This Research Topic asked the question - which insights have we learned on cardiovascular disease in diabetes and what more can we gain from advanced cardiovascular imaging in the future?The connection between diabetes and cardiovascular disease is clear and individuals with diabetes are at least two times more likely to develop cardiovascular disease, which is the leading cause of morbidity and mortality in diabetes . DiabeteThe earliest non-invasive technique for visualising the contour of the heart is projection radiography, which has been available for more than 120 years. This technique can help to clarify relatively simple anatomical questions but is still used today as an initial examination for many clinical indications. Computed tomography (CT), introduced in the 1970s, enables the acquisition of spatially highly resolved three-dimensional anatomical data sets. With modern CT systems using multi-slice detectors and two X-ray tubes, data acquisition times of about 100 ms are possible for extended volume data sets with submillimetre resolution . UltrasoIn recent years, multimodal and hybrid imaging techniques have been improved and developed into the new frontier of medical molecular imaging with the possibility to overcome restrictions of single modalities and to acquire non-invasive physiological and pathophysiological measurements within an accurate anatomical framework. These advanced imaging methods can directly assess both function and morphology of the heart and vessels and have the capacity to redefine our understanding of cardiovascular disease, to improve the pathological understanding, to refine risk stratification and to select persons for targeted therapies. Moreover, studies using advanced imaging has the potential to improve our understanding of the cardiovascular mode of action of novel therapies. All these aspects are covered in the topic with up-to-date articles on studies in which modern imaging methods were used to elucidate relationships between diabetic conditions and cardiovascular effects.Chen et al. evaluates the utility of color M-mode derived aortic propagation velocity (APV) to recognizing alterations in the fetal vascular endothelial function. The APV was lower in fetuses from women with gestational diabetes and correlated with fetal endothelial function. Thus, this novel metric may represent a promising non-invasive and simple method to assess endothelial function in fetuses. This might identify initial alterations of vascular function, even in women with well-controlled gestational diabetes and the measurement of APV might be used in fetuses referred for a fetal echocardiography, to improve cardiovascular risk estimation, for better selection of high-risk individuals and for corresponding preventive interventions. Along similar lines, the work of Shabani et al. tested the hypothesis that soft tissue calcification could be triggered by prolonged hyperglycaemia. For this purpose, costal cartilage calcification in non-contrast CT images of 2305 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) was correlated with prior fasting blood glucose levels in a sex-dependent manner. The hypothesis was only confirmed in women regardless of coronary artery calcium score. Further validation of the potential role for APV and costal cartilage calcification for risk stratification is needed, including studies in larger prospective cohorts with follow-up data.Two papers were within the frame of novel methods aimed for better risk stratification. The work of Mavrogeni et al. provides an overview of common MRI questions regarding myocardium and vascular system in diabetic patients. Examples and the state-of-the-art MRI methods for anatomical and functional investigations in ischaemia, infarction and structural changes of the myocardium with fatty degeneration and fibrosis are presented. To further build upon this Research Topic, Seetharam et al. discuss the potential role of machine learning in the field of advanced cardiovascular imaging. The authors conclude that machine learning-driven algorithms will be inevitable, as they have the potential to significantly augment the workflow of the very large information content of the recorded data.The article by Petersen et al. ask the important question on how to facilitate the use of non-invasive cardiovascular imaging in clinical practice. The study compares the activity of non-invasive cardiovascular imaging in the US  and England . The imaging activity was three-times higher in the US compared to England. This highlights the importance of reimbursement as a main driver for the clinical application, central knowledge for the policy makers.Jensen et al. report on a patient study with 26 weeks of therapy with the glucagon-like peptide-1 receptor agonist liraglutide to investigate if this substance has a direct anti-inflammatory effect in the coronary arteries. The effect of this medication on the uptake of the novel radiotracer [64Cu]Cu-dotatate, which binds to somatostatin receptors, was investigated in the coronary arteries using hybrid PET/CT imaging. Liraglutide treatment caused a significant reduction in [64Cu]Cu-DOTATATE uptake in the coronary arteries whereas this was not seen in the placebo treated group. The difference in change in uptake between the two groups did however only reach borderline statistical significance.One paper applies advanced imaging to improve our understanding of the cardiovascular mode of action of a novel therapy. In this Research Topic, Laursen et al. aims to enhance our understanding of the development of cardiovascular disease using advanced imaging. The study investigates the relationship between baseline cardiovascular autonomic function and diabetic renal and myocardial sequelae over six years in 24 persons with type 2 diabetes and a group of healthy controls. The coronary function was measured using cardiac 82Rb PET/CT. Cardiac autonomic dysfunction at baseline was found associated with a larger decline in kidney function during six years of follow up, but not with changes in coronary function or atherosclerotic burden. The investigated population was however small and a considerable risk of selection- and survival bias was present. Thus, the results should be interpreted as exploratory and further studies in larger populations are warranted.The paper from All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.BJvS is employed at the company Novo Nordisk.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state. The ancient disease of rabies continues to spread unchecked in the free-roaming dog populations across much of the developing world. Whilst examples of elimination through mass dog vaccination stretch back a century , these mWhilst considerable progress has been made to increase accessibility to post-exposure prophylaxis in India , the conThe use of oral rabies vaccination (ORV) in dogs has been proposed for the past 30 years , and hasIn this review we consider aspects of mass dog vaccination and ORV pertinent to rabies control in India and present a risk analysis for a hypothetical campaign using the oral-bait-handout approach in Goa state, India.There are three commonly used parenteral vaccination strategies for mass dog vaccination: static point (SP), door-to-door (DDV) and capture-vaccinate-release (CVR) . The effSP vaccination involves vaccination teams establishing temporary dog vaccination clinics at which dogs are brought by dog owners for vaccination. This method has been used to great effect at a continental scale in Latin America where 50 million dogs were vaccinated during a single week every year ,15. HighWhilst the SP or DDV approaches are able to achieve high dog vaccination coverage in many endemic settings, they are unlikely to access sufficiently high proportions of the population in areas where a large number of dogs are difficult or impossible to restrain by hand for parenteral vaccination . TherefoThe issue of high CVR fixed operational costs can be somewhat offset by incorporating DDV as the primary method to efficiently vaccinate dogs readily available for restraint by hand, followed by CVR to access the inaccessible population ,20. ThisWhen it comes to stray dogs, concerns over rabies are generally superseded by other perceived issues caused by roaming dogs, including barking, road traffic accidents and hygiene . AlthougThe juxtaposition between the desire to control canine reproduction through surgical sterilization and the need for pan-societal annual dog vaccination to achieve rabies control has the potential to limit the impact of both. ORV would enable vaccination of difficult-to-catch dogs without the need to handle them, thus allowing for the intensive annual vaccination of stray populations without impacting the likelihood of being able to capture dogs for surgical sterilization later as a part of dog population management efforts.There are two types of ORV currently being used under commercial license for the vaccination of various wildlife species; these are modified live vaccines (MLVs)  and vector-based vaccines (VBVs) . The actAlmost all modified live rabies virus vaccines in use today are derived from a single rabies virus strain, named Street Alabama Dufferin (SAD), isolated by the CDC in the USA in 1935. This strain underwent extensive passaging through non-neural cell lines  and thermal stabilization to varying degrees to form a range of highly attenuated ORVs, including SAD-Bern, ERA and SAD-B19. This first generation of ORVs were the foundation of rabies control in Europe and remain the most widely used ORVs globally .The safety profile of first-generation ORVs was improved by inducing selection mutations using monoclonal antibodies, resulting in the creation of the second generation ORVs, including SAG1 and SAG2 . The devAttenuated live rabies virus vaccines rely on mutations to the rabies glycoprotein gene, which is a major contributor to viral pathogenicity through its role in viral uptake, budding and avoiding neuronal impairment ,32,33. TThe primary concern with using MLVs is the potential for reversion to virulence through natural random mutation of the virus, enabling the vaccine virus to regain its capacity to cause rabies . The comOrthopoxvirus genus) as the vector . Th. Th28]. pulation . After spulation ,50, the pulation ,52. Contpulation ,50. Overation [2 , equivalMephitis mephitis) and racoons (Procyon lotor) in many parts of North America [In contrast to the red fox rabies reservoir in Europe and Canada , enzooti America ,54. Diff America ,55,56. V America . Table 1ORVs are administered orally via a bait construct . The baiAs in wildlife species, the effective vaccination of dogs using ORV requires a bait construct designed to maximize uptake and release of the vaccine suspension in the oral cavity. Aspects of smell, taste, texture and size are all likely to play a role in palatability and inducing chewing to perforate the vaccine sachet. Baits which are too small and are swallowed without perforating the sachet will not be immunized. Numerous studies have performed to evaluate preference for different bait casing materials, including fishmeal, animal intestine, chicken head, egg and dog food based materials ,63,64,65The oral-bait-handout method has been described for the distribution of ORV in urban settings ,67. In tThe formal process of vaccine licensure requires a national regulatory authority to review the safety and efficacy of a product in target species, non-target species and humans. This is