Search Results (448)

Retinopathy of prematurity (ROP) has a dual-phase disease pathology; in phase 1, hyperoxia-induced vaso-obliteration occurs in the retinal vasculature due to increased oxidative stress (OS) and inflammation, followed by phase 2, where hypoxia increases the overproduction of growth factors, inducing retinal neovascularization. Toll-like receptor 2 and -4 (TLR2 and TLR4) overactivation, hyper-inflammation, macrophages, and neutrophil infiltration contribute to the developing ROP. AVR-121 and AVR-123 are novel classes of small-molecule dual inhibitors of TLR2/4 tested in a human leukemia monocytic cell line (THP-1) and cord-blood-derived mononuclear cells (CBMCs). Both compounds inhibited TLR2/4 signaling-related inflammatory cytokines in THP-1 cells and inhibited VEGF-induced neovascularization in human retinal endothelial cells (HRECs), which are hallmarks of ROP. In an oxygen-induced retinopathy (OIR) murine model, the intraperitoneal injection of AVR-123 in the hyperoxia phase (P7–P12) or a nanosuspension eyedrop of AVR-123 in the hypoxic phase (P12–P17) significantly reduced vaso-obliteration, angiogenesis, and inflammatory cytokine profiles while not inhibiting the necessary growth factor VEGF in the juvenile mouse eyes. The results are consistent with our hypothesis that targeting the dual TLR2/4 pathway will reduce inflammation, angiogenesis, and vaso-obliteration in vitro and in vivo and reduce cytotoxic immune cells. AVR-123 has the potential to be developed as a therapy for ROP. Full article

Accurate evaluation of retinopathy of prematurity (ROP) severity is vital for screening and proper treatment. Current deep-learning-based automated AI systems for assessing ROP severity do not follow clinical guidelines and are opaque. The aim of this study is to develop an interpretable AI system by mimicking the clinical screening process to determine ROP severity level. A total of 6100 RetCam Ⅲ wide-field digital retinal images were collected from Guangdong Women and Children Hospital at Panyu (PY) and Zhongshan Ophthalmic Center (ZOC). A total of 3330 images of 520 pediatric patients from PY were annotated to train an object detection model to detect lesion type and location. A total of 2770 images of 81 pediatric patients from ZOC were annotated for stage, zone, and the presence of plus disease. Integrating stage, zone, and the presence of plus disease according to clinical guidelines yields ROP severity such that an interpretable AI system was developed to provide the stage from the lesion type, the zone from the lesion location, and the presence of plus disease from a plus disease classification model. The ROP severity was calculated accordingly and compared with the assessment of a human expert. Our method achieved an area under the curve (AUC) of 0.95 (95% confidence interval [CI] 0.90–0.98) in assessing the severity level of ROP. Compared with clinical doctors, our method achieved the highest F1 score value of 0.76 in assessing the severity level of ROP. In conclusion, we developed an interpretable AI system for assessing the severity level of ROP that shows significant potential for use in clinical practice for ROP severity level screening. Full article

Retinopathy of prematurity (ROP) is a vascular disorder affecting the retinas of preterm infants. This condition arises when preterm infants in incubators are exposed to high oxygen levels, leading to oxidative stress, inflammatory responses, and a downregulation of vascular endothelial growth factors, which causes the loss of retinal microvascular capillaries. Upon returning to room air, the upregulation of vascular growth factors results in abnormal vascular growth of retinal endothelial cells. Without appropriate intervention, ROP can progress to blindness. The prevalence of ROP has risen, making it a significant cause of childhood blindness. Current treatments, such as laser therapy and various pharmacologic approaches, are limited by their potential for severe adverse effects. Therefore, a deeper understanding of ROP’s pathophysiology and the development of innovative treatments are imperative. Natural products from plants, fungi, bacteria, and marine organisms have shown promise in treating various diseases and have gained attention in ROP research due to their minimal side effects and wide-ranging beneficial properties. This review discusses the roles and mechanisms of natural products that hold potential as therapeutic agents in ROP management. Full article

