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1.
Article in English | MEDLINE | ID: mdl-39126587

ABSTRACT

Ship-breaking yards are recognized for releasing hazardous polycyclic aromatic hydrocarbons (PAHs), leading to severe environmental pollution in the sediment of ship-breaking areas. This study assessed the concentrations of 16 priority PAHs in surface sediments collected from the intertidal zone adjacent to the Sitakund ship-breaking yards. The samples underwent Soxhlet extraction and detection using PerkinElmer GC-Clarus 690 and MS-Clarus SQ8C with an Elite-5MS capillary column (30 m × 0.25 mm ID × 0.25 µm). The study utilized PAH concentrations to reveal spatial distribution patterns, identify point sources, and assess potential toxicity. The total PAH concentration ranged from 1899.2 to 156,800.08 ng g-1 dw, while the concentration of 7 carcinogenic PAHs ranged from 822.03 to 1899.15 ng g-1 dw. High molecular weight PAHs dominated among the 16 PAHs, whereas low molecular weight PAHs, such as 2-ring PAHs, were negligible. Source characterization based on different molecular ratios suggested that PAHs in the area originated from pyrolytic processes related to ship dismantling, fishing activities, and water transportation for people. The observed PAH concentrations exceeded both national and international standards for sedimentary PAH levels, indicating significant ecological risks. The total TEQcarc values of sediment samples varied from 564.41 to 10,695.12 ng g-1, with a mean value of 3091.25 ng g-1. The study's findings underscore the immediate biological damage that PAH contamination in the Sitakund ship-breaking area could cause, emphasizing the need for effective control measures to ensure ecological and human safety.

2.
Chemosphere ; : 143129, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39159762

ABSTRACT

In this study, we investigated the interaction between arsenate (AsV) and phosphate (PO43-) in freshwater phytoplankton using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS). This study aimed to elucidate the influence of varying PO43- concentrations on arsenic (As) uptake and distribution at the single-cell level, providing insights into intraspecies diversity. Two species of freshwater phytoplanktons, Scenedesmus acutus and Pediastrum duplex, were cultured under different concentrations of PO43- and AsV in a controlled laboratory environment. Scenedesmus acutus, a species with strong salt tolerance, and Pediastrum duplex, known for its weak salt tolerance, were selected based on their contrasting behaviors in previous studies. SC-ICP-MS revealed non-uniform uptake of As by individual phytoplankton cells, with distinct variations in response to PO43- availability. Arsenic uptake by both species declined with a high PO43- level after 7 days of exposure. However, after 14 days, As uptake increased in S. acutus with higher PO43- concentrations, but decreased in P. duplex. Moreover, our findings revealed differences in cell morphology and membrane integrity between the two species in response to AsV and various PO43- concentrations. S. acutus maintained cell integrity under all experimental culture conditions, whereas P. duplex experienced cell lysis at elevated AsV and PO43- concentrations. This study highlights the varying responses of freshwater phytoplankton to changes in AsV and PO43- levels and underscores the advantages of SC-ICP-MS over conventional ICP-MS in providing detailed, cellular level insights. These findings are crucial for understanding and managing As pollution in aquatic ecosystems.

3.
PLoS One ; 19(7): e0305138, 2024.
Article in English | MEDLINE | ID: mdl-38985804

ABSTRACT

Distributed power generation systems may necessitate connecting multiple independent energy sources that employ various converter topologies. A recent development in this field is the emergence of impedance source converters, offering the ability to deliver buck-boost functionality within a single stage. The split-source inverter (SSI) has been introduced as a novel choice in between this family. Many control strategies have emerged for electrical power systems control. Among the recent emerging controllers, model predictive control strategies have become an effective technique for control systems. Model predictive controllers (MPCs) offer a number of features compared to the conventional and counterpart models such as enhanced system response and improved system transients with reduced steady-state error. This research suggests a finite control-set MPC for three-phase single-stage SSI supporting a standalone load for remote area applications. Considering the proposed FCS-MPC, the output load current tracks its reference magnitude with minimized error. In addition, the proposed FCS-MPC enhances the proposed SSI system performance with a settling time of 10 µs, and approximately without overshoot in the output current. The system has been validated using Opal-RT OP-4510 and the power loss model of the inverter has been explained. In the end two comparisons have been presented to clarify the main points in the topology structure and the control technique.


