Publications by authors named "Walid Fakhouri"

Background: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy are now standard of care in the first- or second-line settings for hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-) patients with advanced / metastatic breast cancer (ABC/MBC). Abemaciclib was first authorised in the United Kingdom (UK) in 2018 via patient access schemes before approval for routine use. This study assessed the treatment patterns and outcomes of abemaciclib in combination with endocrine therapy in a real-world setting.

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Previous studies implicate immune dysregulation in the metabolic changes accompanying obesity and type 2 diabetes. This study investigated the interplay between metabolic and immunological parameters during the progression of type 2 diabetes in an obese Mexican American cohort from Starr County, Texas. Individuals matched for age, gender, and BMI were stratified into five categories: diabetes-free, isolated impaired glucose tolerance, combined glucose impairment (fasting or post-load), type 2 diabetes without complications, and type 2 diabetes with lower extremity complications.

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Objective: To investigate the mechanism of Interferon Regulatory Factor 6 (IRF6) function in regulating adherens junction proteins and inflammatory cytokines in human salivary acinar cells and Sjögren's syndrome biopsies.

Design: We used mouse model, salivary cell lines, and human salivary gland (SG) biopsies to investigate IRF6 function in SG cellular integrity and immunomodulation.

Results: In Irf6-null mice, we observed myoepithelial cell detachment from acinar cells of major SGs, and the acini were remarkably disorganized compared to wild-type littermates.

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Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and pain. Baricitinib, a targeted JAK inhibitor indicated for moderate to severe RA, has shown efficacy and safety, but real-world data on effectiveness and discontinuation rates are limited. This study aimed to report time to discontinuation, effectiveness, and patient-reported outcomes in patients initiating baricitinib or other biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in the Spanish clinical practice.

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While the prognosis is generally good for hormone receptor-positive (HR+), human epidermal growth factor-negative (HER2-) early breast cancer (EBC) patients, up to 30% of patients with high-risk clinical and/or pathologic features experience recurrence. This retrospective cohort study was designed to estimate the proportion of BC patients meeting the high-risk criteria used in monarchE, a phase III study of abemaciclib, and to describe the characteristics, survival, and disease recurrence in a Danish patient population. The study cohort included all women with BC diagnosis registered in the Danish Breast Cancer Cooperative Group registry, and lumpectomy or mastectomy performed between January 1, 2010, and December 31, 2019.

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: An individual's genetic makeup influences their organ development, orofacial structures, and overall health. Though many studies have been conducted to determine the inheritance of oral diseases and conditions, there is a lack of comprehensive research classifying these disorders based on the genetic and environmental etiology. : This systematic review aimed to analyze the existing body of literature using the PubMed and Cochrane databases and answer the following question: "What evidence exists supporting the role of genetic factors in oral conditions?" This systematic-narrative review methodically categorizes oral diseases and conditions based on their genetic or environmental linkages.

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Introduction: We aim to assess the association of patient-reported pain and remission or low disease activity (LDA) at 3 months (M) in patients receiving baricitinib or other treatments in RA-BE-REAL.

Methods: RA-BE-REAL reports on patients with rheumatoid arthritis (RA) who were prescribed, for the first time, baricitinib (cohort A) or a tumour necrosis factor inhibitor (TNFi) (cohort B-TNFi) or any other mode of action (OMA) (cohort B-OMA). Pain was measured using the visual analogue scale (VAS) (0-100 mm) and clinically meaningful pain improvement thresholds of ≥ 30%, ≥ 50% and ≥ 70% from baseline to 3, 6, 12 and 24 M.

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Article Synopsis
  • In Finland, isolated cleft palate (CP) occurs more frequently than cleft lip with or without cleft palate (CL/P), which is the opposite trend seen in other European countries.
  • A genome-wide association study revealed a specific single nucleotide polymorphism (rs570516915) strongly linked to CP in the Finnish population, showing significant statistical results and confirmed in other cohorts.
  • The risk allele for rs570516915 disrupts a binding site for the IRF6 transcription factor, leading to decreased IRF6 expression, indicating that this genetic alteration may be a key factor in the mechanism causing CP.
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Background: The psoriatic arthritis (PsA) Observational Study of Persistence of Treatment (PRO-SPIRIT) assesses effectiveness and persistence of real-world PsA treatments. Ixekizumab (IXE) is an interleukin (IL)-17A inhibitor (i) (IL-17Ai), approved for the treatment of adult PsA.

Methods: The aim of this predefined interim analysis was to report baseline characteristics along with early (3-month) descriptive and comparative real-world effectiveness in patients with PsA prescribed with advanced treatment including IL-17Ai; IXE or secukinumab (SEC), IL-12/23i, IL-23i, tumour necrosis factor (TNFi) or Janus kinase (JAKi).

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The effectiveness of incorporating an audience response system (ARS) in improving the learning environment and student performance was assessed in a didactic biomedical science course at a large US dental school. Instructors and students were surveyed for their experiences of using Top Hat-based ARS in a multi-disciplinary biomedical science course. Average exam scores and grade distribution for challenging sections on immunology and developmental biology were compared before and after incorporating ARS.

