Mapping the dynamics of epigenetic adaptation in S. pombe during heterochromatin misregulation.

Epigenetic mechanisms enable cells to develop novel adaptive phenotypes without altering their genetic blueprint. Recent studies show histone modifications, such as heterochromatin-defining H3K9 methylation (H3K9me), can be redistributed to establish adaptive phenotypes. We developed a precision-engineered genetic approach to trigger heterochromatin misregulation on-demand in fission yeast. This enabled us to trace genome-scale RNA and H3K9me changes over time in long-term, continuous cultures. Adaptive H3K9me establishes over remarkably slow timescales relative to the initiating stress. We captured dynamic H3K9me redistribution events which depend on an RNA binding complex MTREC, ultimately leading to cells converging on an optimal adaptive solution. Upon stress removal, cells relax to new transcriptional and chromatin states, establishing memory that is tunable and primed for future adaptive epigenetic responses. Collectively, we identify the slow kinetics of epigenetic adaptation that allow cells to discover and heritably encode novel adaptive solutions, with implications for drug resistance and response to infection.

Knowledge, attitude, and practice of Egyptian medical students towards healthcare workers' recommended vaccines: a nationwide cross-sectional survey.

BACKGROUND: Vaccination of healthcare workers (HCWs) is pivotal in decreasing the incidence of contagious infections in hospital settings. In this study, we assessed the knowledge, attitude, and practice regarding HCWs' recommended vaccines among medical students and interns in Egypt. METHODS: A multicenter, cross-sectional study was conducted using a structured, pilot-tested, and self-administered questionnaire among Egyptian medical students and interns. We invited 1332 participants to our survey using a systematic random sampling that included participants across nine medical schools in Egypt during the 2021-2022 academic year. RESULTS: Out of 1332 participants, 1141 completed our questionnaire with a response rate of 85.7%. Overall, 43% of the participants had intermediate knowledge (knew 2-3 HCWs' recommended vaccines). Furthermore, 36.7% had received a booster dose of at least one of the HCWs' recommended vaccines over the last 10 years, with only 6.1% having received all recommended vaccines. Hepatitis B vaccine was the most widely known (71%) and received (66.7%). Interns were more likely to know, receive, and recommend HCWs' recommended vaccines. The majority (> 90%) agreed that vaccination is beneficial and safe, with a median score of eight (interquartile range [IQR: Q25-Q75]: 7-9) out of ten for vaccine efficacy and eight (IQR: 7-8) for safety. However, the median score for hesitancy was five (IQR: 2-7). The most common influential and limiting factors for vaccination were scientific facts (60.1%) and fear of vaccine side effects (44.9%). CONCLUSION: Although medical students in Egypt have good knowledge of and attitudes towards vaccination, there is a gap in their practices. Interventions are needed to improve vaccination uptake among medical students in Egypt.

Recurrence of Non-Small Cell Lung Cancer With Visceral Pleural Invasion: A Seconday Analysis of a Randomized Clinical Trial.

