Comparison of the RPE at early AMD showed high risk versus low and mixed risk had the greatest differences in the content of mitochondrial proteins, including those involved in metabolism, mitochondrial organization, and membrane potential. Other altered pathways involved lipid metabolism, translation, and the stress response. Differences were magnified at more advanced stages of AMD. These results show fundamental difference in AMD onset and progression, supporting the idea that the pathway to late AMD may be mechanistically different and influenced by the individual's genetic background. These genotype‐specific differences in the RPE proteome provide new insight into disease mechanism and will help guide development of therapies that prevent progression to advanced AMD.
Excimer‐ and femto‐assisted PKP – still an option?
Authors: Seitz Berthold
Published: January 2025

The evolution of non‐mechanical laser keratoplasty started in Erlangen in 1986. Because of undisputed clinical advantages, especially in eyes with keratoconus and instable thin corneas after PKP, noncontact Excimer laser trephination with orientation teeth/notches is still favored in Homburg/Saar in daily practice. The Femtosecond laser‐assisted keratoplasty technique has been very exciting with respect to profiled incisions but due to major lack of all‐suture‐out data after introduction of the technique 15 years ago – the superiority of this high price and difficult to maintain option has not been proven, yet! Femtosecond laser‐assisted PKP without liquid interface seems to have major disadvantages (astigmatisms and immune reactions) in comparison to Excimer laser‐assisted PKP especially in keratoconus.
Macular oedema due to brvo: Timing for vitrectomy
Authors: Gkizis Ilias
Published: January 2025

Retinal vein occlusion (RVO), either central (CRVO), branch RVO or hemiretinal RVO is the second most common retinal vascular disease after diabetic retinopathy. It may lead to irreversible visual loss if left untreated. The most common cause of decreased vision in patients affected with BRVO is the accumulation of fluid within the macula.

Currently, in our clinical practice we have various treatment options for macular edema associated with BRVO. As a first line treatment the use of anti‐VEGF injections is very common and can be combined with the use of Grid‐pattern laser photocoagulation. Furthermore, in cases resistant to anti‐VEGF the intravitreal steroid implant (DEX) is an alternative choice.

Epiretinal membrane is a fibroglial cellular tissue proliferation in the macula and is most commonly idiopathic, generated after a posterior vitreous detachment (PVD). Secondary ERM has been described in ocular trauma, retinal detachment, retinal surgery, retinal vasculopathies, and ocular inflammation. The prevalence of ERM in patients with RVO ranges between 14 and 16% and may exacerbate macular edema and reduce drug penetration of anti‐VEGF agents.

In cases with BRVO, resistant macular edema despite of continuous anti‐VEGF treatment overtime and the presence of ERM the surgical removal of the membrane could potentially benefit patients, with a favorable final anatomical and functional result. Many parameters must be evaluated preoperatively, such as the integrity of the photoreceptor IS/OS, external limiting membrane (ELM), the absence of macular ischemia and the absence of disorganization of inner retinal layers (DRIL) before proceeding with retinal surgery.

Vitrectomy with ERM peeling in these patients could lead to significant improvement in visual acuity and macular thickening, with resolution of macular edema and reduce the need for anti‐VEGF injections.
Monogenic disease associated with uveitis
Authors: Heissigerova Jarmila
Published: January 2025

The aetiology of non‐infectious uveitis is usually multifactorial, involving both genetic and environmental risk factors. The association of human leucocyte antigens (HLA) with some types of uveitis is well recognized, such as HLA‐A29 and Birdshot chorioretinitis, or HLA‐B27 and acute anterior uveitis alone or with ankylosing spondylitis. The monogenic associations with uveitis, such as in Blau syndrome or Haploinsufficiency of A20, are extremely rare and as such due to limited experience with the disease difficult to treat or manage if the inflammation is of sight‐threatening nature. The paper will report patients from Centre for diagnosis and treatment of uveitis in Prague, and our diagnostic and therapeutic experience with monogenic diseases associated with uveitis, especially with Blau syndrome.

