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1.
Nat Commun ; 15(1): 5414, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926353

RESUMO

Borgs are huge extrachromosomal elements (ECE) of anaerobic methane-consuming "Candidatus Methanoperedens" archaea. Here, we used nanopore sequencing to validate published complete genomes curated from short reads and to reconstruct new genomes. 13 complete and four near-complete linear genomes share 40 genes that define a largely syntenous genome backbone. We use these conserved genes to identify new Borgs from peatland soil and to delineate Borg phylogeny, revealing two major clades. Remarkably, Borg genes encoding nanowire-like electron-transferring cytochromes and cell surface proteins are more highly expressed than those of host Methanoperedens, indicating that Borgs augment the Methanoperedens activity in situ. We reconstructed the first complete 4.00 Mbp genome for a Methanoperedens that is inferred to be a Borg host and predicted its methylation motifs, which differ from pervasive TC and CC methylation motifs of the Borgs. Thus, methylation may enable Methanoperedens to distinguish their genomes from those of Borgs. Very high Borg to Methanoperedens ratios and structural predictions suggest that Borgs may be capable of encapsulation. The findings clearly define Borgs as a distinct class of ECE with shared genomic signatures, establish their diversification from a common ancestor with genetic inheritance, and raise the possibility of periodic existence outside of host cells.


Assuntos
Genoma Arqueal , Metano , Filogenia , Metano/metabolismo , Oxirredução , Archaea/genética , Archaea/metabolismo , Sequenciamento por Nanoporos/métodos , Metilação de DNA , Microbiologia do Solo
2.
Ophthalmic Epidemiol ; : 1-8, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833629

RESUMO

PURPOSE: To elicit associations between vision difficulties and physical or psychosocial challenges in children in the United States. METHODS: Children aged 2-17 years old from the 2021 National Health Interview Survey with data pertaining to vision difficulty were included in our retrospective, population-based analysis. Our primary aim was investigating physical and psychosocial challenges as predictors of vision difficulty. Logistic regression models were performed on Stata version 17.0 (StataCorp LLC, College Station, Texas). Analyses were accompanied by an odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 7,373 children had data pertaining to their level of vision difficulty and were included in our sample. In our multivariable analysis, children with a good/fair (OR = 1.84, 95% CI = [1.31, 2.60], p < 0.01), or poor (OR = 5.08, 95% CI = [1.61, 16.04], p < 0.01) general health status had higher odds of vision difficulty relative to children with an excellent/very good health status. Furthermore, children with difficulties hearing (OR = 8.67, 95% CI = [5.25, 14.31], p < 0.01), communicating (OR = 1.96, 95% CI = [1.18, 3.25], p < 0.01), learning (OR = 1.93, 95% CI = [1.27, 2.93], p < 0.01), and making friends (OR = 1.94, 95% CI = [1.12, 3.36], p = 0.02) had higher odds of vision difficulty. Nonetheless, the following factors were only predictors of vision difficulty in our univariable analysis: requiring equipment for mobility (p < 0.01), experiencing anxiety (p < 0.01), and experiencing depression (p < 0.01). CONCLUSION: Several factors pertaining to physical and psychosocial challenges in children are associated with vision difficulty. Future research should further explore potential causal links between vision difficulty and physical or psychosocial factors to aid in coordinating public health efforts dedicated to vision health equity.