invariably an expensive and complex process, often requiring studies of ethical concern. The development of global human health initiatives in the 1970s required assurance of consistent standards of vaccine quality, safety and efficacy, however it was infeasible to seek licensure in every country of use . This chSuch mechanisms are yet to be developed for the veterinary vaccine sector, however there is broad consensus on the need for international scrutiny of ORVs to make the required evidence readily accessible to national regulatory authorities for decisions of ORV implementation . The CDCOff-label use of vaccines is common, even for large scale national immunization initiatives, where safety and efficacy has been demonstrated, but licensure has not been completed . TherefoMany ORVs have undergone the stringent process of licensure for use in wildlife in North America and Europe. Such authorization through national regulatory agencies such as US Department of Agriculture Center for Veterinary Biologics or the European Medicines Agency include comprehensive assessment of human safety in the context of distribution in areas proximal to human habitats. The CDC developed a Markov chain model to evaluate the human safety of environmental distribution of ORV for vaccination of dogs . SimulatTo evaluate the human safety of a hypothetical dog vaccination campaign in India, we applied the model using local parameters from Goa State. The simulated campaign consisted of the distribution of 40,000 baits of SPBN GASGAS over a 12-day period in urban cities and towns as well as rural villages. The full report of this analysis is provided in the We performed two analytical methods: the first being a standard analysis, using predicted parameters based on local data sources and published literature, and the second, a sensitivity analysis, using Latin Hypercube sampling from the distribution of each possible parameter values . For botThe standard analysis estimated that a mean of 32,006 dogs would be vaccinated and that no dogs or non-target animals would get vaccine-induced rabies. A mean of 5.1 human exposures were estimated , resulting in 4.0 extra health care visits , but no serious adverse events (SAE) of human deaths during the campaign , as well as no human deaths when extrapolated per 10 million baits distributed . In all Simulations from the sensitivity analysis predicted a mean of 27,919 dogs and 201 non-target animals would be vaccinated and no dogs or non-target animals would develop vaccine-induced rabies. The model predicted a mean of 4.9 human exposures resulting in 3.4 extra health care visits, no SAEs, and no human deaths. Values from the standard analysis are expected to be more accurate than the simulated outputs from the sensitivity analysis due to the use of predicted parameters based on available data . NeverthIt is likely that ORV will be required to complement parenteral dog vaccination campaigns in both rural and urban settings. The simulation analysis predicted low rates of human exposure through the hand-out method in such areas; however vaccine safety remains of paramount importance especially due to the close dog–human relationship in India.The prediction of no severe adverse events and no human deaths per 10 million SPBN GASGAS bait distributions reflects the robust safety profile of this 3rd generation MLV. SPBN GASGAS resulted from site-directed mutations to the SAD-B19 vaccine strain, altering all three nucleotides at amino acid positions 194 and 333 of the glycoprotein gene, reducing the likelihood of natural random mutation resulting in a reversion to virulence. The insertion of a second identical modified glycoprotein gene further enhances the safety profile of the vaccine over first and second generation MLVs. The attenuating effect of the insertion of additional genes is believed to be due to the reduced expression in downstream genes, which subsequently decrease the rate of replication of the virus in vitro and in vivo, as opposed to dominance of the non-pathogenic glycoprotein gene ,137,138.SPBN GASGAS has been shown to effectively generate an immune response in dogs comparable to parenteral vaccination, with regards to rabies virus neutralizing (RFFIT) and binding (ELISA) antibodies . The higSPBN GASGAS has been shown not to be shed in the environment for prolonged periods following the vaccination of an animal. The virus does not continue to replicate in the vaccinated animal and so there is an insignificant risk of onward transmission to other non-target animals or people and no risk of circulation of the virus in the environment . The vacRabitec®, the trade name for SPBN GASGAS, is currently licensed for use in foxes and raccoon dogs in the European Union , and undOral rabies vaccination of dogs has been shown to improve the coverage of mass vaccination efforts in situations where dogs cannot be readily restrained or caught for parenteral vaccination. The long-standing and increasing support for the implementation of pilot field activities using modern ORVs from the WHO, OIE and other international experts provides reassurance to national authorities in their assessment of the suitability of these products. With the highest estimated incidence of human and canine rabies globally and a free-roaming dog population of tens of millions of dogs, India requires an efficient and effective operational solution to the mass vaccination of dogs that cannot be readily handled. Whilst the benefits of parenteral vaccination make it crucial for the vaccination of the accessible dog population, complementary use of ORV has the potential to enable the rapid scaling of high-coverage campaigns reaching the free-roaming reservoir population.Based on our experience with mass dog vaccination in numerous states of India, including Goa, Tamil Nadu, Karnataka, Jharkhand, West Bengal and Maharashtra, the benefit of ORV as a complementary tool to parenteral vaccination methods to hasten the control of canine rabies is clear. Oral rabies vaccine is a strong tool that India is missing while striving to reach the Zero by 30 target to eliminate dog-mediated human rabies by 2030.


Culicoides imicola, the main competent vector of Bluetongue virus (BTV) in sheep in Tunisia. Fifty-three records covering the whole distribution range of C.imicola in Tunisia were obtained during a 2-year field entomological survey (August 2017 – January 2018 and August 2018 – January 2019). The ecological niche of C. imicola is described using ecological-niche factor analysis (ENFA) and Mahalanobis distances factor analysis (MADIFA). An environmental suitability map (ESM) was developed by MaxEnt software to map the optimal habitat under the current climate background. The MaxEnt model was highly accurate with a statistically significant area under curve (AUC) value of 0.941. The location of the potential distribution of C. imicola is predicted in specified regions of Tunisia. Our findings can be applied in various ways such as surveillance and control program of BTV in Tunisia.The increasing threat of vector-borne diseases (VBDs) represents a great challenge to those who manage public and animal health. Determining the spatial distribution of arthropod vector species is an essential step in studying the risk of transmission of a vector-borne pathogen (VBP) and in estimating risk levels of VBD. Risk maps allow better targeting surveillance and help in designing control measures. We aimed to study the geographical distribution of  Culicoides (Diptera: Ceratopogonidae). Between 1999 and 2002, BTV serotype 2 epizootics have occurred in Tunisia  pose a major threat to human and animal health. Despite considerable success in controlling communicable diseases, VBDs have caused and still cause damage on different continents. Bluetongue (BT), an emerging and re-emerging VBD, is caused by double-stranded ribonucleic acid (RNA) orbiviruses of the Reoviridae family. Bluetongue virus (BTV) infects domestic and wild ruminants and it is transmitted by biting midges of the genus  Hammami .Determining the spatial distribution of arthropod vector species is an essential step in studying the risk of transmission of a vector-borne pathogen (VBP) and in estimating the level of risk. Geospatial technologies are commonly used to evaluate vector patterns or human or animal case distributions and to estimate the risk of disease transmission based on entomological, epidemiological and environmental factors. Diverse modelling methods have been developed and are commonly used to predict the geographic range of a species given presence-only (PO) occurrence data and environmental variables assumed to influence its distribution  approach to model C. imicola presence and mapping habitat suitability (HS) -light traps manufactured by the Onderstepoort Veterinary Institute . Insects were collected in a beaker containing 200 millilitres (mL) – 250 mL of water and 3–4 drops of detergent, as a wetting agent. Each catch was transported to the laboratory, then covered and preserved in 70% ethanol for further study. Culicoides imicola were identified according to wing patterns, using stereoscopic microscope and taxonomic keys and subsequently confirmed by mounting specimens on microscope slides  and averaged over a 50 year period between 1950 and 2000 at the same spatial resolution. First WorldClim data files are converted to Esri ASCII format in DIVA-GIS (http://www.diva-gis.org) and trimmed in the region of Tunisia. The final step was to convert the trimmed grid files to the ESRI ASCII format. The files are then ready to be used in R-Studio and in MaxEnt software.To determine which environmental variables most influence the distribution of ur model . The selur model . The bioC. imicola and the availability of habitats  because it has been shown to perform better with small sample sizes compared with other modelling methods  were eliminated from further models  and an overall specialisation of s = 2.663, which means that we found C. imicola in a small range of conditions. If we observe the marginality coefficients of every eco-geographical variable  and first specialisation axis (y-axis). Marginality was strong as the dot representing the centroid of the distribution of used units shifted from the origin of the axes, the centroid of the distribution of available weights. The polygons correspond to the minimum convex polygons of the distributions of available (light grey area) and used (dark grey area) resource units. The polygon of the used habitat  was narrow in its extent on the y-axis meaning that specialisation was also high. The direction and length of the arrows are a metric of the contribution of the variables to marginality and specialisation.The ecological-niche factor analysis results displayed by the marginality axis  .During this procedure, variables that did not contribute to the ecological niche or highly correlated variables (with a coefficient of correlation higher than 0.95), were not used in the statistical analyses in MaxEnt.The reduction of predictor variables resulted in the inclusion of only height variables for MaxEnt model. C. imicola probability distribution in Tunisia provided satisfactory results, with an AUC value of 0.941 (±0.001), which is higher than 0.5 of a random model  (61%), followed by Mean Temperature of Warmest Quarter (Bio10) and the Annual Precipitation (Bio12). The cumulative contribution of these three factors is 86%. During the warmer months (June–September), the precipitation was the most influential