Importance: The randomized clinical trial Cancer and Leukemia Group B (CALGB) 140503 showed that for patients with clinically staged T1N0 non-small cell lung cancer (NSCLC; ≤2 cm), sublobar resections were associated with similar oncological outcomes to those after lobar resection. The association of the extent of parenchymal resection with recurrence and survival in patients with tumors pathologically upstaged to T2 based on visceral pleural invasion (VPI) is controversial. Objective: To determine survival and recurrence rates in patients with small peripheral pT2 NSCLC (≤2 cm) that was treated by either lobar or sublobar resection in CALGB 140503. Design, Participants, and Setting: CALGB 140503, a randomized multicenter noninferiority trial, included 697 patients with small peripheral NSCLC that was clinically staged as T1N0. Enrollment was from June 2007 through March 2017 at 83 participating institutions, and after a median follow-up of 7 years, the primary outcome of disease-free survival after sublobar resection was noninferior to that after lobar resection. Intervention: Lobar or sublobar resection. Main Outcomes and Measures: Survival end points were estimated by the Kaplan-Meier estimator. Hazard ratios and 95% CIs were estimated using stratified Cox proportional hazard models. Results: Of 679 participants, 390 (57.4%) were female, and the median (range) age was 67.8 (37.8-89.7) years. Among 697 patients randomized, 566 (81.2%) had pT1 tumors (no VPI) and 113 (16.2%) had pT2 tumors (VPI). Five-year disease-free survival was 65.9% (95% CI, 61.9%-70.2%) in patients with pT1 compared with 53.3% (95% CI, 44.3%-64.1%) in patients with pT2 tumors (stratified log-rank: P = .02). Disease recurrence developed in 27.6% of patients with pT1 (locoregional only: 60 [10.8%]; distant only: 81 [14.6%]) and 41.6% of those with pT2 (locoregional only: 17 [15.0%]; distant only: 27 [23.9%]). Five-year recurrence-free survival was 73.1% (95% CI, 69.2%-77.1%) for pT1 tumors and 58.2% (95% CI, 49.2%-68.8%) for pT2 tumors (stratified log-rank: P = .01). There were no intergroup differences in disease-free or recurrence-free survival based on the extent of parenchymal resection. Conclusions and Relevance: The results of this secondary analysis suggest that compared with patients with tumors without VPI, patients who had tumors with VPI had worse disease-free and recurrence-free survival and a higher rate of local and distant disease recurrence. These high rates of recurrence were independent of the extent of parenchymal resection, and these data support the inclusion of these patients in adjuvant therapy trials. Trial Registration: ClinicalTrials.gov Identifier: NCT0049933.

Enamel Deproteinization or Sandblasting for Enamel Reconditioning Before Acid Etching to Enhance the Shear Bond Strength of Metallic Brackets in a Third Bonding: An In Vitro Study.

BACKGROUND: Enamel conditioning with 37% phosphoric acid is the most common technique during orthodontic bracket bonding procedures. However, due to the repeated de-bonding of the orthodontic brackets during treatment, other methods were needed to condition the enamel surface and increase the bond strength. This study aimed to compare the effect of conditioning the enamel surface by sandblasting with aluminum oxide particles or 5.25% sodium hypochlorite gel in combination with acid etching compared to acid etching alone on shear bond strength (SBS). MATERIAL AND METHODS: One hundred eight extracted upper premolars were randomly divided into three groups according to the conditioning enamel surface method. After the first and second bonding of metal brackets, new metal brackets were bonded with a total-etching adhesive after enamel conditioning using different methods: acid etching only (37% phosphoric acid for 30 seconds) (AE group), sodium hypochlorite associated with acid etching (5.25% NaOCl gel for 60 seconds and then acid etching for 30 seconds) (NaOCl-AE group), and sandblasting associated with acid etching (sandblasting for five seconds and then acid etching for 30 seconds) (SB-AE group). The shear bond strengths of the brackets were tested with a universal testing machine. One-way analysis of variance (ANOVA) and Tukey's honestly significant difference (HSD) tests were used to detect significant differences in shear bond strength among groups at the third bonding. Repeated-measure ANOVA and Bonferroni's tests were used to detect significant differences in shear bond strength among the bonding attempts within each group. RESULTS: 5.25% sodium hypochlorite associated with the acid etching method produced significantly greater shear bond strength than sandblasting associated with acid etching and acid etching only methods at the third bonding (16.40 ± 5.80 MPa, 13.60.47 ± 6.40 MPa, and 9.90 ± 4.40 MPa, respectively; P < 0.001). However, there was no significant difference between the AE and SB-AE groups (P = 0.247). In addition, we found a significant decrease in the shear bond strength within each group after each bonding attempt. CONCLUSION: Conditioning the enamel surface with 5.25% sodium hypochlorite associated with acid etching produced greater bond strength than conditioning by sandblasting associated with acid etching and acid etching only at the third bonding. The bond strength of the metal bracket decreased with increasing bonding attempts, even with the application of enamel surface conditioning methods.