3.
Eye (Lond) ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615098

RESUMO

PURPOSE: With the popularization of ChatGPT (Open AI, San Francisco, California, United States) in recent months, understanding the potential of artificial intelligence (AI) chatbots in a medical context is important. Our study aims to evaluate Google Gemini and Bard's (Google, Mountain View, California, United States) knowledge in ophthalmology. METHODS: In this study, we evaluated Google Gemini and Bard's performance on EyeQuiz, a platform containing ophthalmology board certification examination practice questions, when used from the United States (US). Accuracy, response length, response time, and provision of explanations were evaluated. Subspecialty-specific performance was noted. A secondary analysis was conducted using Bard from Vietnam, and Gemini from Vietnam, Brazil, and the Netherlands. RESULTS: Overall, Google Gemini and Bard both had accuracies of 71% across 150 text-based multiple-choice questions. The secondary analysis revealed an accuracy of 67% using Bard from Vietnam, with 32 questions (21%) answered differently than when using Bard from the US. Moreover, the Vietnam version of Gemini achieved an accuracy of 74%, with 23 (15%) answered differently than the US version of Gemini. While the Brazil (68%) and Netherlands (65%) versions of Gemini performed slightly worse than the US version, differences in performance across the various country-specific versions of Bard and Gemini were not statistically significant. CONCLUSION: Google Gemini and Bard had an acceptable performance in responding to ophthalmology board examination practice questions. Subtle variability was noted in the performance of the chatbots across different countries. The chatbots also tended to provide a confident explanation even when providing an incorrect answer.

5.
Int Ophthalmol ; 44(1): 186, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643220

RESUMO

PURPOSE: This study introduces the Order of Magnitude (OM), a cost-effective, indigenous, virtual reality-based visual field analyzer designed for detecting glaucomatous visual field loss. METHODS: The OM test employs a two-step supra-thresholding algorithm utilizing stimuli of 0.43°diameter (equivalent to Goldmann size III) at low and high thresholds. A comparative analysis was conducted against the Humphrey visual field (HVF) test, considered the gold standard in clinical practice. Participants, including those with glaucoma and normal individuals, underwent comprehensive eye examinations alongside the OM and HVF tests between April and October 2019. Diagnostic sensitivity and specificity of the OM test were assessed against clinical diagnoses made by specialists. RESULTS: We studied 157 eyes (74 glaucomatous, 83 control) of 152 participants. Results demonstrated a high level of reliability for both OM and HVF tests, with no significant difference observed (P = 0.19, Chi-square test). The sensitivity and specificity of the OM test were found to be 93% (95% CI 86-100%) and 83% (95% CI 72.4-93%), respectively, while the HVF test showed sensitivity and specificity of 98% (95% CI 93.9-100%) and 83% (95% CI 73.9-92.8%), respectively. CONCLUSION: These findings suggest that the OM test is non-inferior to the reference standard HVF test in identifying glaucomatous visual field loss.


Assuntos
Glaucoma , Campos Visuais , Humanos , Reprodutibilidade dos Testes , Glaucoma/diagnóstico , Testes de Campo Visual/métodos , Transtornos da Visão/diagnóstico , Sensibilidade e Especificidade
7.
Ecancermedicalscience ; 18: 1667, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38439810

RESUMO

Background: Lorlatinib, an anaplastic lymphoma kinase (ALK)-inhibitor, is approved as frontline as well as subsequent line of therapy in ALK-rearranged advanced non-small cell lung cancer (NSCLC). There is limited literature about safety and efficacy of lorlatinib in Indian patients. Materials and methods: This was a retrospective multicentre study on patients with ALK-rearranged advanced NSCLC received lorlatinib as second line and beyond between May 2017 and December 2021. ALK was tested either by immunohistochemistry or fluorescent in-situ hybridisation. Clinicopathologic features, treatment details, toxicity and outcomes were analysed. Results: A total of 38 patients were enrolled with a median age of 54 years (range: 30-72) and male: female ratio of 20:18. Fifteen (44%) patients had brain metastases at baseline. Lorlatinib use was - second line in 11 (29%), third line in 21 (55%) and fourth line in 4 (11%) of patients, respectively. The best radiologic response to lorlatinib was - complete response in 9 (24%), partial response in 17 (46%), stable disease in 9 (24%) and progressive disease in 2 (5%) of patients, respectively. After a median follow-up of 76.6 months (95% CI: 68.9-100), the median progression-free survival (PFS) of lorlatinib was not reached (95% CI: 24.3-not reached) and median overall survival (OS) of the whole cohort was 93.1 months (95% CI: 62-not reached). Both median PFS (p = 0.48) and median OS (p = 0.74) was similar between second line and later line use of lorlatinib. Thirty-three (87%) patients experienced treatment-related toxicity and six (16%) patients required dose modification. Conclusion: Lorlatinib was highly efficacious in terms of overall response rate, median PFS and median OS in this small real-world cohort of advanced ALK+ve NSCLC with a manageable safety profile.

