Aberrant Changes Research Articles

Classification of colorectal cancer patients based on serum micronutrients: An exploratory investigation.

Colorectal cancer (CRC) is a growing global health challenge with a multifactorial etiology encompassing genetic susceptibility, nutrition, and inflammation in the bowel. To examine micronutrient status in CRC patients undergoing CRC resection. We performed a case-control study including 13 consecutive CRC patients and 10 healthy controls (CTRL) comparing the serum levels of 29 micronutrients, namely Copper, Zinc, Selenium, Chromium, Manganese, Carnitine, Choline, Inositol, Methylmalonic acid (MMA), Vitamin (Vit) B1, Vit B2, Vit B3, Vit B5, Vit B6, Vit C, Vit A, Vit D3, Vit E, Vit K1, Vit K2 and the amino acids Serine, Valine, Leucine, Isoleucine, Asparagine, Glutamine, Arginine, Citrulline and Cysteine. After considering the effect of age and sex, copper, arginine, and cysteine were increased, while zinc, selenium, chromium, Vit B1, Vit K1, and Vit A were decreased in CRC patients in comparison with CTRL. Zinc levels perfectly predicted the diagnosis of CRC, and were associated with lymph nodes (pN), of the pTNM staging. Copper levels in serum were strongly associated with the pathological pTNM staging of CRC. Though this is a preliminary study that needs confirmation with a larger longitudinal cohort, our results show that serum micronutrients are linked to tumor growth, likely caused by increased demand from tumor tissue associated with an aberrant cell proliferation and changes in the antioxidant function.

Exploring Changes in Ocular Aberrations for Different Fixation and Accommodation Stimuli

Background: Given the lack of standardization in stimulus types for assessing accommodation, we aimed to evaluate accommodative response (AR) and Zernike coefficients using four different stimuli. Methods: Sixteen healthy subjects aged 22–32 years participated. Four black transilluminated stimuli (Snellen 6/12 “E”, 6/6 “e”, Maltese Cross 6/12 “X”, 6/6 “x”) were used to stimulate accommodation from 0 D to 5 D, in 1 D increments, using the irx3 aberrometer. From the results, AR was calculated with Seidel defocus and the change in Zernike coefficient value between the non-accommodative state and the fully accommodative state (5 D) was determined. Results: Larger pupils were observed with stimulus “E” (p-value < 0.05). The mean AR at the maximum accommodative level (5 D) for the different stimuli was −1.88 ± 1.00 for “E”, −2.60 ± 1.44 for “X”, −2.00 ± 1.32 for “e”, and −2.40 ± 1.27 for “x”. No statistically significant differences were found between AR and Zernike coefficients with the four different accommodative stimuli (p-value > 0.05, one-way ANOVA). Conclusions: The study evaluated accommodative stimulus design and size on AR and Zernike coefficients and found no significant differences. However, stimuli with higher spatial frequencies (“e” and “E”) provided larger ARs compared to the other stimuli.

Long-term effects of sub-chronic exposure to L-NAME on reproductive system of male rats.

Nω-nitro-l-arginine methyl ester (L-NAME) has been utilized as a nitric oxide synthase antagonist for many years in both basic and clinical research settings to assess its therapeutic potential. Though a number of studies have shown the effect of L-NAME on testicular function, the information regarding the reversibility of these effects upon L-NAME withdrawal is limited. In the present study, male rats (68-80days old) divided randomly into three groups received different doses of L-NAME, i.e. 20mg/kg bw (L20) and 10mg/kg bw (L10) in drinking water, and drinking water only (control) through oral gavage daily for three weeks. The rats were monitored for and sacrificed after 60days of L-NAME treatment termination. The animals had a significantly higher (p < 0.01) mean blood pressure compared to control. Aberrant histological changes were observed in the testes of L-NAME-treated rats. A significant reduction (p < 0.05) in the sperm count and an increase in abnormal sperm morphology (p < 0.05) was observed in L-NAME treated rats. Moreover, the spermatogenic cycle was found to be altered in L-NAME treated rats. No change was observed in serum estradiol levels, while serum testosterone levels were significantly increased (p < 0.05) in L10 and L20 animals. The intra-testicular testosterone was increased significantly (p < 0.01) in L20 animals. A significant decrease (p < 0.05) in superoxide dismutase activity was observed in L20 animals. The sub-chronic exposure to L-NAME resulted in higher mean arterial blood pressure and long-term testicular tissue damage, affecting sperm quality and spermatogenesis.

