Inhibition ratio (I.R.) and transformation index (T.I.): new indexes to compare the effectiveness and clinical behaviour of modern progestin-only pills (POP).

Progestin-only pills (POPs) have emerged as a crucial contraceptive option for women, particularly those contraindicated to oestrogens. This opinion paper introduces two new indices, the Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.), to evaluate and compare the efficacy and clinical behaviour of modern POPs. The I.R. quantifies the ratio between the progestin dosage in a POP and the minimum dose required to inhibit ovarian function, providing insights into contraceptive efficacy. The T.I., on the other hand, assesses its clinical impact by considering the ratio between the total progestin dose and the dose required to induce endometrial luteinising changes. Both indices thus offer valuable tools for comparing progestins even at significantly different dosages and regimens, providing information on clinical characteristics and drug effects. The newest formulations of POPs (Desogestrel 28 and Drospirenone 24 + 4) have demonstrated higher I.R. and T.I. in comparison to older versions, indicating significant improvements in contraceptive efficacy and clinical impact with better menstrual cycle control. We believe that using these indices will ensure a more informed and personalised choice of progestin not only for contraceptive purposes but also for therapeutic use in gynaecology. The future goal is to develop other progestins with even more advantageous I.R. and T.I., ensuring the best contraceptive efficacy with fewer side effects, even in women at risk (obese, etc.).

The Inhibition Ratio (I.R.) (cyclical and daily) and the Transformation Index (T.I.) are two new proposed indexes to evaluate and compare the efficacy and clinical behaviour of modern and future POPs.

Modular Synthesis of Azines Bearing a Guanidine Core from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Reagents.

N-Heterocyclic carbene (NHC)-derived selenoureas comprise a fundamentally important class of NHC derivatives, with key applications in coordination chemistry and the determination of NHC electronic properties. Considering the broad reactivity of chalcogen-containing compounds, it is surprising to note that the use of NHC-derived selenoureas as organic synthons remains essentially unexplored. The present contribution introduces a novel, straightforward transformation leading to azines bearing a guanidine moiety, through the reaction of a wide range of NHC-derived selenoureas with commercially available diazo compounds, in the presence of triphenylphosphine. This transformation offers a new approach to such products, having biological, materials chemistry, and organic synthesis applications. The guanidine-bearing azines are obtained in excellent yields, with all manipulations taking place in air. A reaction mechanism is proposed, based on both experimental mechanistic findings and density functional theory (DFT) calculations. A one-pot, multicomponent transesterification reaction between selenoureas, α-diazoesters, alcohols, and triphenylphosphine was also developed, providing highly functionalized azines.

Recurrent and transformation of borderline to malignant phyllodes tumour with osteoid differentiation: a case report and literature review.

Phyllodes tumours or cystosarcoma phyllodes are fibroepithelial tumours of the breast and represent 1% of breast tumours. A 20-year-old nullipara presented with an enlarging left breast mass over 6 months. Although widely excised, it was reported to be a 12 × 10 × 5.5-cm borderline phyllodes tumour with involvement of the superior and inferior margins. Seven months later, she presented with a new ipsilateral breast lump measuring 8.5 × 7.5 × 4.6 cm. She underwent a left mastectomy, a three-rib resection with titanic rods for the thoracic cage reconstruction, and a latissimus dorsi flap wound closure. Histopathology revealed a high-grade malignant phyllodes tumour with features of osteoid differentiation with the nearest deep margin measuring 3 mm. She developed metastasis to the ipsilateral axillary lymph nodes and contralateral lung 2 months postoperatively. She was given palliative radiotherapy 60 Gy in 30 fractions to the left axilla. She developed sudden lower-limb weakness due to spinal metastases. The symptoms resolved with radiotherapy to the thoracic spine (T4-T8). As the lesion continued to grow rapidly from the anterior chest wall encircling towards the back, it was deemed unresectable. She was given palliative chemotherapy (doxorubicin six cycles, followed by ifosfamide one cycle) but had disease progression. She passed away 3 months later. The mainstay of treatment for phyllodes tumour is excision with a minimal margin of 1 cm. Although margins were involved after the first surgery, she was followed up as the pathology was a borderline phyllodes. When the lump recurred and had transformed, despite extensive surgery, it returned shortly and progressed. A borderline phyllodes should be excised to obtain a minimal margin of 1 cm, even if it means performing a mastectomy, to minimise recurrence. A recurrence may undergo malignant transformation which is largely chemotherapy and radiotherapy resistant. This will result in a poor outcome and decreased survival.

