Intravitreal Infliximab for the Treatment of Proliferative Vitreoretinopathy (FIXER): A Randomized Controlled Phase 2 Trial.

OBJECTIVE: To study the safety and efficacy of intravitreal infliximab administered at the conclusion of pars plana vitrectomy (PPV) in the treatment of proliferative vitreoretinopathy (PVR) associated with rhegmatogenous retinal detachment (RRD). DESIGN: Randomized controlled phase 2 clinical trial. SUBJECTS: Patients with primary RRD and Grade C PVR, according to the updated Retina Society Classification. METHODS: Sixty-six Patients were randomized in a 1:1 ratio to undergo PPV and silicone oil (SO) injection with or without intravitreal injection of 1 mg/0.05 mL of infliximab in the air-filled globe before SO injection at PPV conclusion. Surgeons were masked to treatment allocation until PPV conclusion. MAIN OUTCOME MEASURES: The primary outcome measure was anatomic success (defined as complete retinal reattachment without a tamponade at 6 months post SO removal). Secondary outcome measures were final best corrected visual acuity (BCVA), single operation success rate (SOSR), rate of recurrent detachment, central macular thickness (CMT) by macular optical coherence tomography (OCT), macular function by multifocal electroretinogram and macular vascular density (VD) by OCT angiography. RESULTS: 60 eyes of 60 patients, 30 eyes in each group, completed the study. At baseline, there were no differences regarding age, gender, history of trauma, lens status, duration of RRD, BCVA, intraocular pressure (IOP), intra-ocular inflammation (IOI), detachment extent in clock hours, number/size of breaks, presence of vitreous hemorrhage, axial length, or grade/extent of PVR between both groups. For the outcome measures, 30 eyes in the infliximab group achieved anatomic success vs 29 eyes in the control group. The SOSR was higher in the infliximab group (26) vs the control (23), but this was not statistically significant (p = 0.317). Final BCVA was better in the infliximab group (mean logMAR (SD) = 0.96 (0.4), Snellen equivalent ≈ 20/180) vs the control (1.14 (0.4), Snellen equivalent ≈ 20/280) (p = 0.044). There were no differences regarding IOP, IOI, time of SO removal, macular function, CMT, or VD. CONCLUSION: PPV with SO tamponade with or without intravitreal infliximab is effective in treating PVR-associated RRD. Infliximab may be associated with modest improvement in final visual outcomes but not anatomical outcomes.

Enhancing simultaneous determination of some angiotensin II receptor antagonists and amlodipine in plasma using HPTLC with fluorescence densitometry: Independent fluorescence detection of the co-administrative drugs in the mixture across various pH conditions.

A novel and highly sensitive high-performance thin-layer chromatographic (HPTLC) method was developed and validated to quantify a combination of five pharmaceutical mixtures spiked to human plasma. The compounds comprised Amlodipine (AML) along with five angiotensin II receptor antagonist drugs (AIIRAs), namely Olmesartan (OLM), Telmisartan (TLM), Candesartan (CAN), Losartan (LOS), and Irbesartan (IRB). HPTLC was performed on silica gel 60 F254 plates using a mobile phase of Toluene: ethyl acetate: methanol: acetone: acetic acid (6:1.5:1:0.5:1, v/v/v/v/v). In a pioneering move, a reflectance/fluorescence detection mode was employed to identify two concurrently administered drugs at different pH levels for the first time. This method utilized the same chromatographic system, incorporating a specific measurement for AML at a neutral medium to achieve its maximum fluorescence at a 360 nm excitation wavelength, and measuring emission using a 540 nm optical filter. The process involved obtaining a very low fluorescence response from AIIRA. Subsequently, to enhance AIIRA's fluorescence, the plate was sprayed with perchloric acid to transition to a strong acidic medium, ultimately attaining the maximum fluorescence of AIIRA using various excitation wavelengths and a 400 nm emission filter. Through this strategic process, we could optimize the fluorescence signals of both drugs, thereby elevating the sensitivity of detection for this drug combination. AML demonstrated a linear range of 18-300 ng/band, while AIIRAs drugs exhibited a linear range of 6-150 ng/band. The method satisfied the International Conference on Harmonization (ICH) criteria for recovery, precision, repeatability, and robustness, showcasing exceptional sensitivity. The approach was successfully applied to quantify AML and AIIRAs drugs in both bulk drug and plasma samples, achieving high recovery percentages and minimal standard deviations.

Suture characteristics after exposure to amniotic fluid from an in vitro model of fetal surgery.