Supported by AZV MZ CR NU23‐05‐00133.
Storytelling as a tool for engaging communication of eye research
Authors: Gallar Angeles
Published: January 2025

On one occasion, chemist John Dalton (1766‐1844) committed an etiquette error due to his color blindness. Thinking he wore a gray robe, he met King William IV in bright red attire. Perhaps the Protestant monarch mistook the Quaker chemist for a Catholic cardinal. In the mid‐18th century, doctors believed color blindness resulted from a cerebral defect. Still, Dalton theorized his vitreous humor had a blue tint absorbing certain wavelengths, like wearing tinted sunglasses. Did he discover the true issue?

Storytelling and science get along great. Stories are coherent narrations of interconnected events using context and imagery. Also, they ‘stick’ because they engage our emotions. Moreover, emotions can drive change. Stories enhance the visibility, credibility, and clarity of scientific messages.

Scientific storytelling can be learned through outstanding storytelling examples of science communication. A structure for scientific storytelling can be achieved by finding the hook, the trigger, the action, and the climax of a particular research story. Learning how to draw the story map of scientific research will help audiences (and grant reviewers!) connect the dots for a logical flow of your ideas. It will engage readers. With these storytelling techniques, anyone can write clearer, more memorable grant proposals, papers, presentations, and press releases, improving the impact of scientific research.

References

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Cormick, C. (2019). Who doesn’t love a good story? — What neuroscience tells about how we respond to narratives. Journal of Science Communication, 18(5), Y01.

Gallar, A. (2020) Los ojos de Dalton y el color de los átomos [Dalton's eyes and the color of atoms] UMHSapiens.com

Green, S. J., Grorud‐Colvert, K., & Mannix, H. (2018). Uniting science and stories: Perspectives on the value of storytelling for communicating science. FACETS.

Joubert, M., Davis, L., & Metcalfe, J. (2019). Storytelling: The soul of science communication. Journal of Science Communication, 18(5), E.

Yang, Y., & Hobbs, J. E. (2020). The Power of Stories: Narratives and Information Framing Effects in Science Communication. American Journal of Agricultural Economics.

Neeley et al. (2020). Linking Scholarship and Practice: Narrative and Identity in Science. Frontiers in Communication, 5, 35.

Olson, Randy. Houston, we have a narrative. University of Chicago Press, 2021.
New insights on the genetic basis underlying hereditary high myopia in a cohort of more than 100 spanish families
Authors: González Laura , Ferrer Xènia , de Lima Yasmin Soares , Busto Sandra Suescun , Méndez‐Vendrell Pilar , Ruiz‐Nogales Sheila , Lora Laura Zahino , Del Saz Ana Nolla , Garrido Claudia , Recasens Oscar , Navarro Rafael , Pomares Esther
Published: January 2025

Aims/Purpose: This study focuses on the identification of new mutations and novel genes associated with hereditary high myopia, in order to determine the most prevalent variants in the Spanish population and to stablish the clinical characterization through the study of genotype‐phenotype correlations.

Methods: 119 Spanish families (390 patients) were recruited. DNA samples from 347 patients were analysed by Whole Exome Sequencing. In silico analyses were carried out prioritising a custom‐designed panel of 549 genes related to myopia. Clinical ophthalmological assessments were performed to all the study subjects.

Results: Genetic analysis was performed in 102 families affected by high myopia. In more than 20% of them, a clear genetic cause was identified in genes already involved with high myopia. Additionally, potentially pathogenic variants in the myopia‐related genes were identified in about 25% of the cases, and in 15% of the families, we identified likely pathogenic variants in candidate genes that have not yet been directly associated to myopia. These evidence lead us to estimate the genetic diagnosis in approximately 50% of the families. High myopia genes found can be classified into 4 groups according to their function: extracellular matrix, retina expression, SMAD family and others. Differences in clinical characterization between groups were observed.

Conclusions: We were able to point out a possible genetic cause in about 50% of the families. Furthermore, we target new genes that could be involved in the molecular basis of hereditary high myopia, expanding the knowledge of this condition. High pathological myopia can be correlated to the gene function.