10.
Nat Commun ; 15(1): 2434, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509081

RESUMO

Extracellular electron transfer (EET) via microbial nanowires drives globally-important environmental processes and biotechnological applications for bioenergy, bioremediation, and bioelectronics. Due to highly-redundant and complex EET pathways, it is unclear how microbes wire electrons rapidly (>106 s-1) from the inner-membrane through outer-surface nanowires directly to an external environment despite a crowded periplasm and slow (<105 s-1) electron diffusion among periplasmic cytochromes. Here, we show that Geobacter sulfurreducens periplasmic cytochromes PpcABCDE inject electrons directly into OmcS nanowires by binding transiently with differing efficiencies, with the least-abundant cytochrome (PpcC) showing the highest efficiency. Remarkably, this defined nanowire-charging pathway is evolutionarily conserved in phylogenetically-diverse bacteria capable of EET. OmcS heme reduction potentials are within 200 mV of each other, with a midpoint 82 mV-higher than reported previously. This could explain efficient EET over micrometres at ultrafast (<200 fs) rates with negligible energy loss. Engineering this minimal nanowire-charging pathway may yield microbial chassis with improved performance.


Assuntos
Geobacter , Nanofios , Oxirredução , Periplasma/metabolismo , Elétrons , Transporte de Elétrons , Citocromos/metabolismo , Geobacter/metabolismo
11.
Sci Immunol ; 9(93): eadi7038, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517952

RESUMO

The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (just EGFP death inducing) CD8+ T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8+ T cell-mediated killing-unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells-despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8+ T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8+ T cells neither cleared nor prevented MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8+ T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes.


Assuntos
Linfócitos T CD8-Positivos , Norovirus , Camundongos , Humanos , Animais , Células em Tufo , Norovirus/fisiologia , Privilégio Imunológico , Intestinos
12.
Indian J Surg Oncol ; 15(1): 63-70, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511033

RESUMO

The practice of boost to the tumor bed after treatment with oncoplastic breast-conserving surgery (BCS) remains variable. Using a survey, the present study evaluated the current practice of tumor bed boost administered in women after oncoplastic BCS. Actively practicing radiation oncologists across India were sent a questionnaire on the practice of adjuvant whole-breast radiotherapy and tumor bed boost after oncoplastic BCS via email and encouraged to participate. Of the 54 radiation oncologists who participated, most (98.1%) used a linear accelerator for radiotherapy. Hypofractionation was preferred by 59.26%, standard fractionation by 7.41%, and the remaining selected the fractionation strategy based on various patient factors. In addition, 83.33% participants reported that they always planned tumor boost, 51.85% preferred photons for the boost, and 75.93% administered sequential boost. The most common dose for the boost was 12.5 Gy in five fractions (40.74%). Most participants (77.78%) revealed that they used a combination of methods for identifying the tumor bed. With respect to clip placement, most surgeons (96%) at the participants' centers placed ≥ 4 clips at the tumor site, with both the base and margins being preferred by surgeons (81.48%) for placement. Finally, 12.96% participants revealed that the surgeons always involved them during surgical planning, whereas 7.4% participants reported that they always included the surgeons during radiotherapy planning, suggesting that radiation oncologists and oncoplastic surgeons do not involve each other during surgical and radiotherapy planning, possibly leading to suboptimal treatment. This may be attributed to the absence of guidelines regarding boost practices after oncoplastic BCS.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38531020

