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This work was carried out in Provincial Enterprise from Hydraulicai Resources of Santiago de Cuba and a Genetic Laboratory from Central Research Station of Coffee and Cacao, Tercer Frente, Santiago de Cuba province, from February to June of 1996 period. The "in vitro" culture of Coffea arabica L. 'Catuai Rojo' var. embryos was made as substitute the traditionally culture media using wastewater of Neat Enterprise of Santiago de Cuba as alone and mixed form with coconut milk and ammonium nitrate. Main chemical components were analysed at 19, 27, 36 and 44 days after culturing, the stem and root length were evaluated. The statistical analysis showed a significative difference between treatments. The best behaviour culture media were wastewater complemented with 500 mg. l1 or 1000 mg. V of ammonium nitrate.

We analyse the stochastic properties of the 49 pulsars that comprise the first International Pulsar Timing Array (IPTA) data release. We use Bayesian methodology, performing model selection to determine the optimal description of the stochastic signals present in each pulsar. In addition to spin-noise and dispersion-measure (DM) variations, these models can include timing noise unique to a single observing system, or frequency band. We show the improved radio-frequency coverage and presence of overlapping data from different observing systems in the IPTA data set enables us to separate both system and band-dependent effects with much greater efficacy than in the individual pulsar timing array (PTA) data sets. For example, we show that PSR J1643-1224 has, in addition to DM variations, significant band-dependent noise that is coherent between PTAs which we interpret as coming from time-variable scattering or refraction in the ionized interstellar medium. Failing to model these different contributions appropriately can dramatically alter the astrophysical interpretation of the stochastic signals observed in the residuals. In some cases, the spectral exponent of the spin-noise signal can vary from 1.6 to 4 depending upon the model, which has direct implications for the long-term sensitivity of the pulsar to a stochastic gravitational-wave (GW) background. By using a more appropriate model, however, we can greatly improve a pulsar's sensitivity to GWs. For example, including system and band-dependent signals in the PSR J0437-4715 data set improves the upper limit on a fiducial GW background by ~60 per cent compared to a model that includes DM variations and spin-noise only.

BackgroundeConsulta is a tele-consultation service involving doctors and patients, and is part of Catalonia's public health information technology system. The service has been in operation since the end of 2015 as an adjunct to face-to-face consultations. A key factor in understanding the barriers and facilitators to the acceptance of the tool is understanding the sociodemographic characteristics of general practitioners who determine its use. ObjectiveThis study aimed to analyze the sociodemographic factors that affect the likelihood of doctors using eConsulta. MethodsA retrospective cross-sectional analysis of administrative data was used to perform a multivariate logistic regression analysis on the use of eConsulta in relation to sociodemographic variables. ResultsThe model shows that the doctors who use eConsulta are 45-54 years of age, score higher than the 80th percentile on the quality of care index, have a high degree of accessibility, are involved in teaching, and work on a health team in a high socioeconomic urban setting. ConclusionsThe results suggest that certain sociodemographic characteristics associated with general practitioners determine whether they use eConsulta. These results must be taken into account if its deployment is to be encouraged in the context of a public health system.

Purpose: The optimal physiologic parameters to monitor after a session of awake prone positioning in patients with acute respiratory failure are not well understood. This study aimed to identify which early physiologic changes after the first session of awake prone positioning are linked to the need for invasive mechanical ventilation or death in patients with acute respiratory failure., Methods: We performed a secondary analysis of a prospective cohort study of adult patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) treated with awake prone positioning. We assessed the association between relative changes in physiological variables (oxygenation, respiratory rate, pCO 2 and respiratory rate-oxygenation [ROX] index) within the first 6 h of the first awake prone positioning session with treatment failure, defined as endotracheal intubation and/or death within 7 days., Results: 244 patients [70 female (29%), mean age 60 (standard deviation [SD] 13) years] were included. Seventy-one (29%) patients experienced awake prone positioning failure. ROX index was the main physiologic predictor. Patients with treatment failure had lower mean [SD] ROX index at baseline [5 (1.4) versus 6.6 (2.2), p < 0.0001] and within 6 h of prone positioning [5.6 (1.7) versus 8.7 (2.8), p < 0.0001]. After adjusting for baseline characteristics and severity, a relative increase of the ROX index compared to baseline was associated with lower odds of failure [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.25-0.54 every 25% increase]., Conclusion: Relative changes in the ROX index within 6 h of the first awake prone positioning session along with other known predictive factors are associated with intubation and mortality at day 7., Competing Interests: Declarations Conflicts of interest MO received a research award from the American Thoracic Society´s Methods in Epidemiologic, Clinical and Operations Research (MECOR) Program. DLG received research grants from Fisher and Paykel and GE. Also receives travel accommodation/personal fees by Fisher and Paykel, Getinge, Draeger and Hamilton. The other authors declare that they have no conflicts of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates., Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD., Design, Setting, and Participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe])., Intervention: Patients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks., Main Outcomes and Measures: The primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated., Results: Among 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P < .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P < .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P < .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P < .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site., Conclusions and Relevance: In 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability., Trial Registration: ClinicalTrials.gov Identifiers: NCT04773587, NCT04773600.

PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic mosaic variants that result in constitutive activation of the phosphatidylinositol-3-kinase/AKT/mTOR pathway. Promising responses to molecularly targeted therapy have been reported, although identification of an appropriate agent can be hampered by the mosaic nature and corresponding low variant allele frequency of the causal variant. Moreover, our understanding of the molecular consequences of these variants-for example how they affect gene expression profiles-remains limited. Here we describe in vitro expansion of a human capillary malformation followed by molecular characterization using exome sequencing, single cell gene expression, and targeted long-read single cell RNA-sequencing in a patient with clinical features consistent with Megalencephaly-Capillary Malformation Syndrome (MCAP, a PROS condition). These approaches identified a targetable PIK3CA variant with expression restricted to PAX3+ fibroblast and undifferentiated keratinocyte populations. This study highlights the innovative combination of next-generation single cell sequencing methods to better understand unique transcriptomic profiles and cell types associated with MCAP, revealing molecular intricacies of this genetic syndrome., (© 2024. The Author(s).)

Objective: To compare the effectiveness of the awake-prone position on relevant clinical outcomes in patients with COVID-19-related acute respiratory failure requiring high-flow nasal oxygen between different waves in Argentina., Methods: This multicenter, prospective cohort study included adult patients with COVID-19-related acute respiratory failure requiring high-flow nasal oxygen. The main exposure position was the awake-prone position (≥ 6 hours/day) compared to the non-prone position. The primary outcome was endotracheal intubation, and the secondary outcome was in-hospital mortality. The inverse probability weighting-propensity score was used to adjust the conditional probability of treatment assignment. We then adjusted for contextual variables that varied over time and compared the effectiveness between the first and second waves., Results: A total of 728 patients were included: 360 during the first wave and 368 during the second wave, of whom 195 (54%) and 227 (62%) remained awake-prone for a median (p25 - 75) of 12 (10 - 16) and 14 (8 - 17) hours/day, respectively (Awake-Prone Position Group). The ORs (95%CIs) for endotracheal intubation in the Awake-Prone Position Group were 0.25 (0.13 - 0.46) and 0.19 (0.09 - 0.31) for the first and second waves, respectively (p = 0.41 for comparison between waves). The ORs for in-hospital mortality in the awake-prone position were 0.35 (0.17 - 0.65) and 0.22 (0.12 - 0.43), respectively (p = 0.44 for comparison between waves)., Conclusion: The awake-prone position was associated with a reduction in the risk of endotracheal intubation and in-hospital mortality. These effects were independent of the context in which the intervention was applied, and no differences were observed between the different waves.

The skin microbiome is essential for skin barrier function because it inhibits pathogen colonization, and decreased microbiome diversity correlates with increased Staphylococcus aureus (S. aureus) burden and atopic dermatitis (AD) severity. Managing S. aureuss-driven AD in clinical practice remains problematic due to complications such as AD exacerbation, impetigo, abscesses, and invasive infections. This project used a modified Delphi process comprising face-to-face discussions followed by a blinded vote to define 5 final consensus statements. A panel of 6 pediatric dermatologists developed a consensus on S. aureus-driven AD exacerbation, challenges in current treatments for AD with secondary bacterial infections, and new developments to improve patient care and outcomes. The panel's 5 consensus statements provide recommendations for dermatologists, pediatricians, and healthcare providers treating patients with secondary infected AD. These recommendations underscore the importance of recognizing and managing S. aureus skin infection in AD clinical practice and promoting antibiotic stewardship to mitigate resistance. The panel defined a significant unmet need for a single topical AD therapy effective against all symptoms, including pruritus, S. aureus-driven AD exacerbation, infection, and inflammation, across AD severity levels. J Drugs Dermatol. 2024;23(10):825-832. doi:10.36849/JDD.8240.