References: High myopia occurs when the spherical refractive error exceeds ‐6.00 diopters or the axial length of the eye is greater than 26 mm. Genetic factors play a crucial role in its development, since it has an estimated heritability in more than 70% of cases, according to the literature.
Predictive factors of final visual outcome in patients with leber hereditary optic neuropathy treated with lenadogene nolparvovec gene therapy
Authors: Barboni Piero , Newman Nancy , Biousse Valérie , Yu‐Wai‐Man Patrick , Carelli Valerio , Vignal‐Clermont Catherine , Josse Constant , Taiel Magali , Sahel José‐Alain , Sergott Robert
Published: January 2025

Aims/Purpose: To identify the predictive factors of final best‐corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) due to the m.11778G>A MT‐ND4 mutation who received lenadogene nolparvovec gene therapy in clinical studies.

Methods: The following covariates were studied to identify those that might influence final BCVA: age, gender, timing of treatment, baseline BCVA value and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE and REFLECT), using BCVA at 1.5 years post‐treatment as the dependent variable. In RESCUE and REVERSE, ND4‐LHON patients received an injection of gene therapy in one eye and a sham injection in the other. In REFLECT, the first‐affected eye received gene therapy, while the other eye was randomly injected with gene therapy or placebo.

Results: In 290 untreated/treated eyes, the covariates statistically significantly associated with an improvement in final BCVA were a longer time from vision loss to treatment (p < 0.05), and thicker optical coherence tomography (OCT) parameters at baseline: ganglion cell layer (GCL) temporal outer segment, GCL superior outer segment, GCL nasal outer segment, and GCL inferior outer segment at ETDRS analysis, and retinal nerve fiber layer (RNFL) inferior quadrant, RNFL nasal quadrant and RNFL superior quadrant (p < 0.05). The greatest effects [95% confidence interval] were observed for the thickness of the inferior and superior outer GCL segments at baseline (‐0.1 [‐0.163; ‐0.037] and ‐0.09 [‐0.146; ‐0.033], respectively; both p = 0.002). A worse baseline BCVA was associated with a worse final BCVA (p < 0.0001).

Conclusions: Timing of treatment administration, baseline BCVA value and baseline thickness of OCT parameters are predictive of the BCVA 1.5 years after treatment in patients with MT‐ND4 LHON who received lenadogene nolparvovec.
Adaptive optics fundus images: Automatic vs manual vessel segmentation
Authors: Bernardes Rui , Jordão João , Rodrigues Sérgio , Domingues Joana , Serranho Pedro , Guimarães Pedro
Published: January 2025

Aims/Purpose: This work aims to assess the performance of an automatic method for segmenting the lumen of retinal arterioles from adaptive optics (AO) high‐resolution fundus images in comparison to manual segmentation and its potential impact on the determination of the neurovascular coupling (NVC) response.

Methods: A total of 944 fundus images (4x4 degrees) within the macular region were acquired from 30 healthy adults (age (m+/‐sd): 33.7+/‐11.2 yrs.) and 15 type 1 Diabetes Mellitus (T1DM) patients (36.3+/‐13.3 yrs.), gender and imaged eye balanced by group, using the rtx1 AO camera (ImagineEyes, Orsay, France). Manual segmentations were performed by an experienced technician and assessed by an experienced retina specialist, and the average lumen diameter over a vessel segment was determined.

The automatic method first identifies the vessel axis using a low‐pass filter followed by morphological operations. Images are Gabor filtered, and lumen‐wall interfaces are detected by analyzing intensity profiles perpendicular to the vessel axis. Candidate locations are kept or removed based on vessel curvature smoothness and the vessel wall's parallelism. Local polynomial fits establish final lumen‐wall interfaces, and the lumen diameter is determined by their distance as measured perpendicularly to the vessel axis.

Results: The absolute value of the relative error (AVRE) (%) between methods was assessed, and outliers were determined based on their distribution, of which 89% (838/944) were inliers. Furthermore, all images for the same subject presented a systematic (positive or negative) difference uncorrelated to the lumen diameter (r=‐0.17). The AVRE ranged from 0.0% to 6.3%, with an average of 1.8% (Q1: 0.9, Q2: 1.8, Q3: 3.1).