Subject(s)
Models, Theoretical , Electric Power Supplies , Equipment Design , Algorithms
4.
Cureus ; 16(7): e64230, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38988898

ABSTRACT

Leave against medical advice (LAMA) is defined as 'a decision to leave the hospital before the treating physician recommends discharge', and is associated with higher rates of readmission, longer subsequent hospitalization, and worse health outcomes. In addition to this, they also contribute to poor healthcare resource utilization. We conducted a single-center audit to establish patient demographics and contributing factors of patients leaving against medical advice from our emergency department (ED). We benchmarked our data against locally available clinical policy guidelines. We interrogated our electronic health record system (known as Salamtak®), which is a Cerner-based platform (Cerner Corporation, Kansas City, MO 64138) for patients who signed LAMA from ED from 2018 to 2023. We selected a convenience pilot sample of 120 subjects. Based on a literature review, we identified patient demographics (age, gender, nationality, socioeconomic status, marital status, religion), possible contributing factors (time of attendance, insurance status, length of ED stay), and patient outcomes (reattendances within 1 week and mortality) to evaluate. Based on locally available guidance, we formulated six criteria to audit with a standard set at 100% for each. A team of emergency medicine residents collected data that was anonymized on an Excel spreadsheet (Microsoft Excel, Microsoft Corporation. (2018). Basic descriptive statistics were used to collate results. About 93 patients (77.5%) were 16 years and above, and 27 patients (22.5%) were below 16 years. There was a slight preponderance of males (64 patients, 53.3%) than females (56 patients, 46.6%). The majority of LAMA cases presented in the evening and night (97 patients, 80.8%). About 57 (47.5%) patients had an ED length of stay of 3 hours or more. The average ED length of stay for these patients was 3.4 hours. About 73 patients (60.3%) were insured. Out of 120 patients, only 12 (10%) had a mental capacity assessment documented. The commonest reason for signing LAMA was a social reason in 45 (37.5%) cases. In the remaining cases, the causes were a combination of family, financial, waiting, or other/undocumented reasons). When faced with a decision to LAMA, the involvement of a Public Relationship Officer (PRO) was only documented to be consulted in seven (5.8%) cases. About 14 cases were re-attended within 1 week (11.6%) and no mortalities were reported in any of the reattendances. LAMA is a not-so-rare phenomenon often occurring in EDs, and often a cause of trepidation for healthcare workers. Treating this as an aberrant behavior on the part of the patient, or laying the responsibility for this action on the healthcare provider is primitive, counter-productive, and not patient-centric. Familiarity with local guidelines around this contentious area is essential. Revised nomenclature like 'premature discharge' may be less stigmatizing for the patient. Where possible, a harm reduction approach should be used and frontline healthcare workers must be prepared with an escalation plan. In the United Arab Emirates, familiarity with Wadeema's Law as a child protection measure is essential.

