Abstract Background: Medulloblastoma (MB) is the most common malignant pediatric brain tumor and a major cause of childhood cancer mortality. It comprises four molecular subgroups: WNT, SHH, Group 3, and Group 4. Group 3 MB, often marked by c-MYC amplification, has the worst prognosis. Despite surgery, radiation, and chemotherapy, high-risk patients face low 5-year survival and frequent relapse. Current treatments cause severe side effects. Cancer stem cells (CSCs) drive MB aggressiveness, therapy resistance, and recurrence. This project aims to uncover mechanisms sustaining CSCs and MB progression. Methods: MB cell lines (HD-MB03, D556, D425, DAOY) with ALKBH5 overexpression, knockdown (siRNA), or knockout (CRISPR), along with controls, were analyzed using viability, migration, invasion, colony formation, cell cycle, and apoptosis assays. RNA sequencing identified ALKBH5-regulated genes, validated by RT-qPCR, western blot, and RNA immunoprecipitation. An orthotopic intracranial xenograft model assessed ALKBH5’s tumor-promoting role in vivo. Results: To explore the role of m6A RNA methylation in medulloblastoma (MB), we silenced key regulators (writers: METTL3, METTL14; erasers: ALKBH5, FTO) in MB cell lines. ALKBH5 depletion caused the greatest reduction in proliferation, suggesting its therapeutic potential. Analysis of pediatric cancer datasets and tissue microarrays confirmed ALKBH5 overexpression and amplification in MB. Knockdown of ALKBH5 increased global m6A levels and reduced MB cell viability, migration, invasion, and stemness (medullosphere formation and NANOG, OCT4, SOX9 expression). Apoptosis assays showed elevated Annexin V-positive cells, and in vivo studies demonstrated suppressed tumor growth in orthotopic xenografts. ALKBH5 loss also increased DNA damage markers (γH2AX, 53BP1). RNA-seq and IPA revealed downregulation of genes involved in glycolysis, lipogenesis, and c-MYC targets, including ChREBP. Western blot confirmed decreased protein levels in these pathways. Conclusion: ALKBH5 is a critical regulator of MB tumorigenesis and CSC maintenance via m6A RNA demethylation. Targeting ALKBH5 may offer a promising therapeutic strategy to inhibit MB progression, overcome therapy resistance, and improve outcomes for high-risk MB patients. Citation Format: Panneerdoss Subbarayalu, Daisy Medina, Prabhakar Pitta Venkata, Shahad Abdulsahib, Saif Nirzhor, Santosh Timilsina, Deepika Singh, Phat Do, Desiree Denman, Krishna Priya Evani, Dhiya Billa, Meera Nair, Esha Reddy, Yogesh Gupta, Peter Houghton, Yidong Chen, Suryavathi Viswanadhapalli, Gangadhara R. Sareddy, Andrew Brenner, Ratna K. Vadlamudi, Manjeet Rao. Targeting ALKBH5 mediated ChREBP signaling impairs cancer stem cell metabolism and tumor growth in medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3492.
PURPOSE:To compare the deviation in cases of horizontal strabismus as assessed from photographs with the measurements as obtained in the strabismus clinic. METHODS:After obtaining informed consent, we recruited subjects with manifest horizontal strabismus. We took a frontal flash photograph from a distance of 50 cm using smart-phone-based cameras with the flash light vertically aligned with the lens. After projecting the photograph on a laptop and using a vernier caliper, we measured the horizontal corneal diameter of the non-strabismic eye and the decentration of reflex in the strabismic eye taking limbus as the reference point. We converted these values to degrees by using a conversion factor of 7.5°/mm and further to prism diopters (PD) by the standard mathematical formula 100*tanθ. RESULTS:We included 74 subjects aged between 5 and 40 years with manifest horizontal deviation from 20 to 85 PD. We found a statistically significant correlation of 82.6% (P value < 0.001) between the clinic and photographic measurements. Agreement analysis suggested that the photographic measurements measured on average 7 PD less (95% confidence interval: 4.6 to 9.2) than clinical measurements along all values of misalignment, although the difference between the two methods decreased as the quantum of deviation increased. Linear regression revealed an r2 of 68% and provided a predictive equation to derive clinic equivalent measurements from photographic estimates. CONCLUSION:We believe our simple method provides robust evidence that a photographic estimation can provide the basic information of the size of the deviation to plan possible surgeries, especially in situations of a tele-consultation. This is an easy approach to both understand and master and should form the armamentarium of most orthopticians and strabismologists.