Abstract B063: DiMMER: A robust computational pipeline for differential methylation marker evaluation in R of cell-free DNA fragments

Abstract Background: Decoding the origins of cell-free DNA (cfDNA) released from dying cells in a liquid biopsy sample offers the potential to provide insight into the dynamic, organism-wide changes reflective of health and disease, making cfDNA an ideal target for serial, minimally invasive monitoring of disease-related changes. To this end, cell-type specific DNA methylation patterns offer a promising target to facilitate tissue of origin analysis, yet limited methods exist to identify differentially methylated regions that distinguish cell-types. Methods: We develop a robust differentially methylated marker region identification pipeline, DiMMER, that leverages cfDNA fragment level information of neighboring, co-regulated CpG sites on methylome-wide sequencing reads. Compared to prior methods that utilize simple heuristics in one-vs-all average methylation rate comparisons, we implement an individual pairwise statistical test procedure across all cell-types or groups under consideration. We assess the cell-specific nature of identified differentially methylated marker regions by generating in-silico mixtures from known cell-type of origin at each region, and calculating the area under the receiver operating characteristic curve (AUROC). We utilize our differentially methylated marker finding pipeline to identify melanocyte specific methylation marker regions and assess their functional role through annotations. We show these cell-specific regions are conserved in melanoma cell-lines and are distinct from the aberrant changes in a cancer context. Results: We identified the most cell-type specific differentially methylated marker regions across 24 distinct cell-type groups using our pipeline. Compared to a simpler one-vs-all heuristic, we demonstrate improved cell-type specificity evidenced by a higher AUROC on average. Using our pipeline we identified melanocyte-specific marker regions, which were commonly found in intronic and promoter regions of genes related to melanocyte development and differentiation. When comparing methylation patterns between melanocytes and melanoma cell-lines, we demonstrate melanocyte specific methylation marks are conserved through the transformation to malignant melanoma. Conclusion: As methylome-wide sequencing methods continue to rapidly develop and more cell-specific methylation data is generated, there is unmet need for more statistically robust differentially methylated marker finding tools. Here we present one such tool, DiMMER, and demonstrate the potential utility of identifying such regions to be used to assess organ-specific load as a measure of residual disease, as opposed to traditional circulating tumor DNA quanitification. Citation Format: Arthur P McDeed, Sidharth S Jain, Megan E McNamara, Amber Alley, Anton Wellstein, Jaeil Ahn. DiMMER: A robust computational pipeline for differential methylation marker evaluation in R of cell-free DNA fragments [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B063.

Changes in Corneal Higher Order Aberrations Following Cataract Surgery With Different Incision Sites: A Prospective, Randomized Study.

To compare the effect of superior and temporal clear corneal incisions, regardless of the steep axis, on postoperative changes in corneal higher order aberrations (HOAs) in patients with healthy corneas and mild preoperative corneal astigmatism. In this prospective cohort study, the right eyes of study participants were randomly assigned to one of two groups prior to cataract surgery: temporal incision (TI) and superior incision (SI). Preoperatively and 6 weeks after surgery, measurements were taken of corneal HOAs over a 6-mm optical zone. The study included 102 eyes (50 eyes in the TI group and 52 eyes in the SI group) that underwent routine phacoemulsification using a 2.4-mm clear corneal incision. Significant changes in vertical coma (P = .019), horizontal coma (P = .042), and vertical trefoil (P = .001) were observed in the SI group. In the subgroup analysis of the SI group, significant changes in vertical coma (P = .025) and vertical trefoil (P = .047) were observed in the eyes with preoperative with-the-rule corneal astigmatism, and significant changes in horizontal coma (P = .038) were observed in eyes with preoperative against-the-rule corneal astigmatism. The TI group showed no significant difference between the preoperative and postoperative periods. The SI induced vertical and horizontal coma in accordance with the preoperative axis of the steep meridian. These alterations in corneal HOAs may affect the quality of vision after surgery. TI may potentially provide an advantage over SI in terms of corneal HOAs. [J Refract Surg. 2024;40(11):e792-e796.].

Accommodating version of a schematic eye for emmetropia and myopia.