5.
Radiol Cardiothorac Imaging ; 6(4): e230328, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39023373

ABSTRACT

Purpose To investigate the impact of plaque size and density on virtual noncontrast (VNC)-based coronary artery calcium scoring (CACS) using photon-counting detector CT and to provide safety net reconstructions for improved detection of subtle plaques in patients whose VNC-based CACS would otherwise be erroneously zero when compared with true noncontrast (TNC)-based CACS. Materials and Methods In this prospective study, CACS was evaluated in a phantom containing calcifications with different diameters (5, 3, and 1 mm) and densities (800, 400, and 200 mg/cm3) and in participants who underwent TNC and contrast-enhanced cardiac photon-counting detector CT (July 2021-March 2022). VNC images were reconstructed at different virtual monoenergetic imaging (55-80 keV) and quantum iterative reconstruction (QIR) levels (QIR,1-4). TNC scans at 70 keV with QIR off served as the reference standard. In vitro CACS was analyzed using standard settings (3.0-mm sections, kernel Qr36, 130-HU threshold). Calcification detectability and CACS of small and low-density plaques were also evaluated using 1.0-mm sections, kernel Qr44, and 120- or 110-HU thresholds. Safety net reconstructions were defined based on background Agatston scores and evaluated in vivo in TNC plaques initially nondetectable using standard VNC reconstructions. Results The in vivo cohort included 63 participants (57.8 years ± 15.5 [SD]; 37 [59%] male, 26 [41%] female). Correlation and agreement between standard CACSVNC and CACSTNC were higher in large- and medium-sized and high- and medium-density than in low-density plaques (in vitro: intraclass correlation coefficient [ICC] ≥ 0.90; r > 0.9 vs ICC = 0.20-0.48; r = 0.5-0.6). Small plaques were not detectable using standard VNC reconstructions. Calcification detectability was highest using 1.0-mm sections, kernel Qr44, 120- and 110-HU thresholds, and QIR level of 2 or less VNC reconstructions. Compared with standard VNC, using safety net reconstructions (55 keV, QIR 2, 110-HU threshold) for in vivo subtle plaque detection led to higher detection (increased by 89% [50 of 56]) and improved correlation and agreement of CACSVNC with CACSTNC (in vivo: ICC = 0.51-0.61; r = 0.6). Conclusion Compared with TNC-based calcium scoring, VNC-based calcium scoring was limited for small and low-density plaques but improved using safety net reconstructions, which may be particularly useful in patients with low calcium scores who would otherwise be treated based on potentially false-negative results. Keywords: Coronary Artery Calcium CT, Photon-Counting Detector CT, Virtual Noncontrast, Plaque Size, Plaque Density Supplemental material is available for this article. © RSNA, 2024.


Subject(s)
Coronary Artery Disease , Phantoms, Imaging , Plaque, Atherosclerotic , Humans , Male , Female , Prospective Studies , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/pathology , Middle Aged , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/pathology , Aged , Photons , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Vascular Calcification/diagnostic imaging , Vascular Calcification/pathology , Tomography, X-Ray Computed/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Coronary Angiography/methods , Contrast Media
6.
Clin Imaging ; 113: 110235, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39059085

ABSTRACT

OBJECTIVE: This study aims to assess the efficacy of polyenergetic reconstruction methods in reducing streak artifacts caused by dual source imaging in Photon Counting Detector Computed Tomography (PCD-CT) imaging, thereby improving image quality and diagnostic accuracy. METHODS: A retrospective cohort study was conducted, involving 50 patients who underwent chest Computed Tomography Angiography with PCD-CT, focusing on those with streak artifacts. Quantitative and qualitative analyses were performed on images reconstructed using monoenergetic and polyenergetic techniques. Quantitative evaluations measured the attenuation of tracheal air density in regions affected by streak artifacts, while qualitative assessments employed a modified Likert scale to rate image quality. Statistical analyses included Wilcoxon's signed-rank tests and Spearman's correlation, alongside assessments of inter-rater reliability. RESULTS: There was significantly lower attenuation of tracheal air density on the polyenergetic reconstructions (Median - 1010 ± 62 HU vs -930 ± 110 HU; P < 0.001), and significantly decreased variation on the polyenergetic reconstructions (Median 65.2 ± 79.5 HU vs 38.8 ± 33.9 HU; P < 0.001). The median modified-Likert scale were significantly better for the polyenergetic reconstructions (median modified-Likert 4 ± 0.5 vs 2.5 ± 1; P < 0.001). The inter-rater agreement was substantial and not significantly different between reconstructions (Gwet's ACPolyenergetic = 0.78 vs Gwet's ACVMI = 0.775). CONCLUSION: Polyenergetic reconstruction significantly mitigates streak artifacts in PCD-CT imaging, enhancing quantitative and qualitative image quality. This advancement addresses a known limitation of current PCD-CT reconstruction techniques, offering a promising approach to improving diagnostic reliability and accuracy in clinical practice. We demonstrate that future software implementations can resolve this artifact.