Feature extraction is an important part of segmentation techniques applied to images. Extraction of various features mean identification of different attributes that characterize an image. This process is quite challenging because of the image resolution and its complexity. In this paper we are trying to detect the cancerous tissues from the liver organ where the extraction of tissue features further requires differentiating between the cancerous and non-cancerous tissue patches. It is important to identity texture features that best describe a healthy and an unhealthy tissue from the digital image. Also, it is necessary to include a good number of texture features for better classification. In this paper, two feature extraction techniques, namely Gray-Level Co-Occurance Matrix (GLCM) and Gray-level run-length matrix (GLRLM) are used for identifying the texture characteristics of tumor in liver organ. These techniques depend on the spatial distribution of intensity values or gray levels in the liver region. The extracted features are then classified using SVM classifier. The accuracy of the model is satisfactory and effective for tumor diagnosis and decision making process for treatment of tumor.
Purpose: To obtain epidemiological data on children with ocular morbidity attending a nodal district early intervention center (DEIC). Methods: After parental consent, we recruited children with ocular morbidity. After detailed history and clinical evaluation, along with pediatric consultation and relevant neuro-radiological and ancillary investigation, information was entered in a pretested proforma: especially looking for perinatal morbidity, including developmental delay (DD). Visual acuity (VA) was assessed by age-appropriate means by an ophthalmic assistant trained to work with children with special needs. We diligently looked for strabismus and performed dilated ophthalmoscopy. Using JASP, we summarized data as means and proportions and reported 95% CIs. We explored the association of disability percentage with possible predictor variables using regression. Results: We enrolled 320 children, with a mean age of 34.43 ± 31.35 months; two-thirds were male; one-third belonged to lower socioeconomic status (36%), with most parents being illiterate. The mean presenting VA was 1.8 logMAR for both eyes, range: 0 to 3. Sixty-one percent were hyperopic and 27% were myopic. High refractive error, (>±6D) occurred in nine; anisometropia in one; strabismus in 149, mostly esotropia; congenital cataract in 25, whereas 63 had abnormal fundus. Seventy-six received a diagnosis of cerebral visual impairment (CVI). On multivariate linear regression (MLR), younger age, presence of DD, and CVI significantly predicted a higher disability percentage. Logistic regression revealed that statutory disability is likely associated with DD (odds ratio [OR]:13.43); whereas older age was protective (OR: 0.977). Conclusion: Our study suggests that in DEIC children with ocular morbidity, younger children, and the presence of DD significantly predict both greater disability and the likelihood of statutory levels.
Purpose: Cycloplegic refraction is mandatory for children to know the eye's refractive status. In this study, we compared cycloplegia induced by cyclopentolate 1% to that induced by atropine 1% by means of retinoscopy. Methods: In this parallel-designed interventional study, we included 67 children aged between 4 and 17 years. After the initial retinoscopy under cyclopentolate 1% (used twice in each eye), we repeated it a week later under atropine ointment 1% (used twice a day for 3 days); both were done by the same trained optometrist masked to the drug. Each eye's refraction was converted to spherical equivalents (SEs), and the values averaged between the two eyes of each child under each drug. We compared SE with paired t -test (JASP 16.4). In addition, we performed correlational analysis, and looked for agreement using the Bland–Altman plot. Significance was set at P < 0.05. Wherever possible, 95% confidence intervals (CIs) are quoted. Results: The mean SE with atropine was +1.93 ± 2.0 D, compared to +1.75 ± 1.95 D under cyclopentolate. On average, atropine induced greater cycloplegia by a mere 0.18 D (95% CI: 0.07 to 0.29 D, P value 0.002). The two cycloplegic refractions correlated significantly (Pearson's r : 0.975, P < 0.001). The Bland–Altman plot revealed the limits of agreement as 1.06 and −0.71 D. Conclusion: Our study suggests that cyclopentolate works for the most part as well as atropine to attain cycloplegia. Atropine may be considered for children less than 15 years of age with greater than 5.0 D of hyperopia. Cycloplentolate, with its advantages of quick action and short duration, should form the first go-to topical cycloplegic in busy outpatient clinics.