Introduction Suture tensile properties have only been tested in extrauterine environments. Amniotic fluid (AF) is a complex milieu of enzymes and inflammatory factors. This study tested the mechanical properties of sutures with a variety of inherent properties, after exposure to AF from patients with conditions prompting fetal intervention. Methods AF was obtained from three patients with twin-twin transfusion syndrome (TTTS), and three patients with neural tube defects (NTD). Six types of 2-0 sutures were placed on 1.2 N of tension to mimic placement in vivo, and incubated in AF at 37° C (98.6° F). These included ethylene terephthalate (Ethibond), glycomer 631 (V-Loc), poliglecaprone 25 (Monocryl), poly-4-hydroxybutyrate (Monomax), polydioxanone (PDS), and polyglactin 910 (Vicryl). Failure load, stress, strain, and initial modulus were tested after 24 hours of incubation and after 4 weeks, and compared with control (unincubated) sutures using t tests, Kruskal-Wallis tests, and stress-strain curves. Results Poliglecaprone 25 and polyglactin 910 dissolve more quickly in AF compared to outside the uterus, disintegrating at 4 weeks. Ethylene terephthalate and polydioxanone experienced little change across 4 weeks of incubation. Glycomer 631 and poly-4-hydroxybutyrate exhibited interesting behavior in AF: glycomer 631 became more deformable at 24 hours but later regained toughness by 4 weeks, while poly-4-hydroxybutyrate became tougher and in some cases stronger with time in AF. As a class, braided sutures act more like rigid materials, and monofilaments act like deformable plastics. Conclusion These findings along with other suture characteristics such as ease of handling and availability may inform fetal intervention teams as they optimize procedures in a relatively new surgical field.

Effects of immersing Japanese quail eggs in various doses of riboflavin on reproductive, growth performance traits, blood indices and economics.

This investigation aimed to evaluate the impact of immersion (IM) riboflavin treatment on the hatchability, production efficiency, and carcass characteristics of Japanese quail eggs. A total of 260 eggs of Japanese quail birds were used for hatching and were randomly divided into 4 treatments with 5 replicates (13 eggs/replicate) in a fully randomized design. Hatching eggs were immersed in riboflavin for 2 min before incubation. The experiment treatments were designed as follows: G1 control group with no treatment, G2 treated with 3 g/L vit. B2 (IM), G3 treated with 4 g/L vit. B2 (IM) and G4 were treated with 5 g/L vit. B2 (IM). After hatching, 128 Japanese quail chicks, aged 7 d, were randomly grouped into 4 treatment groups, with 32 birds in each group. When quails were given vitamin B2 via immersion, they demonstrated significant enhancements in live body weight, body weight gain, feed consumption, and feed conversion ratio at different stages compared to the control group. Compared to control and other groups, the carcass parameters of Japanese quails given a 4 g/L immersion solution showed a significant improvement (P < 0.05). Hatchability and fertility (%) were considerably raised by Vit.B2 treatments of 3, 4, and 5g; the group immersed in 5 g/L had the highest percentages compared to the other groups. Furthermore, treated chickens with all concentrations of vitamin B2 had significantly higher blood indices than the controls. During the exploratory phase (1-6 wk) of age, the highest returns were reported in G4 treated with 5g/L vit. B2 (IM). Treating Japanese quail eggs with different dosages of vitamin B2 by immersion may be recommended to improve their productive and reproductive performance, blood indices, carcass traits, and economic efficiency.

In-silico and in-vitro studies revealed alpha-amyrin as a potent pnhibitor of TLR2 for the therapeutics of bacterial infection and sepsis.

This study employed a multifaceted approach to investigate the inhibitory potential of alpha-amyrin against TLR2, a key player in bacterial infection and sepsis. A high-resolution TLR2 model was constructed using Swiss-MODEL, exhibiting excellent quality with 100% sequence identity and coverage. Cavity detection revealed five significant cavities on TLR2. Molecular docking identifies alpha-amyrin as a potent inhibitor, displaying a strong binding affinity of -8.6 kcal/mol. Comprehensive analyses, including ADMET predictions, PASS analysis, and SwissTargetPrediction, affirm alpha-amyrin's drug-like properties and diverse biological activities. Cytotoxicity assays on HEK-293 cells confirm its safety, and fluorescence-based inhibition assays provide empirical evidence of its inhibitory potency on TLR2 enzymatic activity. Further validations in HUVECs show a significant decrease in TLR2 mRNA expression (p<0.01) and activity (p<0.05) upon alpha-amyrin treatment. In conclusion, this integrative study positions alpha-amyrin as a promising therapeutic candidate for TLR2 inhibition, emphasizing its potential in combating bacterial infections with safety and efficacy.

