CsSnI3 is a promising lead-free material that shows potential as a substitute for lead-based material in the development of ecologically benign perovskite solar cells (PSCs) due to its low cost, high ...efficiency, and excellent thermal stability. This research is intended to enhance the efficiency of CsSnI3-based PSCs by employing numerical simulation through the One Dimensional Solar Cell Capacitance Simulator (SCAPS-1D) to optimize the optoelectronic properties of the electron transport layer (ETL), absorber layer, hole transport layer (HTL), and different interface layers. An investigation was conducted to evaluate the influence of different ETLs namely WS2, ZnSe, C60 and PCBM on the performance of CsSnI3-based PSCs utilizing poly (3-hexylthiophene-2,5-diyl) (P3HT) as the HTL. Moreover, the influence of variations in the thickness, doping density, and defect density of the absorber layer, ETL, and HTL on key photovoltaic parameters including power conversion efficiency (PCE), short-circuit current density (Formula Omitted), open circuit voltage (Formula Omitted), and fill factor (FF) was observed. The findings revealed that depending on the ETL employed, the PCE varies between the structures. For structures using WS2, ZnSe, C60, and PCBM as ETL, the corresponding PCE values are 31.63%, 29.64%, 29.75%, and 29.62%. Additionally, for all PSC structures, the effects of interface defect, temperature, series-shunt resistance, capacitance-voltage characteristics, and Mott-Schottky plot have been observed, and the corresponding current density-voltage (J-V), quantum efficiency (QE), generation, and recombination rates have been computed. Finally, the outcomes of this analysis were compared with prior research conducted on CsSnI3-based PSCs, thereby offering significant perspectives for their advancement and commercial viability.
Antibiotics changed medical practice by significantly decreasing the morbidity and mortality associated with bacterial infection. However, infectious diseases remain the leading cause of death in the ...world. There is global concern about the rise in antimicrobial resistance (AMR), which affects both developed and developing countries. AMR is a public health challenge with extensive health, economic, and societal implications. This paper sets AMR in context, starting with the history of antibiotics, including the discovery of penicillin and the golden era of antibiotics, before exploring the problems and challenges we now face due to AMR. Among the factors discussed is the low level of development of new antimicrobials and the irrational prescribing of antibiotics in developed and developing countries. A fundamental problem is the knowledge, attitude, and practice (KAP) regarding antibiotics among medical practitioners, and we explore this aspect in some depth, including a discussion on the KAP among medical students. We conclude with suggestions on how to address this public health threat, including recommendations on training medical students about antibiotics, and strategies to overcome the problems of irrational antibiotic prescribing and AMR.
In efforts to develop effective anticancer therapeutics with greater selectivity toward cancerous cell and reduced side-effects, such as emetic effects due to detrimental action of the drug toward ...the intestinal flora, a series of linear diarylheptanoids (LDHs) were designed and synthesized in 7 steps with good-to-moderate yields. All synthesized compounds were evaluated for their antibacterial, antiproliferative, and topoisomerase-I and -IIα inhibitory activity. Overall, all compounds showed little to no activity against the bacterial strains tested. Most of the synthesized compounds showed good antiproliferative activity against human breast cancer cell lines (T47D); specifically, the IC
50
values of compounds
6a
,
6d
,
7j
, and
7e
were 0.09, 0.64, 0.67, and 0.99 μM, respectively. Among the tested compounds,
7b
inhibited topo-I by 9.3% (camptothecin 68.8%),
7e
and
7h
inhibited topo-IIα by 38.4 and 47.4% (etoposide 76.9%), respectively, at the concentration of 100 μM. These results suggest that a set of promising anticancer agents can be obtained by reducing inhibitory actions on different microbes to provide enhanced selectivity against cancerous cells.