Predictors for Hemorrhagic Transformation among Patients with Ischemic Stroke Admitted in a Tertiary Hospital in the Philippines from July 2018-July 2019.

Background: Among the multiple scoring systems for hemorrhagic transformation, only few of these address spontaneous hemorrhagic transformation after an ischemic stroke, with most done with Western population data. Objectives: This study aims to identify the predictors for hemorrhagic transformation among patients with ischemic stroke admitted in a tertiary hospital in Cebu City, Philippines. Methods: This is a retrospective cohort study of patients with ischemic stroke admitted in a tertiary hospital in Cebu City. Patients' baseline characteristics, clinical, and radiologic data were collected. Chi square test and t-test were used to determine which variables were significantly different between patients with and without hemorrhagic transformation. Odds ratio (OR) and 95% confidence interval (CI) were determined to measure the association between the different variables and hemorrhagic transformation. Results: A total of 500 ischemic stroke patients were included in the study. There were 28 (6%) ischemic stroke patients with Hemorrhagic Transformation. The mean age of these patients is 66.93 ± 12.42 years, 48.8% male, 10.8% had atrial fibrillation, and 2.4% had myocardial infarction. Controlling for the effect of confounders, white blood cell count (OR 1.11; 95% CI 1.03-1.19), myocardial infarction (OR 5.25; 95% CI 1.13-24.34), and presence of brain edema (OR 2.86; 95% CI 1.05-7.80) were significant predictors of hemorrhagic transformation. Conclusion: White blood cell count, presence of brain edema, and myocardial infarction were significantly associated with hemorrhagic transformation among ischemic stroke patients.

Preparing for Value: Evaluating Organizational Culture in Health Care Transformation.

The health care industry is experiencing a transformative shift from traditional fee-for-service models to value-based care (VBC), emphasizing improved patient outcomes, enhanced quality, and reduced costs. While Centers for Medicare & Medicaid Services Innovation Center models focus on financial and quality outcomes, a critical opportunity for reform lies in organizational culture. VBC signifies a cultural and systemic evolution aligned with the quintuple aim of enhancing equitable patient outcomes, improving quality, reducing costs, and prioritizing provider well-being. Cultural impacts play a pivotal role in this transformation.

Backwater makes the tributaries of large river becoming phosphorus "sink".

The complex hydrological conditions caused by the backwater effect at the confluence inevitably modify the geochemical processes of elements. However, there is still a lack of comprehensive understanding regarding the precise transformation mechanisms of nutrients in large river systems. This study aimed to investigate the hydrodynamic characteristics and their impact on phosphorus transfer in the lower Han River, which is influenced by backwater from the Yangtze River (the largest river in China). By establishing a hydrodynamic-water quality model, we have determined that the discharge ratio (the ratio of flow between the Han River discharge and the Yangtze River discharge) can be utilized as a representative indicator of the backwater effect from the Yangtze River on the Han River. Three distinct patterns were identified in this study: mixing, backwater, and intrusion. The corresponding discharge ratio values were categorized as >0.08, 0.01∼0.08, and <0.01 respectively. Additionally, the extent of the backwater zone was determined, revealing that the length of the backwater zone increased from 50 km (XG) to 100 km (FS) as the discharge ratio decreased from 0.08 to 0.01. Furthermore, it was observed that the water level at the confluence rose from 2.52 m to 6.83 m in accordance with these changes in discharge ratio values. The migration pattern of phosphorus primarily involved the settling and retention of particulate phosphorus, particularly the labile particulate organic phosphorus (LOP) and dissolved organic phosphorus (DOP). When the confluent patterns became the intrusion pattern, the backwater zone expanded to 150 m (XT), causing a 10.40 m increase in water level at the confluence. An intrusion zone formed, and its phosphorus concentrations were same as Yangtze River's. Above the intrusion area, a backwater region formed and its concentrations of LOP and DOP decreased, while the concentration of PO43- increased due to the release from resuspended particles. This release was induced by higher velocity of bottom water brought about by the water exchange of two rivers. The discharge ratio of 0.01-0.08 resulted in the sedimentation of LOP and DOP, causing the lower Han River to act as a "sink" for phosphorus, potentially exacerbating phosphorus pollution. Higher discharge ratios in spring led to phosphorus release from sediment, increasing dissolved phosphorus concentrations and raising the risk of algal blooms in the lower Han River. These findings have significant implications for larger rivers worldwide and provide insights into strategies for ecological management and prevention of algal blooms.