To develop an accommodating, wide-angle, schematic eye for emmetropia and myopia in which spectacle refraction and accommodation level are input parameters. The schematic eye is based on an earlier unaccommodated refraction-dependent eye for myopia developed by Atchison in 2006. This has a parabolic gradient index lens and parameters derived from biometric and optical measurements on young adults. Several parameters are linearly dependent upon spectacle refraction (anterior radius of curvature of the cornea, axial length and vertex radii of curvature and conic asphericities of a biconic retina). The new accommodated schematic eye incorporates accommodation-dependent changes in several lens-related parameters. These changes are based on literature values for anterior chamber depth, lens thickness, vitreous chamber depth, lens surface radii of curvature and lens front surface asphericity. A parabolic variation of refractive index with relative distance from the lens centre is retained, with the same edge and centre refractive indices as the earlier model, but the distribution has been manipulated to maintain focus near the retina for the emmetropic case at 0 and 4 D accommodation. The asphericity of the lens back surface is changed so that spherical aberration and peripheral refraction approximately match typical literature trends. The model is used to compare spherical aberration and peripheral refraction in eyes with up to 4 D of myopia and 4 D of accommodation. The levels of spherical aberration in the unaccommodated schematic eyes are similar to literature values for young adults, but the changes in spherical aberration with accommodation are approximately two-thirds of that found in an experimental study. As intended, peripheral refractions in the accommodated schematic eyes are similar to those of their unaccommodated counterparts. The wide-angle model extends the range of schematic eyes to include both refraction and accommodation as variable input parameters. It may be useful in predicting aspects of retinal image quality.

CLASSIFICATION OF COLORECTAL CANCER PATIENTS BASED ON SERUM MICRONUTRIENTS: AN EXPLORATORY INVESTIGATION

Abstract Introduction/Objective Colorectal cancer (CRC) is a growing global health challenge with a multifactorial etiology encompassing genetic susceptibility, nutrition, and inflammation in the bowel. To examine micronutrient status in CRC patients undergoing CRC resection. Methods/Case Report We performed a pilot case-control study including 13 consecutive CRC patients and 10 healthy controls (CTRL) comparing the serum levels of 29 micronutrients, namely Copper, Zinc, Selenium, Chromium, Manganese, Carnitine, Choline, Inositol, Methylmalonic acid (MMA), Vitamin (Vit) B1, Vit B2, Vit B3, Vit B5, Vit B6, Vit C, Vit A, Vit D3, Vit E, Vit K1, Vit K2 and the amino acids Serine, Valine, Leucine, Isoleucine, Asparagine, Glutamine, Arginine, Citrulline and Cysteine. The analysis of trace metals (copper, zinc, selenium, chromium, manganese) in serum was done using the Inductively coupled plasma mass spectrometry (ICP-MS) methodology using the Agilent 8900 QQQ instrument. The analysis of serum water-soluble and fat-soluble vitamins and amino acids was conducted using the LC/MS (Xevo-TQ-XS) mass spectrometer (WBA0127). Elution of the fat-soluble vitamins was performed using a solid-phase extraction system with an OASIS Prime HLB plate containing 10 mg of sorbent per well, in a Waters vacuum manifold equipped with a waste collection plate. Comparison among continuous biological variables was carried out by multivariate ANOVA model (MANOVA), accounting for the effect of sex and age Results (if a Case Study enter NA) After considering the effect of age and sex, copper, arginine, and cysteine were increased, while zinc, selenium, chromium, Vit B1, Vit K1, and Vit A were decreased in CRC patients in comparison with CTRL. Zinc levels perfectly predicted the diagnosis of CRC, and was associated with lymph nodes (pN), of the pTNM staging. Copper levels in serum was strongly associated with the pathological pTNM staging of CRC. Conclusion Though this is a preliminary study which needs confirmation with a larger longitudinal cohort, our results show that serum micronutrients are linked to tumor growth, likely caused by increased demand from tumor tissue associated with an aberrant cell proliferation and changes in the antioxidant function.

High-Order Aberrations: A Key Factor in Accommodative Dysfunctions

This study investigated the relationship between high-order aberrations (HOAs) and accommodative dysfunctions by analyzing their changes with accommodation. Understanding this relationship is important for understanding the mechanisms underlying these conditions. Sixty-three subjects were divided into five groups: control, infacility of accommodation (INFA), excess of accommodation (EA), insufficiency of accommodation (INSA), and symptomatic without dysfunction (SWD). Variations in root-mean-square (RMS) of the 3rd, 4th, 5th, and 6th orders and HOAs, and fluctuations of RMS HOAs, were measured using a Shack–Hartmann aberrometer at different accommodative stimuli and during residual accommodation after their removal, in the following order: 0.00 D, 1.00 D, 0.00 D, 2.45 D, 0.00 D, 4.73 D and 0.00 D. The SWD group showed a significant increase in RMS HOAs during accommodation and residual accommodation. In contrast, the EA group showed an improvement in the ocular optical quality at higher stimuli. Different patterns of changes in the 3rd, 4th, 5th, and 6th orders were observed across all groups, and fluctuations of RMS HOAs increased significantly in the SWD group during accommodation and residual accommodation. These distinct patterns of aberration changes in different accommodative dysfunctions suggest a potential link between their underlying mechanisms, providing insights that may aid their earlier diagnosis and improved management.