RESUMO

BACKGROUND AND OBJECTIVE: This review consolidates findings from studies that used a preoperative visual acuity (VA) threshold as an indication for epiretinal membrane (ERM) surgery. METHODS: The literature was systematically searched using Ovid MEDLINE, EMBASE, and Cochrane Library from January 2000 to October 2022 to select studies reporting on pars plana vitrectomy (PPV) for ERM that used a preoperative VA threshold as an inclusion criterion. Primary outcomes were final best-corrected visual acuity (BCVA) and change in BCVA relative to baseline. Secondary outcomes included risk of intra- and postoperative complications. RESULTS: A total of 639 eyes from seven studies were included. The most liberal preoperative VA threshold was 20/28.5 or worse, whereas the most conservative threshold was worse than 20/60. The mean preoperative BCVA was 0.55 logarithm of the minimum angle of resolution (logMAR) (∼20/70), and the mean postoperative BCVA was 0.35 logMAR (∼20/45). Generally, VA improved relative to baseline, regardless of the preoperative VA threshold. The smallest improvement in VA was observed in a study where the pre-operative VA to consider surgery was liberal (20/30 or worse), whereas the greatest VA improvement was observed in a study that used a conservative preoperative VA threshold (worse than 20/60). CONCLUSIONS: The greatest improvement in BCVA was observed in studies where a conservative pre-operative VA threshold was used. The decision to operate should involve a patient-centered approach with a thorough discussion of the risks and benefits of PPV, regardless of the preoperative VA threshold used. [Ophthalmic Surg Lasers Imaging Retina 2024;55:xx-xx.].

14.
Sci Rep ; 14(1): 4224, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378730

RESUMO

Biosimilar insulin analogues are increasing market access for diabetic patients globally. Scientific establishment of biosimilarity is cornerstone of this key change in the medical landscape. BGL-ASP is a biosimilar insulin aspart developed by BioGenomics Limited, India. BioGenomics has considered a stepwise approach in generating the totality of evidence required to establish similarity with reference product. Insulin aspart is a recombinant rapid-acting human insulin analogue utilised in the treatment of type-1 and type-2 diabetes mellitus. The single amino acid substitution at position B28 where proline is replaced with aspartic acid results in a decreased propensity to form hexamers, thus increasing the absorption rate on subcutaneous administration compared to native insulin. In order to establish the safety and efficacy of BGL-ASP, the critical quality attributes (CQAs) of BGL-ASP are identified based on the impact created on biological activity, pharmacokinetic/pharmacodynamic (PK/PD), immunogenicity and safety. The CQAs of insulin aspart are related to product structure, purity and functionality and are characterised using a series of state-of-the-art orthogonal analytical tools. The primary protein sequence, the secondary, tertiary and quaternary structure are found to be highly similar for BGL-ASP and reference product. The product related impurities of insulin aspart and the assay content are determined using high performance liquid chromatography (HPLC) based analysis and is similar for BGL-ASP and reference insulin aspart sourced from United States of America (US), Europe Union (EU) and India. The safety, efficacy and immunogenicity of BGL-ASP is also found to be comparable with reference product and is confirmed through the clinical trials conducted as recommended by International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) and European Medicines Agency (EMA) guidelines. The data encompassed in this study demonstrates that reference insulin aspart and BGL-ASP are highly similar in terms of structural, physicochemical, and biological properties, thus confirming its safety and efficacy for usage as potential alternative economical medicinal treatment for diabetes mellitus.


Assuntos
Medicamentos Biossimilares , Diabetes Mellitus Tipo 2 , Humanos , Medicamentos Biossimilares/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Índia , Insulina/uso terapêutico , Insulina Aspart/uso terapêutico , Estados Unidos
15.
Artigo em Inglês | MEDLINE | ID: mdl-38416196