Digital transformation and enterprise low-carbon innovation: A new perspective from innovation motivation.

From the perspective of innovation motivation, low-carbon innovation is divided into substantive low-carbon innovation and strategic low-carbon innovation. On this basis, this study empirically investigates the impact and mechanism of digital transformation on enterprise low-carbon innovation using data from China's A-share listed enterprises from 2005 to 2019. The results show that digital transformation promotes the overall level of enterprise low-carbon innovation, substantial low-carbon innovation, and strategic low-carbon innovation, with a more significant impact on strategic low-carbon innovation. For enterprises with large-scale, belonging to high-monopoly industries and located in high-marketization regions, the promotion of digital transformation is more significant and facilitates strategic low-carbon innovation more than substantive low-carbon innovation. Based on the internal capability perspective, enhancing management capability, R&D capability, and environmental information disclosure capability are three important channels of digital transformation affecting low-carbon innovation.

Changing ALK-TKI mechanisms of resistance in re-biopsies of ALK-rearranged NSCLC: ALK mutations followed by SCLC-like histologic transformation: A case report.

Anaplastic lymphoma kinase (ALK) inhibitors are the recommended treatment of ALK-rearranged non-small cell lung cancer but are prone to eventual drug resistance. Herein we report a 45-year-old Asian woman diagnosed with EML4-ALK rearranged lung adenocarcinoma. Small cell lung cancer-like phenotypic transformation occurred when resistance to crizotinib treatment. Next-generation sequencing was performed and detected an ALK rearrangement co-existent with a TP53 gene mutation in the small cell specimens. The patient had a good response to alectinib with a progression-free survival >7 months. After disease progression, newly emerged ALK p.G1269A and p.L1196 M gene mutations co-existent with ALK rearrangement were detected. The patient had a good initial response to ceritinib treatment, which last for >12 months. After ceritinib failure, however, more complicated mutations within the ALK kinase domain (p.G1269A, p.L1196 M, newly emerged p.D1203 N, and p.L1122V) were detected. Ultimately, due to terminal rapid progression and resistance to lorlatinib, the overall survival was nearly 3 years. Our case showed that next-generation ALK-tyrosine kinase inhibitors (TKIs) may be an appropriate choice after transformation to small cell lung cancer and failure to one ALK-TKI. Sequential biopsies and gene mutation monitoring are important to arrange the sequence of different generation ALK-TKIs. Appropriate sequential therapies may yield a prolonged response with a satisfactory quality of life in patients with advanced ALK-rearranged non-small cell lung cancer.

Clonal evolution process from essential thrombocythemia to acute myeloid leukemia in the original patient from whom the CALR-mutated Marimo cell line was established.