Subject(s)
Artifacts , Humans , Retrospective Studies , Male , Female , Middle Aged , Aged , Reproducibility of Results , Radiographic Image Interpretation, Computer-Assisted/methods , Computed Tomography Angiography/methods , Aged, 80 and over , Adult , Tomography, X-Ray Computed/methods , Radiography, Thoracic/methods
7.
Helminthologia ; 61(2): 124-141, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39040803

ABSTRACT

The current study assessed the efficacy of Acyclovir (ACV) and Ivermectin (IVM) as monotherapies and combined treatments for intestinal and muscular stages of Trichinella spiralis infection. One-hundred Swiss albino mice received orally 250 ± 50 infectious larvae and were divided into infected-untreated (Group-1), IVM-treated (Group-2), ACV-treated (Group-3), combined IVM+ACV (Group-4), and healthy controls (Group-5). Each group was subdivided into subgroup-A-enteric phase (10 mice, sacrificed day-7 p.i.) and subgroup-B-muscular phase (10 mice, sacrificed day-35 p.i.). Survival rate and body weight were recorded. Parasite burden and intestinal histopathology were assessed. In addition, immunohistochemical expression of epithelial CDX2 in the intestinal phase and CyclinD1 as well as CD34 in the muscular phase were evaluated. Compared, IVM and ACV monotherapies showed insignificant differences in the amelioration of enteric histopathology, except for lymphocytic counts. In the muscle phase, monotherapies showed variable disruptions in the encapsulated larvae. Compared with monotherapies, the combined treatment performed relatively better improvement of intestinal inflammation and reduction in the enteric and muscular parasite burden. CDX2 and CyclinD1 positively correlated with intestinal inflammation and parasite burden, while CD34 showed a negative correlation. CDX2 positively correlated with CyclinD1. CD34 negatively correlated with CDX2 and CyclinD1. IVM +ACV significantly ameliorated CDX2, CyclinD1, and CD34 expressions compared with monotherapies. Conclusion. T. spiralis infection-associated inflammation induced CDX2 and CyclinD1 expressions, whereas CD34 was reduced. The molecular tumorigenic effect of the nematode remains questionable. Nevertheless, IVM +ACV appeared to be a promising anthelminthic anti-inflammatory combination that, in parallel, rectified CDX2, CyclinD1, and CD34 expressions.

8.
J Cardiovasc Dev Dis ; 11(7)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39057647

ABSTRACT

BACKGROUND: The choice of prosthesis for aortic valve replacement (AVR) remains challenging. The risk of anticoagulation complications vs. the risk of aortic valve reintervention should be weighed. This study compared the outcomes of bioprosthetic vs. mechanical AVR in patients older and younger than 50. METHODS: This retrospective study was conducted from 2009 to 2019 and involved 292 adult patients who underwent isolated AVR. The patients were divided according to their age (above 50 years or 50 years and younger) and the type of valves used in each age group. The outcomes of bioprosthetic valves (Groups 1a (>50 years) and 1b (≤50 years)) were compared with those of mechanical valves (Groups 2a (>50 years) and 2b (≤50 years)) in each age group. RESULTS: The groups had nearly equal rates of preexisting comorbidities except for Group 1b, in which the rate of hypertension was greater (32.6% vs. 14.7%; p = 0.025). This group also had higher rates of old stroke (8.7% vs. 0%, p = 0.011) and higher creatinine clearance (127.62 (108.82-150.23) vs. 110.02 (84.87-144.49) mL/min; p = 0.026) than Group 1b. Patients in Group 1a were significantly older than Group 2a (64 (58-71) vs. 58 (54-67) years; p = 0.002). There was no significant difference in the NYHA class between the groups. The preoperative ejection fraction and other echocardiographic parameters did not differ significantly between the groups. Re-exploration for bleeding was more common in patients older than 50 years who underwent mechanical valve replacement (p = 0.021). There was no difference in other postoperative complications between the groups. The groups had no differences in survival, stroke, or bleeding rates. Aortic valve reintervention was significantly greater in patients ≤ 50 years old with bioprosthetic valves. There were no differences between groups in the changes in left ventricular mass, ejection fraction, or peak aortic valve pressure during the 5-year follow-up. CONCLUSIONS: The outcomes of mechanical and bioprosthetic valve replacement were comparable in patients older than 50 years. Using bioprosthetic valves in patients younger than 50 years was associated with a greater rate of valve reintervention, with no beneficial effect on the risk of bleeding or stroke.