12427 MKRN3 Methylation Abnormalities In Patients With Pubertal Disorders

Abstract Disclosure: N.C. Grosek: None. T. Silva: None. J.C. Magnotto: None. A. Latronico: None. A.P. Canton: None. Y. Chan: None. R.S. Carroll: None. U.B. Kaiser: None. Background and Objectives: Central Precocious Puberty (CPP) is caused by early reactivation of pulsatile GnRH secretion before age 8 years in girls and 9 years in boys. Delayed puberty (DP) is defined by the absence or incomplete development of sexual characteristics by age 13 years in girls and 14 years in boys. Environmental cues affect the HPG axis and timing of puberty via epigenetic mechanisms such as DNA methylation (DNAm). Inactivating mutations in the maternally imprinted Makorin Ring Finger 3 (MKRN3) gene are the most common genetic defect associated with CPP, representing ∼9% of patients with sporadic and familial CPP. Genomic imprinting occurs through differential methylation of CpG islands at a gene promoter or enhancer region. Differentially methylated regions (DMRs) regulate genetic imprinting. We hypothesized that transcription factor binding sites (TFBS) for ZFP57 (CpG57) andNRF1 (CpGs54+55) within the islet 3.7kb upstream of MKRN3 (MRKN3 islet) may impact expression. This study aimed to analyze if aberrant MKRN3 islet DNAm changes are associated with disorders of pubertal timing. Methods and Results: Germline DNA from 2 control patients was used to analyze the MKRN3 promoter region and islet DNAm profile. Bisulfite-treated DNA was amplified by PCR with primers targeting MKRN3 promoter and islet and submitted to Sanger sequencing. All CpG islands in the promoter region were 100% methylated, but those in the MKRN3 islet were differentially methylated with ∼50-60% methylated. DNA from our CPP cohort (n=71) underwent Next-Generation Sequencing analysis of bisulfite-treated DNA of these regions to identify the DMR potentially associated with MKRN3 imprinting. The MKRN3 islet covered CpG59-CpG49. Next, samples from our CPP cohort and patients with DP (n=44) and normal pubertal timing (n=33; 45% prepubertal, 55% pubertal) underwent pyrosequencing analyses of MKRN3islet. To compare DNAm levels between controls and our cohorts at each CpG island, T-tests were used: reported as mean±SEM. In the CPP cohort, 4/11 CpGs were significantly hypomethylated compared to controls (CpGs 54, 53, 51, 50). Specifically, the NRF1 TFBS was hypomethylated compared to controls (37.8 vs 41.6 ± 1.1, p&amp;lt;0.001) and DP (41.4 vs 43.8 ± 0.83, p=0.044). In the DP group, we found no significant difference in DNAm compared to controls. But they had hypermethylation of 4/11 CpGs compared to the CPP group, including the NRF1 TFBS (CpGs 55, 53, 51,50). Neither the CPP nor DP cohorts had significant DNAm differences at the ZFP57 TFBS compared to controls. Conclusion: Our study showed hypomethylation of 4 out of 11 CpGs in MKRN3 islet, including the NRF1 TFBS, in CPP compared to control and DP groups. On the other hand, NRF1 TFBS was hypermethylated in DPP compared to CPP. Further studies are needed to determine if these alternations in methylation are associated with MKRN3 expression levels and pubertal initiation. Presentation: 6/1/2024