Assistive tools for classifying neurological disorders using fMRI and deep learning: A guide and example.

BACKGROUND: Deep-learning (DL) methods are rapidly changing the way researchers classify neurological disorders. For example, combining functional magnetic resonance imaging (fMRI) and DL has helped researchers identify functional biomarkers of neurological disorders (e.g., brain activation and connectivity) and pilot innovative diagnostic models. However, the knowledge required to perform DL analyses is often domain-specific and is not widely taught in the brain sciences (e.g., psychology, neuroscience, and cognitive science). Conversely, neurological diagnoses and neuroimaging training (e.g., fMRI) are largely restricted to the brain and medical sciences. In turn, these disciplinary knowledge barriers and distinct specializations can act as hurdles that prevent the combination of fMRI and DL pipelines. The complexity of fMRI and DL methods also hinders their clinical adoption and generalization to real-world diagnoses. For example, most current models are not designed for clinical settings or use by nonspecialized populations such as students, clinicians, and healthcare workers. Accordingly, there is a growing area of assistive tools (e.g., software and programming packages) that aim to streamline and increase the accessibility of fMRI and DL pipelines for the diagnoses of neurological disorders. OBJECTIVES AND METHODS: In this study, we present an introductory guide to some popular DL and fMRI assistive tools. We also create an example autism spectrum disorder (ASD) classification model using assistive tools (e.g., Optuna, GIFT, and the ABIDE preprocessed repository), fMRI, and a convolutional neural network. RESULTS: In turn, we provide researchers with a guide to assistive tools and give an example of a streamlined fMRI and DL pipeline. CONCLUSIONS: We are confident that this study can help more researchers enter the field and create accessible fMRI and deep-learning diagnostic models for neurological disorders.

Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes.

Background: Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes. Design: Post-hoc analysis of a prospective observational cohort. Setting: Single-center study. Participants: 2569 women receiving embryo transfer. Intervention: None. Main outcome measures: The main outcomes were oocyte and embryo quality as well as pregnancy outcomes. Results: DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R2 = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R2=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes. Conclusion: DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.

Neuronal activity-driven O-GlcNAcylation promotes mitochondrial plasticity.

Neuronal activity is an energy-intensive process that is largely sustained by instantaneous fuel utilization and ATP synthesis. However, how neurons couple ATP synthesis rate to fuel availability is largely unknown. Here, we demonstrate that the metabolic sensor enzyme O-linked N-acetyl glucosamine (O-GlcNAc) transferase regulates neuronal activity-driven mitochondrial bioenergetics in hippocampal and cortical neurons. We show that neuronal activity upregulates O-GlcNAcylation in mitochondria. Mitochondrial O-GlcNAcylation is promoted by activity-driven glucose consumption, which allows neurons to compensate for high energy expenditure based on fuel availability. To determine the proteins that are responsible for these adjustments, we mapped the mitochondrial O-GlcNAcome of neurons. Finally, we determine that neurons fail to meet activity-driven metabolic demand when O-GlcNAcylation dynamics are prevented. Our findings suggest that O-GlcNAcylation provides a fuel-dependent feedforward control mechanism in neurons to optimize mitochondrial performance based on neuronal activity. This mechanism thereby couples neuronal metabolism to mitochondrial bioenergetics and plays a key role in sustaining energy homeostasis.

Metastatic Breast Cancer Presenting as Acute Appendicitis: A Case Report and Literature Review.

Breast cancer is considered one of the most common cancers worldwide. The most common sites for breast cancer to metastasize are the lymph nodes, bones, lungs, brain, and liver. Involvement of the gastrointestinal tract is uncommon, and metastasis to the appendix is rare. We report a case involving a 43-year-old woman with no previous history of malignancy who presented with acute appendicitis and underwent laparoscopic appendectomy, with the final histopathological assessment revealing metastatic breast cancer.

The Relationship of Mitral Annular Calcification and Aortic Valve Sclerosis to Endothelial Dysfunction.