9.
bioRxiv ; 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38948751

ABSTRACT

Cancer genomic studies have identified frequent alterations in components of the SWI/SNF (SWItch/Sucrose Non- Fermenting) chromatin remodeling complex including SMARCA4 and ARID1A . Importantly, clinical reports indicate that SMARCA4 -mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. However, the mechanistic basis of immunotherapy resistance is unknown. Here, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, we show that SMARCA4 loss caused decreased response to anti-PD1 immunotherapy associated with significantly reduced infiltration of dendritic cells (DCs) and CD4+ T cells into the tumor microenvironment (TME). Mechanistically, we show that SMARCA4 loss in tumor cells led to profound downregulation of STING, IL1ß and other components of the innate immune system as well as inflammatory cytokines that are required for efficient recruitment and activity of immune cells. We establish that this deregulation of gene expression is caused by cancer cell-intrinsic reprogramming of the enhancer landscape with marked loss of chromatin accessibility at enhancers of genes involved in innate immune response such as STING, IL1ß, type I IFN and inflammatory cytokines. Interestingly, we observed that transcription factor NF-κB binding motif was highly enriched in enhancers that lose accessibility upon SMARCA4 deficiency. Finally, we confirmed that SMARCA4 and NF-κB co-occupy the same genomic loci on enhancers associated with STING and IL1ß, indicating a functional interplay between SMARCA4 and NF-κB. Taken together, our findings provide the mechanistic basis for the poor response of SMARCA4 -mutant tumors to anti-PD1 immunotherapy and establish a functional link between SMARCA4 and NF-κB on innate immune and inflammatory gene expression regulation.

10.
J Bioenerg Biomembr ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39083188

ABSTRACT

The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE2), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE2 inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE2 inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE2 inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE2 inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors.

11.
J Cell Biol ; 223(8)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38865088

ABSTRACT

Super-resolution microscopy, or nanoscopy, enables the use of fluorescent-based molecular localization tools to study molecular structure at the nanoscale level in the intact cell, bridging the mesoscale gap to classical structural biology methodologies. Analysis of super-resolution data by artificial intelligence (AI), such as machine learning, offers tremendous potential for the discovery of new biology, that, by definition, is not known and lacks ground truth. Herein, we describe the application of weakly supervised paradigms to super-resolution microscopy and its potential to enable the accelerated exploration of the nanoscale architecture of subcellular macromolecules and organelles.


Subject(s)
Artificial Intelligence , Microscopy , Animals , Humans , Image Processing, Computer-Assisted/methods , Machine Learning , Microscopy/methods , Microscopy, Fluorescence/methods
12.
Eur J Gastroenterol Hepatol ; 36(8): 1000-1009, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38829956

ABSTRACT

BACKGROUND: There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE: The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS: The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.


Subject(s)
Anti-Bacterial Agents , Clarithromycin , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Proton Pump Inhibitors , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/diagnosis , Helicobacter pylori/drug effects , Ireland , Anti-Bacterial Agents/therapeutic use , Adult , Proton Pump Inhibitors/therapeutic use , Clarithromycin/therapeutic use , Metronidazole/therapeutic use , Consensus , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Treatment Outcome , Bismuth/therapeutic use
13.
Heliyon ; 10(11): e32214, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38912496

ABSTRACT

Typically, parasitic capacitances exist between the ground and the solar panel terminals in grid-connected PV systems. These parasitic capacitances provide a path for a leakage current, which leads to significant safety concerns, observable and seriously hazardous harmonic orders aligned with the injected grid current, and significant safety difficulties. In this research, a robust PWM controlling method that used competently in reducing the level of the leakage current and improving the power quality of a switched-capacitor Multilevel Inverter. This technique creates developed reference signals from the main signal to generate the switching scheme for the converter circuit. Additionally, the suggested control strategy only works with a small number of carrier signals, resulting in a quick system response and a simpler controller algorithm. Likewise, this controlling approach offers a stable way to maintain a constant output voltage in the suggested converter by adjusting the switching capacitors' voltages, which is not possible with traditional control techniques. MATLAB/Simulink is used to simulate the outcomes for both the suggested control approach and the traditional Phase Disposition (PD) PWM control method whereas the leakage current component reduces to 25 % compared to the captured component with the PDPWM. The simulation and the practical results based on the dSPACE-1103 hardware are quite similar.