We previously reported the Marimo cell line, which was established from the bone marrow cells of a patient with essential thrombocythemia (ET) at the last stage after transformation to acute myeloid leukemia (AML). This cell line is widely used for the biological analysis of ET because it harbors CALR mutation. However, genetic processes during disease progression in the original patient were not analyzed. We sequentially analyzed the genetic status in the original patient samples during disease progression. The ET clone had already acquired CALR and MPL mutations, and TP53 and NRAS mutations affected the disease progression from ET to AML in this patient. Particularly, the variant allele frequency of the NRAS mutation increased along with the disease progression after transformation, and the NRAS-mutated clone selectively proliferated in vitro, resulting in the establishment of the Marimo cell line. Although CALR and MPL mutations co-existed, MPL was not expressed in Marimo cells or any clinical samples. Furthermore, mitogen-activated protein kinase (MAPK) but not the JAK2-STAT pathway was activated. These results collectively indicate that MAPK activation is mainly associated with the proliferation ability of Marimo cells.

Virtual Objective Structured Clinical Examination (OSCE) Training in the Pandemic Era: Feasibility, Satisfaction, and the Road Ahead.

INTRODUCTION: Objective Structured Clinical Examinations (OSCEs) are essential assessments for evaluating the clinical competencies of medical students. The COVID-19 pandemic caused a significant disruption in medical education, prompting institutions to adopt virtual formats for academic activities. This study analyzes the feasibility, satisfaction, and experiences of pediatric board candidates and faculty during virtual or electronic OSCE (e-OSCE) training sessions using Zoom video communication (Zoom Video Communications, Inc., San Jose, USA). METHODS: This is a post-event survey assessing the perceptions of faculty and candidates and the perceived advantages and obstacles of e-OSCE. RESULTS: A total of 142 participants were invited to complete a post-event survey, and 105 (73.9%) completed the survey. There was equal gender representation. More than half of the participants were examiners. The overall satisfaction with the virtual e-OSCE was high, with a mean score of 4.7±0.67 out of 5. Most participants were likely to recommend e-OSCE to a friend or colleague (mean score 8.84±1.51/10). More faculty (66.1%) than candidates (40.8%) preferred e-OSCE (P=0.006). CONCLUSION: Transitioning to virtual OSCE training during the pandemic proved feasible, with high satisfaction rates. Further research on virtual training for OSCE in medical education is recommended to optimize its implementation and outcomes.

A facilitator's reflection on the democratizing potential of emancipatory practice development.

Emancipatory practice development (ePD) is a practitioner-led research methodology which enables workplace transformation. Underpinned by the critical paradigm, ePD works through facilitation and workplace learning, with people in their local context on practice issues that are significant to them. Its purpose is to embed safe, person-centred learning cultures which transform individuals and workplaces. In this article, we critically reflect on a year-long ePD study in an acute care hospital ward. We explore the challenges of practice change within systems, building collective strength with frontline collaborations and leadership to sustain new learning cultures. Our work advances practice development dialogue through working closely with the underpinning theories. Our critique analyses how ePD can enact and sustain change within a complex system. We argue that ePD works to strengthen safety cultures by challenging antidemocratic practices through communicative action. By opening communicative spaces, ePD enables staff to collectively deliberate and reach consensus. Their raised awareness supports staff to resist ways of working which conspire against safe patient care. Sustainability of practice change is fostered by the co-operative democracies created within the frontline team and meso level enablement. We conclude that the democratising potential of ePDt generates staff agency at the frontline.

Non-target discovery and risk prediction of per- and polyfluoroalkyl substances (PFAS) and transformation products in wastewater treatment systems.

Wastewater treatment plants (WWTPs) serve as the main destination of many wastes containing per- and polyfluoroalkyl substances (PFAS). Here, we investigated the occurrence and transformation of PFAS and their transformation products (TPs) in wastewater treatment systems using high-resolution mass spectrometry-based target, suspect, and non-target screening approaches. The results revealed the presence of 896 PFAS and TPs in aqueous and sludge phases, of which 687 were assigned confidence levels 1-3 (46 PFAS and 641 TPs). Cyp450 metabolism and environmental microbial degradation were found to be the primary metabolic transformation pathways for PFAS within WWTPs. An estimated 52.3 %, 89.5 %, and 13.6 % of TPs were believed to exhibit persistence, bioaccumulation, and toxicity effects, respectively, with a substantial number of TPs posing potential health risks. Notably, the length of the fluorinated carbon chain in PFAS and TPs was likely associated with increased hazard, primarily due to the influence of biodegradability. Ultimately, two high riskcompounds were identified in the effluent, including one PFAS (Perfluorobutane sulfonic acid) and one enzymatically metabolized TP (23-(Perfluorobutyl)tricosanoic acid@BTM0024_cyp450). It is noteworthy that the toxicity of some TPs exceeded that of their parent compounds. The results from this study underscores the importance of PFAS TPs and associated environmental risks.