Underwater images undergo quality degradation issues of an image, like blur image, poor contrast, non-uniform illumination etc. Therefore, to process these degraded images, image processing come into existence. In this paper, two important image processing methods namely Image restoration and Image enhancement are compared. This paper also discusses the quality measures parameters of image processing which will be helpful to see clear images.
Supplementary Figure from M6A RNA Methylation Regulates Histone Ubiquitination to Support Cancer Growth and Progression
Underwater image processing is the key research of the last decade. Due to attenuation and scattering of light into beneath of ocean, it is impossible to find capture image. Therefore image processing keeps into picture. To automate process and find relevant information, there is a need of good quality image. There are many of the applications, where need of processed image due to unclear of original images. In the artificial intelligence the image processing is also one of the important research domains. The machine learning (ML), deep learning (DL) approaches based image processing like image enhancement, denoising, encryption, fusion etc. are emerging trend of the research. Under-water imagery is an important carrier and presentation of under-water information, which plays a vital role in the exploration, exploitation and utilization of marine resources. This paper studied about under-water image restoration and enhancement based on machine and deep learning algorithms, it also suggest an approach to restore and enhance image.
Abstract Osteosarcoma is the most common malignancy of the bone, yet the survival for patients with osteosarcoma is virtually unchanged over the past 30 years. This is principally because development of new therapies is hampered by a lack of recurrent mutations that can be targeted in osteosarcoma. Here, we report that epigenetic changes via mRNA methylation holds great promise to better understand the mechanisms of osteosarcoma growth and to develop targeted therapeutics. In patients with osteosarcoma, the RNA demethylase ALKBH5 was amplified and higher expression correlated with copy-number changes. ALKBH5 was critical for promoting osteosarcoma growth and metastasis, yet it was dispensable for normal cell survival. Methyl RNA immunoprecipitation sequencing analysis and functional studies showed that ALKBH5 mediates its protumorigenic function by regulating m6A levels of histone deubiquitinase USP22 and the ubiquitin ligase RNF40. ALKBH5-mediated m6A deficiency in osteosarcoma led to increased expression of USP22 and RNF40 that resulted in inhibition of histone H2A monoubiquitination and induction of key protumorigenic genes, consequently driving unchecked cell-cycle progression, incessant replication, and DNA repair. RNF40, which is historically known to ubiquitinate H2B, inhibited H2A ubiquitination in cancer by interacting with and affecting the stability of DDB1-CUL4–based ubiquitin E3 ligase complex. Taken together, this study directly links increased activity of ALKBH5 with dysregulation of USP22/RNF40 and histone ubiquitination in cancers. More broadly, these results suggest that m6A RNA methylation works in concert with other epigenetic mechanisms to control cancer growth. Significance: RNA demethylase ALKBH5 upregulates USP22 and RNF40 to inhibit histone H2A ubiquitination and induces expression of key replication and DNA repair–associated genes, driving osteosarcoma progression.