factor determining the distribution of C. imicola in Tunisia. Field observations indicate that the population of C. imicola peaks in the September–October period and it seems that the summer rainfall has a direct impact on this population. This is in accordance with the observations from Sghaier et al. . The fact that mean rainfall was negatively associated with C. imicola abundances could confirm that rainfall can inhibit the activity of some Culicoides imicola species as shown by Murray . This variable is negatively correlated to species occurrence. High temperatures combined with elevated dryness  are fatal for Culicoides species. In general, temperature is known to influence greatly the development and survival of all stages of the life cycle of Culicoides species  and farming practices. It is assumed that crop irrigation practice is a supporting factor for isia OIE . The effC. imicola is most likely linked to its preference for breeding in areas where soil is moist and nutrient-rich and with full exposure to sunlight, characteristics, which are more commonly found in the centre and coastal areas of Tunisia. This hypothesis should be further investigated.The high abundance of C. imicola in Tunisia. The map presented here can be used to determine areas where the vector can be found. This would facilitate the implementation of control and surveillance programmes by Tunisian veterinary authorities. It is important to note that the high abundance of C. imicola in some regions of Tunisia underlines the real risk of spreading a new disease. Thus, it is important to improve our understanding of climatic factors in C. imicola activity influencing its distribution and seasonal pattern. Further studies are needed to continue the monitoring of other potential vectors in an attempt to limit the potential incursion and spread of the disease in other regions of Tunisia. We expect this approach to be promising in predicting the potential distribution of other arthropod vectors and can be an effective tool to assess and visualise the risk of the establishment and spread of VBD.We present here the potential ecological niche for


Eudyptes robustus) and Fiordland penguins (Eudyptes pachyrhynchus), closely related species breeding between 100–350 km apart whose migration phenology differs by two months. Using light geolocation tracking, we examined the degree of overlap given the observed allochrony and a hypothetical scenario where the species commence migration simultaneously. We found that Fiordland penguins migrated to the Sub-Antarctic Frontal Zone and Polar Frontal Zone in the austral autumn whereas Snares penguins disperse westwards staying north of the Sub-Tropical Front in the austral winter. Our results suggest that allochrony is likely to be at the root of segregation because the relative profitability of the different water masses that the penguins forage in changes seasonally which results in the two species utilising different areas over their core non-breeding periods. Furthermore, allochrony reduces relatively higher levels of spatiotemporal overlap during the departure and arrival periods, when the close proximity of the two species’ colonies would cause the birds to congregate in similar areas, resulting in high interspecific competition just before the breeding season. Available evidence from other studies suggests that the shift in phenology between these species has arisen from adaptive radiation and phenological matching to the seasonality of local resource availability during the breeding season and reduced competitive overlap over the non-breeding season is likely to be an incidental outcome.Mechanisms promoting coexistence between closely related species are fundamental for maintaining species diversity. Mechanisms of niche differentiation include allochrony which offsets the peak timing of resource utilisation between species. Many studies focus on spatial and temporal niche partitioning during the breeding season, few have investigated the role allochrony plays in influencing interspecific segregation of foraging distribution and ecology between congeneric species during the non-breeding season. We investigated the non-breeding migrations of Snares ( A key problem in ecological theory is understanding how species diversity arises and how it is maintained over time , 2. The Morphologically similar species that share an area provide a useful model for understanding mechanisms that allow coexistence. According to the theory of phylogenetic niche conservatism, closely related species are expected to be similar in terms of their ecological niches  but whenSpatial segregation involves using similar resources at similar times in different locations. Temporal segregation includes allochrony, which offsets the peak timing of resource utilisation between sympatric species  that feeMarine predators, such as seabirds, face different constraints during the breeding and non-breeding seasons. Most seabirds breed in colonies and foraging is confined to a restricted radius around this central place owing to the need to return to the nest to care for offspring, which may lead to high intra- and interspecific competition between individuals and species , 21. OncEudyptes occupy broadly similar ecological niches, feeding primarily on swarming crustaceans and myctophid fish [Eudyptes chrysolophus) and Eastern rockhopper penguins (Eudyptes chrysocome filholi) at Marion Island [Eudyptes schlegeli) and Eastern rockhopper penguins at Macquarie Island [Eudyptes penguins are therefore good models to study niche partitioning and coexistence in relation to allochrony.Penguins of the genus hid fish  within thid fish . Severaln Island , Royal pe Island , and Eree Island . Additioe Island –31. EudyEudyptes penguins endemic to the New Zealand region, Snares penguins (Eudyptes robustus) and Fiordland penguins/tawaki (Eudyptes pachyrhynchus). These two species have diverged recently and are still morphologically very similar [In this study we investigated two  similar  and breeEudyptes penguin species, the post-moult non-breeding period of Snares penguins occurs during the austral winter, whereas that of Fiordland penguins starts two months earlier, with the majority of their post-moult non-breeding period taking place in the austral autumn [Snares and Fiordland penguins both have stable population trends and are similar in many life history traits but show a marked difference in the timing of their annual cycles. As is typical of most l autumn , 34. Seal autumn , 22 whicWe studied the post-moult migrations of Snares and Fiordland penguins to determine the relative importance of spatial and temporal niche partitioning of their non-breeding distribution. Our aims were to: (1) quantify spatial and temporal overlap during the post-moult migrations under the observed level of allochrony and (2) examine how segregation patterns change in a scenario where both species initiate their non-breeding migrations simultaneously. We use these comparisons to infer the relative importance of differences in habitat selection and allochrony in separating the distributions of the non-breeding seasons of the two species.Tagging work at Snares Island was conducted under permit issued by the New Zealand Department of Conservation (Wildlife Act Authority 35682-FAU) and was approved by the animal ethics committee at the National Institute of Water and Atmospheric Research in New Zealand. Tagging work of Fiordland penguins was conducted under permit issued by the New Zealand Department of Conservation (permit number RES-38882) and was approved by the animal ethics committee at the University of Otago in New Zealand (AEC-04/14). The duration of handling times of all penguins lasted less than 10 minutes and all field team members involved were experienced and minimised stress to the animals during tag deployment and retrieval.Eudyptes penguins finish their breeding season, they go on a pre-moult trip which lasts between four to eight weeks. They return ashore to perform what is known as a catastrophic moult, when they moult all their feathers at once. The moult takes places over three to four weeks during which the penguins have no waterproofing and cannot go to sea. Once the birds have moulted, they embark on their post-moult migration and will not return ashore again until the following breeding season.The differences in the phenology of the two species are consistent through time and an accepted aspect of their natural history , 34. MigAround half of the pre-moult trip of Snares penguins overlaps with the first part of the post-moult migration of Fiordland penguins. We could therefore expect some overlap between them during these periods as both species are likely to be near their colonies. Unfortunately, we do not have pre-moult data for Snares penguins and so could not include this in our study. The post-moult migrations are the focus of this study and will be referred as the non-breeding season .Fieldwork on Snares penguins was conducted on North-East Island  in April 2013 and on Fiordland penguins at Jackson Head , Harrison Cove  and Codfish Island  in September 2017. Devices were deployed on Snares penguins at the end of the moult in April and retrieved when the penguins returned to breed the following September, thus only spanning the non-breeding period. For Fiordland penguins, devices were deployed at the beginning of the breeding season in August and were left on the birds for a year. While tags were deployed at the end of 2017, the data spanning the non-breeding season the following year (2018) was used.Eudyptes penguins from the same colonies have consistent migration routes and foraging habitats during their non-breeding season across multiple years [Sampling occurred in different years. If changes in oceanography over time alter the distributions of the species among years, it would compromise our comparisons of spatio-temporal overlap. However, we expect that the changes in distribution within species across years will be smaller than the differences between species within years. This is because we know that other le years –37. Furtle years , 39. Finvs dry state: e.g. Mattern et al. [Geolocation devices were deployed on 52 Fiordland penguins and 44 Snares penguins . These devices recorded light level, time, sea temperature and activity by means of salt-water immersion . Birds n et al. , 34. Forn et al. . The devSGAT and BAStag [BAStag, which automatically detects when the threshold is crossed and allows the user to adjust times to account for obvious shading events. Thereafter, location estimates are provided based on times of twilights inferred from the light data and three priors. The first prior is a gamma distribution of penguin swimming speeds to restrict the distances between consecutive locations. The second prior was a beta distribution of errors of the estimated times of twilight. The third prior was a Gaussian distribution of water temperatures recorded by the tag which was used to constrain potential locations by comparison to remotely sensed sea surface temperature (SST) obtained from The National Oceanic and Atmospheric Administration (https://psl.noaa.gov). This is useful for constraining latitude during the equinoxes, when daylength is uniform across the globe. This third prior was not included in the analysis of the Snares penguin data because a fault in the temperature chip in their batch of tags meant no SST data were collected. This had little impact on the quality of the tracks as the