RESUMO

The present study aimed to investigate the anti-cancer mechanism of canagliflozin (CANA) and dapagliflozin (DAPA), sodium-glucose co-transporter-2 (SGLT2) inhibitors, using in silico and in vitro approaches. Network pharmacology was employed to predict the targets of the inhibitors and GO gene enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation conducted to explore the interacting pathways. Molecular docking and molecular dynamic (MD) simulation studies were performed to confirm the important targets and assess conformational stability. In vitro cytotoxicity assays, MIA-PaCa-2 and DU-145 cell lines CANA and DAPA was performed. Protein-protein interaction (PPI) network analysis indicated that CANA and DAPA exert anticancer effects through MAPK, mTOR, EGFR-KRAS-BRAF, FGFR, and PI3KA pathways. KEGG analysis revealed that these inhibitors could be used in the treatment of various cancers, including breast, prostate, pancreatic, chronic myeloid leukemia, thyroid, small cell lung, gastric, and bladder cancer. Docking results showed highest affinity for MAPK1 for CANA (- 9.60 kcal/mol) and DAPA (- 9.58 kcal/mol). MD simulation results showed that RMSD values for the MAPK1-compound exhibit remarkable stability over a timeframe of 100 ns. In cytotoxicity assays using MIA-PaCa-2 and DU-145 cell lines, CANA demonstrated a potential antiproliferative effect on the pancreatic cell line MIA-PaCa-2 after 48 h of treatment at a concentration of 100 µg/ml. Furthermore, CANA arrested the cell cycle in the sub-G1 phase and induced late apoptosis and necrosis in MIA-PaCa-2 cell line. Based on these findings, CANA shows promise as a potential novel treatment strategy for pancreatic cancer.

16.
Am J Ophthalmol ; 263: 81-92, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38387827

RESUMO

PURPOSE: To investigate the association between social determinants of health (SDH) in the domains of social and community context, education access, environmental context, economic stability, and healthcare access, with glaucoma prevalence. DESIGN: Cross-sectional study. METHODS: The study population consisted of adult participants who answered glaucoma-related questions on the 2017 National Health Interview Survey (NHIS), the most recent iteration that includes glaucoma-related questions. The main outcome measures included the relationships between SDH-related factors and self-reported glaucoma diagnosis as well as self-reported glaucomatous vision loss were examined using univariable and multivariable regression models. RESULTS: In total, 26,696 of 26,742 (99.83%) NHIS respondents were included, of whom 880 (3.30%) reported a glaucoma diagnosis and 275 (1.03%) reported glaucomatous vision loss. Participants were predominantly middle-aged (50.95 ± 18.60 years), female (54.75%), and non-Hispanic White (70.49%). In age-adjusted multivariable regression (n = 25,456), non-Hispanic Black race (odds ratio [OR] = 1.87, 99% CI = [1.37, 2.55], P < .001, compared to non-Hispanic White race) and poor health status (OR = 1.54, 99% CI = [1.00, 2.37], P = .01, compared to good health status) were significant predictors of glaucoma diagnosis. For glaucomatous vision loss, having an income below the poverty threshold (OR = 2.41, 99% CI = [1.12, 5.20], P = .003, compared to income ≥5 times the poverty threshold) was the only significant predictor in univariable analyses. No SDH-related factors were significantly associated with glaucomatous vision loss in multivariable analysis (n = 848). Multicollinearity was minimal (variation inflation factor<1.6 for all independent variables). CONCLUSIONS: Non-Hispanic Black race and poor health status were associated with self-reported glaucoma diagnosis. Physicians and policymakers may consider SDH when assessing clinical risk and designing public health interventions.


Assuntos
Glaucoma , Inquéritos Epidemiológicos , Autorrelato , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Glaucoma/epidemiologia , Glaucoma/diagnóstico , Estados Unidos/epidemiologia , Idoso , Adulto , Prevalência , Fatores Sociodemográficos , Determinantes Sociais da Saúde , Fatores de Risco , Adulto Jovem
17.
JAMA Ophthalmol ; 142(4): 321-326, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38421670