Fluoride-induced hypertension by regulating RhoA/ROCK pathway and phenotypic transformation of vascular smooth muscle cells: In vitro and in vivo evidence.

Fluoride exposure has been implicated as a potential risk factor for hypertension, but the underlying mechanisms remain unclear. This study investigated the role of the RhoA/ROCK signaling pathway in fluoride-induced hypertension. Male Wistar rats were divided into different groups and exposed to varying concentrations of sodium fluoride (NaF) or sodium chloride (NaCl) via drinking water. The rats' blood pressure was measured, and their aortic tissue was utilized for high-throughput sequencing analysis. Additionally, rat and A7r5 cell models were established using NaF and/or Fasudil. The study evaluated the effects of fluoride exposure on blood pressure, pathological changes in the aorta, as well as the protein/mRNA expression levels of phenotypic transformation indicators (a-SMA, calp, OPN) in vascular smooth muscle cells (VSMCs), along with the RhoA/ROCK signaling pathway (RhoA, ROCK1, ROCK2, MLC/p-MLC). The results demonstrated that fluoride exposure in rats led to increased blood pressure. High-throughput sequencing analysis revealed differential gene expression associated with vascular smooth muscle contraction, with the RhoA/ROCK signaling pathway emerging as a key regulator. Pathological changes in the rat aorta, such as elastic membrane rupture and collagen fiber deposition, were observed following NaF exposure. However, fasudil, a ROCK inhibitor, mitigated these pathological changes. Both in vitro and in vivo models confirmed the activation of the RhoA/ROCK signaling pathway and the phenotypic transformation of VSMCs from a contractile to a synthetic state upon fluoride exposure. Fasudil effectively inhibited the activities of ROCK1 and ROCK2 and attenuated the phenotypic transformation of VSMCs. In conclusion, fluoride has the potential to induce hypertension through the activation of the RhoA/ROCK signaling pathway and phenotypic changes in vascular smooth muscle cells. These results provide new insights into the mechanism of fluoride-induced hypertension.

[Recycled formalin: A new environmental mitigation tool in pathology?] / Le formol recyclé : un nouvel outil d'atténuation de l'impact environnemental de l'ACP ?

Formalin is the international gold-standard fixative in pathology laboratories. However it is not the ideal one considering its deleterious effects on individuals and the environment. Complete formalin removal or even substitution does not seem possible in the near future. In this update, we present various tools allowing to integrate the use of formalin into an ecocare approach. Among them, formalin recycling according to the protocol developed by the University Hospital of Bordeaux is simple to implement and delivers rapid and significant results, allowing pathology professionals to meet the sustainable development objectives included in the France 2030 agenda.

Topological Transformation of Hydrogen-Terminated Germanium to Germanium Nanosheets for Fast Lithium Storage.

Germanium has been recognized as a promising anode material for lithium-ion batteries (LIBs) due to its high theoretical capacity and excellent lithium-ion diffusivity. Nonetheless, it is challenging to enhance both the high-rate performance and long-term cycling stability simultaneously. This study introduces a novel heterostructure composed of germanium nanosheets integrated with graphene (Ge NSs@Gr). These nanosheets undergo an in situ phase transformation from a hydrogen-terminated multilayer germanium compound termed germanane (GeH) derived via topochemical deintercalation from CaGe2. This approach mitigates oxidation and prevents restacking by functionalizing the exfoliated germanane with octadecenoic organic molecules. The resultant germanium nanosheets retain their structural integrity from CaGe2 and present an exposed, active (111) surface that features an open crystal lattice, facilitating swift lithium-ion migration conducive to lithium storage. The composite material delivers a substantial reversible capacity of 1220 mA h g-1 at a current density of 0.2 C and maintains a capacity of 456 mA h g-1 even at an ultrahigh current density of 10 C over extended cycling. Impressively, a capacity of 316 mA h g-1 remains after 5000 cycles. The exceptional high-rate performance and durable cycling stability underscore the Ge NSs@Gr anode's potential as a highly viable option for LIBs.