migration period of the species does not overlap with the solar equinoxes. Latitude is calculated from day length and longitude is calculated from the time of midday and midnight relative to Coordinated Universal Time. So, the latitude estimation of positions for the Snares tracks from light alone was sufficiently accurate without SST priors.The tag data were processed using the R packages d BAStag , 43. We We calculated two sets of location outputs: one corresponding to the mean location at the time instant of each twilight  and anotSGAT, using all intermediate location estimates across all individuals and chains and then binned these full posterior distribution estimates into percentiles to represent the core and the peripheral areas of use of the animals. To produce the distribution estimate that represented the 50% utilisation distribution (UD), we split the full posterior distribution estimates by the 50th percentile. We then enclosed this top 50th percentile of data with a polygon to produce an isopleth that encompassed the area where 50% of the distribution estimates were located. The same was done for the 90th percentile to produce the 90% UD. In this way, we preserved all location estimates per location for each point in between the fixed twilights. For ease of reference, these will be referred to as the 50% UD and the 90% UD. The data for the mainland and Codfish Island colonies of the Fiordland penguins were pooled for the purposes of this study as the UDs were sufficiently similar .The proportion of locations found within the distinct inter-Oceanic frontal zones was calculated using the full range of posterior location outputs for the full migration and dynamic sea surface height extracted from the Copernicus Marine Environment Monitoring Service (marine.copernicus.eu). To determine the usage of the seas in terms of different frontal zones, we calculated the proportion of locations within each of the frontal zones as a percentage of the full posterior distribution locations within the 90% UD. The locations of the fronts were calculated by using the southern extents of the fronts defined by sea surface height contours following Venables et al. . The souWe used the mean coordinates for each twilight (rather than the full posterior of intermediate locations) for calculation of trip metrics. As penguins do not come ashore over the duration of their non-breeding season, we considered the birds to have departed the colony once the activity data registered 24 hours of being fully immersed  and similarly, they were considered to have returned to their breeding colony once the activity data registered 24 hrs of being dry . The furthest distance from the colony and the cumulative distance travelled during the non-breeding season were calculated using the great circle route. We related trip metrics to species and sex using GLMs with model selection by Akaike’s information criterion (AICc).Eudyptes studies [To distinguish periods of increased time spent per sector from periods of intense travelling, we calculated mean monthly speed anomalies. Monthly time periods were used to be comparable with other  studies , 48 as wi.e. the number of putative locations in a pixel), the higher the relative importance of that pixel for that species. We plotted the monthly 50% and 90% UDs (using the percentile method described above).To visualise the degree of spatial separation due to allochrony, we simulated a scenario in which allochrony was absent by delaying the departure date of Fiordland penguins by two months to give the same median departure dates as Snares penguins. This method provides a mechanism to disentangle the degree to which allochrony and space use separate the observed migration distributions. Monthly usage maps were produced using the posterior estimates, by summing all possible locations within a month, among all the individuals for each species. This allowed us to produce estimated usage maps incorporating all the information from the estimation process. The greater the usage of an area by multiple animals within a species . We used utilisation distribution overlapping statistics for the two scenarios (observed and synchronous) across the number of weeks that spanned the non-breeding periods (30 weeks for the observed migrations and 22 weeks for the synchronous migrations); and calculated the area under the curve (AUC) for each. To make the periods of time comparable we converted the weeks to a percentage of the relative migration time. Utilisation distribution overlapping statistics (as a measure between 0- no overlap- and 1- full overlap: y-axis) were plotted against the relative migration time (x-axis). The differences in the AUC provides an index of the reduction in overlap that arises from allochrony . This waOf the 52 devices deployed on Fiordland penguins 28 (54%) were recovered, compared to 34 of the 44 devices (77%) for Snares penguins. Snares penguins breed in large colonies of up to 1,300 nests, whereas Fiordland penguins breed singly or in small groups in dense forest, making recovering devices from birds far more difficult for the latter. The number of devices that had sufficient data to fully estimate locations for the complete non-breeding season was 27 for both Snares and Fiordland penguins (13 for the mainland and 14 for Codfish Island). The poor performance of the Snares tags was due to a manufacturing defect that caused premature battery expiry.Both Snares penguins and Fiordland penguins showed consistent, directed migrations of similar extents to the west of New Zealand in oceanic waters with depths of over 3,500 m . HoweverThe water mass north of the Sub-Tropical Front and three inter-frontal zones were used by the two species within the 90% UDs. Snares penguins were located mainly North of the STF (77.5%), returning to their breeding colony via the SAFZ (15.3%) and PFZ 7.01%; . The perEudyptes penguins, females from both species returned ashore after males, which is reflected in the females accumulating longer swimming distances over the non-breeding season than males.Both species were at sea for approximately four and a half months . Broadly, trip characteristics were similar in terms of their duration and the cumulative distances travelled, with expected marked differences in the timing of migration Tables . Unexpec-1 and 0.63 ± 0.4 m.s-1 for Fiordland penguins and Snares penguins, respectively while those during the resident period were 0.46 ± 0.1 m.s-1 and 0.45 ± 0.2 m.s-1, respectively. Speeds were significantly lower during the resident period compared to the migratory period for Fiordland penguins , but not for Snares penguins .Fiordland penguins had the slowest speeds during the months of April and May, and Snares penguins during the months of June and July . These aThe Fiordland penguins move rapidly at the start of their migration so that when the Snares penguins set out in April, there is very little overlap in their distributions . There cWhen quantifying the spatial overlap across the migration, there is no overlap for the first 30% of the migration  and broad-billed prions (P. vittata) from Gough Island that show a high spatial overlap between migration distributions in the absence of allochrony [Procellariidae that also exhibit both allochrony and low spatial overlap in non-breeding distributions. Quillfeldt et al. [Allochrony usually evolves between species that breed in sympatry and show high character displacement, as in the case of MacGillivray’s prions  [Nyctiphanes australis [Eudyptes penguins elsewhere show that pelagic zooplankton account for >84% of their diets [Euphausia lucens, E. vallentini, as well as Thysanoessa gregaria, Primno macropa, Themisto gaudichaudii [E. similis var. armata, E. spinifera and Thysanoessa gregaria [Snares and Fiordland penguins are likely using different frontal zones to exploit different prey communities. During the breeding season Fiordland penguins feed primarily on fish and Arrow squid ( sloani)  and Snarustralis  that areir diets . Composiir diets . The SAFichaudii , the samichaudii . Communigregaria , 63 whicSpheniscidae, this has also been found true for the Common guillemot  as well, a seabird with high wing-loading and similar pursuit diving to penguins [Eudyptes penguins, and not two months, as only one species secures the benefit of arriving in the absence of the other.Penguins experience two periods of hyperphagia (or persistent feeding): before the catastrophic moult  and before the breeding season starts. Penguins fast for three to four weeks ashore throughout the moult . At the penguins . This repenguins . Regardlpenguins . Our finEudyptes chrysocome) breeding in these two areas into the Southern and Northern rockhopper species [Eudyptes penguins and so, to reduce competition between closely related competitors, we could expect a shift in phenology which could result in a winter breeding niche. Southern and Northern rockhopper penguins, like Snares and Fiordland penguins, have distinct mitochondrial DNA and also show marked allochrony. However, Northern rockhopper penguins have evolved to breed in late winter/early spring, 8 weeks before Southern rockhoppers in the absence of competition from other diving seabird species [An alternative explanation for allochrony arising due to competition , is that species  roughly  species . Summer  species . Compara species .There is considerable evidence that seabird behaviour and performance are driven largely by food availability . As SnarReproductive isolation would have evolved between the penguins breeding on Snares Island, south of New Zealand, and the New Zealand mainland coast of Southwestland via philopatry and allochrony as the birds shifted their phenology to match different timing of local prey availability. Due to this, it is less likely that Fiordland penguins adopted earlier breeding because of interspecific competition with Snares penguins driving temporal niche partitioning. It may simply be that foraging and/or breeding conditions are better for them in early spring , and allNiche switching has been hypothesised to be a derived trait compared to niche conservatism which is considered the primitive state  in the eS1 FigFront locations were broadly similar across years.(DOCX)Click here for additional data file.S2 Figa) Fiordland penguins and b) Snares penguins tracked over the non-breeding migrations from February 2018 to July 2018 and April 2013 to September 2013 respectively. Within a species, most birds dispersed in the same direction, except for one female Fiordland penguin from Codfish Island/Whenua Hou, which spent the entire winter period on the Campbell Plateau, and one Snares penguin which returned via the Bass Strait.(DOCX)Click here for additional data file.S3 Figa) Fiordland penguins and b) Snares penguins tracked over the non-breeding migrations from February 2018 to July 2018 and April 2013 to September 2013, respectively. The areas of green denote grid cells of high usage by the penguins.(DOCX)Click here for additional data file.S4 FigThe Southwestland Fiordland penguins are represented by the blue 50% (darker polygon) and 90% (lighter polygon) utilisation distributions (UDs). The Fiordland penguins that bred on Codfish Island are represented by the green 50% (darker polygon) and 90% (lighter polygon) UDs. The third map shows that the UDs are sufficiently similar for the data to be pooled for the purposes of this study. This data was collected February 2018 to July 2018.(DOCX)Click here for additional data file.