Conclusions: Achieved results show a consistent difference between manual and automatic segmentations, which might be explained by the difficulty in visually determining the exact interface location over grayscale images. However, these results show that no impact is expected in determining NVC response.
A new light‐adaptive lens improves contrast sensitivity when transitioning from bright to dark environments
Authors: Duarte‐Toledo Raul , Mompean Juan , Paniagua‐Diaz Alba , Lakhchaf Nacer , Kobia‐Acquah Emmanuel , Artal Pablo , Barrau Coralie
Published: January 2025

Aims/Purpose: Light‐adaptive lenses, known as photochromic, adjust dynamically light intake. We recently evaluated the effect of a new ultra‐responsive light‐adaptive lens on contrast sensitivity recovery during fade back compared to the older photochromic generation, showing that faster fadeback speed improves contrast sensitivity. However, data was lacking in varying light, specifically when moving from bright to dark environments, and in comparison to a static clear lens. This study assessed dynamic contrast sensitivity changes with the new light‐adaptive lens after exposure to a transient bright light, compared to the older photochromic lens and to a static clear lens.

Methods: Ten healthy subjects (28.7 ± 3.4 years, spherical equivalent ‐1.8 ± 1.8 D, astigmatism < 1D) were trained to control contrast of a sinusoidal grating (24 cycles/degree) at 3 m. Three lenses were used in a double‐blind cross‐over design; a clear lens, a photochromic TO2, and a new light‐adaptive TO1, twice as fast as TO2 in returning to clear state. Subjects were exposed to a bright light (8000 lux) for 30 seconds, then transitioned to darkness where contrast sensitivity was measured dynamically for 100 seconds. Recovery times for first contrast perception and 90% contrast sensitivity were recorded for each lens, tested three times. MANOVA with Tukey tests were performed.

Results: TO1 recovered 90% contrast sensitivity 35% faster than clear lens (p < 0.01) and 23% faster than TO2 (p < 0.01). Initial contrast perception recovery was 55% faster with TO1 compared to clear lens (p < 0.001).

Conclusions: The new light‐adaptive lens TO1 significantly improves visual performance in dynamic light conditions compared to the older photochromic lens TO2 and the static clear lens. This performance enhancement reduces light stress and improves visual function under normal viewing conditions.
Quantifiying epithelial cell viability on whole porcine lenses using triple Hoechst‐Ethidium‐Calcein‐AM staining in a chemical toxicity model
Authors: Poinard Sylvain , Coulomb Louise , Chapelon Gabriel , Cortez Oliver Dorado , Thomas Justin , He Zhiguo , Perrache Chantal , Ganeau Alice , Forest Fabien , Mascarelli Frederic , Gain Philippe , Thuret Gilles
Published: January 2025

Aim: Establishing an ex vivo model of the crystalline lens will be a driving force for further research on this tissue. The epithelium plays an essential role in maintaining osmolarity, volume, and lens transparency. Therefore, it is crucial to have a tool to control the lens epithelium ex vivo. We have previously validated a method for quantifying epithelial cell viability on whole lenses ex vivo by triple labeling with Hoechst 33342, ethidium homodimer and calcein‐AM (HEC) using a model of acute frostbite necrosis. We now demonstrate the application of this triple labeling to a model of chemical toxicity by Staurosporine (STS) which induces cell death scattered all over the epithelial surface with a mild severity.

Methods: Ten fresh pairs of 6‐month‐old porcine lens were retrieved. On one lens, a diffuse epithelial lesion was induced by an incubation in STS solution (0.5 μM in CorneaMax, Eurobio) during 24 hours at 37°C. The other was incubated in CorneaMax solution without STS in the same conditions. The day after, both were incubated for 1 hour at 20°C in a HEC mixture. Images were acquired with a macroscope (macro zoom microscope) and analyzed with ImageJ. Calcein‐AM and Ethidium images were used to calculate the area covered by living epithelial cells. Hoescht images allowed to count cell nuclei per unit area. Viable epithelial cell density (vEpCD) was defined as the number of viable cells per unit area. Different strategies were developed to reduce the background noise.

Results: There was no interfering lens auto‐fluorescence for the exposure times used. The median vEpCD was 3804 cells/mm2 [10th‐90th percentiles = 2922–4862] for STS treated‐lenses versus 3896 cells/mm2 [3169–4980] for control lenses (p = 0.002).