14.
Nat Commun ; 15(1): 3741, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702301

ABSTRACT

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Drug Resistance, Neoplasm , Lung Neoplasms , Signal Transduction , Transcription Factors , YAP-Signaling Proteins , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Signal Transduction/drug effects , Transcription Factors/metabolism , Transcription Factors/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , YAP-Signaling Proteins/metabolism , Cell Line, Tumor , Animals , Drug Resistance, Neoplasm/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Neoplasm, Residual , Mice , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , ErbB Receptors/metabolism , ErbB Receptors/genetics , Anaplastic Lymphoma Kinase/metabolism , Anaplastic Lymphoma Kinase/genetics , Anaplastic Lymphoma Kinase/antagonists & inhibitors , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Xenograft Model Antitumor Assays
15.
Heliyon ; 10(10): e31190, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803968

ABSTRACT

Due to its high gravimetric capacity of hydrogen (10.5 wt%), LiAlH4 has been regarded as a promising material for solid-state hydrogen storage material for onboard usage. However, high decomposition temperature, poor kinetics and irreversibility retard its application. To counter this problem, various weight percentages of BaMnO3 are introduced into the LiAlH4 system as an additive in this work. As a result, the starting hydrogen release of LiAlH4 was reduced to 109-115 °C and the second desorption temperature occurred at around 134-158 °C, much lower than pure LiAlH4. The isothermal desorption kinetics also proved that faster desorption kinetics can be observed at 90 °C for 80 min. About 2.00-2.60 wt% of H2 could be desorbed by the composite, whereas only <1.00 wt% of H2 was desorbed by undoped LiAlH4. Additionally, adding BaMnO3 reduced the activation energies by 30 kJ/mol for the first stages and 34 kJ/mol for the second stages. Based on the X-ray diffraction result, the active species formed of MnO2 and Ba or Ba-containing materials are believed to be responsible for the noticeable enhancement in the desorption properties of LiAlH4.

17.
Sci Rep ; 14(1): 7993, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580708

ABSTRACT

The current work aimed to improve the combustion behavior of a non-premixed twin-jet inlet. The effect of fuel and air inlet shape under different velocities was studied using ANSYS as the process takes place in species transport and finite rate/eddy dissipation, and the flow is considered to be turbulent. Two different shapes (circular-circular and circular-elliptic inlet jets) were investigated, and the results show that the behavior and intensity of the fire are affected by variations in the speed and, geometry of the inlet which affects temperature, heat release rate, combustion efficiency, and equivalent ratios. The optimum air/fuel velocities were found to be 2.5/1.5 with circular-circular inlet jets.

18.
J Recept Signal Transduct Res ; 44(1): 35-40, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38666646

ABSTRACT

BACKGROUND: The pineal product melatonin (MEL) modulates blood vessels through G protein-coupled receptors (GPCRs) called melatonin type 1 receptor (MT1R) and melatonin type 2 receptor (MT2R), in that order. The renin-angiotensin system (RAS), which breaks down angiotensin II (Ang II) to create Ang 1-7, is thought to be mostly controlled by angiotensin-converting enzyme-2 (ACE2). AIM: The current work examines the involvement of ACE2 inhibitor, MEL, and ramelteon (RAM) in the vascular response to Ang II activities in the endothelial denuded (E-) and intact (E+) rat isolated thoracic aortic rings. METHOD: The isometric tension was measured to evaluate the vascular Ang II contractility using dose response curve (DRC). RESULTS: MEL and RAM caused a rightward shift of Ang II in endothelium E + and endothelium E- aorta. CONCLUSION: According to the current study, the distribution of MEL receptors and the endothelium's condition are related to the vasomodulatory effect of MEL and ACE2 on Ang II attenuation. These physiological interactions can control vascular tone and increase Ang II reactivity denude endothelial layaer.