Although it is widely recognized that the osteoclast differentiation induced by RANKL is linked to the anti-proliferative activity of the cytokine, we report here that RANKL in the presence of M-CSF ...actually stimulates DNA synthesis and cell proliferation during the early proliferative phase (0-48 h) of osteoclastogenesis ex vivo, while the same cytokine exerts an anti-proliferative activity in the latter half (48-96 h). A tracing of the individual cells using Fucci cell cycle indicators showed that waves of active DNA synthesis in the S phase during the period 0-48 h are followed by cell-cycle arrest and cell fusion after 48 h. Inhibition of DNA synthesis with hydroxyurea (HU) during the first half almost completely inhibited osteoclastogenesis; however, the same HU-treated cells, when re-plated at 48 h at increasing cell densities, exhibited restored osteoclast formation, suggesting that a sufficient number of cells, rather than prior DNA synthesis, is the most critical requirement for osteoclast formation. In addition, varying either the number of bone marrow macrophages at the start of osteoclastogenic cultures or pre-osteoclasts halfway through the process had a substantial impact on the number of osteoclasts that finally formed, as well as the timing of the peak of osteoclast formation. Thus, caution should be exerted in the performance of any manipulative procedure, whether pharmacological or genetic, that affects the cell number prior to cell fusion. Such procedures can have a profound effect on the number of osteoclasts that form, the final outcome of "differentiation", leading to misinterpretation of the results.
Objective:
Routine symptom assessment represents the cornerstone of symptom management of patients with advanced incurable diseases in palliative care. At present, there is no validated tool to ...assess symptoms among the Bengali-speaking population with incurable diseases. The aim of the study is to translate, culturally adapt, and validate the Edmonton Symptom Assessment Scale (Revised) into Bengali language.
Methods:
The study was conducted in two phases. Forward and backward translations of the English version of the Edmonton Symptom Assessment Scale (Revised) into Bengali were conducted by four independent translators. After obtaining reviews from an expert committee, pre-testing and cognitive debriefing the Bengali version of the tool was finalized. The final validation was conducted among 110 patients admitted to the Palliative Medicine Department of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Validity (content, face, and construct validity) and reliability (internal consistency) were assessed in the final validation phase.
Result:
All participants responded to all items. Seventy percent of the participants completely understood all questions but 30% had difficulty with three questions. The expert committee expressed their satisfaction regarding the face and content validity of the questionnaire. The Bengali version also had high reliability (α = 0.862). Principal component analysis with the distribution of varimax rotation of Edmonton Symptom Assessment Scale (Revised) Bengali ranged from 0.41 to 0.83.
Conclusion:
After the translation and cross-cultural adaptation, the Bengali version of the Edmonton Symptom Assessment Scale (Revised) achieved good levels of validity and reliability. It can be used as a symptom assessment tool for Bengali speaking population receiving palliative care.
Galeon, a natural cyclic-diarylheptanoid (CDH), which was first isolated from
L., is known to have potent cytotoxicity against A549 cell lines, anti-tubercular activity against
H37Rv, ...chemo-preventive potential, and moderate topoisomerase inhibitory activity. Here, in silico metabolism and toxicity prediction of galeon by CYP450, in vitro metabolic profiling study in rat liver microsomes (RLMs), and molecular interactions of galeon-CYP450 isoforms were performed. An in silico metabolic prediction study showed demethyl and mono-hydroxy galeon were the metabolites with the highest predictability. Among the predicted metabolites, mono-hydroxy galeon was found to have plausible toxicities such as skin sensitization, thyroid toxicity, chromosome damage, and carcinogenicity. An in vitro metabolism study of galeon, incubated in RLMs, revealed eighteen Phase-I metabolites, nine methoxylamine, and three glutathione conjugates. Identification of possible metabolites and confirmation of their structures were carried out using ion-trap tandem mass spectrometry. In silico docking analysis of galeon demonstrated significant interactions with active site residues of almost all CYP450 isoforms.
Na-amino acid co-transporters (NaAAcT) are uniquely affected in rabbit intestinal villus cell brush border membrane (BBM) during chronic intestinal inflammation. Specifically, Na-alanine co-transport ...(ASCT1) is inhibited secondary to a reduction in the affinity of the co-transporter for alanine, whereas Na-glutamine co-transport (B0AT1) is inhibited secondary to a reduction in BBM co-transporter numbers. During chronic intestinal inflammation, there is abundant production of the potent oxidant peroxynitrite (OONO). However, whether OONO mediates the unique alteration in NaAAcT in intestinal epithelial cells during chronic intestinal inflammation is unknown. In this study, ASCT1 and B0AT1 were inhibited by OONO in vitro. The mechanism of inhibition of ASCT1 by OONO was secondary to a reduction in the affinity of the co-transporter for alanine, and secondary to a reduction in the number of co-transporters for B0AT1, which were further confirmed by Western blot analyses. In conclusion, peroxynitrite inhibited both BBM ASCT1 and B0AT1 in intestinal epithelial cells but by different mechanisms. These alterations in the villus cells are similar to those seen in the rabbit model of chronic enteritis. Therefore, this study indicates that peroxynitrite may mediate the inhibition of ASCT1 and B0AT1 during inflammation, when OONO levels are known to be elevated in the mucosa.