Neurologic Symptoms After 177Lu-Prostate-Specific-Membrane Antigen-617 Therapy: A Single-Center Experience.

Treatment with 177Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-vipivotide tetraxetan [Pluvicto]) prolongs both progression-free and overall survival in advanced PSMA-positive metastatic castration-resistant prostate cancer. Data examining specifically neurologic symptoms after 177Lu-PSMA-617 treatment are scarce. In this study, we aimed to review the neurologic findings in a large cohort of metastatic castration-resistant prostate cancer patients undergoing 177Lu-PSMA-617 therapy. Methods: The clinical records and imaging data of patients who received their initial dose of 177Lu-PSMA-617 between March 2022 and November 2022 were retrospectively reviewed. All patients presenting for medical evaluation, regardless of specific specialty appointments, with new or worsening neurologic symptoms were included in the study. Results: A total of 185 patients underwent 177Lu-PSMA-617 therapy. The median age was 70 y (range, 58-90 y). The mean follow-up time was 12.04 ± 2.87 mo. Fifty-five new or worsening neurologic symptoms were observed in 50 patients (27%, 50/185). Of these, 27 (11.9%, 27/185) reported altered taste. Eleven patients (6%, 11/185) experienced dizziness with no other clear etiology; 2 of these patients were admitted to the emergency department (ED). Paresthesia symptoms were reported in 6 patients (3.2%, 6/185). Five patients (2.7%, 5/185) reported headaches, 3 of these patients were admitted to the ED because of the severity of the symptoms. Two patients (1.08%, 2/185) presented with extremity weakness. Two patients (1.08%, 2/185) had an ischemic stroke and were admitted to the ED. One patient (0.05%, 1/185) exhibited gait disturbances. In total, 7 patients (3.78%, 7/185) were admitted to the ED because of neurologic symptoms. None of the patients discontinued or failed to complete the 177Lu-PSMA-617 therapy because of neurologic symptoms. Conclusion: After 177Lu-PSMA-617 treatment, the most common neurologic symptoms were dysgeusia and dizziness. In this study, our follow-up period and population size might not have been sufficient to detect delayed or uncommon neurologic symptoms. In patients without neurologic symptoms or central nervous system metastases before treatment, we found the development of severe neurologic problems to be rare and unlikely to require discontinuation of treatment.

Unraveling the Rare Entity of KIT D816V-Negative Systemic Mastocytosis.

Systemic mastocytosis (SM) is a rare type of myeloproliferative neoplasm characterized by abnormal proliferation and infiltration of different tissue by clonal mast cells. The uncontrolled proliferation and activation of mast cells trigger the release of vasoactive and inflammatory mediators, resulting in a cascade of systemic symptoms. Around 95% of SM arise from a gain-of-function mutation at the KIT gene, specifically at codon 816, which highlights its essential role in SM and makes it an attractive target for therapy. Although KIT-negative SM is exceptionally rare, the increased number of cases documented in the literature makes it an intriguing dimension of this disorder. The reported clinical manifestations of KIT-negative SM are widely variable, but many are similar to KIT-positive SM. KIT-targeted therapeutic options have been a game-changer in KIT-positive SM, however their role in KIT-negative SM remains controversial. This report aimed to further understand KIT-negative SM by presenting two cases of KIT-negative SM, one of which was responsive to KIT-targeted therapy, and analyzing reported cases in the existing literature.

Exploring the most promising anti - Depressant drug targeting Microtubule Affinity Receptor Kinase 4 involved in Alzheimer's Disease through molecular docking and molecular dynamics simulation.