ATLAS (Antimicrobial Testing Leadership and Surveillance) detects trends in multi-drug resistance longitudinally over time. In the present study, the in vitro activity of ceftazidime-avibactam and comparators was analyzed against Escherichia coli (n = 458) and Klebsiella pneumoniae (n = 455) isolates obtained from 9 centers across India. The overall susceptibility to ceftazidime-avibactam was observed to be 72% among K. pneumoniae isolates and 87% among E. coli isolates. Among the tested carbapenem resistant isolates, 51% of CR-K. pneumoniae and 24% of CR-E. coli were susceptible to ceftazidime- avibactam. OXA-48 like was identified in 52% of the K. pneumoniae isolates followed by co-production of NDM with OXA-48 like in 27%. NDM was predominantly identified in 68% of the E. coli isolates followed by OXA-48 like in 24% isolates. The findings suggest that ceftazidime- avibactam is a reasonable alternative to standard therapy for management of carbapenem resistant Enterobacterales infections particularly with K. pneumoniae and E. coli with the OXA-48 like genotype.
Under-water picture enhancement has received much attention in under-water vision research. Under-water picture suffers from serious color distortion and low contrast problems because of complex light propagation in the ocean. However, raw under-water pictures easily suffer from underexposure, and fuzz caused by the under-water scene. Many of the research are going on to recover this under-water blurred image. Artificial intelligence based machine learning (ML) and deep learning (DL) techniques are optimizing better restoration rather than the conventional approaches. This paper presents an artificial intelligence based techniques for underwater image restoration and enhancement.
The effect of soil-structure interaction (SSI) on the seismic responses of multi-storey buildings is investigated. The execution of SSI effects is conducted in two ways viz. Winkler approach and soil continuum approach. Time-history analysis methods are used for the seismic evaluation of parameters like time period, modal mass participation, base shear, lateral displacement, storey drift and inter-storey drift ratio. The present study consists of two parts; one is fixed base analysis i.e. without SSI, and the other is flexible base analysis i.e. with SSI. The buildings are modelled using finite element-based software SAP2000, where the equilibrium equations are solved by Hilber-Hughes-Taylor (HHT) method. A parametric study is performed with existing ground motion and varying numbers of stories to inherit the above parameters' responses. The results obtained from flexible base conditions are compared to those corresponding to fixed base conditions. The study shows that the behaviour of the structure changes under the SSI conditions and it may become vital in some cases; however, ambiguity also subsists with SSI.
Image Restoration is a significant phase to process images for their enhancement. Underwater photographs are subject to quality issues such as blurry photos, poor contrast, uneven lighting, etc. Image processing is crucial in the processing of these degraded images. This research introduced an ensemble-based classifier based on the bagging approach to enhance UW images. The support vector machine and random forest classifiers serve as the ensemble classifier's main classifiers. Additionally, to complement the feature optimization technique, the proposed ensemble classifier leverages particle swarm optimization. The feature selection method for the classifier is improved by the feature optimization process. To validate results, underwater images are collected by the Kaggle repository. In this process, Extreme Learning (EL) and Convolution Neural Network (CNN) are compared with suggested algorithms. The simulation results indicate that the proposed algorithm outperformed the existing work.
Purpose: To evaluate the Canon CP-TX1 camera as a screening tool for ARFs in a pediatric population and estimate the prevalence of ARFs. Methods: In a pediatric outpatient space, largely in the immunization clinic, after obtaining parental consent, we encouraged children to be photographed from a distance of 5 feet in a dim room by using a CP-TX1 camera with the red-eye reduction feature off. Based on the captured red reflex, children were labeled as normal (symmetrical red reflexes in the two eyes, with no visible crescents); all others were considered as abnormal or positive for ARFs. All photographed children were assessed by an optometrist/refractionist for VA by age-appropriate methods. Data were entered into a 2 × 2 contingency table on statpages.org, and diagnostic indices were calculated with 95%CI. Results: With a sample of 262 children, we obtained a sensitivity of 0.82, a specificity of 0.98, a positive predictive value of 0.92, a negative predictive value of 0.94, a positive likelihood ratio of 41.06, a negative likelihood ratio of 0.17, and a prevalence of 0.24 for ARFs. Conclusion: CP-TX1 performed well as a screening tool to identify ARFs in children. Placing such a camera in an immunization clinic offers a chance to identify children with ARFs at a time when amblyopia is eminently reversible.