12672 MKRN3 Methylation Abnormalities In Patients With Pubertal Disorders

Abstract Disclosure: N.C. Grosek: None. T. Silva: None. J.C. Magnotto: None. A. Latronico: None. A.P. Canton: None. Y. Chan: None. R.S. Carroll: None. U.B. Kaiser: None. Background and Objectives: Central Precocious Puberty (CPP) is caused by early reactivation of pulsatile GnRH secretion before age 8 years in girls and 9 years in boys. Delayed puberty (DP) is defined by the absence or incomplete development of sexual characteristics by age 13 years in girls and 14 years in boys. Environmental cues affect the HPG axis and timing of puberty via epigenetic mechanisms such as DNA methylation (DNAm). Inactivating mutations in the maternally imprinted Makorin Ring Finger 3 (MKRN3) gene are the most common genetic defect associated with CPP, representing ∼9% of patients with sporadic and familial CPP. Genomic imprinting occurs through differential methylation of CpG islands at a gene promoter or enhancer region. Differentially methylated regions (DMRs) regulate genetic imprinting. We hypothesized that transcription factor binding sites (TFBS) for ZFP57 (CpG57) andNRF1 (CpGs54+55) within the islet 3.7kb upstream of MKRN3 (MRKN3 islet) may impact expression. This study aimed to analyze if aberrant MKRN3 islet DNAm changes are associated with disorders of pubertal timing. Methods and Results: Germline DNA from 2 control patients was used to analyze the MKRN3 promoter region and islet DNAm profile. Bisulfite-treated DNA was amplified by PCR with primers targeting MKRN3 promoter and islet and submitted to Sanger sequencing. All CpG islands in the promoter region were 100% methylated, but those in the MKRN3 islet were differentially methylated with ∼50-60% methylated. DNA from our CPP cohort (n=71) underwent Next-Generation Sequencing analysis of bisulfite-treated DNA of these regions to identify the DMR potentially associated with MKRN3 imprinting. The MKRN3 islet covered CpG59-CpG49. Next, samples from our CPP cohort and patients with DP (n=44) and normal pubertal timing (n=33; 45% prepubertal, 55% pubertal) underwent pyrosequencing analyses of MKRN3islet. To compare DNAm levels between controls and our cohorts at each CpG island, T-tests were used: reported as mean±SEM. In the CPP cohort, 4/11 CpGs were significantly hypomethylated compared to controls (CpGs 54, 53, 51, 50). Specifically, the NRF1 TFBS was hypomethylated compared to controls (37.8 vs 41.6 ± 1.1, p&amp;lt;0.001) and DP (41.4 vs 43.8 ± 0.83, p=0.044). In the DP group, we found no significant difference in DNAm compared to controls. But they had hypermethylation of 4/11 CpGs compared to the CPP group, including the NRF1 TFBS (CpGs 55, 53, 51,50). Neither the CPP nor DP cohorts had significant DNAm differences at the ZFP57 TFBS compared to controls. Conclusion: Our study showed hypomethylation of 4 out of 11 CpGs in MKRN3 islet, including the NRF1 TFBS, in CPP compared to control and DP groups. On the other hand, NRF1 TFBS was hypermethylated in DPP compared to CPP. Further studies are needed to determine if these alternations in methylation are associated with MKRN3 expression levels and pubertal initiation. Presentation: 6/1/2024

Aberrant dynamic functional and effective connectivity changes of the primary visual cortex in patients with retinal detachment via machine learning.

Previous neuroimaging studies have identified significant alterations in brain functional activity in retinal detachment (RD) patients, these investigations predominantly concentrated on local functional activity changes. The potential directional alterations in functional connectivity within the primary visual cortex (V1) in RD patients remain to be elucidated. In this study, we employed seed-based functional connectivity analysis along with Granger causality analysis to examine the directional alterations in dynamic functional connectivity (dFC) within the V1 region of patients diagnosed with RD. Finally, a support vector machine algorithm was utilized to classify patients with RD and healthy controls (HCs). RD patients exhibited heightened dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) between the Visual Network (VN) and default mode network (DMN), as well as within the VN, compared to HCs. Conversely, dFC between VN and auditory network (AN) decreased, and dEC between VN and sensorimotor network (SMN) significantly reduced. In state 4, RD patients had higher frequency. Notably, variations in dFC originating from the left V1 region proved diagnostically effective, achieving an AUC of 0.786. This study reveals significant alterations in the connectivity between the VN and the default mode network in patients with RD. These changes may disrupt visual information processing and higher cognitive integration in RD patients. Additionally, alterations in the left V1 region and whole-brain dFC show promising potential in aiding the diagnosis of RD. These findings offer valuable insights into the neural mechanisms underlying visual and cognitive impairments associated with RD.

A 6-Month Follow-Up Comparative Study of Single-Step Transepithelial Photorefractive Keratectomy (Trans-PRK) Using the StreamLight Software with and without Epithelial Thickness Customization.

To compare corneal aberrometry, densitometry, and refractive outcomes of single-step Transepithelial Photorefractive Keratectomy (Trans-PRK) with and without epithelial thickness customization. This was a prospective, interventional, randomized controlled study. Patients undergoing Trans-PRK using the WaveLight EX500 laser with StreamLight software (Alcon Laboratories, Forth Worth, TX, USA) were randomly assigned to control (55µm standard epithelial thickness) or customized (thinnest point of epithelial thickness for each patient) groups. MS-39 (CSO, Italy) anterior segment optical coherence tomography was used to measure the epithelial thickness. Inclusion criteria were spherical equivalent <6 diopters (D), astigmatism <4D, and CDVA 20/25 or better. The assessments were at baseline and 6 months post-op: visual acuity, refraction, aberrometry, and corneal densitometry. 108 eyes were enrolled, [control group (n=56) and customized group (n=52)]. Mean epithelial ablation thickness in the customized group was 54.81±3.56µm (p=0.470 vs control group). Both groups experienced significant postoperative increases in higher-order aberrations (HOA) and spherical aberrations, with no significant intergroup differences. Mean HOA RMS (µm) of the frontal cornea and total cornea increased by 0.27, and 0.29, respectively, in the control group, and 0.26 and 0.28, respectively, in the customized group (p<0.001 for all). Mean change in spherical aberrations in the frontal cornea and total cornea was 0.23µm (p<0.001) and 0.25µm (p<0.001), in the control group, and 0.19µm (p<0.001) and 0.20µm (p<0.001), in the customized group. Mean corneal densitometry in anterior cornea decreased by 0.63GSU (p=0.021) and 1.18GSU (p<0.001) in the control and customized groups. In the posterior cornea, it increased by 1.67GSU (p=0.004) and 0.38GSU (p=0.006). No significant differences in refractive and aberrometry outcomes between control and customized Trans-PRK groups, with corneal densitometry changes not affecting visual acuity.

