Publications by authors named "Yaron Rabinowitz"

Shedding light on the validity of sentence completion test (SCT) verbal defensiveness as an index of defensive behavior, the current two-part study examined the relationship between psychological threat and verbal defensiveness among military security and mission-critical team candidates using SCTs. Our study showed that as the threatening nature of SCT stems increased, defensive responses also increased, substantiating the link between psychological threat and defensive behavior. In addition, expert ratings of stem content revealed moderately strong relationships with defensive responses across two different SCTs, irrespective of their structural characteristics.

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Aims/hypothesis: Diabetes is associated with epigenetic modifications including DNA methylation and miRNA changes. Diabetic complications in the cornea can cause persistent epithelial defects and impaired wound healing due to limbal epithelial stem cell (LESC) dysfunction. In this study, we aimed to uncover epigenetic alterations in diabetic vs non-diabetic human limbal epithelial cells (LEC) enriched in LESC and identify new diabetic markers that can be targeted for therapy to normalise corneal epithelial wound healing and stem cell expression.

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Purpose: To evaluate the safety and efficacy of epithelium-off (epi‑off) corneal cross-linking (CXL) in patients with post-LASIK corneal ectasia (PLE) SETTING: Private clinical practice DESIGN: Prospective clinical trial METHODS: 82 eyes of adult patients post-LASIK, ages 21-67, with a topography pattern consistent with corneal ectasia, corrected distance visual acuity (CDVA) worse than 20/20, and minimum corneal pachymetry > 400 µm underwent epi‑off CXL. Exclusion criteria were patients with corneas that were thinner than 400 μm or demonstrated central corneal scarring, history of herpetic eye disease, pregnancy or nursing. Follow up examinations of spherical equivalent, uncorrected distance visual acuity (UDVA), CDVA, steep keratometry (K) and minimum pachymetry occurred on different but highly overlapping subsets of the operated eyes yearly until 5 years post-CXL.

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Purpose: To evaluate the safety and efficacy of epithelium-off (epi-off) corneal crosslinking (CXL) in adolescents with progressive keratoconus (KC).

Setting: Private clinical practice.

Design: Nonrandomized prospective clinical trial.

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Article Synopsis
  • * A large-scale study involving nearly 4,700 keratoconus cases and over 116,000 controls identified 36 genomic regions linked to the disease, highlighting issues with collagen integrity and cell differentiation as crucial factors.
  • * The findings reveal shared genetic mechanisms with other corneal diseases and suggest that the identified genetic variants account for 12.5% of keratoconus's genetic risk, paving the way for future diagnostic tests to assess susceptibility.
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  • * Genome-wide studies have confirmed existing gene associations and discovered new susceptibility variants related to corneal thickness and biomechanical properties.
  • * New findings on familial keratoconus, including a mouse model, and emerging genomic insights are paving the way for personalized treatment approaches in clinical practice.
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Human diabetic corneas develop delayed wound healing, epithelial stem cell dysfunction, recurrent erosions, and keratitis. Adenoviral gene therapy modulating c-Met, cathepsin F and MMP-10 normalized wound healing and epithelial stem cells in organ-cultured diabetic corneas but showed toxicity in stem cell-enriched cultured limbal epithelial cells (LECs). For a safer treatment, we engineered a novel nanobiopolymer (NBC) that carried antisense oligonucleotide (AON) RNA therapeutics suppressing cathepsin F or MMP-10, and miR-409-3p that inhibits c-Met.

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Both genetic and environmental factors have been considered to play a role in the etiology keratoconus. Eye rubbing, and more recently eye compression due to sleeping position, have been identified to be highly related to the condition, and are present in a high percentage of patients. Today, the predominant model is that these factors can provide the "second hit" necessary to generate the condition in a genetically susceptible individual.

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Article Synopsis
  • Keratoconus is a condition where the cornea thins and bulges, impairing vision and often requiring corneal transplants; researchers aimed to find genetic factors linked to the disease through a genome-wide study.
  • The study involved participants from various eye clinics across Australia, the U.S., and Northern Ireland, using advanced genetic testing methods to analyze and replicate findings across multiple cohorts.
  • Ultimately, the research assessed over 6 million genetic variants for connections to keratoconus and utilized various statistical methods, including logistic regression, to ensure accurate results.
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Article Synopsis
  • - Keratoconus (KC) is a common corneal disorder affecting over 300,000 people in the US, usually beginning during adolescence and worsening into the 30s and 40s, leading to significant vision-related quality of life issues.
  • - Researchers identified potential genetic variants related to familial KC by analyzing a four-generation family through whole exome and genome sequencing, focusing on the PPIP5K2 and PCSK1 genes.
  • - They conducted studies using both in vitro models and a gene-trap mouse model, revealing that the PPIP5K2 gene plays a crucial role in corneal health and KC development, highlighting new methods for studying corneal characteristics that could inform future diagnosis and treatment.
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  • A case study reports a woman with keratoconus who suffered bilateral corneal perforations after undergoing corneal cross-linking (CXL), potentially linked to mutations in the ZNF469 gene that she shares with her daughter.
  • Both individuals displayed similar corneal issues, but the daughter, who didn't have the procedure, did not experience perforation, suggesting that CXL may pose risks for certain genetic backgrounds.
  • The research highlights the need for identifying genetic risk factors like ZNF469 mutations to prevent severe complications from CXL in individuals with keratoconus.
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Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.

