Due to lack of sufficient data on the psychological toll of the COVID-19 pandemic on adolescent mental health, this systematic analysis aims to evaluate the impact of the pandemic on adolescent ...mental health. This study follows the PRISMA guidelines for systematic reviews of 16 quantitative studies conducted in 2019-2021 with 40,076 participants. Globally, adolescents of varying backgrounds experience higher rates of anxiety, depression, and stress due to the pandemic. Secondly, adolescents also have a higher frequency of using alcohol and cannabis during the COVID-19 pandemic. However, social support, positive coping skills, home quarantining, and parent-child discussions seem to positively impact adolescent mental health during this period of crisis. Whether in the United States or abroad, the COVID-19 pandemic has impacted adolescent mental health. Therefore, it is important to seek and to use all of the available resources and therapies to help adolescents mediate the adjustments caused by the pandemic.
Triple-negative breast cancer (TNBC), accounting for 10–15% of all breast malignancies, is more prevalent in women under 40, particularly in those of African descent or carrying the BRCA1 mutation. ...TNBC is characterized by the absence of estrogen and progesterone receptors (ER, PR) and low or elevated HER2 expression. It represents a particularly aggressive form of breast cancer with limited therapeutic options and a poorer prognosis. In our study, we utilized the protein of TNBC collected from the Protein Data Bank (PDB) with the most stable configuration. We selected Scutellarein, a bioactive molecule renowned for its anti-cancer properties, and used its derivatives to design potential anti-cancer drugs employing computational tools. We applied and modified structural activity relationship methods to these derivatives and evaluated the probability of active (Pa) and inactive (Pi) outcomes using pass prediction scores. Furthermore, we employed in-silico approaches such as the assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and quantum calculations through density functional theory (DFT). Within the DFT calculations, we analyzed Frontier Molecular Orbitals, specifically the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO). We then conducted molecular docking and dynamics against TNBC to ascertain binding affinity and stability. Our findings indicated that Scutellarein derivatives, specifically DM03 with a binding energy of -10.7 kcal/mol and DM04 with -11.0 kcal/mol, exhibited the maximum binding tendency against Human CK2 alpha kinase (PDB ID 7L1X). Molecular dynamic simulations were performed for 100 ns, and stability was assessed using root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) parameters, suggesting significant stability for our chosen compounds. Furthermore, these molecules met the pharmacokinetics requirements for potential therapeutic candidates, displaying non-carcinogenicity, minimal aquatic and non-aquatic toxicity, and greater aqueous solubility. Collectively, our computational data suggest that Scutellarein derivatives may serve as potential therapeutic agents for TNBC. However, further experimental investigations are needed to validate these findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ammonia, a molecule that is gaining more interest as a fueling vector, has been considered as a candidate to power transport, produce energy, and support heating applications for decades. However, ...the particular characteristics of the molecule always made it a chemical with low, if any, benefit once compared to conventional fossil fuels. Still, the current need to decarbonize our economy makes the search of new methods crucial to use chemicals, such as ammonia, that can be produced and employed without incurring in the emission of carbon oxides. Therefore, current efforts in this field are leading scientists, industries, and governments to seriously invest efforts in the development of holistic solutions capable of making ammonia a viable fuel for the transition toward a clean future. On that basis, this review has approached the subject gathering inputs from scientists actively working on the topic. The review starts from the importance of ammonia as an energy vector, moving through all of the steps in the production, distribution, utilization, safety, legal considerations, and economic aspects of the use of such a molecule to support the future energy mix. Fundamentals of combustion and practical cases for the recovery of energy of ammonia are also addressed, thus providing a complete view of what potentially could become a vector of crucial importance to the mitigation of carbon emissions. Different from other works, this review seeks to provide a holistic perspective of ammonia as a chemical that presents benefits and constraints for storing energy from sustainable sources. State-of-the-art knowledge provided by academics actively engaged with the topic at various fronts also enables a clear vision of the progress in each of the branches of ammonia as an energy carrier. Further, the fundamental boundaries of the use of the molecule are expanded to real technical issues for all potential technologies capable of using it for energy purposes, legal barriers that will be faced to achieve its deployment, safety and environmental considerations that impose a critical aspect for acceptance and wellbeing, and economic implications for the use of ammonia across all aspects approached for the production and implementation of this chemical as a fueling source. Herein, this work sets the principles, research, practicalities, and future views of a transition toward a future where ammonia will be a major energy player.