Objective: Our paper aims to report an unusual case of phacogenic uveitis with secondary glaucoma occurring after spontaneous rupture of the lens capsule in a patient with hypermature age-related cataract, to describe its particularities and to review the classification of the lens-induced uveitis.Methods: We described the case of an 83-year-old male with a history of hypermature cataract, who presented to our clinic for right eye pain. Examination revealed circumciliary congestion, diffuse corneal edema, lens debris floating in the anterior chamber, pseudohypopyon and the opacification of the whole lens. An elevated intraocular pressure was also associated. We did not observe any history of previous intraocular surgery or trauma.Results: We diagnosed the case as a phacogenic uveitis with secondary glaucoma and we planned to remove the inflammation trigger, namely the lens and its fragments by the most adequate technique, in order to control the inflammation and the IOP spikes, to alleviate the pain and to improve the patient’s visual function and the quality of life. Conclusions: Phacogenic uveitis may present a cloudy cornea and a turbid anterior chamber that mimics endophthalmitis. Careful examination, medical history and ancillary investigations are helpful in establishing an accurate diagnosis and the appropriate treatment can reduce or eliminate the inflammation completely, decrease the intraocular pressure, being able to allow, depending on the particularities of the case, the visual gain.  Currently, cataract surgery is performed earlier than before due to the progress of technology and better outreach programs, so complications of hypermature cataracts are rare. However, we still meet Morgagnian cataract and its complications in some parts of the developing countries of the world. The lens can become a source of intraocular inflammation through surgical or traumatic rupture of the capsule or by leakage of lens proteins through an intact capsule.This case report described a case of phacoanaphylactic uveitis presenting as diffuse corneal haze and raised intraocular pressure with turbid fluid in the anterior chamber due to a spontaneous rupture in the anterior lens capsule. Fig. 1) and mature cataract in the left eye . He was supposed to undergo a cataract extraction in the left eye first, and then in the right eye, according to his demands.An 83-year-old Caucasian male, farmer, presented to our Department of Ophthalmology with complaints of sudden onset pain and redness in his right eye. The patient did not offer any history of ocular trauma or previous ocular surgery. He had no relevant family history or ophthalmological afflictions. He was not taking any topical or systemic medication. The patient had been known to our clinic for 3 months when he was diagnosed with hypermature cataract in the right eye  with the presence of suspended white particles in the anterior chamber and in the pupillary area .At the clinical examination, visual acuity was light perception in the right eye and counting fingers in the left one. Intraocular pressure was 50 mmHg GAT in the right eye and 13 mmHg GAT in the left eye. Slit lamp biomicroscopy in the right eye revealed circumciliary congestion, diffuse corneal edema, pseudohypopyon, the opacification of the whole lens .The ultrasonography for both eyes revealed no pathological changes except for a hyper-reflective band between the middle and posterior third of the vitreous in the right eye, probably due to the detached posterior hyaloid . The differential diagnosis included causes of other lens-induced glaucoma, as well as other causes of hypopyon. Acute infectious endophthalmitis, toxic anterior segment syndrome (TASS), and flare-up of pre-existing uveitis were also taken into consideration . The goal of immediate treatment was to reduce inflammation and the IOP spikes, for which systemic ocular hypotensive therapy  was administrated. We also initiated the combined regimen of topical steroids and topical antiglaucoma drugs . The cataract extraction was delayed for 2 days until moderate control of inflammation and intraocular pressure allowed the procedure to be safe. The patient subsequently underwent manual extracapsular cataract extraction. The surgery was performed under local anesthesia with peribulbar block and consisted of: aspiration of the lenticular matter from the anterior chamber, mechanical pupil dilation using iris-hooks, staining the anterior capsule by Trypan Blue dye, evidence of the area of the spontaneously ruptured anterior capsule, aspiration of the cortical matter, gentle hydrodissection and manual extracapsular extraction of the opaque lens, irrigation and aspiration of the residual cortical lens matter, removal of the fibrotic material with a 23-gauge curved scissor, removal of the iris hooks, corneal suturing and reformation of the anterior chamber by BSS and sterile air .Over the next month, the anterior chamber inflammation gradually resolved and the patient achieved a best-corrected visual acuity of 20/ 40  and an IOP of 17 mmHg  represents a relatively rare disease  and can occur after spontaneous rupture of the capsule in case of hypermature age-related cataract, or in other situations such as rupture of the anterior lens capsule following trauma [6-8]. The term “phacolytic” uveitis or “phacolytic” glaucoma is used when the capsule is macroscopically intact, but there is a leakage of lens proteins that causes a non-granulomatous inflammatory reaction .Nowadays, LIU can be classified based on the integrity of the capsule. When the capsule is ruptured, the terms phacogenic or phacoanaphylactic uveitis are used [10].Phacotoxic uveitis or phacogenic non-granulomatous uveitis represents a chronic intraocular inflammation related to lens proteins after rupture of the lens capsule [Lens-induced glaucoma is a secondary glaucoma in which the lens is involved in the mechanism of increased intraocular pressure. The glaucoma can occur in open-angle or angle-closure forms.11-13].Lens induced glaucoma can be subdivided into two major categories. In the first category, the anterior flow of aqueous humor is blocked due to the lens. This category includes phacomorphic glaucoma (pupillary block glaucoma caused by an intumescent cataractous lens) and ectopia lentis (lens dislocation). The second category is characterized by the blocking of the trabecular network by lens proteins (phacolytic glaucoma), lens material or debris or by phacoanaphylactic response to the lens material [14].Pupillary block glaucoma is characterized by the obstruction of the aqueous outflow by the apposition of the iris root to the trabecular meshwork. A senile cataractous lens that has progressed enough to become intumescent, has an increased anteroposterior length, and can cause pupillary block. The iridolenticular apposition interrupts the normal flow of aqueous humor from the anterior chamber to the posterior chamber. This leads to an accumulation of aqueous humor in the posterior chamber, pushing the iris root forward, eventually leading to an angle closure [11].Phacoanaphylactic glaucoma occurs in the setting of a ruptured lens capsule and is characterized by a granulomatous antigenic reaction to lens protein that leaks from the capsule after trauma or is retained as lens fragments after intraocular surgery .The eye is considered a privileged immune organ. The lens is isolated from the fetal circulation early in the embryonic life, being devoid of vascularization and innervation. Nowadays, lens-induced uveitis is recognized as an autoimmune disease resulting from an abnormal recognition of lens proteins as non-self. The immunopathogenesis of lens-induced uveitis is the result of self-sensitization to the lens proteins. After rupture of the capsule and sensitization of the lens proteins, an inflammatory reaction is formed either granulomatous or non-granulomatous and involves a hypersensitivity reaction  [18].In most of the cases, LIU remains a challenging diagnosis. In order to obtain the right diagnosis, the clinicians should perform needle biopsy and histopathology. Aqueous humor cytology can be helpful in elucidating the correct diagnosis. Cytopathological examination may reveal a zonal granulomatous inflammatory reaction, with polymorphonuclear leukocytes surrounding a nidus of damaged or retained material lens . When it is available, scanning electron microscopy can detect a possible rupture of the anterior lens capsule [14-18].An important part of the diagnosis is to determine the status of the lens capsule, whether it is intact or disrupted . In order to control the inflammation and the IOP spikes, intra- or extra-capsular cataract extraction must be performed. Among the intraoperative complications that may occur in these patients are: posterior capsular rent, zonular dehiscence, vitreous loss, etc. Phacoemulsification can be difficult to perform, given the lax zonules and the hard lens due to the hypermature cataract. Under these conditions, a better choice may be manual ECCE or a small incision cataract surgery [21-23]. Irvine was the first to support the idea of extracapsular surgery in 1957, affirming that this technique could prevent forward movement of the vitreous and therefore loss of the vitreous [8-10]. In a study performed in India, Singh et al. have shown that ECCE with PC IOL implantation is a safe and effective method of visual rehabilitation in cases of LIU. With a follow-up period of two years, all patients maintained a normal postoperative intraocular pressure of less than 20 mmHg without any additional medical therapy [22]. The efficacy of manual small incision cataract surgery was demonstrated in a study conducted by Venkatesh et al. on 33 patients who showed that this may be a safe and effective method of cataract extraction for patients with phacolytic glaucoma [23].Lens-induced uveitis represents an emergency condition that needs cataract extraction without delay. It is imperative to control intraocular pressure with medical therapy before surgery to prevent possible complications such as suprachoroidal effusions or hemorrhage and expulsive hemorrhage due to sudden decompression of the globe [Cataract surgery is the definitive treatment of phacogenic uveitis. Trabeculectomy may lower the intraocular pressure but it does not remove the inciting agent of the increased intraocular pressure, namely the cataract itself. There is increased risk of expulsive hemorrhage and/ or choroidal effusion with elevated perioperative intraocular pressures. Therefore, lowering the IOP to physiologic range is indicated pre-operatively with topical and oral agents.Conflict of Interest statementThe authors state no conflict of interest.Informed Consent and Human and Animal Rights statementInformed consent has been obtained from all individuals included in this study.Authorization for the use of human subjectsEthical approval: The research related to human use complies with all the relevant national regulations, institutional policies, is in accordance with the tenets of the Helsinki Declaration, and has been approved by the review board of “Prof. Dr. Agrippa Ionescu” Clinical Emergency Hospital, Bucharest, Romania.AcknowledgementsNot applicable.Sources of FundingNone of the authors has any financial or proprietary interests to disclose.DisclosuresNone.


Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic. Breast cancer is the most prevalent malignancy and the foremost cause of cancer-related death in women worldwide . DespiteBone metastases not only considerably reduce the OS but also the health-related quality of life due to pain, fatigue, and skeletal-related events (SREs) ,9,10. SeIn this review, we provide an overview of the biological models and the molecular heterogeneity that characterizes bone metastasis in breast cancer. Emphasis is also placed on the currently available systemic therapies and bone-modifying agents through a broad overview of the main trials involving patients with breast cancer and bone metastasis, in order to highlight the current and future therapeutic implications.The metastatic process is defined as the dissemination of neoplastic cells from the primary neoplasm to secondary sites . Based uIn osteolytic lesions, osteoclast-mediated bone resorption is a key and early step . The intPatients with breast cancer metastatic to the bone require a multidisciplinary approach that should consider not only the clinical scenario but also the tumor specific biology ,70,71,72Bisphosphonates have a dual role in decreasing bone resorption by exerting an apoptotic effect on osteoclasts and increasing mineralization by inhibiting osteoclast activity . First-gThe RANK/RANKL interaction significantly affects the progression of the deleterious vicious cycle between circulating breast cancer cells and the bone microenvironment. Therapeutic approaches targeting these molecules mainly rely on denosumab, a fully human monoclonal anti-RANKL antibody. This drug inhibits the RANKL/RANK signaling-mediated bone resorption, suppressing bone turnover and leading to the reduction of SRE risk ,83. ClinAdditional therapeutic targets with potential clinical utility in the treatment of bone MBC are still under investigation. In this regard, odanacatib is an antagonist of cathepsin K, a protease produced by osteoclasts directly involved in bone resorption . AlthougAn improved understanding of the mechanisms that drive the metastatic dissemination of breast cancer to the bone and the development of therapy resistance are essential to concretely establish the most suitable clinical management strategies for these patients. Pathways leading to bone remodeling represent the ideal target for future translational and clinical research studies. These discoveries would lead to a possible improvement in the precision medicine approach in the treatment of breast cancer with bone metastasis, not only for patients’ survival but also for their health-related quality of life. Novel agents including bisphosphonates and denosumab may now be administered along with the traditional therapeutic regimens. Despite the positive results of these drugs in reducing the risk of SREs, no significant effect has been observed in terms of OS. Future research should focus on a deeper understanding of metastatic heterogeneity as well as on identifying key regulators of molecular signaling pathways, which might be potential therapeutic targets.