Optical quality changes of the eye during peak SARS-CoV-2 pandemic in young adults

IntroductionTo determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects corneal morphology and optical quality. MethodsIn this cross-sectional study, ophthalmological indicators were examined during the peak of SARS-CoV-2 infection after adjusting for public health control measures. Participants were divided into control (remained uninfected), A (infected during follow-up), and B (infected prior to the first consultation) groups. Effects of varying SARS-CoV-2 infection levels were determined using reverse transcription polymerase chain reaction. Changes in corneal morphology, backscatter, and aberrations were measured. Corneal parameters, such as flat keratometry, steep keratometry, and surface variance, vertical asymmetry, height asymmetry, and height decentration indices were considered. ResultsOverall, 110 participants (208 eyes, 42.7% male; age 17–31 years) were enrolled. Eighteen (16.3%) were infection-free during the outbreak with unchanged corneal morphology, backscatter, and aberration. In group A, 34.73 ± 9.30 days after infection, the backscatter of the anterior corneal layer and central layer (both p=0.000) decreased. Total low-order aberration, defocus, horizontal coma, and spherical aberration of the cornea increased (p<0.05), while corneal morphology after infection did not change (p>0.05). In group B, a decrease in backscattering in the corneal middle layer and an increase in horizontal coma (p<0.05) were noted. ConclusionBackscattering of the anterior and intermediate layers of the cornea decreased and corneal aberrations increased after SARS-CoV-2 infection, which affected corneal optical quality. However, corneal morphology and thickness remained unchanged. Ophthalmological indicators and optical quality should be monitored during SARS-CoV-2 infection.

Evaluating the impact of artificial intelligence-based assessment of body composition on primary artificial urinary sphincter placement outcomes.

Sarcopenia, characterized by low muscle mass, and aberrant adiposity changes, including visceral fat accumulation, has been associated with impaired physiologic stress response and wound healing. Artificial urinary sphincter (AUS) placement is the preferred surgical treatment for men with severe post-prostatectomy incontinence. Given the higher rates of maladaptive body composition changes in this older, high comorbidity population, this study explores their impact on AUS outcomes. A retrospective analysis was performed including men who underwent primary AUS placement at the Mayo Clinic from 1999 to 2023 for post-prostatectomy incontinence and had cross sectional imaging available within 12 months prior to AUS implant. Sarcopenia and body composition were assessed from the available computed tomography (CT) scan using an algorithm that measures the area of different tissues at the L3 abdominal cross-section. The study investigated the association between sarcopenia [defined as skeletal muscle index (SMI) <52.4 cm2/m2] and adiposity (defined by total visceral and subcutaneous fat area) with all-cause reoperation, including specific etiologies of device infection/erosion, urethral atrophy, and device malfunction, using Cox proportional hazards models. There were 111 patients who had available imaging within the study timeframe, 61 (55%) of whom were classified as sarcopenic. Follow-up did not differ significantly between the two groups [2.11 (0.53-4.78) vs. 2.52 (0.36-5.80) years, P=0.52]. Sarcopenic patients had a lower body mass index (BMI) (29.1 vs. 32.7 kg/m2; P<0.001). No significant difference in overall device survival was observed between sarcopenic and non-sarcopenic patients (P=0.94) on Cox survival analysis. Sarcopenic patients had higher device infection rates, accounting for 16.7% (3/18) of device failures in the sarcopenic cohort compared to none in the non-sarcopenic cohort. Sarcopenia was prevalent among AUS patients but did not significantly impact overall device survival. These findings suggest that AUS placement may be feasible to perform in well-selected sarcopenic patients.