Lung cancer, also known as pulmonary cancer, is one of the deadliest cancers, but yet curable if detected at the early stage. At present, the ambiguous features of the lung cancer nodule make the ...computer-aided automatic diagnosis a challenging task. To alleviate this, we present LungNet, a novel hybrid deep-convolutional neural network-based model, trained with CT scan and wearable sensor-based medical IoT (MIoT) data. LungNet consists of a unique 22-layers Convolutional Neural Network (CNN), which combines latent features that are learned from CT scan images and MIoT data to enhance the diagnostic accuracy of the system. Operated from a centralized server, the network has been trained with a balanced dataset having 525,000 images that can classify lung cancer into five classes with high accuracy (96.81%) and low false positive rate (3.35%), outperforming similar CNN-based classifiers. Moreover, it classifies the stage-1 and stage-2 lung cancers into 1A, 1B, 2A and 2B sub-classes with 91.6% accuracy and false positive rate of 7.25%. High predictive capability accompanied with sub-stage classification renders LungNet as a promising prospect in developing CNN-based automatic lung cancer diagnosis systems.
•Reliable CNN-based automatic diagnosis with global access helps early diagnosis of Lung Cancer.•Both CT images and physiological information are good indicators of the level of malignancy of lung cancer.•A hybrid classifier considers image features and symptomatic data in lung cancer classification.•A trained deep Convolutional Neural Network (CNN) with a hybrid classifier operated from a centralized server allows ubiquitous access with reliable diagnosis service.
Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been ...revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular
,
, and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of "safer" antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative "superbugs," every effort must be made to improve the clinical utility of the last-line polymyxins. SIGNIFICANCE STATEMENT: Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.
Small molecule inhibitors, such as lapatinib, are effective against breast cancer in clinical trials, but tumor cells ultimately acquire resistance to the drug. Maintaining sensitization to drug ...action is essential for durable growth inhibition. Recently, adaptive reprogramming of signaling circuitry has been identified as a major cause of acquired resistance. We developed a computational framework using a Bayesian statistical approach to model signal rewiring in acquired resistance. We used the p1-model to infer potential aberrant gene-pairs with differential posterior probabilities of appearing in resistant-vs-parental networks. Results were obtained using matched gene expression profiles under resistant and parental conditions. Using two lapatinib-treated ErbB2-positive breast cancer cell-lines: SKBR3 and BT474, our method identified similar dysregulated signaling pathways including EGFR-related pathways as well as other receptor-related pathways, many of which were reported previously as compensatory pathways of EGFR-inhibition via signaling cross-talk. A manual literature survey provided strong evidence that aberrant signaling activities in dysregulated pathways are closely related to acquired resistance in EGFR tyrosine kinase inhibitors. Our approach predicted literature-supported dysregulated pathways complementary to both node-centric (SPIA, DAVID, and GATHER) and edge-centric (ESEA and PAGI) methods. Moreover, by proposing a novel pattern of aberrant signaling called V-structures, we observed that genes were dysregulated in resistant-vs-sensitive conditions when they were involved in the switch of dependencies from targeted to bypass signaling events. A literature survey of some important V-structures suggested they play a role in breast cancer metastasis and/or acquired resistance to EGFR-TKIs, where the mRNA changes of TGFBR2, LEF1 and TP53 in resistant-vs-sensitive conditions were related to the dependency switch from targeted to bypass signaling links. Our results suggest many signaling pathway structures are compromised in acquired resistance, and V-structures of aberrant signaling within/among those pathways may provide further insights into the bypass mechanism of targeted inhibition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Shigellaa Gram-negative, non-motile bacillus, is the primary causative agent of the infectious disease shigellosis, which kills 1.1 million people worldwideevery year. The children under the age of ...five are primarily the victims of this disease. This study has been conducted to assess the prevalence of shigellosis through selective plating, biochemical test and conventional PCR assays, where the samples were collected from suspected diarrheoal patients. Invasive plasmid antigen H (ipaH) and O-antigenic rfc gene were used to identify Shigella spp. and S. flexneri respectively. For validation of these identification, PCR product of ipaH gene of a sample (Shigella flexneri MZS 191) has been sequenced and submitted to NCBI database (GenBank accession no- MW774908.1). Further this strain has been used as positive control. Out of 204, around 14.2% (n = 29)(P> 0.01) pediatric diarrheoal cases were screened as shigellosis. Another interesting finding was that most of shigellosis affected children were 7 months to 1 year (P> 0.01).The significance of this study lies in the analyses of the occurrenceand the molecular identification of Shigellaspp. and S. flexneri that can be utilized in improving the accurate identification and the treatment of the most severe and alarming shigellosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nanotechnology is utilized well in the development and improvement of the performance in Solid Oxide Fuel Cells (SOFCs). The high operating temperature of SOFCs (700–900°C) has resulted in serious ...demerits regarding their overall performance and durability. Therefore, the operating temperature has been reduced to an intermediate temperature range of approximately 400–700°C which improved performance and, subsequently, commercialized SOFCs as portable power sources. However, at reduced temperature, challenges such as an increase in internal resistance of the fuel cell components arise. Although, this may not be as serious as problems encountered at high temperature, it still significantly affects the performance of SOFCs. This review paper addresses the work of researchers in the application of nanotechnology in fabricating SOFCs through distinct methods. These methods have successfully omitted or at least reduced the internal resistance and showed considerable improvement in power density of the SOFCs at reduced temperatures.
The emergence of multidrug-resistant (MDR) Gram-negative pathogens is an urgent global medical challenge. The old polymyxin lipopeptide antibiotics (polymyxin B and colistin) are often the only ...therapeutic option due to resistance to all other classes of antibiotics and the lean antibiotic drug development pipeline. However, polymyxin B and colistin suffer from major issues in safety (dose-limiting nephrotoxicity, acute toxicity), pharmacokinetics (poor exposure in the lungs) and efficacy (negligible activity against pulmonary infections) that have severely limited their clinical utility. Here we employ chemical biology to systematically optimize multiple non-conserved positions in the polymyxin scaffold, and successfully disconnect the therapeutic efficacy from the toxicity to develop a new synthetic lipopeptide, structurally and pharmacologically distinct from polymyxin B and colistin. This resulted in the clinical candidate F365 (QPX9003) with superior safety and efficacy against lung infections caused by top-priority MDR pathogens Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae.
Fog-collecting meshes show a great potential in ensuring the availability of a supply of sustainable freshwater in certain arid regions. In most cases, the meshes are made of hydrophilic smooth ...fibers. Based on the study of plant surfaces, we analyzed the fog collection using various polyethylene terephthalate (PET) fibers with different cross sections and surface structures with the aim of developing optimized biomimetic fog collectors. Water droplet movement and the onset of dripping from fiber samples were compared. Fibers with round, oval, and rectangular cross sections with round edges showed higher fog-collection performance than those with other cross sections. However, other parameters, for example, width, surface structure, wettability, and so forth, also influenced the performance. The directional delivery of the collected fog droplets by wavy/v-shaped microgrooves on the surface of the fibers enhances the formation of a water film and their fog collection. A numerical simulation of the water droplet spreading behavior strongly supports these findings. Therefore, our study suggests the use of fibers with a round cross section, a microgrooved surface, and an optimized width for an efficient fog collection.
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