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Article Synopsis
  • The study investigates the differences in RNA expression between corneas from patients with keratoconus (KC) and healthy controls, using advanced RNA sequencing techniques.
  • A total of 436 coding RNAs and 584 long noncoding RNAs were found to have significant differential expression, highlighting genes linked to cell migration and other biological processes.
  • The results suggest specific genes and pathways that could play important roles in the development of keratoconus, potentially guiding future research and therapeutic strategies.
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  • Central corneal thickness (CCT) is a genetic trait linked to eye diseases like keratoconus and glaucoma, and a meta-analysis identified 19 new genetic regions associated with CCT.
  • The study highlights known genetic pathways related to connective tissue and discovers new gene sets, with over 20% of the CCT-related genes near those linked to Mendelian disorders.
  • A significant negative correlation was found between CCT and keratoconus (suggesting they influence each other), while no similar correlation was observed with primary open-angle glaucoma.
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Purpose: To comprehensively review the available published literature for cross-linking in the pediatric population.

Methods: Review of the literature published in English in PubMed.

Results: Two hundred ten publications were considered.

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Article Synopsis
  • The study aimed to investigate the involvement of TSC1 and TSC2 genes in a family affected by tuberous sclerosis complex (TSC) and bilateral keratoconus (KC), testing the idea that mutations in the same gene could also lead to nonsyndromic KC.
  • Researchers used next-generation sequencing and confirmed findings with Sanger sequencing to identify mutations in the TSC1 gene in patients with TSC and KC, as well as variants associated with nonsyndromic KC.
  • The results revealed a specific TSC1 mutation linked to both conditions, highlighting that different genetic mutations in TSC1 can lead to related yet distinct disorders, such as TSC and nonsyndromic KC.
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Purpose: To compare the visual, refractive, keratometric, topographic, and pachymetric outcomes of corneal collagen cross-linking (CXL) for progressive keratoconus following epithelial removal by transepithelial phototherapeutic keratectomy (PTK) or manual debridement.

Methods: In this analysis, 339 eyes (78% male, 22% female) that had undergone CXL following manual epithelial debridement (n = 180) or ablation via PTK (n = 159) were evaluated preoperatively and at 6, 12, and 24 months postoperatively for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), maximum corneal keratometry, pachymetry, and spherical equivalent. The data were analyzed in a t test to evaluate the relative efficacy of each epithelial removal procedure.

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Article Synopsis
  • * Recent studies, including genome-wide linkage and association studies, have improved understanding of KC genetics, revealing significant genes like LOX, ZNF469, and TGFBI that are linked to the condition.
  • * The use of quantitative endophenotypes in research has been effective in identifying genetic determinants, highlighting that various connective tissue disorders may share similar genetic links.
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  • This study aims to explore gene expression changes related to extracellular matrix (ECM) proteins in keratoconus (KC), corneal scarring, and normal corneas.
  • RNA was extracted from corneal tissues of 13 KC patients, 2 with scarring, and 4 normal controls, and analyzed to find significant changes in gene expression.
  • Results showed 21 genes with altered expression in KC patients, including downregulated collagens and upregulated TGFBI, suggesting these changes could serve as clinical markers for the disease.
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Purpose: To examine the expression of putative limbal epithelial stem cell (LESC) markers and wound healing rates in primary healthy and diabetic human limbal epithelial cells (LECs) cultured on different substrata.

Methods: Primary limbal epithelial cells were isolated from human autopsy corneas and discarded corneoscleral rims with dispase II treatment. LECs were cultured in EpiLife medium on human amniotic membrane (AM) denuded with mild alkali treatment, on plastic dishes and on glass slides coated with a mixture of human fibronectin, collagen type IV, and laminin (FCL).

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Purpose: Renal cell carcinoma (RCC) is the most common cancer of kidney. Evidences have shown that RCC is sensitive to various immunotherapies. Tim-3 plays a role in suppressing Th1-mediated immune responses.

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Helicobacter pylori infection occurs in more than half of the world's population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H.

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