A 73-year-old Japanese woman visited our department complaining of a nodule on the scalp which had appeared four years previously. Physical examination revealed a 12-mm semi-pedunculated black nodule on the left side of the head . DermoscEccrine poroma is a benign adnexal tumor mainly composed of poroid cells and often present as a reddish nodule. While eccrine poroma does not appear to have a bias for occurrence between races, pigmented variants of eccrine poroma often develop in non-white races. Pigmented eccrine poroma have been reported especially from Japan, and according to a clinicopathological analysis in Japan, among the 421 cases with pathological diagnosis of poroid cell neoplasms, 114 cases (27.1%) had melanin pigment in the tumor cells.3As shown in the present case, pigmented eccrine poroma on the scalp can clinically mimic BCC. Previous studies have shown that pigmented eccrine poroma has dermoscopic findings of arborizing vessels and blue-gray ovoid nests, and pigmented eccrine poroma on the face was clinically similar to BCC.Minagawa and Koga found in their case series study that the most frequent dermoscopic structures in pigmented eccrine poromas were vascular structures such as arborizing vessels, hairpin vessels, and polymorphous vessels.None.Masato Ishikawa: Designed the study; performed the research and contributed to analysis and interpretation of data; wrote the initial draft of the manuscript; read and approved the final version of the manuscript.Mikio Ohtsuka: Performed the research and contributed to analysis and interpretation of data; read and approved the final version of the manuscript.Toshiyuki Yamamoto: Designed the study; assisted in the preparation of the manuscript; read and approved the final version of the manuscript.None declared.


To evaluate all available evidence on the prediction of rotational tooth movements with aligners.Seven databases of published and unpublished literature were searched up to 4 August 2020 for eligible studies.Studies were deemed eligible if they included evaluation of rotational tooth movement with any type of aligner, through the comparison of software-based and actually achieved data after patient treatment.Data extraction was done independently and in duplicate and risk of bias assessment was performed with the use of the QUADAS-2 tool. Random effects meta-analyses with effect sizes and their 95% confidence intervals (CIs) were performed and the quality of the evidence was assessed through GRADE.P < 0.001), although high levels of heterogeneity were identified . Contrary, mandibular incisors presented the highest percentage accuracy for predicted rotational movement . Risk of bias was unclear to low overall, while quality of the evidence ranged from low to moderate.Seven articles were included in the qualitative synthesis, of which three contributed to meta-analyses. Overall results revealed a non-accurate prediction of the outcome for the software-based data, irrespective of the use of attachments or interproximal enamel reduction (IPR). Maxillary canines demonstrated the lowest percentage accuracy for rotational tooth movement (three studies: effect size = 47.9%; 95% CI = 27.2–69.5; Allowing for all identified caveats, prediction of rotational tooth movements with aligner treatment does not appear accurate, especially for canines. Careful selection of patients and malocclusions for aligner treatment decisions remain challenging. The advent of aligner treatment in orthodontic clinical practice dates back to the late 1990s, with the introduction of two different set-up aligner systems, grounded on the level and amount of displacement to be achieved . InteresLately, there has been an increasing interest with regard to treatment outcomes related to aligner therapy , 2020b, Compromised treatment outcomes after use of aligners might be related to the inherent inability of the appliances to reach the amount of tooth movement anticipated at the beginning of the treatment, this being prescheduled through prediction models or company-driven prediction software . SpecifiIn view of the above, the aim of the present study was to review systematically the scientific evidence on the prediction potential of aligner software programs for rotational orthodontic tooth movements with the use of aligners. The null hypothesis was that there was no difference between predicted tooth movement and that achieved at the end of treatment.https://osf.io/cu4yz/) (The protocol was registered to the Open Science Framework (/cu4yz/) . The rep/cu4yz/)  and PRIS/cu4yz/) .Clinical (in vivo) studies referred to the predictability and accuracy of prediction of tooth movement. Eligible studies were observational designs, retrospective or prospective cohorts, and cross-sectional or case-control studies. In addition, randomised controlled trials were considered if these included a diagnostic accuracy section and at least one treatment group with aligners.There were no age or gender restrictions. Patients undergoing aligner orthodontic treatment were included. Any type of tooth with rotational movement plan was considered in maxillary and/or mandibular arch. Use of any adjuncts such as attachments or interproximal enamel reduction (IPR) strategies was also included.Index tests included virtual treatment plan and tooth movement, ClinCheck (Align Technology) for prediction of tooth movement and other prediction software models.Any study with achieved final orthodontic tooth movement (rotation), measured in casts , was included.Studies not reporting on specific diagnostic methods for accuracy of tooth movement prediction related to rotation and other than in vivo studies were excluded. Studies not reporting on rotational movements were also excluded.www.clinicaltrials.gov), the National Research Register . Keywords and MeSH terms included: ‘aligner’, ‘Invisalign’, ‘predicted tooth movement’ and ‘tooth rotation’. Search strategy for PubMed is presented in Initially, an electronic search of seven databases was conducted up to 4 August 2020. This was supplemented by a hand search of the included studies for additional relevant publications. The databases included the following: PubMed via Medline, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR). Unpublished literature was searched within Open Grey, the ClinicalTrials.gov  tool . Four doPatient selection: studies with a non-random or non-consecutive sample of patients, were judged as high risk of bias concerning the patient selection.Index test: when diagnostic methods were interpreted without knowledge of the results of the reference standard, the index test domain was classified as high risk.Reference standard: when reference standards were performed without knowledge of the index test results, the domain reference standard was classified as low risk of bias. Moreover, studies that did not report a reference standard were a priori excluded.Flow and timing: when the reference standard was not used on all patients, or if all samples were not included in the analysis, the flow and time domain was classified as high risk of bias. Furthermore, when a long period had elapsed between the index test and the reference standard, the flow and time domain was classified as high risk.Concerns about the applicability of the studies were determined as follows:Patient selection: studies implemented with the inclusion of only a small sample size (< 10 patients) were characterised as having a high concern regarding applicability.Index test: when the index test implementation was different from the review question, a high concern was documented for the specific study.Reference standard: studies assessing the validation of the target condition by cast analysis and reliability assessment received a score of low concern regarding applicability.A qualitative as well as a quantitative analysis of the study outcomes was performed.Quantitative syntheses of the studies’ findings were performed after exploring heterogeneity levels across individual reports. Random effects meta-analyses were conducted in view of the potential heterogeneity anticipated. Summary estimates for efficacy of prediction or prediction estimate with appropriate confidence bounds were presented for all applicable comparisons. The estimates were based on a percentage accuracy presentation based on ‘achieved’ against ‘predicted’ rotational tooth movement. Pooled estimates were ultimately presented if two or more studies were deemed eligible for a single comparison. Study authors were contacted for data request when information was missing within the published report.Meta-regression analytical techniques were performed for the assessment of the effect of tooth on the pooled estimate (Monte-Carlo permutation test). In addition, sensitivity analyses were planned, with the exclusion of high risk of bias studies from the syntheses, if both high and lower risk of bias studies were finally included, in order to isolate and explore the effect of high risk of bias studies. Publication bias was planned to be examined through standard funnel plots if more than 10 studies were included in the quantitative syntheses.The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the overall quality of the evidence stemming from the index/reference conditions and outcomes for evaluation . AccordiStudy selection process, breakdown and number of included articles in qualitative and quantitative synthesis are presented in Detailed characteristics of included studies are presented in Of the seven studies included in the review , three wThe overall risk of bias was rated as unclear in three out of seven studies , 2009 anP < 0.001) and lower canines exhibiting an accuracy of 49.9%  (P < 0.001) as well as mandibular premolars  appeared higher  . In contd higher .P = 0.04)  .Further sensitivity analyses were not implemented, and publication bias could not be assessed, due to the low number of studies included in the meta-analyses.The quality of the existing evidence for the percentage accuracy of rotational tooth movements, between predicted and achieved movement, was rated as low to moderate overall. This pertained to anterior teeth and premolars of both maxillary and mandibular arch. A large observed effect was the most common reason for upgrade. High heterogeneity levels, denoting inconsistency, contributed to downgrading the quality of the evidence . ApparenThe findings of this systematic review suggest an inaccurate prediction potential for rotational tooth movements through the use of the currently industry-available simulation programs; this might allow for speculations with regard to a diminished aligner efficacy for certain types of tooth movements. The null hypothesis was therefore rejected. Canine derotation strategies for prediction was the most afflicted type of tooth movement in terms of prediction accuracy and this finding was further supported through the meta-regression. The constraints with regard to rotational tooth movement with specific identification of canines, have been originally documented by the first clinical study in the field , 2009. CFollowing advancements in technology, the biomedical field has