BACKGROUND: Calcific aortic valve disease (CAVD) and mitral annular calcification (MAC) are associated with various cardiovascular diseases and may influence systemic vascular pathologies. However, their relationship with endothelial dysfunction and carotid intima-media thickness (CIMT) remains poorly elucidated. This research aims to explore the associations between MAC, aortic valve sclerosis (AVS), and markers of vascular dysfunction, specifically CIMT and endothelial function. METHODS: This prospective observational study included 200 patients undergoing routine echocardiographic evaluation at the National Heart Institute between May 2022 and April 2023. Patients were stratified into four groups namely isolated MAC (38 patients), isolated AVS (72 patients), combined MAC and AVS (50 patients), and a control group without MAC or AVS (40 patients). All participants underwent comprehensive cardiovascular evaluation, including transthoracic echocardiography (TTE) and carotid duplex ultrasonography. Endothelial function was determined by measuring reactive hyperemia-induced alterations in brachial artery diameter. RESULTS: The mean age of participants was 60.6±8.4 years, with a predominance of male subjects (64%). No significant differences were noted in baseline demographic and clinical characteristics across the groups. Patients with isolated AVS, isolated MAC, and both conditions demonstrated increased CIMT compared to controls, with significant differences noted in the combined MAC and AVS group compared to controls (p-value=0.031). Endothelial dysfunction was observed in 14.8% of the AVS group and 21.1% in the combined group, but no significant differences existed when compared to controls. The study also revealed that patients with AVS are more likely to exhibit increased CIMT (p-value=0.008). CONCLUSIONS: Both MAC and AVS are connected to increased CIMT, suggesting a link with systemic atherosclerotic processes. Although the existence of endothelial dysfunction was not significantly higher in patients with valvular calcifications, the findings support the need for further research into the cardiovascular implications of CAVD and MAC.

Laparoscopic Right Donor Nephrectomy: A Two-Center Comparative Study.

Introduction As the field of laparoscopic living donor nephrectomy (LLDN) has progressed over the years, there has been a growing emphasis on optimizing surgical techniques and outcomes to ensure the safety and well-being of living kidney donors. The early experiences with right LLDN, marked by challenges and concerns such as high conversion rates to open surgery and early graft loss due to technical reasons, prompted a reevaluation of the approach toward right-sided donor nephrectomies. In this article, we aim to compare the safety and efficacy of right LLDN to left LLDN performed in our centers and to provide valuable insights that can ultimately enhance patient outcomes and ensure the well-being of living organ donors. Methods Between January 2018 and January 2022, we conducted 16 cases of right LLDN and compared them with 134 cases of left LLDN procedures done in the Kingdom of Bahrain and Jordan over the same time period. We analyzed differences in donor age, sex, operative time, warm ischemia time (WIT), graft function, complications, and conversion to open technique. Patient data and surgical outcomes were extracted from medical records and surgical databases. Statistical analysis was conducted to identify significant differences between the two groups. Categorical variables such as complications and safety outcomes were compared using chi-square tests and logistic regression analysis. The primary outcomes of interest included safety metrics such as complication rates, vascular complications, graft loss, and postoperative serum creatinine levels for the recipients. Results Our study showed similar demographics in both groups. However, the operative time was shorter for the left LLDN, with 81 minutes compared to 96 minutes for the right. Warm ischemia times (WITs) were comparable at 4.5 minutes for the left and 5.2 minutes for the right. There was less incidence of delayed graft function on the left side (none in the left group compared to one case in the right group). Both groups had similar six-month graft function in terms of serum creatinine levels (0.98 mg/dL for the left and 1.2 mg/dL for the right), hospital stays (2.5 days for the left and 2.8 days for the right), and estimated blood loss (EBL) (90 mL for the left and 50 mL for the right). Additionally, no blood transfusions were required in either group, but there was one case of conversion to open surgery in the right LLDN group. Conclusion Our data confirm the safety and efficacy of the right LLDN, consistent with the current literature. This increases the cumulative evidence supporting the use of laparoscopic retrieval on the right side when indicated.

Radiographic assessment of the quality of post and core restorations performed by general dental practitioners in Saudi Arabia.