Conclusion: The assessment of lens epithelial cell viability has been proposed only in cell culture or isolated capsule models. Thanks to a simple sample preparation, triple HEC staining allows fluorescence imaging on large series of whole lens in order to respect the architecture of the epithelium. This STS model induces a subtle change in mortality, confirming the sensitivity of the technique and its use for cytotoxicity studies of new therapeutics targeting the lens.

References

Mechanisms of staurosporine induced apoptosis in a human corneal endothelial cell line. Thuret G & al. Br J Ophthalmol. 2003
Genetic variations in human opsin genetics: Understanding color vision phenotypes and defects
Authors: Lilja Olivia , Backlund Michael , Tiihonen Jussi , Kangas Harri , Donner Kati , Ala‐Laurila Petri , Turunen Joni
Published: January 2025

Purpose: The aim of this study was to analyze human opsin genes, OPN1LW and OPN1MW, for single nucleotide polymorphisms (SNP) and structural variants (SV) impacting color vision in subjects diagnosed with color vision deficiency.

Methods: Nineteen subjects underwent anomaloscope examination to diagnose color vision deficiency phenotypes (dichromatic: protanopia and deuteranopia). First, a previously published method of long range‐PCR and sequencing was performed to identify variations in OPN1LW, OPN1MW, and OPN1SW. In the case of discrepancy, ultra‐long nanopore sequencing was utilized to identify possible SVs.

Results: The long range‐PCR and sequencing genetically validated the color vision diagnosis for 17 of the 19 individuals. For two individuals the genetic and functional diagnoses conflicted. Ultra‐long nanopore sequencing of these two revealed possible rearrangements in the opsin gene cluster that could affect the color vision and explain the conflicting results based on the long‐PCR method.

Conclusions: The large size of the human opsin gene cluster and the high degree of sequence homology between OPN1LW and OPN1MW genes have been a challenge for genetic studies of color vision deficiencies. The development of ultra‐long nanopore sequencing technology allows for a more comprehensive genetic analysis of this region, especially for the detection of pathogenic SVs. In this study, we were able to identify possible SVs underlying color vision deficiency in cases that were missed by the long range‐PCR. However, alignment of the ultra‐long sequences to the reference genome at the variable opsin gene cluster region remains a challenge for the data analysis.
Retinal vessel flicker light responsitiviness and its relation to analysis protocols, static and metabolic data in healthy subjects
Authors: Artemiev Dmitri , Todorova Margarita
Published: January 2025

Aims/Purpose: To assess agreement between different analysis protocols for determination of retinal vessel dilation response to flicker light (FL) and its relation to static‐ and metabolic parameters of retinal vessels in healthy subjects.

Methods: 24 right eyes of 24 healthy controls (mean age: 35.87 ±SD 14.20 years), who underwent dynamic‐ and static retinal diameter‐ and oxygen saturation measurements on Retinal Vessel Analyser were included (RVA, Imedos, Jena, Germany). Using repeated video analyses, responses to FL were measured within the superior‐temporal (ST) area. Taking the length and the location into account, the FL data were evaluated in 3 groups: length < 1 optic disc (OD) (group 1); length > 1OD: close to the OD (group 2) and within the VesselMap area (group 3).

For comparability, the static‐ (CRA, CRV, AVR) and oxygen saturation parameters (A‐V SO2, V‐SO2, A‐V SO2) were calculated in the ST peripapillary area using the VesselMap tool of RVA and were evaluated in relation to the corresponding dynamic ones (group 3).

Results: In all groups, vascular FL response of arteries was less pronounced compared to venules (p = 0.023). Event thought, FL responses (mean ±SD: FL‐A; FL‐V, %) in group 1 to be more pronounced (mean 3.36 ±2.31; 4.42 ±1.69) compared to those in groups 2 (mean: 2.97 ±2.40; 4.08 ±1.55) and 3 (2.84 ±2.29; 4.21± 2.03) they did not reach statistically significant values (p > 0.44).

The mean flicker response of venules showed negative correlations to the corresponding static‐ and metabolic parameters: CRV (r = ‐0.489; p = 0.015) and V‐SO2 (r = ‐0.375; p = 0.001).

Conclusions: Our study confirms, that flicker light response, even showing slight difference about its length and location, allows agreeable measurements. However, even in healthy subjects, the effect of the static‐ and metabolic retinal vessel measurements on retinal venular flicker response should be taken in consideration.