Real‐world data (RWD) and real‐world evidence (RWE) are increasingly used to support regulatory decision making, but regulatory agencies and stakeholders may apply different definitions for RWD and ...use different criteria to determine when analysis of such data are considered RWE in decisions on drug approvals. To explore this issue, we reviewed two prominent publications that operationalized the definitions of RWD and RWE when describing the use of RWE in drug approvals by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Both publications considered noninterventional (observational) studies, RWD as a comparator arm for a single‐arm trial, product‐related literature reviews, and RWD to support clinical trial implementation (e.g., to identify potential participants) as generating RWE. In contrast, inconsistencies were identified regarding types of data sources and study designs that were considered as not generating RWE. For example, a lack of agreement existed regarding whether RWE is generated when RWD describe therapeutic contexts or are used in phase I/II interventional trials, open‐label extension studies, or pharmacovigilance activities. These discrepancies highlight opportunities to develop a consistent understanding of the role of RWE in regulatory decision making for drug approvals among regulatory agencies and stakeholders.
In acute cardiovascular disease management, the delay between the admission in a hospital emergency department and the assessment of the disease from a Delayed Enhancement cardiac MRI (DE-MRI) scan ...is one of the barriers for an immediate management of patients with suspected myocardial infarction or myocarditis.
This work targets patients who arrive at the hospital with chest pain and are suspected of having a myocardial infarction or a myocarditis. The main objective is to classify these patients based solely on clinical data in order to provide an early accurate diagnosis.
Machine learning (ML) and ensemble approaches have been used to construct a framework to automatically classify the patients according to their clinical conditions. 10-fold cross-validation is used during the model's training to avoid overfitting. Approaches such as Stratified, Over-sampling, Under-sampling, NearMiss, and SMOTE were tested in order to address the imbalance of the data (i.e. proportion of cases per pathology). The ground truth is provided by a DE-MRI exam (normal exam, myocarditis or myocardial infarction).
The stacked generalization technique with Over-sampling seems to be the best one providing more than 97% of accuracy corresponding to 11 wrong classifications among 537 cases. Generally speaking, ensemble classifiers such as Stacking provided the best prediction. The five most important features are troponin, age, tobacco, sex and FEVG calculated from echocardiography.
Our study provides a reliable approach to classify the patients in emergency department between myocarditis, myocardial infarction or other patient condition from only clinical information, considering DE-MRI as ground-truth. Among the different machine learning and ensemble techniques tested, the stacked generalization technique is the best one providing an accuracy of 97.4%. This automatic classification could provide a quick answer before imaging exam such as cardiovascular MRI depending on the patient's condition.
Simvastatin (SV) is a hypolipidemic agent, and it is the 2nd most widely prescribed lipid-lowering drug. Here, the detection and characterization of SV and its metabolites was studied in selected ...organs/tissues (lung, liver, brain, heart and kidney) and biological samples (blood, urine and feces) of rats. MALDI Orbitrap MS was used as a high-resolution mass analyzer. 2,5-Dihydroxybenzoic acid (DHB) and 1,5-diaminonaphthalene (DAN) were used as matrices. Several sample loading methods onto the MALDI plate were attempted and dried droplet method was found to be superior. Two different cell disruption methods, pulverization and homogenization, were also evaluated for the optimum sensitivity in MALDI. Pulverization allowed the detection of more metabolites in all organs except the liver, where homogenization led to the detection of more metabolites. Altogether, 13 metabolites were detected, and one metabolite tentatively identified as a reduced product is being reported for the first time. SV and its metabolites were distributed to all the tissues studied except the brain. Overall, the results implied that the pulverized samples were more uniform and larger in surface area, resulting in their more efficient and complete extraction during sample preparation. As shown in the present study, MALDI Orbitrap MS is a useful tool to study drug and metabolite detection and characterization.
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