Background: Dentists utilize various techniques and materials for post and core restoration of endodontically treated teeth, which remains a noteworthy health concern and can be addressed through interdisciplinary strategies to enhance outcomes. Therefore, this study aimed to evaluate the technical quality of the residual gutta-percha (GP) and posts by analysing the periapical radiographs of endodontically restored teeth. Methods: A total of 594 periapical digital radiographs were evaluated for tooth type, post material, post shape, design, diameter, length, residual GP, GP length, GP tapering, GP homogeneity, and final restoration. Frequency distribution and cross-tabulation of the variables were performed. Results: Maxillary molars had the highest frequency of restorations, including posts, accounting for 27.4 %, followed by maxillary premolars (25.4 %) and maxillary anterior teeth (19.2 %). The prefabricated metallic posts were most commonly used (81.0 %), among these, 50.4 % were screwed posts. Tapered posts were the most commonly used (65.6 %). The percentage of posts with an acceptable length was 58.2 %. The most commonly used posts exhibited a width of one-third of the root diameter, accounting for 87.0 %. Suitable GP lengths were observed in 61.1 % of the restorations, and 62.8 % demonstrated adequate GP homogeneity. The findings of this study revealed that crown restoration accounted for 42.6 % of the studied sample. Conclusions: The technical quality of the remaining GP after restoration was comparable to that of previous epidemiological investigations. However, the technical quality of the post was deemed suboptimal.

Foodborne botulism outbreak with potential new management options.

OBJECTIVES: To shed some light on a potential therapeutic modality that may facilitate resolution of botulism symptoms, namely 3,4-diaminopyridine (3,4-DAP). METHODS: In Riyadh, Saudi Arabia, we recently encountered a foodborne botulism outbreak that, luckily, was discovered early. In Prince Sultan Military Medical city, we admitted, during a period of approximately 3 weeks, 15 probable cases, 2 of which were excluded due to more likely alternative diagnoses. We report in this case series 13 highly suspected cases of botulism that we encountered during the outbreak. RESULTS: A total of 12 out of 13 patients required intensive care unit (ICU) admission, one of which required intubation. Symptoms included cranial nerve palsies, gastrointestinal symptoms, limb and respiratory muscle weakness. Patients showed clinical improvement when received botulinum antitoxin and 3,4-DAP if given early in the course of the disease. CONCLUSION: Early admisntration of 3,4-DAP may facilitate recovery and prevent disease progression. Larger prospective trials should be carried out to confirm that.

Vertebral Fracture Associated With Extracorporeal Shock Wave Lithotripsy: A Case Report.

Extracorporeal shock wave lithotripsy (ESWL) is considered a safe, reliable, and non-invasive modality for kidney stone management. However, there are well-established complications related to ESWL documented in the literature in the form of renal and extrarenal complications. Skeletal complications related to ESWL are rarely recorded; as far as we know, there is only one documented case report of an ESWL-related burst vertebral fracture seen in an osteoporotic patient, diagnosed as granulomatous spondylitis. Here, we present a novel case of a transverse process fracture of the third lumbar vertebra related to ESWL in a young patient otherwise free from any medical illness.

Sequential graph convolutional network and DeepRNN based hybrid framework for epileptic seizure detection from EEG signal.

Automated epileptic seizure detection from ectroencephalogram (EEG) signals has attracted significant attention in the recent health informatics field. The serious brain condition known as epilepsy, which is characterized by recurrent seizures, is typically described as a sudden change in behavior caused by a momentary shift in the excessive electrical discharges in a group of brain cells, and EEG signal is primarily used in most cases to identify seizure to revitalize the close loop brain. The development of various deep learning (DL) algorithms for epileptic seizure diagnosis has been driven by the EEG's non-invasiveness and capacity to provide repetitive patterns of seizure-related electrophysiological information. Existing DL models, especially in clinical contexts where irregular and unordered structures of physiological recordings make it difficult to think of them as a matrix; this has been a key disadvantage to producing a consistent and appropriate diagnosis outcome due to EEG's low amplitude and nonstationary nature. Graph neural networks have drawn significant improvement by exploiting implicit information that is present in a brain anatomical system, whereas inter-acting nodes are connected by edges whose weights can be determined by either temporal associations or anatomical connections. Considering all these aspects, a novel hybrid framework is proposed for epileptic seizure detection by combined with a sequential graph convolutional network (SGCN) and deep recurrent neural network (DeepRNN). Here, DepRNN is developed by fusing a gated recurrent unit (GRU) with a traditional RNN; its key benefit is that it solves the vanishing gradient problem and achieve this hybrid framework greater sophistication. The line length feature, auto-covariance, auto-correlation, and periodogram are applied as a feature from the raw EEG signal and then grouped the resulting matrix into time-frequency domain as inputs for the SGCN to use for seizure classification. This model extracts both spatial and temporal information, resulting in improved accuracy, precision, and recall for seizure detection. Extensive experiments conducted on the CHB-MIT and TUH datasets showed that the SGCN-DeepRNN model outperforms other deep learning models for seizure detection, achieving an accuracy of 99.007%, with high sensitivity and specificity.