Background:Candida auris has emerged globally as a multi-drug resistant yeast and is commonly associated with nosocomial outbreaks in ICUs. Methods: We conducted a retrospective observational multicentre study to determine the epidemiology of C. auris infections, its management strategies, patient outcomes, and infection prevention and control practices across 10 centres from five countries. Results: Significant risk factors for C. auris infection include the age group of 61–70 years (39%), recent history of ICU admission (63%), diabetes (63%), renal failure (52%), presence of CVC (91%) and previous history of antibiotic treatment (96%). C. auris was commonly isolated from blood (76%). Echinocandins were the most sensitive drugs. Most common antifungals used for treatment were caspofungin (40%), anidulafungin (28%) and micafungin (15%). The median duration of treatment was 20 days. Source removal was conductedin 74% patients. All-cause crude mortality rate after 30 days was 37%. Antifungal therapy was associated with a reduction in mortality (OR:0.27) and so was source removal (OR:0.74). Contact isolation precautions were followed in 87% patients. Conclusions:C. auris infection carries a high risk for associated mortality. The organism is mainly resistant to most azoles and even amphotericin-B. Targeted antifungal therapy, mainly an echinocandin, and source control are the prominent therapeutic approaches.
We have investigated the problem of underwater hazy image enhancement and restoration in this paper studied. Underwater image processing has several applications in the field of oceanic research work and scientific applications such as archaeology, geology, underwater environmental assessment, laying of long distance gas pipelines and communication links across the continents which demand geo-referential surveying of the oceanic bed and prospection of ancient shipwreck. There are many difficulties for undersea optical imaging. To submerging a camera in underwater enough space is required. The maneuvering of the camera with the help from remote place or in person at the site is likewise a complex task. However, the major challenge is imposed by underwater medium properties. Underwater haze image enhancement has gained widespread importance with the rapid development of modern imaging equipment. Though, the contrast enhancement of single underwater hazy image is a cumbersome task for scientific exploration and computational application. At extreme depth, because of attenuation in light propagation, the underwater images are susceptible to inferior visibility.
AIM: The aim of this study is to study the prevalence, incidence, and the epidemiological characteristics of the patients of acquired dacryocystitis at a tertiary eye care center of Northern India. MATERIALS AND METHODS: It was a prospective, cross-sectional study carried out over a period of 2 years (July 2016–July 2018). The prevalence, incidence, and the epidemiological characteristics of acquired dacryocystitis were studied and analyzed. Chi-square test was used to test the qualitative distribution. RESULTS: A total of 212 cases were included in the study. The prevalence rate of dacryocystitis was 19.5 cases per 10,000 patients, and the incidence rate was 15 cases per 10,000 patients. Chronic dacryocystitis (183; 86.30%) was more commonly encountered clinical type than acute dacryocystitis. Majority of cases (204; 96.23%) were due to the primary acquired nasolacrimal duct (NLD) obstruction, whereas eight cases (3.78%) were due to the secondary acquired NLD obstruction. Females were more commonly affected (156; 73.58%). The mean age was 44.44 ± 18.95 (range: 12–86) years. Majority of the patients 108 (50.94%) belonged to 3rd–6th decades of life. The disease was more prevalent in people belonging to lower-middle socioeconomic class (92; 43.40%) living in rural areas (130; 61.32%) and the majority of them were housewives (125; 59%). CONCLUSIONS: The incidence and prevalence of acquired dacryocystitis were 15 and 19.5 cases per 10,000 patients. It was much more common in females of lower socioeconomic status and is seen commonly in the 3rd to 6th decades of life.
Image segmentation is the most crucial part in image processing techniques. Numerous segmentation techniques are used to segment digital images into smaller regions called segments, consisting of sets of pixels in order to analyze important information from the images. Segmentation simplifies the process of information retrieval from the region of interest (ROI).It helps in converting the digital image into more relevant information and easier to analyze. This paper presents a comparative analysis of existing segmentation techniques and its modification to form new segmentation techniques to overcome some of the drawbacks of the existing image segmentation approaches.