RESUMO

Importance: Ophthalmology is reliant on effective interpretation of multimodal imaging to ensure diagnostic accuracy. The new ability of ChatGPT-4 (OpenAI) to interpret ophthalmic images has not yet been explored. Objective: To evaluate the performance of the novel release of an artificial intelligence chatbot that is capable of processing imaging data. Design, Setting, and Participants: This cross-sectional study used a publicly available dataset of ophthalmic cases from OCTCases, a medical education platform based out of the Department of Ophthalmology and Vision Sciences at the University of Toronto, with accompanying clinical multimodal imaging and multiple-choice questions. Across 137 available cases, 136 contained multiple-choice questions (99%). Exposures: The chatbot answered questions requiring multimodal input from October 16 to October 23, 2023. Main Outcomes and Measures: The primary outcome was the accuracy of the chatbot in answering multiple-choice questions pertaining to image recognition in ophthalmic cases, measured as the proportion of correct responses. χ2 Tests were conducted to compare the proportion of correct responses across different ophthalmic subspecialties. Results: A total of 429 multiple-choice questions from 136 ophthalmic cases and 448 images were included in the analysis. The chatbot answered 299 of multiple-choice questions correctly across all cases (70%). The chatbot's performance was better on retina questions than neuro-ophthalmology questions (77% vs 58%; difference = 18%; 95% CI, 7.5%-29.4%; χ21 = 11.4; P < .001). The chatbot achieved a better performance on nonimage-based questions compared with image-based questions (82% vs 65%; difference = 17%; 95% CI, 7.8%-25.1%; χ21 = 12.2; P < .001).The chatbot performed best on questions in the retina category (77% correct) and poorest in the neuro-ophthalmology category (58% correct). The chatbot demonstrated intermediate performance on questions from the ocular oncology (72% correct), pediatric ophthalmology (68% correct), uveitis (67% correct), and glaucoma (61% correct) categories. Conclusions and Relevance: In this study, the recent version of the chatbot accurately responded to approximately two-thirds of multiple-choice questions pertaining to ophthalmic cases based on imaging interpretation. The multimodal chatbot performed better on questions that did not rely on the interpretation of imaging modalities. As the use of multimodal chatbots becomes increasingly widespread, it is imperative to stress their appropriate integration within medical contexts.


Assuntos
Glaucoma , Oftalmologia , Criança , Humanos , Inteligência Artificial , Estudos Transversais , Retina
18.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255963

RESUMO

Circulating miRNAs are increasingly being considered as biomarkers in various medical contexts, but the value of analyzing isomiRs (isoforms of canonical miRNA sequences) has not frequently been assessed. Here we hypothesize that an in-depth analysis of the full circulating miRNA landscape could identify specific isomiRs that are stronger biomarkers, compared to their corresponding miRNA, for identifying increased CV risk in patients with non-alcoholic fatty liver disease (NAFLD)-a clinical unmet need. Plasma miRNAs were sequenced with next-generation sequencing (NGS). Liver fat content was measured with magnetic-resonance spectrometry (MRS); CV risk was determined, beyond using traditional biomarkers, by a CT-based measurement of coronary artery calcium (CAC) score and the calculation of a CAC score-based CV-risk percentile (CAC-CV%). This pilot study included n = 13 patients, age > 45 years, with an MRS-measured liver fat content of ≥5% (wt/wt), and free of overt CVD. NGS identified 1103 miRNAs and 404,022 different isomiRs, of which 280 (25%) and 1418 (0.35%), respectively, passed an abundance threshold. Eighteen (sixteen/two) circulating miRNAs correlated positively/negatively, respectively, with CAC-CV%, nine of which also significantly discriminated between high/low CV risk through ROC-AUC analysis. IsomiR-ome analyses uncovered 67 isomiRs highly correlated (R ≥ 0.55) with CAC-CV%. Specific isomiRs of miRNAs 101-3p, 144-3p, 421, and 484 exhibited stronger associations with CAC-CV% compared to their corresponding miRNA. Additionally, while miRNAs 140-3p, 223-3p, 30e-5p, and 342-3p did not correlate with CAC-CV%, specific isomiRs with altered seed sequences exhibited a strong correlation with coronary atherosclerosis burden. Their predicted isomiRs-specific targets were uniquely enriched (compared to their canonical miRNA sequence) in CV Disease (CVD)-related pathways. Two of the isomiRs exhibited discriminative ROC-AUC, and another two showed a correlation with reverse cholesterol transport from cholesterol-loaded macrophages to ApoB-depleted plasma. In summary, we propose a pipeline for exploring circulating isomiR-ome as an approach to uncover novel and strong CVD biomarkers.