Rational design, synthesis, biological evaluation, and molecular modeling of novel naphthamide derivatives possessing potent, reversible, and competitive inhibitory mode of action over human monoamine oxidase.

Herein, a novel series of naphthamide derivatives has been rationally developed, synthesized, and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase (ChE) enzymes. Compared to the reported naphthalene-based hit IV, the new naphthamide hybrids 2a, 2c, 2g and 2h exhibited promising MAO inhibitory activities; with an IC50 value of 0.294 µM, compound 2c most potently inhibited MAO-A, while compound 2g exhibited most potent MAO-B inhibitory activity with an IC50 value of 0.519 µM. Compounds 2c and 2g showed selectivity index (SI) values of 6.02 for MAO-A and 2.94 for MAO-B, respectively. On the other hand, most compounds showed weak inhibitory activity against ChEs except 2a and 2h over butyrylcholinesterase (BChE). The most potent compounds 2c and 2g were found to be competitive and reversible MAO inhibitors based on kinetic and reversibility studies. Plausible interpretations of the observed biological effects were provided through molecular docking simulations. The drug-likeness predicted by SwissADME and Osiris property explorer showed that the most potent compounds (2a, 2c, 2g, and 2h) obey Lipinski's rule of five. Accordingly, in the context of neurological disorders, hybrids 2c and 2g may contribute to the identification of safe and potent therapeutic approaches in the near future.

Brd4::Nutm1 fusion gene initiates NUT carcinoma in vivo.

NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a BRD4::NUTM1 fusion gene. Because the BRD4::NUTM1 gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the Brd4::Nutm1 fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, Brd4::Nutm1 can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.

Assessment of modified chitosan composite in acidic reservoirs through pilot and field-scale simulation studies.

Chemical flooding through biopolymers acquires higher attention, especially in acidic reservoirs. This research focuses on the application of biopolymers in chemical flooding for enhanced oil recovery in acidic reservoirs, with a particular emphasis on modified chitosan. The modification process involved combining chitosan with vinyl/silane monomers via emulsion polymerization, followed by an assessment of its rheological behavior under simulated reservoir conditions, including salinity, temperature, pressure, and medium pH. Laboratory-scale flooding experiments were carried out using both the original and modified chitosan at conditions of 2200 psi, 135,000 ppm salinity, and 196° temperature. The study evaluated the impact of pressure on the rheological properties of both chitosan forms, finding that the modified composite was better suited to acidic environments, showing enhanced resistance to pressure effects with a significant increase in viscosity and an 11% improvement in oil recovery over the 5% achieved with the unmodified chitosan. Advanced modeling and simulation techniques, particularly using the tNavigator Simulator on the Bahariya formations in the Western Desert, were employed to further understand the polymer solution dynamics in reservoir contexts and to predict key petroleum engineering metrics. The simulation results underscored the effectiveness of the chitosan composite in increasing oil recovery rates, with the composite outperforming both its native counterpart and traditional water flooding, achieving a recovery factor of 48%, compared to 39% and 37% for native chitosan and water flooding, thereby demonstrating the potential benefits of chitosan composites in enhancing oil recovery operations.

Electronic and Molecular Adsorption Properties of Pt-Doped BC6N: An Ab-Initio Investigation.

In the last two decades, significant efforts have been particularly invested in two-dimensional (2D) hexagonal boron carbon nitride h-BxCyNz because of its unique physical and chemical characteristics. The presence of the carbon atoms lowers the large gap of its cousin structure, boron nitride (BN), making it more suitable for various applications. Here, we use density functional theory to study the structural, electronic, and magnetic properties of Pt-doped BC6N (Pt-BC6N, as well as its adsorption potential of small molecular gases (NO, NO2, CO2, NH3). We consider all distinct locations of the Pt atom in the supercell (B, N, and two C sites). Different adsorption locations are also considered for the pristine and Pt-doped systems. The formation energies of all Pt-doped structures are close to those of the pristine system, reflecting their stability. The pristine BC6N is semiconducting, so doping with Pt at the B and N sites gives a diluted magnetic semiconductor while doping at the C1 and C2 sites results in a smaller gap semiconductor. We find that all doped structures exhibit direct band gaps. The studied molecules are very weakly physisorbed on the pristine structure. Pt doping leads to much stronger interactions, where NO, NO2, and NH3 chemisorb on the doped systems, and CO2 physiorb, illustrating the doped systems' potential for gas purification applications. We also find that the adsorption changes the electronic and magnetic properties of the doped systems, inviting their consideration for spintronics and gas sensing.