Depression recognition using high-order generalized multilayer brain functional network fused with EEG multi-domain information

Major Depressive Disorder (MDD) is a serious and highly heterogeneous psychological disorder. According to the network hypothesis, depression originates from abnormal neural network information processing, typically resulting in aberrant changes in the topological structure of the brain’s functional network. Recent evidence further reveals that depression involves dynamic changes related to both within- and cross-frequency coupling. Therefore, we utilize second-order tensor expansion to integrate frequency- and time-varying multilayer brain functional networks based on node sharing, thus propose a generalized multilayer brain functional network (GMBFN) incorporating multi-domain information. Concurrently, we derive global and local topological properties from both the frequency and temporal domains to characterize the novel network structure. To uncover more reliable biomarkers and explore various coupling features that can assess the interaction between signals from different perspectives, we conduct research in two datasets employing four sets of within- and cross-frequency coupling. Leveraging the novel multi-domain high-order GMBFNs, abnormalities of information integration abilities in patients with MDD are observed, particularly in the theta-band and overall temporal-domain. Through the fusion of topological properties across both domains with multiple classifiers, the alpha-band can serve as a potential biomarker for depression identification. More importantly, the combination of global topological properties from both domains, on average, enhances the classification performance for identifying patients with MDD by 5.18% compared to using just one domain. This study presents a systematic framework for comprehending the aberrant mechanisms of MDD from multiple perspectives, offering significant value for clinical applications aimed at assisting in depression diagnosis and intervention.

The onset and the development of cardiometabolic aging: an insight into the underlying mechanisms.

Metabolic compromise is crucial in aggravating age-associated chronic inflammation, oxidative stress, mitochondrial damage, increased LDL and triglycerides, and elevated blood pressure. Excessive adiposity, hyperglycemia, and insulin resistance due to aging are associated with elevated levels of damaging free radicals, inducing a proinflammatory state and hampering immune cell activity, leading to a malfunctioning cardiometabolic condition. The age-associated oxidative load and redox imbalance are contributing factors for cardiometabolic morbidities via vascular remodelling and endothelial damage. Recent evidence has claimed the importance of gut microbiota in maintaining regular metabolic activity, which declines with chronological aging and cardiometabolic comorbidities. Genetic mutations, polymorphic changes, and environmental factors strongly correlate with increased vulnerability to aberrant cardiometabolic changes by affecting key physiological pathways. Numerous studies have reported a robust link between biological aging and cardiometabolic dysfunction. This review outlines the scientific evidence exploring potential mechanisms behind the onset and development of cardiovascular and metabolic issues, particularly exacerbated with aging.

Analysis of third and fourth corneal high-order aberrations before and after small incision lenticule extraction (SMILE) in myopic and myopic astigmatic eyes using ray tracing aberrometry

BackgroundAim is to analyze alterations in third and fourth corneal higher-order aberrations using a ray tracing aberrometer (iTrace) induced by SMILE (small incision lenticule extraction) refractive surgery on Algerian patients; and also to investigate how corneal aberrations vary with spherical equivalent (SE), corneal central thickness (CCT), and age. Design Prospective, non-randomized case series that were carried out at the Chiali Smile Center, Algiers, Algeria.ParticipantsA total of 219 eyes from 110 myopic patients, with and without astigmatism, successfully concluded the ultimate follow-up. Participants exhibited an average age of 32.48 years, with preoperative mean corneal high-order aberrations (CHOA) measuring 0.005 ± 0.036 μm.MethodsA tracking trend analysis of high-order aberrations (HOAs) was conducted on the three groups of patients, assessing total corneal high-order aberrations after SMILE over periods of two, six, and twelve months.ResultsA substantial increase in total corneal high-order aberrations following SMILE, with a P value < 0.05. Conversely, there was a noteworthy and significant decrease in vertical trefoil for all groups (P value = 0.000). Interestingly, the corneal higher-order aberrations were more pronounced after two months compared to the six and twelve-month intervals. Spherical aberration demonstrated a significant increase with the extent of preoperative myopia and preoperative spherical equivalent both before and after SMILE surgery (P < 0.05), particularly in cases of high myopia. Moreover, there were significant reductions in preoperative and postoperative vertical coma (P = 0.047, P = 0.004, respectively) corresponding to the degree of preoperative myopia, with a more substantial decrease in vertical coma observed in cases of low myopia.ConclusionIn the post-SMILE period, a notable increase in vertical coma and spherical aberrations was observed, accompanied by a significant decrease in vertical trefoil across all eyes. These aberration changes were identified to be closely associated with the spherical equivalent.