Correlating Thickness and Phase of Single Co(OH)2 Micro-Platelets to the Intrinsic Activity of Oxygen Evolution Electrocatalysis.

Morphology, crystal phase, and its transformation are important structures that frequently determine electrocatalytic activity, but the correlations of intrinsic activity with them are not completely understood. Herein, using Co(OH)2 micro-platelets with well-defined structures (phase, thickness, area, and volume) as model electrocatalysts of oxygen evolution reaction, multiple in situ microscopy is combined to correlate the electrocatalytic activity with morphology, phase, and its transformation. Single-entity morphology and electrochemistry characterized by atomic force microscopy and scanning electrochemical cell microscopy reveal a thickness-dependent turnover frequency (TOF) of α-Co(OH)2. The TOF (≈9.5 s-1) of α-Co(OH)2 with ≈14 nm thickness is ≈95-fold higher than that (≈0.1 s-1) with ≈80 nm. Moreover, this thickness-dependent activity has a critical thickness of ≈30 nm, above which no thickness-dependence is observed. Contrarily, ß-Co(OH)2 reveals a lower TOF (≈0.1 s-1) having no significant correlation with thickness. Combining single-entity electrochemistry with in situ Raman microspectroscopy, this thickness-dependent activity is explained by more reversible Co3+/Co2+ kinetics and larger ratio of active Co sites of thinner α-Co(OH)2, accompanied with faster phase transformation and more extensive surface restructuration. The findings highlight the interactions among thickness, ratio of active sites, kinetics of active sites, and phase transformation, and offer new insights into structure-activity relationships at single-entity level.

Symmetric Anion Mediated Dynamic Kinetic Asymmetric Knoevenagel Reaction for N-C and N-N Atropisomers Synthesis.

A symmetric anion mediated dynamic kinetic asymmetric Knoevenagel reaction was established as a general and efficient method for accessing both N-C and N-N atropisomers. The resulting highly enantio-pure pyridine-2,6(1H,3H)-diones exhibit diverse structures and functional groups. The key to excellent regio- and remote enantiocontrol could be owed to the hydrogen bond between the enolate anion and triflamide block of the organocatalyst. This connected the enolate anion and iminium cation by a chiral backbone. The mechanism investigation via control experiments, correlation analysis, and density functional theory calculations further revealed how the stereochemical information was transferred from the catalyst into the axially chiral pyridine-2,6(1H,3H)-diones. The synthetic applications also demonstrated the reaction's potential.

Biomarkers of epithelial-mesenchymal transition: E-cadherin and beta-catenin in malignant transformation of oral lesions.

Objective: Detecting oral lesions at high risk of becoming cancer may enable early interventions to prevent oral cancer. The diagnosis of dysplasia in an oral lesion is used to predict this risk but is subject to interobserver and intraobserver variability. Studying biomarkers or molecular markers that reflect underlying molecular alterations can serve as an additional and objective method of risk assessment. E-cadherin and beta-catenin, molecular markers of epithelial-mesenchymal transition (EMT), potentially contribute to early malignant progression in oral tissue. This narrative review provides an overview of EMT, its relation to oral cancer, and the interaction among E-cadherin, beta-catenin, and the Wnt pathway in malignant progression of oral tissue. Methods: Full-text literature on EMT, E-cadherin, beta-catenin, oral epithelial dysplasia, and oral cancer was retrieved from PubMed and Google Scholar. Results: Sixty original research articles, reviews, and consensus statements were selected for review. Discussion: EMT, a biological mechanism characterized by epithelial and mesenchymal changes, can contribute to cancer development. Molecular markers of EMT including TWIST, vimentin, and N-cadherin may serve as prognostic markers of oral cancer. Dependent on Wnt pathway activity and the loss of membranous E-cadherin, E-cadherin and beta-catenin can play various roles along the spectrum of malignant progression, including tumour inhibition, early tumour progression, and late-stage tumour progression. Cross-sectional immunohistochemical research has found changes in expression patterns of E-cadherin and beta-catenin from normal oral tissue, oral epithelial dysplasia, to oral squamous cell carcinoma. Conclusion: Future research should explore the longitudinal role of EMT markers in predicting malignant progression in oral tissue.