Metaplastic breast carcinomas (mBrCA) are a highly aggressive subtype of triple-negative breast cancer with histologic evidence of epithelial-to-mesenchymal transition and aberrant differentiation. Inactivation of the tumor suppressor gene cellular communication network factor 6 (CCN6; also known as Wnt1-induced secreted protein 3) is a feature of mBrCAs, and mice with conditional inactivation of Ccn6 in mammary epithelium (Ccn6-KO) develop spindle mBrCAs with epithelial-to-mesenchymal transition. Elucidation of the precise mechanistic details of how CCN6 acts as a tumor suppressor in mBrCA could help identify improved treatment strategies. In this study, we showed that CCN6 interacts with the Wnt receptor FZD8 and coreceptor LRP6 on mBrCA cells to antagonize Wnt-induced activation of β-catenin/TCF-mediated transcription. The histone methyltransferase EZH2 was identified as a β-catenin/TCF transcriptional target in Ccn6-KO mBrCA cells. Inhibiting Wnt/β-catenin/TCF signaling in Ccn6-KO mBrCA cells led to reduced EZH2 expression, decreased histone H3 lysine 27 trimethylation, and deregulation of specific target genes. Pharmacologic inhibition of EZH2 reduced growth and metastasis of Ccn6-KO mBrCA mammary tumors in vivo. Low CCN6 is significantly associated with activated β-catenin and high EZH2 in human spindle mBrCAs compared with other subtypes. Collectively, these findings establish CCN6 as a key negative regulator of a β-catenin/TCF/EZH2 axis and highlight the inhibition of β-catenin or EZH2 as a potential therapeutic approach for patients with spindle mBrCAs.  Significance: CCN6 deficiency drives metaplastic breast carcinoma growth and metastasis by increasing Wnt/β-catenin activation to upregulate EZH2, identifying EZH2 inhibition as a mechanistically guided treatment strategy for this deadly form of breast cancer., (©2024 American Association for Cancer Research.)

Background: Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is the preferred first-line treatment for hormone receptor-positive (HR+)/HER2- metastatic breast cancer. Although this is beneficial, acquired resistance leads to disease progression, and patients harboring PIK3CA mutations are treated with targeted therapies such as the PI3Kα inhibitor, alpelisib, alongside ET. Drug-associated resistance mechanisms limit the efficacy of alpelisib, highlighting the need for better combination therapies. This study aimed to evaluate the efficacy of combining alpelisib with a highly specific PLK1 inhibitor, onvansertib, in PIK3CA -mutant HR+ breast cancer preclinical models., Methods: We assessed the effect of the alpelisib and onvansertib combination on cell viability, PI3K signaling pathway, cell cycle phase distribution and apoptosis in PI3K-activated HR+ breast cancer cell lines. The antitumor activity of the combination was evaluated in three PIK3CA -mutant HR+ breast cancer patient-derived xenograft (PDX) models, resistant to ET and CDK4/6 inhibitor palbociclib. Pharmacodynamics studies were performed using immunohistochemistry and Simple Western analyses in tumor tissues., Results: The combination synergistically inhibited cell viability, suppressed PI3K signaling, induced G2/M arrest and apoptosis in PI3K-activated cell lines. In the three PDX models, the combination demonstrated superior anti-tumor activity compared to the single agents. Pharmacodynamic studies confirmed the inhibition of both PLK1 and PI3K activity and pronounced apoptosis in the combination-treated tumors., Conclusions: Our findings support that targeting PLK1 and PI3Kα with onvansertib and alpelisib, respectively, may be a promising strategy for patients with PIK3CA -mutant HR+ breast cancer failing ET + CDK4/6i therapies and warrant clinical evaluation.