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This real-world study aimed to describe patient and clinical characteristics, treatment patterns and outcomes for patients with HR+/HER2- metastatic breast cancer receiving abemaciclib in France, Italy and Spain. A multicenter chart review was conducted for adult females with HR+/HER2- advanced/metastatic breast cancer who received abemaciclib in routine care. Real-world progression-free survival (rwPFS) was estimated via Kaplan-Meier curves.

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Article Synopsis
  • In Finland, isolated cleft palate (CP) occurs more frequently than cleft lip with or without cleft palate (CL/P), which is the opposite trend seen in other European nations.
  • A genome-wide association study identified a specific SNP (rs570516915) that is strongly linked to CP in the Finnish and Estonian populations.
  • This SNP disrupts a binding site for the transcription factor IRF6, leading to decreased enhancer activity and impaired autoregulation, which may contribute to the increased risk of CP.
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  • Disease risk prediction can be enhanced by analyzing genomic sequences and transcriptional profiles, though identifying harmful non-coding DNA variations remains challenging for common diseases.
  • This study explores the interactions between P53 and cMYC proteins in regulation of target genes, revealing co-occupancy patterns in DNA regions that are conserved through evolution.
  • Results indicate that doxorubicin treatment leads to changes in protein levels and gene expression, suggesting a method to connect non-coding variations to gene regulation and disease risk screening.
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  • * Rats treated with TC showed increased testosterone levels in both plasma and saliva but did not experience changes in salivary flow, pH, or buffering capacity; however, certain proteins and minerals in saliva decreased.
  • * The results indicate that TC may harm the parotid and submandibular glands, which could pose risks to oral and overall health for individuals who misuse anabolic steroids.
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Objective: To investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters.

Materials And Methods: Twenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg).

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TWIST1 induces epithelial-to-mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N-terminus antagonizes TWIST1-regulated gene expression, cancer growth and metastasis.

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Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats.

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Article Synopsis
  • * The study focused on the co-occupancy and competitive interactions between the transcription factors P53 and cMYC in regulating gene expression, identifying that approximately 344-366 genomic regions were co-occupied by both factors in human and mouse embryonic stem cells.
  • * Treatment with doxorubicin altered protein levels of P53 and cMYC in certain cell types and resulted in significant changes in the expression of nearby genes, indicating that variations in non-coding DNA influence the binding affinity of these transcription factors, which in turn affects gene regulation
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Objective: This study aimed to analyze the salivary flow rate, biochemical composition, and redox status in orchiectomized spontaneously hypertensive rats (SHR) compared to normotensive Wistar rats.

Design: Thirty-two young adult male SHR and Wistar (3-months-old) rats were randomly distributed into four groups; either castrated bilaterally (ORX) or underwent fictitious surgery (SHAM) as Wistar-SHAM, Wistar-ORX, SHR-SHAM, and SHR-ORX. Two months beyond castration, pilocarpine-induced salivary secretion was collected from 5-month-old rats to analyze salivary flow rate, pH, buffer capacity, total protein, amylase, calcium, phosphate, sodium, potassium, chloride, thiobarbituric acid reactive substances (TBARs), carbonyl protein, nitrite, and total antioxidant capacity.

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Bone metabolism and repair are directly regulated by arachidonic acid metabolites. At present, we analyzed the dose-response effects of a selective cysteinyl leukotriene receptor type-1 antagonist during bone repair after tooth extraction and on non-injured skeleton. Sixty-three 129 Sv/Ev male mice composed the groups: C-Control (saline solution); MTK2-2 mg/Kg of Montelukast (MTK) and MTK4-4 mg/Kg of MTK, daily administered by mouth throughout all experimental periods set at 7, 14, and 21 days post-operative.

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(1) Background: Several studies showed a sustained temperature of 47 °C or 50 °C for one minute resulted in vascular stasis and bone resorption with only limited bone regrowth over a 3-4-week healing period. The purpose of the present study was to evaluate the temperature changes (ΔΤ) that occur during the preparation of dental implant osteotomies using MIS straight drills versus Densah burs in a clockwise (cutting) drilling protocol. (2) Methods: Two hundred forty (240) osteotomies of two different systems' drills were prepared at 6 mm depth at 800, 1000, and 1200 revolutions per minute (RPM), in fresh, unembalmed tibiae, obtained by a female cadaver.

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Introduction: RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment.

Methods: RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any cause (excluding sustained response) at 24 months, (i.

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Cell fate determination is a necessary and tightly regulated process for producing different cell types and structures during development. Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural plate borders into multiple cell lineages that differentiate into bone, cartilage, neurons and glial cells. We have previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation.

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Article Synopsis
  • The study aimed to create and validate prediction models to identify rheumatoid arthritis (RA) patients at high risk for adverse health outcomes while starting first-line methotrexate (MTX) treatment.
  • Data from 15 different claims and health record databases across 9 countries were analyzed, focusing on risks for various conditions at different time frames (3 months, 2 years, and 5 years) after treatment initiation.
  • The models showed good performance in predicting serious infections, myocardial infarction, and stroke, indicating potential for practical clinical application in monitoring RA patients on MTX.
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Oral ulcers are lesions that occur due to disruption of epithelial integrity of the mucosa of the oral cavity. Intraoral ulcers are often associated with pain, redness, symptoms of discomfort, and blood hemorrhage. The etiology for many oral ulcers is local trauma, systemic health conditions, or medication; for other ulcers the cause is less clear.

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