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Background: The mucogingival conditions associated with the recession defects at the mandibular anterior region, not only make plaque control difficult to be performed by the patient but also pose a problem in passively advancing the tissues at the recipient site. This surgical technique is used to treat multiple recession defects in the mandibular anterior region. Materials and Methods: Twenty-five sites in 17 subjects (11 women and 6 men) underwent modified bridge flap and de-epithelized gingival unit graft (d-GUG) as a single-step treatment modality to cover the denuded root surface, as well as increase the width of keratinized gingiva in recession type 1 gingival recession defects in the mandibular anterior region. Results: Nearly 60% of sites in our study showed complete root coverage, with a mean root coverage percentage of 88.08%. Furthermore, keratinized tissue width, keratinized tissue thickness as well as vestibular depth showed statistically significant increases as compared to baseline levels. Conclusion: Thus, the modified bridge flap technique using d-GUG within the limitations of our study design, showed promising results in terms of recession coverage as well as management of the difficult mucogingival conditions at the mandibular anterior region.

Background Accelerating door‐in‐door‐out (DIDO) times at primary stroke centers (PSCs) for patients with large vessel occlusion (LVO) acute ischemic stroke transferred for possible endovascular stroke therapy (EVT) is important to optimize outcomes. Here, we assess whether automated LVO detection coupled with secure communication at non‐EVT performing PSCs improves DIDO time and increases the proportion of patients receiving EVT after transfer. Methods From our prospectively collected multicenter registry, we identified patients with LVO acute ischemic stroke that presented to one of 7 PSCs in the Greater Houston area from January 1, 2021, to February 27, 2022. Noncontrast computed tomography and computed tomographic angiography were performed in all patients at the time of presentation, per standard of care. A machine learning (artificial intelligence [AI]) algorithm trained to detect LVO (Viz.AI) from computed tomographic angiography was implemented at all 7 hospitals. The primary outcome of the study was DIDO at the PSCs and was determined using multivariable linear regression adjusted for sex and on/off hours. Secondary outcomes included likelihood of receiving EVT post‐transfer. Results Among 115 patients who met inclusion criteria, 80 were evaluated pre‐AI and 35 post‐AI. The most common occlusion locations were middle cerebral artery (51.3%) and internal carotid artery (25.2%). There were no substantial differences in demographics or presentation characteristics between the 2 groups. Median time from onset to PSC arrival was 117 minutes (interquartile range, 54–521 minutes). In univariable analysis, patients evaluated at the PSCs after AI implementation had a shorter DIDO time (median difference, 77 minutes; P

Understanding the cell cycle at the single-cell level is crucial for cellular biology and cancer research. While current methods using fluorescent markers have improved the study of adherent cells, non-adherent cells remain challenging. In this study, we addressed this gap by combining a specialized surface to enhance cell attachment, the FUCCI(CA)2 sensor, an automated image analysis pipeline, and a custom machine learning algorithm. This approach enabled precise measurement of cell cycle phase durations in non-adherent cells. This method was validated in acute myeloid leukemia cell lines NB4 and Kasumi-1, which have unique cell cycle characteristics, and we tested the impact of cell cycle-modulating drugs on NB4 cells. Our cell cycle analysis system, which is also compatible with adherent cells, is fully automated and freely available, providing detailed insights from hundreds of cells under various conditions. This report presents a valuable tool for advancing cancer research and drug development by enabling comprehensive, automated cell cycle analysis in both adherent and non-adherent cells., Competing Interests: KH, CS, ES, EC, OE, SP, IN, GB, GF, RC, SM, SR No competing interests declared, (© 2024, Hayatigolkhatmi, Soriani, Soda et al.)