Background: Moderate-to-severe atopic dermatitis (AD) often has a profound impact on the quality of life of young children and their caregivers. One of the most burdensome symptoms reported by patients is skin pain., Methods: This post hoc analysis focuses on the impact of dupilumab treatment on skin pain in young children using data from the LIBERTY AD PRESCHOOL part B (NCT03346434), a 16-week randomized, double-blind, placebo-controlled, phase 3 study in 162 children aged 6 months to 5 years with moderate-to-severe AD receiving dupilumab or placebo, plus topical corticosteroids (TCS). Analyses were performed on the full analysis set and subgroups of patients who did not achieve an Investigator's Global Assessment score of 0 or 1 (IGA >1 subgroup), or who did not achieve a 75% improvement from baseline in the Eczema Area and Severity Index (1 and

Background/purpose: Dystrophic epidermolysis bullosa (DEB), a rare genetic skin disease caused by loss-of-function mutations in COL7A1 , the gene encoding type VII collagen (COL7), is characterized by skin blistering, scarring, and extracutaneous manifestations that markedly reduce patient quality-of-life. Beremagene geperpavec-svdt ('B-VEC') is a gene therapy employing a non-integrating, replication-defective herpes simplex virus type 1 (HSV-1)-based vector encoding two copies of full-length human COL7A1 to restore COL7 protein after topical administration to DEB wounds. B-VEC was approved in the United States in 2023 as the first topical gene therapy and the first approved treatment for DEB. However, few providers have experience with use of this gene therapy., Methods: Data was obtained through literature review and the experience of providers who participated in the B-VEC clinical study or initiated treatment after B-VEC approval., Results: This review discusses the burden of disease, describes the clinical trial outcomes of B-VEC, and provides physician and patient/caregiver recommendations as a practical guide for the real-world use of B-VEC, which can be administered in-office or at the patient's home., Conclusions: By continuing to optimize the practical aspects of B-VEC administration, the focus will continue to shift to patient-centric considerations and improved patient outcomes.

In this study, the effect of biochar from oat hulls (BO) on the rheological properties of a PG 64-22 asphalt binder was evaluated using a full factorial design, which included the following factors: pyrolysis temperature (PT) (300 °C and 500 °C), BO particle size (<20 µm and <75 µm), and the amount of BO (2.5%, 5%, and 7.5%). First, the morphological and physicochemical properties of BO were analyzed by comparing it with graphite powder (CFG) and commercial activated carbon (CAC). The physicochemical properties of the modified asphalt binder were then evaluated using confocal laser microscopy, scanning electron microscopy (SEM-EDX), and Fourier-transform infrared spectroscopy (FTIR). Its storage stability was also evaluated. Subsequently, the rutting parameter G*/sin(δ) and the Fraass breaking point were analyzed to select asphalt binders that extended their viscoelastic range. The asphalt binders selected were those with 2.5%, 5%, and 7.5% BO, produced at a PT of 300 °C with a particle size <20 µm (BO300S). Next, the rheological properties of the selected samples were evaluated by testing for rotational viscosity, rutting parameter G*/sin(δ), multiple stress creep recovery (MSCR), fatigue parameter G*·sin(δ), and creep stiffness by bending beam rheometry (BBR). The rheological aging index according to rutting parameter G*/sin(δ) (RAI) was also evaluated. These tests were conducted in different states of the asphalt binder: original, short-term aged, and long-term aged. According to the results, the application of BO300S significantly increased the resistance of the asphalt binder to rutting and rotational viscosity, proportional to the amount added to the asphalt binder. Moreover, low modifier percentages improved fatigue resistance, outperforming CFG and CAC. In addition, it performs well at low service temperatures, registering better resistance than the control asphalt binders.