gained in knowledge for the benefit and safety of the patients; oral health and orthodontics are surely representative examples of technological applications to practice . AesthetResearch in the field of prognosis and accuracy of prediction of the desired tooth movement has resulted in a small but not insignificant group of primary studies, with the majority being conducted in the last 3–4 years . In-housIn this respect, a number of studies have been identified by the present systematic review and meta-analysis, all published within the last 12 years . PreviouThe efficacy potential of aligner treatment with regard to rotational movement increments of canines appear to lag behind to what is called a desirable effect, or to other tooth types and movements ; howeverStudies included in the quantitative synthesis of this review described no restriction in the use of attachment grips or performance of interproximal enamel reduction strategies, thus most likely representing a real-clinical practice scenario. Although various types/shapes of attachment grips or practices of interproximal enamel reduction have been reported as potential prognostic factors for better efficacy of rotational tooth movement, this does not necessarily translate into an identified substantial effect in practice. The early study by In addition, although the effect of the magnitude of rotational tooth movement could not be formally assessed due to the scarcity of the available evidence, sporadic reports identify an amount of rotation greater than 15° as a significant risk factor for decreased accuracy for rotational prediction; thus, potentially demonstrating a declining efficacy of the aligners to purely accomplish challenging treatment goals . It is nTo our knowledge, this is the first meta-analysis on the comparison of specific types of predicted and actually achieved tooth movements (sp. rotation), after aligner treatment. A comprehensive and up-to-date search strategy to identify all eligible articles within published and unpublished literature was conducted, while the most rigorous guidelines for reporting and risk of bias assessment have been considered. The protocol for this study was a priori registered, thus eliminating the risk of selective reporting .Nevertheless, specific caveats do exist. The generalisability of the study findings is limited at present with any implication made being linked only to rotational type of tooth movement and to certain tooth groups. However, the reported data represent the current state of the evidence with regard to one of the most challenging and most documented types of tooth movement with aligners. Quantitative syntheses were based on a small number of studies, while in some cases statistical heterogeneity was evident . This miAccording to available evidence on the comparison between software predicted and actual rotational tooth movement, the percentage accuracy was low for anterior teeth and premolars. The quality of the existing evidence did not substantiate strong confidence in the estimated and observed effect. Patients eligible for aligner treatment should be selected carefully and considerations of patients’ values and preferences should be prioritised. Efficacy of treatment outcome should be considered along with patient burnout and safety.Click here for additional data file.Supplemental material, sj-doc-1-joo-10.1177_14653125211027266 for Predictability of rotational tooth movement with orthodontic aligners comparing software-based and achieved data: A systematic review and meta-analysis of observational studies by Despina Koletsi, Anna Iliadi and Theodore Eliades in Journal of Orthodontics


Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide, which lacks effective inhibition of progression and metastasis in the advanced clinical stage. Mesoporous silica nanoparticle (MSN)–based cytotoxic or immunoregulatory drug–loading strategies have attracted widespread attention in the recent years. As a representative of mesoporous biomaterials, MSNs have good biological characteristics and immune activation potential and can cooperate with adjuvants against HCC. This review summarizes the possible future development of the field from the perspective of tumor immunity and aims to stimulate the exploration of the immune mechanism of MSN-based therapy. Through this point of view, we hope to develop new clinical immune drugs that can be applied to HCC clinical management in the future. Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer, which remains a great fatal health problem worldwide . Most HCMesoporous silica nanoparticles (MSNs) have been variously designed to explore the comprehensive tumor diagnosis and treatment due to their high biocompatibility and capability of drug loading in recent years . BenefitIn this article, the biological and immune effects of MSNs as a multifunctional carrier at the HCC tumor site are discussed, and the applications of MSN tumor vaccine with other physicochemical interventions such as photothermal and hydroxyl radical for immunotherapy are also involved. Such nano-based immune vaccines are verified to enhance the response of the immune system to HCC and allow the body to acquire long-term immunity against tumor recurrence . SpecifiInjectable MSN solutions are often modified by targeted molecules to increase the chance of endocytosis by tumor cells or macrophages at tumor sites . AlthougCompared to traditional drug delivery and release, immune cell uptake with antigen presenting and molecular interaction of MSNs may play an important role in the immune regulation of HCC TME. For example, regulatory T cells could be enriched with miRNA and growth factors released by MSNs, and such effect is often realized through the PI3K/Akt pathway . Due to + T lymphocytes (Regulating the state and distribution of immune cells are often the ultimate target mediated by MSN-loading strategies for tumor therapy. Immunogenic cancer cell death (ICD) induced by immunogenic chemo drugs in MSNs could amplify the activation and infiltration of CD8phocytes . It is vphocytes . In clinIn addition, modulating the phenotype and immune microenvironment of local tumor cells through small interfering RNAs is playing an increasingly frequent role. As similarly mentioned, siVEGF was used as a gene editing tool to modify the tumor microenvironment without affecting normal tissue . By idenDue to the large specific surface area of the mesoporous structure, MSNs can play a unique role in activating antigen presentation by innate immune cells. For example, MSN-packaged interleukin (IL)-13 in its extra-large-pore could directly activate the macrophages while playing a protective role . MSNs coBy interacting with antigen presenting cells, MSNs can reverse cellular expression and distribution of immune factors in the immunosuppressive tumor microenvironment (TME). The immuno-MSN was specifically designed for the delivery of cdGMP to activate the stimulator of the interferon gene (STING) for antigen-presenting cells (APCs) in TME . The immin situ strategies in in situ  have been used as a good photothermal reagent loading on MSNs due to their unique biocompatibility and tumor site aggregation effect . Such PTAs already mentioned in in situ therapy overcame the toxic effect of traditional systemic therapy on the normal organs and could be combined with angiogenesis and ICD drugs, which had great potential in the antigen presentation for MSN-based immunotherapy. Similar to the side effects of the cytotoxicity of conventional chemotherapy, the cytotoxic ROS produced by kinetic therapy on the immune system, in particular whether it stimulates HCC progression and metastasis, remains unknown. More studies are needed to understand whether the local killing effect of hydroxyl radicals is a long-term benefit or merely a temporary killer of tumors, and more importantly, what immunological agents need to be used in combination to enhance such long-term effects.In order to overcome the dependence of single chemokinetic therapy on substrates, photothermal and acoustic dynamic methods could also be used to enhance the efficacy and thus enhance the above local effects . And becDue to the lack of effective drugs other than sorafenib in the progression of HCC, many studies have focused on monoclonal antibodies in immunoagents considering their application prospects. Monoclonal antibodies against tumor immunity receptors, such as PD-1 and CTLA-4, have become the focus therapy of various tumors like HCC in recent years . Such a The main problems of antibody therapy contain off-target attack of cytotoxic T cells and adaptive desensitization of tumor cells. MSNs can provide a good platform for drug co-delivery of PD-1 and further enhance the sensitivity and specificity of antibodies through other synergistic therapies. For example, inducing the transcription of rRNA to trigger autophagy in tumor cells and disrupting the normal protein transcription and translation process, could be a good complement to immunotherapy . In addiThis mini-review attempts to state the relevant studies of MSNs in HCC immunotherapy, and its advantages are mainly reflected in drug delivery and synergistic multifunctional therapy. As a potential carrier of the tumor nano-vaccine and tumor antigen, MSNs need to be better designed to reduce toxicity and damage to normal tissues. In previous studies, MSNs have shown good efficacy in photothermal therapy, dynamic therapy, and monoclonal antibody therapy and have the potential to be used in combination with immunotherapy . These sAlthough MSNs have the potential to act as immune vectors, there are still some challenges in clinical transformation. First, clinical trials should prove that the basic drug research studies using several medicine are better than the present strategy like PD-1 or CAR-T. Second, both preparation and retention must be taken into account in adapting to diverse hybrid molecular combinations. Finally, stronger evidence of local and systemic immunological reactions is needed to support mechanisms of action in a range of combinatorial applications. As a relatively mature biological carrier, it is not difficult to solve these problems in the application of MSNs in immunity.Despite the lack of directly relevant evidence in some aspects of HCC immunotherapy, we try to describe the potential applications of MSNs in the aforementioned immune-related field by inducing other necessary studies as mentioned. MSNs may play a greater role in overcoming the side effects of immunotherapy and enhancing the sensitivity of tumor cells to immunotherapy. Most relevant researchers have not yet realized the double-sided characters of local nano-based killing of tumors. The key lies in how to make good use of the cytotoxic drugs carried by nanoparticles while avoiding the stimulation of tumor metastasis, which especially relies on the antigen-presenting cells and memory T lymphocytes. We look forward to more and better works in this area to help clinically manage patients with advanced HCC. At the same time, it may help explore the application of inorganic mesoporous nanoparticles in the field of tumor therapy.