Objectif: La détection de lésions buccales présentant un risque élevé d'évoluer en cancer peut permettre des interventions précoces pour prévenir le cancer de la bouche. Le diagnostic de dysplasie dans le cas de lésions buccales sert à prédire ce risque, mais il est soumis à une variabilité d'un observateur à l'autre et avec le même observateur. L'étude de marqueurs biologiques ou de marqueurs moléculaires correspondant à des altérations moléculaires sous-jacentes peut constituer une méthode objective supplémentaire d'évaluation des risques. L'E-cadhérine et la bêta-caténine, des marqueurs moléculaires de la transition épithélio-mésenchymateuse (TEM), pourraient contribuer aux premières étapes de l'évolution maligne du tissu buccal. Cette revue narrative donne un aperçu de la TEM, de ses liens avec le cancer de la bouche et de l'interaction entre l'E-cadhérine, la bêta-caténine et la voie de signalisation Wnt dans l'évolution maligne du tissu buccal. Méthodes: On a obtenu le texte intégral d'études portant sur la TEM, l'E-cadhérine, la bêta-caténine, la dysplasie épithéliale buccale et le cancer de la bouche sur PubMed et Google Scholar. Résultats: Soixante articles sur des études originales, des revues et des déclarations de consensus ont été sélectionnés aux fins d'examen. Discussion: La TEM, un mécanisme biologique caractérisé par des changements épithéliaux et mésenchymateux, peut contribuer à l'apparition d'un cancer. Les marqueurs moléculaires de la TEM, notamment TWIST, la vimentine et la N-cadhérine, peuvent servir de marqueurs pronostiques du cancer de la bouche. En fonction de l'activité de la voie de signalisation Wnt et de la perte de l'E-cadhérine membraneuse, l'E-cadhérine et la bêta-caténine peuvent jouer divers rôles dans le spectre de l'évolution maligne, notamment l'inhibition tumorale, la progression tumorale précoce et l'évolution tumorale avancée. Des études transversales d'immunohistochimie ont révélé des changements dans les modèles d'expression de l'E-cadhérine et de la bêta-caténine avec le passage du tissu buccal normal, de la dysplasie épithéliale buccale au carcinome squameux de la bouche. Conclusion: À l'avenir, des études devraient explorer le rôle longitudinal des marqueurs de la TEM dans la prévision de l'évolution maligne dans les tissus buccaux.

Controversies regarding oral lichen planus and lichenoid-dysplastic lesions.

Objective: Oral lichen planus (OLP) is an immune-mediated condition featuring chronic inflammation. The World Health Organization classifies OLP as potentially malignant, but it is believed that the malignant transformation of OLP occurs in lesions with both lichenoid and dysplastic features (LD). This review discusses the issues surrounding OLP and LD, including their malignancy, classification, and categorization, and whether lichenoid inflammation causes dysplastic changes in LD or vice versa. Methods: English full-text literature on OLP, LD and/or dysplasia was retrieved from PubMed, CINAHL, and Google Scholar. Results: Thirty-six publications including original research articles, reviews, meta-analyses, books, reports, letters, and editorials were selected for review. Discussion: Research suggests that OLP has malignant potential, although small, and that LD should not be disregarded, as dysplasia presenting with or without lichenoid features may develop into cancer. There is also disagreement over the classification and categorization of LD. Different terms have been used to classify these lesions, including lichenoid dysplasia, OLP with dysplasia, and dysplasia with lichenoid features. Moreover, in LD, it is not clear if dysplasia or lichenoid infiltration appears first, and if inflammation is a response to dysplasia or if dysplasia is a response to the persistent inflammation. The main limitation in the literature is the inconsistency and subjective nature of histological diagnoses, which can lead to interobserver and intraobserver variation, ultimately resulting in the inaccurate diagnosis of OLP and LD. Conclusion: Although further research is required to understand OLP and LD, both lesions should be considered potentially malignant and should not be disregarded.