Alzheimer's Disease (AD) is the prevailing type of neurodegenerative illness, characterised by the accumulation of amyloid beta plaques. The symptoms associated with AD are memory loss, emotional variability, and a decline in cognitive functioning. To date, the pharmaceuticals currently accessible in the marketplace are limited to symptom management. According to several research, antidepressants have demonstrated potential efficacy in the management of AD. In this particular investigation, a total of 24 anti-depressant medications were selected as ligands, while the Microtubule Affinity Receptor Kinase 4 (MARK4) protein was chosen as the focal point of our study. The selection of MARK4 was based on its known involvement in the advancement of AD and other types of malignancies, rendering it a highly prospective target for therapeutic interventions. The initial step involved doing ADMET analysis, which was subsequently followed by molecular docking of 24 drugs. This was succeeded by molecular dynamics simulation and molecular mechanics generalised Born surface area (MMGBSA) calculations. Upon conducting molecular docking experiments, it has been determined that the binding affinities observed fall within the range of -5.5 kcal/mol to -9.0 kcal/mol. In this study, we selected six anti-depressant compounds (CID ID - 4184, 2771, 4205, 5533, 4543, and 2160) based on their binding affinities, which were determined to be -9.0, -8.7, -8.4, -8.3, -8.2, and -8.2, respectively. Molecular dynamics simulations were conducted for all six drugs, with donepezil serving as the control drug. Various analyses were performed, including basic analysis and post-trajectory analysis such as free energy landscape (FEL), polarizable continuum model (PCM), and MMGBSA calculations. Based on the findings from molecular dynamics simulations and the MMGBSA analysis, it can be inferred that citalopram and mirtazapine exhibit considerable potential as anti-depressant agents. Consequently, these compounds warrant further investigation through in vitro and in vivo investigations in the context of treating AD.

The Impact of Non-Extraction Orthodontic Treatment on the Oral-Health-Related Quality of Life between a Modified Aligner Appliance with Ni-Ti Springs and the Traditional Fixed Appliances: A Randomized Controlled Clinical Trial.

Background and Objectives: To compare the oral-health-related quality of life (OHRQoL) outcomes between patients treated with modified Ni-Ti spring-based alignment appliances or conventional fixed appliances using the Oral Health Impact Profile 14 (OHIP-14), as well as the levels of satisfaction with the appliance appearance, treatment progress, and outcomes. Materials and Methods: Thirty-six patients (11 males, 25 females) were randomly divided into two groups: either the modified aligner appliance with Ni-Ti springs group (MAA) or the traditional fixed appliances group (FA). The allocation ratio was 1:1, and the randomization process was carried out by an independent investigator not involved in this study. Mild crowding cases were included in this study. The OHRQoL of patients was evaluated using the short-form Oral Health Impact Profile (OHIP-14) at five time points: before the treatment commencement (T0); 2 weeks (T1), 1 month (T2), and 2 months (T3) after the treatment initiation; and post-treatment (T4). The visual analog scale (VAS) was used to evaluate the patient satisfaction. Blinding was performed only during the outcomes assessment. Results: This randomized controlled trial had no dropouts, and the demographic characteristics of the groups were comparable. The MAA group experienced significantly greater functional limitations compared with the FA group at all three evaluation time points (T1, T2, and T3), as evidenced by the statistically significant p-values (p = 0.004, p = 0.001, and p < 0.001, respectively). The psychological disability in the MAA group was significantly lower than in the FA group at both T2 (p = 0.005) and T3 (p = 0.003). The patient satisfaction with the appliance appearance was significantly higher in the MAA group than in the FA group (p = 0.002). Conclusions: The OHRQoL improved in both the modified aligner appliance with Ni-Ti springs and fixed appliance groups after the treatment. Moreover, the functional limitations during the treatment were less severe in the FA group, while the psychological disability was lower, and the patient satisfaction with the appliance appearance was higher in the MAA group.