Background/Objectives: Retinopathy of Prematurity (ROP) remains a leading cause of vision impairment in premature infants, especially those with Respiratory Distress Syndrome (RDS) necessitating respiratory support. This study aimed to identify correlations between plasma levels of Insulin-like Growth Factor 1 (IGF1) and Tumor Necrosis Factor-alpha (TNF-alpha), and the risk of developing ROP. Additionally, it explored the association of ROP severity grades with plasma levels of glucose, lactate dehydrogenase (LDH), creatin phosphokinase (CPK), and other biomarkers, aiming to uncover predictive markers for ROP risk and severity in this population. Methods: This prospective study included premature neonates admitted with RDS requiring respiratory support, conducted over 18 months at the Neonatal Intensive Care Unit of the Louis Turcanu Emergency Clinical Hospital for Children, Timisoara. Plasma levels of IGF1 and TNF-alpha were measured on days 1 and 14 post-birth, alongside the initial assessment of glucose, LDH, and CPK levels. Results: Significant correlations were observed between lower gestational age and elevated LDH levels on day 7–10 (rho = −0.341, p = 0.0123) and between TNF-alpha levels at 2 weeks and ROP severity (rho = 0.512, p = 0.0004). Elevated IGF1 levels were protective against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second, suggesting their potential as biomarkers for ROP risk assessment. Higher levels of TNF-alpha at 2 weeks were associated with an increased risk of ROP (Beta = −0.45, p = 0.0014), whereas higher IGF1 levels offered protective effects against ROP, with Beta coefficients of 0.37 (p = 0.0032) for the first collection and 0.32 (p = 0.0028) for the second. Elevated LDH levels on day 7–10 post-birth were linked to an increased risk of ROP (Beta = 0.29, p = 0.0214). Conclusions: These findings highlight the potential of IGF1 and TNF-alpha as predictive biomarkers for ROP, offering avenues for early intervention and improved management strategies in this high-risk group. Full article

Reduction–oxidation (redox) chemistry plays a vital role in human homeostasis. These reactions play critical roles in energy generation, as part of innate immunity, and in the generation of secondary messengers with various functions such as cell cycle progression or the release of neurotransmitters. Despite this cornerstone role, if left unchecked, the body can overproduce reactive oxygen species (ROS) or reactive nitrogen species (RNS). When these overwhelm endogenous antioxidant systems, oxidative stress (OS) occurs. In neonates, OS has been associated with retinopathy of prematurity (ROP), leukomalacia, and bronchopulmonary dysplasia (BPD). Given its broad spectrum of effects, research has started to examine whether OS plays a role in necrotizing enterocolitis (NEC). In this paper, we will discuss the basics of redox chemistry and how the human body keeps these in check. We will then discuss what happens when these go awry, focusing mostly on NEC in neonates. Full article

Background: Retinopathy of prematurity (ROP) is a significant cause of blindness in infants. Appropriate therapeutic intervention is essential because retinal detachment due to the progression of ROP is critical to visual function. The intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has been increasingly applied to inhibit the development and progression of ROP. In this study, we compared the efficacy of single intravitreal bevacizumab (IVB) and ranibizumab (IVR) injections for the treatment of ROP. Methods: A total of 39 eyes in 21 patients with severe ROP and IVB (15 eyes of 8 patients) and IVR (24 eyes of 13 patients) were retrospectively reviewed. Patient background, the severity of ROP, and the percentage of cases in which ROP regressed without additional treatment were compared between the two groups. Results: Patient background and ROP severity were not significantly different between the two groups. Recurrence was observed in one eye of one patient in the IVB group, and thirteen eyes in seven patients in the IVR group required additional laser photocoagulation, which was significantly different in the two groups (p < 0.01, Fisher’s exact test). In the IVR group, two eyes of two patients underwent vitreous surgery. Conclusion: Compared with IVR, IVB is likely to control the severity of ROP with a single treatment. Full article

Background: Premature children with retinopathy of prematurity (ROP) have been reported to an have increased risk of visual and neurocognitive impairments, yet little is known about whether vision could affect specific neurocognition. This study aimed to clarify the correlations between neurocognition and vision in premature children. Materials and Methods: This is a nonrandomized, cross-sectional, observational study in a pediatric cohort with five groups: (1) full-term (n = 25), (2) prematurity without ROP (n = 154), (3) prematurity with ROP but without treatment (n = 39), (4) prematurity with ROP and with bevacizumab (IVB) treatment (n = 62), and (5) prematurity with ROP and with laser/laser + IVB treatment (n = 20). Neurocognitive function was evaluated by the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) around the age of 4 years. Visual acuity (VA) and refractive errors were tested. Correlations between WPPSI parameters and visual outcomes were analyzed across five groups. Results: Among the 300 recruited children (mean age = 4.02 + 0.97 years, male = 56.3%), 297 were assessed by WPPSI-IV and 142 were assessed by vision tests. The Full-Scale Intelligence Quotient (FSIQ) index was worse in the premature groups. After adjusting for covariates, seven items, including FSIQ-Index (p = 0.047), fluid-reasoning index (p = 0.004), FR-percentile ranking (p = 0.008), object assembly (p = 0.034), picture concept (p = 0.034), zoo locations (p = 0.014) and bug search (p = 0.020), showed significant differences between groups. The better the best corrected VA (BCVA), the higher the scores on Verbal Comprehension Index (VCI), VCI-PR, and the subtest of information. Conclusions: Specific cognitive dysfunctions are related to the BCVA in this large cohort. Subtest performance profiles in WPPSI can be affected by prematurity, ROP treatment, and different ROP treatment. FSIQ is generally lower in premature children and even lower in children with ROP. Full article

Background: Fluorescein angiography (FA) has been a pivotal tool for studying the pathophysiology of retinopathy of prematurity (ROP) in vivo. We examined the course of ROP using FA to assess the predictive value of angiographic features. Methods: This is an observational retrospective cohort study of eyes screened for ROP with a binocular indirect ophthalmoscope and FA. RetCam fundus imaging and video digital fluorescein angiography were performed in the neonatal intensive care unit of Santa Maria Hospital of Perugia. The masked grading of the FA images was retrospectively conducted by two ROP expert ophthalmologists. Results: A total of 80 eyes of 40 patients were included for this study. Among the angiographic features evaluated, leakage, shunts, and tangles were predictive of the development of treatment-requiring ROP (p < 0.05). Conclusions: FA can add to our understanding of the evolution of vascular abnormalities in the course of ROP and can help predict which eyes will go on to treatment. Full article

The promoter of the RECEPTOR-LIKE CYTOPLASMIC KINASE VI_A2 (RLCK VI_A2) gene contains nine binding sites for the REPLUMLESS (RPL) transcription factor. In agreement, the expression of the kinase gene was strongly downregulated in the rpl-4 mutant. Comparing phenotypes of loss-of-function mutants, it was revealed that both genes are involved in stem growth, phyllotaxis, organization of the vascular tissues, and the replum, highlighting potential functional interactions. The expression of the RLCKVI_A2 gene from the constitutive 35S promoter could not complement the rpl-4 phenotypes but exhibited a dominant positive effect on stem growth and affected vascular differentiation and organization. The results also indicated that the number of vascular bundles is regulated independently from stem thickness. Although our study cannot demonstrate a direct link between the RPL and RLVKVI_A2 genes, it highlights the significance of the proper developmental regulation of the RLCKVI_A2 promoter for balanced stem development. Full article

Hypoxia-inducible factor (HIF) plays a crucial role in regulating oxygen sensing and adaptation at the cellular level, overseeing cellular oxygen homeostasis, erythrocyte production, angiogenesis, and mitochondrial metabolism. The hypoxia-sensitive HIF-1α subunit facilitates tissue adaptation to hypoxic conditions, including the stimulation of proangiogenic factors. Retinopathy of prematurity (ROP) is a proliferative vascular disease of the retina that poses a significant risk to prematurely born children. If untreated, ROP can lead to retinal detachment, severe visual impairment, and even blindness. The pathogenesis of ROP is not fully understood; however, reports suggest that premature birth leads to the exposure of immature ocular tissues to high levels of exogenous oxygen and hyperoxia, which increase the synthesis of reactive oxygen species and inhibit HIF expression. During the ischemic phase, HIF-1α expression is stimulated in the hypoxia-sensitive retina, causing an overproduction of proangiogenic factors and the development of pathological neovascularization. Given the significant role of HIF-1α in the development of ROP, considering it as a potential molecular target for therapeutic strategies appears justified. This review synthesizes information from the last six years (2018–2024) using databases such as PubMed, Google Scholar, and BASE, focusing on the role of HIF-1α in the pathogenesis of ROP and its potential as a target for new therapies. Full article

The combination of safety belts and rollover protective structures (ROPSs) is key in improving the safety of agricultural tractors in the event of rollover. However, we also have the opportunity to enhance the security provided by each ROPS; one such example is the combination of this safety device with adequate mechanical energy absorbers (MEAs). Inexpensive disc-shaped MEAs can be included in the anchoring points of a ROPS onto the chassis of a tractor. Three configurations of ROPS combined with MEAs were tested during the application of loads that simulated the effects of side rollover in the vehicle. The tested configurations included a blank MEA as a reference case alongside a single MEA and a stack assembly containing both elements. The results of the tests show that both the deformation of the ROPS itself and the strain energy are larger in the case of blank MEAs; thus, there is also a risk that the clearance zone will be infringed upon and that the protective structure will collapse. We can conclude that the implementation of an appropriate MEA in ROPS reduces the deformation of the ROPS itself and its strain energy in cases of vehicle rollover; hence, the safety provided by such protection systems may be improved at a low cost. Full article