Subject(s)
Angiotensin II , Angiotensin-Converting Enzyme 2 , Melatonin , Animals , Melatonin/pharmacology , Angiotensin II/metabolism , Angiotensin II/pharmacology , Rats , Angiotensin-Converting Enzyme 2/metabolism , Renin-Angiotensin System/drug effects , Aorta, Thoracic/drug effects , Aorta, Thoracic/metabolism , Male , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Peptidyl-Dipeptidase A/metabolism , Aorta/drug effects , Aorta/metabolism , Receptor, Melatonin, MT2/metabolism , Receptor, Melatonin, MT2/antagonists & inhibitors , Angiotensin-Converting Enzyme Inhibitors/pharmacology
19.
Heliyon ; 10(6): e27759, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38515697

ABSTRACT

Avian pathogenic Escherichia coli (APEC) has been identified as a sub-group of extraintestinal pathogenic E. coli (ExPEC). Recent studies indicate APEC as a potential foodborne zoonotic pathogen and a source or reservoir of human extraintestinal infections. The slaughtering and processing of poultry in low-income countries such as Jordan occurs in two distinct ways: in informal facilities known as Natafat and in formal slaughterhouses. This study compared E. coli phenotypes and genotypes according to slaughtering conditions (formal slaughterhouses vs. informal slaughter facilities). Therefore, liver samples (n = 242) were collected from formal (n = 121) and informal slaughter facilities (n = 121). Results revealed a high prevalence (94.2%) of E. coli among all isolates, with 59 (17 formal and 42 informal) isolates considered avian pathogenic E. coli (APEC) based on the virulence-associated genes. The prevalence of resistance among isolates was relatively high, reaching up to 99% against penicillin and 97% against nalidixic acid. However, the prevalence of resistance was the lowest (1.3%) against both meropenem and imipenem. Based on the MIC test findings, colistin resistance was 46.9% (107/228). The mcr -1 gene prevalence was 51.4% (55/107), of which 17.1 % were from formal plants (6/36) and 68.1% from informal facilities (49/72). Interestingly, only one isolate (0.9%) expressed mcr-10. Escherichia coli O157:H7 and associated virulence genes were found more in informal (n = 15 genes) than in formal slaughterhouses (n = 8). Phylogroups B1, C, and A were the most frequent in 228 E. coli isolates, while G, B2, and clade were the least frequent. In conclusion, these findings highlight the importance of implementing biosecurity measures in slaughterhouses to reduce antibiotic-resistant E. coli spread. Furthermore, this study provides valuable insights into the effects of wet market (Natafat) slaughter conditions on increasing bacterial resistance and virulence.

20.
Heliyon ; 10(5): e26597, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38434285

ABSTRACT

The generation of power and fuel sustainability that contributes to a cleaner output of exhaust gases is one of the most important objectives the world seeks. In this paper, oxyhydrogen gas is used to retrofit into a two-stroke engine. The water was electrolysed and generated a mixture of oxygen (O2) and hydrogen (H2) or known as oxyhydrogen (HHO) gas via an electrolytic dry cell generator. The HHO was retrofitted experimentally to investigate the engine emissions and exhaust gas temperature from a 1.5 kW gasoline engine. The engine was tested with different power ratings (84-720 W) to investigate the performance and emissions of the engine using gasoline followed by the addition of HHO. The emissions of CO and NOx were measured with different amounts of HHO added. The exhaust temperature was calculated as one of the variables to be considered in relation to pollution. The air-fuel ratios are varied from 12 to 20% in the experiment. The most appropriate air-fuel ratio needed to start the generator with the most environmentally friendly gas emission was analysed. The results showed that the addition of HHO to the engine is successful in reducing fuel consumption up to 8.9%. A higher percentage of HHO added also has improved the emissions and reduced exhaust gas temperature. In this study, the highest quantity of HHO added at 0.15% of the volume fraction reduced CO gas emission by up to 9.41%, NOx gas up to 4.31%, and exhaust gas temperature by up to 2.02%. Generally, adding oxyhydrogen gas has significantly reduced the emissions, and exhaust temperature and provided an eco-friendly environment.

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