Client's satisfaction with healthcare services received at the hospital outpatients department and the primary healthcare facilities in Al-Qassim, Saudi Arabia: A review of service users' satisfaction.

OBJECTIVES: To assess the level of satisfaction expressed for services rendered in the public health sector to clients who were seen at outpatient departments (OPDs) and primary healthcare (PHC) facilities in Al-Qassim Health Cluster in Saudi Arabia. METHODS: This study used a comparative cross-sectional study design, and data were obtained as secondary data from The Patient's Experience Platform. Data analysis was carried out using Stata (version 16), and the significance level was 5%. RESULTS: In comparing the mean satisfaction in 9 domains, statistically significantly higher means for the PHC facilities than the OPDs were seen across 7 domains: patients navigating health facilities (p=0.008), nursing services (p<0.001), physicians' services (p=0.004), radiological services (p<0.001), personal issues (p=0.003), the pharmacy (p=0.005), and general experience (p=0.036). CONCLUSION: This study's findings are significant. They indicate that client satisfaction with services at PHC facilities was significantly higher than with services at hospital OPDs in Al-Qassim region. This underscores the need to improve the quality of services provided at OPDs to bring them to the same level as those provided by PHC facilities. Policymakers and implementers should, therefore, sustain efforts to make OPDs and PHC facilities more desirable for clients.

Extended Spectrum beta-Lactamase Bacteria and Multidrug Resistance in Jordan are Predicted Using a New Machine-Learning system.

Background: The incidence of microorganisms with extended-spectrum beta-lactamase (ESBL) is on the rise, posing a significant public health concern. The current application of machine learning (ML) focuses on predicting bacterial resistance to optimize antibiotic therapy. This study employs ML to forecast the occurrence of bacteria that generate ESBL and demonstrate resistance to multiple antibiotics (MDR). Methods: Six popular ML algorithms were initially trained on antibiotic resistance test patient reports (n = 489) collected from Al-Hussein/Salt Hospital in Jordan. Trained outcome models predict ESBL and multidrug resistance profiles based on microbiological and patients' clinical data. The results were utilized to select the optimal ML method to predict ESBL's most associated features. Results: Escherichia coli (E. coli, 82%) was the most commonly identified microbe generating ESBL, displaying multidrug resistance. Urinary tract infections (UTIs) constituted the most frequently observed clinical diagnosis (68.7%). Classification and Regression Trees (CART) and Random Forest (RF) classifiers emerged as the most effective algorithms. The relevant features associated with the emergence of ESBL include age and different classes of antibiotics, including cefuroxime, ceftazidime, cefepime, trimethoprim/ sulfamethoxazole, ciprofloxacin, and gentamicin. Fosfomycin nitrofurantoin, piperacillin/tazobactam, along with amikacin, meropenem, and imipenem, had a pronounced inverse relationship with the ESBL class. Conclusion: CART and RF-based ML algorithms can be employed to predict the most important features of ESBL. The significance of monitoring trends in ESBL infections is emphasized to facilitate the administration of appropriate antibiotic therapy.

Observation of Medium-Induced Yield Enhancement and Acoplanarity Broadening of Low-p_{T} Jets from Measurements in pp and Central Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high p_{T}) hadron trigger in proton-proton and central Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb-Pb collisions. Recoil jet distributions are reported for jet resolution parameter R=0.2, 0.4, and 0.5 in the range 7

Comparative Study of Two Himalayan Snow Trouts, Schizothorax esocinus and Schizothorax curvifrons Within the Schizothoracinae and Other Nearest Relatives of Cyprinidae, Inferred from Mitochondrial Sequences of Cytochrome b (Cyt-b) and Cytochrome Oxidase I (Co-I) Gene.