Objectif: Le lichen plan buccal (LPB) est une pathologie auto-immune qui se présente sous la forme d'une inflammation chronique. Selon la classification de l'Organisation mondiale de la santé, le LPB est une pathologie potentiellement maligne. Toutefois, on soupçonne que la transformation maligne du LPB se produit dans des lésions présentant à la fois des caractéristiques lichénoïdes et dysplasiques (LD). Cet examen porte sur les questions relatives au LPB et aux LD, notamment leur malignité, leur classification et leur catégorisation, et pour savoir si l'inflammation du lichénoïde entraîne des changements dysplasiques des LD ou vice versa. Méthodes: On a utilisé le texte intégral de documents rédigés en anglais sur le LPB, les LD et la dysplasie issus de PubMed, de CINAHL et de Google Scholar. Résultats: Trente-six publications, notamment des articles sur des études originales, des revues, des méta-analyses, des livres, des rapports, des lettres et des éditoriaux, ont été sélectionnées aux fins d'examen. Discussion: Des études suggèrent que le LPB est potentiellement malin, bien que ce potentiel soit faible, et que les LD ne doivent pas être ignorés : en effet, une dysplasie peut évoluer en cancer, qu'elle présente des caractéristiques lichénoïdes ou non. On constate également un désaccord quant à la classification et à la catégorisation des LD. Différents termes ont été utilisés pour la classification de ces lésions, notamment « dysplasie lichénoïde ¼, « LPB dysplasique ¼ et « dysplasie à caractéristiques lichénoïdes ¼. De plus, dans le cas des LD, on ne sait pas avec certitude si la dysplasie ou l'infiltration lichénoïde apparaît en premier, ni si l'inflammation découle de la dysplasie ou si la dysplasie est une conséquence de l'inflammation persistante. La principale limite de la littérature est due aux incohérences et à la nature subjective des diagnostics histologiques, qui peut entraîner des variations d'un observateur à l'autre ou même avec un même observateur, ce qui entraîne à terme des diagnostics erronés de LPB et de LD. Conclusion: Bien que d'autres études soient nécessaires pour comprendre le LPB et les LD, les lésions de ces 2 catégories doivent être considérées comme potentiellement malignes et ne doivent pas être ignorées.

Simultaneous genetic transformation and genome editing of mixed lines in soybean (Glycine max) and maize (Zea mays).

Robust genome editing technologies are becoming part of the crop breeding toolbox. Currently, genome editing is usually conducted either at a single locus, or multiple loci, in a variety at one time. Massively parallel genomics platforms, multifaceted genome editing capabilities, and flexible transformation systems enable targeted variation at nearly any locus, across the spectrum of genotypes within a species. We demonstrate here the simultaneous transformation and editing of many genotypes, by targeting mixed seed embryo explants with genome editing machinery, followed by re-identification through genotyping after plant regeneration. Transformation and Editing of Mixed Lines (TREDMIL) produced transformed individuals representing 101 of 104 (97%) mixed elite genotypes in soybean; and 22 of 40 (55%) and 9 of 36 (25%) mixed maize female and male elite inbred genotypes, respectively. Characterization of edited genotypes for the regenerated individuals identified over 800 distinct edits at the Determinate1 (Dt1) locus in samples from 101 soybean genotypes and 95 distinct Brown midrib3 (Bm3) edits in samples from 17 maize genotypes. These results illustrate how TREDMIL can help accelerate the development and deployment of customized crop varieties for future precision breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00173-5.