Assuntos
Doenças Cardiovasculares , MicroRNA Circulante , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , Pessoa de Meia-Idade , MicroRNAs/genética , Cálcio , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , Projetos Piloto , Fatores de Risco , Cálcio da Dieta , MicroRNA Circulante/genética , Biomarcadores , Fatores de Risco de Doenças Cardíacas , Colesterol
19.
Retina ; 44(3): 381-391, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38166007

RESUMO

PURPOSE: To compare the efficacy and safety of pars plana vitrectomy with and without internal limiting membrane (ILM) peeling for macular hole (MH). METHODS: A systematic literature search on Ovid MEDLINE, Embase, Cochrane Library, and Google Scholar was performed from January 2000 to 2023. The primary outcome was the final best-corrected visual acuity (BCVA). Secondary outcomes included MH closure rates and the need for repeat surgery. The authors performed a random-effects meta-analysis on Review Manager 5.4. RESULTS: Fourteen studies on 880 eyes were included. Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA ( P = 0.66). However, pars plana vitrectomy without ILM peeling achieved a significantly better final BCVA in eyes with closed MHs (WMD = 0.05 logMAR, 95% CI, 0.01-0.10, P = 0.02). Pars plana vitrectomy with ILM peeling achieved a significantly higher primary MH closure rate (RR = 1.21, 95% CI, 1.04-1.42, P = 0.02) and lower incidence of MH reoperation (RR = 0.19, 95% CI, 0.11-0.33, P < 0.001). The final MH closure rate ( P = 0.12) and incidence of MH recurrence ( P = 0.25) were similar between groups. CONCLUSION: Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA. However, pars plana vitrectomy without ILM peeling achieved a better final BCVA in eyes with closed MHs. ILM peeling achieved a greater primary MH closure rate and reduced need for reoperation.


Assuntos
Membrana Epirretiniana , Perfurações Retinianas , Humanos , Vitrectomia , Perfurações Retinianas/cirurgia , Retina , Reoperação , Acuidade Visual , Membrana Basal/cirurgia , Estudos Retrospectivos , Membrana Epirretiniana/cirurgia
20.
Retina ; 44(6): 950-953, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38215455

RESUMO

INTRODUCTION: To determine whether the two popular artificial intelligence chatbots, ChatGPT and Bard, can provide high-quality information concerning procedure description, risks, benefits, and alternatives of various ophthalmic surgeries. METHODS: ChatGPT and Bard were prompted with questions pertaining to the description, potential risks, benefits, alternatives, and implications of not proceeding with various surgeries in different subspecialties of ophthalmology. Six common ophthalmic procedures were included in the authors' analysis. Two comprehensive ophthalmologists and one subspecialist graded each response independently using a 5-point Likert scale. RESULTS: Likert grading for accuracy was significantly higher for ChatGPT in comparison with Bard (4.5 ± 0.6 vs. 3.8 ± 0.8, P < 0.0001). Generally, ChatGPT performed better than Bard even when questions were stratified by the type of ophthalmic surgery. There was no significant difference between ChatGPT and Bard for response length (2,104.7 ± 271.4 characters vs. 2,441.0 ± 633.9 characters, P = 0.12). ChatGPT responded significantly slower than Bard (46.0 ± 3.0 vs. 6.6 ± 1.2 seconds, P < 0.0001). CONCLUSION: Both ChatGPT and Bard may offer accessible and high-quality information relevant to the informed consent process for various ophthalmic procedures. Nonetheless, both artificial intelligence chatbots overlooked the probability of adverse events, hence limiting their potential and introducing patients to information that may be difficult to interpret.


Assuntos
Inteligência Artificial , Procedimentos Cirúrgicos Oftalmológicos , Humanos , Educação de Pacientes como Assunto/métodos , Internet
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