The Himalayan region encompasses varied aquatic ecosystems, characterized by the presence of diverse ichthyofauna, particularly represented by members of the Schizothorax genus, commonly referred to as snow trout. The primary objective of this work was to examine the molecular phylogeny of Schizothoracinae, specifically focusing on the two species, Schizothorax esocinus and Schizothorax curvifrons, which are known to inhabit the northern and north-eastern regions of the Himalayas. This investigation was conducted by analyzing the entire mitochondrial Cyt-b and Co-I gene sequences. The aligned Cyt-b and Co-I sequences for S. esocinus, S. curvifrons, and related members within the subfamily Schizothoracinae, spanned 1130 to 1141 and 1536 to 1551 base pairs, respectively. Using these gene, phylogenetic trees were created to compare Schizothoracinae species to other subfamilies of the family Cyprinidae (Barbinae, Alburninae, Leuciscinae, Xenocyprinae, Cyprininae, and Cultrinae). Genetic distances for Cyt-b and Co-I sequence at three hierarchical levels shows significant disparities in their average score. For Cyt-b, average p-distances for intraspecies, intragenus, and intrafamily were 2.13%, 4.1%, and 15.23%, respectively. Similarly, for Co-I, average p-distances were 1.19%, 3.6%, and 13.8% for intraspecies, intragenus, and intrafamily, respectively. Total number of haplotypes (h) based on Cyt-b and Co-I gene were 6 and 12 within the target Schizothorax spp. In the present study, the observed range of haplotype diversity (hd) for the Cyt-b gene varied from 0.00 to 0.847, with an average haplotype diversity of 0.847 ± 0.034. Similarly, for the Co-I gene, the observed haplotype diversity ranged from 0.00 to 0.931, with an average value of haplotype diversity estimated to be 0.931 ± 0.024. The results of the present study clearly shows that the representative species exhibited close affinities with members of Barbinae and Cyprininae, while other subfamilies formed distinct groups. The findings of the study also indicated that the Cyt-b and Co-I gene exhibits polymorphism and has the potential to serve as a marker for identifying genetic differentiation among populations based on ecological habitats. Mitochondrial Cyt-b and Co-I have been established as a universally accepted and validated genetic marker within a comprehensive bio-identification system at the species level.

Evaluation of the Best Method for Orthodontic Correction of Skeletal Deep Bites in Growing Patients: A Systematic Review.

This review aimed to evaluate the currently available evidence regarding the best method of correcting deep bites in growing patients. In September 2023, a search was conducted electronically across the following databases: PubMed®, Web of Science™, Scopus®, Embase®, Google™ Scholar, and Cochrane Library. In this systematic review, randomized control trials (RCTs), controlled clinical trials (CCTs), and cohort studies of growing patients with deep bite malocclusion who received treatment with the primary objective of treating the deep bite were included. Risk of bias of the included studies was assessed using two different tools; one tool was applied for RCTs and the other one for the CCTs and cohort studies. One RCT, one CCT, and one cohort study were included (85 patients). The flat fixed acrylic bite plane was superior in terms of duration of treatment when compared to the inclined fixed acrylic bite plane and the utility arch with posterior intermaxillary elastics. Limited evidence indicates that the inclined fixed acrylic bite plane causes a significant increase in the lower incisor inclination and a significant increase in the angle between the mandible and the anterior cranial base (SNB). However, limited evidence indicates that the utility arch with posterior intermaxillary elastics causes a significant decrease in the angle between the maxilla and the anterior cranial base (SNA). Regarding the vertical skeletal changes, it was found that the three methods were comparable; in each case, the vertical dimension of the face increased because of a significant increase in the lower first molar height. There is a need for further studies to strengthen the evidence of the treatment efficacy of the employed methods, with more RCTs to be conducted in this regard.

Optimizing charge transport in hybrid GaN-PEDOT:PSS/PMMADevice for advanced application.