In this study, a negative replica layer of leaf surface microstructures was used to cover the top surfaces of semitransparent thin-film luminescent solar concentrators (LSCs) to enhance the concentrators’ performance. With low reflection on the air–glass interface of the glass plate in a thin-film LSC, a negative replica layer enables the scattering of incident sunlight and increases the path of light transmitted into the LSC and the thin phosphor layer at the bottom surface of the LSC. The incident sunlight is therefore more likely to interact with the phosphor particles in the thin-film phosphor layer, thereby enhancing the performance of the LSC. In this study, semitransparent thin-film LSCs with different inorganic phosphors were examined. The experimental results revealed that the optical collection efficiency of semitransparent thin-film LSCs covered with negative replica layers of leaf surface microstructures was higher than that of the semitransparent thin-film LSCs without negative replica layers. Furthermore, the LSCs with negative replica layers with high haze ratios exhibited high optical collection efficiency. Integrating negative replica layers of leaf surface microstructures as semitransparent layers in thin-film LSCs may optimize the application of LSCs in building-integrated photovoltaics (BIPVs). Harvesting sunlight using photovoltaic (PV) technologies is one of the most promising solutions to the world’s energy demand problem. However, the implementation of such technologies has been impeded by competition between solar power generation and agricultural productivity due to the high number of new installations in the past few years. Building-integrated photovoltaics (BIPVs) are PV materials or systems that are integrated into building envelopes such as roofs, facades, and windows ,2,3. BecLuminescent solar concentrators (LSCs) consist of semitransparent plates containing or coated with luminescent materials, such as dyes or quantum dots, that have been designed for facile installation within other structures for BIPV applications. The luminescent material absorbs the incoming sunlight and re-emits it in longer wavelengths. A fraction of the re-emitted light undergoes total internal reflection and eventually reaches the edge of the semitransparent plate; this light is collected by the solar cells along the edges . LSCs arWhite light-emitting inorganic phosphors may be appropriate luminescent materials for LSCs used in BIPV systems. Because of their long lifetimes, photostability at high temperatures, excellent ultraviolet (UV) stability and chemical compatibility, low cost, and simplicity of use, inorganic phosphors are suitable for outdoor usage . HoweverIn this study, the effect of negative replica layers of leaf surface microstructures on the performance of semitransparent thin-film LSCs containing commercial phosphors was evaluated. PDMS was used to produce the thin layer with negative microstructures replicated directly from fresh plant leaves. To enhance the harvest of incident light, a thin layer with negative microstructures was fixed on the top surface of a semitransparent thin-film LSC, and the thin phosphor layer was then positioned on the bottom surface of the LSC, as illustrated in Bauhinia (orchid tree), Epipremnum aureum (centipede tongavine) and Pachira macrocarpa (lychee). These large leaves were selected according to their sizes (20–70 μm) and the distinct morphologies of their surface microstructures. To maintain their natural surface features and to avoid dehydration artefacts, the leaves were freshly picked just before each replication process [For the use of negative replica layers with leaf surface microstructures on semitransparent thin-film LSCs, the negative replica layer with a large size was certainly preferred for BIPV applications. Thus, the common large-leafed plants in north Taiwan were chosen in this study. At the meantime, the size and morphology of the surface microstructure were also important for the negative replica layers on semitransparent thin-film LSCs. Then three different large-leafed plants were selected for this study: ir sizes –70 μm an process ,22. The To realize the application of the negative replica layers of plant leaf microstructures in semitransparent thin-film LSCs, the LSCs were fabricated using commercial phosphors . Each LS2) conditions. A Keithley 2400 was used to determine the current–voltage curves of the PV cells attached to the LSCs with different negative replica layers of leaf surface microstructures.The excitation spectra, emission spectra, and quantum yields of the YAG4454-EL, RR6436, and LWR6931 phosphor powders were measured using a FluoroMax 4 spectrometer (Horiba) with an integrating sphere. Bauhinia leaf microstructures had the highest haze ratios, followed by those with Epipremnum aureum and Pachira macrocarpa leaf microstructures. When light irradiates the negative replica layers with leaf surface microstructures, the transmitted light is scattered by the microstructures before it penetrates the layers of the LSC, causing the transmitted illumination spot to be larger than the incident beam. Furthermore, negative replica layers with higher haze ratios produce larger illumination spots.Multiple reflections on each air/encapsulation interface considerably dissipate the energy transmitted to a solar cell system, thereby decreasing the efficiency of a PV module. A glass shield or encapsulation layer with surface microstructures can reduce reflection on the air/encapsulation interface of a module, thereby enhancing its optical efficiency ,16,17,18PV is the efficiency of the edge-mounted PV cell under the downshifted flux of the luminophore, ηopt is the optical collection efficiency, JSC is the short-circuit current density, VOC is the open-circuit voltage, FF is the fill factor, and Pin is the incident solar power density on the top surface of the LSC. Since the area receiving incident power is the front surface of the LSC, the measured short-circuit current density JSC should be divided by the area of the LSC front surface. In this study, the relative optical collection efficiency ηopt is used to measure LSC performance and is defined as follows:The power conversion efficiency (PCE) is one of the key performances for PV device. The overall PCE of the LSC system can be defined as :(1)ηLSC opt of the LSCs with the negative replica layers of Bauhinia, Epipremnum aureum, and Pachira macrocarpa as a function of YAG4454-EL phosphor concentration. The optical collection efficiency ηopt increases as the phosphor concentration increases. The high fractions of light re-emitted by the thin phosphor layers with high concentrations increase the light trapped within the LSCs, thereby increasing the optical collection efficiencies of the LSCs. At any given phosphor concentration, the optical collection efficiency of the LSC with the negative replica layer of Bauhinia leaf microstructures was higher than those of the LSCs with other negative replica layers. The LSC with a negative replica layer of Bauhinia leaf microstructures exhibited the greatest optical efficiency, followed by those with negative replica layers of Epipremnum aureum, and Pachira macrocarpa leaf microstructures and the LSC with the flat PDMS layer, in that order. When the negative replica layer of a plant leaf is placed on the top surface of a glass plate, the negative replica layer facilitates the scattering of incident sunlight and increases the path of light transmitted into the glass plate and thin phosphor layer at the bottom surface of the LSC. Thus, the incident sunlight has a greater probability of interacting with the phosphor particles in the thin phosphor layer, thereby increasing the light available to the LSC PV cell, as illustrated in Bauhinia, Epipremnum aureum, and Pachira macrocarpa. The negative replica layer of Bauhinia leaf microstructures had the highest haze ratio, followed by those of Epipremnum aureum, and Pachira macrocarpa leaf microstructures and the flat PDMS layer, in that order.opt of LSCs with negative replica layers on the top surface of the glass plate with different concentrations of RR6436 and LWR6931 phosphors, respectively. The characteristics of the semitransparent thin-film LSCs using inorganic phosphors RR6436 and LWR6931 were similar to those of the LSC using the YAG4454-EL phosphor. The optical collection efficiency ηopt of an LSC increases with phosphor concentration. At any given phosphor concentration, the optical collection efficiency of the LSC with the negative replica layer of Bauhinia leaf microstructures was higher than those of the LSCs with other negative replica layers. The LSC with a negative replica layer of Bauhinia leaf microstructures exhibited the greatest optical efficiency, followed by those with negative replica layers of Epipremnum aureum, and Pachira macrocarpa leaf microstructures and the LSC with the flat PDMS layer, in that order, which indicates that the use of negative replica layers of plant leaf can improve the optical collection efficiency of semitransparent thin-film LSCs regardless of the phosphor used in the thin phosphor films. However, the optical collection efficiency of the semitransparent thin-film LSC using LWR6931 was higher than those of the LSCs using RR6436 and YAG4454-EL because of the broad overlap of the LWR6931 absorption band and solar spectrum; greater overlap between the absorption band of the phosphor used in an LSC and the solar spectrum results in greater optical collection efficiency [ficiency .Bauhinia leaf microstructures was higher than those of the LSCs with negative replica layers of Epipremnum aureum, and Pachira macrocarpa leaf microstructures. This difference is attributable to the higher haze ratio of the negative replica layers of Bauhinia leaf microstructures relative to those of the other negative replica layers; a higher haze ratio results in higher optical collection efficiency. However, the optical collection efficiency of the semitransparent thin-film LSC using LWR6931 was higher than those of the LSCs using RR6436 and YAG4454-EL because of the broad overlap of the LWR6931 absorption band and solar spectrum. The greater overlap between the absorption band of the LWR6931 and the solar spectrum results in greater optical collection efficiency. This study elucidates the effects of negative replica layers of plant leaf microstructures on the behavior of semitransparent thin-film LSCs containing inorganic phosphor, and the results of the study may inform guidelines for the design of new semitransparent thin-film LSCs.In this study, the effects of different negative replica layers of plant leaf microstructures used on semitransparent thin-film LSCs containing inorganic phosphor were investigated. Negative replica layers of plant leaf surface microstructures can reduce the high reflection on the air/glass interfaces of the glass plates in semitransparent thin-film LSCs, thereby enhancing the optical collection efficiency of the LSCs. Furthermore, a negative replica layer of plant leaf microstructures placed at the top surface of the glass plate can facilitate the scattering of incident sunlight and increase the path of light transmitted into the glass plate and thin phosphor layer at the bottom surface of an LSC. Thus, the incident sunlight has a greater probability of interacting with the phosphor particles in the thin-film phosphor layer, thereby increasing the amount of light collected by the PV cell on the edge of glass plate. At any given phosphor and phosphor concentration, the optical collection efficiency of the semitransparent thin-film LSCs with negative replica layers of