Fractal Biology — Evolution from Molecular to Cognitive, and Psychological Dimensions

Biological and artificial intelligence (BI and AI) share the fundamental principles of space-time information processing based on symmetry transformation. Therefore, cognitive-science-inspired AI represents a promising area of exploration. A convincing example are the fractal structure of human languages and protein assembly. Biological processes’ temporal and spatial plasticity links them to basic laws of physics. Continuous advances in fundamental physical theories allow understanding of all aspects of space-time symmetry (STS) natively intertwined with the principle of relativity and causality. Spatial aspects of symmetry represented by three sub-domains such as chirality, fractality, and topology, are widely studied in biology. The role of chirality in biology has been analyzed in several recent reviews. However, the fractals and topological states of biological structures is a relatively new and fast-developing branch of science. Here, we trace publications exploring the role of fractal symmetry in all hierarchical states of biological organization, including at the molecular, cellular, morphological, physiological, perceptual, cognitive, and psychological levels. The coverage of the above-listed areas in current studies is sharply unequal and unsystematic. A broad view of biological fractality opens a unique opportunity to discriminate between a healthy state and a wide range of disease conditions. Psychiatric, neurological, and immune disorders are associated with aberrant molecular assembly and morphological changes in neural circuits, suggesting that the chain of chirality/fractality transfer through all levels of physiological organization deserves persistent attention.

PHF8/KDM7B: A Versatile Histone Demethylase and Epigenetic Modifier in Nervous System Disease and Cancers.

Many human diseases, such as malignant tumors and neurological diseases, have a complex pathophysiological etiology, often accompanied by aberrant epigenetic changes including various histone modifications. Plant homologous domain finger protein 8 (PHF8), also known as lysine-specific demethylase 7B (KDM7B), is a critical histone lysine demethylase (KDM) playing an important role in epigenetic modification. Characterized by the zinc finger plant homology domain (PHD) and the Jumonji C (JmjC) domain, PHF8 preferentially binds to H3K4me3 and erases repressive methyl marks, including H3K9me1/2, H3K27me1, and H4K20me1. PHF8 is indispensable for developmental processes and the loss of PHF8 enzyme activity is linked to neurodevelopmental disorders. Moreover, increasing evidence shows that PHF8 is highly expressed in multiple tumors as an oncogenic factor. These findings indicate that studying the role of PHF8 will facilitate the development of novel therapeutic agents by the manipulation of PHF8 demethylation activity. Herein, we summarize the current knowledge of PHF8 about its structure and demethylation activity and its involvement in development and human diseases, with an emphasis on nervous system disorders and cancer. This review will update our understanding of PHF8 and promote the clinical transformation of its predictive and therapeutic value.

Comparison of objective visual quality between SMILE and FS-LASIK in moderate-to-high myopia.

This study aims to compare the changes in the corneal wavefront aberrations and the objective visual quality resulting from two types of eye surgery-small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK)-in patients with moderate-to-high myopia. A prospective analysis was performed on 98 eyes of 51 patients who underwent SMILE. Additionally, 88 eyes of 45 patients who underwent FS-LASIK were analyzed. All patients underwent ocular examination preoperatively and at 1 day, 1 week, 1 month, and 3 months postoperatively. Corneal aberrations and objective visual quality were measured using the Optical Quality Analysis System II (OQAS II) and Optical Path Difference Scan III (OPD-Scan III). At postoperative 1 day and 1 week, there was a statistically significant difference in uncorrected distance visual acuity (UDVA) between SMILE and FS-LASIK (P < 0.05). Postoperative spherical (S), cylinder (C) and spherical equivalent refraction (SE) were similar between the two groups (P > 0.05). In both groups, the absolute magnitude of total higher-aberrations (tHOA), piston, vertical tilt, vertical coma, and spherical aberration (SA) increased after surgery compared to preoperative values (P < 0.05). There was no significant difference in Δhorizontal tHOA, Δhorizontal tilt, Δhorizontal coma, and Δhorizontal trefoil between the two groups (P > 0.05), and the FS-LASIK had higher Δvertical trefoil and ΔSA (P < 0.05) but lower Δpiston, Δvertical tilt, and Δvertical coma than the SMILE group (P < 0.05). There was a rise in objective scattering index (OSI) and a decline in both modulation transfer function (MTF) cutoff and Strehl ratio (SR) after surgery compared to preoperative values in both groups (P < 0.05). There was a statistically significant difference in the OSI at 1 day and 3 months between the two groups (P < 0.05). Postoperative MTF cutoff and SR were similar between the two groups (P > 0.05). Postoperative OSI was positively correlated with corneal tHOA (0.261 ≤ R ≤ 0.483, P < 0.05) and was negatively correlated with vertical tilt and vertical coma (-0.315 ≤ R ≤ -0.209, P < 0.05) in both groups. While both SMILE and FS-LASIK can effectively correct moderate-to-high myopia, there is an increase in corneal aberrations and a postoperative delay in objective visual quality. The cornea may require a longer recovery period in the SMILE. OPD-Scan III combined with OQAS II is a useful supplementary inspection for assessing the optical quality following refractive surgery.