Organic-inorganic hybrid light-emitting devices have garnered significant attention in the last few years due to their potential. These devices integrate the superior electron mobility of inorganic semiconductors with the remarkable optoelectronic characteristics of organic semiconductors. The inquiry focused on analyzing the optical and electrical properties of a light-emitting heterojunction that combines p-type GaN with organic materials (PEDOT, PSS, and PMMA). This heterojunction is an organic-inorganic hybrid. The procedure entailed utilizing a spin-coating technique to apply a layer of either poly(methyl methacrylate) (PMMA) or a mixture of PMMA and poly(3,4ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT: PSS) onto an indium tin oxide (ITO) substrate. Subsequently, different Nd:YAG laser pulses (200, 250, and 300 pulses) were used to administer a GaN inorganic layer onto the prepared organic layer using a pulsed laser deposition approach. Subsequently, the thermal evaporation technique was employed to deposit an aluminum electrode on the top of the organic and inorganic layers, while laser pulses were fine-tuned for optimal performance. The Hall effect investigation verifies the p-type conductivity of the GaN material. The electroluminescence studies confirmed the production of blue light by the GaN-based devices throughout a range of voltage situations, spanning from 45 to 72 V.

Photoproduction of K

K^{+}K^{-} pairs may be produced in photonuclear collisions, either from the decays of photoproduced ϕ(1020) mesons or directly as nonresonant K^{+}K^{-} pairs. Measurements of K^{+}K^{-} photoproduction probe the couplings between the ϕ(1020) and charged kaons with photons and nuclear targets. The kaon-proton scattering occurs at energies far above those available elsewhere. We present the first measurement of coherent photoproduction of K^{+}K^{-} pairs on lead ions in ultraperipheral collisions using the ALICE detector, including the first investigation of direct K^{+}K^{-} production. There is significant K^{+}K^{-} production at low transverse momentum, consistent with coherent photoproduction on lead targets. In the mass range 1.1

Recent developments in solar-powered membrane distillation for sustainable desalination.

The freshwater shortage continues to be one of the greatest challenges affecting our planet. Although traditional membrane distillation (MD) can produce clean water regardless of climatic conditions, the process wastes a lot of energy. The technique of solar-powered membrane distillation (SPMD) has received a lot of interest in the past decade, thanks to the development of photothermal materials. SPMD is a promising replacement for the traditional MD based on fossil fuels, as it can prevent the harmful effects of emissions on the environment. Integrating green solar energy with MD can reduce the cost of the water purification process and secure freshwater production in remote areas. At this point, it is important to consider the most current progress of the SPMD system and highlight the challenges and prospects of this technology. Based on this, the background, recent advances, and principles of MD and SPMD, their configurations and mechanisms, fabrication methods, advantages, and current limitations are discussed. Detailed comparisons between SPMD and traditional MD, assessments of various standards for incorporating photothermal materials with desirable properties, discussions of desalination and other applications of SPMD and MD, and energy consumption rates are also covered. The final section addresses the potential of SPMD to outperform traditional desalination technology while improving water production without requiring a significant amount of electrical or high-grade thermal energy.

Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor.

Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-propagating conformations, leading to rapid-onset dementia and death. However, elimination of endogenous PrP halts prion disease progression. In this study, we describe Coupled Histone tail for Autoinhibition Release of Methyltransferase (CHARM), a compact, enzyme-free epigenetic editor capable of silencing transcription through programmable DNA methylation. Using a histone H3 tail-Dnmt3l fusion, CHARM recruits and activates endogenous DNA methyltransferases, thereby reducing transgene size and cytotoxicity. When delivered to the mouse brain by systemic injection of adeno-associated virus (AAV), Prnp-targeted CHARM ablates PrP expression across the brain. Furthermore, we have temporally limited editor expression by implementing a kinetically tuned self-silencing approach. CHARM potentially represents a broadly applicable strategy to suppress pathogenic proteins, including those implicated in other neurodegenerative diseases.

Management Approaches in WHO Grade III Meningioma: A National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK Multi-Centre Retrospective Study.

AIMS: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. MATERIALS AND METHODS: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. RESULTS: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. CONCLUSION: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context.