We propose a novel reception scheme for twin single-sideband (twin-SSB) signals using just a single photodetector (PD), significantly reducing the system complexity and cost. To detect a twin-SSB with power-unbalanced quadrature-phase shift keying (QPSK) sidebands upon detection via a single PD at the receiver side, two QPSKs carried in two sidebands are coherently superposed and detected in a 16-ary quadrature amplitude modulation (16-QAM) format. This technique notably diminishes the linearity and effective number of bits required for the transmitter components in high-speed optical transmission systems. Moreover, a hierarchical blind-phase search (HBPS) algorithm is proposed to compensate for the imperfect phase rotation of QPSK signals during transmission. To demonstrate the effectiveness of our proposed method, we successfully conducted simulations of 112 Gb/s 16-QAM signal transmission over a 10 km standard single-mode fiber (SSMF), achieving bit error ratios (BERs) of $7.84\times {10}^{-4}$, well below the 7% hard-decision forward error correction (HD-FEC) threshold of $3.8\times {10}^{-3}$. In addition, the synthetic transmission scheme proposed in this paper is compared with the traditional 16-QAM signal transmission scheme, and the results show that the proposed scheme does not introduce a performance cost with the same received optical power (ROP) and transmission distance. Full article

Background: Large language models (LLMs) are becoming increasingly important as they are being used more frequently for providing medical information. Our aim is to evaluate the effectiveness of electronic artificial intelligence (AI) large language models (LLMs), such as ChatGPT-4, BingAI, and Gemini in responding to patient inquiries about retinopathy of prematurity (ROP). Methods: The answers of LLMs for fifty real-life patient inquiries were assessed using a 5-point Likert scale by three ophthalmologists. The models’ responses were also evaluated for reliability with the DISCERN instrument and the EQIP framework, and for readability using the Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), and Coleman-Liau Index. Results: ChatGPT-4 outperformed BingAI and Gemini, scoring the highest with 5 points in 90% (45 out of 50) and achieving ratings of “agreed” or “strongly agreed” in 98% (49 out of 50) of responses. It led in accuracy and reliability with DISCERN and EQIP scores of 63 and 72.2, respectively. BingAI followed with scores of 53 and 61.1, while Gemini was noted for the best readability (FRE score of 39.1) but lower reliability scores. Statistically significant performance differences were observed particularly in the screening, diagnosis, and treatment categories. Conclusion: ChatGPT-4 excelled in providing detailed and reliable responses to ROP-related queries, although its texts were more complex. All models delivered generally accurate information as per DISCERN and EQIP assessments. Full article

Measure while drilling (MWD) refers to the acquisition of real-time data associated with the drilling process, including information related to the geological characteristics encountered in hard-rock mining. The availability of large quantities of low-cost MWD data from blast holes compared to expensive and sparsely collected orebody knowledge (OBK) data from exploration drill holes make the former more desirable for characterizing pre-excavation subsurface conditions. Machine learning (ML) plays a critical role in the real-time or near-real-time analysis of MWD data to enable timely enhancement of OBK for operational purposes. Applications can be categorized into three areas, focused on the mechanical properties of the rock mass, the lithology of the rock, as well as, related to that, the estimation of the geochemical species in the rock mass. From a review of the open literature, the following can be concluded: (i) The most important MWD metrics are the rate of penetration (rop), torque (tor), weight on bit (wob), bit air pressure (bap), and drill rotation speed (rpm). (ii) Multilayer perceptron analysis has mostly been used, followed by Gaussian processes and other methods, mainly to identify rock types. (iii) Recent advances in deep learning methods designed to deal with unstructured data, such as borehole images and vibrational signals, have not yet been fully exploited, although this is an emerging trend. (iv) Significant recent developments in explainable artificial intelligence could also be used to better advantage in understanding the association between MWD metrics and the mechanical and geochemical structure and properties of drilled rock. Full article

Poly-3-hydroxybutyrate (P3HB) is a biodegradable polyester produced mainly by bacterial fermentation in an isotactic configuration. Its high crystallinity (about 70%) and brittle behavior have limited the process window and the application of this polymer in different sectors. Atactic poly-3-hydroxybutyrate (a-P3HB) is an amorphous polymer that can be synthesized chemically and blended with the isotactic P3HB to reduce its crystallinity and improve its processability Ring-opening polymerization (ROP) is the most cited synthesis route for this polymer in the literature. In this work, a new synthesis route of a-P3HB by self-polycondensation of racemic ethyl 3-hydroxybutyrate will be demonstrated. Different catalysts were tested regarding their effectiveness, and the reaction parameters were optimized using titanium isopropoxide as the catalyst. The resulting polymers were compared by self-polycondensation for their properties with those of a-P3HB obtained by the ROP and characterized by Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC), and the double bond content (DBC) was determined by UV–VIS spectroscopy by using 3-butenoic acid as a standard. Additionally, a life cycle analysis (LCA) of the new method of synthesizing has been carried out to assess the environmental impact of a-P3HB. Full article