Patients with moderate-to-severe atopic dermatitis (AD) experience intense chronic itch and impaired sleep. Reports from parents and teachers suggest that AD patients may also have attention problems. However, attention has not yet been directly assessed in AD patients. We utilized an objective, computer-based continuous performance test (CPT) validated for use in attention-deficit/hyperactivity disorder (ADHD) diagnosis to formally evaluate attention in adolescent AD subjects. This was a single-visit, cross-sectional, non-interventional study of moderate-to-severe (Investigator's Global Assessment [IGA] ≥ 3) AD subjects aged 12-17 years without clinician-diagnosed ADHD. Attention was evaluated using two performance-based measures: Conners, CPT-3 and the Stroop Color and Word Test. The primary parameter was CPT-3 detectability (d') measure. Lesional severity measures included Eczema Area and Severity Index (EASI) and body surface area (BSA) involvement. Subjects completed self-report rating scales assessing sensory responsiveness patterns (Adult/Adolescent Sensory Profile [AASP]), itch (Peak Pruritus Numerical Rating Scale [PP-NRS]), skin pain, quality of life, sleep, anxiety, and depressive symptoms. A total of 44 subjects were included in the study (61.4% female; mean age 15.0 [SD 1.78] years; mean EASI 20.4 [SD 7.8]; mean PP-NRS 7.0 [SD 1.8]). Results indicated substantial disease impact on sleep, quality of life, and comorbid anxiety and depressive symptoms. The mean (SD) Conners, CPT-3 d' T-score was 48.7 (SD 10.7), similar to the expected mean from a randomly selected age/gender-matched sample of the general population (50 [SD 10], by definition). Overall, 13.6% of subjects exhibited a d' T-score ≥ 60 (clinically significant poor performance), which was not greater than the expected general population value (15.9%). Subject-level data review by two psychologists determined that only 2 subjects demonstrated an overall response pattern that clearly indicated attention deficit. Many subjects had atypical sensory responsiveness profiles: sensory hypersensitivity (38.6%), sensory avoidance (50%), and low registration (hypo-sensitivity, 36.4%). Adolescents with moderate-to-severe AD without existing ADHD diagnosis did not demonstrate greater attention problems on performance-based measures than would be expected in age/gender-matched peers.Trial registration NCT05203380., (© 2024. The Author(s).)

Dermatologists routinely see patients with inflammatory skin conditions and aesthetic concerns that involve substantial psychological comorbidity. However, most dermatologists do not receive formal training in this area, and many are unsure how to best help treat certain patients holistically. Body dysmorphic disorder (BDD) is a common and distressing psychiatric condition that disproportionately impacts dermatology patients, including patients living with chronic inflammatory skin conditions such as acne and atopic dermatitis. BDD is characterized by preoccupation with nonexistent or minimally noticeable flaws in physical appearance that cause clinically significant distress or impairment in functioning. Adolescent populations may be particularly vulnerable to clinically significant body image dissatisfaction, including BDD, due to the high prevalence of acne and the pervasive role of social media platforms. The rise of social media may exacerbate body image issues through repetitive exposure to idealized and often unrealistic beauty standards. Though screening questionnaires can assist dermatologists in recognizing BDD, dermatologists must collaborate with mental health providers to provide comprehensive care to vulnerable patients, including adolescents.J Drugs Dermatol. 2024;23(7):545-550.&nbsp; doi:10.36849/JDD.8156.

Background: Evidence from randomized studies support complete over culprit-only revascularization for patients with acute coronary artery syndrome (ACS) and multivessel coronary artery diseases (MVD). Whether these findings extend to elderly patients, however, has not been thoroughly explored., Methods: We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age ≥75 years) with ACS and MVD submitted to complete vs partial-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios with 95% confidence intervals (CI) to preserve time time-to-event data., Results: We included 7 studies, of which 2 were RCT and 5 were multivariable adjusted cohorts, comprising a total 10 147, of whom 43.8% underwent complete revascularization. As compared with partial-only PCI, complete revascularization was associated with a lower all-cause mortality (hazard ratio 0.71; 95% CI 0.60-0.85; P < 0.01), cardiovascular mortality (hazard ratio 0.64; 95% CI 0.52-0.79; P < 0.01), and recurrent myocardial infarction (hazard ratio 0.65; 95% CI 0.50-0.85; P < 0.01). There was no significant difference between groups regarding the risk of revascularizations (hazard ratio 0.80; 95% CI 0.53-1.20; P = 0.28)., Conclusion: Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent myocardial infarction., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Early detection and diagnosis of cancer is critical for achieving positive therapeutic outcomes. Biomarkers that can provide clinicians with clues to the outcome of a given therapeutic course are highly desired. Oxygen is a small molecule that is nearly universally present in biological tissues and plays a critical role in the effectiveness of radiotherapies by reacting with DNA radicals and subsequently impairing cellular repair of double strand breaks.Techniques for measuring oxygen in biological tissues often use blood oxygen saturation to approximate the oxygen partial pressure in surrounding tissues despite the complex, nonlinear, and dynamic relationship between these two separate oxygen populations., Methods and Materials: We combined a directly oxygen-sensitive, tumor-targeted, chemical contrast nanoelement with the photoacoustic lifetime-based (PALT) oxygen imaging technique to obtain image maps of oxygen in breast cancer tumors in vivo. The oxygen levels of patient-derived xenografts in a mouse model were characterized before and after a course of radiotherapy., Results: We show that, independent of tumor size, radiotherapy induced an increase in the overall oxygenation levels of the tumor. Further, this increase in the oxygenation of the tumor significantly correlated with a positive response to radiotherapy, as demonstrated by a reduction in tumor volume over the twenty-day monitoring period following therapy and histological staining., Conclusion: Our PALT imaging presented here is simple, fast, and non-invasive. Facilized by the PALT approach, imaging of tumor reoxygenation may be utilized as a simple, early indicator for evaluating cancer response to radiotherapy. Further characterization of the reoxygenation degree, temporal onset, and possible theragnostic implications are warranted.