Background and Aims: Immediate factor Xa (FXa) inhibition exerts direct antiplatelet effects in the context of arterial thrombosis but little is known about the impact of long-term therapy on platelet function in ischemic cardiovascular diseases., Methods: We evaluated the effect of acute versus chronic FXa inhibition on thromboinflammation following acute myocardial infarction (AMI) and stroke in mice in vivo. Mechanistically, we identified changes in platelet gene expression and proteome under chronic FXa NOAC and characterized its functional consequence on platelet physiology. In a prospectively recruited cohort of AMI patients, we determined CMR based cardiac endpoints under FXa NOAC effects on clinical endpoints in a cohort of AMI patients., Results: Chronic but not acute FXa inhibition reduced cerebral and myocardial infarct size and improved cardiac function 24h after AMI in mice. Mechanistically, we identified an attenuated thromboinflammatory response with reduced NET formation in mice and patient samples. Proteome and RNA expression analysis of FXa-inhibitor treated patients revealed a reduction of key regulators within the membrane trafficking and secretion machinery hampering platelet alpha and dense granule release. Subsequent, thromboinflammatory NET density in thrombi isolated from stroke and myocardial infarction patients was reduced. AMI patients treated with FXa inhibitors showed decreased infarct size after myocardial infarction compared to patients without anticoagulation treatment., Conclusions: Long-term FXa inhibition induces anti-thromboinflammatory proteome signatures in platelets, improving infarct size after myocardial infarction and stroke., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Esophageal cancer is the eighth most common cause of cancer-related deaths worldwide. There are two main histological subtypes of esophageal cancer: adenocarcinoma and squamous cell carcinoma. Among the factors associated with the development of esophageal cancer, estrogen receptor beta (ERβ) has been found to have a clinical significance., Aim: To investigate the relationship between ERβ expression and esophageal cancer., Methods: English Medical literature searches were conducted for ERβ expression in patients with esophageal cancer versus healthy controls. Searches were performed up to August 31, 2023, using MEDLINE, PubMed, Embase and Google Scholar. Meta-analysis was performed by using Comprehensive meta-analysis software (Version 4, Biostat Inc., Englewood, NJ, USA). Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated. Heterogeneity was evaluated using Cochrane Q-test, and it was considered present if the Q-test P value was less than 0.10. I 2 statistic was used to measure the proportion of inconsistency in individual studies, with I 2 > 50% representing heterogeneity. We also calculated a potential publication bias., Results: Ten studies representing 11 substudies were selected according to the inclusion criteria. The odds ratio of ERβ expression in fixed effect analysis was 0.448, 95% CI: 0.237 to 0.846, 55.2% lower in esophageal cancer than in normal mucosa. Heterogeneity and inconsistency were low, and no publication bias was demonstrated., Conclusion: This meta-analysis showed that ERβ expression is lower in esophageal cancer biopsy specimens than in healthy controls, this finding may have a significant effect on survival and can lead to new therapeutic avenues.

Background and Objectives: Early in the global COVID-19 pandemic, a concern was raised that potentially high volumes of COVID-19 inpatients in general hospitals might compromise the hospitals' capabilities to maintain high-quality care for routine patients and, thereby, to comply with indicators specifying quality of care. The objective of this study is to evaluate the impact of the surges of COVID-19 inpatients into general hospitals in Israel on the compliance rates for selected quality indicators reported by these hospitals within the Israeli National Program for Quality Indicators (NPQI)., Methods: Compliance rate data were collected from the quality indicators reports made to the NPQI by participating hospitals. COVID-19 inpatient volume data were obtained from the Ministry of Health Digital Technologies and Data Division. Both datasets were analyzed on a week-by-week basis and plotted one alongside the other on a time scale. Association of each quality indicator's compliance rate with the number of COVID-19 inpatients was tested by Pearson's correlation analysis. The study included data from July 1, 2019 through June 30, 2022, spanning the duration of the COVID-19 pandemic in Israel. Five quality indicators included in the study were: Surgical repair of femoral neck fracture within 48 h of admission; Assessment of cerebral ischemic event risk for patients with atrial fibrillation; Duplex carotid ultrasound within 72 h of emergency department admission for patients with suspected transient ischemic attack; Antibiotic prophylaxis for caesarean sections; and Percutaneous coronary intervention within 90 min for patients presenting with ST-elevation myocardial infarction., Results: Compliance rates for five quality indicators, representing different aspects of routine health care, remained steady - even at times with high volumes of COVID-19 inpatients in general hospitals. This lack of effect was prominent throughout the analyzed period, i.e., general hospitals maintained similar compliance rates for all quality indicators both during the surges of COVID-19 patients and between these periods. Statistical analysis showed no correlation between the quality indicators' compliance rates and the number of COVID-19 inpatients., Conclusions: Our findings indicate that high volumes of COVID-19 inpatients in general hospitals did not affect the hospitals' capability to comply with routine health care quality indicators. The results of our study imply that general hospitals in Israel were able to withstand the challenges associated with the care of COVID-19 inpatients while preserving high quality of care for routine patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To establish initial validity of "U-Rate-UE", a single-question scale regarding perceived recovery of the stroke affected upper extremity (UE)., Design: A retrospective longitudinal study of data collected at rehabilitation admission, 6 weeks, and 6 months since stroke., Setting: Stroke rehabilitation and community-based., Participants: A convenience sample of 87 individuals, median (interquartile range) age 71.5 (65-80) years, 15.0 (12-20) days post-stroke., Interventions: Not applicable., Main Outcome Measures: The affected UE was assessed using the Fugl-Meyer Motor Assessment, grip strength, Action Research Arm Test, the Box and Block Test (BBT), and The Rating of Everyday Arm-Use in the Community and Home. Participants also rated how much they perceive that their affected UE recovered from the stroke using U-Rate-UE; 0-100 (no to full recovery). Longitudinal changes in U-Rate-UE ratings were assessed. In addition, at 6 weeks and 6 months post-stroke, the change in BBT was calculated and participants were grouped into achieved/did not achieve the minimal detectable change (MDC). Correlations between U-Rate-UE to the other UE assessments were assessed at all 3 timepoints., Results: Significant changes in U-Rate-UE were seen over time (P<.05). At 6 weeks and 6 months, participants who achieved BBT-MDC rated their recovery significantly higher than participants who did not. U-Rate-UE was moderately-strongly significantly correlated to UE assessments (rho=.61-.85, P<.001)., Conclusions: The U-Rate-UE is supported for use with UE assessments contributing to comprehensive clinical understanding of the recovery of the affected UE in adults post-stroke., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

RAC1 P29S is the third most prevalent hotspot mutation in sun-exposed melanoma. RAC1 alterations in cancer are correlated with poor prognosis, resistance to standard chemotherapy, and insensitivity to targeted inhibitors. Although RAC1 P29S mutations in melanoma and RAC1 alterations in several other cancers are increasingly evident, the RAC1-driven biological mechanisms contributing to tumorigenesis remain unclear. Lack of rigorous signaling analysis has prevented identification of alternative therapeutic targets for RAC1 P29S -harboring melanomas. To investigate the RAC1 P29S -driven effect on downstream molecular signaling pathways, we generated an inducible RAC1 P29S expression melanocytic cell line and performed RNA-sequencing (RNA-seq) coupled with multiplexed kinase inhibitor beads and mass spectrometry (MIBs/MS) to establish enriched pathways from the genomic to proteomic level. Our proteogenomic analysis identified CDK9 as a potential new and specific target in RAC1 P29S -mutant melanoma cells. In vitro, CDK9 inhibition impeded the proliferation of in RAC1 P29S -mutant melanoma cells and increased surface expression of PD-L1 and MHC Class I proteins. In vivo, combining CDK9 inhibition with anti-PD-1 immune checkpoint blockade significantly inhibited tumor growth only in melanomas that expressed the RAC1 P29S mutation. Collectively, these results establish CDK9 as a novel target in RAC1-driven melanoma that can further sensitize the tumor to anti-PD-1 immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)