Background: Atopic dermatitis (AD) typically starts in infancy and early childhood. The chronic skin disorder is associated with recurrent flares, pruritus, and genetic predisposition. Daily use of moisturizers that contain lipids, such as ceramides, reduces the rate of AD flares and the need for topical steroid treatment. We aimed to provide insights on AD attenuation to tailor AD prescription therapy, skin care, and maintenance treatment to improve pediatric patients with AD and families., Methods: A panel of 6 pediatric dermatologists and dermatologists who treat neonates, infants, and children developed a consensus paper on AD attenuation for pediatric patients. The modified Delphi process comprised a face-to-face panel meeting and online follow-up to discuss the systematic literature search results and draw from clinical experience and opinion of the panel to adopt and agree on 5 statements.&nbsp; Results: Understanding the functional properties of newborn and infant skin, discussing skincare product use with parents, and recommending tailored prescription and skincare routines can improve newborn, infant, and children&rsquo;s skin health. Studies on the prophylactic application of moisturizers initiated in early infancy suggest moisturizers may delay rather than prevent AD, especially in high-risk populations and when used continuously. Increasingly there is evidence that moisturizer application reduces the severity of AD and extends the time to flares, which may help attenuate the atopic march. The protective effect of skin care for AD has been observed in studies where its daily use is ongoing; these beneficial effects may be lost in less than 1year after cessation. It is therefore important to emphasize that skin care should be routinely used when counseling patients and caregivers.&nbsp; Conclusion: Healthcare providers can improve patient outcomes in atopic-prone infants and children by providing instructions regarding the daily benefits of applying skin care with gentle cleansers and moisturizers. Using gentle cleansers and moisturizers containing barrier lipids from birth onward may delay AD occurrence and mitigate severity in predisposed infants.J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7894.

The importance of EZH2 as a key methyltransferase has been well documented theoretically. Practically, the first EZH2 inhibitor Tazemetostat (EPZ6438), was approved by FDA in 2020 and is used in clinic. However, for most solid tumors it is not as effective as desired and the scope of clinical indications is limited, suggesting that targeting its enzymatic activity may not be sufficient. Recent technologies focusing on the degradation of EZH2 protein have drawn attention due to their potential robust effects. This review focuses on the molecular mechanisms that regulate EZH2 protein stability via post-translational modifications (PTMs), mainly including ubiquitination, phosphorylation, and acetylation. In addition, we discuss recent advancements of multiple proteolysis targeting chimeras (PROTACs) strategies and the latest degraders that can downregulate EZH2 protein. We aim to highlight future directions to expand the application of novel EZH2 inhibitors by targeting both EZH2 enzymatic activity and protein stability., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Patients with triple-negative breast cancer remain at risk for metastatic disease despite treatment. The acquisition of chemoresistance is a major cause of tumor relapse and death, but the mechanisms are far from understood. We have demonstrated that breast cancer cells (BCCs) can engulf mesenchymal stem/stromal cells (MSCs), leading to enhanced dissemination. Here, we show that clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-α. We show that hybrid cells form in primary tumors and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance.